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.Study on primary screening technique for children with autism spectrum disorder
Yuying HE ; Chunmei WEN ; Yingyu YAN ; Xifeng YANG ; Lei LONG ; Wuyue YANG ; Xiaoyan YANG ; Jingjing ZHENG ; Yang ZHOU ; Yanni CHEN
Chinese Journal of Preventive Medicine 2024;58(1):81-86
To explore screening tools for children with autism spectrum disorder (ASD), which are convenient for primary hospitals, it can provide basic data for formulating ASD prevention policies. This was a cross-sectional study by cluster sampling. Huyi District and Xincheng District were extracted for investigation in Xi′an City. From July 2021 to September 2022, all children aged from 3 months to 36 months who live in the two districts were subjected to primary screening. The child care physician used the routine screening tool "warning signs checklist for screening psychological, behavioral and developmental problems of children" and cartoon pictures of "early high-risk warning signs of autism", the children who were positive in the initial screening were referred to the district level maternal and child health hospital for re-screening, and those who were positive in the re-screening were referred to Xi ′an Children′s Hospital for diagnosis. The results showed that a total of 17 905 children aged from 3 months to 36 months were initially screened in the two districts, including 10 588 children aged from 18 months to 36 months, 50 children who were positive in the initial screening and 50 children who were re-screened. 23 children (18 boys and 5 girls) were diagnosed with ASD. The prevalence rate of ASD in children was 2.17‰ (95% confidence interval:1.29‰-3.06‰). 42 children were positive for "warning signs checklist" at the preliminary screening, and 19 were confirmed as ASD. 27 children were positive for "cartoon pictures" in the preliminary screening, and 23 were confirmed with ASD. The "cartoon pictures" in the preliminary screening and diagnosis of consistent rate was higher than the "warning signs checklist", two kinds of screening methods comparison were statistically significant difference in the odds of consistent (χ 2=11.01, P=0.001). In conclusion, relying on the three-level network of maternal and child health care, it is conducive to the whole process management of screening and diagnosis of children with ASD, and to guide the formulation of prevention policies. The cartoon pictures of "early high-risk warning signs of autism" can assist the identification of children with ASD based on the "warning signs checklist", which is simple, effective and suitable for promotion in the community health care.
3.Multicenter study on the etiology characteristics of neonatal purulent meningitis
Yanli LIU ; Jiaojiao CAI ; Xiaoyi ZHANG ; Minli ZHU ; Zhenlang LIN ; Yicong PAN ; Junhu ZHENG ; Yiwei ZHAO ; Xiang WANG ; Hongping LU ; Meifang LIN ; Ji WANG ; Haihong GU ; Lizhen WANG ; Keping CHENG ; Yuxuan DAI ; Yuan GAO ; Junsheng LI ; Hongxia FANG ; Na SUN ; Lihua LI ; Xiaoquan LI ; Ying LIU ; Yingyu LI ; Wa GAO ; Minxia LI
Chinese Journal of Infectious Diseases 2023;41(6):393-400
Objective:To study the distribution and antibiotics resistance of the main pathogens of neonatal purulent meningitis in different regions of China.Methods:A retrospective descriptive clinical epidemiological study was conducted in children with neonatal purulent meningitis which admitted to 18 tertiary hospitals in different regions of China between January 2015 to December 2019. The test results of blood and cerebrospinal fluid, and drug sensitivity test results of the main pathogens were collected. The distributions of pathogenic bacteria in children with neonatal purulent meningitis in preterm and term infants, early and late onset infants, in Zhejiang Province and other regions outside Zhejiang Province, and in Wenzhou region and other regions of Zhejiang Province were analyzed. The chi-square test was used for statistical analysis.Results:A total of 210 neonatal purulent meningitis cases were collected. The common pathogens were Escherichia coli ( E. coli)(41.4%(87/210)) and Streptococcus agalactiae ( S. agalactiae)(27.1%(57/210)). The proportion of Gram-negative bacteria in preterm infants (77.6%(45/58)) with neonatal purulent meningitis was higher than that in term infants (47.4%(72/152)), and the difference was statistically significant ( χ2=15.54, P=0.001). There were no significant differences in the constituent ratios of E. coli (36.5%(31/85) vs 44.8%(56/125)) and S. agalactiae (24.7%(21/85) vs 28.8%(36/125)) between early onset and late onset cases (both P>0.05). The most common pathogen was E. coli in different regions, with 46.7%(64/137) in Zhejiang Province and 31.5%(23/73) in other regions outside Zhejiang Province. In Zhejiang Province, S. agalactiae was detected in 49 out of 137 cases (35.8%), which was significantly higher than other regions outside Zhejiang Province (11.0%(8/73)). The proportions of Klebsiella pneumoniae, and coagulase-negative Staphylococcus in other regions outside Zhejiang Province (17.8%(13/73) and 16.4%(12/73)) were both higher than those in Zhejiang Province (2.9%(4/137) and 5.1%(7/137)). The differences were all statistically significant ( χ2=14.82, 12.26 and 7.43, respectively, all P<0.05). The proportion of Gram-positive bacteria in Wenzhou City (60.8%(31/51)) was higher than that in other regions in Zhejiang Province (38.4%(33/86)), and the difference was statistically significant ( χ2=6.46, P=0.011). E. coli was sensitive to meropenem (0/45), and 74.4%(32/43) of them were resistant to ampicillin. E. coli had different degrees of resistance to other common cephalosporins, among which, cefotaxime had the highest resistance rate of 41.8%(23/55), followed by ceftriaxone (32.4%(23/71)). S. agalactiae was sensitive to penicillin, vancomycin and linezolid. Conclusions:The composition ratios of pathogenic bacteria of neonatal purulent meningitis are different in different regions of China. The most common pathogen is E. coli, which is sensitive to meropenem, while it has different degrees of resistance to other common cephalosporins, especially to cefotaxime.
4.Temporal and spatial stability of the EM/PM molecular subtypes in adult diffuse glioma.
Jing FENG ; Zheng ZHAO ; Yanfei WEI ; Zhaoshi BAO ; Wei ZHANG ; Fan WU ; Guanzhang LI ; Zhiyan SUN ; Yanli TAN ; Jiuyi LI ; Yunqiu ZHANG ; Zejun DUAN ; Xueling QI ; Kai YU ; Zhengmin CONG ; Junjie YANG ; Yaxin WANG ; Yingyu SUN ; Fuchou TANG ; Xiaodong SU ; Chuan FANG ; Tao JIANG ; Xiaolong FAN
Frontiers of Medicine 2023;17(2):240-262
Detailed characterizations of genomic alterations have not identified subtype-specific vulnerabilities in adult gliomas. Mapping gliomas into developmental programs may uncover new vulnerabilities that are not strictly related to genomic alterations. After identifying conserved gene modules co-expressed with EGFR or PDGFRA (EM or PM), we recently proposed an EM/PM classification scheme for adult gliomas in a histological subtype- and grade-independent manner. By using cohorts of bulk samples, paired primary and recurrent samples, multi-region samples from the same glioma, single-cell RNA-seq samples, and clinical samples, we here demonstrate the temporal and spatial stability of the EM and PM subtypes. The EM and PM subtypes, which progress in a subtype-specific mode, are robustly maintained in paired longitudinal samples. Elevated activities of cell proliferation, genomic instability and microenvironment, rather than subtype switching, mark recurrent gliomas. Within individual gliomas, the EM/PM subtype was preserved across regions and single cells. Malignant cells in the EM and PM gliomas were correlated to neural stem cell and oligodendrocyte progenitor cell compartment, respectively. Thus, while genetic makeup may change during progression and/or within different tumor areas, adult gliomas evolve within a neurodevelopmental framework of the EM and PM molecular subtypes. The dysregulated developmental pathways embedded in these molecular subtypes may contain subtype-specific vulnerabilities.
Humans
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Brain Neoplasms/pathology*
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Neoplasm Recurrence, Local/metabolism*
;
Glioma/pathology*
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Neural Stem Cells/pathology*
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Oligodendrocyte Precursor Cells/pathology*
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Tumor Microenvironment
5.Effects of magnesium sulfate wet compress nursing on prognosis of child′s scrotum hematoma after indirect inguinal hernia
Yingyu SU ; Shanshan ZHUANG ; Guili WU ; Ruihong ZHENG
Chinese Journal of Modern Nursing 2015;(27):3325-3326,3327
Objective To investigate effects of magnesium sulfate wet compress nursing on prognosis of child′s scrotum hematoma after indirect inguinal hernia. Methods A total of 54 pediatric children were collected for inguinal hernia operation by convenient sampling method, and random number table method were used to averagely divide patients into control group ( received routine nursing ) and observation group ( given conventional care and magnesium sulfate local wet dressing care) . The child′s length of hematoma vanishing and incidence of complications were compared between two groups. Results In the observation group, the length of hematoma vanishing was 4-10 d, the average time (5. 8 ± 1. 45)d, while the length of hematoma vanishing was 6-14 d, the average (7. 8 ± 2. 11)d in the control group (P<0. 05). There was no incidence of ulcer, local infection and other complications in the observation group whereas 3 cases of ulcer and 1 cases of local infection in the control group (P<0. 05). Conclusions Magnesium sulfate wet compress nursing can shorten the length of child′s scrotum hematoma vanishing after indirect inguinal hernia surgery and reduce the incidence of complications.
6.The application of three-dimensional cell culture technology in the field of cancer research
Yingyu WANG ; Yin LU ; Weiwei ZHANG ; Zhiguang SUN ; Shizhong ZHENG ; Lei CHEN
Chinese Pharmacological Bulletin 2009;25(12):1545-1548
Traditional 2D cell culture technology is widely used in cell culture field, but it lacks the formation of 3D matrix scaffold and lacks specific cytokines in vivo.Cells in 3D cell culture system are similar to cells in vivo for gene expression and cell activity. The article focuses on the application of three-dimensional cell culture technology in cancer research, including the construction of tumor microenvironment,tumor biological behavior, tumor angiogenesis, drug resistance and so on and provides a reference for cancer research workers.
7.Effects of Zhiling capsule on apoptosis and expressions of hTERT,CD44 in small cell lung cancer cell line NCI-H446
Yingyu CHEN ; Yunling PAN ; Zhihong ZHENG ; Mingji PAN ; Jianda HU ; Tingbo LIU
Chinese Pharmacological Bulletin 2003;0(10):-
Aim To explore the mechanisms of the apoptosis induction and the effects of adhesion suppression of Zhiling capsule (ZLJN) in small cell lung cancer cell line NCI-H446.Methods According to the different components of ZLJN,NCI-H446 cells were treated with traditional Chinese medicine,western medicine and ZLJN composite groups.Apoptotic cells were tested by light microscopy,Hochest33258 staining method.The mRNA and protein expressions of bcl-2,bax and hTERT were analyzed by RT-PCR and Western blot respectively.The expressions of CD44 were detected by flow cytometry.Results After NCI-H446 cells were treated with different drug groups,The morphological changes of apoptotic cells were found by light microscopy and Hochest33258 staining method.The mRNA and protein expressions of bcl-2 were down-regulated while the expressions of bax were up-regulated compared to the control groups(P
8.The effects of Zhiling capsule on the proliferation inhibition and apoptosis induction in K562 cell line via caspase-3 pathway
Zhihong ZHENG ; Yunling PAN ; Yingyu CHEN ; Mingji PAN ; Tingbo LIU ; Jianda HU
Chinese Pharmacological Bulletin 2003;0(09):-
Aim To investigate the effects of Zhiling capsule (ZLJN) on the proliferation inhibition and apoptosis induction in K562 cell line.Methods According to the different components of ZLJN,K562 cells were treated respectively with tradtional Chinese medicine,Western medicine and ZLJN compound groups.The cell viability and colony formation were observed by MTT assay and colony formation assay respectively.Apoptotic cells were detected by Annexin V-FITC/PI staining and DNA fragmentation assay.Caspase-3 activity was detected by flow cytometry,and pro-caspase-3 was detected by Western blot.Results Treated with drug,K562 cell growth and cell colony formation were significantly inhibited.Apoptosis occurring in the early stage was identified by Annexin V-FITC/PI staining.Typical DNA ladder was seen from gel electrophoresis and apparent apoptotic peaks were observed by flow cytometer.The level of caspase-3 activity increased after the treatment,while the level of pro-caspase-3 decreased.Conclusion ZLJN can efficiently inhibit proliferation and induce apoptosis in K562 cells,which may be related with the up-regulation of caspase-3 activity.
9.Expression of TFAR19 in Apoptotic Processes of Jurkat Cells Induced with Various Methods
Li LI ; Yingyu CHEN ; Rui ZHENG ; Dalong MA ; Debing WANG
Journal of Experimental Hematology 2000;8(2):81-84
A new apoptosis-related gene TFAR19 was recently cloned. A primary functional analysis indicates its role in the apoptotic process of TF-1 cells. To clarify TFAR19 was involved in which apoptotic pathway, the changes in TFAR19 expression were observed during the apoptotic processes of Jurkat cells induced with various methods: serum deprivation, VP-16 treatment and Fas McAb activation. Then TFAR19 expression in Jurkat cells was detected with flow cytometry and Western blot, and TFAR19 mRNA with RT-PCR. Our results showed that expression of TFAR19 in Jurkat cells was increased at 12 hours after serum deprivation, 2 hours after VP-16 treatment and 2 hours after Fas McAb activation, respectively. These observations suggested that TFAR19 was involved in the apoptotic process of Jurkat cells induced with serum deprivation, DNA destruction and death receptor activation. It might take effect in the early apoptotic process. TFAR19 is a participant of the "final common pathway" in the apoptotic pathway.

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