Relatively Increased Number of Liver Foxp3^+ Regulatory T Cells against Hepatic Lesions in Murine Lupus

Systemic lupus erythematosus（SLE） is a multiple organ autoimmune disorder,including the liver,but the possible reason in impairment in the liver is still unclear.Our present study assessed alterations of transcription factor Foxp3＋ regulatory T cells（Tregs） and several other immune molecules [programmed cell death 1 and its ligand（PD1 and PD-L1）,and interleukin 10（IL-10） and transform growth factor β（TGF-β）] in the liver and other major organs of lupus-prone BXSB mice by flow cytometry,real-time quantitative reverse transcription PCR,and enzyme-linked immunosorbent assay.Results showed that both frequency and number of Foxp3＋ Tregs were dramatically reduced in the thymus,spleen and kidney of the BXSB mice（P0.05）,but those in the liver were kept in nearly normal range,when compared to negative control C57BL/6 mice.In comparison to control mice,the mRNA levels of Foxp3,PD1 and PD-L1 were significantly decreased in the kidneys of BXSB mice（P0.05）,but there was no significant difference in the livers of the BXSB mice（P0.05）.Protein levels of IL-10 and TGF-β in serum showed no significant difference between BXSB and C57BL/6 mice,but were significantly increased in the kidneys and livers of BXSB mice as compared with those in C57BL/6 mice（P0.05）.These results suggest that reduced Foxp3＋ Tregs are involved in the pathogenesis of SLE in BXSB mice,and relatively higher number of these cells in the livers than in the other target organs could constitute a protective mechanism against hepatic lesions in lupus-prone mice,which may provide insights into development of new therapeutic approaches in SLE patients.

Clinical diagnosis and treatment of alpha-fetoprotein-negative small hepatic lesions

Objective： We examined 103 cases over the last five years and discussed diagnosis and treatment of alpha- fetoprotein （AFP）-negative small hepatic lesions. Background： Small hepatic lesions （less than 2 cm in diameter） usually have no typical imaging characteristics and therefore are difficult to diagnose, especially when AFP tests provide a negative result. Methods： A total of 103 patients with AFP-negative small hepatic lesions from January 2003 to December 2008 were retrospectively reviewed. Differential diagnosis was performed by digital subtraction angiography （DSA）, dynamic contrast-enhanced magnetic resonance imaging （DCE-MRI）, contrast-enhanced ultrasound （CEUS）, or positron emission tomography-computed tomography （PET-CT） based on the multiplicity of lesions. Ninety-four patients with suspected cancers underwent partial hepatectomy. Clinical data were collected from hospital records and follow-up questionnaires. Results： Hepatocellular carcinoma （HCC） diagnostic sensitivity of DSA, DCE-MRI, CEUS and PET-CT was 88.2%, 93.9%, 88.9% and 88.9%, respectively. The surgery-related complication rate was 6.4%. Prognosis was good, with 1- and 3-year survival rates of 98.8% and 76.1%, respectively. Conclusions： DSA, DCE-MRI, CEUS and PET-CT are valuable for diagnosis of small hepatic lesions. Partial hepatectomy is a preferred surgical procedure. Surgery for small liver cancers usually has little risk and good prognosis, therefore it can be actively applied in suspected HCC cases.

Complementary comments on metastatic liver lesions with exceptional and rare cases

Liver metastases can appear in different forms in magnetic resonance imaging.Contrary to popular belief,while radiologists report hypovascular or hypervascular metastatic lesions,exceptional examples may be detected in various tumors.The aim of this article is to improve this review by presenting rare and atypical examples of liver metastasis,as well as cases that might potentially be misdiagnosed as metastases during the process of differential diagnosis.

Role of endoscopic ultrasound and endoscopic ultrasound-guided tissue acquisition in diagnosing hepatic focal lesions

BACKGROUND Endoscopic ultrasonography(EUS)has become an established method in diagnostic and therapeutic procedures in gastroenterology;however,it has recently gained a growing role in hepatology.AIM To evaluate the role of EUS features,strain elastography(SE),and EUS-tissue acquisition in diagnosing hepatic focal lesions(HFLs)that could affect further management.METHODS This cross-sectional study included 215 patients with pancreatic,biliary,or gastrointestinal malignancies referred for EUS examination.HFLs were identified in 43 patients(20%),and EUSguided tissue acquisition was performed from these lesions.RESULTS EUS features were highly sensitive(100%)but much less specific(57%)in diagnosing HFLs;the overall accuracy was 94%.Real-time elastography was also very sensitive(97%)but less specific(67%)in diagnosing HFLs;however,the overall accuracy was 92%.EUS tissue acquisition was extremely sensitive(100%)and specific(100%),with a 100%overall diagnostic accuracy.CONCLUSION The diagnostic utility of EUS-guided tissue acquisition was extremely accurate in diagnosing HFLs.EUS characteristics and real-time SE accurately predicted the histological diagnosis of both benign and malignant HFLs.

Value of a virtual hepatic segment model in assisting in the ultrasonic localization of intrahepatic lesions

Background During scanning of the right hypochondrium and right intercostal regions with an ultrasonic transducer,several ultrasonic images of oblique sections are obtained.It is still a challenge for ultrasonography to divide these nonconventional sections into an accurate hepatic segmentation pattern.The aim of this research was to investigate the value of the virtual hepatic segment model （VHSM） in assisting the ultrasonic localization of space-occupying hepatic lesions.Methods VHSM was constructed via 3D reconstruction according to the first Chinese visible human dataset.Preoperative ultrasonography,contrast-enhanced CT scan and VHSM techniques were performed in 100 patients with spaceoccupying focal lesions in the liver parenchyma for segmental localization.The results of these three techniques were compared with the operative findings.Results VHSM was successfully detected on 2D sectional images by 3D reconstruction through surface rendering and volume rendering.The model could simulate ultrasonic directions to conduct a virtual dissection on any section plane,and fine liver segmentation could be displayed in any virtual plane.In 100 patients,there were 112 liver space-occupying focal lesions distributed in 148 liver segmentations.Regarding the positioning accuracies for lesions of different sizes and the lesion segmental distribution accuracies estimated using the three methods mentioned above,ultrasonography exhibited a significantly lower accuracy than VHSM for the segmental localization of lesions （P ＜0.05）,and contrast-enhanced CT was not significantly different from ultrasonography plus VHSM （P ＞0.05）.Conclusion VHSM increased the accuracy of ultrasonic localization of space-occupying hepatic lesions,particularly in hepatic hypovascular regions.

Promotive action of 2-acetylaminofluorene on hepatic precancerous lesions initiated by diethylnitrosamine in rats:Molecular study

BACKGROUND Diethylnitrosamine(DEN)induces hepatic neoplastic lesions over a prolonged period.AIM To investigate the promotive action of 2-acetylaminofluorene(2-AAF)when combined with DEN in order to develop a rat model for induction of precancerous lesion and investigate the molecular mechanism underlying the activity of 2-AAF.METHODS The pre-precancerous lesions were initiated by intraperitoneal injection of DEN for three weeks consecutively,followed by one intraperitoneal injection of 2-AAF at three different doses(100,200 and 300 mg/kg).Rats were separated into naïve,DEN,DEN+100 mg 2-AAF,DEN+200 mg 2-AAF,and DEN+300 mg 2-AAF groups.Rats were sacrificed after 10 wk and 16 wk.Liver functions,level of alpha-fetoprotein,glutathione S-transferase-P and proliferating cell nuclear antigen staining of liver tissues were performed.The mRNA level of RAB11A,BAX,p53,and Cyclin E and epigenetic regulation by long-noncoding RNA(lncRNA)RP11-513I15.6,miR-1262(microRNA),and miR-1298 were assessed in the sera and liver tissues of the rats.RESULTS 2-AAF administration significantly increased the percent area of the precancerous foci and cell proliferation along with a significant decrease in RAB11A,BAX,and p53 mRNA,and the increase in Cyclin E mRNA was associated with a marked decrease in lncRNA RP11-513I15.6 expression with a significant increase in both miR-1262 and miR-1298.CONCLUSION 2-AFF promoted hepatic precancerous lesions initiated through DEN by decreasing autophagy,apoptosis,and tumor suppression genes,along with increased cell proliferation,in a time-and dose-dependent manner.These actions were mediated under the epigenetic regulation of lncRNA RP11-513I15.6/miR-1262/miR-1298.

Value of shear wave elastography with maximal elasticity in differentiating benign and malignant solid focal liver lesions

BACKGROUND It is important to differentiate benign and malignant focal liver lesions(FLLs)accurately.Despite the wide use and acceptance of shear wave elastography(SWE),its value for assessing the elasticity of FLLs and differentiating benign and malignant FLLs is still investigational.Previous studies of SWE for FLLs used mean elasticity as the parameter to reflect the stiffness of FLLs.Considering the inhomogeneity of tumor stiffness,maximal elasticity(Emax)might be the suitable parameter to reflect the stiffness of FLLs and to differentiate malignant FLLs from benign ones.AIM To explore the value of SWE with Emax in differential diagnosis of solid FLLs.METHODS We included 104 solid FLLs in 95 patients and 50 healthy volunteers.All the subjects were examined using conventional ultrasound(US)and virtual touch tissue quantification(VTQ)imaging.A diagnosis of benign or malignant FLL was made using conventional US.Ten VTQ values were acquired after 10 consecutive measurements for each FLL and each normal liver,and the largest value was recorded as Emax.RESULTS There were 56 cases of malignant FLLs and 48 cases of benign FLLs in this study.Emax of malignant FLLs(3.29±0.88 m/s)was significantly higher than that of benign FLLs(1.30±0.46 m/s,P<0.01)and that of livers in healthy volunteers(1.15±0.17 m/s,P<0.01).The cut-off point of Emax was 1.945,and the area under the curve was 0.978.The sensitivity and specificity of Emax were 92.9%and 91.7%,respectively,higher(but not significantly)than those of conventional US(80.4%for sensitivity and 81.3%for specificity).Combined diagnosis of conventional US and Emax using parallel testing improved the sensitivity to 100%with specificity of 75%.CONCLUSION SWE is a convenient and easy method to obtain accurate stiffness information of solid FLLs.Emax is useful for differential diagnosis of FLLs,especially in combination with conventional US.

Expression of Redox Factor-1 in Early Injury Period after Liver Transplantation in Rat Model

The aims of this study were to observe the relationship between injury of graft and expression of redox factor-1 （Ref-1） in early period （24 h） after liver transplantation in rat model One hundred and fifty adult male Wister rats were randomly divided into three groups including liver transplant group, sham surgery group and untreated control group. After liver transplantation, animals were sacrificed at different time points, and the changes and significance of the expression of Ref-1 were then explored by immunohistochemistry, serology and histopathology. As compared with sham surgery group and untreated control group, the expression of Ref-1 protein in transplant group was stronger in early period after liver transplantation. With pathology analysis, lots of infiltrating inflammation cells were found around the portal veins. Hepatic tissues were injury. However, the injury in sham surgery and untreated control group were comparatively slight. The serum ALT and AST levels reached the peak at 6-12 h, and decreased significantly after 12 h. These data suggested that the degree of liver injury in earlier period after transplantation peaked at 6 h and then decreased. And Ref-1 protein induced by hepatic ischemic reperfusion injury might play critical role in repairing the injury.