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.

Objective To compare different drainage methods after right hepatectomy. Methods From April 2017 to February 2018, 90 patients who underwent right hepatectomy at Zhongshan Hospital of Fudan University were prospectively randomized to the latex tube group (right subphrenic drain with a latex tube connecting to a collection bag, n=30), the silicone tube group (right subphrenic drain with a silicone tube connecting to a closed-suction, n=30) or the combination group ( right subphrenic drain with a latex tub, combined with a silicone tube, n=30). The amount of fluid collection after the operation, complications after surgery, recovery of liver function, and length of hospital stay after operation were compared. Results There were no significant differences in the clinicopathological features among the 3 groups, including gender, age, cirrhosis status, extent of hepatectomy, and blood loss (P＞0. 05). There were no significant differences among the three groups on the incidences of postoperative complications [ the latex tube group, 20. 0% (6/30); the silicone tube group, 23. 3% (7/30); the combination group, 16. 7% (5/30); P＞0. 05]. Ultrasonography showed significantly lower rates of subphrenic collection in the combination group compared with the latex tube group and the silicone tube group [16. 7% (5/30) vs. 63. 3% (19/30) vs. 53. 3% (16/30); P＜0. 05]. The rates of postoperative fever, serum total bilirubin, ALT and postoperative hospital stay were similar among the three groups (P＞0. 05). Conclusions Drainage using the combina-tion of a latex tube connecting to a collection bag and a silicone tube connecting to closed-suction after right hepatectomy significantly reduced postoperatively subphrenic collection and prevented infection of the collec-tion. However, the treatment strategy did not delay liver function recovery, prolong hospital stay nor increase post-operative infection rate.

Smad3 is a major transporter in the transforming growth factor β (TGF-β) signaling pathway.It is in charge of the transfer of TGF-β signal from the surface of the cell membrane into the nucleus.The TGF-β signal can be bound to the target gene in the nucleus and regulate its expression.Abnormalities in Smad3 expression level and functional status will lead to abnormal signal transduction,involving cell growth,proliferation,development,differentiation,migration,apoptosis and other basic life activities.This review focused on the differential expression of Smad3 in hepatocellular carcinoma (HCC)and the adjacent tissue.The character of Smad3 in HCC is outlined in three parts:Smad3 upstream signaling source,Smad3 self-assembly maturation and Smad3 downstream effects,which may provide a summary and reference for the follow-up study on Smad3.

Objective To investigate the efficacy and safety of radical nephrectomy associated with venous thrombectomy and the role of preoperative angioembolization.Methods From Sep 2006 to Dec 2014,the data from 15 cases with renal cell carcinoma and venous tumor thrombus were collected and analyzed retrospectively.The 15 patients included 8 men and 7 women,whose age ranged from 16 to 75 years.Before operation,all patients underwent imaging examinations which demonstrated the renal tumor and venous thrombus.The tumors size ranged from 5.4 to 14.5 cm.The levels of venous thrombus included 0 grade in 4 cases,Ⅰ grade in 2 cases,Ⅱ grade in 6 cases and Ⅲ grade in 3 cases.The 15 patients were divided into angioembolization group (n =5) and non-angioembolization group (n =10) according to the conduction of preoperative angioembolization.Results All cases successful accepted the nephrectomy.The venous thrombectomy were undergone in 14 cases except for one case due to the severe adhesion between renal vein and aorta.The average operative time was 243.3 ± 77.0 min.The mean blood loss was 1 373.3 ± 1 440.9 ml and the volume of blood transfusion was 533.3 ± 521.9 ml.The average time of postoperative hospital stay was 12.7 ± 5.2 days.Symptomatic tumor thrombus embolism didn't occur in all cases,perioperatively.There were no significant difference between these two groups in operative time,blood loss,blood transfusion volume and postoperative hospital stay (P ＞ 0.05).Eight cases were followed up with a period of 6 to 69 months.Four cases had disease-free survival during follow up.Two cases died at 30 and 55 months after surgery,respectively.One had tumor recurrence at 6 months after surgery.One patient accepted a 6-months target therapy (sunitinib) before surgery.However,his thrombus could not be removed during the operation.After the operation,he continued to choose the target drug therapy for 18 months.No progression for thrombosis or metastasis has been found.Conclusions Nephrectomy and venous thrombectomy could be safe and effective for renal cell carcinoma associated with venous thrombosis.Preoperative angioembolization could not reduce the perioperative risk such as blood loss.

Objective:To establish an improved model of mouse partial hepatectomy for study on liver regeneration .Methods :Healthy 8~10 week old male C57BL/6 mice were anesthetized by intraperitoneal injection .Then ,common hepatic pedicle of left lateral lobe of liver and middle lobe of liver was wrapped around with 6-0 proline suture .6-0 proline was fixed on the sur-face of right middle lobe of liver ,which was 0 .2 cm away from the hepatic pedicle .Hepatic pedicle was ligated and left lateral lobe and middle lobe of liver were resected 0 .2 cm away from ligature .The postoperative survival rate and the situation of liver weight vecovery at 3rd day ,7th day ,and 14th day after the operation were observed .Results:An improved mouse model of partial hepatectomy ,of which left lateral lobe of liver and middle lobe of liver were resected ,was established .The weight of removed liver accounted for 66 .7% of total liver and the survival rate of mice was 100% .After liver resection ,the compensa-tory regeneration of remaining liver achieved 58 .2% of the total liver weight at the 3rd day ,78 .0% at the 7th day ,and 93 .2%at the 14th day after the operation .Conclusions :An improved mouse model of partial hepatectomy was successfully established for study on liver regeneration ,which has advantages such as simplicity ,operability and high success rate .

Objective:To study the expression of UHRF1 and its relationships with the clinicopathological characteristics in hepatocellular carcinoma(HCC) .Methods :The expression of UHRF1 was analyzed in 556 cases of tumor tissues and peritumor tissues of HCC by immunohistochemistry .The relationships of UHRF1 with the clinicopathological characteristics of HCC were assayed .Results:Immunohistochemistry showed that positive staining of UHRF1 located in the nucleus of HCC cells .The ex-pression levels of UHRF1 protein were higher in tumor tissues than in peritumor tissues .HCC patients with positive expression of UHRF1 protein accounted for 59% of the whole cohort .The expression of UHRF1 protein was significantly correlated with the size of tumor ( P<0 .01) ,differentiation (P<0 .05) and microvessel invasion(P<0 .01) .Conclusions :The overexpression of UHRF1 is correlated with the malignant phenotypes of HCC and probably implicated in the invasion and metastasis of HCC .

Objective To investigate the risk factors influencing early and late recurrences after resection of primary clear cell carcinoma of the liver (PCCCL).Methods 214 PCCCL patients treated by curative resection from January 1996 to March 2006 were retrospectively analyzed.Recurrences were classified into early (≤1 year) and late (＞1 year) recurrences.Results 99 patients developed recurrences,with early recurrence in 28 patients and late recurrence in 71 patients.The 3-and 5-year overall survival (OS) rates for recurrent PCCCL were significantly worse than those with no recurrence (68.7％ and 46.2％ vs 72.2％ and 64.3％,P=0.003).The 1-,3-and 5-year OS rates for late recurrence were 100％,80.3％ and 54.6％,which were significantly better than those with early recurrence (85.7％,39.3％ and 25.0％,P=0.001).On multivariate analysis,aminoleucine transferase (ALT) level and vascular invasion were independent risk factors for early recurrence,while age was the only significant risk factor for late recurrence.Conclusions The time to recurrence was the main determinant for prognosis of recurrent PCCCL,Clarifying the different risk factors for early and late recurrences will help postoperative follow-up,early detection of recurrence,and hopefully will improve survival.

Objective To study the risk factors of post-hepatectomy hepatic decompensation (PHD) in patients with hepatocellular carcinoma.MethodWe reviewed 562 patients with Child-Pugh A classification,who underwent partial hepatectomy for hepatocellular carcinoma at Zhongshan Hospital,Fudan University between July 1st 2007 to December 31st 2007,to study the risk factors of hepatic decompensation.ResultsPreoperative high total bilirubin (TB) and low prealbumin (PA) were independent risk factors of PHD by logistic multivariate analysis ROC analysis revealed the cut-offs of preoperative PA predicting PHD were 0.14 g/L (sensitivity 41.4％; specificity 83.1％).The incidence of PHD was 16.0％ when TB≥20.4 μmol/L and PA＜0.14 g/L(OR=7.276,P=0.002).ConclusionThe Child-Pugh A patients recovered well when the preoperative liver function was as follows:TB＜20.4 μmol/L and PA≥0.14 g/L.

Objective To investigate the role and mechanism of TMPRSS4 in radiation induced metastasis of hepatocellular carcinoma (HCC).Methods Metastatic model of human HCC was established by orthotopic implantation of histologically intact human HCC tissue into the liver of nude mice.Mice bearing xenografts in liver were killed after radiation and the residual tumors were resected and reimplanted into the liver of normal nude mice.At the end of sixth week,the mice were killed and the histopathological features,tumor volume,intrahepatic and lung metastasis were evaluated.Expression of epithelial-mesenchymal transition (EMT) related genes including N-cadherin,Vimentin,SIP1 and TMPRSS4 were measured by Western blotting and RT-PCR.Results The tumor volume and frequency of lung metastasis of control group was 2.25±0.52 cm3 and 66.7％,respectively.Compared to control group,tumor diameter (1.61±0.51 cm3,P＜0.05) and lung metastasis (12.5％,P＜0.05) were significantly inhibited 2 days after radiation.Whereas,30 days after radiation,tumor growth recovered (2.60±0.61 cm3,P＞0.05) and lung metastasis was enhanced (100％,P＜0.05).There were no intrahepatic metastasis in the control group and in the group of reimplantation of HCC 2 days after radiation,while the tumors from those 30 days after radiation showed enhanced intrahepatic metastasis (18 ± 8.05,P＜ 0.01 ),with overexpression of SIP1,N-cadherin,Vimentin and TMPRSS4,and reduced expression of E-cadherin.Conclusion The metastasis potential of residual HCC after radiation was first inhibited and then promoted.Overexpression of TMPRSS4 plays a critical role in radiation induced long-term metastasis of HCC by facilitating EMT.

Objective To compare the Barcelona clinic liver cancer staging classification (BCLC), the Japan integrated staging score (JIS), the cancer of the liver Italian program score (CLIP) and Chinese staging system in terms of their ability to predict outcomes and to guide option of therapy in patients with hepatocellular carcinoma (HCC) in China.Methods Clinical data of 861 HCC patients from Zhongshan Hospital between 2001 and 2002 were retrospectively analyzed. Patients were classified acccording to different staging systems. Survival for patients in different stages and the effects of therapeutic methods on survival time were compared. Results BCLC, JIS and Chinese staging system showed the ability in predicting survival for patients in different staging. CLIP failed to show significant difference in survival rates for each subgroup. There was no significant difference in survival rate between surgery and transarterial chemoembolization (TACE)/transarterial embolization (TAE) for patients classified as BCLC stage C, CLIP scores more than 3 or Chinese stage Ⅲ a.The survival rate, however, was higher in patients received operation than those received TACE/TAE if they were classified as earlier stages. Conclusions The BCLC, JIS and Chinese staging systems show prospective ability for Chinese HCC patients in prediction outcomes, whereas the BCLC and the Chinese staging systems are better at both predicting outcomes and guiding the option of treatment.