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  • 11
    Online Resource
    Online Resource
    The effect of biliary obstruction, biliary drainage and bile reinfusion on bile acid metabolism and gut microbiota in mice
    Wiley ; 2022
    In:  Liver International Vol. 42, No. 1 ( 2022-01), p. 135-148
    Details
    In: Liver International, Wiley, Vol. 42, No. 1 ( 2022-01), p. 135-148
    Abstract: Preoperative obstructive jaundice is usually associated with higher post‐operative mortality. Although external biliary drainage (EBD) has been widely used to relieve obstructive jaundice, the role of bile reinfusion after EBD is still controversial. The aim of our study was to study the effects of biliary obstruction, biliary drainage and bile reinfusion on bile acid metabolism and gut microbiota. Methods Firstly, we created a mice bile drainage collection (BDC) model to simulate the process of biliary obstruction, drainage and bile reinfusion. Then, we analysed the faecal, serum, liver and bile samples to investigate the effects of the process on bile acid profiles and gut microbiota. Finally, we evaluated the clinical effects of bile reinfusion. Results We evaluated the bile acid profiles of faeces, serum, liver and bile of normal mice. During biliary obstruction, secondary bile acids can still be produced, and increased in the liver and serum of mice. Compared with no bile reinfusion, bile reinfusion was beneficial to the recovery of T‐ωMCA in the liver and bile, and can restore the colon crypt length shortened by biliary obstruction. Only Ruminococcus_1 proliferated when the biliary obstruction lasted for 12 days. In the clinic, bile reinfusion cannot accelerate the patient's perioperative recovery or prolong long‐term survival. Conclusion We have successfully created a mice bile drainage collection model. Short‐term bile reinfusion can partially benefit the recovery of the secondary bile acids in the liver and bile, but hardly benefit the patient's perioperative recovery or long‐term survival. (247 words).
    Type of Medium: Online Resource
    ISSN: 1478-3223 , 1478-3231
    URL: Issue
    URL: Article
    DOI: 10.1111/liv.v42.1
    DOI: 10.1111/liv.15047
    Language: English
    Publisher: Wiley
    Publication Date: 2022
    detail.hit.zdb_id: 2124684-1
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  • 12
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    Development of a nomogram model for prediction of new adjacent vertebral compression fractures after vertebroplasty
    Springer Science and Business Media LLC ; 2023
    In:  BMC Surgery Vol. 23, No. 1 ( 2023-07-10)
    Details
    In: BMC Surgery, Springer Science and Business Media LLC, Vol. 23, No. 1 ( 2023-07-10)
    Abstract: Vertebroplasty is the main minimally invasive operation for osteoporotic vertebral compression fracture (OVCF), which has the advantages of rapid pain relief and shorter recovery time. However, new adjacent vertebral compression fracture (AVCF) occurs frequently after vertebroplasty. The purpose of this study was to investigate the risk factors of AVCF and establish a clinical prediction model. Methods We retrospectively collected the clinical data of patients who underwent vertebroplasty in our hospital from June 2018 to December 2019. The patients were divided into a non-refracture group (289 cases) and a refracture group (43 cases) according to the occurrence of AVCF. The independent predictive factors for postoperative new AVCF were determined by univariate analysis, least absolute shrinkage and selection operator (LASSO) logistic regression, and multivariable logistic regression analysis. A nomogram clinical prediction model was established based on relevant risk factors, and the receiver operating characteristic curve (ROC), calibration curve, and decision curve analysis (DCA) were used to evaluate the prediction effect and clinical value of the model. After internal validation, patients who underwent vertebroplasty in our hospital from January 2020 to December 2020, including a non-refracture group (156 cases) and a refracture group (21 cases), were included as the validation cohort to evaluate the prediction model again. Results Three independent risk factors of low bone mass density (BMD), leakage of bone cement and “O” shaped distribution of bone cement were screened out by LASSO regression and logistic regression analysis. The area under the curve (AUC) of the model in the training cohort and the validation cohort was 0.848 (95%CI: 0.786–0.909) and 0.867 (95%CI: 0.796–0.939), respectively, showing good predictive ability. The calibration curves showed the correlation between prediction and actual status. The DCA showed that the prediction model was clinically useful within the whole threshold range. Conclusion Low BMD, leakage of bone cement and “O” shaped distribution of bone cement are independent risk factors for AVCF after vertebroplasty. The nomogram prediction model has good predictive ability and clinical benefit.
    Type of Medium: Online Resource
    ISSN: 1471-2482
    URL: Article
    DOI: 10.1186/s12893-023-02068-6
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2023
    detail.hit.zdb_id: 2050442-1
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  • 13
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    Online Resource
    Immunomodulatory Layered Double Hydroxide Nanoparticles Enable Neurogenesis by Targeting Transforming Growth Factor Receptor 2
    American Chemical Society (ACS) ; 2021
    In:  ACS Nano Vol. 15, No. 2 ( 2021-02-23), p. 2812-2830
    Details
    In: ACS Nano, American Chemical Society (ACS), Vol. 15, No. 2 ( 2021-02-23), p. 2812-2830
    Type of Medium: Online Resource
    ISSN: 1936-0851 , 1936-086X
    URL: Article
    URL: Article
    DOI: 10.1021/acsnano.0c08727
    DOI: 10.1021/acsnano.0c08727.s001
    Language: English
    Publisher: American Chemical Society (ACS)
    Publication Date: 2021
    detail.hit.zdb_id: 2383064-5
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  • 14
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    Prediction of subsequent osteoporotic vertebral compression fracture on CT radiography via deep learning
    Wiley ; 2022
    In:  VIEW Vol. 3, No. 6 ( 2022-12)
    Details
    In: VIEW, Wiley, Vol. 3, No. 6 ( 2022-12)
    Abstract: Combination of computed tomography (CT) radiography and deep learning to predict subsequent osteoporotic vertebral compression fracture (OVCF) has not been reported. To do so, we analyzed retrospectively CT images from 103 patients who experienced twice OVCF in Tongji Hospital from 2011 to 2022. Meanwhile, CT images from 70 age‐matched osteoporotic patients without vertebral fracture were used as the negative control. Convolutional neural network was used for classification and the Adam optimizer combining the momentum and exponentially weighted moving average gradients methods were used to update the weights of the networks. In the prediction model, we split 80% data of each type of the patient as the training group, while the other 20% was held as the independent testing group. We found that the number of subsequent fracture in women is higher than that in men (81 vs. 22). Additionally, the incidence rate of adjacent vertebral fracture is higher than that of remote vertebral fracture (64.1 vs. 35.9%), while the onset time of the former was 11.9 ± 12.8 months, significantly less than 22.3 ± 18.2 months of the latter ( p   〈  .001). For the prediction of subsequent fracture, our model attained .839 of accuracy and .883 of receiver operating characteristic–area under curve on the whole testing dataset. Furthermore, our model gained .867 and .719 of accuracy on the single‐class testing dataset separated from the former, .817 of accuracy on the independent test. In conclusion, we managed to generate a deep learning‐based model, which is able to predict subsequent OVCF in a precise and unbiased way just using CT images.
    Type of Medium: Online Resource
    ISSN: 2688-268X , 2688-268X
    URL: Issue
    URL: Article
    DOI: 10.1002/viw2.v3.6
    DOI: 10.1002/VIW.20220012
    Language: English
    Publisher: Wiley
    Publication Date: 2022
    detail.hit.zdb_id: 3021474-9
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  • 15
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    Online Resource
    Hepatobiliary Tumor Organoids Reveal HLA Class I Neoantigen Landscape and Antitumoral Activity of Neoantigen Peptide Enhanced with Immune Checkpoint Inhibitors
    Wiley ; 2022
    In:  Advanced Science Vol. 9, No. 22 ( 2022-08)
    Details
    In: Advanced Science, Wiley, Vol. 9, No. 22 ( 2022-08)
    Abstract: Neoantigen‐directed therapy lacks preclinical models recapitulating neoantigen characteristics of original tumors. It is urgent to develop a platform to assess T cell response for neoantigen screening. Here, immunogenic potential of neoantigen‐peptides of tumor tissues and matched organoids ( n = 27 pairs) are analyzed by Score tools with whole genome sequencing (WGS)‐based human leukocyte antigen (HLA)‐class‐I algorithms. The comparisons between 9203 predicted neoantigen‐peptides from 2449 mutations of tumor tissues and 9991 ones from 2637 mutations of matched organoids demonstrate that organoids preserved majority of genetic features, HLA alleles, and similar neoantigen landscape of original tumors. Higher neoantigen load is observed in tumors with early stage. Multiomics analysis combining WGS, RNA‐seq, single‐cell RNA‐seq, mass spectrometry filters out 93 candidate neoantigen‐peptides with strong immunogenic potential for functional validation in five organoids. Immunogenic peptides are defined by inducing increased CD107aCD137IFN‐ γ expressions and IFN‐ γ secretion of CD8 cells in flow cytometry and enzyme‐linked immunosorbent assay assays. Nine immunogenic peptides shared by at least two individuals are validated, including peptide from TP53 R90S . Organoid killing assay confirms the antitumor activity of validated immunogenic peptide‐reactive CD8 cells, which is further enhanced in the presence of immune checkpoint inhibitors. The study characterizes HLA‐class‐I neoantigen landscape in hepatobiliary tumor, providing practical strategy with tumor organoid model for neoantigen‐peptide identification in personalized immunotherapy.
    Type of Medium: Online Resource
    ISSN: 2198-3844 , 2198-3844
    URL: Issue
    URL: Article
    DOI: 10.1002/advs.v9.22
    DOI: 10.1002/advs.202105810
    Language: English
    Publisher: Wiley
    Publication Date: 2022
    detail.hit.zdb_id: 2808093-2
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  • 16
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    miRNA and lncRNA as biomarkers in cholangiocarcinoma(CCA)
    Impact Journals, LLC ; 2017
    In:  Oncotarget Vol. 8, No. 59 ( 2017-11-21), p. 100819-100830
    Details
    In: Oncotarget, Impact Journals, LLC, Vol. 8, No. 59 ( 2017-11-21), p. 100819-100830
    Type of Medium: Online Resource
    ISSN: 1949-2553
    URL: Issue
    URL: Article
    DOI: 10.18632/oncotarget.v8i59
    DOI: 10.18632/oncotarget.19044
    Language: English
    Publisher: Impact Journals, LLC
    Publication Date: 2017
    detail.hit.zdb_id: 2560162-3
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  • 17
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    EVs-mediated delivery of CB2 receptor agonist for Alzheimer's disease therapy
    Elsevier BV ; 2023
    In:  Asian Journal of Pharmaceutical Sciences Vol. 18, No. 4 ( 2023-07), p. 100835-
    Details
    In: Asian Journal of Pharmaceutical Sciences, Elsevier BV, Vol. 18, No. 4 ( 2023-07), p. 100835-
    Type of Medium: Online Resource
    ISSN: 1818-0876
    URL: Article
    DOI: 10.1016/j.ajps.2023.100835
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2023
    detail.hit.zdb_id: 2650931-3
    SSG: 15,3
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  • 18
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    Genome-wide mapping of 5-hydroxymethylcytosines in circulating cell-free DNA as a non-invasive approach for early detection of hepatocellular carcinoma
    BMJ ; 2019
    In:  Gut Vol. 68, No. 12 ( 2019-12), p. 2195-2205
    Details
    In: Gut, BMJ, Vol. 68, No. 12 ( 2019-12), p. 2195-2205
    Abstract: The lack of highly sensitive and specific diagnostic biomarkers is a major contributor to the poor outcomes of patients with hepatocellular carcinoma (HCC). We sought to develop a non-invasive diagnostic approach using circulating cell-free DNA (cfDNA) for the early detection of HCC. Design Applying the 5hmC-Seal technique, we obtained genome-wide 5-hydroxymethylcytosines (5hmC) in cfDNA samples from 2554 Chinese subjects: 1204 patients with HCC, 392 patients with chronic hepatitis B virus infection (CHB) or liver cirrhosis (LC) and 958 healthy individuals and patients with benign liver lesions. A diagnostic model for early HCC was developed through case-control analyses using the elastic net regularisation for feature selection. Results The 5hmC-Seal data from patients with HCC showed a genome-wide distribution enriched with liver-derived enhancer marks. We developed a 32-gene diagnostic model that accurately distinguished early HCC (stage 0/A) based on the Barcelona Clinic Liver Cancer staging system from non-HCC (validation set: area under curve (AUC)=88.4%; (95% CI 85.8% to 91.1%)), showing superior performance over α-fetoprotein (AFP). Besides detecting patients with early stage or small tumours (eg, ≤2.0 cm) from non-HCC, the 5hmC model showed high capacity for distinguishing early HCC from high risk subjects with CHB or LC history (validation set: AUC=84.6%; (95% CI 80.6% to 88.7%)), also significantly outperforming AFP. Furthermore, the 5hmC diagnostic model appeared to be independent from potential confounders (eg, smoking/alcohol intake history). Conclusion We have developed and validated a non-invasive approach with clinical application potential for the early detection of HCC that are still surgically resectable in high risk individuals.
    Type of Medium: Online Resource
    ISSN: 0017-5749 , 1468-3288
    URL: Article
    DOI: 10.1136/gutjnl-2019-318882
    RVK:
    XA 10000
    Language: English
    Publisher: BMJ
    Publication Date: 2019
    detail.hit.zdb_id: 1492637-4
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  • 19
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    The identification and functional analysis of CD8+PD-1+CD161+ T cells in hepatocellular carcinoma
    Springer Science and Business Media LLC ; 2020
    In:  npj Precision Oncology Vol. 4, No. 1 ( 2020-10-30)
    Details
    In: npj Precision Oncology, Springer Science and Business Media LLC, Vol. 4, No. 1 ( 2020-10-30)
    Abstract: Immunotherapy is a powerful therapeutic strategy for end-stage hepatocellular carcinoma (HCC). It is well known that T cells, including CD8+PD-1+ T cells, play important roles involving tumor development. However, their underlying phenotypic and functional differences of T cell subsets remain unclear. We constructed single-cell immune contexture involving approximate 20,000,000 immune cells from 15 pairs of HCC tumor and non-tumor adjacent tissues and 10 blood samples (including five of HCCs and five of healthy controls) by mass cytometry. scRNA-seq and functional analysis were applied to explore the function of cells. Multi-color fluorescence staining and tissue micro-arrays were used to identify the pathological distribution of CD8+PD-1+CD161 +/− T cells and their potential clinical implication. The differential distribution of CD8+ T cells subgroups was identified in tumor and non-tumor adjacent tissues. The proportion of CD8+PD1+CD161+ T cells was significantly decreased in tumor tissues, whereas the ratio of CD8+PD1+CD161− T cells was much lower in non-tumor adjacent tissues. Diffusion analysis revealed the distinct evolutionary trajectory of CD8+PD1+CD161+ and CD8+PD1+CD161− T cells. scRNA-seq and functional study further revealed the stronger immune activity of CD8+PD1+CD161+ T cells independent of MHC class II molecules expression. Interestingly, a similar change in the ratio of CD8+CD161+/ CD8+CD161− T cells was also found in peripheral blood samples collected from HCC cases, indicating their potential usage clinically. We here identified different distribution, function, and trajectory of CD8+PD-1+CD161+ and CD8+PD-1+CD161− T cells in tumor lesions, which provided new insights for the heterogeneity of immune environment in HCCs and also shed light on the potential target for immunotherapy.
    Type of Medium: Online Resource
    ISSN: 2397-768X
    URL: Article
    DOI: 10.1038/s41698-020-00133-4
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2020
    detail.hit.zdb_id: 2891458-2
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  • 20
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    Discovery of a Carbamoyl Phosphate Synthetase 1–Deficient HCC Subtype With Therapeutic Potential Through Integrative Genomic and Experimental Analysis
    Ovid Technologies (Wolters Kluwer Health) ; 2021
    In:  Hepatology Vol. 74, No. 6 ( 2021-12), p. 3249-3268
    Details
    In: Hepatology, Ovid Technologies (Wolters Kluwer Health), Vol. 74, No. 6 ( 2021-12), p. 3249-3268
    Abstract: Metabolic reprogramming plays an important role in tumorigenesis. However, the metabolic types of different tumors are diverse and lack in‐depth study. Here, through analysis of big databases and clinical samples, we identified a carbamoyl phosphate synthetase 1 (CPS1)‐deficient hepatocellular carcinoma (HCC) subtype, explored tumorigenesis mechanism of this HCC subtype, and aimed to investigate metabolic reprogramming as a target for HCC prevention. Approach and Results A pan‐cancer study involving differentially expressed metabolic genes of 7,764 tumor samples in 16 cancer types provided by The Cancer Genome Atlas (TCGA) demonstrated that urea cycle (UC) was liver‐specific and was down‐regulated in HCC. A large‐scale gene expression data analysis including 2,596 HCC cases in 7 HCC cohorts from Database of HCC Expression Atlas and 17,444 HCC cases from in‐house hepatectomy cohort identified a specific CPS1‐deficent HCC subtype with poor clinical prognosis. In vitro and in vivo validation confirmed the crucial role of CPS1 in HCC. Liquid chromatography–mass spectrometry assay and Seahorse analysis revealed that UC disorder (UCD) led to the deceleration of the tricarboxylic acid cycle, whereas excess ammonia caused by CPS1 deficiency activated fatty acid oxidation (FAO) through phosphorylated adenosine monophosphate–activated protein kinase. Mechanistically, FAO provided sufficient ATP for cell proliferation and enhanced chemoresistance of HCC cells by activating forkhead box protein M1. Subcutaneous xenograft tumor models and patient‐derived organoids were employed to identify that blocking FAO by etomoxir may provide therapeutic benefit to HCC patients with CPS1 deficiency. Conclusions In conclusion, our results prove a direct link between UCD and cancer stemness in HCC, define a CPS1‐deficient HCC subtype through big‐data mining, and provide insights for therapeutics for this type of HCC through targeting FAO.
    Type of Medium: Online Resource
    ISSN: 0270-9139 , 1527-3350
    URL: Article
    DOI: 10.1002/hep.32088
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2021
    detail.hit.zdb_id: 1472120-X
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