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.

Objective:To evaluate the effect of short-chain fatty acid(SCFA) on perioperative cognitive dysfunction in aged rats through mitogen-activated protein kinase p38(p38 MAPK)/nuclear factor-κB p65(NF-κB p65) pathway.Methods:According to random number table method, 32 healthy SPF-grade male SD rats, aged 16 months and weighing 520~620 g, were divided into control group, short-chain fatty acid group (SCFA group), perioperative cognitive dysfunction group (PCD group) and perioperative cognitive dysfunction+ short-chain fatty acid group (SCFA+ PCD group), with 8 rats in each group. The perioperative cognitive dysfunction model was established by sevoflurane anesthesia plus internal fixation of tibial fractures. Rats in SCFA group and SCFA+ PCD group freely drank water added with SCFA for 28 days. On the 29th day, rats in SCFA+ FCD group underwent tibial fracture internal fixation surgery. Morris water maze test was performed on the 7th day after surgery to evaluate the cognitive function of rats. The Nissl bodies of hippocampus were observed by Nissl's staining. The hippocampus tissue was collected to analyze the expressions of interleukin-1β (IL-1β), interleukin-6 (IL-6), p38 MAPK, phosphorylated p38 MAPK, NF-κB p65 and phosphorylated NF-κB p65 by Western blot.The SPSS 27.0 software was used for statistical analysis. One-way ANOVA was used for comparison among multiple groups, and LSD- t test was used for further pairwise comparison. Results:(1) The results of Morris water maze test showed that the times of crossing the original platform, the escape latency and the residence time in the original platform quadrant were statistically significant among the four groups on the 7th day after surgery ( F=13.80, 47.80, 6.46, all P<0.05). The escape latencies of the SCFA+ PCD group and PCD group were both longer than that in the control group (both P<0.05). The times of crossing the original platform in SCFA+ PCD group and PCD group were less than that of control group (both P<0.05). The residence time in the original platform quadrant in SCFA+ PCD group and PCD group was shorter than that of control group (both P<0.05).Compared with PCD group, the escape latency was shorter, the times of crossing the original platform were more and the residence time in the original platform quadrant was longer in SCFA+ PCD group (all P<0.05). (2) The expression levels of IL-1β, IL-6, phosphorylated p38 MAPK and phosphorylated NF-κB p65 were statistically significant among the four groups ( F=184.28, 139.27, 19.40, 58.47, all P<0.05). The expression levels of IL-1β, IL-6, phosphorylated p38 MAPK and phosphorylated NF-κB p65 were higher in SCFA+ PCD group (0.49±0.10, 0.60±0.05, 0.489±0.012, 0.435±0.005) and PCD group (0.85±0.05, 1.12±0.08, 0.519±0.028, 0.473±0.008) than those in control group (0.13±0.02, 0.42±0.10, 0.437±0.010, 0.362±0.013)(all P<0.05). The expression levels of IL-1β, IL-6, phosphorylated p38 MAPK and phosphorylated NF-κB p65 were lower in SCFA+ PCD group than PCD group (all P<0.05). (3) The average gray value of Nissl bodies was statistically significant different among the four groups ( F=14.65, P<0.05). The average gray value of Nissl bodies was lower in SCFA+ PCD group (193.2±8.1) and PCD group (160.5±14.1) than that of control group (221.2±14.8) (both P<0.05). The average gray value of Nissl bodies was higher in SCFA+ PCD group than that in PCD group( P<0.05). Conclusion:Short-chain fatty acid attenuates cognitive dysfunction, which may be related with inhibiting p38 MAPK/NF-κB p65 pathway and reducing the neuroinflammation.

Objective:To explore the association of blood and urinary cadmium levels with lipid profile levels and dyslipidemia in Chinese adults aged 18 to 79 years.Methods:Based on the China National Human Biomonitoring (CNHBM) program, a cross-sectional survey was conducted from 2017 to 2018 using a multi-stage stratified random sampling method, including a total of 10 713 adults aged 18 to 79 years. Data was obtained through questionnaires, physical examinations, biological sample collection, and laboratory testing. Multiple linear mixed effect model (MLMM) and generalized linear mixed effect model (GLMM) were used to analyze the association of blood and creatinine-corrected urinary cadmium levels with lipid profile levels as well as dyslipidemia among adults.Results:The age of 10 713 participants was (47.23±0.24) years, with 5 372 males accounting for 61.3% of the national population. The weighted mean±standard error (SE) of total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) was (5.21±0.03), (1.86±0.03), (2.96±0.03), and (1.43±0.01) mmol/L, respectively. The prevalence rate of hypercholesterolemia, hypertriglyceridemia, mixed hyperlipidemia, low HDL-C, and high LDL-C was 16.0%, 21.6%, 6.6%, 13.5%, and 10.0%, respectively. MLMM showed that, after adjusting for relevant confounders, log-transformed blood cadmium levels were positively associated with increased levels of TC, TG and LDL-C ( P<0.05). When blood cadmium levels were categorized into quartiles, compared to the lowest exposure group ( Q1), participants in the highest blood cadmium exposure group ( Q4) had increases of 0.19 (95% CI: 0.06, 0.32) mmol/L in TC and 0.25 (95% CI: 0.08, 0.43) mmol/L in TG. GLMM indicated that, after adjusting for confounders, higher blood cadmium exposure levels were associated with increased risks of hypercholesterolemia, hypertriglyceridemia, mixed hyperlipidemia, and high LDL-C ( P<0.05). Further analysis by quartiles showed that, compared to the blood cadmium Q1 exposure group, the OR value (95% CI) for the Q4 group was 1.53 (1.12, 2.08) for hypercholesterolemia, 1.54 (1.09, 2.17) for hypertriglyceridemia, 2.24 (1.47, 3.40) for mixed hyperlipidemia, and 1.49 (1.07, 2.09) for high LDL-C. Conclusion:The cadmium internal exposure levels are associated with blood lipid profile levels as well as the incidence of dyslipidemia in Chinese adults aged 18 to 79.

Objective:To evaluate the effect of short-chain fatty acid(SCFA) on perioperative cognitive dysfunction in aged rats through mitogen-activated protein kinase p38(p38 MAPK)/nuclear factor-κB p65(NF-κB p65) pathway.Methods:According to random number table method, 32 healthy SPF-grade male SD rats, aged 16 months and weighing 520~620 g, were divided into control group, short-chain fatty acid group (SCFA group), perioperative cognitive dysfunction group (PCD group) and perioperative cognitive dysfunction+ short-chain fatty acid group (SCFA+ PCD group), with 8 rats in each group. The perioperative cognitive dysfunction model was established by sevoflurane anesthesia plus internal fixation of tibial fractures. Rats in SCFA group and SCFA+ PCD group freely drank water added with SCFA for 28 days. On the 29th day, rats in SCFA+ FCD group underwent tibial fracture internal fixation surgery. Morris water maze test was performed on the 7th day after surgery to evaluate the cognitive function of rats. The Nissl bodies of hippocampus were observed by Nissl's staining. The hippocampus tissue was collected to analyze the expressions of interleukin-1β (IL-1β), interleukin-6 (IL-6), p38 MAPK, phosphorylated p38 MAPK, NF-κB p65 and phosphorylated NF-κB p65 by Western blot.The SPSS 27.0 software was used for statistical analysis. One-way ANOVA was used for comparison among multiple groups, and LSD- t test was used for further pairwise comparison. Results:(1) The results of Morris water maze test showed that the times of crossing the original platform, the escape latency and the residence time in the original platform quadrant were statistically significant among the four groups on the 7th day after surgery ( F=13.80, 47.80, 6.46, all P<0.05). The escape latencies of the SCFA+ PCD group and PCD group were both longer than that in the control group (both P<0.05). The times of crossing the original platform in SCFA+ PCD group and PCD group were less than that of control group (both P<0.05). The residence time in the original platform quadrant in SCFA+ PCD group and PCD group was shorter than that of control group (both P<0.05).Compared with PCD group, the escape latency was shorter, the times of crossing the original platform were more and the residence time in the original platform quadrant was longer in SCFA+ PCD group (all P<0.05). (2) The expression levels of IL-1β, IL-6, phosphorylated p38 MAPK and phosphorylated NF-κB p65 were statistically significant among the four groups ( F=184.28, 139.27, 19.40, 58.47, all P<0.05). The expression levels of IL-1β, IL-6, phosphorylated p38 MAPK and phosphorylated NF-κB p65 were higher in SCFA+ PCD group (0.49±0.10, 0.60±0.05, 0.489±0.012, 0.435±0.005) and PCD group (0.85±0.05, 1.12±0.08, 0.519±0.028, 0.473±0.008) than those in control group (0.13±0.02, 0.42±0.10, 0.437±0.010, 0.362±0.013)(all P<0.05). The expression levels of IL-1β, IL-6, phosphorylated p38 MAPK and phosphorylated NF-κB p65 were lower in SCFA+ PCD group than PCD group (all P<0.05). (3) The average gray value of Nissl bodies was statistically significant different among the four groups ( F=14.65, P<0.05). The average gray value of Nissl bodies was lower in SCFA+ PCD group (193.2±8.1) and PCD group (160.5±14.1) than that of control group (221.2±14.8) (both P<0.05). The average gray value of Nissl bodies was higher in SCFA+ PCD group than that in PCD group( P<0.05). Conclusion:Short-chain fatty acid attenuates cognitive dysfunction, which may be related with inhibiting p38 MAPK/NF-κB p65 pathway and reducing the neuroinflammation.

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 analyze the relationship between umbilical cord blood chemokines regulated upon activation normal T cell expressed and secreted(RANTES),C-X-C motif chemokine ligand 12(CXCL12),C-X-C motif chemokine receptor 4(CXCR4)and neonatal septicemia inflammatory response and outcome.Meth-ods A total of 242 children with neonatal septicemia admitted to a hospital from January 2020 to January 2024 were selected as the study subjects,and were divided into non-critical group(101 cases),critical group(79 cases)and extremely critical group(62 cases)according to neonatal critical case score.According to the prognosis,the subjects were divided into good prognosis group and bad prognosis group.The levels of RAN-TES,CXCL12,CXCR4 and inflammatory factors[C-reactive protein(CRP),interleukin-6,IL-1β]in umbilical cord blood of each group were detected.The correlation between RANTES,CXCL12,CXCR4 and inflammato-ry factors in umbilical cord blood of neonatal septicemia was analyzed by Pearson correlation,and the influen-cing factors of poor prognosis of neonatal septicemia were analyzed by multivariate Logistic regression.Re-ceiver operating characteristic(ROC)curve was drawn to analyze the value of umbilical cord blood RANTES,CXCL12 and CXCR4 in predicting the poor prognosis of neonatal septicemia.Results The levels of RAN-TES,CXCL12,CXCR4,CRP,IL-6 and IL-1β in umbilical cord blood of extremely critical group were higher than those of critical group and non-critical group,and the differences were statistically significant(P＜0.05).The levels of RANTES,CXCL12 and CXCR4 in umbilical cord blood of neonatal septicemia were posi-tively correlated with CRP,IL-6 and IL-1β(P＜0.05).Multivariate Logistic regression analysis showed that extremely severe,early-onset septicemia,high RANTES,high CXCL12 and high CXCR4 were risk factors for poor prognosis of neonatal septicemia(P＜0.05).ROC curve analysis results showed that the area under the curve(AUC)of umbilical cord blood RANTES,CXCL12 and CXCR4 in predicting poor prognosis of neonatal septicemia were 0.810,0.814 and 0.763,respectively,and the AUC of three indicators combined prediction was 0.914,which was higher than that of single prediction.Conclusion The increased levels of RANTES,CX-CL12 and CXCR4 in umbilical cord blood of neonatal septicemia are associated with inflammation,aggravation and poor prognosis,and the combination of RANTES,CXCL12 and CXCR4 can predict the risk of poor prog-nosis of neonatal septicemia.

Objective To investigate the correlation between serum levels of collagen triple helix repeat containing protein 1(CTHRC1)and galectin-10 and disease severity in patients with psoriasis vulgaris(PV).Methods From October 2021 to March 2023,a total of 105 confirmed PV patients treated in the hospital were regarded as the research objects.According to the disease severity,they were separated into a severe group(46 cases)and mild to moderate group(59 cases).Additionally,105 healthy individuals who came to the hospital for physical examination were selected as the control group.The levels of CTHRC1 and galectin-10 in serum were compared and analyzed.Multivariate Logistic regression analysis was conducted to identify the influen-cing factors for the development of severe PV in patients.Receiver operating characteristic(ROC)curve was applied to analyze the predictive value of serum CTHRC1 and galectin-10 levels for the development of severe PV in patients.Results Compared with the control group,the serum levels of CTHRC1 and galectin-10 in the severe group and mild to moderate group were significantly increased(P＜0.05).Compared with the mild to moderate group,the serum levels of CTHRC1 and galectin-10 in the severe group were significantly increased(P＜0.05).Compared with the mild to moderate group,the levels of inflammatory factors interleukin-26(IL-26),interleukin-22(IL-22),and interleukin-17(IL-17)were all increased in the severe group(P＜0.05).Ser-um IL-26,IL-22,CTHRC1,and galectin-10 levels were all influencing factors for the development of severe PV in patients(P＜0.05).The area under the curve(AUC)of serum IL-26,IL-22,CTHRC1 and galectin-10 levels for predicting the development of severe PV in patients were 0.809,0.784,0.863 and 0.874,respective-ly,the AUC predicted by the combination of the four was 0.966,and the combined prediction of the four was better than the prediction of the four separately(Z combination of the four-IL-26=3.581,Zcombination of the four-IL-22=3.285,Zcombination of the four-CTHRC1=2.671,Zcombination of the four-galectin10=2.434,P＜0.05).Conclusion The increased levels of CTHRC1 and galectin-10 in the serum of PV patients are related to the severity of the disease.