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.Clinical value of high frequency ultrasound in the diagnosis of hip joint involvement in patients with ankylosing spondylitis
Guo-Yan XUE ; Ying-Qi LI ; Rui WANG ; Wen-Xing WANG ; Zhuang DONG ; Jian-Feng DING
China Journal of Orthopaedics and Traumatology 2024;37(4):374-380
Objective To analyze the correlation between hip joint musculoskeletal ultrasound score and ankylosing spondylitis(AS)disease activity,as well as to investigate the value of high frequency ultrasound in the assessment of hip joint involvement in AS.Methods The clinical data of 244 patients with AS who were treated in the rheumatology department of from March 2019 to March 2022 were retrospectively analyzed.Among them,there 174 males and 70 females,aged from 19 to 58 years old with an average of(34.22±9.49)years old;the disease duration of AS patients ranged from 8 months to 26 years,with an average of(13.68±4.04)years.The 244 patients were divided into disease group(83 cases)and control group(161 cases)based in the presence of hip joint involuement.According to the the disease activity,patients in the disease group were further categorezed into active phase(45 cases)and stable phase(38 cases).The ultrasound scores of patients in the active and stable phases of the disease group and the control group were compared.Relevant factors of hip joint involvement in AS patients were analyzed,and analyze the correlation between ultrasound score and Bath ankylosing spondylitis disease activity score index(BASD AI),Bath ankylosing spondylitis functional index(BASFI),visual analogue score of pain(VAS),C-reactive protein(CRP),erythrocyte sedimentation rate(ESR),and the correlation between hip joint capsule score and tendon attach-ment end score and BASDAI,BASFI,VAS,CRP and ESR.Results The hip joint capsule score(3.06±1.12),femoral head score(1.45±0.43),tendon attachment end score(3.28±1.30)and total ultrasound score(6.65±2.31)of the disease group were higher than those of the control group(1.51±0.48)、(0.66±0.27)、(1.61±0.53)、(3.81±1.44)scores(P<0.05).Multifactor Logstic re-gression analysis showed that the course of disease,hip joint capsule score and total ultrasound score were independent risk factors for hip involvement in AS patients.The hip capsule score(3.65±1.22)and total ultrasound score(8.28±2.33)in the ac-tive phase of the disease group were higher than those in the stable phase(2.48±1.04)、(6.82±1.96)scores(P<0.05).The hip joint capsule score and total ultrasonic score of AS patients were positively correlated with BASDAI,BASFI,VAS,CRP,and ESR(P<0.05,P<0.01).The score of tendon attachment end was positively correlated with CRP(P<0.05).The score of joint capsule effusion in AS patients was positively correlated with BASDAI,BASFI and VAS(P<0.05,P<0.01).The synovial blood flow score was positively correlated with BASDAI,VAS,CRP and ESR(P<0.05,P<0.01).The synovial thickening score was positively correlated with BASDAI,BASFI,VAS,CRP and ESR(P<0.05,P<0.01).There was no correlation between the score of tendon attachment end and BASDAI,BASFI,VAS,CRP and ESR.Conclusion There is a correlation between hip joint ul-trasonic score of hip joint and clinical indexes in AS patients.Hip joint capsule score and total ultrasonic score were indepen-dent risk factors for hip involvement in AS patients.High frequency ultrasound exhibits clinical value in the diagnosis of hip joint involvement in AS patients.
5.Reasons and strategies of reoperation after oblique lateral interbody fusion
Zhong-You ZENG ; Deng-Wei HE ; Wen-Fei NI ; Ping-Quan CHEN ; Wei YU ; Yong-Xing SONG ; Hong-Fei WU ; Shi-Yang FAN ; Guo-Hao SONG ; Hai-Feng WANG ; Fei PEI
China Journal of Orthopaedics and Traumatology 2024;37(8):756-764
Objective To summarize the reasons and management strategies of reoperation after oblique lateral interbody fusion(OLIF),and put forward preventive measures.Methods From October 2015 to December 2019,23 patients who under-went reoperation after OLIF in four spine surgery centers were retrospectively analyzed.There were 9 males and 14 females with an average age of(61.89±8.80)years old ranging from 44 to 81 years old.The index diagnosis was degenerative lumbar intervertebral dics diseases in 3 cases,discogenie low back pain in 1 case,degenerative lumbar spondylolisthesis in 6 cases,lumbar spinal stenosis in 9 cases and degenerative lumbar spinal kyphoscoliosis in 4 cases.Sixteen patients were primarily treated with Stand-alone OLIF procedures and 7 cases were primarily treated with OLIF combined with posterior pedicle screw fixation.There were 17 cases of single fusion segment,2 of 2 fusion segments,4 of 3 fusion segments.All the cases underwent reoperation within 3 months after the initial surgery.The strategies of reoperation included supplementary posterior pedicle screw instrumentation in 16 cases;posterior laminectomy,cage adjustment and neurolysis in 2 cases,arthroplasty and neuroly-sis under endoscope in 1 case,posterior laminectomy and neurolysis in 1 case,pedicle screw adjustment in 1 case,exploration and decompression under percutaneous endoscopic in 1 case,interbody fusion cage and pedicle screw revision in 1 case.Visu-al analogue scale(VAS)and Oswestry disability index(ODI)index were used to evaluate and compare the recovery of low back pain and lumbar function before reoperation and at the last follow-up.During the follow-up process,the phenomenon of fusion cage settlement or re-displacement,as well as the condition of intervertebral fusion,were observed.The changes in in-tervertebral space height before the first operation,after the first operation,before the second operation,3 to 5 days after the second operation,6 months after the second operation,and at the latest follow-up were measured and compared.Results There was no skin necrosis and infection.All patients were followed up from 12 to 48 months with an average of(28.1±7.3)months.Nerve root injury symptoms were relieved within 3 to 6 months.No cage transverse shifting and no dislodgement,loosening or breakage of the instrumentation was observed in any patient during the follow-up period.Though the intervertebral disc height was obviously increased at the first postoperative,there was a rapid loss in the early stage,and still partially lost after reopera-tion.The VAS for back pain recovered from(6.20±1.69)points preoperatively to(1.60±0.71)points postoperatively(P<0.05).The ODI recovered from(40.60±7.01)%preoperatively to(9.14±2.66)%postoperatively(P<0.05).Conclusion There is a risk of reoperation due to failure after OLIF surgery.The reasons for reoperation include preoperative bone loss or osteoporosis the initial surgery was performed by Stand-alone,intraoperative endplate injury,significant subsidence of the fusion cage after surgery,postoperative fusion cage displacement,nerve damage,etc.As long as it is discovered in a timely manner and handled properly,further surgery after OLIF surgery can achieve better clinical results,but prevention still needs to be strengthened.
6.Detection of five tick-borne pathogens in Maanshan City,Anhui Province,China
Guo-Dong YANG ; Kun YANG ; Liang-Liang JIANG ; Ming WU ; Ying HONG ; Ke-Xia XIANG ; Jia HE ; Lei GONG ; Dan-Dan SONG ; Ming-Jia BAO ; Xing-Zhou LI ; Tian QIN ; Yan-Hua WANG
Chinese Journal of Zoonoses 2024;40(4):308-314
Here,5 important pathogens carried by ticks in Maanshan City,Anhui Province,China were identified.In to-tal,642 ticks were collected from 13 villages around Maanshan City and identified by morphological and mitochondrial COI genes.The 16S rRNA gene of Francisella tularensis,ssrA gene of Bartonella,16S rRNA,ompA and ompB genes of Rickett-sia,16S rRNA and gltA genes of Anaplasma,and groEL and rpoB genes of Coxiella were sequenced.Reference sequences were retrieved from a public database.Phylogenetic trees were constructed with MEG A1 1.0 software.In total,36 Rickettsiae isolates were detected in 640 Haemaphysalis longicornis ticks,which included 20 isolates of Rickettsia heilongjian-gensis,16 of Candidatus Rickettsia jingxinensis,2 of Ana-plasma bovis,and 186 of Coxiella-like endosymbiont.R.hei-longjiangensis HY2 detected in this study and Anhui B8 strain,Ca.R.jingxinensis QL3 and those from Shanxi Prov-ince and Jiangsu Province,A.bovis JX4 and those from Shanxi Province were clustered on the same branch.Overall,17 ticks had combined infections and none of the 5 bacteria were detected in two Amblyomma testudinarium ticks.This is the first report of Ca.R.jingxinensis detected in H.longicornis ticks from Anhui Province.It is recommended that the two types of Rickettsia that cause spotted fever and A.bovis should be reported to local health authorities to initiate appropriate prevention and control measures.
7.Functional Studies on the Regulation of Flowering by PfFT3,a Member of the Perilla PEBP Gene Family
Qi-Feng WANG ; Xiao-Yan FENG ; Hui LI ; Fu-Peng HOU ; Xi GUO ; Jun-Xing LU ; Jian HU ; Tao ZHANG
Chinese Journal of Biochemistry and Molecular Biology 2024;40(8):1173-1184
Perilla frutescens,a short-day plant,is rich in biologically active substances and nutrients.Current research on Perilla frutescens focuses on agronomic traits such as yield and fatty acid accumula-tion,with limited exploration of the flowering process and floral organ development.The molecular regu-latory mechanisms underlying these aspects remain unclear.FLOWERING LOUC T(FT)is a florigen in Arabidopsis,plays critical roles in floral transition.PfFT3 is unannotated by genome but annotated by transcriptomics data to the FT-like subfamily.Its function in controlling flowering is yet to be explored.Here subcellular localization analysis showed that PfFT3 is localized in the nucleus and cytoplasm.The plant over-expression vector pCAMBIAI1303-PfFT3 was constructed and transformed into wild-type(Col-0)and mutant fd-2,fd-3,and ft-10 plants by agrobacterium-mediated inflorescence infiltration as a means of obtaining genetically stable and pure overexpression and backfill transgenic lines in Arabidopsis,respectively.Analysis of the results showed that overexpression of PfFT3 significantly promoted early flowering in Arabidopsis and rescued the late-flowering phenotype of the mutants fd-2,fd-3,and ft-10,and that expression of the exogenous PfFT3 promoted the expression of the downstream endogenous flow-ering genes AtSOC1,AtAP1,AtFUL,and AtLFY.This study demonstrates the positive role of PfFT3 in promoting flowering,providing a foundation for further investigation of PfPEBP function and advancing the breeding of early-flowering Perilla frrutescens cultivars.
8.Diagnostic value of transvaginal contrast-enhanced ultrasound in identifying benign and malignant endometrial lesions and assessing myometrial invasion
Fang GUO ; Yulin YAN ; Chengsheng HUANG ; Xia WANG ; Xing WU ; Yanli XU ; Tao YING
Ultrasonography 2024;43(6):448-456
Purpose:
The objective of this study was to evaluate the diagnostic value of transvaginal contrastenhanced ultrasound (CEUS) in differentiating benign from malignant endometrial lesions and assessing the extent of myometrial invasion.
Methods:
A total of 70 patients who underwent surgery for endometrial lesions at the authors’ hospital were selected. Transvaginal ultrasound examination and CEUS were performed for quantitative and qualitative analysis. Based on the CEUS results, an International Federation of Gynecology and Obstetrics (FIGO) disease grade was assigned and compared with pathological findings.
Results:
Postmenopausal vaginal bleeding is a key clinical manifestation of endometrial carcinoma. Among the patients with endometrial carcinoma, compared with normal myometrium, the lesion areas exhibited a greater rate of rise (defined as enhanced intensity divided by enhancement time) and a shorter half-clearance time (P<0.05). These findings suggest that in endometrial carcinoma, the contrast agent displays a "fast-in/fast-out/hyperenhancement" perfusion pattern. In contrast, the characteristic perfusion pattern for benign endometrial lesions is low enhancement (P<0.05). The diagnostic accuracy of CEUS in detecting myometrial invasion was 88% (22 of 25 cases).
Conclusion
Transvaginal CEUS is a practical and effective diagnostic imaging method for distinguishing between benign and malignant endometrial lesions. It can also be used to evaluate the depth of myometrial invasion in patients with early-stage endometrial carcinoma.
9.Analysis of the prevalence and risk factors of frailty among older persons in a Beijing community
Yue WU ; Yiwei ZHAO ; Zhibin WANG ; Yiwen XING ; Xue GAO ; Yu WANG ; Lina MA ; Yi TANG ; Yansu GUO ; Yumin WANG
Chinese Journal of Health Management 2024;18(8):571-575
Objective:To investigate the prevalence of frailty among elders aged ≥60 years in the Beijing community and analyze the risk factors of frailty.Methods:This is a cross-sectional study. A total of 1936 older persons in Baizhifang Community in Beijing were included between May and September 2023. Their frailty was evaluated by Fried Frailty Phenotype Scale. Mini Nutritional Assessment-Short Form (MNA-SF), Short Physical Performance Battery (SPPB), and Geriatric Depression Scale (GDS) were used to evaluate nutritional status, physical function, and depression, respectively. The prevalence and risk factors of frailty among the elderly in the community were analyzed.Results:A total of 168 individuals met the criteria for frailty, and the prevalence of frailty was 8.7%. Compared to the non-frail group, the frail group was predominantly female (71.4% vs 62.2%; χ 2=5.59, P=0.018), older [(72.1±6.6) vs (69.9±6.0) ages; t=-5.25, P<0.001], unmarried (1.8% vs 0.8%; χ 2=8.60, P=0.014), with lower education levels (10.7% vs 3.5%; χ 2=23.38, P<0.001), poorer self-assessed health (22.6% vs 6.5%; χ 2=69.80, P<0.001), lower MNA-SF scores [(12.2±2.2) vs (13.0±1.4) scores; t=6.29, P<0.001], lower SPPB scores [(8.4±1.9) vs (10.2±1.6) scores; t=14.62, P<0.001], higher GDS scores [(4.0±3.8) vs (1.9±2.1) scores; t=-11.48, P<0.001], and worse vision, hearing, and olfactory functions (48.2% vs 34.1%, 36.9% vs 23.0%, 9.5% vs 3.0%; χ 2=13.37, 16.11, 40.58, all P<0.001). They were also more likely to suffer from hypertension (70.8% vs 56.7%; χ 2=12.52, P<0.001), diabetes (42.3% vs 29.4%; χ 2=12.06, P<0.001), osteoarthritis (46.4% vs 30.3%; χ 2=18.39, P<0.001) and stroke (19.0% vs 13.3%; χ 2=4.28, P=0.039). Logistic regression analysis showed that frailty was independently associated with nutritional status ( OR=0.8, 95% CI: 0.7-0.9, P<0.001), depressive symptoms ( OR=1.1, 95% CI: 1.1-1.2, P<0.001), olfactory function ( OR=2.1, 95% CI: 1.4-3.0, P<0.001; OR=2.9, 95% CI: 1.4-5.9, P=0.003), and physical function ( OR=0.6, 95% CI: 0.6-0.7, P<0.001) after adjusting for covariates. Conclusions:The prevalence of frailty among elderly people in community is relatively high. Frailty in community elders is associated with physical function, psychological function, nutritional status, and olfactory function decline.
10.Mobility limitation condition and its relationship with cognitive function in community-dwelling older adults
Yiwen XING ; Yiwei ZHAO ; Zhibin WANG ; Yue WU ; Xue GAO ; Yu WANG ; Xi CHU ; Yansu GUO ; Yi TANG ; Yumin WANG ; Lina MA
Chinese Journal of Health Management 2024;18(9):662-667
Objective:To analyze mobility limitation condition and its relationship with cognitive function in community-dwelling elderly.Methods:In this cross-sectional study, a total of 1 935 older adults aged≥60 years were recruited from May to September 2023 in Beijing Baizhifang Community Health Service Center and its five subordinate health service stations (Baizhifang Hutong health service station, Nancaiyuan community health service station, Youanmen community health service station, Younei West Street health service station and Shuanghuaili community health service station). The Short Physical Performance Battery (SPPB) was used to assess the mobility capacity of the elderly, and the elderly were divided into two groups with SPPB, the elderly with a SPPB≤9 points were grouped into mobility limitation group (645 cases), and the ones with a SPPB≥10 points were considered with normal mobility capacity (1 290 cases). The cognitive function of the older adults was assessed with the mini-mental state examination; and the gender, age, calf circumference, history of chronic disease, frailty status, cognitive function, nutritional status, depression status, hearing and vision condition of the two groups were compared with χ2 test or Mann-Whitney U non-parametric test. Multiple logistic regression analysis was used to analyze the mobility limitation and its relationship with cognitive function in the older adults. Results:Mobility limitation was found in 33.33% (645/1 935) of community-dwelling older adults. The proportions of advanced age, female, hypertension, diabetes, coronary heart disease, stroke, chronic obstructive pulmonary disease, frailty, depression, cognitive impairment, hearing decline, and vision decline in the mobility limitation group were all significantly higher than those in the normal mobility capacity group (31.32% vs 13.41%, 69.92% vs 59.61%, 65.27% vs 54.03%, 33.80% vs 28.60%, 27.91% vs 19.53%, 17.83% vs 11.47%, 10.54% vs 7.36%, 13.18% vs 2.02%, 18.45% vs 6.59%, 14.73% vs 7.75%, 30.54% vs 20.31%, 45.58% vs 30.39%) (all P<0.05). Advanced age ( OR=2.542, 95% CI: 1.977-3.269), female ( OR=1.736, 95% CI: 1.390-2.167), stroke ( OR=1.426, 95% CI: 1.065-1.911), depression ( OR=2.292, 95% CI: 1.656-3.174), cognitive impairment ( OR=1.601, 95% CI: 1.154-2.220), frailty ( OR=5.199, 95% CI: 3.219-8.397) and vision decline ( OR=1.405, 95% CI: 1.124-1.756) were all positively correlated with the mobility limitation in the community-dwelling older adults (all P<0.05). Conclusion:The older adults in the community have a higher risk of mobility limitation, mobility limitation is a positive correlation factor of cognitive impairment.

Result Analysis
Print
Save
E-mail