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.Textual Research and Analysis of Historic Origin and Ancient and Modern Application of Classic Formula Shengjiangsan
Lyuyuan LIANG ; Jialei CAO ; Xinghang LYU ; Weixiao LI ; Wenxi WEI ; Bingqi WEI ; Zhe WANG ; Yiping WANG ; Bingxiang MA ; Wenli SHI
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(9):219-227
Shengjiangsan is a classic formula for treating warm diseases with wide clinical application and accurate efficacy. There are different opinions on the origin of this formula and lacks key information research on this formula. Therefore, in this study, we conducted systematic research into the historic origin, composition, and other key information of this Shengjiangsan. Results showed that Shengjiangsan has different versions, with "Neixian Fufang", "Jiawei Jianghuangwan", "Peizhensan", and "Taijiwan" being the same formula with different names. Shengjiangsan was first recorded as "Neixian Fufang" in Wanbing Huichun written by GONG Tingxian from the Ming dynasty, inherited and developed by YANG Lishan from Qing dynasty, and has been passed down to modern times. Pills and powder are two main forms of Shengjiangsan, and powder has become more popular nowadays. According to the measurement system of Ming and Qing dynasties, the recommended dosage and usage of Shengjiangsan are as follows. For the pill version of Shengjiangsan, Bombyx Batryticatus of 74.6 g, Curcumae Longae Rhizoma of 9.325 g, Cicadae Periostracum of 9.325 g, and Rhei Radix et Rhizoma of 149.2 g were processed into pills for preparation. Single dosage is Bombyx Batryticatus of 1.15 g, Curcumae Longae Rhizoma of 0.14 g, Cicadae Periostracum of 0.14 g, and Rhei Radix et Rhizoma of 2.3 g, with halved dosage applied for children. For the powder version of Shengjiangsan, the dosage varied in accordance with the severity of the disease. Bombyx Batryticatus of 1.84 g, Curcumae Longae Rhizoma of 0.28 g, Cicadae Periostracum of 0.92 g, and Rhei Radix et Rhizoma of 3.68 g were processed into powder for patients with mild symptoms. Bombyx Batryticatus of 2.48 g, Curcumae Longae Rhizoma of 0.37 g, Cicadae Periostracum of 1.23 g, and Rhei Radix et Rhizoma of 4.91 g were processed into powder for patients with severe symptoms. Bombyx Batryticatus of 3.68 g, Curcumae Longae Rhizoma of 1.84 g, Cicadae Periostracum of 0.55 g, and Rhei Radix et Rhizoma of 7.36 g were processed into powder for patients with critical conditions. In this formula, four herbs were ground to fine powder. For patients with mild symptoms, the whole formula was divided into four dosages, and each dosage weighed 6.71 g. The 200 mL yellow rice wine and 18.65 g honey were added, and the solution was stirred and taken cold till full recovery. For patients with severe symptoms, the whole formula was divided into three dosages, and each weighed 8.95 g. 300 mL yellow rice wine and 27.98 g honey were added, and the solution was stirred and taken cold. For patients with critical conditions, the whole formula was divided into two dosages, and each weighed 13.43 g. 400 mL yellow rice wine and 37.3 g honey were added, and the solution was stirred and taken cold. Shengjiangsan has the effect of ascending lucidity and descending turbidity, dissipating wind, and clearing heat. It is specialized in treating severe heat in exterior, interior, and triple energizers in warm diseases and has a wide modern clinical application. In this study, the historic evolution and key information of Shengjiangsan were reviewed and analyzed, and the key information table of Shengjiangsan was attached, serving as a reference for scholars' research and a theoretical basis for its market transformation.
3.Advances in the establishment and application of preclinical tumor models of pancreatic cancer
Changwei DU ; Yueze LIU ; Zhe CAO ; Taiping ZHANG
Journal of Clinical Hepatology 2025;41(4):605-610
This article reviews the research advances in the characteristics and application progress of various new models for preclinical cancer research on pancreatic cancer, analyzes and discusses the history, current research status, and advantages and disadvantages of new models of pancreatic cancer, including patient-derived tissue xenograft, conditional reprogramming, and patient derived organoids, and it also reviews the studies that have achieved clinical transformation from preclinical models and proposes possible research prospects in the future.
4.Analysis of Ancient and Modern Literature of Xiaoyaosan and Examination of Its Key Information
Zhe WANG ; Jialei CAO ; Lyuyuan LIANG ; Yiping WANG ; Chen CHEN ; Weixiao LI ; Bingqi WEI ; Yinli LI ; Yongbin YAN
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(15):227-237
First recorded in an official medical book from the Northern Song Dynasty called Taiping Huimin Heji Ju Fang (Prescriptions of the Bureau of Taiping People's Welfare Pharmacy), Xiaoyaosan has been developed and refined over generations and is preserved to this day. It specializes in soothing the liver,resolving stagnation,fortifying the spleen,and nourishing blood. In this study,ancient traditional Chinese medicine (TCM) books and contemporary studies were reviewed to obtain information on Xiaoyaosan using bibliometrics,including its historical development,dosage,origin,processing methods,decoction dosage,and ancient and modern indications. Furthermore,a question regarding the presence of Zingiberis Rhizoma Recens and Menthae Haplocalycis Herba in Xiaoyaosan was investigated,and a table of key information on Xiaoyaosan was compiled,providing references for developing Xiaoyaosan preparations. According to the weight and measurement system of the Song dynasty,the contemporary equivalent formulation of the decocted Xiaoyaosan consists of 20.65 g of Glycyrrhizae Radix et Rhizoma and 41.3 g of Angelica Sinensis Radix,Poria,Paeoniae Radix Alba,Atractylodis Macrocephalae Rhizoma,and Bupleuri Radix. The formulation is processed to obtain a mixed powder with a particle size of 10 mesh. For each dose,8.25 g of the mixed powder is combined with 1 g of unprocessed Zingiberis Rhizoma Recens and 0.62 g of Menthae Haplocalycis Herba in 300 mL of water. The mixture is decocted until the volume reaches 210 mL,and the residue is then removed,with no specific timing required for administration. After the processing,each dose consists of approximately 0.75 g of Glycyrrhizae Radix et Rhizoma and 1.50 g of Radix Angelica Sinensis,Poria,Paeoniae Radix Alba,Atractylodis Macrocephalae Rhizoma,and Bupleuri Radix. Ancient medical literature shows that Xiaoyaosan primarily treats blood deficiency and overstrain,specifically for symptoms including heat caused by blood deficiency and fatigue,irregular menstruation,headache,eye soreness,pain in the ribs and limbs,and emaciation and bone steaming. In the Qing Dynasty,ZHANG Lu clearly proposed the pathogenesis of liver depression,and since then,the use of Xiaoyaosan in treating various syndromes associated with liver depression has been highly praised by physicians in the Qing dynasty and modern times. Xiaoyaosan has a wide application in modern clinical practices,involving digestive diseases,gynecological diseases,psychological diseases,nervous system diseases,and otorhinolaryngologic diseases. Moreover,it is most commonly used to treat depression and other diseases complicated with depression,hyperplasia of the mammary gland,etc. The key information on Xiaoyaosan and its clinical applications in ancient and modern times investigated in the study could serve as a scientific reference for in-depth research and extended clinical applications of the prescription.
5.Identification and Analysis of MHCⅡ Genes in Wuzhishan Pigs
Yuanyuan LIU ; Wenshui XIN ; Zhe CHAO ; Zongxi CAO ; Yifei CAI ; Qiang LI ; Lingwei LI ; Guangliang LIU
Laboratory Animal and Comparative Medicine 2025;45(3):340-348
ObjectiveTo obtain the gene sequences of major histocompatibility complex (MHC ) Ⅱgenes of Wuzhishan pigs, analyze their genetic information, and explore the biological functions of their MHC system. MethodsSpleen samples were collected from 3 adult male Wuzhishan pigs. Primers were designed according to MHCⅡ gene sequences, and the coding sequences of Wuzhishan pig MHCⅡ genes were amplified by RT-PCR. Sanger sequencing was performed to determine the full-length sequences. Bioinformatics tools were employed to analyze the physicochemical properties, phylogenetic relationships, conserved motifs, structural domains, chromosomal localization, and syntenic relationships of these genes. ResultsEight MHCⅡ genes were identified in Wuzhishan pigs, designated as SLA-DRA, SLA-DQA, SLA-DQB, SLA-DRB, SLA-DOB, SLA-DMB, SLA-DMA and SLA-DOA. The full-length sequences of these genes were determined by Sanger sequencing and subsequently deposited in GenBank under accession numbers PQ182796, PQ182797, PQ182798, PQ182799, PQ182800, PQ182801, PQ182802, and PQ164779. Phylogenetic analysis showed that the six MHCⅡ genes of Wuzhishan pigs clustered separately from their counterparts in Duroc, Meishan, Large White, and Bama pigs, indicating distinct evolutionary trajectories. Bioinformatics analysis demonstrated that most MHC Ⅱ proteins were hydrophobic, with molecular weights ranging from 27 700 to 30 000 Da. Genes within the same subregion shared conserved motifs. Specifically, four MHCⅡ proteins encoded by SLA-DQB, SLA-DRB, SLA-DOB, and SLA-DMB contained the MHCⅡβ conserved domain, while those encoded by the genes SLA-DRA, SLA-DQA, SLA-DMA, and SLA-DOA contained the MHCⅡα conserved domain. The eight MHCⅡ genes were scattered along the long arm of chromosome 7 in the Wuzhishan pigs, exhibiting syntenic relationships with three human genes and five Duroc pig genes. ConclusionThe MHCⅡ genes of Wuzhishan pigs may possess a unique evolutionary origin.
6.Identification and Analysis of MHCⅡ Genes in Wuzhishan Pigs
Yuanyuan LIU ; Wenshui XIN ; Zhe CHAO ; Zongxi CAO ; Yifei CAI ; Qiang LI ; Lingwei LI ; Guangliang LIU
Laboratory Animal and Comparative Medicine 2025;45(3):340-348
ObjectiveTo obtain the gene sequences of major histocompatibility complex (MHC ) Ⅱgenes of Wuzhishan pigs, analyze their genetic information, and explore the biological functions of their MHC system. MethodsSpleen samples were collected from 3 adult male Wuzhishan pigs. Primers were designed according to MHCⅡ gene sequences, and the coding sequences of Wuzhishan pig MHCⅡ genes were amplified by RT-PCR. Sanger sequencing was performed to determine the full-length sequences. Bioinformatics tools were employed to analyze the physicochemical properties, phylogenetic relationships, conserved motifs, structural domains, chromosomal localization, and syntenic relationships of these genes. ResultsEight MHCⅡ genes were identified in Wuzhishan pigs, designated as SLA-DRA, SLA-DQA, SLA-DQB, SLA-DRB, SLA-DOB, SLA-DMB, SLA-DMA and SLA-DOA. The full-length sequences of these genes were determined by Sanger sequencing and subsequently deposited in GenBank under accession numbers PQ182796, PQ182797, PQ182798, PQ182799, PQ182800, PQ182801, PQ182802, and PQ164779. Phylogenetic analysis showed that the six MHCⅡ genes of Wuzhishan pigs clustered separately from their counterparts in Duroc, Meishan, Large White, and Bama pigs, indicating distinct evolutionary trajectories. Bioinformatics analysis demonstrated that most MHC Ⅱ proteins were hydrophobic, with molecular weights ranging from 27 700 to 30 000 Da. Genes within the same subregion shared conserved motifs. Specifically, four MHCⅡ proteins encoded by SLA-DQB, SLA-DRB, SLA-DOB, and SLA-DMB contained the MHCⅡβ conserved domain, while those encoded by the genes SLA-DRA, SLA-DQA, SLA-DMA, and SLA-DOA contained the MHCⅡα conserved domain. The eight MHCⅡ genes were scattered along the long arm of chromosome 7 in the Wuzhishan pigs, exhibiting syntenic relationships with three human genes and five Duroc pig genes. ConclusionThe MHCⅡ genes of Wuzhishan pigs may possess a unique evolutionary origin.
7.Efficacy of robot-assisted versus laparoscopic parenchymal-sparing pancreatectomy in treatment of pancreatic neuroendocrine neoplasm
Guihu WENG ; Zhe CAO ; Yueze LIU ; Taiping ZHANG
Journal of Clinical Hepatology 2025;41(6):1156-1160
ObjectiveTo compare and analyze the clinical application of robot-assisted parenchymal-sparing pancreatectomy (R-PSP) and laparoscopic parenchymal-sparing pancreatectomy (L-PSP) in the treatment of pancreatic neuroendocrine neoplasm (pNEN), and to evaluate the safety and efficacy of the R-PSP procedure. MethodsA retrospective analysis was performed for the clinical data of pNEN patients who underwent parenchymal-sparing pancreatectomy in Department of General Surgery, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, from December 2017 to August 2023, and according to the minimally invasive surgical procedure, they were divided into R-PSP group and L-PSP group. R-PSP and L-PSP were compared in terms of the efficacy of minimally invasive procedure, the outcome of postoperative complications, and oncological efficacy. The independent-samples t test or the Mann-Whitney U test was used for comparison of continuous data between two groups; the chi-square test or the Fisher’s exact test was used for comparison of categorical data between two groups; the Mann-Whitney U test was used for comparison of ranked data between two groups. ResultsA total of 45 pNEN patients were included, with 9 in the R-PSP group and 36 in the L-PSP group, and there were no significant differences in baseline data between the two groups (all P>0.05). There were no significant differences between the two groups in time of operation, intraoperative blood loss, intraoperative blood transfusion, and the rate of conversion to laparotomy (all P>0.05). Compared with the L-PSP group, the R-PSP group had a significantly longer length of postoperative hospital stay [10.00 (9.00 — 15.00) days vs 7.50 (6.00 — 10.00) days, Z=-2.356, P=0.017] and significantly higher hospital costs [86 610.44 (81 905.39 — 114 401.24) yuan vs 38 781.20 (31 708.39 — 50 514.76) yuan, Z=-4.001, P<0.001]. There were no significant differences between the two groups in the incidence rates of serious postoperative complications (Clavien-Dindo grade ≥Ⅲ), clinically relevant pancreatic fistula, delayed gastric emptying, and intra-abdominal infection (all P>0.05). The postoperative 90-day mortality rate was 0% for both groups. ConclusionR-PSP has acceptable safety and efficacy in pNEN patients in clinical practice.
8.Preliminary investigation on a method for determining the cumulative dose of low-energy neutrons independently
Lei DENG ; Faming CAO ; Zhe WANG ; Yu TU ; Ning ZHOU
Chinese Journal of Radiological Health 2025;34(4):578-583
Objective To study a method for determining the cumulative dose of low-energy neutrons ( < 100 keV) independently based on a CR-39 detector. Methods According to the theory of track etching kinetics, the differences in the tracks formed by low-energy neutrons or fast neutrons in a BN + CR-39 detector under broad-spectrum neutron irradiation were analyzed. A method was proposed to identify the tracks produced by low-energy neutrons under specific etching conditions while avoiding interference from fast neutron tracks. Results Experimental results demonstrated that the BN + CR-39 detector using TASTRAK PADC CR-39 track-detecting plastic could independently detect the tracks of low-energy neutrons when etched in a 6.25 mol/L NaOH solution for 1 h. The track density showed a good linear relationship with the ambient dose equivalent of low-energy neutrons, and the calibration coefficient was
9.Correlation analysis between stenosis characteristics and trans-stenotic pressure gradient using a 3D-printed hemodynamic simulation system for cerebral venous sinuses
Jia-Hao ZHANG ; Lei GENG ; Zhi-Tao XIAO ; Xing CHEN ; Zhe JI ; Xiang-Yu CAO
Medical Journal of Chinese People's Liberation Army 2025;50(11):1426-1432
Objective To analyze the relationship between different degrees of cerebral venous sinus stenosis and the trans-stenotic pressure gradient using a 3D-printed hemodynamic simulation system for cerebral venous sinuses.Methods Based on the double elastic cavity model,a complete morphological model of the superior sagittal sinus,transverse sinus,and sigmoid sinuses was constructed using 3D printing technology.An in vitro hemodynamic simulation system incorporating pulsatile blood flow was established to simulate the hemodynamic environment of cerebral venous sinus stenosis.Using this system,both unilateral dominant drainage and bilateral balanced drainage were simulated.The degree of stenosis and the pressure upstream and downstream of the stenosis were measured.The pressure difference and pressure ratio were calculated to analyze the correlation between stenosis degree and the trans-stenotic pressure gradient.Results In the unilateral dominant drainage model,as the stenosis severity increased,the upstream pressure increased,whereas the downstream pressure remained relatively stable,leading to an increased pressure gradient between the two ends.The regression equation for stenosis degree(X)and pressure gradient(pressure difference ΔP)was:YΔP=1.962X-1.417(R=0.867,R2=0.753,P<0.001).In the bilateral balanced drainage model of cerebral venous sinuses,when the stenosis degree on one side of the model increased,the pressure gradient between the two ends changed slightly and eventually reached a stable state.The regression equation between X and ΔP was:YΔP=0.62X+1.047(R=0.98,R2=0.96,P<0.001).Conclusions Stenosis in cerebral venous sinuses with unilateral dominant drainage has a more significant impact on the pressure gradient,while unilateral stenosis in bilateral cerebral venous sinuses with balanced drainage has a smaller impact on the pressure gradient.This result suggests that for bilateral venous sinus stenosis,stent implantation can be prioritized in one side of the cerebral venous sinuses.
10.Clinical value of quantitative artificial intelligence imaging parameters for predicting the benign and malignant nature and the risk of recurrence of lung nodules ≤2 cm
Yujie MA ; Zhe PIAO ; Yuhe YOU ; Wenjun CAO ; Hongsheng XUE ; Zhilong ZHAO
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2025;32(10):1384-1392
Objective To evaluate the value of imaging quantification parameters in artificial intelligence (AI) assisted diagnosis systems in clinical decision-making for lung nodules≤2 cm and the diagnostic efficacy of AI. Methods Lung nodule patients admitted to Affiliated Zhongshan Hospital of Dalian University from 2020 to 2023 were included. Imaging parameters of lung nodules were extracted using AI assisted diagnosis systems. Multifactor analysis was used to screen predictors for distinguishing benign and malignant nodules and high-risk predictors for recurrent invasive adenocarcinoma, and a diagnostic model was established and its performance evaluated. The diagnostic efficacy of the AI system was judged according to pathological results. Results A total of 594 patients with lung nodules were included, including 202 males and 392 females, with an average age of (58.75±11.55) years. Volume, average CT value, and 3D maximum diameter of non-solid nodules were independent predictors of malignant nodules, with thresholds of 287.4 mm3, −491 HU, and 12.0 mm, respectively. The area under the curve (AUC) for diagnostic efficacy was ranked from high to low as combined model (0.802), volume (0.783), average CT value (0.749), and 3D maximum diameter (0.714). The average CT value and 3D long diameter of solid nodules were independent predictors of malignant nodules, with thresholds of −81 HU and 17.5 mm, respectively, and AUC values of 0.874 and 0.686, respectively, with the combined prediction AUC of 0.957. The mass of cystic nodules was an independent predictor of malignancy when the mass>180.7 mg. Independent predictors of high recurrence risk of invasive adenocarcinoma in non-solid nodules were consolidation-tumor ratio (CTR), average CT value, 3D long diameter, and volume, with thresholds of 0.14, −386 HU, 15.6 mm, and 1018.9 mm3, respectively, and diagnostic efficacy was ranked from high to low as combined model (0.788), 3D long diameter (0.735), volume (0.725), average CT value (0.720), and CTR (0.697). The accuracy of AI in predicting benign and malignant target nodules was 87.4%, with positive predictive value of 96.6% and negative predictive value of 58.9%. Conclusion In clinical decision-making for lung nodules ≤2 cm, AI assisted diagnosis systems have high application value.

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