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.Comparison of clinical characteristics and prognostic influence factors between patients with or without hypertrophic cardiomyopathy complicated by microvascular dysfunction
Chuwen WU ; Mengling PENG ; Yu FU ; Shanshan ZHOU
Journal of Jilin University(Medicine Edition) 2025;51(6):1630-1637
Objective:To discuss the clinical characteristics of the patients with hypertrophic cardiomyopathy(HCM)complicated with microcirculatory dysfunction(CMD),and to analyze the impact of concurrent CMD on the prognosis of the HCM patients.Methods:A total of 211 patients diagnosed with HCM and having complete cardiac magnetic resonance imaging(CMR)examination results from January 1,2019 to September 30,2023 were collected.They were divided into HCM complicated with CMD group(68 cases)and HCM complicated without CMD group(143 cases)based on CMR assessment.The clinical data such as age,gender,admission symptoms,and past medical history,blood test data such as troponin,electrocardiogram,echocardiography,and CMR data including abnormal Q wave,ST segment depression,inverted T wave,PR interval,QRS wavelength,corrected QT interval,ejection fraction(EF),left atrial diameter(LAD),left and right ventricular end-diastolic diameters,cardiac output,E peak,A peak,and maximum wall thickness(MWT)of the patients were compared between two groups.Logistic regression was used to analyze the clinical characteristics of the HCM patients complicated with CMD;multivariate modified Poisson regression was used to analyze the risk factors for major adverse cardiovascular events(MACE)in the HCM patients.Results:Compared with HCM complicated without CMD group,the percentage of palpitation patients in HCM complicated with CMD group was significantly increased(P<0.05),the percentage of tachycardia episode patients was significantly increased(P<0.05),the troponin level was significantly increased(P<0.05),and the percentage with a history of hypertension patients was significantly decreased(P<0.05).Compared with HCM complicated without CMD group,the percentage of abnormal Q wave on electrocardiogram in the patients in HCM complicated with CMD group were significantly increased(P<0.05),the percentage of inverted T wave and the EF of the patients was significantly decreased(P<0.05),the LAD was significantly increased(P<0.05),and the MWT was significantly increased(P<0.05).The multivariate Logistic regression analysis results showed that increased LAD(OR=1.05,95%CI:1.00-1.11,P=0.048)and increased MWT(OR=1.11,95%CI:1.03-1.19,P=0.007)were the risk factors for concurrent CMD in the HCM patients;history of hypertension(OR=0.40,95%CI:0.20-0.80,P=0.010)was a protective factor for concurrent CMD in the HCM patients.The average follow-up time in this study was 20.5 months.A total of 27 patients experienced MACE,with an overall incidence of 12.80%,including 12 patients in HCM complicated with CMD group and 15 patients in HCM complicated without CMD group.The multivariate modified Poisson regression analysis results showed that history of diabetes(RR=2.34,95%CI:1.09-5.06,P=0.030),history of arrhythmia(RR)=4.00,95%CI:1.82-8.83,P=0.001),and decreased ejection fraction(RR=0.96,95%CI:0.94-0.99,P=0.001)were risk factors for MACE in the HCM patients.Conclusion:The HCM patients complicated with CMD have unique clinical characteristics,including higher symptom burden,left atrial enlargement,myocardial hypertrophy,and increased troponin levels.Concurrent CMD does not increase the short-term risk of adverse events;diabetes,arrhythmia,and decreased EF are key risk factors for prognosis;early intervention and complication management for HCM complicated with CMD patients may improve the long-term prognosis of the HCM 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.Role and potential mechanisms of lactylation modification in ischemic stroke
Xinlei HUANG ; Shanshan LIU ; Hequn LYU ; Yana CAO ; Yongjun PENG
Chinese Journal of Neurology 2025;58(12):1351-1357
Lactylation, a newly discovered post-translational modification, has been reported to be involved in various physiological and pathological processes. Recent studies have found that lactylation is potentially linked to the pathological processes and repair mechanisms of ischemic stroke. This article explores the impact and role of lactylation after the occurrence of ischemic stroke on neuroinflammation, energy metabolism regulation, oxidative stress, signaling pathway modulation, and angiogenesis. It may serve as a bridge connecting lactylation and ischemic stroke, offering insights and guidance for future research and clinical strategies in ischemic stroke.
5.Efficacy analysis of an improved radiofrequency ablation method for primary great saphenous vein varicose
Yingying QING ; Yuang ZHANG ; Gang DONG ; Jie WU ; Jiamin SUN ; Shanshan ZHANG ; Mengfan PENG ; Wenwen YUE
Chinese Journal of Ultrasonography 2025;34(10):897-903
Objective:To investigate the safety and efficacy of a modified radiofrequency ablation(RFA)treatment method for primary great saphenous vein varicose.Methods:Clinical data of 90 patients with primary great saphenous vein varicose treated with ultrasound-guided RFA from January 2021 to April 2024 in the Ultrasound Department of the First Affiliated Hospital of Zhengzhou University were retrospectively analyzed. Among them,45 patients were treated with traditional RFA treatment method(traditional group)and 45 patients were treated with improved RFA treatment method(improved group). Number of punctures,operation time,foam hardener dosage,intraoperative and postoperative complications were recorded in the two groups. The preoperative and postoperative venous clinical severity score(VCSS)and chronic venous insufficiency questionnaire(CIVIQ-14)were compared. The closure rate and recurrence rate of great saphenous vein varicose were followed up and the efficacy of the two methods were analyzed.Results:The success rate of the improved group and the traditional group was 100%.The number of punctures in the improved group was less than those of the traditional group[1(1,1) vs. 2(2,3), Z = -7.431, P<0.001],and the operation time of the modified group was shorter than that of the traditional group[(15.89 ± 3.63)min vs.(30.91 ± 5.58)min, t=-15.145, P<0.001],the average volume of lauryl foam was lower than that of the traditional RFA group[(7.96 ± 2.36)ml vs.(15.69 ± 2.89)ml, t=-13.892, P<0.001]. The incidence of complications was similar between the two groups,with no statistical significance(all P>0.05). Postoperative VCSS and CIVIQ-14 scores were significantly improved compared with before(all P<0.001),with no statistical significance between the two groups(all P>0.05). At 12 months after the operation,there was no significant difference in the closure rate of the saphenous vein between the improved group and the traditional group( P>0.05),and the recurrence rate of varicose veins in both groups was 0. Conclusions:This modified RFA treatment method for the treatment of lower extremity varicose veins is minimally invasive,safe,and has the same efficacy as the traditional RFA treatment method. Compared with the traditional RFA treatment method,the modified RFA treatment method has the advantages of convenient operation,less puncture times and shorter operation time,and is worthy of clinical promotion.
6.Diagnostic value of endoscopic ultrasound-guided fine needle aspiration for biopsy-negative esophageal strictures
Mireayi NUERMAIMAITI ; Dehua TANG ; Congqiang SHEN ; Xinyu TIAN ; Yuhang ZHUANG ; Shanshan SHEN ; Chunyan PENG ; Lei WANG ; Shu ZHANG ; Ying LYU
Chinese Journal of Digestive Endoscopy 2025;42(1):60-65
Objective:To investigate the diagnostic value of endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) for biopsy-negative esophageal strictures suspected for malignancy.Methods:Patients who underwent EUS-FNA for esophageal strictures with negative endoscopic biopsies in Nanjing Drum Tower Hospital from January 2014 to March 2022 were analyzed retrospectively. The final diagnosis was based on the pathological outcomes of EUS-FNA or surgery, complemented by follow-up data. Diagnostic efficacy and complication rates of EUS-FNA were analyzed.Results:A total of 64 patients were included in this study,with 54 ultimately diagnosed with malignant lesions and 10 with benign lesions. Malignant lesions were diagnosed by EUS-FNA in 50 cases, suspected malignant lesions in 3 cases, and no clear basis for malignancy was observed in 11 cases. The diagnostic accuracy of EUS-FNA was 98.4% (63/64), with the malignant tumor detection rate of 98.1% (53/54). No post-procedure complications such as bleeding, perforation, or infection were observed in any patient.Conclusion:EUS-FNA is safe and effective for the diagnosis of biopsy-negative suspected malignant esophageal stricture with a high malignant lesion detection rate.
7.Long-term outcomes of endoscopic papillectomy for duodenal papillary adenomas and risk factors for incomplete resection
Kun LIU ; Xintong ZHANG ; Xiang ZHANG ; Muhan NI ; Peng YAN ; Bei TANG ; Wenting LI ; Dan XU ; Wen LI ; Pin WANG ; Dehua TANG ; Xiaoping ZOU ; Lei WANG ; Shanshan SHEN
Chinese Journal of Digestive Endoscopy 2025;42(7):545-551
Objective:To evaluate long-term outcomes of endoscopic papillectomy (EP) for duodenal papillary adenomas and to identify risk factors for incomplete resection.Methods:Clinical data of 180 patients diagnosed as having duodenal papillary adenoma via postoperative pathology after EP in Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School from January 2010 to December 2022 were retrospectively analyzed. Patients were divided into two groups based on their postoperative margin status: the complete resection group (negative resection margins) and the incomplete resection group (positive/uncertain resection margins). Recurrence rates were compared between the two groups, and logistic regression analysis was performed to identify risk factors for incomplete resection.Results:Among the 180 patients included in the study, 137 underwent complete resection, and 43 had incomplete resections. Recurrence rate was significantly higher in the incomplete resection group than that in the complete resection group (30.2% VS 15.3%, χ2=4.75, P=0.029). logistic regression analysis indicated that high-grade intraepithelial neoplasia was an independent risk factor for incomplete resection ( OR=2.43, 95% CI:1.12-5.26, P=0.024). Conclusion:Patients with incomplete resection after EP have a higher recurrence rate in the long-term follow-up. High-grade intraepithelial neoplasia is an independent risk factor for incomplete resection. Close surveillance and aggressive management are warranted for patients with positive or uncertain resection margins to mitigate the recurrence risk.
8.Analysis of the therapeutic effect of double nylon rope purse string suture closing the postoperative wounds of the treatment of endoscopic full thickness resection for gastric submucosal tumors
Shanshan WANG ; Mengyao JI ; Shuai PENG ; Lei SHEN
China Journal of Endoscopy 2025;31(4):25-31
Objective To evaluate the clinical value and safety of double nylon rope purse string suture closing the postoperative wounds of the treatment of endoscopic full thickness resection(EFR)for gastric submucosal tumors(SMT).Methods We retrospectively analyzed the clinical data of 104 patients with gastric SMT originating from the muscularis propria,from June 2020 to March 2023.According to different suture methods,they were divided into single nylon rope purse string suture group(48 cases)and double nylon rope purse string suture group(56 cases).The patients'operative,postoperative,and long-term follow-up conditions were evaluated.Results All tumors were completely resected under endoscopic guidance.The terms of lesion diameter in double nylon rope purse string suture group was bigger than that in single nylon rope purse string suture group,there was statistically significant difference between the two groups(P=0.040).In the single nylon rope purse string suture group,postoperative perforation occurred in 1 case,low fever occurred in 4 cases,and mild pain in the upper abdomen occurred in 6 cases,in the double nylon rope purse string suture group,there was no postoperative perforation,5 patients had low fever,and 6 patients had mild pain in the upper abdomen,there was no significant difference in postoperative complications between the two groups(P>0.05).No postoperative cases were transferred to gastrointestinal surgery,and all patients were discharged smoothly.After 3 months,7 cases in the single nylon rope purse string suture group had titanium clips and/or nylon rope residue,while 18 cases in the double nylon rope purse string suture group still had titanium clips and/or nylon rope residue,and the difference between the two groups was statistically significant(P=0.037).Conclusion Compared with single nylon rope purse string suture,double nylon rope purse string suture can effectively close the postoperative wounds following gastric SMT with EFR(≥3 cm).
9.Application of tabletop deduction and simulation drills in the training of infection prevention and control for acute respiratory infectious diseases on hospital ships
Anhua QIAO ; Zhengmei XU ; Li GUI ; Fei PENG ; Jing CHEN ; Zhihao YUE ; Yi CHEN ; Shanshan YANG
Journal of Navy Medicine 2025;46(7):662-666
Objective To carry out a joint simulation exercise of tabletop deduction for the staff performing overseas medical services on hospital ships,so as to improve the infection prevention and control.Methods Sixty mission members were selected by convenience sampling to carry out joint simulation drills for tabletop deduction.The effects of the drills were assessed by the survey on the satisfaction and participation of mission members,before-and-after control study,and mission execution.Results Overseas medical service tasks were successfully completed through the desktop-propelled joint simulation drills.The total score of response for infectious emergencies,prevention score,preparedness score,and rescue score after training were higher than those before training(P<0.05).There were high degrees of participation and satisfaction in the drills(≥4.5 points).Conclusion The tabletop deduction and simulation exercise achieve good results in the infection prevention and control of hospital ships.The scheme of tabletop deduction combined with simulation drills will be optimized to continuously improve the infection prevention and control of hospital ships.
10.Construction and Application Evaluation of an Integrated Traditional Chinese and Western Medicine Risk Prediction Model for Readmission in Patients with Stable Angina of Coronary Heart Disease:A Prospective Study Based on Real-World Clinical Data
Wenjie HAN ; Mingjun ZHU ; Xinlu WANG ; Rui YU ; Guangcao PENG ; Qifei ZHAO ; Jianru WANG ; Shanshan NIE ; Yongxia WANG ; Jingjing WEI
Journal of Traditional Chinese Medicine 2025;66(6):604-611
ObjectiveBy exploring the influencing factors of readmission in patients with stable angina of coronary heart disease (CHD) based on real-world clinical data, to establish a risk prediction model of integrated traditional Chinese and western medicine, in order to provide a basis for early identification of high-risk populations and reducing readmission rates. MethodsA prospective clinical study was conducted involving patients with stable angina pectoris of CHD, who were divided into a training set and a validation set at a 7∶3 ratio. General information, traditional Chinese medicine (TCM)-related data, and laboratory test results were uniformly collected. After a one-year follow-up, patients were classified into a readmission group and a non-readmission group based on whether they were readmitted. Univariate and multivariate logistic regression analyses were performed to identify independent risk factors for readmission. A risk prediction model of integrated traditional Chinese and western medicine was constructed and visualized using a nomogram. The model was validated and evaluated in terms of discrimination, calibration, and clinical decision curve analysis. ResultsA total of 682 patients were included, with 477 in the training set and 205 in the validation set, among whom 89 patients were readmitted. Multivariate logistic regression analysis identified heart failure history [OR = 6.93, 95% CI (1.58, 30.45)], wiry pulse [OR = 2.58, 95% CI (1.42, 4.72)], weak pulse [OR = 3.97, 95% CI (2.06, 7.67)], teeth-marked tongue [OR = 4.38, 95% CI (2.32, 8.27)], blood stasis constitution [OR = 2.17, 95% CI (1.06, 4.44)], phlegm-stasis mutual syndrome [OR = 3.64, 95% CI (1.87, 7.09)], and elevated non-high-density lipoprotein cholesterol [OR = 1.30, 95% CI (1.01, 1.69)] as influencing factors of readmission. These factors were used as predictors to construct a nomogram-based risk prediction model for readmission in patients with stable angina. The model demonstrated moderate predictive capability, with an area under the receiver operating characteristic curve (AUC) of 0.818 [95% CI (0.781, 0.852)] in the training set and 0.816 [95% CI (0.779, 0.850)] in the validation set. The Hosmer-Lemeshow test showed good calibration (χ² = 4.55, P = 0.80), and the model's predictive ability was stable. When the threshold probability exceeded 5%, the clinical net benefit of using the model to predict readmission risk was significantly higher than intervening in all patients. ConclusionHistory of heart failure, teeth-marked tongue, weak pulse, wiry pulse, phlegm-stasis mutual syndrome, blood stasis constitution, and non-high-density lipoprotein cholesterol are influencing factors for readmission in patients with stable angina of CHD. A clinical prediction model was developed based on these factors, which showed good discrimination, calibration, and clinical utility, providing a scientific basis for predicting readmission events in patients with stable angina.

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