Background/Aims: Early detection and effective prognosis prediction in patients with hepatocellular carcinoma (HCC) provide an avenue for survival improvement, yet more effective approaches are greatly needed. We sought to develop the detection and prognosis models with ultra-sensitivity and low cost based on fragmentomic features of circulating cell free mtDNA (ccf-mtDNA). Methods: Capture-based mtDNA sequencing was carried out in plasma cell-free DNA samples from 1168 participants, including 571 patients with HCC, 301 patients with chronic hepatitis B or liver cirrhosis (CHB/LC) and 296 healthy controls (HC). Results: The systematic analysis revealed significantly aberrant fragmentomic features of ccf-mtDNA in HCC group when compared with CHB/LC and HC groups. Moreover, we constructed a random forest algorithm-based HCC detection model by utilizing ccf-mtDNA fragmentomic features. Both internal and two external validation cohorts demonstrated the excellent capacity of our model in distinguishing early HCC patients from HC and highrisk population with CHB/LC, with AUC exceeding 0.983 and 0.981, sensitivity over 89.6% and 89.61%, and specificity over 98.20% and 95.00%, respectively, greatly surpassing the performance of alpha-fetoprotein (AFP) and mtDNA copy number. We also developed an HCC prognosis prediction model by LASSO-Cox regression to select 20 fragmentomic features, which exhibited exceptional ability in predicting 1-year, 2-year and 3-year survival (AUC=0.8333, 0.8145 and 0.7958 for validation cohort, respectively). Conclusions We have developed and validated a high-performing and low-cost approach in a large clinical cohort based on aberrant ccf-mtDNA fragmentomic features with promising clinical translational application for the early detection and prognosis prediction of HCC patients.

Background/Aims: Early detection and effective prognosis prediction in patients with hepatocellular carcinoma (HCC) provide an avenue for survival improvement, yet more effective approaches are greatly needed. We sought to develop the detection and prognosis models with ultra-sensitivity and low cost based on fragmentomic features of circulating cell free mtDNA (ccf-mtDNA). Methods: Capture-based mtDNA sequencing was carried out in plasma cell-free DNA samples from 1168 participants, including 571 patients with HCC, 301 patients with chronic hepatitis B or liver cirrhosis (CHB/LC) and 296 healthy controls (HC). Results: The systematic analysis revealed significantly aberrant fragmentomic features of ccf-mtDNA in HCC group when compared with CHB/LC and HC groups. Moreover, we constructed a random forest algorithm-based HCC detection model by utilizing ccf-mtDNA fragmentomic features. Both internal and two external validation cohorts demonstrated the excellent capacity of our model in distinguishing early HCC patients from HC and highrisk population with CHB/LC, with AUC exceeding 0.983 and 0.981, sensitivity over 89.6% and 89.61%, and specificity over 98.20% and 95.00%, respectively, greatly surpassing the performance of alpha-fetoprotein (AFP) and mtDNA copy number. We also developed an HCC prognosis prediction model by LASSO-Cox regression to select 20 fragmentomic features, which exhibited exceptional ability in predicting 1-year, 2-year and 3-year survival (AUC=0.8333, 0.8145 and 0.7958 for validation cohort, respectively). Conclusions We have developed and validated a high-performing and low-cost approach in a large clinical cohort based on aberrant ccf-mtDNA fragmentomic features with promising clinical translational application for the early detection and prognosis prediction of HCC patients.

Background/Aims: Early detection and effective prognosis prediction in patients with hepatocellular carcinoma (HCC) provide an avenue for survival improvement, yet more effective approaches are greatly needed. We sought to develop the detection and prognosis models with ultra-sensitivity and low cost based on fragmentomic features of circulating cell free mtDNA (ccf-mtDNA). Methods: Capture-based mtDNA sequencing was carried out in plasma cell-free DNA samples from 1168 participants, including 571 patients with HCC, 301 patients with chronic hepatitis B or liver cirrhosis (CHB/LC) and 296 healthy controls (HC). Results: The systematic analysis revealed significantly aberrant fragmentomic features of ccf-mtDNA in HCC group when compared with CHB/LC and HC groups. Moreover, we constructed a random forest algorithm-based HCC detection model by utilizing ccf-mtDNA fragmentomic features. Both internal and two external validation cohorts demonstrated the excellent capacity of our model in distinguishing early HCC patients from HC and highrisk population with CHB/LC, with AUC exceeding 0.983 and 0.981, sensitivity over 89.6% and 89.61%, and specificity over 98.20% and 95.00%, respectively, greatly surpassing the performance of alpha-fetoprotein (AFP) and mtDNA copy number. We also developed an HCC prognosis prediction model by LASSO-Cox regression to select 20 fragmentomic features, which exhibited exceptional ability in predicting 1-year, 2-year and 3-year survival (AUC=0.8333, 0.8145 and 0.7958 for validation cohort, respectively). Conclusions We have developed and validated a high-performing and low-cost approach in a large clinical cohort based on aberrant ccf-mtDNA fragmentomic features with promising clinical translational application for the early detection and prognosis prediction of HCC patients.

Sirtuin2(SIRT2)is an NAD+dependent histone deacetylase that plays a key role in maintaining cellular REDOX potential and modulating pro-inflammatory immune responses.How-ever,its role in acute kidney injury(AKI)has not been proven.To explore the role of SIRT2 in AKI,AKI models were constructed in wild-type(WT)and SIRT2 knockout(SIRT2-/-)mice by injection of lipopolysaccharide(LPS).HE results showed that kidney damage in SIRT2-/-mice was more significant than that in LPS treated WT mice.qRT-PCR and Western blot results showed that more significant changes in inflammatory genes,proteins and oxidative stress proteins in SIRT2-/-mice.The results suggest that SIRT2 deficiency exacerbates LPS induced AKI.

Objective:To analyze the influencing factors of clinically relevant postoperative pancreatic fistula (CR-POPF) in children with pancreatic tumors after surgery.Methods:The clinical data of 123 children undergoing surgery for pancreatic tumor in Beijing Children's Hospital, Capital Medical University from January 2007 to March 2020 were retrospectively analyzed, including 39 males and 84 females, with a median age of 9.8 years (6.7 to 11.8). Patients without pancreatic fistula and with biochemical leakage were included in control group ( n=95), while patients with grade B and C pancreatic fistula were divided into CR-POPF group ( n=28). The independent influencing factors of CR-POPF were analyzed by univariate and multivariate logistic regression. Results:Among 123 children, 28 cases (22.8%) developed CR-POPF, including 24 cases (85.7%, 24/28) of grade B pancreatic fistula and 4 cases (14.3%, 4/28) of grade C pancreatic fistula. There were significant differences between CR-POPF and control groups in the age > 8 years and 4 months, tumor location, operation time >390 min and procedures (all P<0.05). Multivariate logistic regression analysis showed an increased risk of CR-POPF in children aged > 8 years and 4 months ( OR=8.226, 95% CI: 1.813-37.333, P=0.006) and undergoing duodenum-preserving pancreatic head resection (DPPHR) ( OR=3.353, 95% CI: 1.282-8.767, P=0.014). Conclusion:Age>8 years and 4 months and DPPHR are independent risk factors for CR-POPF in children with pancreatic tumors after surgery.

The negative effects of low temperature can readily induce a variety of diseases. We sought to understand the reasons why cold stress induces disease by studying the mechanisms of fine-tuning in macrophages following cold exposure. We found that cold stress triggers increased macrophage activation accompanied by metabolic reprogramming of aerobic glycolysis. The discovery, by genome-wide RNA sequencing, of defective mitochondria in mice macrophages following cold exposure indicated that mitochondrial defects may contribute to this process. In addition, changes in metabolism drive the differentiation of macrophages by affecting histone modifications. Finally, we showed that histone acetylation and lactylation are modulators of macrophage differentiation following cold exposure. Collectively, metabolism-related epigenetic modifications are essential for the differentiation of macrophages in cold-stressed mice, and the regulation of metabolism may be crucial for alleviating the harm induced by cold stress.
Acetylation ; Animals ; Cold-Shock Response ; Epigenesis, Genetic ; Macrophages/metabolism* ; Mice ; Mitochondria/metabolism*

Objective:To investigate the regulatory mechanism and clinical significance of RASSF5 in cutaneous melanoma.Methods:We used GEPIA and HPA online tools and TCGA and GSE53118 data sets for differential expression analysis and prognosis analysis; cBioPortal was applied to analyze the correlation between RASSF5 expression and gene mutation and methylation; "limma" R package was used to screen differential genes for GO analysis, KEGG analysis and protein-protein interaction analysis, and we also performed GSEA analysis on all genes; finally we used ESTIMATE and CIBERSORTx online tools to evaluate immune cell infiltration. The kruskal test was used to compare the differences between the groups for measurement data, the Kaplan-Meier method was used to draw the survival curve, and the Cox proportional hazard regression model was used for univariate and multivariate analysis.Results:This study found that in cutaneous melanoma, the expression level of RASSF5 was significantly lower than that of normal tissues, and the methylation level was negatively correlated. KEGG analysis and GSEA analysis showed that RASSF5 can be related to multiple signaling pathways such as immune regulation, KRAS, and P53. Further analysis showed that the expression level of RASSF5 was positively correlated with the degree of infiltration of a variety of tumor immune cells. Survival analysis found that the expression level of RASSF5 was correlated with the overall survival rate of patients with cutaneous melanoma, and multivariate regression analysis found that RASSF5 was an independent predictor of cutaneous melanoma. Finally, using the GSE53118 dataset to verify again, RASSF5 is related to the overall survival rate of patients with cutaneous melanoma and can be used as an independent predictor.Conclusions:RASSF5 may regulate the occurrence and development of cutaneous melanoma cells through a variety of ways. It is a potential biological prognostic marker and therapeutic target.

Objective:To investigate the regulatory mechanism and clinical significance of RASSF5 in cutaneous melanoma.Methods:We used GEPIA and HPA online tools and TCGA and GSE53118 data sets for differential expression analysis and prognosis analysis; cBioPortal was applied to analyze the correlation between RASSF5 expression and gene mutation and methylation; "limma" R package was used to screen differential genes for GO analysis, KEGG analysis and protein-protein interaction analysis, and we also performed GSEA analysis on all genes; finally we used ESTIMATE and CIBERSORTx online tools to evaluate immune cell infiltration. The kruskal test was used to compare the differences between the groups for measurement data, the Kaplan-Meier method was used to draw the survival curve, and the Cox proportional hazard regression model was used for univariate and multivariate analysis.Results:This study found that in cutaneous melanoma, the expression level of RASSF5 was significantly lower than that of normal tissues, and the methylation level was negatively correlated. KEGG analysis and GSEA analysis showed that RASSF5 can be related to multiple signaling pathways such as immune regulation, KRAS, and P53. Further analysis showed that the expression level of RASSF5 was positively correlated with the degree of infiltration of a variety of tumor immune cells. Survival analysis found that the expression level of RASSF5 was correlated with the overall survival rate of patients with cutaneous melanoma, and multivariate regression analysis found that RASSF5 was an independent predictor of cutaneous melanoma. Finally, using the GSE53118 dataset to verify again, RASSF5 is related to the overall survival rate of patients with cutaneous melanoma and can be used as an independent predictor.Conclusions:RASSF5 may regulate the occurrence and development of cutaneous melanoma cells through a variety of ways. It is a potential biological prognostic marker and therapeutic target.

Objective:To analyze the clinicopathological characteristics and treatment strategies of hepatoblastoma with macrotrabecular structures.Methods:To retrospectively analyze the data of children with hepatoblastoma treated in the Department of Oncology at Beijing Children's Hospital affiliated to Capital Medical University amd Baoding Children's Hospital from January 1, 2011 to December 31, 2019. The study structure consisted of collecting clinical data and formulating treatment plan, including clinical stage, alpha-fetoprotein (AFP), chemotherapy plan, surgical margin, pathological classification and follow-up data to study the long-term prognosis of these patients.Results:Among 17 patients, 13 males and 4 females, age 5 to 134 months; 5 patients had the macrotrabecular type, 10 patients had the epithelial type with macrotrabecular, 2 patients had the mixed epithelial and mesenchymal with macrotrabecular type. For the PRETEXT staging, 1 patient had stage I, 2 patients had stage II, 14 patients had stage III and IV. A total of 15 patients received preoperative chemotherapy, and 6 achieved partial response. Among 17 patients, 10 had negative resection margins. The AFP of 7 patients was normal after chemotherapy, and 10 patients relapsed after surgery. The 2-year event-free survival was 26.18%.Conclusions:Patients with hepatoblastoma containing giant trabecular components are very rare. Among them, the recurrence rate of patients with giant trabecular and epithelial and giant trabecular components was high. Preoperative neoadjuvant chemotherapy (vincristine + irinotecan), transcatheter arterial chemoembolization and liver transplantation are treatment options for this type of hepatoblastoma.

Objective To analyze the short-term complications and long-term outcomes of spleenpreserving distal pancreatectomy (SPDP) in pediatric pancreatic tumors.Methods A retrospective analysis was conducted on 43 patients with tumors of the body and tail of the pancreas in Beijing Children's Hospital from Jan 2007 to Jan 2018.Results There were 17 boys (39.53％) and26girls (60.47％),with a median age of 123 (80,141) months.The median maximum diameter of primary tumor was 7.60 cm.Diagnoses included solid pseudopapillary tumor (n =28),pancreatoblastoma (n =10),neuroendocrine tumor (n =4),and pancreatic cyst (n =1).Two cases (4.65％) received tumor enucleation,4 cases (9.30％) did distal pancreatectomy plus splenectomy,and 37 cases (86.05％) did SPDP.16 cases (37.21％) had short-term complications,including pancreatic fistula (n =13),delayed gastric emptying (n =3),abdominal infection (n =7) and postoperative bleeding (n =2).After a median follow-up of 46 (23,71) months,38 cases (88.37％) were disease-free;two cases (4.65％) with tumor recurrence;one case of pancreatoblastoma died of tumor recurrence.Two cases lost to follow-up.Three patients had long-term complications,including chronic fatty diarrhea (n =2) and hypoglycemia (n =1).Three patients underwent second operation for recurrent tumor (one pancreatoblastoma and two solid pseudopapillary tumor).Conclusions SPDP is safe and effective in the treatment of tumors of the body and tail of the pancreas in children.