NAP1L1 regulates BIRC2 ubiquitination modification via E3 ubiquitin ligase UBR4 and hence determines hepatocellular carcinoma progression.

We have previously shown that nucleosome assembly protein 1-like 1 (NAP1L1) plays an important role in the abnormal proliferation of hepatocellular carcinoma (HCC) cells. However, the effects of NAP1L1 on the malignant behaviour of HCC cells, including cell migration, invasion and apoptosis, remain unclear. Baculoviral IAP repeat-containing 2 (BIRC2) plays a key role in initiating the abnormal proliferation, apoptotic escape and multidrug resistance of HCC cells; however, the mechanisms through which its stability is regulated in HCC remain elusive. Here, we found that knockdown of NAP1L1 inhibited the proliferation of HCC cells and activated apoptotic pathways but did not remarkably affect the migratory and invasive abilities of HCC cells. In addition, knockdown of NAP1L1 did not alter the expression of BIRC2 at the transcriptional level but substantially reduced its expression at the translational level, suggesting that NAP1L1 is involved in the post-translational modification (such as ubiquitination) of BIRC2. Furthermore, BIRC2 was highly expressed in human HCC tissues and promoted the proliferation and apoptotic escape of HCC cells. Co-immunoprecipitation (Co-IP) assay and mass spectrometry revealed that NAP1L1 and BIRC2 did not bind to each other; however, ubiquitin protein ligase E3 component n-recognin 4 (UBR4) was identified as an intermediate molecule associating NAP1L1 with BIRC2. Knockdown of NAP1L1 promoted the ubiquitin-mediated degradation of BIRC2 through the ubiquitin-protein junction of UBR4, which in turn inhibited the proliferation and apoptotic escape of HCC cells and exerted anti-tumour effects. In conclusion, this study reveals a novel mechanism through which NAP1L1 regulates the ubiquitination of BIRC2 through UBR4, thereby determining the progression of HCC. Based on this mechanism, suppression of NAP1L1 may inhibit tumour progression in patients with HCC with high protein expression of NAP1L1 or BIRC2.

TM4SF1 upregulates MYH9 to activate the NOTCH pathway to promote cancer stemness and lenvatinib resistance in HCC.

TM4SF1, a member of the transmembrane 4 superfamily, is crucial for both healthy and malignant human tissues. The significant function of TM4SF1 in the incidence and progression of cancer has been widely recognized in recent years. Although some achievements have been made in the study of TM4SF1, the effect of TM4SF1 on cancer stemness in hepatocellular carcinoma (HCC) and its molecular basis are yet to be reported. We found through abundant in vitro and in vivo experiments which the expression of TM4SF1 was positively correlated with the progression and cancer stemness of HCC. We identified the downstream protein MYH9 of TM4SF1 and its final regulatory target NOTCH pathway using bioinformatics analysis and protein mass spectrometry. We cultivated a Lenvatinib-resistant strain from HCC cells to examine the relationship between cancer stemness and tumor drug resistance. The study confirmed that TM4SF1 could regulate the NOTCH pathway by upregulating MYH9, thus promoting cancer stemness and Lenvatinib resistance in HCC. This study not only provided a new idea for the pathogenesis of HCC but also confirmed that TM4SF1 might become a new intervention point to improve the clinical efficacy of Lenvatinib in treating HCC.

WD repeat domain 48 promotes hepatocellular carcinoma progression by stabilizing c-Myc.

The role of protein members containing the WD40 repeat domain in many diseases, including cancer, is well documented. However, the role of WD repeat domain 48 (WDR48) in hepatocellular carcinoma (HCC) and its molecular basis remain to be further investigated. In the present study, we report that WDR48 is downregulated in clinical HCC samples and evaluate the relationship between its expression and clinical features of HCC. In vitro experiments showed that WDR48 positively regulated the proliferation, invasion and metastasis of HCC cells and in vivo experiments showed that downregulation of WDR48 significantly inhibited the tumorigenicity of HCC cells. Mechanistically, WDR48 binds to the proto-oncogene transcriptional regulator c-Myc and stabilizes c-Myc expression by mediating its deubiquitination, thereby enhancing cell proliferation and EMT signalling. Our study demonstrates the oncogenic role of WDR48 and suggests that WDR48 can be an important target in HCC.

miR-3682-3p directly targets FOXO3 and stimulates tumor stemness in hepatocellular carcinoma via a positive feedback loop involving FOXO3/PI3K/AKT/c-Myc.

BACKGROUND: Cancer stem cells (CSCs) have been implicated in tumorigenesis and tumor recurrence and metastasis are key therapeutic targets in cancer treatment. MicroRNAs display therapeutic potential by controlling the properties of CSCs; however, whether an association exists between miR-3682-3p and CSCs is unknown. AIM: To investigate the mechanism by which miR-3682-3p promotes stemness maintenance in hepatocellular carcinoma (HCC). METHODS: MiR-3682-3p expression in HCC cell lines and 34 pairs of normal and HCC specimens was assayed by quantitative polymerase chain reaction. The functional role of miR-3682-3p was investigated in vitro and in vivo. Dual-luciferase reporter and chromatin immunoprecipitation assays were performed for target asse ssment, and western blotting was utilized to confirm miR-3682-3p/target relationships. RESULTS: We found that miR-3682-3p plays a key role in HCC pathogenesis by promoting HCC cell stemness. The upregulation of miR-3682-3p enhanced CSC spheroid-forming ability, side population cell fractions, and the expression of CSC factors in HCC cells in vitro and the tumorigenicity of transplanted HCC cells in vivo. Furthermore, silencing miR-3682-3p prolonged the survival of HCC-bearing mice. Mechanistically, we found that miR-3682-3p targets FOXO3 and enables FOXO3/ß-catenin interaction, which promotes c-Myc expression through PI3K/AKT; c-Myc, in turn, activates miR-3682-3p, forming a positive feedback loop. Intriguingly, miR-3682-3p expression was induced by hepatitis B virus X protein (HBx) and was involved in HBx-induced tumor stemness-related pathogenesis. CONCLUSION: Our findings reveal a novel mechanism by which miR-3682-3p promotes stemness in HCC stem cells. Silencing miR-3682-3p may represent a novel therapeutic strategy for HCC.

DNASE1L3 inhibits proliferation, invasion and metastasis of hepatocellular carcinoma by interacting with ß-catenin to promote its ubiquitin degradation pathway.

As a member of the deoxyribonuclease 1 family, DNASE1L3 plays a significant role both inside and outside the cell. However, the role of DNASE1L3 in hepatocellular carcinoma (HCC) and its molecular basis remains to be further investigated. In this study, we report that DNASE1L3 is downregulated in clinical HCC samples and evaluate the relationship between its expression and HCC clinical features. In vivo and in vitro experiments showed that DNASE1L3 negatively regulates the proliferation, invasion and metastasis of HCC cells. Mechanistic studies showed that DNASE1L3 recruits components of the cytoplasmic ß-catenin destruction complex (GSK-3ß and Axin), promotes the ubiquitination degradation of ß-catenin, and inhibits its nuclear transfer, thus, decreasing c-Myc, P21 and P27 level. Ultimately, cell cycle and EMT signals are restrained. In general, this study provides new insight into the mechanism for HCC and suggests that DNASE1L3 can become a considerable target for HCC.

NAP1L1 Functions as a Tumor Promoter via Recruiting Hepatoma-Derived Growth Factor/c-Jun Signal in Hepatocellular Carcinoma.

NAP1L1 has been reported to be significantly involved in the carcinogenesis of hepatocellular carcinoma (HCC). Yet, its detailed molecular basis is still to be determined. Based on the analysis of The Cancer Genome Atlas (TCGA) database, NAP1L1 mRNA was found to be upregulated and predicted the poor prognosis initially. Subsequently, consistent with the prediction, the upregulated expression of NAP1L1 mRNA and protein levels was confirmed by quantitative polymerase chain reaction (qPCR), Western blot, and immunohistochemistry assays. Upregulated NAP1L1 protein positively promoted the disease progression and poor prognosis of HCC. In addition, NAP1L1 protein expression was considered as an independent prognostic factor in HCC. Inhibition of NAP1L1 expression by siRNA or shRNA pathway significantly reduced the cell proliferation and cell cycle transformation in vitro and in vivo. Mechanism analysis first showed that the function of NAP1L1 was to recruit hepatoma-derived growth factor (HDGF), an oncogene candidate widely documented in tumors. Furthermore, the latter interacted with c-Jun, a key oncogenic transcription factor that can induce the expression of cell cycle factors and thus stimulate the cell growth in HCC. Finally, transfecting HDGF or c-Jun could reverse the suppressive effects on HCC growth in NAP1L1-suppressed HCC cells. Our data indicate that NAP1L1 is a potential oncogene and acts via recruiting HDGF/c-Jun in HCC.

miR-29b restrains cholangiocarcinoma progression by relieving DNMT3B-mediated repression of CDKN2B expression.

Numerous studies have reported the important role of microRNAs (miRNAs) in human cancers. Although abnormal miR-29b expression has been linked to tumorigenesis in several cancers, its role in cholangiocarcinoma remains largely unknown. We found that miR-29b expression is frequently downregulated in human cholangiocarcinoma QBC939 cells and in clinical tumor samples. In cholangiocarcinoma patients, low miR-29b expression predicts poor overall survival. Overexpression of miR-29b in QBC939 cells inhibited proliferation, induced G1 phase cycle arrest, and promoted apoptosis. Methylation-specific PCR (MSP) analysis revealed a decreased methylation imprint at the promoter of the cell cycle inhibitor gene CDKN2B in cells overexpressing miR-29b. After identifying the DNA methyltransferase DNMT3B as a putative miR-29b target, luciferase reporter assays confirmed a suppressive effect of miR-29b on DNMT3B expression. Accordingly, we detected an inverse correlation between miR-29b and DNMT3B expression in clinical cholangiocarcinoma specimens. In QBC939 cells, DNMT3B overexpression promoted proliferation and inhibited apoptosis. DNMT3B silencing, in turn, led to increased CDKN2B expression. We also observed significant growth arrest in subcutaneous tumors formed in nude mice by QBC939 cells overexpressing miR-29b. These findings suggest miR-29b functions as a tumor suppressor in cholangiocarcinoma by relieving DNMT3B-mediated repression of CDKN2B expression.

Recovery from a biliary stricture of a common bile duct ligature injury: A case report.

BACKGROUND: Cholecystectomy is a common elective procedure for cholecystic diseases, including cholecystitis and cholelithiasis. Common bile duct injury is a major complication in both open and laparoscopic cholecystectomy (LC). The number of cholecystectomies performed has increased due to popularization and application of the laparoscopic technique, which has led to an increase in the number of bile duct injuries. CASE SUMMARY: A 65-year-old man presented to the General Surgery Department with a complaint of repeated right upper quadrant pain for 2 years that had worsened over the previous day. The patient had a history of gallstones and hypertension. A LC was performed; it was found that a biliary stricture of 53 h duration was caused by a ligature injury of the common bile duct during the LC. Another laparoscopic exploration was performed, and the stricture was released. CONCLUSION: LC is a common surgical procedure, but if a complication occurs, it is important for the surgeon to consider another exploratory surgery.

Emergency Responses to Covid-19 Outbreak: Experiences and Lessons from a General Hospital in Nanjing, China.

BACKGROUND: The novel coronavirus 2019 (SARS-CoV-2) has caused wide dissemination across the world. Global health systems are facing the unprecedented challenges. Here we shared the experiences and lessons in emergency responses and management from our hospital, a government-assigned regional anti-Covid-19 general hospital in Nanjing, Jiangsu Province, China. METHODS: Our periodic strategies in dealing with Covid-19 were described in detail. An administrative response including the establishment of Emergency Leadership Committee that was in full charge of management was established. Modifications of infrastructure including the Fever Clinic, inpatient ward, outpatient clinic and operation room were carried out. Special arrangements for outpatient services, hospitalization and surgeries were introduced. Medical personnel training and patient educations were performed. Initiations of Covid-19 researches and application of information technology were introduced. FINDINGS: Since January 16, three cases have been confirmed in our hospital and no healthcare-associated infection was found. During the epidemics, 6.46% staffs suffered depression, 9.87% had anxiety, and 98% were satisfied with the infection control policy. Shortages in staffs and medical consumables, and limitation in space were the obstacles we encountered. INTERPRETATION: As the cost of in-hospital transmission is unbearable, our experiences and lessons suggested that prompt actions should be taken immediately to decrease or eliminate potential in-hospital transmission. Experience shared herein may be useful for those facilities that are and may encounter Covid-19.

Exosome-Mediated MiR-155 Transfer Contributes to Hepatocellular Carcinoma Cell Proliferation by Targeting PTEN.

BACKGROUND Most eukaryocytes release nano vesicles (30-120 nm), named exosomes, to various biological fluids such as blood, lymph, and milk. Hepatocellular carcinoma (HCC) is one of the tumors with the highest incidence rate in primary malignant carcinoma of the liver. However, the mechanism of HCC proliferation remains elusive. In this study, we aim to explore whether HCC cell-derived exosomes affect the proliferation of cancer cells. MATERIAL AND METHODS Exosomes were isolated from HCC cells by ultracentrifugation and were visualized the phenotype by transmission electron microscopy. Cell proliferation was detected by Cell Counting Kit-8 assays and EdU (5-ethynyl-2-deoxyuridine) incorporation assays. Dual-luciferase assays were performed to validate the paired correlation of miR-155 and 3'-UTR of PTEN (gene of phosphate and tension homology deleted on chromosome 10). A xenograft mice model was constructed to verify the effect of exosome-mediated miR-155 on cell proliferation in vivo. RESULTS Our finding showed that miR-155 was enriched in exosomes released from HCC cells. The exosome-containing miR-155 transferred into new HCC targeted cells and lead to the elevation of HCC cells' proliferation. Besides, the exosomal miR-155 directly bound to 3'-UTR of PTEN leading to the reduction of relevant targets in recipient liver cells. The knockdown of PTEN attenuated the proliferation of HCC cells treated with the exosomal miR-155. Moreover, nude-mouse experiment results revealed a promotional effect of the exosomal miR-155 on HCC cell-acquired xenografts. CONCLUSIONS Our study indicated that exosomal-specific miR-155 transfers to adjacent and/or more distant cells and stimulates the proliferation of HCC cells.

Long-Term Results of Concurrent Chemoradiotherapy for Advanced N2-3 Stage Nasopharyngeal Carcinoma.

BACKGROUND: N-stage is related to distant metastasis in nasopharyngeal carcinoma (NPC) patients. The purpose of this study was to evaluate the efficacy and toxicity of different nedaplatin-based chemotherapy regimens in advanced N2-3 stage NPC patients treated with intensity modulated radiation therapy (IMRT). PATIENTS AND METHODS: Between April 2005 and December 2009, a total of 128 patients with N2-3 advanced NPC were retrospectively analyzed. Patients were treated with IMRT concurrent with 2 cycles of chemotherapy consisting of either nedaplatin plus paclitaxel (NP group, n = 67) or nedaplatin plus fluorouracil and paclitaxel (NFP group, n = 61). Two to four cycles of adjuvant chemotherapy were then administered every 21 days following concurrent chemoradiotherapy. RESULTS: With a median follow-up of 60 months, the 5-year overall survival (OS), progression-free survival (PFS), local-regional recurrence-free survival (LRRFS), and distant metastasis-free survival (DMFS) for all patients were 81.4%, 71.5%, 87.8% and 82.0%, respectively. No significant difference in PFS (66.6% vs. 76.7%, P = 0.212) and LRRFS rates (89.0% vs. 86.3%, P = 0.664) was observed between the NP and NFP groups. The 5-year OS (75.4% vs. 88.5%, P = 0.046) and DMFS (75.1% vs. 89.0%, P = 0.042) rate were superior in the NFP group compared with the NP group. The NFP group had a higher incidence of grade 3-4 acute toxicities including bone marrow suppression (leukopenia: χ2 = 3.935, P = 0.047; anemia: χ2 = 9.760, P = 0.002; thrombocytopenia: χ2 = 8.821, P = 0.003), and both liver and renal dysfunction (χ2 = 5.206, P = 0.023) compared with the NP group. Late toxicities were moderate and no difference was observed between the two groups. CONCLUSION: IMRT concurrent with nedaplatin-based chemotherapy is an advocated regimen for patients with advanced N2-3 stage NPC. Patients with advanced N2-3 stage may be better candidates for the NFP regimen although this regimen was associated with a high acute toxicity rate.

A new index comparable to BED for evaluating the biological efficacy of hypofractionated radiotherapy schemes on early stage non-small cell lung cancer: analysis of data from the literature.

BACKGROUND AND PURPOSE: Hypofractionated radiotherapy has been the principal curative treatment option for early stage NSCLC patients who are medically inoperable or those who refuse surgery and achieved favorable clinical outcomes. Evidence demonstrated that the linear quadratic model widely used in normally fractionated radiotherapy cannot work well to fit outcome data by use of BED to predict the effect of hypofractionation schemes. New models and the related metrics need to be developed to quantify the effect of high-dose ablative regimens for early stage NSCLC. PATIENTS AND METHODS: Trials using hypofractionated radiotherapy without chemotherapy to treat early stage (T1 or T2N0M0) primary NSCLC and providing information on patient numbers, age, T stage and local control rates were eligible. The endpoint was local relapse and the covariates analyzed were total radiotherapy dose, dose per fraction or combinations of the two parameters, treatment duration, T stage and median age of patients within the trial. The model used was a multivariate logistic regression. RESULTS: 19 trials were included (767 patients) in which 90 patients suffered local relapse. Only total dose × dose per fraction (D × d) and stage T had statistically significant effect on local control. Smaller T stage (p=0.000) and increasing D × d (p=0.006) were associated with improved probability of local control. In contrast, BED10 had no significant impact on local control, which probably indicated that D × d might be a more effective metric than BED10 to predict tumor control rate and assess the efficacy of the large dose fractionation schemes for early stage NSCLC. CONCLUSIONS: BED was not an ideal metric to estimate the effect of the schemes of high-dose ablative radiotherapy for early stage NSCLC, and total dose × fraction dose could be considered as a comparable index, though the result need to be further validated.

Terahertz Wave Propagation in a Nanotube Conveying Fluid Taking into Account Surface Effect.

In nanoscale structure sizes, the surface-to-bulk energy ratio is high and the surface effects must be taken into account. Surface effect plays a key role in accurately predicting the vibration behavior of nanostructures. In this paper, the wave behaviors of a single-walled carbon nanotube (CNT) conveying fluid are studied. The nonlocal Timoshenko beam theory is used and the surface effect is taken into account. It is found that the fluid can flow at a very high flow velocity and the wave propagates in the terahertz frequency range. The surface effects can significantly enhance the propagating frequency. This finding is different from the classical model where the surface effect is neglected.

Multi-target lentivirus specific to hepatocellular carcinoma: in vitro and in vivo studies.

BACKGROUND & AIMS: We aimed at investigating the effects of the targeted transduction of the Wtp53-pPRIME-miR30-shRNA gene into liver cancer cells, under the mediation of anti-alpha fetoprotein scFv-directed lentivirus, and the inhibitory effect of this system on liver cancer cells. METHODS: The result of infection was observed by fluorescence microscopy. Polymerase chain reaction and Western blotting were used to demonstrate the successful transduction and transcription of the Wtp53-pPRIME-miR30-shRNA-IGF1R gene. Cell growth was observed via the Cell-Counting Kit-8 Method, and cell apoptosis was detected by terminal deoxynucleotidyl transferase biotin-dUTP nick end labeling. To observe further the effects of AFP-Wtp53-pPRIME-miR30-shRNA-IGF1R therapy in animals, models of BALB-C nude mice bearing subcutaneous human hepatocellular carcinoma were established. The influence of the growth of subcutaneously transplanted tumor, expression of Wtp53 protein, apoptosis, and microvessel formation on the overall level of AFP-Wtp53 pPRIME-miR30-shRNA-IGF1R were also evaluated. RESULTS: Recombinant lentivirus was successfully constructed, and its functional plaque-forming unit titer was determined as 4.58 × 10(9)plaque-forming units/ml. A positive strand was detected by polymerase chain reaction and Western blotting. Lentiviral construction worked effectively in AFP-positive liver cancer cells. In vitro and in vivo experiments showed that the recombinant lentivirus was more efficacious in inhibiting the proliferation of Hep3B cells. CONCLUSIONS: The Wtp53-pPRIME-miR30-shRNA gene can be subjected to targeted transduction into liver cancer cells under the mediation of anti-alpha fetoprotein scFv-directed lentivirus. The Wtp53-pPRIME-miR30-shRNA system has targeting ability and lethal effects on liver cancer cells.

[Clinical features and prognosis of solid-pseudopapillary tumor of the pancreas].

OBJECTIVE: To study the clinicopathological and immunohistochemical features, histogenesis and biological behavior, clinical treatment and prognosis of solid pseudopapillary tumor of the pancreas (SPT). METHODS: Routine HE and immunohistochemical (SP) stainings were used in the pathological examination of 18 cases of SPT. Their clinical data were retrospectively analyzed. All the 18 postoperative patients were followed-up for 3 months to 10 years with an average of 29.2 months. RESULTS: There were 16 females and 2 males, age ranging from 9 to 65 years with mean age of 25.3 years. Abdominal pain and palpable mass were among the major complains. Tumors were encapsulated and mixed with solid and cystic tissues. Histological features were pseudopapillary structure with a fibrovascular core. Immunhistologically, most tumors were positive for alpha-AT, alpha-ACT and Vim, with a high percentage of 94.4%. The eighteen cases were followed-up from 3 to 120 months. Five cases received reoperation after recurrence, and 14 cases were alive. Maximum survival time was 121 months and the minimum survival time was 3 months, with a median survival time of 23.0 months. The 5-year survival rate was 72.2%. A Kaplan-Meier analysis revealed that patient's age, tumor size, pathologic features, metastasis were major prognostic factors for SPT. CONCLUSION: SPT is a tumor of low-grade malignancy and may be derived from multipotent stem cells. SPT most frequently affects young female, and has distinct clinicopathologic manifestation with excellent prognosis after surgical treatment.

[Total body irradiation of the donor in a spontaneous tolerance rat liver transplantation model and the effects on CD4(+)CD25(+) regulatory T cells content].

OBJECTIVE: To study the effect of total body irradiation of the donor in a spontaneous tolerance rat liver transplantation model and the role of CD4(+)CD25(+) regulatory T cells on induction of immunotolerance in the recipient. METHODS: Liver transplantation was performed using male Lewis rats as donors and male DA rats as recipients. These rats were randomly allocated into the following groups:Control group, Homogeneity Liver Transplantation group, Idio-immunotolerance group and Acute Rejection group. After transplantation, survival time rate of each group were observed. Serum ALT, TB level, Foxp3(+)CD4(+)CD25(+) regulatory T cells, expression of GITR on T cell subgroup, histopathology of the hepatic graft on day 14, spleen CTL lytic activity on day 14 were measured. RESULTS: In the Idio-immunotolerance group, the recipients suffered from transient rejection after surgery but acquired immunotolerance and survived long. In the Acute Rejection group, the donors were preconditioned with total body irradiation before liver transplantation. All recipients died between day 17 to 21. Serum ALT and TB increased significantly and the ratio of Foxp3(+)CD4(+)CD25(+) regulatory T cells decreased significantly compared with the Idio-immunotolerance group, the Homogeneity Liver Transplantation group and the Control group. The expression of GITR on CD3(+)CD4(+)T cells in the peripheral blood decreased, the expression of GITR on CD3(+)CD8(+) T cells and CTL lytic activity of the recipients increased by preconditioning of the donors with total body irradiation. CONCLUSIONS: Preconditioning of the donors with total body irradiation eliminated the passenger lymphocytes of the liver graft, decreased the expression of Foxp3(+)CD4(+)CD25(+) regulatory T cells in peripheral blood, and increased the expression of GITR on CD3(+)CD8(+) T cells, thus affected the course of tolerance and induced acute rejection after liver transplantation.

Adenoviral cardiotrophin-1 transfer improves survival and early graft function after ischemia and reperfusion in rat small-for-size liver transplantation model.

This study was to investigate the effect of donor liver adenoviral cardiotrophin-1 (CT-1) gene transfer on early graft survival and function in rat small-for-size liver transplantation. We constructed a recombinant murine CT-1 adenoviral vector. Donor rats were transduced in vivo with adenoviruses expressing CT-1 (AdCT-1) or control vector (AdEGFP). Livers were harvested 4 days later, reduced to 40% of weight, and transplanted. A syngeneic rat orthotopic liver transplantation model was performed using 40% small-for-size grafts. Graft survival, liver function, hepatic architecture change, the degree of necrosis and apoptosis, and cell survival signaling pathways were assessed. AdCT-1 pretreatment markedly improved liver function and the survival of small-for-size grafts. In the CT-1 treatment group, hepatic architecture was well protected, apoptotic and necrotic cells were reduced; anti-apoptotic protein bcl-2 was up-regulated and pro-apoptotic cleaved caspase-3 was down-regulated, cell survival signaling pathways were activated by phosphorylation of protein kinase B (Akt), extracellular-regulated kinase (ERK) and Signal transducer and activator of transcription-3 (Stat-3) after transplantation. In conclusion, donor liver adenoviral CT-1 transfer ameliorated ischemia/reperfusion injury by decreasing hepatic necrosis and apoptosis in small-for-size liver transplantation, mediated in part by activation of the Akt, ERK, and Stat-3 survival signaling pathways. These results may provide a potential clinical strategy to improve the outcome of small-for-size liver grafts.

[Application of irradiated allograft vascular in the liver transplantation].

OBJECTIVE: To study the substitute portal vein by irradiated allograft saphenous vein during liver transplantation and investigate the changes in morphology and immunology. METHODS: All the recipients were divided into 3 groups randomly:irradiated allograft group (n = 11) (group A), fresh allograft group (n = 9) (group B) and fresh self-graft group (n = 14) (group C). The number of non-jam graft vessels in each group was explored at 1st week, 2nd week, 1st month, 2nd month and 3rd month post-operation. Also, the infiltration of CD(4)(+), CD(8)(+) T cells and histological changes in grafted vessels were detected. RESULTS: No obvious histological changes were observed in group A, as well as under naked eyes. There were 9, 3 and 12 non-jam vessels in group A, B and C and there were significant differences between group A and B (P < 0.05). The endothelial cells of graft vessels were observed both in group A and C two weeks post-operation and covered the graft vessels two months later. There were infiltration of lymphocytes and inflammatory cells at early stage, obvious damage and no endothelial cells growth in graft vessels in group B. Compared with group B, the percentage of CD(4)(+), CD(8)(+) T cells in group A was lower significantly, but higher slightly than that in group C. CONCLUSIONS: Irradiated allograft saphenous veins have the quality of ideal vascular transplantation prosthesis and weak antigenicity at the same time. The changes of CD(4)(+), CD(8)(+) T cells after allograft vessels can be detected as immunology index for acute immunological rejection.

[Expression of urokiase-type plasminogen activator and matrix metalloproteinases in human tissue of abdominal aortic aneurysm].

OBJECTIVE: To explore the expression of urokinase-type plasminogen activator (u-PA) and matrix metalloproteinases in human abdominal aortic aneurysm (AAA) tissue. METHODS: Immunohistochemistry and in situ hybridization were employed to detect the protein and mRNA expression of u-PA, gelatinase A (MMP-2) and gelatinase B (MMP-9) in the tissue sections of 30 AAA specimens and 30 normal human abdominal aorta specimens. RESULTS: The expressions of u-PA and MMP-9 were mainly found in the macrophages in AAA tissue, but not in normal human abdominal aorta tissues. The expression of MMP-2 was found mainly in the smooth muscle cells in AAA tissues, but not in normal human abdominal aorta tissues. CONCLUSION: u-PA produced by macrophages may immediately activate proMMP-2 and proMMP-9, which play a pivotal role in the formation and development of AAA.