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.

Cancer has become a significant global public health issue， severely impacting public health and societal development. Despite advances in tumor treatment methods in recent years and a gradual decline in cancer mortality rates， drug-related adverse reactions and drug resistance remain substantial challenges. Traditional Chinese medicine （TCM） has demonstrated significant clinical efficacy in cancer treatment and small side effects， making it widely applied in the field of oncology. Xuefu Zhuyutang， derived from Yilin Gaicuo， is known for its abilities to invigorate blood circulation， dispel blood stasis， promote Qi flow， and alleviate pain. It was specifically formulated by the esteemed WANG Qingren of the Qing dynasty for the "blood stasis syndrome in the blood mansion" and is commonly used to treat Qi stagnation and blood stasis syndrome. Clinical studies have shown that Xuefu Zhuyutang， when combined with conventional Western medications， produces significant effects in the treatment of malignant tumors such as liver cancer， lung cancer， and cervical cancer. It substantially reduces the incidence of adverse reactions following Western treatments， including radiation esophagitis， radiation encephalopathy， radiation-induced oral mucositis， and edema. Additionally， it alleviates cancer-related pain and fever， blood hypercoagulability， and associated complications such as depression and anxiety， and also mitigates chemotherapy-induced side effects like hand-foot syndrome. Basic research has demonstrated its potential anti-tumor mechanisms， including the inhibition of Wnt/β-catenin signaling pathway activation， suppression of mitogen-activated protein kinase （MAPK） pathway activation， and anti-tumor angiogenesis. Pharmacological studies have revealed that its active components inhibit tumor cell proliferation and migration， induce tumor cell apoptosis， suppress tumor angiogenesis， enhance the cytotoxicity of natural killer cells against tumors， improve the tumor microenvironment， and regulate immune function. This paper reviewed the latest research progress on Xuefu Zhuyutang in the treatment of malignant tumors from four aspects： theoretical exploration， clinical studies， mechanisms of action， and pharmacological basis， aiming to provide insights and methods for the clinical diagnosis and treatment of malignant tumors.

Cancer has become a significant global public health issue， severely impacting public health and societal development. Despite advances in tumor treatment methods in recent years and a gradual decline in cancer mortality rates， drug-related adverse reactions and drug resistance remain substantial challenges. Traditional Chinese medicine （TCM） has demonstrated significant clinical efficacy in cancer treatment and small side effects， making it widely applied in the field of oncology. Xuefu Zhuyutang， derived from Yilin Gaicuo， is known for its abilities to invigorate blood circulation， dispel blood stasis， promote Qi flow， and alleviate pain. It was specifically formulated by the esteemed WANG Qingren of the Qing dynasty for the "blood stasis syndrome in the blood mansion" and is commonly used to treat Qi stagnation and blood stasis syndrome. Clinical studies have shown that Xuefu Zhuyutang， when combined with conventional Western medications， produces significant effects in the treatment of malignant tumors such as liver cancer， lung cancer， and cervical cancer. It substantially reduces the incidence of adverse reactions following Western treatments， including radiation esophagitis， radiation encephalopathy， radiation-induced oral mucositis， and edema. Additionally， it alleviates cancer-related pain and fever， blood hypercoagulability， and associated complications such as depression and anxiety， and also mitigates chemotherapy-induced side effects like hand-foot syndrome. Basic research has demonstrated its potential anti-tumor mechanisms， including the inhibition of Wnt/β-catenin signaling pathway activation， suppression of mitogen-activated protein kinase （MAPK） pathway activation， and anti-tumor angiogenesis. Pharmacological studies have revealed that its active components inhibit tumor cell proliferation and migration， induce tumor cell apoptosis， suppress tumor angiogenesis， enhance the cytotoxicity of natural killer cells against tumors， improve the tumor microenvironment， and regulate immune function. This paper reviewed the latest research progress on Xuefu Zhuyutang in the treatment of malignant tumors from four aspects： theoretical exploration， clinical studies， mechanisms of action， and pharmacological basis， aiming to provide insights and methods for the clinical diagnosis and treatment of malignant tumors.

Digestive system tumors are the leading cause of cancer incidence and mortality globally， and their occurrence and development generally follow the key pathological process of inflammation-cancer transformation. Therefore， intervening in the precancerous lesion stage is an important strategy to block malignant transformation of the disease and reduce the incidence rate of tumors. Banxia Xiexin Tang-related prescriptions （including Banxia Xiexin Tang， Shengjiang Xiexin Tang， and Gancao Xiexin Tang） originated from the Shanghan Zabinglun They follow the principle of pungent dispersing and bitter descending， combination of cold and warm medicinals， and tonifying deficiency and purging excess， which aligns with the core pathogenesis of digestive system precancerous lesions characterized by cold-heat intermingling and disorder of ascending and descending. These prescriptions are widely used in the clinical treatment of various digestive system inflammatory disorders such as atrophic gastritis， ulcerative colitis， and reflux esophagitis. This review systematically summarizes the theoretical basis， clinical evidence， and therapeutic mechanisms of such prescriptions in preventing and treating the inflammation-cancer transformation process in the digestive system. Clinical studies have shown that whether used alone or in combination with modern therapies， Banxia Xiexin Tang can effectively alleviate symptoms， repair histopathological changes， and improve patients' quality of life. Basic research further reveals that their efficacy stems from multi-target systemic regulatory effects： ameliorating the chronic inflammatory microenvironment， antagonizing oxidative stress， reshaping the gut microbiota， restoring the immune balance， regulating cell proliferation and apoptosis， etc. On the basis of the convergence of traditional Chinese and Western medicine understanding of inflammation-cancer transformation， this article constructs a research framework centered on regulating the inflammatory microenvironment homeostasis to systematically elucidate the mechanism of treating different diseases with the same method （Banxia Xiexin Tang）. In view of the limitations of current research in terms of evidence level， disease-syndrome combination models， and overall mechanism analysis of compound prescriptions， this article proposes future research directions of integrating high-quality clinical research， systems biology， and cutting-edge technologies， providing a new theoretical basis and translational ideas for the precise prevention and control of digestive system tumors with traditional Chinese medicine.

Objective To investigate the relationship between cerebrospinal fluid(CSF)colony stimulating factor 1 receptor(CSF1R)and CSF biomarkers of Alzheimer disease(AD),and to analyze whether CSF1R is associated with mild cognitive impairment patients'cognition.Methods Data from non-demented adults were collected from the Alzheimer Disease Neuroimaging Initiative database,and participants were divided into four groups(A-/TN-,A+/TN-,A+/TN+and A-/TN+),according to the NIA-AA criteria,and the dynamic changes of CSF1R in CSF at different pathological stages of AD were tracked.Multiple linear regression models were used to analyze the relationship between CSF1R and AD biomarkers and cognition,and mediation models were used to investigate the potential association between CSF1R and AD pathology.Results A total of 451 non-demented adults were enrolled in this study,and we found that CSF CSF1R levels were increased in the A-/TN+group(P<0.05)and the A+/TN+group(P<0.05)compared with the A+/TN-group.CSF CSF1R levels were significantly and positively correlated with CSF tau protein(P<0.001)and phosphorylated tau protein(P<0.001)levels but not with amyloid β-protein(P=0.123),and similar results were obtained in the cognitively normal and mild cognitive impairment groups.In the mild cognitive impairment group,higher CSF CSF1R levels were associated with lower cognitive(P<0.05)levels.Furthermore,the relationship between CSF1R and AD pathology was mediated in part by soluble triggering receptor expressed on myeloid cells 2(sTREM2)(percentage:19.3%to 31.4%).Conclusions This study is the first study to discover the association of CSFIR with AD biomarkers and cognition,and CSF1R may influence AD pathology through soluble TREM2(sTREM2).

Objective To investigate the relationship between cerebrospinal fluid(CSF)colony stimulating factor 1 receptor(CSF1R)and CSF biomarkers of Alzheimer disease(AD),and to analyze whether CSF1R is associated with mild cognitive impairment patients'cognition.Methods Data from non-demented adults were collected from the Alzheimer Disease Neuroimaging Initiative database,and participants were divided into four groups(A-/TN-,A+/TN-,A+/TN+and A-/TN+),according to the NIA-AA criteria,and the dynamic changes of CSF1R in CSF at different pathological stages of AD were tracked.Multiple linear regression models were used to analyze the relationship between CSF1R and AD biomarkers and cognition,and mediation models were used to investigate the potential association between CSF1R and AD pathology.Results A total of 451 non-demented adults were enrolled in this study,and we found that CSF CSF1R levels were increased in the A-/TN+group(P<0.05)and the A+/TN+group(P<0.05)compared with the A+/TN-group.CSF CSF1R levels were significantly and positively correlated with CSF tau protein(P<0.001)and phosphorylated tau protein(P<0.001)levels but not with amyloid β-protein(P=0.123),and similar results were obtained in the cognitively normal and mild cognitive impairment groups.In the mild cognitive impairment group,higher CSF CSF1R levels were associated with lower cognitive(P<0.05)levels.Furthermore,the relationship between CSF1R and AD pathology was mediated in part by soluble triggering receptor expressed on myeloid cells 2(sTREM2)(percentage:19.3%to 31.4%).Conclusions This study is the first study to discover the association of CSFIR with AD biomarkers and cognition,and CSF1R may influence AD pathology through soluble TREM2(sTREM2).

Objective: This study aims to elucidate the role of aryl hydrocarbon receptor nuclear transporter 2 (ARNT2) in cervical cancer (CC) and explore the potential mechanism by which ARNT2 promotes the progression of CC through the protein phosphatase 2A (PP2A)/Akt signaling pathway. Methods: Bioinformatics tools were used to analyze the expression level of ARNT2 in cancer and its correlation with cancer prognosis. Western Blot and immunohistochemistry staining were used to detect the expression of ARNT2 protein in CC tissues and cells. ARNT2 was knocked down in SiHa and HeLa cells, respectively. Cell Counting Kit-8 assay and colony formation assay were used to detect changes in cell proliferation. Transwell assay and plate scratch assay were used to detect changes in cell migration and invasion. Western Blot assay was used to detect changes in the expression of PP2A/Akt signaling pathway after ARNT2 expression was downregulated. Finally, a CC xenograft tumor model was constructed to evaluate the effect of ARNT2 on SiHa cell tumorigenesis in vivo. Results: ARNT2 is highly expressed in tumor tissues and cell lines. ARNT2 knockdown can significantly inhibit the proliferation, invasion and migration of SiHa and HeLa cells in vitro and in xenograft models. Further studies have shown that ARNT2 may promote tumor formation by regulating the PP2A/Akt pathway. Conclusion ARNT2 promotes the malignant biological behavior of CC cells through the PP2A/Akt signaling pathway, confirming its potential as a prognostic marker for CC.

Objective To investigate the effects of circ_UBE2C on the proliferation and glycolysis of lung cancer cells and its mechanism of action.Methods The expression of circ_UBE2C,miR-107,and hexokinase 2(HK2)in lung cancer tissues and normal lung tissues were analyzed based on the The Cancer Genome Atlas(TCGA)database.Kaplan-Meier survival curve was plotted to analyze the correlation between circ_UBE2C/miR-107/HK2 expression and survival of the lung cancer patients.qRT-PCR was used to detect the expression of circ_UBE2C and miR-107,and Western blotting was employed to measure the expression of HK2 and PCNA in human normal lung epithelial cells(BEAS-2B)and human lung cancer cell lines(A549,NCI-H460,and NCI-H1299).Then A549 and NCI-H1299 cells were divided into the blank group(NC),circ_UBE2C knockdown group(si-circ),HK2 knockdown group(si-HK2),simultaneous knockdown of miR-107+HK2 group(miR-inhibitor+si-HK2),and simultaneous knockdown of circ_UBE2C+miR-107 group(si-circ+miR-inhibitor).CCK-8 assay and colony formation assay were employed to measure the proliferation of above cell groups.The glucose uptake,lactate generation,and ATP production in the cells were measured by glucose uptake colorimetric assay kit,lactic acid detection kit,and ATP content determination kit,respectively.Seahorse XF glycolytic stress test and Seahorse XF cellular mitochondrial stress test were respectively performed to detect the extracellular acidification ratio(ECAR)and cellular oxygen consumption ratio(OCR).The targeting relationship between the circ_UBE2C and miR-107,and miR-107 and HK2 was validated by dual-luciferase reporter gene assay.Results Compared with normal lung tissues,the expression of circ_UBE2C and HK2 was up-regulated,while that of miR-107 was down-regulated in lung cancer tissues(P＜0.05).The expression of circ_UBE2C and HK2 was elevated,and that of miR-107 was reduced in A549 and NCI-H1299 cells when compared with BEAS-2B cells(P＜0.05).Survival analysis showed that the patients with high expression of circ_UBE2C and HK2 or low expression of miR-107 had shorter survival(P＜0.05).Compared with the NC group,both si-circ and si-HK2 resulted in significantly reduced proliferation,glucose uptake,lactate generation,ATP production,and ECAR and OCR values in A549 and NCI-H1299 cells(P＜0.05).Dual luciferase reporter gene assay confirmed that circ_UBE2C could directly bind to and negatively regulate miR-107 expression.HK2 was then identified as a downstream target of miR-107.Compared with the si-HK2 group,the proliferative ability and glycolysis level of A549 and NCI-H1299 cells were significantly increased in the miR-inhibitor+si-HK2 group and the si-circ+miR-inhibitor group.Conclusion Knockdown of circ_UBE2C significantly suppresses the proliferation and glycolysis of lung cancer cells via targeting up-regulation of miR-107 and then exerting inhibitory effect on HK2 expression.

Objective:To compare the effects of different test meals on postprandial triglycerides and to optimize the standard meal composition and the blood sampling protocol for the oral fat tolerance test.Methods:This study is a prospective, open-label, randomized, cross-over trial. In March 2023, 36 volunteers were recruited in Hebei General Hospital. They underwent a health examination and oral glucose tolerance test. Twenty-six healthy volunteers(11 males and 15 females) were included in this study, with an average age of(39.08±4.56) years. Each volunteer received 75 g protein meal, 75 g fat meal, 700 kcal fixed-calorie high-fat mixed meal, and a high-fat mixed meal with energy adjusted based on 10 kcal/kg body weight. A one-week washout period of regular diet was applied before each trial. Blood was collected at fasting status and 1, 2, 3, 4, 5, and 6 hours after a meal to detect serum triglycerides, total cholesterol, low density lipoprotein-cholesterol(LDL-C), high density lipoprotein-cholesterol(HDL-C), glucose, and insulin. The variations of postprandial metabolic indicators over time following the consumption of different test meals were analyzed. The disparities in postprandial metabolic responses between the two types of mixed meals were compared.Results:The protein meal, fat meal, fixed-calorie high-fat mixed meal, and adjusted-calorie high-fat mixed meal resulted in postprandial triglyceride increases of 22.45%, 115.40%, 77.14%, and 63.63%, and insulin increase of 560.43%, 85.69%, 554.18%, and 598.97%, respectively, and with reductions in total cholesterol, LDL-C, and HDL-C ranging from 5.64%-21.81%, respectively. The blood glucose changed slightly. Changes in metabolic indicators mainly occured within 4 hours. The comparison of the characteristics of postprandial triglycerides between the two high-fat mixed meals showed no statistically significant differences( P>0.05). Conclusion:A standardize protocol with a 700 kcal fixed-calorie high-fat mixed meal as test meal, and blood lipid levels measured at fasting and at 1, 2, 3, and 4 hours after consumption, can serve as an optimized approach for oral fat tolerance test.