1.Plasma miRNA testing in the differential diagnosis of very early-stage hepatocellular carcinoma: a multicenter real-world study
Jie HU ; Ying XU ; Ao HUANG ; Lei YU ; Zheng WANG ; Xiaoying WANG ; Xinrong YANG ; Zhenbin DING ; Qinghai YE ; Yinghong SHI ; Shuangjian QIU ; Huichuan SUN ; Qiang GAO ; Jia FAN ; Jian ZHOU
Chinese Journal of Clinical Medicine 2025;32(3):350-354
Objective To explore the application of plasma 7 microRNA (miR7) testing in the differential diagnosis of very early-stage hepatocellular carcinoma (HCC). Methods This study is a multicenter real-world study. Patients with single hepatic lesion (maximum diameter≤2 cm) who underwent plasma miR7 testing at Zhongshan Hospital, Fudan University, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Anhui Provincial Hospital, and Peking University People’s Hospital between January 2019 and December 2024 were retrospectively enrolled. Patients were divided into very early-stage HCC group and non-HCC group, and the clinical pathological characteristics of the two groups were compared. The value of plasma miR7 levels, alpha-fetoprotein (AFP), and des-gamma-carboxy prothrombin (DCP) in the differential diagnosis of very early-stage HCC was evaluated using receiver operating characteristic (ROC) curves and area under the curve (AUC). In patients with both negative AFP and DCP (AFP<20 ng/mL, DCP<40 mAU/mL), the diagnostic value of plasma miR7 for very early-stage HCC was analyzed. Results A total of 64 528 patients from 4 hospitals underwent miR7 testing, and 1 682 were finally included, of which 1 073 were diagnosed with very early-stage HCC and 609 were diagnosed with non-HCC. The positive rate of miR7 in HCC patients was significantly higher than that in non-HCC patients (67.9% vs 24.3%, P<0.001). ROC curves showed that the AUCs for miR7, AFP, and DCP in distinguishing HCC patients from the non-HCC individuals were 0.718, 0.682, and 0.642, respectively. The sensitivities were 67.85%, 43.71%, and 44.45%, and the specificities were 75.70%, 92.78%, and 83.91%, respectively. The pairwise comparison of AUCs showed that the diagnostic efficacy of plasma miR7 detection was significantly better than that of AFP or DCP (P<0.05). Although its specificity was slightly lower than AFP and DCP, the sensitivity was significantly higher. Among patients negative for both AFP and DCP, miR7 maintained an AUC of 0.728 for diagnosing very early-stage HCC, with 67.82% sensitivity and 77.73% specificity. Conclusions Plasma miR7 testing is a potential molecular marker with high sensitivity and specificity for the differential diagnosis of small hepatic nodules. In patients with very early-stage HCC lacking effective molecular markers (negative for both AFP and DCP), miR7 can serve as a novel and effective molecular marker to assist diagnosis.
2.Intervention effect of three formulations of Chinese herbs in rats with silicosis
Jiansheng LI ; Runsu HOU ; Xinhua YAN ; Fan YANG ; Xiangcheng WANG ; Xinrong TIAN ; Yuanyuan HU ; Peng ZHAO
China Occupational Medicine 2024;51(6):629-637
Objective To investigate the intervention effects of Yangqing Chenfei Fang (YCF), Baojin Chenfei Fang (BCF), and Jinshui Chenfei Fang (JCF) at different pathological stages of silicosis in a rat model. Methods A total of 216 specific pathogen free rats were randomly divided into control group, silicosis group, tetrandrine group, YCF group, BCF group and JCF group, with 35-36 rats in each group (11-12 rats at each time point). The rats in control group were treated with intragastric administration of pure water [administration volume at 2.5 mL/(kg·time)], while the rats of other five groups were treated with silica suspension at 250 mg/kg body weight to induce a silicosis model using the one-time non-exposed tracheal method. Intragastric administration of the corresponding drugs was performed at three time points at days 1-14 (early stage of silicosis), days 15-28 (middle stage of silicosis), and days 29-42 (late stage of silicosis) after modeling. Pulmonary function enhanced pause (Penh), forced vital capacity (FVC), and dynamic lung compliance (Cdyn) of rats in the six groups was assessed on days 15, 29, and 43 after modeling. Histopathological changes in lung tissues were observed, and relative expression levels of tumor necrosis factor (TNF)-α, interleukin (IL)-6, IL-1β, hydroxyproline, collagenⅠ(COL-Ⅰ), and α-smooth muscle actin (α-SMA) were detected in lung tissues. Results i) Pulmonary function index. The index of Penh in three stages of silicosis of rats in YCF group, BCF group and JCF group was lower than that in the silicosis group at the same stage (all P<0.05), and the index of Penh was higher than that in the tetrandrine group at the same stage (all P<0.05). The index of FVC of rats in YCF group, BCF group and JCF group at the middle stage was higher than that in the silicosis group at the same stage (all P<0.05), as well as the index of Cdyn was higher than that in the tetrandrine group at the same stage (all P<0.05). ii) Histopathology of lung tissue. Rats of the silicosis group exhibited alveolitis, fibro stripe, and collagen deposition in lung tissues in the early stage compared with rat of the control group, with fibrosis progressively worsening over time and inflammation persisting throughout the disease course. Pathological changes of lung tissues were alleviated to varying degrees in the tetrandrine groups, YCF group, BCF group and JCF group compared with that of the silicosis group. Compared with the same stage of silicosis group, the Ashcroft scores of lung tissues in the YCF group and BCF group were lower in the middle and late stages (all P<0.05). The Ashcroft score of lung tissues in the BCF group in the middle and late stages was lower than that in tetrandrine group at the same stage (all P<0.05), while the Ashcroft score in the middle stages was lower than that in YCF group at the same stage (P<0.05). The Ashcroft score of lung tissue in the JCF group was lower than that in the silicosis group, tetrandrine group and YCF group at all three stages (all P<0.05), and was lower than that in BCF group at the early and late stage of silicosis (all P<0.05). iii) Inflammatory factors. IL-6 level in the lung tissues in the YCF group, BCF group and JCF group decreased compared with that in the silicosis group at the same stage (all P<0.05), while IL-1β and TNF-α levels decreased at the early and middle stages (all P<0.05), hydroxyproline level decreased at all three stages (all P<0.05). iv) Collagen. The relatively expression of COL-Ⅰ in the lung tissues in the YCF group decreased at the late stage of silicosis compared with that in the silicosis group at the same stage (all P<0.05), while the relatively expression of α-SMA decreased at the middle and late stages (all P<0.05). Compared with the same stage of silicosis group, the relative expression of COL-Ⅰ and α-SMA of the lung tissues reduced in the BCF group and JCF group at all stages (all P<0.05). The relative expression of COL-Ⅰ of the lung tissues reduced in the BCF group at the late stage compared with that in the YCF group in the same stage (all P<0.05), while the relative expression of α-SMA decreased at the early and middle stages (all P<0.05). The relative expression of COL-Ⅰ of the lung tissues reduced in the JCF group at late stage of silicosis (all P<0.05), while the relative expression of α-SMA decreased at all three stages (all P<0.05), compared with the same stage of YCF group. Conclusion All three formulations of Chinese herbs are effective in improving lung function and alleviating the progress of lung inflammation and fibrosis. YCF is the most effective in suppressing inflammation in the early stage of silicosis. BCF excels in delaying fibrosis in the early and middle stages. JCF is the most effective in improving lung function and delaying fibrosis progression in the late stage.
3.Chinese expert guidance on overall application of lenvatinib in hepatocellular carcinoma
Xinrong YANG ; Huichuan SUN ; Qing XIE ; Wanguang ZHANG ; Weidong JIA ; Ming ZHAO ; Haitao ZHAO ; Xiufeng LIU ; Ledu ZHOU ; Sheng YAN ; Li XU ; Nanya WANG ; Yuan DING ; Xiaodong ZHU ; Jian ZHOU ; Jia FAN
Chinese Journal of Digestive Surgery 2023;22(2):167-180
Lenvatinib mesylate is an oral receptor tyrosine kinase inhibitor against targets of vascular endothelial growth factor receptors 1-3, fibroblast growth factor receptors 1-4, platelet-derived growth factor receptor α, stem cell growth factor receptor, and rearranged during transfection, et al. Lenvatinib has been approved by the National Medical Products Administration of China on September 4,2018, for the first-line treatment of patients with unresectable hepatocellular carcinoma who have not received systematic treatment before. Up to February 2023, Lenvatinib has been listed in China for more than 4 years, accumulating a series of post-marketing clinical research evidences. Based on the clinical practice before and after the launch of lenvatinib and referring to the clinical experience of other anti-angiogenesis inhibitors, domestic multidisciplinary experts and scholars adopt the Delphi method to formulate the Chinese Expert Guidance on Overall Application of Lenvatinib in Hepatocellular Carcinoma after repeated discussions and revisions, in order to provide reference for reasonable and effective clinical application of lenvatinib for clinicians.
4.Chinese expert guidance on overall application of lenvatinib in hepatocellular carcinoma
Xinrong YANG ; Huichuan SUN ; Qing XIE ; Wanguang ZHANG ; Weidong JIA ; Ming ZHAO ; Haitao ZHAO ; Xiufeng LIU ; Ledu ZHOU ; Sheng YAN ; Li XU ; Nanya WANG ; Yuan DING ; Xiaodong ZHU ; Jian ZHOU ; Jia FAN
Chinese Journal of Hepatology 2023;31(10):1018-1029
Lenvatinib mesylate is an oral receptor tyrosine kinase inhibitor against targets of vascular endothelial growth factor receptors 1-3, fibroblast growth factor receptors 1-4, platelet-derived growth factor receptor α, stem cell growth factor receptor, and rearranged during transfection, et al. Lenvatinib has been approved by the National Medical Products Administration of China on September 4, 2018, for the first-line treatment of patients with unresectable hepatocellular carcinoma who have not received systematic treatment before. Up to February 2023, Lenvatinib has been listed in China for more than 4 years, accumulating a series of post-marketing clinical research evidences. Based on the clinical practice before and after the launch of lenvatinib and referring to the clinical experience of other anti-angiogenesis inhibitors, domestic multidisciplinary experts and scholars adopt the Delphi method to formulate the Chinese Expert Guidance on Overall Application of Lenvatinib in Hepatocellular Carcinoma after repeated discussions and revisions, in order to provide reference for reasonable and effective clinical application of lenvatinib for clinicians.
5.Expert guidance on overall management of liver cancer during the COVID-19
Huichuan SUN ; Xinrong YANG ; Zhiping YAN ; Zhenggang REN ; Rong LIU ; Lan ZHANG ; Yang XU ; Yifeng HE ; Zihan ZHANG ; Jia FAN ; Jian ZHOU
Chinese Journal of Digestive Surgery 2022;21(5):557-563
The pandemic of Corona Virus Disease 2019 (COVID-19) continues, which shows the concentrated or sporadic cases in multiple places. Current COVID situation is still complex. During the COVID-19, routine diagnosis and treatment of liver cancer patients has been affected in different degrees. Under the premise of following the treatment guidelines, how to reduce the risk of infection of patients and medical staff, utilize limited medical resources to maximally ensure anti-tumor treatment and related emergency treatment, and help patients get through the epidemic period is a problem for liver oncologists. Thus, experts of liver cancer treatment related disciplines of Zhongshan Hospital, Fudan University have written the Expert guidance on overall management of liver cancer during the COVID-19, which aims to provide references for liver oncolo-gists to conduct clinical work safely and effectively under the epidemic prevention and control, and to help patients fight against the epidemic smoothly.
6.Review on role of NLRP3 inflammasome in pathogenesis of silicosis
Zhenzhen FAN ; Yehong ZHAO ; Bing LI ; Yang LIU ; Junyu JIANG ; Min MU ; Xinrong TAO
Journal of Environmental and Occupational Medicine 2022;39(8):931-936
Silicosis is one of the most common forms of pneumoconiosis globally. Workers who engage in mining, construction, ceramics, and many other industries have a high risk of developing silicosis. Chronic and repeated inhalation of free silica (SiO2) dust (<5 μm) during working can lead to inflammatory reactions, resulting in interstitial lung disease characterized by extensive nodular fibrosis in both lungs. Once silicosis occurs, it will develop progressively even when the workers are removed from the silica dust environment. The pathogenesis of silicosis is complex, especially the role of nod-like receptor family protein 3 (NLRP3) inflammasome in the pathogenesis and progression of silicosis remains to be further studied. NLRP3 inflammasome, a multi-protein complex composed of NLRP3, apoptosis-associated speck-like protein, and cysteinyl aspartate specific proteinase 1 is involved in oxidative stress, inflammatory response, apoptosis, and pyroptosis, and has become one of the hot spots in silicosis research. This review summarized the structure, function, and activation mechanism of NLRP3 inflammasome. Furthermore, the cellular and molecular mechanisms of NLRP3 in mediating oxidative stress, inflammatory response, apoptosis, and pyroptosis in the progression of silicosis were reviewed. Finally, the potential therapeutic drugs for silicosis based on NLRP3-associated mechanisms were outlined. More attention should be paid to the role of NLRP3 inflammasome in the pathogenesis and progression of silicosis in the future, which will provide new ideas for the prevention and treatment of silicosis.
7.Analysis of pain management and satisfaction on pain management of home-based advanced cancer patients with pain
Xia LI ; Xinrong LUO ; Xiaoping FAN
Chinese Journal of Endocrine Surgery 2021;15(2):197-201
Objective:To detect the pain status and the pain management of home-based advanced cancer patients, and to investigate the key factors impacting the satisfaction on pain management.Methods:Totally the data of 138 cases from the hospice department in the duration from Jan. 2019 to Jun. 2019 were collected and analyzed by χ2 test with SPSS 23.0. Results:109 cases in 138 cases received analgesics treatment before, 54.13% of these participants expressed satisfaction with the effect of their pain management, and 45.87% showed unsatisfied on their pain management. Cancer clinical stage and PMI (pain management index) were both detected to be the significant factors for satisfaction of pain management ( P<0.05, P=0.029; P<0.01, P=0.001) . Conclusions:Cancer clinical stage and PMI are found to be related to the satisfaction for pain management. The percentage of patients who use opioids increased. while there was still a part of patients suffering from inadequacy of pain management. The pain management for home-based advanced patients needs to be paid more attention by medical staff.
8.Mechanisms and control measures of COVID-19 related liver injuries
Ao HUANG ; Xinrong YANG ; Huichuan SUN ; Jia FAN ; Jian ZHOU
Chinese Journal of Digestive Surgery 2020;19(3):248-250
Although the epidemic situation of Corona Virus Disease 2019 (COVID-19) has been controlled, the epidemic situation remains grim. The COVID-19 is highly infectious, with various clinical manifestations including liver injury. The authors make a preliminary investigation on the mechanisms of liver injury related to COVID-19, and put forward correspon-ding control measures for reference.
9.Overall management strategies for liver cancer patients during the COVID-19 outbreak
Xinrong YANG ; Huichuan SUN ; Yang XU ; Yifeng HE ; Ao HUANG ; Jia FAN ; Jian ZHOU
Chinese Journal of Digestive Surgery 2020;19(3):244-247
The Corona Virus Disease 2019 (COVID-19) that occurred December of 2019 has a wide range of impacts, and its epidemic situation is grim. China has a large population of liver cancer, accounting for 50% of new cases of liver cancer worldwide. How to ensure the diagnosis, treatment and rehabilitation of liver cancer patients while preventing and controlling the epidemic situation is an issue that urgently need specialists pay attention to. The authors propose an overall management model for patients with liver cancer, combined with their own experience, in order to guide specialists to safely and effectively carry out clinical diagnosis and treatment of liver cancer during the prevention and control of epidemics, and to help liver cancer patients receive treatment.
10.Study on the value of serum des-γ-carboxy prothrombin in predicting hepatocellular carcinoma recurrence after liver transplantation
Yang XU ; Pengxiang WANG ; Jianwen CHENG ; Xiaowu HUANG ; Jian ZHOU ; Jia FAN ; Xinrong YANG
Chinese Journal of Hepatology 2020;28(11):918-923
Objective:To explore the clinical value of serum des-γ-carboxy prothrombin (DCP) in predicting hepatocellular carcinoma recurrence after liver transplantation.Methods:A total of 115 cases with hepatocellular carcinoma who underwent liver transplantation in Zhongshan Hospital Affiliated to Fudan University from October 2016 to December 2018 were retrospectively analyzed. Receiver operating characteristic curve analysis, Mann-Whitney U test, Kaplan-Meier method, Log-Rank test, χ2 test, univariate and multivariate Cox regression analysis and other statistical methods were used to explore the value of DCP in predicting tumor recurrence after liver transplantation and its correlation with clinicopathological characteristics.Results:The preoperative serum DCP level in recurrent population after liver transplantation was significantly higher than that in non-recurrent population ( P < 0.001). The optimal cut-off value of preoperative DCP for predicting recurrence was 200mAU/ml with the use of receiver operating characteristic curve. The sensitivity, specificity, Youden’s index and the receiver operating characteristic curve was 87.90%, 57.30%, 0.452, and 0.726, respectively. Survival analysis results grouped by this cut-off value showed that patients with preoperative DCP ≥200mAU/ml had a higher probability of recurrence ( P < 0.001). Further, subgroup survival analysis showed that patients with preoperative DCP≥200 mAU/ ml had a higher probability of recurrence than other cases of alpha-fetoprotein negative subgroup, cumulative tumor diameter ≤ 9 cm subgroup and Milan criteria subgroup ( P < 0.05). Cox regression analysis showed that preoperative DCP≥200 mAU/ ml ( P = 0.017) and cumulative tumor diameter > 9 cm ( P = 0.014) was an independent risk factor for recurrence after liver transplantation. χ2 test results showed that preoperative serum DCP level was correlated with gender, serum gamma glutamyltransferase level, serum alpha fetoprotein level, cumulative tumor diameter, vascular invasion, tumor differentiation and liver cancer transplant criteria ( P < 0.05). Conclusion:Preoperative serum DCP can be used as a supplement to the existing liver cancer transplant criteria to predict hepatocellular carcinoma recurrence after liver transplantation. In addition, the accurate screening of patients with low risk of HCC recurrence after liver transplantation can improve the prognosis and efficacy of liver transplant patients.

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