1.Pre-operative risk assessment of hepatocellular carcinoma recurrence in liver transplant recipients by non-invasive detection of pre-existing genetic lesions
Suqin YANG ; Sunbin LING ; Jianhua LI ; Yan WANG ; Jiapei WANG ; Qiwei HUANG ; Fanming LIU ; Yiqi ZHUANG ; Yingyu ZHENG ; Rui WANG ; Zhe YANG ; Xiaoping ZHENG ; Kai WANG ; Zhikun LIU ; Jun CHEN ; Jianguo WANG ; Haiyang XIE ; Lin ZHOU ; Leiming CHEN ; Guoqiang CAO ; Dandan CHEN ; Junfang JI ; Bin ZHAO ; Chao JIANG ; Di LU ; Xuyong WEI ; Hangjin JIANG ; Qiaonan SHAN ; Hengbo SHI ; Yong-Zhen XU ; Shusen ZHENG ; Zhengxin WANG ; Shengda LIN ; Xiao XU
Clinical and Molecular Hepatology 2026;32(2):884-903
Background/Aims:
Liver transplantation (LT) following total hepatectomy is a life-saving treatment for hepatocellular carcinoma (HCC). The HCC recurrence after LT hinders the effectiveness of the procedure. The objective of this study is to develop a pre-operative risk stratification model based on a liquid biopsy.
Methods:
We conducted a comprehensive multi-omics study of 260 HCC patients from three centers, including clinical data, low-coverage whole-genome sequencing of cell-free DNA (cfDNA) from plasma, as well as whole-exome, single-nucleus RNA, and spatial transcriptomics from matched tumor and non-tumor tissues.
Results:
We identified cfDNA-derived copy number alteration (CNA) signatures associated with post-transplant recurrence. By integrating cfDNA-derived CNA profiles with single-cell transcriptomic data, we traced recurrence-associated cfDNA to a distinct subpopulation of malignant cells within the primary tumor. These cells were embedded in a pro-metastatic microenvironment of specialized endothelial subtypes and cancer-associated fibroblasts. Notably, most recurrence-associated lesions were detectable in cfDNA prior to liver transplantation (LT). Building on these insights, we developed the ZJU Criteria based on CNA fragments and tumor markers, a pre-LT risk prediction tool that integrates conventional clinical factors with cfDNA-derived CNA signatures, and validated it using internal and independent external cohorts.
Conclusion
Our findings suggest that post-transplant recurrence commonly originates from advanced subclones that emerge late during tumor evolution. The ZJU Criteria provides an accurate, non-invasive strategy that significantly improves pre-LT risk stratification and clinical decision-making for patients with HCC.
2.Characterization of a Physiological Mock Circulation System Based on Capillary-Bundle Resistance Element
Dengji LIU ; Xinke CHEN ; Lisha HAN ; Zhen CAO ; Qingzhuo CHI ; Kai YIN ; Ying HE
Journal of Medical Biomechanics 2025;40(5):1256-1264
Objective To investigate the feasibility of parallel capillary bundle arrays for physiomimetic impedance modeling and establish a parametric quantification framework,thereby providing a customizable impedance characterization methodology for diverse in-vitro mock circulation researches.Methods Based on the parallel flow resistance and Poiseuille equation,a tube resistance element with multiple parallel-aligned capillary glass tubes was designed and fabricated.The resistance values of the capillary-bundle and a ball valve were measured through constant flow experiments analogous to electrical resistance measurement method.Moreover,a simple lumped-parameter mock circulation loop was constructed and the pressure and flow rate for each node of the loop were measured under different input flow waveforms.An 0D-Windkessel model corresponding to the experiment was developed.The impedance and compliance were adjusted to match the simulated and experimental pressure and flow waveforms.The accuracy of the capillary bundle impedance in pulsatile experiments was verified by using the computational resistance values.Results The constant-flow impedance calibration experiments revealed that the capillary bundle impedance remained unaffected by flow rate variations over a wide flow range.When the capillary bundle impedance was integrated into the pulsatile circulatory system and the same impedance value obtained from the constant-flow calibration was applied in the computational model,the resulting pressure and flow waveforms showed good agreement with those measured in the pulsatile experiments.However,when the ball valves with nominally identical impedance values were inserted in the pulsatile system,the calculated impedance exhibited a two-fold difference,and significant discrepancies were observed between the simulated and experimental terminal flow waveforms.Conclusions The capillary bundle impedance maintains a constant value regardless of flow rate variations.Once the calibrated resistance value is determined through constant flow experiments,it can be directly applied to pulsatile systems.This approach can provide quantitative pulsatile flow conditions for testing various medical devices.
3.The development and validation of the quick self-assessment questionnaire for cochlear implant out-come
Carol PANG ; Qingyuan FENG ; Li YIN ; Yongmao CAO ; Shanxian GAO ; Yanni CHEN ; Xiaoqiang ZHANG ; Qiaoling SHI ; Zhen SU ; Mingyuan SUN
Journal of Audiology and Speech Pathology 2025;33(5):454-459
Objective To develop and validate a"quick self-assessment questionnaire for cochlear implant out-come(QSACI)".Methods A research team,composed of audiologists,otolaryngologists,data analysis experts,and cochlear implant(CI)recipients,was formed to establish objectives,research subject criteria,and framework of the QSACI.An item pool was creaed through literature review and brainstorming.Question items were evaluated and screened,and the framework and answer options of the questionnaire were established.The comprehensibility,etc.,was analyzed and refined through pilot test,interviews,and expert consultation,leading to the development of the final version.A total of 39 post-lingually deafened adults with known stable outcomes completed the question-naire.The split-half and test-retest reliabilty of the questionnaire was analyzed,and the validity was quantitatively analyzed by comparing scores with the categories of auditory performance(CAP)scores.Results The initial item pool of the questionnaire had 18 items,and the final questionnaire consisted of 12 questions in four dimensions:com-munication status,audiological status,medical factors,and other factors.The average score of 39 recipients was 88.81±6.17 and CAP was 6.19±0.94.The questionnaire showed good reliability and validity,with a Cronbach's alpha coefficient of 0.71 and a test-retest reliability of 0.824(P<0.05).The criterion-related validity,assessed by the correlation between the self-assessment questionnaire scores and CAP scores,showed a significant moderate pos-itive correlation(r=0.512,P<0.05).The correlation coefficient between self-assessment and professional assess-ment was 0.720(P<0.05),indicating a significant correlation.The area under the receiver operating characterstic(ROC)curve was 0.82(P<0.05),the cutoff values corresponding to the maximal Youden index were 82.5 and 88.6,therefore score of 85 was taken as the median threshold score of judgement.Conclusion The QSACI reflects the post-imlplant outcomes,and it can serve as a tool for people with postlingually deafness and their families to un-derstand the eligbility of CI and the expected outcomes,helping to establish realistic expectations before CI surgery.
4.Risk factor analysis of monozygotic twin pregnancy in IVF/ICSI and its impact on perinatal outcomes
Mingmei ZHANG ; Jianrui ZHANG ; Aihua GENG ; Zhuolin YAO ; Shanshan WU ; Bingnan REN ; Yuan CAO ; Yiping WANG ; Xin WANG ; Yichun GUAN ; Zhen LI
Chinese Journal of Reproduction and Contraception 2025;45(3):234-239
Objective:To investigate the influencing factors and perinatal outcomes associated with monozygotic twins (MZT) following elective single embryo transfer (eSET) via in vitro fertilization or intracytoplasmic sperm injection and embryo transfer (IVF/ICSI-ET). Methods:A retrospective cohort study was conducted on 12 079 patients who achieved pregnancy after undergoing IVF/ICSI-eSET at Reproductive Health Hospital of the Third Affiliated Hospital of Zhengzhou University between January 2015 and September 2023. Patients were stratified into two groups based on ultrasound findings 30 d post-transfer: singleton pregnancy group and MZT pregnancy group. Finally, 300 MZT and 1 500 single pregnancies, which were randomly matched according to 1∶5 were included by study period. General patients' characteristics, embryo-related factors, and perinatal outcomes were compared between the two groups. A multivariate logistic regression model was employed to identify risk factors for MZT after single embryo transfer, adjusting for potential confounding variables.Results:The incidence of twin pregnancy following single embryo transfer was 2.48% (300/12 079), which was higher than that of naturally conceived monozygotic twin pregnancy. No significant difference was found in baseline characteristics between the two groups (all P>0.05). The blastocyst transfer rate was higher in the MZT pregnancy group [93.3% (280/300)] than in the singleton pregnancy group [88.8% (1 332/1 500), P=0.022]. Multivariate logistic regression analysis also showed that blastocyst transfer was associated with an increased risk of MZT ( OR=0.552, P=0.016, 95% CI: 0.341-0.894). Analysis of blastocyst cycles showed that the risk of MZT was higher when transferring high-quality blastocysts [79.6% (223/280) vs. 67.8% (903/1 332), P<0.001], where as a trophectoderm (TE) grading of C [20.4% (57/280) vs. 32.2% (429/1 332), P<0.001] had a lower risk of MZT. After adjusting for confounding factors, the risk of MZT was found to increase with the transfer of blastocysts with a B-grade inner cell mass (ICM) ( OR=0.601, P=0.001, 95% CI: 0.442-0.819) and A/B grade TE (grade A: OR=2.951, P<0.001, 95% CI: 1.980-4.399; grade B: OR=1.840, P<0.001, 95% CI: 1.315-2.576). The risk of complications during pregnancy [47.7% (143/300) vs. 19.3% (289/1 500), P<0.001], preterm labor [55.1% (140/254) vs. 7.4% (101/1 368), P<0.001], and the risk of stillbirth [3.7% (11/300) vs. 1.5% (22/1 500), P=0.016] were significantly higher in the MZT pregnancy group than in the singleton pregnancy group. Conclusion:Assisted reproductive technology may contribute to the risk of MZT. Transfer of blastocysts, particularly those with loose ICM arrangement and dense TE arrangement, appears to increase the risk of MZT in patients undergoing eSET.
5.Maintenance of Bausch&Lomb BL11110 phacoemulsification system:Three case reports
An-hai WEI ; Rui NIE ; Li-dong FAN ; Ke-xin PAN ; Zhen-zhen CAO ; Qing-hui REN ; He-hua ZHANG
Chinese Medical Equipment Journal 2025;46(4):118-120
The working principle of Bausch&Lomb BL11110 phacoemulsification system was described.Three cases of typical faults of the phacoemulsification system were introduced,and the causes were analyzed,then the maintenance measures were given accordingly.References were provided for diagnosing and eliminating the faults of the phacoemulsification system.[Chinese Medical Equipment Journal,2025,46(4):118-120]
6.Effects of Orexin-A/OX1R/OX2R on iron death and lipid peroxidation regulation in chronic unpredictable mild stress depressed rats
Zhen ZHANG ; Ming CHENG ; Zhaoshu JIANG ; Jie YANG ; Zhenliang LUO ; Feng CAO
The Journal of Practical Medicine 2025;41(16):2507-2514
Objective To investigate whether orexin A(orexin-A),orexin receptor 1(OX1R)and orexin receptor 2(OX2R)are involved in iron death and lipid peroxidation regulation in chronically unpredictable mild stress(CUMS)depressed rats.Methods Forty rats were randomly divided into a normal group(NC group),a modeling group(Mod group),an exogenous Orexin-A group(Orexin-A group,),and an OX1R/OX2R blocker group(TCS1102 group),with 10 rats in each group.After modeling,behavioral changes were observed using the absent field test(OFT),sugar-water preference test(SPT)and forced swimming test(FST),action potential(PA)and resting membrane potential(Vm)were detected by diaphragm-clamp technique,Orexin-A/OX1R/OX2R protein expression in orbital frontal cortex(OFC)tissues was detected by protein immunoblotting(WB)method,RT-PCR The mRNA expression of glutathione peroxidase 4(GPX4),long chain acyl coenzyme A synthase 4(ACSL4)and cysteine/glutamate transporter light chain(SLC7A11)were detected by RT-PCR method,and the intensity of the expression of rat glial fibrillary acidic protein(GFAP)and lipid peroxidation product 4-hydroxynon-enal(4-HNE)was labeled by immunofluorescence.Results Compared with the NC group,there were significant differences in OFT,SPT and FST behavioral in the Mod group(P<0.01),with lower number of PA issuance(P<0.001),higher Vm(P<0.01),and higher expression of Orexin-A/OX1R/OX2R proteins(P<0.01,P<0.001,and P<0.001).GPX4/SLC7A11 mRNA expression was decreased(P<0.01),ACSL4 mRNA expression was elevated(P<0.01),and the fluorescence intensity expression of both GFAP and 4-HNE was elevated(P<0.001);the number of PA issuance was decreased in the Orexin-A group compared to the Mod group(P<0.05),and the Orexin-A/OX1R/OX2R protein expression was elevated(P<0.05,P<0.01),GPX4/SLC7A11 mRNA ex-pression was decreased(P<0.05),ACSL4 mRNA expression was elevated(P<0.05),and the fluorescence in-tensity of GFAP and 4-HNE expression was elevated(P<0.05,P<0.01);the TCS1102 group had higher expres-sion of GFAP and 4-HNE in the behavioral,Orexin-A/OX1R/OX2R protein expression,PA and Vm,GPX4/SLC7A11/ACSL4 mRNA,and GFAP and 4-HNE fluorescence intensity expression showed a reversed trend.Con-clusions Orexin-A/OX1R/OX2R is involved in the regulation of iron death and lipid peroxidation in CUMS de-pressed rats,and the mechanism may be that Orexin-A enhances the excitability of OFC neurons by activating the OX1R/OX2R signaling pathway,up-regulates the expression of the key factor of iron death,ACSL4/4-HNE,and decreases the expression of GPX4/SLC7A11,which promotes lipid peroxidation and iron death.
7.Characterization of a Physiological Mock Circulation System Based on Capillary-Bundle Resistance Element
Dengji LIU ; Xinke CHEN ; Lisha HAN ; Zhen CAO ; Qingzhuo CHI ; Kai YIN ; Ying HE
Journal of Medical Biomechanics 2025;40(5):1256-1264
Objective To investigate the feasibility of parallel capillary bundle arrays for physiomimetic impedance modeling and establish a parametric quantification framework,thereby providing a customizable impedance characterization methodology for diverse in-vitro mock circulation researches.Methods Based on the parallel flow resistance and Poiseuille equation,a tube resistance element with multiple parallel-aligned capillary glass tubes was designed and fabricated.The resistance values of the capillary-bundle and a ball valve were measured through constant flow experiments analogous to electrical resistance measurement method.Moreover,a simple lumped-parameter mock circulation loop was constructed and the pressure and flow rate for each node of the loop were measured under different input flow waveforms.An 0D-Windkessel model corresponding to the experiment was developed.The impedance and compliance were adjusted to match the simulated and experimental pressure and flow waveforms.The accuracy of the capillary bundle impedance in pulsatile experiments was verified by using the computational resistance values.Results The constant-flow impedance calibration experiments revealed that the capillary bundle impedance remained unaffected by flow rate variations over a wide flow range.When the capillary bundle impedance was integrated into the pulsatile circulatory system and the same impedance value obtained from the constant-flow calibration was applied in the computational model,the resulting pressure and flow waveforms showed good agreement with those measured in the pulsatile experiments.However,when the ball valves with nominally identical impedance values were inserted in the pulsatile system,the calculated impedance exhibited a two-fold difference,and significant discrepancies were observed between the simulated and experimental terminal flow waveforms.Conclusions The capillary bundle impedance maintains a constant value regardless of flow rate variations.Once the calibrated resistance value is determined through constant flow experiments,it can be directly applied to pulsatile systems.This approach can provide quantitative pulsatile flow conditions for testing various medical devices.
8.Prediction of Peritumoral Brain Tissue Invasion in Atypical Meningioma by Multimodality MRI-Based Nomogram Model
Yijing ZHAO ; Jianping HU ; Mengcheng LI ; Dairong CAO ; Zhen XING
Chinese Journal of Medical Imaging 2025;33(1):12-17,47
Purpose To evaluate the value of multimodality MRI-based nomogram model for predicting peritumoral brain tissue invasion in atypical meningioma.Materials and Methods A total of 187 patients with pathologically diagnosed atypical meningioma in the First Affiliated Hospital Fujian Medical University from January 2018 to January 2023 were retrospectively enrolled,including 130 cases of peritumoral brain tissue invasion and 57 cases of none peritumoral brain tissue invasion.Clinical data and multimodality MRI features,including age,gender,tumor location,maximum diameter,peritumoral oedema,tumor-brain interface,lobulated sign,dural tail sign,cyst degeneration/necrosis,relative minimum apparent diffusion coefficient(rADCmin)and intratumoral susceptibility signal were analyzed.Univariate and multivariate Logistic regression analysis were performed to screen the independent predictors of peritumoral brain tissue invasion in atypical meningioma,then a multimodality MRI prediction model was constructed,and was visualized as a nomogram.The prediction performance of multimodality MRI-based nomogram model and each independent predictor were assessed using receiver operating characteristic curve.Results The maximum diameter(OR=0.705,95%CI 0.539-0.920,P=0.010),peritumoral oedema(OR=1.333,95%CI 1.095-1.624,P=0.004),tumor-brain interface(OR=5.121,95%CI 2.045-12.806,P<0.001)and rADCmin(OR=0.126,95%CI 0.033-0.483,P=0.002)were independent predictors of peritumoral brain tissue invasion in atypical meningioma.The area under the curve,sensitivity and specificity of the multimodality MRI-based nomogram model for predicting peritumoral brain tissue invasion in atypical meningioma was 0.80(95%CI 0.73-0.88),87.69%and 66.67%,respectively.The multimodality MRI-based nomogram model showed significantly higher area under the curve than that of the maximum diameter,peritumoral oedema,tumor-brain interface and rADCmin of atypical meningioma(all Z=3.665,3.904,4.359,3.701,P<0.05).Conclusion The multimodality MRI-based nomogram model may be helpful for the prediction of peritumoral brain tissue invasion in atypical meningioma.
9.Risk factors and nomogram construction for predicting long-term survival in hepatoid adenocarcinoma of the stomach
Yuyuan LU ; Hao CUI ; Bo CAO ; Qixuan XU ; Jingwang GAO ; Ruiyang ZHAO ; Huiguang REN ; Zhen YUAN ; Jiajun DU ; Jiahong SUN ; Jianxin CUI ; Bo WEI
Chinese Journal of Gastrointestinal Surgery 2025;28(2):157-168
Objective:This study aimed to analyze the prognostic risk factors for hepatoid adenocarcinoma of the stomach (HAS) and construct two nomogram-based clinical prediction models to predict overall survival (OS) and recurrence-free survival (RFS) in patients with HAS.Methods:Data were retrospectively collected from 82 patients (64 males, 18 females; mean age 60.3 ± 9.4 years) who underwent radical gastrectomy and were pathologically diagnosed with gastric hepatoid adenocarcinoma at the First Medical Center of the PLA General Hospital between February 2006 and September 2023. Statistical analyses were conducted using SPSS 25.0 and R 4.3.2. Survival analyses were performed using the Kaplan-Meier method, and univariate analyses were used to identify clinical and pathological factors associated with prognosis. Variables with P<0.05 in the univariate analysis were included in multivariate Cox regression models to identify independent risk factors for OS and RFS. These factors were incorporated into the prediction models to construct nomograms. The discriminatory power of the models was assessed using the area under the curve (AUC) of receiver operating characteristic (ROC) analyses, while calibration curves, decision curve analysis (DCA), and comparisons with the 8th edition of the TNM staging system of the American Joint Committee on Cancer (AJCC) were employed to evaluate model performance. Results:Among the 82 patients, 36 (43.9%) exhibited vascular infiltration, 61 (74.4%) had nerve infiltration, and lymph node metastasis was observed in 60 cases (73.2%). Pathological stages I, II, III, and IV were distributed as 11 (13.4%), 26 (31.7%), 44 (53.7%), and 1 (1.2%) cases, respectively. Inflammatory markers included neutrophil-to-lymphocyte ratio (NLR) ≥ 4.33 in 22 cases (26.8%), platelet-to-lymphocyte ratio (PLR) ≥ 142.2 in 50 cases (61.0%), monocyte-to-lymphocyte ratio (MLR) ≥ 0.411 in 22 cases (26.8%), α-fetoprotein (AFP) ≥ 2.48 μg/L in 64 cases (78.0%), and C-reactive protein (CRP) ≥ 7.506 mg/L in 12 cases (14.6%). Among the 82 patients, 3 cases (3.6%) were lost to follow-up. The median follow-up time was 52 (range: 8–147) months, with a median OS of 61(2–147) months. The 1-year and 3-year OS rates were 78.5% and 58.5%, respectively, while the 1-year and 3-year RFS rates were 77.3% and 60.3%, respectively. Multivariate analysis identified several independent risk factors influencing OS in patients with HAS: advanced pathological stage, MLR ≥ 0.411, AFP ≥ 2.545 μg/L, and CRP ≥ 7.51 mg/L. The hazard ratios (HRs) and 95% confidence intervals (CIs) were as follows: 5.218 (1.230–22.143), 2.610 (1.287–5.294), 2.950 (1.013–8.589), and 2.594 (1.145–5.877), respectively (all P < 0.05). For RFS, advanced pathological stage, PLR ≥ 152.0, and MLR ≥ 0.411 were independent risk factors, with HRs (95% CIs) of 4.735 (1.080–20.760), 3.759 (1.259–11.226), and 2.714 (1.218–6.048), respectively (all P < 0.05). The AUC values for OS prediction at 1 year, 3 years, and 5 years were 0.7765, 0.7525, and 0.7702, respectively. For RFS, the AUC values were 0.7304, 0.8137, and 0.8307 at 1 year, 3 years, and 5 years, respectively. The calibration curves demonstrated strong agreement between nomogram- predicted outcomes and observed survival data. DCA indicated that both TNM staging and the nomogram-based clinical prediction models provided a net positive benefit in predicting OS and RFS in HAS patients, with the nomogram model demonstrating superior performance. Conclusion:The nomogram-based clinical prediction models developed in this study demonstrated robust performance in predicting long-term OS and RFS in patients with HAS.
10.Analysis of clinical outcome of IVF/ICSI with dual-stimulation protocol in POSEIDON patients with low expected prognosis
Zhuolin YAO ; Zhen LI ; Caihua ZHANG ; Mingmei ZHANG ; Ruolin JIA ; Yuan CAO ; Yiping WANG ; Yichun GUAN
The Journal of Practical Medicine 2025;41(4):580-587
Objective To compare the clinical outcomes of the clomiphene citrate(CC)dual stimulation protocol and the luteal phase ovarian stimulation protocol after natural cycle oocytes retrieved in POSEIDON patients with low expected prognosis.Methods The clinical data from patients who underwent in vitro fertilization(IVF)or intracytoplasmic sperm injection(ICSI)at the Reproductive Center of the Third Affiliated Hospital of Zhengzhou University from May 2016 to December 2023 were analyzed retrospectively.According to the POSEI-DON criteria,including POSEIDON group 3 and group 4,which were treated with the CC dual stimulation protocol(the CC group)and the luteal-phase ovarian stimulation protocol after the natural cycle oocytes retrieval(the natural cycle group).The basic data and clinical outcomes of the two ovulation protocols were analyzed,and the main observations included the number of oocytes retrieved,the cumulative clinical pregnancy rate and the cumulative live birth rate,and explored the impact of ovulation promotion regimens on clinical outcomes through binary logis-tic regression.Results On the whole,there was no significant difference in the total number of oocytes retrieved,cumulative clinical pregnancy rate and live birth rate between the CC group and the natural cycle group(all P>0.05),And in POSEIDON group 4,the numbers of oocytes retrieved in the follicular phase of the CC group were higher than those in the natural cycle group,whereas the number of oocytes retrieved in the luteal phase of natural cycle group were higher,and the difference was statistically significant(P<0.05).After logistic regression analysis,the ovulation stimulation protocols did not affect the cumulative clinical pregnancy rate and live birth rate of POSEI-DON 3 and 4 group(P>0.05).Conclusions For the POSEIDON patients with a low expected prognosis,the clinical effectiveness of the luteal phase ovarian stimulation protocol after natural cycle oocytes retrieved is not inferior to that of the CC dual stimulation protocol.In POSEIDON group 4,on the premise that the AMH levels of patients in the natural cycle group were lower than those in the CC group,who underwent natural cycle ovulation followed by luteal phase induction achieved similar clinical outcomes to those of the CC dual stimulation protocol group.Therefore,the luteal phase ovarian stimulation protocol after natural cycle oocytes retrieved should be more clinically recommended for POSEIDON group 4 patients.

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