1.Aberrant fragmentomic features of circulating cell-free mitochondrial DNA enable early detection and prognosis prediction of hepatocellular carcinoma
Yang LIU ; Fan PENG ; Siyuan WANG ; Huanmin JIAO ; Kaixiang ZHOU ; Wenjie GUO ; Shanshan GUO ; Miao DANG ; Huanqin ZHANG ; Weizheng ZHOU ; Xu GUO ; Jinliang XING
Clinical and Molecular Hepatology 2025;31(1):196-212
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.
2.Aberrant fragmentomic features of circulating cell-free mitochondrial DNA enable early detection and prognosis prediction of hepatocellular carcinoma
Yang LIU ; Fan PENG ; Siyuan WANG ; Huanmin JIAO ; Kaixiang ZHOU ; Wenjie GUO ; Shanshan GUO ; Miao DANG ; Huanqin ZHANG ; Weizheng ZHOU ; Xu GUO ; Jinliang XING
Clinical and Molecular Hepatology 2025;31(1):196-212
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.
3.Aberrant fragmentomic features of circulating cell-free mitochondrial DNA enable early detection and prognosis prediction of hepatocellular carcinoma
Yang LIU ; Fan PENG ; Siyuan WANG ; Huanmin JIAO ; Kaixiang ZHOU ; Wenjie GUO ; Shanshan GUO ; Miao DANG ; Huanqin ZHANG ; Weizheng ZHOU ; Xu GUO ; Jinliang XING
Clinical and Molecular Hepatology 2025;31(1):196-212
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.
4.Expert Consensus on Standard Terminology for Hair Transplantation (2024 Edition)
Yong MIAO ; Wei WU ; Zhenyu GONG ; Wenjie JIANG ; Yufei LI ; Zhiqi HU ; Hua XIAN ; Xiang XIE ; Weiqi YANG ; Dongyi ZHANG ; Jufang ZHANG ; Jiaxian ZHANG ; Chunhua ZHANG ; HAIR TRANSPLANTATION EXPERT GROUP OF PLASTIC AND AESTHETIC NATIONAL MEDICAL QUALITY CONTROL CENTER
Medical Journal of Peking Union Medical College Hospital 2024;15(6):1301-1310
In order to promote the development of hair transplantation, particularly the establishment of standards, the Hair Transplantation Expert Group of Plastic and Aesthetic National Medical Quality Control Center invited experts in the field of hair transplantation across China and formed a draft of the
5.Expert Consensus on Standard Terminology for Hair Transplantation (2024 Edition)
Yong MIAO ; Wei WU ; Zhenyu GONG ; Wenjie JIANG ; Yufei LI ; Zhiqi HU ; Hua XIAN ; Xiang XIE ; Weiqi YANG ; Dongyi ZHANG ; Jufang ZHANG ; Jiaxian ZHANG ; Chunhua ZHANG
Medical Journal of Peking Union Medical College Hospital 2024;15(6):1301-1310
In order to promote the development of hair transplantation, particularly the establishment of standards, the Hair Transplantation Expert Group of Plastic and Aesthetic National Medical Quality Control Center invited experts in the field of hair transplantation across China and formed a draft of the
6.Research progress of single cell transcriptomics in ocular fundus diseases
Xiying MAO ; Wenjie YIN ; Miao XU ; Songtao YUAN ; Qinghuai LIU
Chinese Journal of Ocular Fundus Diseases 2024;40(3):243-246
Single cell RNA sequencing technique provides a strong technical support for the analysis of cell heterogeneity in biological tissues, and has been widely used in biomedical research. In recent years, considerable scRNA-seq data have been accumulated in the research of ocular fundus diseases. The ocular fundus is abundant for the network of vessel and neuron, which leads to the complicated pathogenesis of fundus diseases. Through single cell RNA sequencing technique, the expression of thousands of genes of certain cell types or even subtypes can be obtained in the disease environment. Single cell RNA sequencing technique accurately reveals the pathogenic cell types and pathogenic mechanisms of ocular fundus diseases such as neovascular retinopathy, which provides a theoretical basis for the birth of new diagnosis and treatment targets. The construction of multi-omics single-cell database of ocular fundus diseases will enable high-quality data to be further explored and provide an analysis platform for ophthalmic researchers.
7.Effect of laryngeal function reconstruction of sternohyoid muscle inversion for treatment of glottic carcinoma
Wenjie MIAO ; Huimin WANG ; Hang ZHOU ; Baocai LU ; Rong LIAN
Journal of Clinical Medicine in Practice 2024;28(17):41-44
Objective To observe effect of laryngeal function reconstruction of sternohyoid muscle inversion for treatment of glottic carcinoma. Methods A total of 106 patients with glottic carcinoma admitted to the Department of Otolaryngology in our hospital from January 2020 to December 2023 were selected and randomly divided into control group and observation group, with 53 patients in each group. The control group underwent vertical partial laryngectomy, while the observation group received vertical partial laryngectomy combined with thyrohyoid muscle inversion laryngeal reconstruction. Both groups were assessed for voice-related parameters[normalized noise energy (NNE), harmonic-to-noise ratio (HNR), jitter, shimmer], swallowing function[videofluoroscopic swallowing study (VFSS) score], quality of life[voice handicap index (VHI) score], improvement in phonation function, and incidence of complications (irritative cough, pharyngeal pain, dyspnea, laryngeal stenosis, local adhesion). Results Three months postoperatively, both groups showed significant decrease in NNE, jitter, and shimmer, and an increase in HNR compared to preoperative levels (
8.Effect of intratympanic injection of dexamethasone in the treatment of middle-aged and elderly patients with sudden deafness
Wenjie MIAO ; Chuntao WU ; Baocai LU
Journal of Clinical Medicine in Practice 2024;28(19):114-117
Objective To compare the efficacy and safety of intravenous infusion and intratympanic injection of dexamethasone in the treatment of sudden deafness (SD) in middle-aged and elderly patients. Methods A total of 115 middle-aged and elderly SD patients in the hospital from July 2018 to November 2023 were randomly divided into group A (
9.Determination of biological exposure limit of damage in red blood cells caused by exposure to polycyclic aromatic hydrocarbons using benchmark dose method in general population
Qingqing WANG ; Jing CUI ; Wenjie PENG ; Ting ZHANG ; Miao YUAN ; Lin PANG ; Xiaolin ZHOU ; Hongmei YU
Journal of Public Health and Preventive Medicine 2023;34(2):16-20
Objective To explore the biological exposure limit of blood system damage caused by long-term exposure to polycyclic aromatic hydrocarbons (PAHs) in non-occupational population by using the benchmark dose method, and to provide relevant reference for further improving the assessment of PAHs-induced health damage effects. Methods Adult residents living in downwind direction of a coke-oven plant in Shanxi Province were selected as the research subjects, and the information collected from baseline was used as the control. The metabolites of PAHs in urine were used as exposure biomarker, and the abnormal rate of red blood cell index was used as response biomarker. The relationship between urinary OH-PAHs and the erythrocyte damage rate was analyzed, and the benchmark dose (BMD) and the lower confidence limitation for the benchmark dose (BMDL) were calculated using Bayesian dose-optimizing software. Results The urinary PAH metabolites were mainly naphthalene and fluorene. The detection concentrations of 2-OHFlu and 1-OHPhe in the final year were higher than those in the baseline (P<0.05). With the increase of exposure years, the abnormal rate of red blood cells in the final year was higher than that in the baseline (P<0.05). In addition, the abnormal rate of red blood cells increased with the increase of the concentrations of five metabolites of PAHs in urine, and the chi-square trend test was significant (P<0.05). The benchmark dose (BMD) of OH-PAHs was 0.67 μmol/mol Cr, 0.82 μmol/mol Cr, 1.40 μmol/mol Cr and 0.78 μmol/mol Cr, respectively. The BMD of 2-OHNap in people with barbecue diet habits was 0.23 μmol/mol Cr. The BMD of 2-OHNap in people without barbecue diet habits was 1.44 μmol/mol Cr. Conclusion There is a dose-response relationship between the concentration of PAHs metabolites in urine and the damage of red blood cells. Long-term exposure to PAHs can lead to hematological damage. It is suggested that targeted public health interventions should be formulated to reduce the exposure of the general population to PAHs.
10.Effect of hypothermia on polarization of microglia and TLR4/NF-κB signaling pathway during oxygen-glucose deprivation/restoration
Kaiyue SHAN ; Miao XIN ; Rui DONG ; Huailong CHEN ; Gaofeng ZHANG ; Wenjie LIU ; Mingshan WANG
Chinese Journal of Anesthesiology 2022;42(9):1098-1102
Objective:To evaluate the effect of hypothermia on the polarization of microglia and TLR4/NF-κB signaling pathway during oxygen-glucose deprivation/restoration (OGD/R).Methods:BV2 microglia were cultured in vitro and divided into 3 groups ( n=18 each) using the random number table method: control group (group C), group OGD/R and OGD/R plus hypothermia group (group OGD/R+ HT). Group C was cultured normally for 24 h. In group OGD/R, the cells were exposed to 5% CO 2-1% O 2 at 37 ℃ for 2 h in a glucose-free medium, followed by restoration of glucose and oxygen for 24 h. In group OGD/R+ HT, the high-glucose medium was replaced with a glucose-free medium, the cells were exposed to 5% CO 2-1% O 2 for 2 h in a 33 ℃ cryostat, followed by restoration of glucose and oxygen for 24 h. The cell survival rate was measured by CCK-8 assay.The expression of M1 microglia markers CD32 and iNOS protein and mRNA and M2 microglia markers CD206 and Arg-1 and mRNA was detected by immunofluorescence and real-time quantitative polymerase chain reaction.The expression of TLR-4 and NF-κB in cells was detected by Western blot, and the expression of TLR4 and NF-κB mRNA in cells was detected by real-time quantitative polymerase chain reaction.The concentrations of tumor necrosis factor α (TNF-α), interleukin 1β (IL-1β) and interleukin 10 (IL-10) in the cell supernatant were detected by enzyme-linked immunosorbent assay. Results:Compared with group C, the cell survival rate was significantly decreased, the expression of CD32, iNOS, CD206, Arg-1, TLR4 and NF-κB protein and mRNA was up-regulated, and the concentrations of TNF-α, IL-1β and IL-10 in supernatant were increased in OGD/R and OGD/R+ HT groups ( P<0.05). Compared with group OGD/R, the cell survival rate was significantly increased, the expression of CD32, iNOS, TLR4 and NF-κB protein and mRNA was down-regulated, the expression of CD206 and Arg-1 protein and mRNA was up-regulated, the concentrations of TNF-α and IL-1β in supernatant were decreased, and the concentration of IL-10 was increased in group OGD/R+ HT ( P<0.05). Conclusions:Hypothermia can significantly inhibit microglia polarization toward M1 phenotype, increase microglia polarization toward M2 phenotype and inhibit the development of inflammatory responses during OGD/R, and the mechanism may be related to inhibition of TLR4/NF-κB signaling pathway.


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