[Tanshinone â ¡A activates PI3K/AKT signaling pathway to inhibit the apoptosis of mice cochlear pericytes induced by high glucose].

Objective: To investigate whether tanshinone ⅡA can protect the apoptosis of mice cochlear pericytes induced by high glucose and its specific protective mechanism, so as to provide experimental evidence for the prevention and treatment of diabetic hearing loss. Methods: C57BL/6J male mice were used to prepare type 2 diabetes model, which were divided into normal (NG) group, diabetic (DM) group, diabetic+tanshinone ⅡA (HG+tanshinone ⅡA) group and tanshinone ⅡA group. Each group had 10 animals. Primary cochlear pericytes were divided into NG group, HG group (high glucose 35 mmol/L), HG+tanshinone ⅡA (1, 3, 5 µmol/L) group, HG+Tanshinone ⅡA+LY294002 (PI3K/AKT pathway inhibitor) group, LY294002 group, tanshinone ⅡA group and DMSO group. Auditory brainstem response (ABR) was used to measure hearing threshold. Evans blue was used to detect the permeability of blood labyrinth barrier in each group. TBA methods were used to detect oxidative stress levels in various organs of mice. Morphological changes of stria vascularis were observed by hematoxylin-eosin staining (HE). Evans blue was used to detect the vascular labyrinth barrier permeability in cochlea. The expression of apoptosis protein in stria vascularis pericytes was observed by immunofluorescence. Pericytes apoptosis rate was observed by flow cytometry. DCFH-DA was combined with flow cytometry to detect intracellular ROS content, and Western blot was used to detect the expression of apoptotic proteins (Cleaved-caspase3, Bax), anti-apoptotic proteins (BCL-2) and pathway proteins (PI3K, p-PI3K, AKT, p-AKT). SPSS software was used for statistical analysis. Independent sample t test was performed, and P<0.05 was considered statistically significant. Results: Animal experiments: Tanshinone ⅡA decreased the hearing threshold of DM group [(35.0±3.5) dB SPL vs. (55.3±8.1) dB SPL] (t=4.899, P<0.01), decreased the oxidative stress level in cochlea (t=4.384, P<0.05), improved the structure disorder, atrophy of cochlea vascular lines, vacuole increased phenomenon. Tanshinone ⅡA alleviated the increased permeability of the blood labyrinth barrier [Evans blue leakage (6.84±0.27) AU vs. (8.59±0.85) AU] in the cochlea of DM mice (t=2.770, P<0.05), reversed the apoptotic protein: Caspase3 (t=4.956, P<0.01) and Bax (t=4.388, P<0.05) in cochlear vascularis. Cell experiments: Tanshinone ⅡA decreased intracellular ROS content in a concentration-dependent way (t=3.569, P<0.05; t=4.772, P<0.01; t=7.494, P<0.01); Tanshinone ⅡA decreased apoptosis rate and apoptotic protein, and increased the expression of anti-apoptotic protein, p-PI3K/PI3K and p-AKT/AKT in concentration-dependent manner (all P values<0.05); LY294002 reversed the protective effect of tanshinone ⅡA on pericytes apoptosis (all P values<0.05). Conclusion: Tanshinone ⅡA can inhibit the apoptosis of cochlear pericytes induced by high glucose by reducing oxidative stress level and activating PI3K/AKT signaling pathway under high glucose environment, thus playing a protective role in diabetic hearing loss.

[Effect of microvascular pericytes of cochlear stria vascularis on endothelial cell permeability in C57BL/6J mice].

Objective: To study the changes in the permeability of the blood labyrinth barrier of the aging cochlea in mice, and to establish a non-contact co-culture model of endothelial cells (EC) and pericytes (PC) to furtherly investigate the cochlear stria vascularis microvascular pericytes impact on the permeability of endothelial cells. Methods: C57BL/6J mice were divided into two groups, three months old as young group, 12 months old as senile group. Cell experiment was divided into four groups, EC group, EC+PC co-culture group, D-gal+EC group and D-gal+EC+PC co-culture group. Auditory brainstem response (auditory brain response, ABR) was used to detect the auditory function of the two groups of mice. Evans blue staining was applied to detect the permeability of the cochlear blood labyrinth barrier of the two groups of mice. Transmission electron microscopy was used to observe the ultrastructure of blood labyrinth barrier endothelial cells, pericytes and tight junctions in the two groups of mice. Immunohistochemistry was used to detect the expression levels of tight junction proteins in the stria vascularis of the cochlea of the two groups of mice. Transwell chamber was used to detect the permeability of endothelial cells. Western blot and immunofluorescence technology were used to detect the expression level of tight junction protein on endothelial cells. SPSS 20.0 software was used to analyze the data. Results: Compared with the young group, the ABR threshold of the aging group was significantly increased, the latency of wave I was prolonged (t=10.25, P<0.01;t=5.61, P<0.05), the permeability of the cochlear blood labyrinth barrier was increased and the expression of tight junction protein on the vascular stria was decreased (P<0.05). The cochlear ultrastructure showed that the cochlear vascular stria microvascular lumen was deformed, the basement membrane thickened and the tight junction gap between endothelium enlarged. The positive rate of ECs and PCs in primary culture was more than 95%. The cells induced by 15 g/L D-gal were determined to be senescent cells. Compared with EC group, the expression of tight junction protein in endothelial cells of D-gal+EC group decreased（t=7.42，P<0.01；t=13.19，P<0.05）and the permeability increased (t=11.17, P<0.01). In the co-culture group, the expression of tight junction protein between endothelial cells in EC+PC co-culture group and D-gal+EC+PC co-culture group increased and the permeability decreased. Conclusions: In aging mice, the permeability of cochlear blood labyrinth barrier will increase and the level of tight junction protein will decrease; in aging state, cochlear vascular stria microvascular pericytes may affect endothelial cell permeability by regulating the expression of tight junction protein.

LncRNA ANRIL impacts the progress of osteoarthritis via regulating proliferation and apoptosis of osteoarthritis synoviocytes.

OBJECTIVE: Long noncoding RNAs (lncRNAs) have been indicated to play an important role in many different diseases. Osteoarthritis (OA) is a disease which causes a change of morphology and function in articular cartilage and synovium, leading to cartilage degradation. Synovitis is a common pathological feature of OA, owing to the proliferation of synoviocytes. In this research, we want to verify the role of lncRNA ANRIL in osteoarthritis. PATIENTS AND METHODS: qRT-PCR was used to detect the expression of lncRNA ANRIL in normal synoviocytes and osteoarthritis synoviocytes. The cell proliferation in normal synoviocytes and osteoarthritis synoviocytes after transfection with lncRNA-NC or lncRNA-ANRIL were tested. The apoptosis rate and cell cycle in normal synoviocytes and osteoarthritis synoviocytes were detected by the Flow Cytometry analysis. Western blot was used to analyze the possible mechanism that ANRIL regulated the cells' proliferation in osteoarthritis. RESULTS: We indicated that the expression of ANRIL was significantly improved in OAS compared to NS. The expression of ANRIL was decreased and the cell proliferation was reduced in OAS after transfected with siRNA. And the cell cycle was suspended in G0/G1 phase and the cell apoptosis was improved in OAS after transfected with siRNA. Moreover, ANRIL could regulate the proliferation and apoptosis of OAS via miR-122-5p/DUSP4 axis. CONCLUSIONS: We suggest that lncRNA ANRIL was closely related to osteoarthritis. ANRIL may be involved in the development and progression of osteoarthritis and become a potential target for diagnosis and treatment in OA.

Knockdown of MiR-140-5 promotes osteogenesis of adipose-derived mesenchymal stem cells by targeting TLR4 and BMP2 and promoting fracture healing in the atrophic nonunion rat model.

OBJECTIVE: This study aims to assess the effect and mechanism of genetically modified adipose-derived mesenchymal stem cells (ASCs) with recombinant lentiviruses mediated knockdown of miR-140-5p in ASCs' osteogenesis in vitro and atrophic nonunion rat model. MATERIALS AND METHODS: This study included 36 male adult Sprague-Dawley (SD) rats weighing 400 g to 450 g from the experimental animal facility of our university. Approval was obtained from the University Animal Care Committee before the study. Rats' ASCs were prepared and genetically modified with lentivirus (Lv)-empty (NC) or Lv-miR-140-5p-TuD (inhibitors). After that, the expressions of RUNX2 and osteocalcin (OCN) were detected in the ASCs. To confirm the mechanisms of miR-140-5p in ASCs, we predicted the target genes by bioinformatics analysis and then the target genes were verified by luciferase reporting assay. The artificial atrophic nonunion was created in the rat's femoral bone. Animals were randomly divided into three groups according to the material implanted into bone defects space: AT scaffolds (AT group, n=12), AT scaffold with Lv-NC modified (AT+ASCs+Lv-NC group, n=12), AT scaffold with the Lv-miR-140-5p-TuD modified ASCs (AT+ASCs+Lv-miR-140-5p-TuD group, n=12). After four weeks, the rats were euthanized for the following radiographic examination, histologic study and biomechanical testing. RESULTS: MiR-140-5p was down-regulated during osteogenic differentiation of ASCs, and inhibition of MiR-140-5p promoted osteogenesis of ASCs in vitro. Inhibition of MiR-140-5p promoted osteogenesis of ASCs and enhanced fracture in the atrophic nonunion rat model: AT+ASCs+Lv-NC group, AT+ASCs+Lv-miR-140-5p-TuD group resulted in a better bone formation and higher BMD and BMC than AT group, while excellent bone formation and the highest BMD and BMC were observed in AT+ASCs+Lv-miR-140-5p-TuD group. Both AT+ASCs+Lv-NC group and AT+ASCs+Lv-miR-140-5p-TuD group presented more mature characteristics in the micro-architecture than AT group, whereas AT+ASCs+Lv-miR-140-5p-TuD group presented the highest BV/TV, Tb.Th and Tb.N as well as the lowest Tb.Sp. The peak load of the operated femur increased by 94.43% AT+ASCs+Lv-miR-140-5p-TuD group, 50.68% in AT+ASCs+Lv-NC group compared to the control AT group, respectively. The result of luciferase reporting assay showed that miR-140-5p could directly target TLR4 and BMP2. CONCLUSIONS: This study demonstrates that lentiviruses-mediated knockdown of miR-140-5p can significantly promote osteogenesis of ACSs by directly regulating its' target genes, TLR4 and BMP2, and that combined adipose scaffold with genetically modified ASCs can significantly enhance fracture-healing and bone formation in the atrophic nonunion rat model.

Imaging Validation of Drug-Eluting Beads Transarterial Chemoembolization of Hepatocellular Carcinomas in Living Donor Liver Transplantation.

OBJECTIVE: The aim of this study is to determine whether post-transarterial chemoembolization imaging (computed tomography or magnetic resonance imaging) could accurately predict the tumors' necrosis on pathologic specimens. BACKGROUND: Transarterial chemoembolization with drug-eluting beads has been proven to be an effective way to bridge patients with hepatocellular carcinomas to liver transplantation. MATERIALS AND METHODS: From September 2012 to June 2017, 59 patients with a total of 78 hepatocellular carcinomas, who received transarterial chemoembolization with drug-eluting beads before liver transplantation in Kaohsiung Chang Gung Memorial Hospital, were included in the study. All patients and hepatocellular carcinomas have pre-transarterial chemoembolization and post-transarterial chemoembolization images (computed tomography or magnetic resonance imaging) and pathological findings for correlation. Tumor response was evaluated according to modified Response Evaluation Criteria in Solid Tumors. The ranges of necrotic percentage are 100%, 91-99%, 51-90%, and <50%. RESULTS: The accuracy rate between the imaging and pathology correlation was 40% for computed tomography and 42% for magnetic resonance imaging. The recurrent rate of the complete respond group is 11.5%, the partial respond group is 16.0%, and the stationary group is 28.6%. CONCLUSION: Computed tomography and magnetic resonance imaging sensitivity is not satisfactory for microscopic evaluation of residual tumors after transarterial chemoembolization with drug-eluting beads. However, survival is good after liver transplantation no matter what the microscopic findings were.

Diffusion-Weighted Magnetic Resonance Imaging in Liver Graft Rejection.

OBJECTIVE: The purpose of this study is to evaluate the use of diffusion-weighted magnetic resonance imaging (DWMRI) in the assessment of graft rejection after liver transplantation (LT). METHODS: From June 2017 to January 2018, 32 patients were included in the study with a mean age of 52.3 years. All patients underwent LT. The DWMRI was performed using the apparent diffusion coefficient map and measuring the different b-values (b-400, b-600, b-800, and b-1000). These measurements were compared with the histopathology results. Statistical analysis included t test, analysis of variance, and area under the curve for receiver operating characteristic (ROC). RESULTS: There were 17 patients without rejection and 15 patients with liver graft rejection diagnosed by histopathology. The mean (SD) results between the nonrejection and rejection groups were as follows: b-400 = 1.568 (0.265) vs 1.519 (0.119) (P = .089), b-600 = 1.380 (0.181) vs 1.284 (0.106) (P = .039), b-800 = 1.262 (0.170) vs 1.170 (0.086) (P = .035), b-1000 = 1.109 (0.129) vs 1.098 (0.078) (P = .095); B-values × 10-3 mm2/s. Only b-600 (P = .04) and b-800 (P = .04) values have significant differences between the 2 groups. B-600 showed 90.48% sensitivity and 83.33% specificity (ROC area under the curve = 0.784; P < .001), and b-800 showed 90.38% sensitivity and 83.03% specificity (ROC area under the curve = 0.816; P < .001). The values obtained with the apparent diffusion coefficient in b-800 were clearly differentiated between the mild, moderate, and severe degrees of rejection (P < .001). CONCLUSION: Measurement of b-600 and b-800 values using DWMRI may be used for the diagnosis of graft rejection after LT.

Acoustic Radiation Force Impulse Elastography in Post-transplant Recurrent Hepatitis C in Living Donor Liver Transplantation.

OBJECTIVE: The aim of the study was to evaluate the efficacy of liver fibrosis (LF) with acoustic radiation force impulse (ARFI) elastography for post-transplant (post-LT) HCV recurrence. PATIENTS AND METHODS: We enrolled 89 adult recipients of living donor liver transplantation (LDLT) who had HCV, with or without post-LT HCV recurrence and treated or not treated. The post-LT HCV recurrence was diagnosed on the basis of RNA viral load present. ARFI examination was performed every 3 months for all patients, with shear wave velocity (SWV) obtained quantitatively in m/s and correlated with histopathologic fibrosis scoring of liver biopsy (LB). RESULTS: There were 50 (50 of 89) patients without HCV recurrence and 39 (39 of 89) with post-LT recurrence in the 89 patients studied. The recurrent group had significantly higher median SWVs (1.87 ± 0.52 vs 1.37 ± 0.52 m/s, P < .0001), in which 18 (18 of 39) patients had antiviral drug treatment and obtained significant improvement with SWVs from 1.83 ± 0.49 to 1.68 ± 0.56 m/s, P = .043. The correlations of LF staging between ARFI elastography and Ishak histopathologic LF scores showed great significance, P = .045. The HCV RNA titer after antiviral treatment decreased from 3,831,750 to 0, P < .0001, but the RNA titer of nontreated patients remained high and the median SWV increased. The Ishak LF staging in the nontreated group progressed from stage 1 to 2, P = .012 and SWV increased from 1.69 ± 0.54 to 1.91 ± 0.66 m/s, P = .085 at 1-year follow-up. CONCLUSION: ARFI elastography has efficient quantitative LF monitoring correlated with histopathologic staging for post-LT HCV recurrence. It could be an alternative, noninvasive method for frequent LB in the disease follow-up.

Efficiency of Transluminal Angioplasty of Hepatic Venous Outflow Obstruction in Pediatric Liver Transplantation.

BACKGROUND: Our aim in this study was to evaluate long-term efficiency of hepatic venous balloon angioplasty (BA) and stent placement (SP) for hepatic venous outflow obstruction (HVOO) in pediatric liver transplantation (LT). METHODS: From January 1999 to September 2016, 262 pediatric patients underwent LT at our hospital. Ten were diagnosed with HVOO, which included 8 living donor grafts and 2 split liver grafts. BA and SP were used in management of these 10 patients with HVOO. After intervention, Doppler ultrasound (DUS) was the major follow-up modality for comparing efficiency of BA and SP. RESULTS: The incidence of HVOO was 3.8% (10 of 262) in our pediatric LTs. Of the 10 HVOO cases, 5 had SP, 3 had BA once, 1 had BA twice, and 1 had BA twice along with SP. The patent hepatic vein was maintained after a mean follow-up of 7.4 (range, 0.04-17) years. Recurrent rate of HVOO after BA was 42%. Neither recurrent HVOO nor stent migration occurred after SP and throughout long-term follow-up. CONCLUSION: Hepatic venous SP was found to be more effective and safe than BA for treatment of HVOO in pediatric LT for long-term follow-up.

Donor Outcomes After Liver Donation in Adult to Adult Living Donor Liver Transplantation.

OBJECTIVES: This study aims to investigate postdonation outcomes of adult living donor liver transplantation donors and remnant liver regeneration in different graft types. METHODS: A total of 236 adult living donor liver transplantation donors were classified into different groups: donors with <35% remnant liver volume (group A; n = 56) and donors with remnant liver volume ≥35% (group B, n = 180); left lobe grafts (LLG group; n = 98) including middle hepatic vein (MHV) and right lobe grafts (RLG group; n = 138) without MHV. The 98 LLG group donors were further classified into 2 subgroups based on hepatic venous drainage patterns: MHV-dominant (n = 20) and non-MHV-dominant (n = 78). The demographic data, postoperative laboratory data, complications, graft weight, remnant liver volume, remnant liver growth rate, and remnant liver regeneration rate (RLRR) after partial liver donation were analyzed. RESULTS: The postoperative aspartate aminotransferase, alanine aminotransferase, total bilirubin, intensive care unit stays, and hospitalization stays were higher in A and RLG group donors. All the donor complications in our series were minor complications. The postoperative complication rate was higher in the A and RLG group, but failed to reach statistical significance. There was no significant difference in RLRR between the RLG/LLG and A/B groups. However, the MHV-dominant group had significantly lower RLRR than the non-MHV-dominant group (P < .05). CONCLUSIONS: Small remnant liver volume donors (<35% remnant liver) have higher risks of developing postdonation minor complications. Left lobe liver donation in MHV-dominant donor candidates are a major concern.

Broad expansion of optical frequency combs by self-Raman scattering in coupled-cavity self-mode-locked monolithic lasers.

Broad expansion of optical frequency comb (OFC) by the self-Raman scattering is numerically analyzed and experimentally accomplished in a coupled-cavity self-mode-locked (SML) monolithic Yb:KGW laser. The gain medium is coated to achieve the monolithic SML operation and a partially reflective mirror is further exploited to form the coupled cavity and to multiply the repetition rate up to 128.9 GHz. With a coupled reflectivity of 95%, it is experimentally found that not only the first-order but also second-order stimulated Raman scattering (SRS) can be efficiently generated. The mode-locked OFC can be consequently expanded to reach approximately 8.4 THz, leading the pulse width to be as narrow as 53 fs. At the pump power of 8.7 W, the total output power for the fundamental and the first- and second-Stokes waves can be maintained at 1.6 W. The present exploration provides a promising way to generate the ultrahigh-repetition-rate broadband OFC via the simultaneous SML and SRS processes.

Monolithic dual-polarization self-mode-locked Nd:YAG 946-nm lasers: controlling beat frequency and observation of temporal chaos.

The self-mode-locked (SML) operation at 946 nm can be achieved with a monolithic Nd:YAG crystal when the pump power is above the threshold of the multiple-longitudinal-mode generation. The SML output is further found to include two orthogonal polarization components with a beat frequency coming from the birefringence effect in the laser crystal. The beat frequency can be widely adjusted in the range of 5-220 MHz by controlling the cooling temperature. The present experiment also confirms the theoretical prediction that the two-mode operation generally exhibits the chaotic dynamics when the frequency difference is sufficiently close to the relaxation frequency.

Synchronized self-mode-locked 1061-nm and 1064-nm monolithic Nd:YAG laser at cryogenic temperatures with two orthogonally polarized emissions: generation of 670 GHz beating.

A dual-wavelength self-mode-locked monolithic Nd:YAG laser at 1061 and 1064 nm is realized at cryogenic temperatures. At an incident pump power of 5.5 W, the total output power can reach 2.5 W and the mode-locked pulse width is 29 ps at a pulse repetition rate of 7.75 GHz. The synchronization of the dual-wavelength emissions leads to a beat frequency of 670 GHz in the individual mode-locked pulse. It is further discovered that the laser output consists of two orthogonally polarized components with a central frequency difference of 127 MHz. The central frequency difference between two orthogonal polarizations mainly arises from the external mechanical stress introduced by the copper holder for the laser crystal.

Impact of Different Dominant Hepatic Vein Patterns in Left-Lobe Donors of Adult Living Donor Liver Transplantation.

OBJECTIVE: Optimal hepatic venous tributary flow is correlated with liver function and regeneration. In left-lobe graft living donor liver transplantation, the stump of segment 5 and 8 hepatic veins (S5V and S8V) are ligated without performing hepatic tributary reconstruction. The aim of this article was to evaluate the different dominate hepatic vein patterns that affect left-lobe living donor safety. MATERIALS AND METHODS: A total of 44 donors who underwent left-lobe hepatectomy were divided into 2 groups, middle hepatic vein (MHV) dominance (group 1) and right hepatic vein (RHV) dominance (group 2), according to the dominant venous territory drainage from S5V and S8V or RHV. The clinical pathological data, postoperative laboratory data, complication, remnant liver volume and remnant liver regeneration rate at 6 months after surgery were compared. RESULTS: No difference was found in blood loss, postoperative liver function such as alanine transaminase value, complications, and hospital stays between groups. Group 1 had slightly higher total bilirubin level than group 2 (1.99 vs 1.79; P = .49). Group 2 had significantly better remnant liver regeneration rate than group 1 (89.2% vs 82.5%; P = .026). CONCLUSION: It is important to recognize the dominant MHV group. Ligation large S5V and S8V in dominant MHV donors led to lower remnant liver regeneration in our series. This might be critical in extremely small RHV territory and potential large remnant liver congestion donors. Adjusting surgical planning, such as hepatic vein reconstruction, in this kind of donor might be appropriate for donor safety.

Magnetic Resonance Spectroscopy in Living-Donor Liver Transplantation.

OBJECTIVE: The purpose of this study is to evaluate the accuracy rate of the one breath-hold single voxel hydrogen-1 magnetic resonance spectroscopy (MRS) in comparison with intraoperative biopsy for liver fat quantification in living-donor liver transplantation. MATERIALS AND METHODS: A total of 80 living liver donors participated in this study. Each patient underwent both MRS and intraoperative biopsy for evaluation of liver fatty content. MRS was performed using 1.5-T magnetic resonance imaging and placed in segments 2-4, 5-8, and left lateral segment for each donor. Accuracy was assessed through receiver operating characteristic curve analysis. Sensitivity and specificity of MRS fat fractions were also calculated. RESULTS: Eighty living-donor liver transplantation donors were enrolled in this study. There was no fatty liver in 59 subjects (73.8%), 5% to 10% fatty liver in 17 subjects, 11% to 15% fatty liver in 3 subjects, and >16% fatty liver in 1 subject. MRS fat fraction showed excellent parameters to predict between normal liver and fatty liver groups (1.85% ± 0.98, 8.13% ± 3.52, respectively; P < .0001). Linear regression between MRS fat fraction and pathology grading showed high correlation (R(2) = 0.7092). Pearson correlation revealed high correlation between MRS and pathology results (r = 0.936), poor correlation between body mass index and pathology results (r = 0.390). The sensitivity and specificity for detection of liver steatosis in MRS fat fraction were 95.2% and 98.3%, respectively. CONCLUSION: (1)H MRS fat fraction is a highly precise and accurate method in quantification of hepatic steatosis for the living donor and can be finished in a single breath-hold.

Impact of Graft Type in Living Donor Liver Transplantation: Remnant Liver Regeneration and Outcome in Donors.

OBJECTIVES: Liver regeneration and donor safety in right-lobe (RL) and left-lobe (LL) grafts are essential for donors in living donor liver transplantation (LDLT). Our aim was to compare the liver regeneration rate and postoperative outcome between different donor graft types in LDLT. MATERIALS AND METHODS: A total of 95 donors were divided into 2 groups: RL (n = 42) and LL (n = 53). The remnant liver of LL donors were subdivided into 3 subgroups according to the different hepatic venous drainage pattern that dominates from right hepatic vein (dominant RHV; n = 34), middle hepatic vein (dominant MHV; n = 10), and include MHV for left lateral segment (LLS) graft (n = 9). The demographic data, postoperative laboratory data, complications, remnant liver volume (RLV), and remnant liver regeneration rate (RLRR) 6 months after surgery were compared. RESULTS: The postoperative total bilirubin (TB), prothrombin time (PT), and intensive care unit (ICU) stays of the LL group were lower than the RL group (P < .05). The LL group has no significant better regeneration rate 6 months after surgery than the RL group. However, dominant RHV and LLS groups have significantly better RLRR than the RL group (89.2% vs 86% and 95.1% vs 86%, respectively, P < .05), but no significance in the dominant MHV group. CONCLUSION: In conclusion, different hepatic venous drainage patterns of remnant liver grafts may affect the regeneration rate in LL LDLT, especially with dominant RHV donors, may have more comparable outcomes with that of RL, and should be a favorable option during donor selection.

Drug-Eluting Bead Transarterial Chemoembolization as Bridge Therapy for Hepatocellular Carcinoma Before Living-Donor Liver Transplantation.

BACKGROUND: The majority of hepatocellular carcinoma (HCC) patients is diagnosed in late stages and therefore becomes ineligible for potentially curative treatment such as resection or liver transplantation. Transarterial chemoembolization (TACE) with drug-eluting beads (DC beads, Biocompatibles, Farnham, United Kingdom) has been proven with less side effects and better efficacy than conventional TACE, especially among patients with poor liver function. PURPOSE: The aim of this study is to evaluate outcomes of HCC patients who received TACE with DC beads, which resulted to eligibility for liver transplantation. METHODS AND MATERIALS: From January 2012 to June 2015, 60 patients with HCC received pre-liver transplantation evaluation whose cases were managed with TACE using DC beads at Kaohsiung Chang Gung Memorial Hospital were included in the study. DC beads loaded with doxorubicin were used. RESULTS: Forty percent of the patients had complete tumor response. Thirty-three percent of the patients had partial tumor response, of which 15% showed stable disease, 11.7% exhibited disease progression including 3 with portal vein thrombosis, 1 with both hepatic vein and portal vein thrombosis, and 3 with increase in tumor size. Twenty-three patients were beyond University of California, San Francisco (UCSF) criteria initially. The successful downstage rate was 73.9% (17 of 23). Thirty-seven patients fit the USCF criteria initially. The 3-, 6- and 12-month drop rates of these patients were 0%, 3.9%, and 16.8%, respectively. Twenty-four (40%) patients successfully underwent liver transplantation. Three patients (12.5%) demonstrated recurrent HCC after liver transplantation. CONCLUSION: TACE with DC bead can effectively induce tumor necrosis and appears to be a successful approach as bridge therapy for patients with advanced HCC and poor liver function.

Noncontrast Magnetic Resonance Angiography Using Inflow Sensitive Inversion Recovery Technique for Vascular Evaluation in Pre-liver Transplantation Recipients.

OBJECTIVE: Vascular anatomy is essential in pretransplantation survey. The purpose of this study is to investigate the feasibility and diagnostic performance of inflow sensitive inversion recovery (IFIR) magnetic resonance angiography (MRA) to evaluate the recipient's hepatic vasculature before liver transplantation. MATERIALS AND METHODS: Thirty-one pre-liver transplantation patients underwent both IFIR and conventional contrast-enhanced MRA using a 1.5T MR scanner from December 2012 to December 2014. The contrast-to-noise ratios (CNRs) between liver parenchyma and hepatic vasculature were calculated. The image sets of IFIR and contrast-enhanced MRA were assessed for subjective image quality and depiction of hepatic vasculature on vessel-to-vessel basis by two independent radiologists. RESULTS: The quantitative results of CNR for hepatic arteries on IFIR were significantly lower than contrast-enhanced MRA, whereas CNR for portal veins and inferior vena cava on IFIR were significantly higher than contrast-enhanced MRA. For subjective assessment of image quality, the overall agreement of scores of IFIR and contrast-enhanced MRA was substantial (kappa values ranged from 0.650 to 0.767). There was no significant difference in the image quality for portal veins between IFIR and contrast-enhanced MRA. The quality scores of IFIR were significantly lower than contrast-enhanced MRA for hepatic arteries. For inferior vena cava evaluation, the scores of IFIR were significantly higher than contrast-enhanced MRA. CONCLUSION: IFIR MRA is a reproducible and noninvasive tool to assess the hepatic vasculature that can provide adequate to good image quality. In pre-liver transplantation patients, IFIR MRA becomes even more useful if contrast medium is a contraindication due to impaired renal and liver functions.

Combined Hepatocellular Carcinoma and Cholangiocarcinoma: Diagnosis and Prognosis After Resection or Transplantation.

BACKGROUND: Primary liver malignancy is the leading cause of cancer death worldwide, with hepatocellular carcinoma (HCC) and cholangiocarcinoma (CC) representing the majority. Combined HCC-CC, in contrast, accounts for less than 5% of these liver cancers and has not been clearly characterized by imaging, making diagnosis and management difficult. MATERIALS AND METHODS: This retrospective study investigated 32 patients with early-stage combined HCC-CC tumor who underwent hepatectomy (n = 24) or liver transplantation (n = 8). Preoperative imaging and pathologic reports were retrospectively reviewed and correlated. Survival and recurrence rates were then analyzed. RESULTS: Twelve patients with more than 50% CC component showed typical CC enhancement, whereas 17 patients with less than 50% CC component exhibited typical HCC enhancement. Those with equivocal imaging findings resulted near equal tumor component. The majority demonstrated either heterogeneous or peripheral enhancement. Considering the major tumor component, 66% of the images were consistent with histopathology. The over-all 3-year recurrent rate was 59%, with a mean time to recurrence of about 7 months. The 3-year survival rate of combined tumor after hepatectomy was 76% and after transplant was 75%, regardless of major tumor component. However, patients with more than 50% CC component showed a decrease in 3-year survival rate to 50% when transplantation was performed. CONCLUSION: The overall survival rate for combined tumor after either hepatectomy or transplantation seems to be satisfactory but carries a high risk of recurrent when compared to pure HCC. On the other hand, a major CC component tumor after transplantation is associated with poor survival outcome; thus, liver transplantation has no role and is not a good management option.

Sonographic Evaluation of Post-transplantation Portal Vein Stenosis in Pediatric Living-donor Liver Transplant Recipients With Left-liver Grafts.

INTRODUCTION: Portal vein (PV) stenosis is not uncommon in post-transplantation pediatric living-donor liver transplant (PLDLT) recipients. The purpose of this study was to identify specific ultrasound criteria that may be used to detect PV stenosis in PLDLT with left-liver grafts. PATIENTS AND METHODS: From January 2010 to October 2014, 87 pediatric recipients underwent PLDLT with left lobes or left lateral segments at our hospital. All patients underwent routine liver Doppler ultrasound (DUS) as follow-up protocol. The morphologic narrowing and mean time averaged velocity (TAV) at the PV anastomotic site, change in anastomotic/pre-anastomotic TAV (ΔTAV), and the umbilical portal width were evaluated and analyzed. Ultrasound findings were correlated with computed tomography angiography where PV stenosis was suspected. RESULTS: In the liver graft follow-up study, 80.4% (70 of 87 patients) of PV anastomosis was well visualized and measured by Doppler ultrasound. The optimal threshold values for TAV and ΔTAV were 49.6 cm/s and 30 cm/s, respectively, for significant PV anastomosis stenosis. In the other 19.5% (17/87), the PV anastomosis could not be identified properly. The PV anastomosis was not always visible with ultrasound; however, the optimal dilated umbilical portion of the PV indicating possible PV anastomosis narrowing threshold was umbilical portal width >1.5 cm. CONCLUSIONS: Increased anastomotic TAV and ΔTAV are useful features for diagnosing PV stenosis. The identification of a dilated umbilical portion of the left PV helps in detection of PV stenosis in PLDLT recipients especially when the anastomotic narrowed region cannot be visualized.

Mitochondrial DNA variants as genetic risk factors for Parkinson disease.

BACKGROUND AND PURPOSE: Investigation of the relationship between mitochondrial DNA (mtDNA) variants and Parkinson disease (PD) remains an issue awaiting more supportive evidence. Moreover, an affirming cellular model study is also lacking. METHODS: The index mtDNA variants and their defining mitochondrial haplogroup were determined in 725 PD patients and 744 non-PD controls. Full-length mtDNA sequences were also conducted in 110 cases harboring various haplogroups. Cybrid cellular models, composed by fusion of mitochondria-depleted rho-zero cells and donor mitochondria, were used for a rotenone-induced PD simulation study. RESULTS: Multivariate logistic regression analysis revealed that subjects harboring the mitochondrial haplogroup B5 have resistance against PD (odds ratio 0.50, 95% confidence interval 0.32-0.78; P = 0.002). Furthermore, a composite mtDNA variant group consisting of A10398G and G8584A at the coding region was found to have resistance against PD (odds ratio 0.50, 95% confidence interval 0.33-0.78; P = 0.001). In cellular studies, B4 and B5 cybrids were selected according to their higher resistance to rotenone, in comparison with cybrids harboring other haplogroups. The B5 cybrid, containing G8584A/A10398G variants, showed more resistance to rotenone than the B4 cybrid not harboring these variants. This is supported by findings of low reactive oxygen species generation and a low apoptosis rate in the B5 cybrid, whereas a higher expression of autophagy was observed in the B4 cybrid particularly under medium dosage and longer treatment time with rotenone. CONCLUSIONS: Our studies, offering positive results from clinical investigations and cybrid experiments, provide data supporting the role of variant mtDNA in the risk of PD.