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.

Purpose: Leptin interacts not only with leptin receptor (LEPR) but also engages with other receptors. While the pro-oncogenic effects of the adrenergic receptor β2 (ADRB2) are well-established, the role of leptin in activating ADRB2 in triple-negative breast cancer (TNBC) remains unclear. Materials and Methods: The pro-carcinogenic effects of LEPR were investigated using murine TNBC cell lines, 4T1 and EMT6, and a tumor-bearing mouse model. Expression levels of LEPR, NADPH oxidase 4 (NOX4), and ADRB2 in TNBC cells and tumor tissues were analyzed via western blot and quantitative real-time polymerase chain reaction. Changes in reactive oxygen species (ROS) levels were assessed using flow cytometry and MitoSox staining, while immunofluorescence double-staining confirmed the co-localization of LEPR and ADRB2. Results: LEPR activation promoted NOX4-derived ROS and mitochondrial ROS production, facilitating TNBC cell proliferation and migration, effects which were mitigated by the LEPR inhibitor Allo-aca. Co-expression of LEPR and ADRB2 was observed on cell membranes, and bioinformatics data revealed a positive correlation between the two receptors. Leptin activated both LEPR and ADRB2, enhancing intracellular ROS generation and promoting tumor progression, which was effectively countered by a specific ADRB2 inhibitor ICI118551. In vivo, leptin injection accelerated tumor growth and lung metastases without affecting appetite, while treatments with Allo-aca or ICI118551 mitigated these effects. Conclusion This study demonstrates that leptin stimulates the growth and metastasis of TNBC through the activation of both LEPR and ADRB2, resulting in increased ROS production. These findings highlight LEPR and ADRB2 as potential biomarkers and therapeutic targets in TNBC.

Purpose: Leptin interacts not only with leptin receptor (LEPR) but also engages with other receptors. While the pro-oncogenic effects of the adrenergic receptor β2 (ADRB2) are well-established, the role of leptin in activating ADRB2 in triple-negative breast cancer (TNBC) remains unclear. Materials and Methods: The pro-carcinogenic effects of LEPR were investigated using murine TNBC cell lines, 4T1 and EMT6, and a tumor-bearing mouse model. Expression levels of LEPR, NADPH oxidase 4 (NOX4), and ADRB2 in TNBC cells and tumor tissues were analyzed via western blot and quantitative real-time polymerase chain reaction. Changes in reactive oxygen species (ROS) levels were assessed using flow cytometry and MitoSox staining, while immunofluorescence double-staining confirmed the co-localization of LEPR and ADRB2. Results: LEPR activation promoted NOX4-derived ROS and mitochondrial ROS production, facilitating TNBC cell proliferation and migration, effects which were mitigated by the LEPR inhibitor Allo-aca. Co-expression of LEPR and ADRB2 was observed on cell membranes, and bioinformatics data revealed a positive correlation between the two receptors. Leptin activated both LEPR and ADRB2, enhancing intracellular ROS generation and promoting tumor progression, which was effectively countered by a specific ADRB2 inhibitor ICI118551. In vivo, leptin injection accelerated tumor growth and lung metastases without affecting appetite, while treatments with Allo-aca or ICI118551 mitigated these effects. Conclusion This study demonstrates that leptin stimulates the growth and metastasis of TNBC through the activation of both LEPR and ADRB2, resulting in increased ROS production. These findings highlight LEPR and ADRB2 as potential biomarkers and therapeutic targets in TNBC.

Purpose: Leptin interacts not only with leptin receptor (LEPR) but also engages with other receptors. While the pro-oncogenic effects of the adrenergic receptor β2 (ADRB2) are well-established, the role of leptin in activating ADRB2 in triple-negative breast cancer (TNBC) remains unclear. Materials and Methods: The pro-carcinogenic effects of LEPR were investigated using murine TNBC cell lines, 4T1 and EMT6, and a tumor-bearing mouse model. Expression levels of LEPR, NADPH oxidase 4 (NOX4), and ADRB2 in TNBC cells and tumor tissues were analyzed via western blot and quantitative real-time polymerase chain reaction. Changes in reactive oxygen species (ROS) levels were assessed using flow cytometry and MitoSox staining, while immunofluorescence double-staining confirmed the co-localization of LEPR and ADRB2. Results: LEPR activation promoted NOX4-derived ROS and mitochondrial ROS production, facilitating TNBC cell proliferation and migration, effects which were mitigated by the LEPR inhibitor Allo-aca. Co-expression of LEPR and ADRB2 was observed on cell membranes, and bioinformatics data revealed a positive correlation between the two receptors. Leptin activated both LEPR and ADRB2, enhancing intracellular ROS generation and promoting tumor progression, which was effectively countered by a specific ADRB2 inhibitor ICI118551. In vivo, leptin injection accelerated tumor growth and lung metastases without affecting appetite, while treatments with Allo-aca or ICI118551 mitigated these effects. Conclusion This study demonstrates that leptin stimulates the growth and metastasis of TNBC through the activation of both LEPR and ADRB2, resulting in increased ROS production. These findings highlight LEPR and ADRB2 as potential biomarkers and therapeutic targets in TNBC.

Objective:To evaluate the long-term protective efficacy of the recombinant Chinese hamster ovary cell-derived hepatitis B vaccine（CHO-HepB）26 years post-vaccination in the rural China.Methods:Zhengding county，Hebei province was designated as a rural monitoring site for CHO-HepB efficacy. Study participants included individuals born between 1997 and 1999 who had completed the three-dose CHO-HepB primary series without booster doses. A cross-sectional survey was conducted in late 2024 using random sampling. Demographic and vaccination history data were collected via questionnaires，and hepatitis B virus（HBV）serological markers were detected using chemiluminescence. Historical surveillance data were integrated to infer infection statuses of HBsAg-positive individuals and evaluate longitudinal trends in anti-HBs seropositivity and antibody titers.Results:Among 178 participants（mean time since vaccination：26.2 years），the seroprevalence rates were 0.6% for HBsAg（95% CI：0.0%-1.6%），64.6% for anti-HBs（95% CI：57.6%-71.6%），and 1.1% for anti-HBc（95% CI：0.0%-2.7%）. Compared to the pre-vaccination baseline HBsAg positivity of 11.3% in children under 10 years of age，the estimated vaccine protection rate was 95%. Two notable cases were identified：one with concurrent HBsAg and anti-HBc positivity and one with anti-HBs and anti-HBc positivity，suggestive of transient HBV exposure（1999—2009）without chronicity. Natural immune boosting was inferred for the latter case based on anti-HBs titer dynamics. Longitudinal analysis of four prior cross-sectional surveys（2005，2009，2013，and 2017）revealed no significant upward trends in HBsAg and anti-HBc positivity（both P>0.05）over 26 years，while anti-HBs seropositivity declined significantly（ P<0.05）from 6 to 26 years post-vaccination. Conclusion:The CHO-HepB vaccine demonstrates sustained immunological persistence and robust long-term protection up to 26 years post-immunization. Continued emphasis on rigorous implementation of mother-to-child transmission prevention strategies is critical for future hepatitis B control.

Objective:To evaluate the long-term protective efficacy of the recombinant Chinese hamster ovary cell-derived hepatitis B vaccine（CHO-HepB）26 years post-vaccination in the rural China.Methods:Zhengding county，Hebei province was designated as a rural monitoring site for CHO-HepB efficacy. Study participants included individuals born between 1997 and 1999 who had completed the three-dose CHO-HepB primary series without booster doses. A cross-sectional survey was conducted in late 2024 using random sampling. Demographic and vaccination history data were collected via questionnaires，and hepatitis B virus（HBV）serological markers were detected using chemiluminescence. Historical surveillance data were integrated to infer infection statuses of HBsAg-positive individuals and evaluate longitudinal trends in anti-HBs seropositivity and antibody titers.Results:Among 178 participants（mean time since vaccination：26.2 years），the seroprevalence rates were 0.6% for HBsAg（95% CI：0.0%-1.6%），64.6% for anti-HBs（95% CI：57.6%-71.6%），and 1.1% for anti-HBc（95% CI：0.0%-2.7%）. Compared to the pre-vaccination baseline HBsAg positivity of 11.3% in children under 10 years of age，the estimated vaccine protection rate was 95%. Two notable cases were identified：one with concurrent HBsAg and anti-HBc positivity and one with anti-HBs and anti-HBc positivity，suggestive of transient HBV exposure（1999—2009）without chronicity. Natural immune boosting was inferred for the latter case based on anti-HBs titer dynamics. Longitudinal analysis of four prior cross-sectional surveys（2005，2009，2013，and 2017）revealed no significant upward trends in HBsAg and anti-HBc positivity（both P>0.05）over 26 years，while anti-HBs seropositivity declined significantly（ P<0.05）from 6 to 26 years post-vaccination. Conclusion:The CHO-HepB vaccine demonstrates sustained immunological persistence and robust long-term protection up to 26 years post-immunization. Continued emphasis on rigorous implementation of mother-to-child transmission prevention strategies is critical for future hepatitis B control.

Objective:To quantitatively detect plasma ceramide (Cer) levels using high-performance liquid chromatography tandem mass spectrometry (LC-MS/MS) and analyze plasma ceramide levels in homozygous familial hypercholesterolemia (HoFH) patients.Methods:A case-control study was conducted. Plasma samples were collected from 70 healthy individuals who underwent physical examinations at the Health Check-Up Center of Suzhou Municipal Hospital between October 2023 and December 2023, as well as from 34 HoFH patients (including 11 patients with concomitant coronary artery disease) who were treated in the Cardiology Department of the same hospital during the same period. Deuterated isotopes were used as internal standards, and a Phenomenex Kinetex C18 column (2.1×100 mm, 2.6 μm) was employed for separation. An LC-MS/MS method was developed using an AB Sciex 6500+triple quadrupole mass spectrometer for the detection of ceramides, followed by method validation. Additionally, the differences in ceramide levels among healthy individuals, HoFH patients, and HoFH patients with concomitant coronary artery disease were compared. Receiver operating characteristic (ROC) curves were used to evaluate the diagnostic value of various ceramides for HoFH.Results:A method for the quantification of 9 plasma ceramides was established, showing excellent linearity ( r>0.99), precision (1.8%-11.0%), and recovery rates (89.9%-114.7%), meeting the requirements for detection. Compared to the control group, the HoFH group exhibited significantly higher levels of Cer(d18∶1/14∶0), Cer(d18∶1/16∶0), Cer (d18∶1/18∶0), Cer (d18∶1/18∶1), Cer (d18∶1/20∶0), Cer(d18∶1/22∶0), Cer(d18∶1/24∶0), and Cer(d18∶1/24∶1) ( P<0.05). ROC curve analysis revealed that Cer(d18∶1/18∶0) had the highest diagnostic value for HoFH, with an area under the curve (AUC) of 0.83, a cutoff value of 64.6 ng/ml, and sensitivity and specificity of 82.4% and 87.1%, respectively. In HoFH patients complicated with coronary artery disease, the plasma ceramide levels of Cer(d18∶1/18∶0) [(155.7±25.1) ng/ml vs (103.0±11.1) ng/ml, P=0.03] and the ratio of Cer (d18∶1/18∶0) to Cer(d18∶1/24∶0) (0.077±0.012 vs 0.048±0.006, P=0.03) were significantly higher than in HoFH patients without coronary artery disease. Conclusion:A quantitative LC-MS/MS method was developed for detecting ceramides in human plasma, which shows potential diagnostic value for patients with HoFH.

Objective:To quantitatively detect plasma ceramide (Cer) levels using high-performance liquid chromatography tandem mass spectrometry (LC-MS/MS) and analyze plasma ceramide levels in homozygous familial hypercholesterolemia (HoFH) patients.Methods:A case-control study was conducted. Plasma samples were collected from 70 healthy individuals who underwent physical examinations at the Health Check-Up Center of Suzhou Municipal Hospital between October 2023 and December 2023, as well as from 34 HoFH patients (including 11 patients with concomitant coronary artery disease) who were treated in the Cardiology Department of the same hospital during the same period. Deuterated isotopes were used as internal standards, and a Phenomenex Kinetex C18 column (2.1×100 mm, 2.6 μm) was employed for separation. An LC-MS/MS method was developed using an AB Sciex 6500+triple quadrupole mass spectrometer for the detection of ceramides, followed by method validation. Additionally, the differences in ceramide levels among healthy individuals, HoFH patients, and HoFH patients with concomitant coronary artery disease were compared. Receiver operating characteristic (ROC) curves were used to evaluate the diagnostic value of various ceramides for HoFH.Results:A method for the quantification of 9 plasma ceramides was established, showing excellent linearity ( r>0.99), precision (1.8%-11.0%), and recovery rates (89.9%-114.7%), meeting the requirements for detection. Compared to the control group, the HoFH group exhibited significantly higher levels of Cer(d18∶1/14∶0), Cer(d18∶1/16∶0), Cer (d18∶1/18∶0), Cer (d18∶1/18∶1), Cer (d18∶1/20∶0), Cer(d18∶1/22∶0), Cer(d18∶1/24∶0), and Cer(d18∶1/24∶1) ( P<0.05). ROC curve analysis revealed that Cer(d18∶1/18∶0) had the highest diagnostic value for HoFH, with an area under the curve (AUC) of 0.83, a cutoff value of 64.6 ng/ml, and sensitivity and specificity of 82.4% and 87.1%, respectively. In HoFH patients complicated with coronary artery disease, the plasma ceramide levels of Cer(d18∶1/18∶0) [(155.7±25.1) ng/ml vs (103.0±11.1) ng/ml, P=0.03] and the ratio of Cer (d18∶1/18∶0) to Cer(d18∶1/24∶0) (0.077±0.012 vs 0.048±0.006, P=0.03) were significantly higher than in HoFH patients without coronary artery disease. Conclusion:A quantitative LC-MS/MS method was developed for detecting ceramides in human plasma, which shows potential diagnostic value for patients with HoFH.

Radiotherapy is one of the important treatment modalities for malignant tumors. Conventional fractionation is the most commonly-used radiotherapy mode, but it has disadvantages such as long treatment time and low efficiency, etc. With the advancement of radiotherapy equipment and technology, moderately hypofractionated radiotherapy has become the standard treatment for tumors such as breast cancer and prostate cancer, etc. However, the efficacy and safety of moderately hypofractionated radiotherapy have not been fully confirmed in a wider range of tumors. In this article, the application, efficacy, and safety of moderately hypofractionated radiotherapy in malignant tumors were reviewed.