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.A prediction model for hypertension risk among residents aged 18 to 79 years
GONG Haiying ; XUE Fengyu ; LIU Xiaofen ; XING Ruiting ; MIAO Yuyang ; ZHAO Yao
Journal of Preventive Medicine 2025;37(10):1075-1080
Objective:
To construct a hypertension risk prediction model for residents aged 18-79 years, so as to provide an assessment tool for early screening and prevention of hypertension in high-risk groups.
Methods:
The permanent residents aged 18-79 years from 6 townships (streets) in Fangshan District of Beijing Municipality were selected as the study subjects using a multi-stage stratified random sampling method from March to June 2023. Demographic information, lifestyle, body mass index (BMI), blood pressure, fasting blood glucose, and blood lipid were collected through questionnaire survey, physical examination, and laboratory tests. Subjects were randomly divided into training and validation sets at a 7∶3 ratio. The logistic regression model was used to screen the risk factors of hypertension, and a hypertension risk prediction nomogram was constructed. Receiver operating characteristic (ROC) curve, calibration curve, and decision curve analysis were used to verify the discrimination, fit, and clinical application value of the model.
Results:
A total of 4 438 subjects were included, including 2 365 males (53.29%) and 2 073 females (46.71%), with a mean age of (44.99±14.90) years. The prevalence of hypertension was 35.29% (1 566 cases), and the standardized prevalence was 24.74%. The logistic regression model screened out 9 influencing factors of hypertension. The nomogram was established as ln[p/ (1-p)]= -2.873 + 0.935×40-<50 years + 1.463×50-<60 years + 1.908×60-<70 years + 2.346×70-79 years + 0.298×male-0.675×college degree or above + 0.384×smoking + 0.227×drinking + 0.572×overweight + 1.449×obesity + 0.557×heart rate ≥80 beats/min + 0.428×diabetes + 0.484×dyslipidemia. The area under the ROC curve of the validation set was 0.821 (95%CI: 0.798-0.843), and the calibration curve results showed that the calibration curve fitted the actual curve well. Decision curve analysis showed that the threshold probability was in the range of 0.10 to 0.70, and the model had good predictive value and clinical application value.
Conclusion
The nomogram based on age, gender, educational level, smoking, drinking, body mass index, heart rate, diabetes, and dyslipidemia can be used to predict the risk of hypertension among residents aged 18-79 years.
5.Root cause analysis of poor prognosis after successful endovascular treatment in patients with acute ischemic stroke with large vascular occlusion of anterior circulation
Bin ZHANG ; Yu JIN ; Miao YANG ; Guanqing LI ; Shukang YU ; Bing LI ; Min LI ; Hui DAI ; Xiaotian MA ; Boping XING ; Pan SHE ; Xueyu LUO
Chinese Journal of Cerebrovascular Diseases 2024;21(10):654-663,707
Objective To explore root cause of poor prognosis after successful endovascular treatment(EVT)in patients with acute ischemic stroke with large vascular occlusion(AIS-LVO)of anterior circulation.Methods Patients with AIS-LOV of anterior circulation who received successful EVT(postoperative modified thrombolysis incerebral infarction[mTICI]grade≥2b)were retrospectively and continuously collected in the Department of Neurology of Bozhou People's Hospital from January 2022 to March 2024.The baseline and clinical data of the patients were collected,including gender,age,vascular risk factors(hypertension,diabetes,coronary heart disease,hyperlipidemia,valvular heart disease,atrial fibrillation,smoking,and alcohol consumption),prior stroke or transient ischemic attack,baseline blood pressure,baseline National Institutes of Health Stroke scale(NIHSS)score,laboratory test indicators(pre-operative C-reactive protein and D-dimer,post-operative fasting blood glucose,lipid levels,homocysteine,etc).Meanwhile,the data of perioperative indicators was collected,including the time from onset to admission,the time from admission to puncture,the time from puncture to revascularization,the time from onset to puncture,the time from onset to revascularization,remedial measures(balloon dilation,stent placement,arterial thrombolysis)during the surgery or not,using tirofiban or not,postoperative complications(stroke-related pneumonia,stress ulcers,deep vein thrombosis,acute heart failure or renal failure,etc)or not.The patient's medical history and imaging data were collected,and these indicators were defined and collected,including Alberta stroke program early CT score(ASPECTS),location of occlusion(C1 segment of the internal carotid artery,C2 segment to C7 segment of the internal carotid artery,M1 segment of the middle cerebral artery),and the trial of org 10172 in acute stroke treatment(TOAST)classification and a postoperative transformation of cerebral infarction after ischemic stroke and symptomatic intracranial hemorrhage or not.According to the modified Rankin scale(mRS)score at 90 d after surgery,all patients were divided into poor prognosis group(mRS score≥ 3)and good prognosis group(mRS score≤2).The baseline and clinical data of two groups were compared using univariate analysis.Variables with P<0.1 in the univariate analysis were selected as independent variables,and the poor prognosis was used as the dependent variable.Further,multivariate Logistic regression analysis was performed to identify the influencing factors of poor prognosis after EVT.Results Finally,a total of 192 patients with AIS-LVO of anterior circulation who received successful revascularization were included in this study.There were 101 male patients and 91 female patients.The poor prognosis group had 102 cases and the good prognosis group had 90 cases.Univariate analysis showed that the poor prognosis group had statistically significant differences with the good prognosis group in terms of age(Z=-3.088,P=0.002)and age distribution(x2=13.457,P=0.001),fasting blood glucose(Z=-3.347,P=0.001),baseline NIHSS score(Z=-4.469,P<0.01),location of occlusion(x2=10.488,P=0.005),transformation of hemorrhage after ischemic stroke(x2=16.943,P<0.01),and symptomatic intracranial hemorrhage(X2=25.449,P<0.01),and the baseline ASPECTS of the poor prognosis group was significantly lower than that of the good prognosis group(Z=-4.547,P<0.01).There were no significant differences in other baseline and clinical data(all P>0.05).Further multivariate Logistic regression analysis showed that age>80 years(OR,3.224,95%CI 1.033-10.058,P=0.044),baseline NIHSS score(OR,1.102,95%CI 1.013-1.199,P=0.023),baseline ASPECTS(OR,0.375,95%CI 0.212-0.665,P=0.001),and symptomatic intracranial hemorrhage(OR,7.127,95%CI 1.296-39.203,P=0.024)were independent influencing factors of poor prognosis.Conclusion The independent factors of 90 d poor prognosis after successful EVT in patients with AIS-LVO of anterior circulation are age>80 years,baseline NIHSS score,baseline ASPECTS,and symptomatic intracranial hemorrhage.
6.Research on the realization path of county health insurance strategic purchasing under the orientation of strengthening the primary health services
Rui-Bo HE ; Lin-Bin LUO ; Yi-Qing XING ; Hao-Miao LI ; Liang ZHANG
Chinese Journal of Health Policy 2024;17(7):1-7
The health insurance fund acts as the resource for the survival of medical institutions.However,it has shown a development trend of structural friction in the county.By analyzing the relationship between strategic purchasing and the function of health insurance system,this study clarifies the central position of payment and the roles of fund allocation and service compensation.By analyzing the reasons of the imbalance between the health insurance fund and primary services in the county,this study proposes that the strategic purchasing of health care services in the county needs to take into account both the front-end of payment-allocation,and the front-end of service--primary.On this basis,this study put forwards the strategic purchasing of primary health services,which aims to cut off the fund"competition"channel between hospitals and primary health care institutions by changing the fund distribution method;to guide the primary health care to proactively identify and satisfy the changes of the county's residents'service needs by adjusting the service compensation method;and supplemented with joint advocacy and collaborative supervision.The strategic purchasing of primary health services will gradually promote the development of primary health services in the county from sustainable to high-quality.
7.Research progress and development trends of negative pressure isolation treatment equipment
Xin-Miao WANG ; Jin-Hui WU ; Zong-Xing ZHANG ; Yan-Hua FANG ; Ying YI ; Cheng DENG
Chinese Medical Equipment Journal 2024;45(2):97-104
The main components and working principle of the negative pressure isolation treatment equipment were described,and the classification and application scopes of the negative pressure isolation treatment equipment from foreign countries and China were reviewed.The structure,key technical parameters and characteristics of different types of negative pressure isolation treatment equipment were analyzed under different conditions.The problems of the negative pressure isolation treatment equipment were analyzed,and it's pointed out it would be enhanced in component simplification,comfort,intelligence and multifunctionality.[Chinese Medical Equipment Journal,2024,45(2):97-104]
8.The research progress of macrophage glycolysis in sepsis
Xing CAI ; Xinglong MA ; Changjian ZHOU ; Peng XIE ; Songxuan SHEN ; Yanmei MIAO ; Jiamei SONG ; Leiyu XIE
The Journal of Practical Medicine 2024;40(19):2783-2788
Sepsis is a heterogeneous syndrome.It is caused by infections,attributing to immune dysfunction pathologically.The disease is characterized by macrophage-mediated inflammation and immune response throughout its development.During septic development,macrophages metabolize crucially with glycolysis remarkably enhanced.The glycolystic enhancement facilitates septic development by promoting the inflammatory response of macrophages and altering their phenotype.Therefore,direct or indirect inhibition of macrophagic glycolysis can alleviate sepsis and neutralize damages to organs functionally,promoting the polarization of anti-inflammatory phenotype.In this review,we aim to investigate the relationship between macrophagic glycolysis and sepsis,focusing on researching into relevant molecular mechanisms by which glycolysis is regulated for treating sepsis.It is concluded that interfer-ing with macrophagic glycolysis may serve as a novel therapeutic strategy for treating sepsis.
9.Laparoscopy and endoscopy cooperative surgery for early gastric cancer:technical analysis of initial cases
Xing JIYAO ; Miao RULIN ; Wu QI ; Wang JING ; Shan FEI ; Li ZIYU
Chinese Journal of Clinical Oncology 2024;51(13):670-675
Objective:To retrospectively analyze the efficiency of laparoscopic and endoscopic cooperative surgery(LECS)for early gastric cancer treatment.Methods:We retrospectively collected data from patients with early gastric cancer who underwent LECS at the Peking University Cancer Hospital&Institute between May,2013 and April,2024.Patients underwent endoscopic submucosal dissection(ESD)with laparoscopic lymph node biopsy,classical LECS,and other modified procedures.Additionally,clinical and pathological characteristics,post-operative recovery indicators,complications,and survival outcomes of the patients were analyzed.Results:Nine patients(median age:64 years),including six male(66.7% )and three female(33.3% )patients,were involved in this study.Biopsy revealed that all patients had well-differentiated gastric cancer.Five patients(55.6% )underwent ESD with laparoscopic lymph node biopsy,and four patients(44.4% )under-went laparoscopically assisted endoscopic full-thickness resection and sentinel lymph node biopsy.Average anesthesia time was(351.2±91.4)min,and average blood loss was(34.4±15.1)mL.After surgery,three patients(33.3% )experienced complications,with one case each of gastric stasis(CD2),intra-abdominal infection(CD2),and gastrointestinal perforation(CD3).The median follow-up time was 52 months,and no cases of disease recurrence or death were observed.Conclusions:Overall,this study highlights the efficiency of LECS for early gastric cancer treatment.Future studies should assess its oncological safety,along with other technical aspects,patient selection criter-ia,and accuracy of sentinel lymph node biopsy,to facilitate widespread application of LECS.
10.A unicenter real-world study of the correlation factors for complete clinical response in idiopathic inflammatory myopathies
Zhanhong LAI ; Jiachen LI ; Zelin YUN ; Yonggang ZHANG ; Hao ZHANG ; Xiaoyan XING ; Miao SHAO ; Yue-Bo JIN ; Naidi WANG ; Yimin LI ; Yuhui LI ; Zhanguo LI
Journal of Peking University(Health Sciences) 2024;56(2):284-292
Objective:To investigate the correlation factors of complete clinical response in idiopathic inflammatory myopathies(IIMs)patients receiving conventional treatment.Methods:Patients diagnosed with IIMs hospitalized in Peking University People's Hospital from January 2000 to June 2023 were in-cluded.The correlation factors of complete clinical response to conventional treatment were identified by analyzing the clinical characteristics,laboratory features,peripheral blood lymphocytes,immunological indicators,and therapeutic drugs.Results:Among the 635 patients included,518 patients finished the follow-up,with an average time of 36.8 months.The total complete clinical response rate of IIMs was 50.0%(259/518).The complete clinical response rate of dermatomyositis(DM),anti-synthetase syn-drome(ASS)and immune-mediated necrotizing myopathy(IMNM)were 53.5%,48.9%and 39.0%,respectively.Fever(P=0.002)and rapid progressive interstitial lung disease(RP-ILD)(P=0.014)were observed much more frequently in non-complete clinical response group than in complete clinical re-sponse group.The aspartate transaminase(AST),lactate dehydrogenase(LDH),D-dimer,erythrocyte sedimentation rate(ESR),C-reaction protein(CRP)and serum ferritin were significantly higher in non-complete clinical response group as compared with complete clinical response group.As for the treat-ment,the percentage of glucocorticoid received and intravenous immunoglobin(IVIG)were significantly higher in non-complete clinical response group than in complete clinical response group.Risk factor analysis showed that IMNM subtype(P=0.007),interstitial lung disease(ILD)(P=0.001),eleva-ted AST(P=0.012),elevated serum ferritin(P=0.016)and decreased count of CD4+T cells in peripheral blood(P=0.004)might be the risk factors for IIMs non-complete clinical response.Conclu-sion:The total complete clinical response rate of IIMs is low,especially for IMNM subtype.More effec-tive intervention should be administered to patients with ILD,elevated AST,elevated serum ferritin or decreased count of CD4+T cells at disease onset.


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