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Recent progress in molecular mechanisms of postoperative recurrence and metastasis of hepatocellular carcinoma

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World Journal of Gastroenterology 2022年第46期28卷 6433-6477页

作者： zhao-shan niu Wen-Hong Wang Xiao-Jun niu Laboratory of Micromorphology School of Basic MedicineQingdao UniversityQingdao 266071Shandong ProvinceChina Department of Pathology School of Basic MedicineQingdao UniversityQingdao 266071Shandong ProvinceChina Department of Internal Medicine Qingdao Shibei District People's HospitalQingdao 266033Shandong ProvinceChina

Hepatectomy is currently considered the most effective option for treating patients with early and intermediate hepatocellular carcinoma(HCC).Unfortunately,the postoperative prognosis of patients with HCC remains unsatisfactory,predominantly because of high postoperative metastasis and recurrence rates.Therefore,research on the molecular mechanisms of postoperative HCC metastasis and recurrence will help develop effective intervention measures to prevent or delay HCC metastasis and recurrence and to improve the long-term survival of HCC patients.Herein,we review the latest research progress on the molecular mechanisms underlying postoperative HCC metastasis and recurrence to lay a foundation for improving the understanding of HCC metastasis and recurrence and for developing more precise prevention and intervention strategies.

关键词： Hepatocellular carcinoma Recurrence Metastasis Mechanisms Postoperation Intervention

Long non-coding RNAs in hepatocellular carcinoma: Potential roles and clinical implications

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World Journal of Gastroenterology 2017年第32期23卷 5860-5874页

作者： zhao-shan niu Xiao-Jun niu Wen-Hong Wang Laboratory of Micromorphology School of Basic MedicineMedical Department of Qingdao University Oncology Specialty Medical Department of Qingdao University Department of Pathology School of Basic MedicineMedical Department of Qingdao University

Long non-coding RNAs(lnc RNAs) are a subgroup of non-coding RNA transcripts greater than 200 nucleotides in length with little or no protein-coding potential. Emerging evidence indicates that lnc RNAs may play important regulatory roles in the pathogenesis and progression of human cancers, including hepatocellular carcinoma(HCC). Certain lnc RNAs may be used as diagnostic or prognostic markers for HCC, a serious malignancy with increasing morbidity and high mortality rates worldwide. Therefore, elucidating the functional roles of lnc RNAs in tumors can contribute to a better understanding of the molecular mechanisms of HCC and may help in developing novel therapeutic targets. In this review, we summarize the recent progress regarding the functional roles of lnc RNAs in HCC and explore their clinical implications as diagnostic or prognostic biomarkers and molecular therapeutic targets for HCC.

关键词： Hepatocellular carcinoma Long non-coding RNAs Function Biomarker Therapeutic target

Genetic alterations in hepatocellular carcinoma: An update

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World Journal of Gastroenterology 2016年第41期22卷 9069-9095页

作者： zhao-shan niu Xiao-Jun niu Wen-Hong Wang Laboratory of Micromorphology School of Basic Medicine Medical Department of Qingdao University Oncology Specialty Medical Department of Qingdao University Department of Pathology School of Basic Medicine Medical Department of Qingdao University

Hepatocellular carcinoma(HCC) is one of the leading causes of cancer-related deaths worldwide. Although recent advances in therapeutic approaches for treating HCC have improved the prognoses of patients with HCC, this cancer is still associated with a poor survival rate mainly due to late diagnosis. Therefore, a diagnosis must be made sufficiently early to perform curative and effective treatments. There is a need for a deeper understanding of the molecular mechanisms underlying the initiation and progression of HCC because these mechanisms are critical for making early diagnoses and developing novel therapeutic strategies. Over the past decade, much progress has been made in elucidating the molecular mechanisms underlying hepatocarcinogenesis. In particular, recent advances in next-generation sequencing technologies have revealed numerous genetic alterations, including recurrently mutated genes and dysregulated signaling pathways in HCC. A better understanding of the genetic alterations in HCC could contribute to identifying potential driver mutations and discovering novel therapeutic targets in the future. In this article, we summarize the current advances in research on the genetic alterations, including genomic instability, single-nucleotide polymorphisms, somatic mutations and deregulated signaling pathways, implicated in the initiation and progression of HCC. We also attempt to elucidate some of the genetic mechanisms that contribute to making early diagnoses of and developing molecularly targeted therapies for HCC.

关键词：基因改变 Chromosomal 不稳定性体的变化发信号的小径 Hepatocellular 癌

Management of hepatocellular carcinoma:Predictive value of immunohistochemical markers for postoperative survival

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World Journal of Hepatology 2015年第1期7卷 7-27页

作者： zhao-shan niu Xiao-Jun niu Mei Wang Lab of Micromorphology Medical College of Qingdao University Clinical Medicine Specialty Medical College of Qingdao University Institute of Education the University of ReadingRG6 1HY ReadingUnited Kingdom

Hepatocellular carcinoma(HCC) accounts for over 90% of all primary liver cancers. With an ever increasing incidence trend year by year,it has become the third most common cause of death from cancer worldwide. Hepatic resection is generally considered to be one of the most effective therapies for HCC patients,however,there is a high risk of recurrence in postoperativeHCC. In clinical practice,there exists an urgent need for valid prognostic markers to identify patients with prognosis,hence the importance of studies on prognostic markers in improving the prediction of HCC prognosis. This review focuses on the most promising immunohistochemical prognostic markers in predicting the postoperative survival of HCC patients.

关键词： Hepatocellular carcinoma Management Immunohistochemical Prognostic marker Predictivemarker

Role of long noncoding RNA-mediated competing endogenous RNA regulatory network in hepatocellular carcinoma

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World Journal of Gastroenterology 2020年第29期26卷 4240-4260页

作者： zhao-shan niu Wen-Hong Wang Xian-Ning Dong Li-Mei-Li Tian Laboratory of Micromorphology School of Basic MedicineMedical Department of Qingdao UniversityQingdao 266071Shandong ProvinceChina Department of Pathology School of Basic MedicineMedical Department of Qingdao UniversityQingdao 266071Shandong ProvinceChina Department of Pathology the Affiliated Hospital of Qingdao UniversityQingdao 266061Shandong ProvinceChina School of Basic Medicine Medical Department of Qingdao UniversityQingdao 266071Shandong ProvinceChina

Long noncoding RNAs (lncRNAs) and microRNAs (miRNAs) are noncodingRNAs (ncRNAs) that occupy over 90% of the human genome, and their mainfunction is to directly or indirectly regulate messenger RNA (mRNA) expressionand participate in the tumorigenesis and progression of malignances. Inparticular, some lncRNAs can interact with miRNAs as competing endogenousRNAs (ceRNAs) to modulate mRNA expression. Accordingly, these RNAmolecules are interrelated and coordinate to form a dynamic lncRNA-mediatedceRNA regulatory network. Mounting evidence has revealed that lncRNAs thatact as ceRNAs are closely related to tumorigenesis. To date, numerous studieshave established many different regulatory networks in hepatocellular carcinoma(HCC), and perturbations in these ceRNA interactions may result in the initiationand progression of HCC. Herein, we emphasize recent advances concerning thebiological function of lncRNAs as ceRNAs in HCC, with the aim of elucidating themolecular mechanism underlying these HCC-related RNA molecules andproviding novel insights into the diagnosis and treatment of HCC.

关键词： Hepatocellular carcinoma Long noncoding RNA MicroRNA Competing endogenous RNA Function Mechanism

Expression of c-erbB-2 and glutathione S-transferase-pi in hepatocellular carcinoma and its adjacent tissue

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World Journal of Gastroenterology 2005年第28期11卷 4404-4408页

作者： zhao-shan niu Mei Wang Department of Pathology Medical College of Qingdao University Qingdao 266021 Shandong ProvinceChina Institute of Education the University of Reading Britain RG6 IHY Reading United Kingdom

AIM: To investigate the possible role of c-erbB-2 and glutathione S-transferase (GST-Pi) in primary hepatocellular carcinogenesis and the relationship between liver hyperplastic nodule (LHN), liver cirrhosis (LC), and hepatocellular carcinoma (HCC).METHODS: The expression of c-erbB-2 and GST-Pi was detected immunohistochemically in 41 tissue specimens of HCC and 77 specimens of its adjacent tissue.RESULTS: The positive expression of c-erbB-2 in LHN (28.6%) was significantly higher than that in LC (0%)(P = 0.032＜0.05), but no significant difference was seen between HCC and LHN or LC (P＞0.05,x2 = 0.002, 3.447).The positive expression of GST-Pi in HCC (89.6%) or LHN (71.1%) was significantly higher than that in LC (22.9%, P＜0.001, x2= 49.91, 16.96). There was a significant difference between HCC and LHN (P＜0.05,x2= 6.353).CONCLUSION: The c-erbB-2 expression is an early event in the pathogenesis of HCC. GST-Pi may be a marker enzyme for immunohistochemical detection of human HCC and its preneoplastic lesions. LHN seems to be a preneoplastic lesion related to hepatocarcinogenesis.

关键词：谷光苷肽 S-转移酶肝细胞癌肝硬化

Latest developments in precancerous lesions of hepatocellular carcinoma

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World Journal of Gastroenterology 2016年第12期22卷 3305-3314页

作者： zhao-shan niu Xiao-Jun niu Wen-Hong Wang Jing zhao Laboratory of Micromorphology Medical College of Qingdao University Clinical Medicine Specialty Medical College of Qingdao University Department of Pathology Medical College of Qingdao University Department of Pathology the Affiliated Hospital of Qingdao University

Hepatocarcinogenesis in human chronic liver diseases is a multi-step process in which hepatic precancerous lesions progress into early hepatocellular carcinoma(HCC) and progressed HCC, and the close surveillance and treatment of these lesions will help improve the survival rates of patients with HCC. The rapid development and extensive application of imaging technology have facilitated the discovery of nodular lesions of ambiguous significance, such as dysplastic nodules. Further investigations showed that these nodules may be hepatic precancerous lesions, and they often appear in patients with liver cirrhosis. Although the morphology of these nodules is not sufficient to support a diagnosis of malignant tumor, these nodules are closely correlated with the occurrence of HCC, as indicated by long-term follow-up studies. In recent years, the rapid development and wide application of pathology, molecular genetics and imaging technology have elucidated the characteristics of precancerous lesions. Based on our extensive review of the relevant literature, this article focuses on evidence indicating that high-grade dysplastic nodules are more likely to transform into HCC than low-grade dysplastic nodules based on clinical, pathological, molecular genetic and radiological assessments. In addition, evidence supporting the precancerous nature of large cell change in hepatitis B virus-related HCC is discussed.

关键词： Hepatocellular carcinoma Precancerous lesions High-grade dysplastic nodule Large cell change Small c

A whole-net cooperative positioning method based on CDGNSS and inter-vehicle ranging

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Chinese Journal of Aeronautics 2024年第2期37卷 401-416页

作者： shan HU Hongbo zhao Chen ZHUANG School of Electronics and Information Engineering Beihang UniversityBeijing 100191China

Relative positioning is recognized as an important issue for vehicles in urban environments.Multi-vehicle Cooperative Positioning(CP)techniques which fuse the Global Navigation Satellite System(GNSS)and inter-vehicle ranging have attracted attention in improving the performance of baseline estimation between vehicles.However,current CP methods estimate the baselines separately and ignore the interactions among the positioning information of different baselines.These interactions are called’information coupling’.In this work,we propose a new multivehicle precise CP framework using the coupled information in the network based on the Carrier Differential GNSS(CDGNSS)and inter-vehicle ranging.We demonstrate the benefit of the coupled information by deriving the Cramer-Rao Lower Bound(CRLB)of the float estimation in CP.To fully use this coupled information,we propose a Whole-Net CP(WN-CP)method which consists of the Whole-Net Extended Kalman Filter(WN-EKF)as the float estimation filter,and the Partial Baseline Fixing(PBF)as the ambiguity resolution part.The WN-EKF fuses the measurements of all baselines simultaneously to improve the performance of float estimation,and the PBF strategy fixes the ambiguities of the one baseline to be estimated,instead of full ambiguity resolution,to reduce the computation load of ambiguity resolution.Field tests involving four vehicles were conducted in urban environments.The results show that the proposed WN-CP method can achieve better performance and meanwhile maintain a low computation load compared to the existing methods.

关键词： GNSS Cooperative positioning Baseline Ambiguity resolution Information coupling

The Multi-parameter Test of Gravitational Wave Dispersion with Principal Component Analysis

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Research in Astronomy and Astrophysics 2024年第5期24卷 140-150页

作者： Zhi-Chu Ma Rui niu Wen zhao CAS Key Laboratory for Research in Galaxies and Cosmology Department of AstronomyUniversity of Science and Technology of ChinaHefei 230026China School of Astronomy and Space Sciences University of Science and Technology of ChinaHefei 230026China

In this work, we consider a conventional test of gravitational wave(GW) propagation which is based on the phenomenological parameterized dispersion relation to describe potential departures from General Relativity(GR)along the propagation of GWs. But different from tests conventionally performed previously, we vary multiple deformation coefficients simultaneously and employ the principal component analysis(PCA) method to remedy the strong degeneracy among deformation coefficients and obtain informative posteriors. The dominant PCA components can be better measured and constrained, and thus are expected to be more sensitive to potential departures from the waveform model. Using this method we analyze ten selected events and get the result that the combined posteriors of the dominant PCA parameters are consistent with GR within 99.7% credible intervals. The standard deviation of the first dominant PCA parameter is three times smaller than that of the original dispersion parameter of the leading order. However, the multi-parameter test with PCA is more sensitive to not only potential deviations from GR but also systematic errors of waveform models. The difference in results obtained by using different waveform templates hints that the demands of waveform accuracy are higher to perform the multiparameter test with PCA. Whereas, it cannot be strictly proven that the deviation is indeed and only induced by systematic errors. It requires more thorough research in the future to exclude other possible reasons in parameter estimation and data processing.

关键词： gravitational waves-gravitation-black hole physics