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By using an expressed sequence tag bioinformatic algorithm, we identified that Lin28 homolog B (Lin28B) may have an oncofetal expression pattern which may facilitate detecting cancer cells in adults. It is also reported to be a potential marker for cancer stem cells. Therefore, we sought to verify oncofetal-stemness characters of Lin28B and test its potential as a circulating cancer stem cell-like marker in adult HCC patients. Lin28B mRNA was examined in a panel of fetal tissue, adult tissue and tumors. Lin28B was over-expressed or knocked down in HepG2 cells to evaluate its potential as a stem cell-like marker. RT-qPCR for Lin28B was performed in the peripheral blood mononuclear cells from patients with HCC receiving surgery (n=96) and non-HCC controls (n=60) and analyzed its clinical significance. Lin28B showed an oncofetal expression pattern. Its overexpression could upregulate stemness markers (OCT4, Nanog and SOX2) and enhance tumorsphere formation in vitro. Lin28B knockdown had opposite effects. Circulating Lin28B was detected in peripheral blood mononuclear cells in 3 cases (5%) of non-HCC controls and 32 cases (33.3%) of HCC patients. In HCC patients, circulating Lin28B was associated with high tumor grade (P=0.046), large size (P=0.005), high AJCC stage (P=0.044) and BCLC stage (P=0.017). Circulating Lin28B was significantly associated with decreased recurrence-free survival (P<0.001). Circulating Lin28B separated early stage HCC into 2 recurrence-free survival curves (P=0.003). In multivariate analysis, circulating Lin28B was an independent variable associated with early recurrence (P=0.045) and recurrence in early stage HCC (P=0.006). In conclusion, the oncofetal gene Lin28B is a potential oncofetal cancer-stem-cell-like circulating tumor cell marker that correlates with HCC recurrence after hepatectomy. Circulating Lin28B could refine early AJCC stages. Our finding supports the possible use of a TNMC (C for circulating tumor cells) staging system in HCC.

Objective: To determine whether a tumor necrosis factor-α (TNF-α) inhibitor can reduce the embryotoxicity of the peritoneal fluid (PF) of women with endometriosis., Design: Experimental clinical study., Setting: University hospital., Patient(s): Twelve women with chocolate cysts and 12 control women without endometriosis., Intervention(s): None., Main Outcome Measure(s): We collected the PF from patients with chocolate cysts (CH-PF) and patients without endometriosis (N-PF) during laparoscopic surgery. For the in vitro studies, development and apoptosis were evaluated in two-cell stage mouse embryos after incubation with CH-PF and N-PF, with or without a TNF-α inhibitor., Result(s): We found that CH-PF significantly decreased the rate of blastocyst development and increased the percentage of apoptotic cells in the embryos. Cytokine assays showed that the concentrations of several cytokines, including TNF-α, were higher in embryos incubated with CH-PF than in those incubated with N-PF. Furthermore, the treatment of embryos with TNF-α retarded development and induced apoptosis. Important, adalimumab, a TNF-α inhibitor, effectively abrogated the embryotoxicity that was induced by CH-PF., Conclusion(s): These data collectively highlight the crucial role of TNF-α in CH-PF-induced embryotoxicity and suggest that TNF-α inhibitors may be potential therapeutic agents for treating endometriosis-induced infertility., (Copyright © 2013 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Background: Despite its recognized role as a prognostic marker for antiviral treatment, the clinical significance of serum hepatitis B surface antigen (HBsAg) level in the immune-clearance stage of chronic hepatitis B remains unclear., Objectives: To characterize how HBsAg level and various clinical and virological factors are related and analyze the correlation of HBsAg with liver histology., Study Design: A total of 198 treatment-naïve HBeAg-positive chronic hepatitis B patients were enrolled. Serum HBV DNA and HBsAg were determined quantitatively. Mutations of precore or basal core promoter (BCP) were also determined. Finally, liver necroinflammation grading and fibrosis stage were evaluated by Knodell score and Ishak score, respectively., Results: Lower HBsAg levels were found in patients with genotype C HBV infection, or in the presence of precore or mutations, or Knodell necroinflammation grading ≥ 7, or advanced fibrosis (Ishak stage 4-6). HBsAg level displayed a strong correlation with HBV DNA (r = 0.727, P < 0.001) and also exhibited a positive correlation with intrahepatic HBcAg expression in either cytoplasm (r = 0.420, P < 0.001) or nucleus (r = 0.401, P < 0.001). Examining the correlation with advanced liver fibrosis revealed that HBsAg level is a significant factor in univariate analysis and is the only independent factor in multivariate analysis (Coefficient: -0.975, P = 0.039, OR: 0.377, 95% CI: 0.149-0.953)., Conclusions: HBsAg level varied with different clinical or virological categories. Lower baseline levels of HBsAg might reflect the status of advanced liver fibrosis in HBeAg positive chronic hepatitis B patients., (Copyright © 2013 Elsevier B.V. All rights reserved.)

Based on a porcine model with surgically created myocardial infarction (MI) as a pre-clinical scheme, this study investigates the clinical translation of cell sheet fragments of autologous mesenchymal stem cells (MSCs) for cellular cardiomyoplasty. MSC sheet fragments retaining endogenous extracellular matrices are fabricated using a thermo-responsive methylcellulose hydrogel system. Echocardiographic observations indicate that transplantation of MSC sheet fragments in infarcted hearts can markedly attenuate the adverse ventricular dilation and preserve the cardiac function post MI, which is in contrast to the controlled groups receiving saline or dissociated MSCs. Additionally, histological analyses suggest that administering MSC sheet fragments significantly prevents the scar expansion and left ventricle remodeling after MI. Immunohistochemistry results demonstrate that the engrafted MSCs can differentiate into endothelial cells and smooth muscle cells, implying that angiogenesis and the subsequent regional perfusion improvement is a promising mechanism for ameliorating post-infarcted cardiac function. However, according to the data recorded by an implantable loop recorder, the transplanted MSCs may provoke arrhythmia. Nevertheless, the proposed approach may potentially lead to the eventual translation of MSC-based therapy into practical and effective clinical treatments., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Background: Oral cancer, the largest subset of head and neck cancer, has become one of the most lethal malignancies during the last two decades. Although several diagnostic tools have been applied for the early detection of oral malignancies, it is still urgent to identify novel tumor markers. In this study, we explored the cell surface N-glycomes of primary cultured human oral keratinocytes (HOK), immortalized human gingival keratinocytes (SG cells), and oral squamous cell carcinoma (OC2)., Methods: Enzymatically hydrolyzed cell surface N-glycans were analyzed by MALDI-TOF mass spectrometry., Results: High levels of fucosylated N-glycans, especially core-fucosylated N-glycans, were observed on the OC2 cell surface whereas the major N-glycans on SG and HOK cells were high mannose type. In addition, the mRNA expression level of fucosyltransferase 8 was elevated significantly in OC2 cells than in SG and HOK cells. Core-fucosylated glycoproteins of OC2 cells were then purified with lectin affinity chromatography and a key adhesion molecule in cancer cells, CD147, was identified. Finally, overexpression of cell surface CD147 was confirmed on OC2 cells and oral cancer tissues (tissue array)., Conclusions: CD147 was discovered by glycoproteomic approaches and suggested to be a potential novel tumor marker for oral cancer diagnosis., (Copyright © 2012 Elsevier B.V. All rights reserved.)

Objective: To test the feasibility of partial nephrectomy using needle arrays under alternating current (AC) electromagnetic field without renal artery clamping., Methods: We performed an experimental study for partial nephrectomy without renal artery clamping in a porcine model, comparing a new thermal surgery system consisting of an AC electromagnetic field generator and stainless steel needle arrays (using 10 pigs) vs an ultrasonic Harmonic Scalpel (on 8 pigs). Two cm of the upper pole of the kidneys were resected, and then the feasibility, operation time, blood loss, biochemical parameters, pathology, and complications were observed for 14 days., Results: There was no difference by weight in the mean percentage of kidney removed between the 2 groups (8.1 ± 3.4% vs 12.7 ± 5.5%). The estimated blood loss for the partial nephrectomy with electromagnetic thermal surgery system was significantly less compared to the ultrasonic Harmonic Scalpel (53.0 ± 73.0 vs 188.8 ± 49.3 mL). Transection time was shorter with the electromagnetic thermal surgery system (10 vs 12 minutes). Bleeding from the cut surface after partial nephrectomy was noted in 2 pigs (electromagnetic surgery group) and 8 pigs (control group); all the bleeding was controlled with additional monopolar electrocoagulation and sutures. No urinoma was identified in either group when a second laparotomy was performed 2 weeks later., Conclusion: Our study of a partial nephrectomy in a porcine model demonstrates that the heat generated by the electromagnetic thermal surgery system is sufficient to coagulate renal parenchyma and to seal off the blood vessels without pedicle clamping., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Emotional state can modulate the perception of respiratory loads but the range of respiratory load magnitudes affected by emotional state is unknown. We hypothesized that viewing pleasant, neutral and unpleasant affective pictures would modulate the perception of respiratory loads of different load magnitudes. Twenty-four healthy adults participated in the study. Five inspiratory resistive loads of increasing magnitude (5, 10, 15, 20, 45 cm H(2)O/L/s) were repeatedly presented for one inspiration while participants viewed pleasant, neutral and unpleasant affective picture series. Participants rated how difficult it was to breathe against the load immediately after each presentation. Only at the lowest load, magnitude estimation ratings were greater when subjects viewed the unpleasant series compared to the neutral and pleasant series. These results suggest that negative emotional state increases the sense of respiratory effort for single presentations of a low magnitude resistive load but high magnitude loads are not further modulated by emotional state., (Published by Elsevier B.V.)

Background: Pancreatic fistula is still the major postoperative morbidity after distal pancreatectomy (DP). An inductive heat technology via needle arrays in a system of alternating magnetic fields (AMFs) was designed to seal off the pancreatic end., Methods: Twenty Lanyu pigs were divided into 2 groups for DP: the conventional group had hand-sewn closure of the pancreatic end (n = 10), and the AMF group received thermal DP by AMF (n = 10). Pathological examinations of the resected and remnant pancreas were studied immediately after resection and on the 14th postoperative day (POD), respectively. The severity and the incidence of pancreatic abscess were compared., Results: The incidence and severity of pancreatic abscess were significantly decreased in the AMF group than those in the conventional group (P = .009). In the immediate postoperative period, microscopic examination of the pancreatic resected end showed prominent coagulative necrosis, loss of NADPH-diaphorase activity, and significant apoptosis at the resected pancreas in the AMF group compared with the control group. Fourteen days after AMF ablation, the pancreatic stump end was covered with thick fibrosis, and histological study of the remnant pancreas showed that the parenchyma had well recovered with positive NADPH-diaphorase activity, and the pancreatic duct was sealed off successfully by prominent periductal fibrosis and intraductal plug. The body weight gain on the 14th POD was significantly increased in the AMF group (from 23.8 ± 1.8 kg to 25.4 ± 5.5 kg) compared with the conventional group (from 25.3 ± 2.1 to 25.4 ± 6.0 kg; P = .003)., Conclusions: Inductive heats by the AMF system via needle array can be performed easily and can seal the pancreatic cut surface well during DP.

Objective: To report the natural history and prognosis of the uncommon Sertoli-Leydig cell tumor (SLCT) of the ovary., Materials and Methods: A 20-year retrospective review was conducted by the Taiwanese Gynecologic Oncology Group (TGOG), including nine tertiary medical centers from different regions in Taiwan. The medical records for 40 cases of ovarian SLCT were collected. Pathology reviews were carried out by a panel of expert pathologists., Results: After pathological review, 17 patients were subsequently excluded because the pathology slides were unavailable in five cases, and discrepant results from the initial diagnosis were found in 12 cases (34%). For the remaining 23 patients, the median age was 41 years. The most common symptom was irregular vaginal bleeding followed by an abdominal mass or amenorrhea. Most of the tumors were unilateral and confined to the right ovary, with an average size of 8.2 cm. Preoperative serum markers were available for 12 patients and were elevated for three patients. All patients underwent primary surgery. Six patients accepted adjuvant chemotherapy, and bleomycin, etoposide, and cisplatin were used in four of them. Clinical follow-up information was available in 21 patients with a median of 19 months. Eighty-two percent of patients were alive and free of disease up to the date of the last follow-up. Two patients died of the disease., Conclusion: This study demonstrates the extreme rarity of ovarian SLCT in Taiwan. Histological discordance between the diagnosis and central review proves the need for expertise review before treatment. For an improved understanding of the biological behavior and treatment strategy for this unique tumor, international collaboration is imperative., (Copyright © 2013. Published by Elsevier B.V.)

Objectives: To estimate the effectiveness of combined intervention with the pulmonary recruitment maneuver and intraperitoneal normal saline infusion to reduce postlaparoscopic shoulder and upper abdominal pain., Methods: Patients were randomly assigned to undergo the combined intervention (n=50) or to a control group (n=50). Postlaparoscopic shoulder pain and upper abdominal pain were evaluated at 12, 24, and 48 hours postoperatively., Results: At 12, 24, and 48 hours, the incidence of laparoscopic-induced shoulder pain was lower in the intervention group (54%, 46%, and 30%, respectively) than in the control group (72%, 70%, and 50%, respectively; P=.008, P=.001, and P=.004, respectively). The number needed to treat for benefit to reduce shoulder pain incidence was six (95% confidence interval [CI], 4-21) at 12 hours, five (95% CI, 3-10) at 24 hours, and five (95% CI, 4-15) at 48 hours. The incidence of laparoscopic-induced upper abdominal pain also was lower in the intervention group (78%, 72%, and 58%, respectively) than in the control group (92%, 90%, and 70%, respectively) at 12, 24, and 48 hours postoperatively (P=.006, P=.001, and P=.077, respectively). The number needed to treat for benefit to reduce upper abdominal pain incidence was eight (95% CI, 5-24) at 12 hours and six (95% CI, 4-14) at 24 hours., Conclusions: Combined intervention with the pulmonary recruitment maneuver and intraperitoneal normal saline infusion is easy to implement in daily clinical practice to significantly reduce postlaparoscopic shoulder and upper abdominal pain.

Chronic hepatitis B virus (HBV) infection is the major cause of hepatocellular carcinoma (HCC). The pre-S(2) mutant large HBV surface antigen (LHBS) in type II ground glass hepatocytes (GGHs) has been recognized as an emerging viral oncoprotein; it directly interacts with the c-Jun activation domain-binding protein 1 (JAB1) and subsequently causes hyperphosphorylation of the tumor-suppressor retinoblastoma and, consequently, leads to disturbed cell cycle progression. The interaction of the pre-S(2) mutant LHBS with JAB1 could provide a potential target for chemoprevention. In this study, we found that the preneoplastic type II GGHs showed a significant decrease of the cyclin-dependent kinase inhibitor p27(Kip1), which serves as a marker for pre-S(2) mutant-JAB1 complex formation. The histone deacetylase (HDAC) inhibitor suberoylanilide hydroxamic acid (SAHA) elevated expression of the tumor-suppressor thioredoxin-binding protein 2 (TBP2), which subsequently enhanced the JAB1-TBP2 interaction and abolished the pre-S(2) mutant LHBS-induced degradation of p27(Kip1), which, in turn, recovered the normal cell cycle checkpoint. The pre-S(2) mutant LHBS-induced pro-oncogenic effects: increased cell proliferation, nuclear/cytoplasmic ratio and proliferating cell nuclear antigen expression, were all greatly ameliorated after SAHA treatments, which suggested SAHA as a promising chemopreventive agent for the pre-S(2) mutant oncoprotein-induced HCC. In conclusion, this study provides the mechanism of histone deacetylase (HDAC) inhibitor in preventing the pre-S(2) mutant-induced oncogenic phenotype. The HDAC inhibitor SAHA is therefore a potential chemopreventive agent for high-risk chronic HBV patients who may develop HCC.

A left atrial mass associated with coronary artery disease is often diagnosed as a mural thrombus rather than other possible etiologies such as benign primary cardiac tumor (myxoma, lipoma), a malignant primary cardiac tumor (sarcoma, lymphoma), or secondary involvement for extracardiac tumors. Malignant lymphoma initially presenting as intracardiac masses is very rare. Chest computed tomography with contrast enhancement and cardiac magnetic resonance may be the best methods for distinguishing primary cardiac tumors from direct extension from adjacent mediastinal structures. We report the case of a 59-year-old man with incidentally found mediastinal diffuse large B-cell lymphoma invading the left atrium, which presented with coronary artery disease and a left atrial mass. Improvement in cardiac ventricular function heart after coronary artery bypass grafting may provide the patient with a better chance of receiving an adequate dose of chemotherapy., (Copyright © 2012. Published by Elsevier B.V.)

A special chip for direct and real-time observation of resistive changes, including set and reset processes based on Au/ZnO/Au system inside a transmission electron microscope (TEM), was designed. A clear conducting bridge associated with the migration of Au nanoparticles (NPs) inside a defective ZnO film from anode to cathode could be clearly observed by taking a series of TEM images, enabling a dynamic observation of switching behaviors. A discontinuous region (broken region) nearby the cathode after reset process was observed, which limits the flow of current, thus a high resistance state, while it will be reconnected to switch the device from high to low resistance states through the migration of Au NPs after set process. Interestingly, the formed morphology of the conducting bridge, which is different from the typical formation of a conducting bridge, was observed. The difference can be attributed to the different diffusivities of cations transported inside the dielectric layer, thereby significantly influencing the morphology of the conducting path. The current TEM technique is quite unique and informative, which can be used to elucidate the dynamic processes in other devices in the future.

Ectomesenchymal chondromyxoid tumor (ECMT) is a rare entity of the dorsal tongue first described in 1995. Herein, we report a rare case of lingual ECMT in a 41-year-old man. Patient presented with an asymptomatic, small nodule (0.5 cm in diameter) in the anterior tongue. The pathological findings showed uni-lobular proliferation of fusiform cells, arranged in net-like sheets or swirls, in a chondromyxoid background. The tumor cells were immunoreactive for S-100 and glial fibrillary acidic protein (GFAP), but negative for epithelial markers. Familiarity with this entity helps pathologists make a correct diagnosis.

Purpose: Hepatocellular carcinoma (HCC) is a heterogeneous cancer with active Wnt signaling. Underlying biologic mechanisms remain unclear and no drug targeting this pathway has been approved to date. We aimed to characterize Wnt-pathway aberrations in HCC patients, and to investigate sorafenib as a potential Wnt modulator in experimental models of liver cancer., Experimental Design: The Wnt-pathway was assessed using mRNA (642 HCCs and 21 liver cancer cell lines) and miRNA expression data (89 HCCs), immunohistochemistry (108 HCCs), and CTNNB1-mutation data (91 HCCs). Effects of sorafenib on Wnt signaling were evaluated in four liver cancer cell lines with active Wnt signaling and a tumor xenograft model., Results: Evidence for Wnt activation was observed for 315 (49.1%) cases, and was further classified as CTNNB1 class (138 cases [21.5%]) or Wnt-TGFβ class (177 cases [27.6%]). CTNNB1 class was characterized by upregulation of liver-specific Wnt-targets, nuclear β-catenin and glutamine-synthetase immunostaining, and enrichment of CTNNB1-mutation-signature, whereas Wnt-TGFβ class was characterized by dysregulation of classical Wnt-targets and the absence of nuclear β-catenin. Sorafenib decreased Wnt signaling and β-catenin protein in HepG2 (CTNNB1 class), SNU387 (Wnt-TGFβ class), SNU398 (CTNNB1-mutation), and Huh7 (lithium-chloride-pathway activation) cell lines. In addition, sorafenib attenuated expression of liver-related Wnt-targets GLUL, LGR5, and TBX3. The suppressive effect on CTNNB1 class-specific Wnt-pathway activation was validated in vivo using HepG2 xenografts in nude mice, accompanied by decreased tumor volume and increased survival of treated animals., Conclusions: Distinct dysregulation of Wnt-pathway constituents characterize two different Wnt-related molecular classes (CTNNB1 and Wnt-TGFβ), accounting for half of all HCC patients. Sorafenib modulates β-catenin/Wnt signaling in experimental models that harbor the CTNNB1 class signature., (©2012 AACR.)

Object: The most currently accepted indication for cervical arthroplasty is 1- or 2-level degenerative disc disease (DDD) refractory to medical treatment. However, the randomized and controlled clinical trials by the US FDA investigational device exemption studies only compared cervical arthroplasty with anterior cervical discectomy and fusion for 1-level disease. Theoretically, 2-level cervical spondylosis usually implicates more advanced degeneration, whereas the 1-level DDD can be caused by merely a soft-disc herniation. This study aimed to investigate the differences between 1- and 2-level cervical arthroplasty., Methods: The authors analyzed data obtained in 87 consecutive patients who underwent 1- or 2-level cervical arthroplasty with Bryan disc. The patients were divided into the 1-level and the 2-level treatment groups. Clinical outcomes were measured using the visual analog scale (VAS) for the neck and arm pain and the Neck Disability Index (NDI), with a minimum follow-up of 30 months. Radiographic outcomes were evaluated on both radiographs and CT scans., Results: The study analyzed 98 levels of Bryan cervical arthroplasty in 70 patients (80.5%) who completed the evaluations in a mean follow-up period of 46.21 ± 9.85 months. There were 22 females (31.4%) and 48 males (68.6%), whose mean age was 46.57 ± 10.07 years at the time of surgery. The 1-level group had 42 patients (60.0%), while the 2-level group had 28 patients (40.0%). Patients in the 1-level group were younger than those in the 2-level group (mean 45.00 vs 48.93 years, p = 0.111 [not significant]). Proportional sex compositions and perioperative prescription of nonsteroidal antiinflammatory drugs were also similar in both groups (p = 0.227 and p = 1.000). The 2-level group had significantly greater EBL during surgery than the 1-level group (220.80 vs 111.89 ml, p = 0.024). Heterotopic ossification was identified more frequently in the 2-level group than the 1-level group (75.0% vs 40.5%, p = 0.009). Although most of the artificial discs remained mobile during the follow up, the 2-level group had fewer mobile discs (100% and 85.7%, p = 0.022) than the 1-level group. However, in both groups, the clinical outcomes measured by VAS for neck pain, VAS for arm pain, and NDI all significantly improved after surgery compared with that preoperatively, and there were no significant differences between the groups at any point of evaluation (that is, at 3, 6, 12, and 24 months after surgery)., Conclusions: Clinical outcomes of 1- and 2-level cervical arthroplasty were similar at 46 months after surgery, and patients in both groups had significantly improved compared with preoperative status. However, there was a significantly higher rate of heterotopic ossification formation and less mobility of the Bryan disc in patients who underwent 2-level arthroplasty. Although mobility to date has been maintained in the vast majority (94.3%) of patients, the long-term effects of heterotopic ossification warrant further investigation.

Background & Aims: Hepatocellular carcinoma (HCC) is a heterogeneous cancer in which sorafenib is the only approved systemic therapy. Histone deacetylases (HDAC) are commonly dysregulated in cancer and therefore represent promising targets for therapies, however their role in HCC pathogenesis is still unknown. We analyzed the expression of 11 HDACs in human HCCs and assessed the efficacy of the pan-HDAC inhibitor panobinostat alone and in combination with sorafenib in preclinical models of liver cancer., Methods: Gene expression and copy number changes were analyzed in a cohort of 334 human HCCs, while the effects of panobinostat and sorafenib were evaluated in three liver cancer cell lines and a murine xenograft model., Results: Aberrant HDAC expression was identified and validated in 91 and 243 HCCs, respectively. Upregulation of HDAC3 and HDAC5 mRNAs was significantly correlated with DNA copy number gains. Inhibiting HDACs with panobinostat led to strong anti-tumoral effects in vitro and vivo, enhanced by the addition of sorafenib. Cell viability and proliferation declined, while apoptosis and autophagy increased. Panobinostat increased histone H3 and HSP90 acetylation, downregulated BIRC5 (survivin) and upregulated CDH1. Combination therapy with panobinostat and sorafenib significantly decreased vessel density, and most significantly decreased tumor volume and increased survival in HCC xenografts., Conclusions: Aberrant expression of several HDACs and copy number gains of HDAC3 and HDAC5 occur in HCC. Treatment with panobinostat combined with sorafenib demonstrated the highest preclinical efficacy in HCC models, providing the rationale for clinical studies with this novel combination., (Copyright © 2012 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)

Object: Cervical arthroplasty is a valid option for patients with single-level symptomatic cervical disc diseases causing neural tissue compression, but postoperative heterotopic ossification (HO) can limit the mobility of an artificial disc. In the present study the authors used CT scanning to assess HO formation, and they investigated differences in radiological and clinical outcomes in patients with either a soft-disc herniation or spondylosis who underwent cervical arthroplasty., Methods: Medical records, radiographs, and clinical evaluations of consecutive patients who underwent single-level cervical arthroplasty were reviewed. Arthroplasty was performed using the Bryan disc. The patients were divided into a soft-disc herniation group and a spondylosis group. Clinical outcomes were measured using the visual analog scale (VAS) for neck and arm pain and the Neck Disability Index (NDI), whereas HO grading was determined by studying CT scans. Radiological and clinical outcomes were analyzed, and the minimum follow-up duration was 24 months., Results: Forty-seven consecutive patients underwent a single-level cervical arthroplasty. Forty patients (85.1%) had complete radiological evaluations and clinical follow-up of more than 2 years. Patients were divided into 1 of 2 groups: soft-disc herniation (16 cases) and the spondylosis group (24 cases). Their mean age was 45.51 ± 11.12 years. Sixteen patients (40%) were female. Patients in the soft-disc herniation group were younger than those in the spondylosis group, but the difference was not statistically significant (42.88 vs 47.26, p = 0.227). The mean follow-up duration was 38.83 ± 9.74 months. Sex, estimated blood loss, implant size, and perioperative NSAID prescription were not significantly different between the groups (p = 0.792, 0.267, 0.581, and 1.000, respectively). The soft-disc herniation group had significantly less HO formation than the spondylosis group (1 HO [6.25%] vs 14 Hos [58.33%], p = 0.001). Almost all artificial discs in both groups remained mobile (100% and 95.8%, p = 0.408). The clinical outcomes were not significantly different between the groups at all postoperative time points of evaluation, and clinical improvements were also similar., Conclusions: Clinical outcomes of single-level cervical arthroplasty for soft-disc herniation and spondylosis were similar 3 years after surgery. There was a significantly higher rate of HO formation in patients with spondylosis than in those with a soft-disc herniation. The mobility of the artificial disc is maintained, but the long-term effects of HO and its higher frequency in spondylotic cases warrant further investigation.

Hepatocellular carcinoma (HCC), a major cause of cancer-related death in Southeast Asia, is frequently associated with hepatitis B virus (HBV) infection. HBV X protein (HBx), encoded by a viral non-structural gene, is a multifunctional regulator in HBV-associated tumor development. We investigated novel signaling pathways underlying HBx-induced liver tumorigenesis and found that the signaling pathway involving IκB kinase β (IKKβ), tuberous sclerosis complex 1 (TSC1), and mammalian target of rapamycin (mTOR) downstream effector S6 kinase (S6K1), was upregulated when HBx was overexpressed in hepatoma cells. HBx-induced S6K1 activation was reversed by IKKβ inhibitor Bay 11-7082 or silencing IKKβ expression using siRNA. HBx upregulated cell proliferation and vascular endothelial growth factor (VEGF) production, and these HBx-upregulated phenotypes were abolished by treatment with IKKβ inhibitor Bay 11-7082 or mTOR inhibitor rapamycin. The association of HBx-modulated IKKβ/mTOR/S6K1 signaling with liver tumorigenesis was verified in a HBx transgenic mouse model in which pIKKβ, pS6K1, and VEGF expression was found to be higher in cancerous than non-cancerous liver tissues. Furthermore, we also found that pIKKβ levels were strongly correlated with pTSC1 and pS6K1 levels in HBV-associated hepatoma tissue specimens taken from 95 patients, and that higher pIKKβ, pTSC1, and pS6K1 levels were correlated with a poor prognosis in these patients. Taken together, our findings demonstrate that HBx deregulates TSC1/mTOR signaling through IKKβ, which is crucially linked to HBV-associated HCC development.

Objective: To evaluate the effectiveness of the pulmonary recruitment maneuver (PRM) and intraperitoneal normal saline infusion (INSI) in removing postlaparoscopic carbon dioxide from the abdominal cavity to decrease laparoscopy-induced abdominal or shoulder pain after surgery., Design, Setting, and Patients: A prospective, randomized, controlled trial was conducted at Taipei Veterans General Hospital, Taipei, Taiwan, from August 1, 2009, through June 30, 2010. One hundred fifty-eight women undergoing laparoscopic surgery for benign gynecologic lesions were randomly assigned to 3 groups: the PRM group (n = 53), the INSI group (n = 54), and the control group (n = 51)., Interventions: Postoperative maneuvers included PRM and INSI., Main Outcome Measures: Evaluation of pain, including abdominal pain and shoulder pain, was performed at 12, 24, and 48 hours postoperatively., Results: The frequency of postoperative shoulder pain at 24 and 48 hours was significantly decreased in the INSI group compared with that of either the PRM or control group (40.7% and 24.1% in the INSI group vs 66.0% and 50.9% in the PRM group [P = .009 and .004, respectively] or vs 72.5% and 54.9% in the control group [both P < .001]). Both methods significantly reduced the frequency of upper abdominal pain compared with the control condition (73.6% in the PRM group at 24 hours [P = .03] or 72.2% at 24 hours [P .02] and 44.4% at 48 hours [P = .01] in the INSI group vs 90.2% at 24 hours and 68.6% at 48 hours in the control group)., Conclusions: Both PRM and INSI could effectively reduce pain after laparoscopic surgery, but INSI might be better for both upper abdominal and shoulder pain.

Rapid induction and creation of functional vascular networks is essential for the success of treating ischemic tissues. The formation of mature and functional vascular networks requires the cooperation of endothelial cells (ECs) and perivascular cells. In the study, we used a thermo-responsive hydrogel system to fabricate core-shell cell bodies composed of cord-blood mesenchymal stem cells (cbMSCs) and human umbilical vascular ECs (HUVECs) for functional vasculogenesis. When seeded on Matrigel, the shelled HUVECs attempted to interact and communicate vigorously with the cored cbMSCs initially. Subsequently, HUVECs migrated out and formed tubular structures; cbMSCs were observed to coalesce around the HUVEC-derived tubes. With time progressing, the tubular networks continued to expand without regression, indicating that cbMSCs might function as perivascular cells to stabilize the nascent networks. In the in vivo study, cbMSC/HUVEC bodies were embedded in Matrigel and implanted subcutaneously in nude mice. At day 7, visible blood-filled vessels were clearly identified within the implant containing cbMSC/HUVEC bodies, indicating that the formed vessels anastomosed with the host vasculature. The cored cbMSCs were stained positive for smooth muscle actin, suggesting that they underwent smooth muscle differentiation and formed microvessels with the shelled HUVECs, as the role of perivascular cells. These data confirm that the formation of mature vessels requires heterotypic cooperation of HUVECs and MSCs. This study provides a new strategy for therapeutic vasculogenesis, by showing the feasibility of using cbMSC/HUVEC bodies to create functional vascular networks., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Object: The long-term outcome of lumbar dynamic stabilization is uncertain. This study aimed to investigate the incidence, risk factors, and outcomes associated with screw loosening in a dynamic stabilization system., Methods: The authors conducted a retrospective review of medical records, radiological studies, and clinical evaluations obtained in consecutive patients who underwent 1- or 2-level lumbar dynamic stabilization and were followed up for more than 24 months. Loosening of screws was determined on radiography and CT scanning. Radiographic and standardized clinical outcomes, including the visual analog scale (VAS) and Oswestry Disability Index (ODI) scores, were analyzed with a focus on cases in which screw loosening occurred., Results: The authors analyzed 658 screws in 126 patients, including 54 women (42.9%) and 72 men (57.1%) (mean age 60.4 ± 11.8 years). During the mean clinical follow-up period of 37.0 ± 7.1 months, 31 screws (4.7%) in 25 patients (19.8%) were shown to have loosened. The mean age of patients with screw loosening was significantly higher than those without loosening (64.8 ± 8.8 vs 59.3 ± 12.2, respectively; p = 0.036). Patients with diabetes mellitus had a significantly higher rate of screw loosening compared with those without diabetes (36.0% vs 15.8%, respectively; p = 0.024). Diabetic patients with well-controlled serum glucose (HbA1c ≤ 8.0%) had a significantly lower chance of screw loosening than those without well-controlled serum glucose (28.6% vs 71.4%, respectively; p = 0.021). Of the 25 patients with screw loosening, 22 cases (88%) were identified within 6.6 months of surgery; 18 patients (72%) had the loosened screws in the inferior portion of the spinal construct, whereas 7 (28%) had screw loosening in the superior portion of the construct. The overall clinical outcomes at 3, 12, and 24 months, measured by VAS for back pain, VAS for leg pain, and ODI scores, were significantly improved after surgery compared with before surgery (all p < 0.05). There were no significant differences between the patients with and without screw loosening at all evaluation time points (all p > 0.05). All 25 patients with screw loosening were asymptomatic, and in 6 (24%) osseous integration was demonstrated on later follow-up. Also, there were 3 broken screws (2.38% in 126 patients or 0.46% in 658 screws). To date, none of these loosened or broken screws have required revision surgery., Conclusions: Screw loosening in dynamic stabilization systems is not uncommon (4.7% screws in 19.8% patients). Patients of older age or those with diabetes have higher rates of screw loosening. Screw loosening can be asymptomatic and presents opportunity for osseous integration on later follow-up. Although adverse effects on clinical outcomes are rare, longer-term follow-up is required in cases in which screws become loose.

Unlabelled: Ground glass hepatocytes (GGHs) harboring hepatitis B virus (HBV) pre-S mutants have been recognized as precursor lesions of hepatocellular carcinoma (HCC). Previously, we observed the activation of mammalian target of rapamycin (mTOR) in GGHs and HCCs, together with a decreased expression of HBV surface antigen (HBsAg) in HCC tissues. It is, therefore, hypothesized that the activation of mTOR during HBV tumorigenesis may potentially down-regulate HBsAg expression. In this study, we verified an inverse relationship between the expression of HBsAg and phosphorylated mTOR (p-mTOR) in 13 of 20 paired nontumorous liver and HCC tissues. In vitro, wild-type or mutant pre-S proteins could activate mTOR in the HuH-7 cell line. Interestingly, the up-regulated mTOR, in turn, suppressed HBsAg synthesis at the transcriptional level via the transcription factor, Yin Yang 1 (YY1), which bound to nucleotide 2812-2816 of the pre-S1 promoter. This inhibitory effect by the mTOR signal could be abolished by the knockdown of histone deacetylase 1 (HDAC1). Furthermore, YY1 was physically associated with HDAC1 in a manner dependent on mTOR activation. Collectively, pre-S protein-induced mTOR activation may recruit the YY1-HDAC1 complex to feedback suppress transcription from the pre-S1 promoter., Conclusion: The activation of mTOR signal in GGHs may feedback suppress HBsAg synthesis during HBV tumorigenesis and explain the observed decrease or absence of HBsAg in HCC tissues. Therapy using mTOR inhibitors for HCCs may potentially activate HBV replication in patients with chronic HBV infection., (Copyright © 2011 American Association for the Study of Liver Diseases.)

Objective: We evaluated compliance with mammography and breast sonography and the factors related to compliance., Study Design: From August 2005 through July 2006, 1239 asymptomatic women, aged 40-49 years, were enrolled in the study. Compliance in the second year was calculated. Telephone interviews examined the impact of the women's experience during mammography or sonography on adherence to rescreening., Results: The rates of compliance with mammography and sonography for breast cancer screening were 73.5% and 80.1%, respectively (p=0.006). More women receiving mammography (12.2%) reported unsatisfactory results (BI-RADS category 0) than those undergoing sonography (6.2%) (p<0.001). During the telephone interview, 74.9% of the women complained of pain during mammography, but none (0%) during sonography (p<0.001); 69.8% felt embarrassed during mammography and 55.6% during sonography (p<0.001). Multivariate logistic regression analysis showed that pain (OR 0.096, 95% CI 0.044-0.213) and unsatisfactory examination results (BI-RADS category 0) (OR 0.042, 95% CI 0.020-0.090) were barriers to not following up mammography. Embarrassment (OR 0.645, 95% CI 0.419-0.994) and unsatisfactory examination results (OR 0.169, 95% CI 0.085-0.336) were barriers to not following up sonography., Conclusions: For young Asian women with dense breast tissue, compliance with sonography for breast cancer screening was better than that with mammography., (Copyright © 2011. Published by Elsevier Ireland Ltd.)

Background: The recurrence of hepatocellular carcinoma (HCC) after hepatectomy is a serious event. It has been demonstrated that different ground-glass hepatocyte (GGH) patterns harbor specific hepatitis B virus (HBV) pre-S deletion mutants and represent preneoplastic lesions in chronic HBV infection. In the current study, the authors investigated whether a specific GGH pattern in nontumorous liver tissues was associated with the recurrence of HBV-related HCC after surgery., Methods: Clinicopathologic data from 82 patients with HBV-related HCC were reviewed. GGH patterns were assessed on hematoxylin and eosin-stained sections. Tissue hepatitis B surface antigen (HBsAg) expression was evaluated by immunohistochemical staining. Serum profiles of pre-S status, viral load, and HBV genotype were determined and correlated with clinical recurrence and survival after surgery., Results: The results indicated that the clustered pattern of GGHs or HBsAg expression was associated significantly with decreased local recurrence-free survival (LRFS) during a mean follow-up of 46.4 months (P<.001). This biomarker was comparable to or better than the prognostic value of other parameters, such as multifocal tumors (P = .022), satellite nodules (P = .005), small cell dysplasia (P = .045), or elevated viral load (P = .027), to predict recurrent HCC. Multivariate analysis also revealed that type II GGHs, which expressed marginal HBsAg and consistently clustered in nodules, were independent variables associated with LRFS (P<.001) and overall survival (P = .003)., Conclusions: The current results indicated that the assessment of GGH patterns or HBsAg expression in nontumorous liver tissues provides an easily recognized, new risk marker for the recurrence of HBV-related HCC after hepatic resection., (Copyright © 2011 American Cancer Society.)

Background and Aims: Hepatocellular carcinoma can be treated with heat-based therapies, especially radiofrequency ablation (RFA). However, RFA has limited efficacy and is quite expensive. We designed a new system using fine needles combined with an alternating magnetic field to generate hyperthermia for the treatment of hepatocellular carcinoma in a rat hepatoma model. Our aims are to assess the efficacy of our method and determine survival up to 30 days., Methods: An N1-S1 cell line was inoculated into the livers of Sprague-Dawley rats, generating tumors after 14 days. The animals were randomized into 5 groups and treated after laparotomy either with normal saline (group I), iron oxide nanoparticles (group II), fine needles (group III), fine needles and iron oxide nanoparticles combined (group IV) or self-designed two-part needles placed under ultrasonographic guidance percutaneously (group V). Every rat was placed in an alternating magnetic field. The temperature in the treatment area was maintained between 55 and 60 °C. At day 30 after treatment, tumor volumes and mortality were assessed and histology samples were studied., Results: Tumor volumes were significantly reduced and survival rate was prolonged in groups III, IV and V versus groups I and II (P < 0.05). On pathological examination, groups III, IV and V presented obvious necrosis, apoptosis, calcifications and inflammatory changes in the treatment area., Conclusion: Our study demonstrates that hyperthermia generated by fine stainless-steel needles combined with an alternating magnetic field effectively inhibits hepatoma growth in rats and prolongs their survival. Further, this method can be applied percutaneously under ultrasonographic guidance., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Background: To investigate recurrence rates and fertility outcomes of patients with borderline ovarian tumors (BOTs) treated with fertility-sparing surgery., Methods: This was a retrospective study. All women with BOTs from 2000 to 2006 were evaluated. Clinical outcomes were compared among groups that underwent radical, unilateral salpingo-oophorectomy, or ovarian cystectomy. The effects of clinical characteristics on recurrence were analyzed by independent t test, chi-square test, and Cox proportional hazard model., Results: After a mean follow-up period of 56.5 months, all 61 patients were alive. Seven (11.5%) had developed disease recurrence, and all were in the fertility-sparing group. Of these, five were in the cystectomy-only group and two in the unilateral salpingo-oophorectomy group. There was significant difference in tumor recurrence rates between the two groups (hazard ratio: 0.26, 95% confidence interval: 0.11-0.61). Nine pregnancies were achieved in six women, resulting in five deliveries, Conclusion: Fertility-sparing surgery is an acceptable and safe option for women with BOTs who wish to preserve fertility. Unilateral salpingo-oophorectomy must be considered as the first choice., (Copyright © 2011. Published by Elsevier B.V.)

Covalently closed circular DNA (cccDNA) of hepatitis B virus (HBV) is difficult to eradicate using current antiviral therapy. This study compares cccDNA reduction with relation to liver histology in nucleoside/nucleotide-naïve chronic hepatitis B patients receiving oral antiviral monotherapy (n=35), including entecavir (ETV, n=13), adefovir dipivoxil (ADV, n=22) or placebo (n=14). Serum HBV DNA, intrahepatic total HBV DNA and cccDNA are quantified. Histological hepatic examination is performed at baseline and at 48 weeks of treatment. Treatment with ETV or ADV shows significant median reduction in serum HBV DNA (-6.21 and -4.27 log(10) copies/mL) and intrahepatic total HBV DNA (-1.69 and -1.23 log(10) copies/cell). Intrahepatic cccDNA levels are reduced slightly in the ETV and the ADV groups, but do not differ statistically from the placebo group (-0.17 vs. -0.01 vs. 0.02 copies/cell). Only the level of intrahepatic cccDNA correlates with Knodell necroinflammation activity (r=0.527, P<0.001) and Ishak fibrosis severity (r=0.348, P=0.015) before treatment. Multivariate logistic regression analysis indicates that treatment-induced cccDNA reduction is associated with improved necroinflammation (P=0.041) and fibrosis (P=0.026). In conclusion, baseline intrahepatic cccDNA loads correlate with histologic activity. Although one-year ETV or ADV treatment is insufficient for cccDNA eradication, oral antiviral therapies may improve liver histology, probably by suppressing intrahepatic cccDNA., (Copyright © 2011 Wiley-Liss, Inc.)

Oncofetal genes are expressed in embryos or fetuses, are downregulated or undetectable in adult tissues, and then re-expressed in tumors. Known oncofetal genes, such as AFP, GCB, FGF18, IMP-1 and SOX1, often have important clinical applications or pivotal biological functions. To find new oncofetal-like genes, we used the public information of expressed sequence tags to systematically analyze gene expression patterns and identified a novel oncofetal-like gene, LRRC16B. It increased the proliferation, anchorage-independent growth and tumorigenesis of transformed cells in xenografts, possibly through its effects on cyclin B1 protein levels. These findings exemplify the feasibility of using bioinformatics to find new oncofetal-like genes and suggest that more genes with important functional roles will be uncovered in the candidate gene list.

During abdominal ultrasonography of a 37-year-old man a 3.2 cm hypoechoic mass in the right hepatic lobe was found incidentally. This prompted an abdominal CT, an FDG PET/CT, and an angiography to evaluate the nature of the mass. Laboratory data showed positive anti-HBs/anti-HBe, and negative HCV antibody. The alfa-fetoprotein and liver function tests were within normal limits. Contrast-enhanced CT found an enhanced hepatic tumor and primary hepatocellular carcinoma was suspected. PET/CT revealed no abnormal FDG accumulation in the right hepatic mass. The digital subtraction angiographies of the right inferior phrenic artery and right renal artery revealed a hypervascular tumor in the right adrenal gland. Therefore, a diagnosis of a right adrenal tumor was made. Serum aldosterone, serum cortisol, and urine vanillylmandelic acid, and catecholamine were all within normal limits. Laparoscopic right adrenalectomy was performed and adrenal cortical adenoma was diagnosed on a histological study.

Purpose: Partial splenectomy is technically more complicated than total splenectomy due to difficulty in haemostasis, but it can preserve splenic function after operation. We evaluated the feasibility and safety of partial splenectomy performed by an electromagnetic thermal surgery system in a porcine model., Methods: Our system was comprised of an alternating electromagnetic field generator, an extensible coil applicator, comb-needle arrays, and a temperature feedback control component. Ten Lanyu pigs were anaesthetised to conduct partial splenectomy. Two rows of comb-like stainless-steel needle arrays were inserted into the tissue at 15 cm from the distal tip of the spleen. The temperature of the tissues around the needle arrays was raised to 150°C for 3 min and the spleen was transected directly between the needle arrays and then sent for histological examination. Two weeks later, the animals underwent a second celiotomy to remove the remaining spleen for histological examination., Results: The average duration of the partial splenectomy was 10 min as timed from insertion of the needle arrays to the transection of the spleen. There was no blood loss during the procedure. The cut surface of the spleen was well coagulated without any oozing sites. During the re-exploration, no intra-abdominal blood was found. There were dense adhesions between the spleen and the surrounding organs. Histological examination of the cut surface of the excised portion of the spleen showed coagulative necrosis with clot formation in the blood vessels., Conclusions: Partial splenectomy using our electromagnetic thermal system can achieve effective haemostasis and is safe and easy to perform.

Background and Purpose: Japanese encephalitis virus (JEV) is a member of the family Flaviviridae and JEV infection is a major cause of acute encephalopathy in children, which destroys cells in the CNS, including astrocytes and neurons. However, the detailed mechanisms underlying the inflammatory action of JEV are largely unclear., Experimental Approach: The effect of JEV on the expression of matrix metalloproteinase (MMP)-9 was determined by gelatin zymography, Western blot analysis, real-time PCR and promoter assay. The involvement of the NADPH oxidase and reactive oxygen species (ROS), MAPKs, and the transcription factor NF-κB in these responses was investigated by using selective pharmacological inhibitors and transfection with appropriate siRNAs., Key Results: JEV induced the expression of the pro-form of MMP-9 in rat brain astrocytes (RBA-1 cells). In RBA-1 cells, JEV induced MMP-9 expression and promoter activity, which was inhibited by pretreatment with inhibitors of NADPH oxidase (diphenylene iodonium chloride or apocynin), MAPKs (U0126, SB203580 or SP600125) and a ROS scavenger (N-acetylcysteine), or transfection with siRNAs of p47(phox) , ERK1, JNK2 and p38. In addition, JEV-induced MMP-9 expression was reduced by pretreatment with an inhibitor of NF-κB (helenalin) or transfection with p65 siRNA. Moreover, JEV-stimulated NF-κB activation was inhibited by pretreatment with the inhibitors of NADPH oxidase and MAPKs., Conclusions and Implications: MMP-9 expression induced by JEV infection of RBA-1 cells was mediated through the generation of ROS and activation of p42/p44 MAPK, p38 MAPK and JNK1/2, leading to NF-κB activation.

Background: Osteopontin (OPN) is a multifunctional secreted glycophosphoprotein involved in miscellaneous physiologic and pathologic processes and is functionally related to the transmembrane receptor CD44. Although OPN expression has been identified to be associated with poor prognosis in several gastrointestinal malignancies, its expression in gastrointestinal stromal tumor (GIST) has not been thoroughly investigated. This study was designed to evaluate the clinicopathologic significance of OPN expression in patients with resectable GIST., Methods: OPN expression was analyzed for its clinicopathologic significance in surgical specimens from 99 patients with resectable GIST by immunohistochemistry. In situ Proximity Ligation Assay was used for examining OPN and CD44 interaction in tumor tissues and GIST cell lines. The in vitro effects of OPN and its interaction with CD44 also were assessed., Results: Increased OPN expression was a significant poor prognostic factor that independently predicted recurrence and poor disease-free survival in patients with resectable GIST. The interaction of OPN and CD44 was confirmed by their significant correlation in both GIST tumor tissues and cell lines by in situ Proximity Ligation Assay analysis. OPN and its interaction with CD44 were related to increased mitosis and significantly enhanced GIST tumor cell proliferation in vitro., Conclusions: Our study identified the clinicopathologic significance and biologic effects of OPN expression in resectable GIST. Increased OPN expression was an independent poor prognostic factor and its interaction with CD44 significantly correlated with increased mitosis as well as in vitro proliferation-promoting effects.

Background and Aim: Thrombocytopenia due to hypersplenism is usually a serious condition in cirrhotic patients who have undergone invasive procedures. We designed a new treatment method using a high-frequency alternating electromagnetic force to treat the disease condition in a rat model., Methods: Sprague-Dawley rats were given thioacetamide in drinking water and injected with methylcellulose intraperitoneally to create a cirrhotic hypersplenism model. Spleen volume was determined using the Carlson method. The Control Group consisted of 14 rats, 15 weeks old, that were used to determine the normal platelet count and normal spleen size. Experimental Group I, consisting of 15 rats, received electromagnetic thermoablation of their spleens, after which the spleen was returned to the abdomen. Group II consisted of 13 rats, receiving the same electromagnetic thermoablation as Group I, but the ablated portion was removed. Group III consisted of 14 rats receiving total splenectomies., Results: Cirrhotic hypersplenism was confirmed during laparotomy and pathological examination. Spleen volume enlarged from 1513 +/- 375 mm(3) (Control Group) to 7943 +/- 2822 mm(3) (experimental groups). Platelet counts increased from 0.35 +/- 0.21 x 10(6)/mm(3) to 0.87 +/- 0.24 x 10(6)/mm(3) for Group I, from 0.52 +/- 0.23 x 10(6)/mm(3) to 1.10 +/- 0.20 x 10(6)/mm(3) for Group II, and from 0.47 +/- 0.23 x 10(6)/mm(3) to 1.18 +/- 0.26 x 10(6)/mm(3) for Group III. No rats died due to the treatment in any of the experimental groups., Conclusions: Our animal model performed successfully and our proposed electromagnetic thermotherapy effectively treated thrombocytopenia due to cirrhotic hypersplenism.

A novel mathematical model is presented to describe the dynamic behavior of plasma glucose and insulin on diabetic subjects. Though various models have been proposed to simulate the short-term (a variety of intravenous glucose or insulin injection) glucose-insulin dynamics, it is intended to construct a modified delay differential equations (DDEs) model based on the human glucose-insulin metabolic system. Five specific adjustable parameters inside the model are defined as the factors of the major physiological functions. Then several clinical data sets (56 subjects) which includes the information of food ingestion and exogenous insulin injection are verified and the model could practically reflect the dynamics and oscillation behavior on diabetic subjects by varying the adjustable parameters. Moreover, the corresponding parameters are fairly helpful to identify the patient's conditions of major physiological functions. This generic glucose-insulin dynamic model can be expected to develop such advanced therapy strategies for diabetics in the future., (Copyright 2010 Elsevier Ltd. All rights reserved.)

Background: CD44 and osteopontin (OPN) are functionally related molecules that, alone or in combination, play miscellaneous biological and pathophysiologic roles. CD44 cleavage, one unique feature of CD44, occurs in human cancers, but its function remains unclear. This study aimed to assess the clinicopathologic significance and mechanism of CD44 cleavage in gastrointestinal stromal tumor (GIST) with respect to OPN and OPN/CD44 interaction., Materials and Methods: CD44 cleavage was evaluated by immunoblotting in 31 primary GIST tumor specimens with paired normal tissues. OPN/CD44 interaction was examined by in situ proximity ligation assay. The associations of CD44 cleavage activity with clinicopathologic parameters, cyclin D1 expression, beta-catenin expression, OPN expression, and OPN/CD44 interaction were analyzed., Results: CD44 cleavage activity was demonstrated in 87.1% of GIST, in contrast to its absence in normal tissues. Increased CD44 cleavage activity was significantly associated with enhanced mitosis by multivariate analysis, in addition to being related to tumor size, recurrence, high-risk status, and poor survival by univariate analysis. Mitosis was significantly higher in GIST with increased CD44 cleavage activity, which also positively correlated with tumor-specific beta-catenin and cyclin D1 overexpression, indicating a mitotic effect through aberrant cell cycle. Both OPN and OPN/CD44 interactions were significantly associated with CD44 cleavage., Conclusion: Our study demonstrates the clinicopathological significance of CD44 cleavage in GIST. There is a significantly increased mitosis associated with CD44 cleavage in relation to OPN/CD44 interaction and dysregulated cell cycle in GIST.

Sexual behavior is variable between individuals, ranging from celibacy to sexual addictions. Within normal populations of individual men, ranging from young to middle aged, testosterone levels do not correlate with libido. To study the genetic mechanisms that contribute to individual differences in male sexual behavior, we used hybrid B6D2F1 male mice, which are a cross between two common inbred strains (C57BL/6J and DBA/2J). Unlike most laboratory rodent species in which male sexual behavior is highly dependent upon gonadal steroids, sexual behavior in a large proportion of these hybrid male mice after castration is independent of gonadal steroid hormones and their receptors; thus, we have the ability to discover novel genes involved in this behavior. Gene expression arrays, validation of gene candidates, and transgenic mice that overexpress one of the genes of interest were used to reveal genes involved in maintenance of male sexual behavior. Several genes related to neuroprotection and neurodegeneration were differentially expressed in the hypothalamus of males that continued to mate after castration. Male mice overexpressing the human form of one of these candidate genes, amyloid beta precursor protein (APP), displayed enhanced sexual behavior before castration and maintained sexual activity for a longer duration after castration compared with controls. Our results reveal a novel and unexpected relationship between APP and male sexual behavior. We speculate that declining APP during normal aging in males may contribute to the loss of sexual function.

Background/aim: Hemostasis is a major difficulty associated with hepatectomies. The authors designed a new thermal surgery system to reduce blood loss., Methods: The newly designed system consists of an alternating magnetic field generator and stainless steel needle arrays with thermosensitive bands. Lanyu pigs were used: 4 for the Kelly crushing method and 4 for the newly designed method. The procedures used were S4-S5 segmentectomies or left lateral segmentectomies, after which the amount of blood loss and operation times were compared. The pigs were observed for 4 weeks, after which liver pathologies were studied., Results: The blood loss in the method proposed by the authors was almost 0 mL, whereas with the Kelly crushing method it was 116 +/- 35 mL. The method proposed in this study can save 15 to 25 minutes of operation time. The resected liver margins exhibited prominent apoptosis and fibrotic change in the remnant livers., Conclusions: The method proposed is a novel new way of performing thermal surgery.

Object: Dynamic stabilization systems are used to stabilize degenerative lumbar spondylosis. Loosening of the pedicle screws in such nonfusion implants is predictable. This retrospective study evaluated the incidence of screw loosening and its effect on clinical outcomes., Methods: Charts, radiographic films, and medical records of 71 consecutive patients who underwent decompression using Dynesys dynamic stabilization for 1- or 2-level lumbar spondylosis were reviewed. Radiographic films were evaluated and compared to detect screw loosening. A visual analog scale (VAS) for back pain and the Oswestry Disability Index (ODI) were used for measuring clinical outcome. Statistical analysis was conducted using the chi-square test and Student t-test., Results: The 71 patients in the study sample had a mean age of 59.2 +/- 11.65 years (range 23-80 years), with slight female predominance (39 women, 32 men). The mean follow-up duration was 16.6 months (range 8-29 months). There were loose screws in 14 of 71 patients (19.7%), for a rate of 4.6% per screw (17 of 368 screws). Most screw loosening occurred in patients >/= 55 years old (13 of 14 patients) although age and sex had no effect on screw loosening (p = 0.233 and 0.109, respectively). Both the loose screw and solid screw groups experienced significant improvement after the surgery in VAS and ODI scores. On the VAS, scores improved from 5.9 +/- 2.99 to 2.1 +/- 2.14 in the loose screw group (p = 0.003), and from 5.7 +/- 3.45 to 2.9 +/- 2.68 in the solid screw group (p < 0.001). For the ODI scale, scores improved from 43.5 +/- 16.78% to 28.0 +/- 18.18% (p = 0.006) in the loose screw group, and from 52.1 +/- 20.92% to 24.6 +/- 19.78% (p < 0.001) in the solid screw group. There were no significant differences between the 2 groups (p = 0.334 for VAS, p = 0.567 for ODI)., Conclusions: The preliminary study of this pedicle-based dynamic stabilization device for 1- and 2-level lumbar spondylosis shows radiographic evidence of screw loosening in 19.7% of patients and 4.6% of screws. Nonetheless, the loosening of screws has no adverse effect on clinical improvement.

This paper aims to present a mathematical model to describe the plasma glucose and insulin daily variations on normal and diabetic subjects. The proposed model consists of two delay differential equations (DDEs) where five adjustable parameters are used to characterize the respective dynamics and oscillation behavior of normal and diabetic subjects. Several clinical data tests demonstrate that the suggested model is practical to approach the daily-life glucose dynamics on normal, diabetic Type 1 and Type 2 subjects. Moreover, the corresponding parameters are fairly persuasive to identify the patients' conditions of physiological functions., (Copyright 2009 Elsevier Ireland Ltd. All rights reserved.)

To investigate the molecular mechanisms of arsenic (As)-associated carcinogenesis, we performed proteomic analysis on E7 immortalized human uroepithelial cells after treatment with As in vitro. Quantitative proteomics was performed using stable isotope dimethyl labeling coupled with two-dimensional liquid chromatography peptide separation and mass spectrometry (MS)/MS analysis. Among 285 proteins, a total of 26 proteins were upregulated (ratio>2.0) and 18 proteins were downregulated (ratio<0.65) by As treatment, which are related to nucleotide binding, lipid metabolism, protein folding, protein biosynthesis, transcription, DNA repair, cell cycle control, and signal transduction. This study reports the potential significance of nucleophosmin (NPM) in the As-related bladder carcinogenesis. NPM was universally expressed in all of uroepithelial cell lines examined, implying that NPM may play a role in human bladder carcinogenesis. Upregulation of NPM tends to be dose- and time-dependent after As treatment. Expression of NPM was associated with cell proliferation, migration and anti-apoptosis. On the contrary, soy isoflavones inhibited the expression of NPM in vitro. The results suggest that NPM may play a role in the As-related bladder carcinogenesis, and soybean-based foods may have potential in the suppression of As/NPM-related tumorigenesis.

Restrictive cardiomyopathy is an extremely rare cause of massive chylous ascites and chylothorax. We report a 56-year-old man patient who presented with chylous ascites and bilateral chylothorax; 12-lead electrocardiography and echocardiography revealed restrictive cardiomyopathy. Endomyocardial biopsy disclosed amyloidosis.

Purpose: Electromagnetic thermal surgery is a new technique. It applies an electrical current through coils to generate a high frequency magnetic field to heat up magnetic materials in the targeted area. Using this technique, we aim to perform liver resection without bleeding in rats and rabbits., Materials and Methods: The electromagnetic machine can produce a high frequency magnetic field, with an input of 220 V-55 A-60 Hz, an output frequency of 62.1 kHz, and a power of 2.2 kW. The magnetic materials used in this study were fine needles made of stainless steel. For ex vivo experiments, we used porcine liver explants; in the animal model, sixteen Sprague-Dawley rats and seven New Zealand White rabbits were used. We inserted one needle array along the attempted resection lines and then used the magnetic coils to heat up the needles for three min. After heating, we resected the designated liver portions using surgical scalpels., Results: In the ex vivo test, the fine needles were heated up effectively to achieve tissue coagulation (more than 90 degrees C). In the animal model the liver resection was performed without bleeding and no bile peritonitis was observed after the surgery. All animals were alive after the surgery until the end of the experiment (30 days)., Conclusions: The experiments showed that our thermal surgery system is very effective in performing bloodless liver resection without further ligation or embolisation needed. Our technique is new and the system has great potential to develop into clinical practice.

A limitation with the use of polymers as stent matrices is their inherent mechanical weakness. In this study, a polymeric stent, made from chitosan-based films fixed by genipin which has a cyclic molecular structure, was developed (the genipin stent). The mechanical properties of the genipin stent were investigated; its counterpart fixed by a linear epoxy compound (the epoxy stent) and a commercially available metallic stent were used as controls. The results indicated that the cyclic crosslinking structures formed within the genipin stent matrix were beneficiary to the improvement of its mechanical property. Additionally, the tolerable compression load of the genipin stent was superior to that of the control metallic stent. The cytotoxicity of the genipin stent was significantly lower than the epoxy stent. The deployment of the genipin stent in rabbit infrarenal abdominal aortas was performed using a French sheath. At 3 months postoperatively, the retrieved arteries remained patent; no thrombosis was observed. A nearly intact layer of endothelial cells was seen on the stent-implanted vessel wall. To evaluate its possibility as a drug delivery vehicle, sirolimus (an anti-proliferative drug) was loaded in the genipin stent. It was found that the genipin stent with heparin coating exhibited a linear sustained-release profile and the released sirolimus still possessed its original activity in inhibiting smooth muscle cell proliferation. These findings suggest that the genipin stent with enhanced mechanical strength can be used as an attractive stent platform for local drug delivery.

The purpose of this study was to assess the effectiveness of a behavioral parent therapy (BPT) program in children with attention-deficit hyperactivity disorder (ADHD) using multidimensional evaluations, the Child Behavior Checklist (CBCL) and the Teacher Report Form (TRF). Between 2001 and 2005, the parents of 21 preschool children with ADHD were divided into six groups and participated in a series of 11 BPT sessions. Before and after BPT, the parents completed the CBCL, and the teachers completed the TRF. The behavioral and emotional problems of the children showed improvement after the BPT sessions, specifically for the following categories: internalizing problems, anxious/depressed syndromes, somatic complaints, externalizing problems, rule-breaking behaviors, aggressive behaviors, social problems, thought problems, and attention problems. In the DSM-oriented scale of the CBCL, affective problems, anxiety problems, somatic problems, ADHD problems, oppositional defiant disorder problems, and conduct disorder problems showed significant improvements. On the DSM scale of the TRF, Inattention syndrome improved significantly after the BPT sessions, while other syndromes showed non-significant changes. We conclude that the BPT program significantly improved the childrens behavioral problems at home and inattention problems at school.

Unlabelled: Ground glass hepatocytes (GGH) in chronic hepatitis B virus (HBV) infection harbor HBV pre-S deletion mutants in endoplasmic reticulum (ER) and exhibit complex biologic features such as ER stress, DNA damage, and growth advantage. The presence of pre-S mutants in serum has been shown to predict the development of hepatocellular carcinoma (HCC) in HBV carriers. GGHs hence represent a potentially preneoplastic lesion. Whether a specific growth factor is overexpressed and activated in GGHs remains to be clarified. In this study, growth factor(s) up-regulated by pre-S mutants was identified using a growth factor array in HuH-7 cells. Immunohistochemistry, reverse-transcriptase polymerase chain reaction, and Western blot analysis were performed to study the participation of these genes and their signal pathways in HuH-7 cells and liver tissues. We demonstrate that vascular endothelial growth factor-A (VEGF-A) was up-regulated by pre-S mutants in HuH-7 cells and further confirmed in GGHs by immunostaining. The VEGF-A up-regulation by pre-S mutants could be suppressed by vomitoxin, an ER stress inhibitor. Furthermore, pre-S mutants-expressed HuH-7 cells exhibited activation of Akt/mTOR (mammalian target of rapamycin) signaling and increased growth advantage, which could be inhibited by VEGF-A neutralization. Consistent with this notion, enhanced expression of VEGF-A and activation of Akt/mTOR signaling, comparable to the levels of paired HCC tissues, were also detected in HBV-related nontumorous livers., Conclusion: The enhanced expression of VEGF-A in GGHs provides potential mechanism to explain the progression from preneoplastic GGHs to HCC in chronic HBV infection.

The hydrophilic nature of hydrogel matrices makes them disadvantageous to entrap poorly soluble therapeutic agents and greatly restricts their applications as drug-delivery systems. In this study, we demonstrated that sustained delivery of lipophilic drugs in hydrogel-based devices can be readily achieved by enhancing retention of drugs within micelles. This nanoscale drug-entrapment strategy was applied to develop a polymeric drug-eluting stent. Sirolimus, a lipophilic anti-proliferative/immunosuppressive drug, was entrapped into the hydrophobic core of Pluronic L121 micelles and then blended in a chitosan-based strip and crosslinked by an epoxy compound to fabricate test stents. It was found that the use of such a nanoscale drug-entrapment strategy was able to significantly increase the loading efficiency of lipophilic drugs, prevent the drug from aggregation and beneficially reduce its initial burst release; thus, the duration of drug release was extended considerably. When implanting the stent in rabbit infrarenal abdominal aortas, in-stent restenosis was markedly reduced and less inflammatory reaction was observed, while unfavorable effects such as delayed endothelial healing caused by the overdose of sirolimus could be significantly evaded.