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.Proteomics combined with bioinformatics analysis of protein markers of dry eye
Yanting YANG ; Yajun SHI ; Guang YANG ; Haiyang JI ; Jie LIU ; Jue HONG ; Dan ZHANG ; Xiaopeng MA
International Eye Science 2025;25(1):104-111
AIM:To analyze differential proteins associated with the pathogenesis of dry eye(DE)using bioinformatics methods, in order to reveal their potential molecular mechanisms.METHODS: Articles published in PubMed and EMBASE databases from the inception of the database to August 31, 2023, that used proteomic methods to detect protein expression in clinical samples of dry eye were searched. Differential proteins were selected and further analyzed using the STRING database and Cytoscape software for hub gene screening and module analysis. Protein-protein interaction(PPI)analysis, gene ontology(GO)functional annotation, and Kyoto encyclopedia of genes and genomes(KEGG)pathway enrichment analysis were performed.RESULTS: A total of 21 articles were included, identifying 74 differentially expressed proteins. The most frequently occurring differential proteins were calgranulin A(SA1008), lipocalin-1(LCN1), lysozyme C(LYZ), mammaglobin-B(SCGB2A1), proline-rich protein 4(PRR4), transferrin(TF), and calgranulinB(S100A9). The top 10 hub genes were serum albumin(ALB), tumor necrosis factor(TNF), interleukin 6(IL6), IL1B, IL8, matrix metalloproteinase 9(MMP9), alpha-1-antitrypsin(SERPINA1), IL10, complement component 3(C3), and lactotransferrin(LTF). Module analysis suggested MMP9 and PRR4 as seed genes. KEGG analysis showed that differential proteins were mainly enriched in the IL17 signaling pathway(61.9%).CONCLUSION: The results reveal potential molecular targets and pathways for DE and confirm the association between the pathogenesis of DE and inflammation. Further in-depth research is needed to confirm the significance of these biomarkers in clinical practice.
3.Preoperative prediction of factors associated with impacted ureteral stones and construction of a nomogram model
Xinyu SHI ; Haiyang WEI ; Changbao XU ; Wuxue LI ; Xiaofu WANG ; Tianhe ZHANG ; Zhiheng HUANG ; Xinghua ZHAO
Chinese Journal of Urology 2025;46(9):669-675
Objective:To explore the predictive factors for ureteral stone impaction preoperatively and to construct a nomogram prediction model for impacted ureteral stones.Methods:A retrospective analysis was conducted on the clinical data of 209 patients with ureteral stones treated at The Second Affiliated Hospital of Zhengzhou University from July 2023 to June 2024. There were 164 males(78.5%)and 45 females(21.5%). The age was 49(47,57)years,and the body mass index(BMI)was 25.10(23.55,27.24)kg/m2. Of the patients,85(40.7%)had comorbid hypertension and 85(40.7%)had comorbid diabetes. Stones were located on the left side in 124 patients(59.3%)and on the right side in 85 patients(40.7%). Hydronephrosis was present in 169 patients(80.9%),and urine culture was positive in 29 patients(13.9%). Patients were divided into impacted and non-impacted groups based on the presence or absence of ureteral stone impaction. Univariate and multivariate logistic regression analyses were performed to determine independent predictive factors for impacted ureteral stones. A nomogram model was constructed based on these results. The performance of the predictive model was evaluated using receiver operating characteristic(ROC)curves,calibration plots,and decision curve analysis(DCA).Results:Among the 209 patients in this study,85(40.7%)experienced ureteral stone impaction. The impacted group had a significantly higher neutrophil-to-lymphocyte ratio(NLR)than the non-impacted group(3.91 ± 2.05 vs. 3.25 ± 2.10, P = 0.024),a higher rate of hydronephrosis[81.2%(69/85)vs. 80.6%(100/124), P = 0.002],larger stone surface area[(64.96 ± 39.96)mm2 vs.(51.86 ± 39.80)mm2, P = 0.021],greater ureteral wall thickness(UWT)[(3.96 ± 1.37)mm vs.(3.06 ± 1.33)mm, P < 0.001],and a higher ratio of the upper ureter diameter(D1)to the lower ureter diameter(D2)(DDR)(2.87 ± 1.58 vs. 2.00 ± 0.99, P < 0.001). Univariate analysis showed that NLR,hydronephrosis,stone length,stone surface area,UWT,D1,D2,and DDR were statistically significant( P < 0.05). After multivariate logistic regression analysis,the following items were identified as independent predictors of impacted ureteral stones:NLR( OR = 1.205,95% CI 1.026 - 1.415, P = 0.023),hydronephrosis( OR = 1.840,95% CI 1.236 - 2.740, P = 0.003),stone length( OR = 1.587,95% CI 1.142 - 2.206, P = 0.006),ureteral wall thickness(UWT)( OR = 1.643,95% CI 1.263 - 2.136, P < 0.001),and DDR( OR = 2.907,95% CI 1.040 - 8.130, P = 0.042).Based on these independent predictive factors,a nomogram prediction model for impacted ureteral stones was constructed. The area under the ROC curve was 0.797(95% CI 0.737 - 0.858),and the calibration curve showed good consistency. The decision curve suggested that the model had good clinical net benefit. Conclusions:NLR,hydronephrosis,stone length,UWT,and DDR are all independent predictors for impacted ureteral stones. The nomogram model constructed based on these factors has good predictive performance.
4.Efficacy comparison of subsequent treatment modalities for locally advanced hypopharyngeal cancer with partial response to neoadjuvant chemotherapy
Ru WANG ; Zheng LI ; Jugao FANG ; Junfang XIAN ; Qi ZHONG ; Yang ZHANG ; Lizhen HOU ; Hongzhi MA ; Ling FENG ; Shizhi HE ; Qian SHI ; Yifan YANG ; Haiyang LI ; Lingwa WANG ; Xinyu LI
Chinese Journal of Otorhinolaryngology Head and Neck Surgery 2025;60(10):1223-1231
Objective:To compare the survival outcomes of different subsequent treatment regimens in patients with locally advanced hypopharyngeal squamous cell carcinoma (HPSCC) who achieved partial response (PR) after neoadjuvant chemotherapy based on the gross tumor volume regression rate (GTVRR).Methods:This retrospective study included patients with locally advanced HPSCC treated at the Department of Head and Neck Surgery, Beijing Tongren Hospital, from January 2011 to December 2023. The cohort included 135 males and 3 females, aged from 35 to 77 years. All patients received 2-3 cycles of TPF regimen (paclitaxel+cisplatin+5-fluorouracil) neoadjuvant chemotherapy. Subsequent treatments included concurrent chemoradiotherapy or surgery combined with postoperative adjuvant radiotherapy. The impacts of different subsequent treatment modalities on the survivals and prognoses of patients were compared based on GTVRR thresholds of 50% and 70%. The χ 2 test was used to analyze influencing factors; survival analysis and intergroup comparisons were performed using the Kaplan-Meier method and Log-rank test; prognostic factors were assessed using univariate and multivariate Cox regression analyses. Results:The 5-year OS and PFS rates were 56.5% and 47.9%, respectively, while, the 10-year OS and PFS rates were 25.8% and 21.2%, respectively. The median OS was 75 months, and the median PFS was 48 months. The laryngeal function preservation rate for the entire cohort was 83.3%. The patients who underwent surgery combined with postoperative radiotherapy had significantly better OS and PFS outcomes than those treated with concurrent chemoradiotherapy ( P<0.05). Stratification based on GTVRR revealed that the surgery plus postoperative radiotherapy regimen was particularly effective for PR patients with a GTVRR of 30%-70%, showing significantly better OS and PFS compared to the concurrent chemoradiotherapy group ( P<0.05). Conclusion:The optimal subsequent treatment for PR-HPSCC may be surgery-based comprehensive treatment, particularly for patients with a GTVRR of 30%-70%. This study offers valuable insights for the stratified treatment of HPSCC, which could contribute to improving overall patient prognosis.
5.Efficacy of intelligent temperature-pressure-controlled flexible ureteroscopy combined with negative-pressure suction sheath lithotripsy in the treatment of ≤2.5 cm upper urinary tract stones
Xiaofu WANG ; Yunxiang ZHANG ; Xinyu SHI ; Yongli ZHAO ; Changbao XU ; Changwei LIU ; Haiyang WEI ; Xinghua ZHAO
Journal of Modern Urology 2025;30(4):311-314
Objective: To investigate the efficacy and safety of intelligent temperature-pressure-controlled flexible ureteroscopy combined with negative-pressure suction sheath lithotripsy in the treatment of upper urinary tract stones ≤2.5 cm. Methods: The clinical data of 225 patients with ≤2.5 cm upper urinary tract stones treated with this surgical method in our department during Aug. 2023 and Jul. 2024 were retrospectively analyzed. The patients were divided into the dual-control group (n=36) and conventional group (n=189) according to whether or not the intelligent temperature and pressure control device was used during operation. In the dual-control group,the intraoperative temperature and pressure in the renal pelvis were monitored and controlled in real time by the temperature and pressure sensors distributed at the end of the ureteral soft lens. The perioperative parameters,stone-removal rate,complication rate and renal function were compared between the two groups. Results: All operations were successfully completed in both groups. The postoperative procalcitonin (PCT) level [(22.75±5.85) ng/L vs. (29.08±6.60) ng/L,P=0.001],difference in the white blood cell (WBC) level [(0.24±2.12)×10
cells/L vs. (1.19±2.17)×10
cells/L,P=0.016],incidence of fever (2.8% vs. 16.9%,P=0.028) and overall complication rate (5.6% vs. 19.6%,P=0.042) were significantly lower in the dual-control group than in the conventional group,while the stone-clearance rate was slightly higher (88.9% vs. 82.5%,P=0.346),with no significant difference. Conclusion: For upper urinary tract stones ≤2.5 cm,intelligent temperature-pressure-controlled ureteroscopy combined with negative-pressure suction sheath lithotripsy has a satisfactory stone-removal rate and a low rate of complications,which is worthy of clinical promotion.
6.Efficacy comparison of subsequent treatment modalities for locally advanced hypopharyngeal cancer with partial response to neoadjuvant chemotherapy
Ru WANG ; Zheng LI ; Jugao FANG ; Junfang XIAN ; Qi ZHONG ; Yang ZHANG ; Lizhen HOU ; Hongzhi MA ; Ling FENG ; Shizhi HE ; Qian SHI ; Yifan YANG ; Haiyang LI ; Lingwa WANG ; Xinyu LI
Chinese Journal of Otorhinolaryngology Head and Neck Surgery 2025;60(10):1223-1231
Objective:To compare the survival outcomes of different subsequent treatment regimens in patients with locally advanced hypopharyngeal squamous cell carcinoma (HPSCC) who achieved partial response (PR) after neoadjuvant chemotherapy based on the gross tumor volume regression rate (GTVRR).Methods:This retrospective study included patients with locally advanced HPSCC treated at the Department of Head and Neck Surgery, Beijing Tongren Hospital, from January 2011 to December 2023. The cohort included 135 males and 3 females, aged from 35 to 77 years. All patients received 2-3 cycles of TPF regimen (paclitaxel+cisplatin+5-fluorouracil) neoadjuvant chemotherapy. Subsequent treatments included concurrent chemoradiotherapy or surgery combined with postoperative adjuvant radiotherapy. The impacts of different subsequent treatment modalities on the survivals and prognoses of patients were compared based on GTVRR thresholds of 50% and 70%. The χ 2 test was used to analyze influencing factors; survival analysis and intergroup comparisons were performed using the Kaplan-Meier method and Log-rank test; prognostic factors were assessed using univariate and multivariate Cox regression analyses. Results:The 5-year OS and PFS rates were 56.5% and 47.9%, respectively, while, the 10-year OS and PFS rates were 25.8% and 21.2%, respectively. The median OS was 75 months, and the median PFS was 48 months. The laryngeal function preservation rate for the entire cohort was 83.3%. The patients who underwent surgery combined with postoperative radiotherapy had significantly better OS and PFS outcomes than those treated with concurrent chemoradiotherapy ( P<0.05). Stratification based on GTVRR revealed that the surgery plus postoperative radiotherapy regimen was particularly effective for PR patients with a GTVRR of 30%-70%, showing significantly better OS and PFS compared to the concurrent chemoradiotherapy group ( P<0.05). Conclusion:The optimal subsequent treatment for PR-HPSCC may be surgery-based comprehensive treatment, particularly for patients with a GTVRR of 30%-70%. This study offers valuable insights for the stratified treatment of HPSCC, which could contribute to improving overall patient prognosis.
7.Preoperative prediction of factors associated with impacted ureteral stones and construction of a nomogram model
Xinyu SHI ; Haiyang WEI ; Changbao XU ; Wuxue LI ; Xiaofu WANG ; Tianhe ZHANG ; Zhiheng HUANG ; Xinghua ZHAO
Chinese Journal of Urology 2025;46(9):669-675
Objective:To explore the predictive factors for ureteral stone impaction preoperatively and to construct a nomogram prediction model for impacted ureteral stones.Methods:A retrospective analysis was conducted on the clinical data of 209 patients with ureteral stones treated at The Second Affiliated Hospital of Zhengzhou University from July 2023 to June 2024. There were 164 males(78.5%)and 45 females(21.5%). The age was 49(47,57)years,and the body mass index(BMI)was 25.10(23.55,27.24)kg/m2. Of the patients,85(40.7%)had comorbid hypertension and 85(40.7%)had comorbid diabetes. Stones were located on the left side in 124 patients(59.3%)and on the right side in 85 patients(40.7%). Hydronephrosis was present in 169 patients(80.9%),and urine culture was positive in 29 patients(13.9%). Patients were divided into impacted and non-impacted groups based on the presence or absence of ureteral stone impaction. Univariate and multivariate logistic regression analyses were performed to determine independent predictive factors for impacted ureteral stones. A nomogram model was constructed based on these results. The performance of the predictive model was evaluated using receiver operating characteristic(ROC)curves,calibration plots,and decision curve analysis(DCA).Results:Among the 209 patients in this study,85(40.7%)experienced ureteral stone impaction. The impacted group had a significantly higher neutrophil-to-lymphocyte ratio(NLR)than the non-impacted group(3.91 ± 2.05 vs. 3.25 ± 2.10, P = 0.024),a higher rate of hydronephrosis[81.2%(69/85)vs. 80.6%(100/124), P = 0.002],larger stone surface area[(64.96 ± 39.96)mm2 vs.(51.86 ± 39.80)mm2, P = 0.021],greater ureteral wall thickness(UWT)[(3.96 ± 1.37)mm vs.(3.06 ± 1.33)mm, P < 0.001],and a higher ratio of the upper ureter diameter(D1)to the lower ureter diameter(D2)(DDR)(2.87 ± 1.58 vs. 2.00 ± 0.99, P < 0.001). Univariate analysis showed that NLR,hydronephrosis,stone length,stone surface area,UWT,D1,D2,and DDR were statistically significant( P < 0.05). After multivariate logistic regression analysis,the following items were identified as independent predictors of impacted ureteral stones:NLR( OR = 1.205,95% CI 1.026 - 1.415, P = 0.023),hydronephrosis( OR = 1.840,95% CI 1.236 - 2.740, P = 0.003),stone length( OR = 1.587,95% CI 1.142 - 2.206, P = 0.006),ureteral wall thickness(UWT)( OR = 1.643,95% CI 1.263 - 2.136, P < 0.001),and DDR( OR = 2.907,95% CI 1.040 - 8.130, P = 0.042).Based on these independent predictive factors,a nomogram prediction model for impacted ureteral stones was constructed. The area under the ROC curve was 0.797(95% CI 0.737 - 0.858),and the calibration curve showed good consistency. The decision curve suggested that the model had good clinical net benefit. Conclusions:NLR,hydronephrosis,stone length,UWT,and DDR are all independent predictors for impacted ureteral stones. The nomogram model constructed based on these factors has good predictive performance.
8.Impact of optimizing stroke green channel on treatment efficiency of acute ischemic stroke treatment efficiency in a county hospital
Yao WANG ; Lei SHI ; Guangbu LI ; Qiyun ZHU ; Xiaoqiang WU ; Maolin LU ; Haiyang LIN ; Wei QI ; Wei GAO ; Ruiyin ZHOU ; Qifeng LU ; Baodong WU
Chinese Journal of Clinical Medicine 2024;31(6):971-976
Objective To evaluate the impact of optimizing the stroke green channel on the efficiency of acute ischemic stroke management in a county hospital. Methods A retrospective analysis of the emergency stroke green channel treatment data from Sixian People’s Hospital from May 2020 to April 2021 (before optimization of the green channel) and from May 2021 to April 2022 (after optimization of the green channel) was conducted. The rates of intravenous thrombolysis (IVT) and mechanical thrombectomy (MT) patients, as well as door-to-needle time (DNT), door-to-puncture time (DPT), and the modified Rankin scale (mRS) scores of patients three months post-treatment before and after the optimization of the stroke green channel were compared. Results Within one year before and after optimization of the green channel, the number of acute visits for ischemic stroke was 3 143 and 2 623, respectively. Before optimization, 84 and 51 underwent IVT and MT, respectively. After optimization of the green channel, the ratios of patients underwent IVT (n=215) and MT (n=103) significantly increased, and both DNT and DPT were significantly shortened (P<0.000 1); the proportion of MT patients with an mRS score of 0-2 at 3 months post-discharge significantly increased (46/99 vs 13/46, P=0.038). Conclusion After optimizing the green channel at Sixian People’s Hospital, the efficiency of stroke treatment has significantly improved, and the patients’ prognosis improved.
9.Role of subminiature and recurrent chromosome copy number variations in recurrent spontaneous abortion
Erfeng YUAN ; Liying SONG ; Yu WANG ; Hongmei DU ; Yang FANG ; Jinshuang GAO ; Yaqing GUO ; Haiyang YU ; Qianqian SHI ; Xinjing YAN ; Linlin ZHANG
Chinese Journal of Reproduction and Contraception 2024;44(8):816-821
Objective:To explore the key copy number variation (CNV) regions, abortion candidate genes and signaling pathways associated with recurrent spontaneous abortion (RSA).Methods:A retrospective cohort study was conducted based on the data of 1 870 miscarriage cases of RSA patients who received CNV analysis by high-throughput sequencing technology in the Laboratory Medicine Department of the Third Affiliated Hospital of Zhengzhou University from January 2016 to September 2022. These cases were divided into different groups based on the age of miscarriage and gestational age of the pregnant women. Chi-square test or Fisher's exact test was used to analyze the distribution of chromosome abnormalities and CNV. Gene functions and signaling pathways in RSA-related CNV were identified by gene enrichment analysis.Results:Among the 1 870 tissues, 1 001 (53.53%) cases were detected with chromosomal abnormalities. A total of 140 CNVs were detected in 93 tissues (9.29%), including 34 submicroscopic CNVs (segment<10 Mb) and 106 large CNVs with segment≥10 Mb. Submicroscopic pathogenicity CNVs with statistical differences were involved 1p36.33p36.23, 2q37.3, 4p16.3, 22q11.21 (χ 2=6.99, P=0.008) in early RSA embryos (≤12 weeks). 16p11.2 and Xp11.23p11.22 microdeletion were firstly reported in abortion cases. Significantly recurrent large CNVs were mainly involved 18q22q23 (del/dup), 4p16p15, 9p24p22, 8p23p22, and Xp22.3 regions, and the candidate genes mainly concentrated on PI3K-Akt and JAK-STAT signaling pathway. Conclusion:Rare submicroscopic CNVs and recurrent large CNVs were associated with RSA in early pregnancy. GO and KEGG database analysis revealed potential abortion candidate genes and signaling pathways, providing new information for the genetic etiology of RSA.
10.Role and mechanism of long non-coding RNA MEG3 in alleviation of myocardial ischemia-reperfusion injury in ovariectomized rats
Haiyang ZHANG ; Jingru FENG ; He SHI ; Zijian WANG ; Guanghui CHENG ; Shengli BI
Chinese Journal of Geriatric Heart Brain and Vessel Diseases 2024;26(12):1483-1488
Objective To investigate the effect and mechanism of long non-coding RNA(lncRNA)maternally expressed gene 3(MEG3)on the alleviation of myocardial ischemia-reperfusion(IR)injury by sponging miR-21 in rats after ovariectomy(OVX).Methods A total of 108 female SD rats were subjected,and 48 of them were randomly divided into sham group,OVX group,IR group and combined group 1(OVX+IR),with 12 rats in each group.And the remaining 60 rats were given an injection with blank adeno-associated virus(AAV,negative control),lncRNA MEG3 AAV and miR-21 AAV,respectively through the tail vein before OVX and myocardial IR modeling,and then consequently assigned into negative sham group,negative model group,lncRNA MEG3 group,miR-21 group,and combined group 2(lncRNA MEG3+miR-21),with 12 rats in each group.Myocardial infarction size,left ventricular ejection fraction(LVEF),left ven-tricular fractional shortening(LVFS),serum lactate dehydrogenase(LDH),creatine kinase(CK),creatine kinase isoenzyme(CK-MB)content,cardiomyocyte apoptotic rate and expression level of cleaved Caspase-3 were determined.Dual luciferase reporter gene assay was used to detect lncRNA MEG3 targeting miR-21 in H9c2 cardiomyocytes.Results Compared with the sham group,the expression of lncRNA MEG3 was decreased and that of miR-21 was increased in the OVX group,IR group and combined group 1(P<0.05).The combination group 1 had significant-ly lower lncRNA MEG3 expression and higher miR-21 expression than the OVX group and IR group(P<0.05).Compared with the negative model group,the myocardial infarction size,serum LDH,CK,CK-MB,cardiomyocyte apoptotic rate,and cleaved Caspase-3 expression were de-creased,while LVFS and LVEF were increased in the lncRNA MEG3 group(P<0.05).Compared with the lncRNA MEG3 group,myocardial infarction size,serum LDH,CK,CK-MB content,car-diomyocyte apoptotic rate,Cleaved Caspase-3 expression were increased,while LVFS and LVEF were decreased in the combined group 2[(43.58±3.32)%vs(50.37±4.29)%,(57.12±4.28)%vs(68.47±5.61)%,P<0.05].Conclusion Overexpression of lncRNA MEG3 alleviates the myo-cardium IR injury in OVX rats by sponging miR-21.

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