We report a new type of memory device based on insulating LaAlO3/SrTiO3 (LAO/STO) hetero-interface. The microstructures of the LAO/STO interface are characterized by Cs-corrected scanning transmission electron microscopy, which reveals the element intermixing at the interface. The inhomogeneous element distribution may result in carrier localization, which is responsible for the insulating state. The insulating state of such interface can be converted to metallic state by light illumination and the metallic state maintains after light off due to giant persistent photoconductivity (PPC) effect. The on/off ratio between the PPC and the initial dark conductance is as large as 105. The metallic state also can be converted back to insulating state by applying gate voltage. Reversible and reproducible resistive switching makes LAO/STO interface promising as a nonvolatile memory. Our results deepen the understanding of PPC phenomenon in LAO/STO, and pave the way for the development of all-oxide electronics integrating information storage devices.
AIM: To detect whether the up-to-seven should be used as inclusion criteria for liver transplantation for hepatocellular carcinoma.
METHODS: Between April 2002 and July 2008, 220 hepatocellular carcinoma (HCC) patients who were diagnosed with HCC and underwent liver transplantation (LT) at our liver transplantation center were included. These patients were divided into three groups according to the characteristics of their tumors (tumor diameter, tumor number): the Milan criteria group (Group 1), the in up-to-seven group (Group 2) and the out up-to-seven group (Group 3). Then, we compared long-term survival and tumor recurrence of these three groups.
RESULTS: The baseline characteristics of transplant recipients were comparable among these three groups, except for the type of liver graft (deceased donor liver transplant or live donor liver transplantation). There were also no significant differences in the pre-operative α-fetoprotein level. The 1-, 3-, and 5-year overall survival and tumor-free survival rate for the Milan criteria group were 94.8%, 91.4%, 89.7% and 91.4%, 86.2%, and 86.2% respectively; in the up-to-seven criteria group, these rates were 87.8%, 77.8%, and 76.6% and 85.6%, 75.6%, and 75.6% respectively (P < 0.05). However, the advanced HCC patients’ (in the group out of up-to-seven criteria) overall and tumor-free survival rates were much lower, at 75%, 53.3%, and 50% and 65.8%, 42.5%, and 41.7%, respectively (P < 0.01).
CONCLUSION: Considering that patients in the up-to-seven criteria group exhibited a considerable but lower survival rate compared with the Milan criteria group, the up-to-seven criteria should be used carefully and selectively.
Up-to-seven criteria; Liver transplantation; Outcome; Hepatocellular carcinoma; Recurrence
The selection criteria for patients with hepatocellular carcinoma (HCC) to undergo liver transplantation should accurately predict posttransplant recurrence while not denying potential beneficiaries. In the present study, we attempted to identify risk factors associated with posttransplant recurrence and to expand the selection criteria.
Patients and Methods
Adult patients with HCC who underwent liver transplantation between November 2004 and September 2012 at our centre were recruited into the current study (N = 241). Clinical and pathological data were retrospectively reviewed. Patients who died during the perioperative period or died of non-recurrence causes were excluded from this study (N = 25). All potential risk factors were analysed using uni- and multi-variate analyses.
Sixty-one recipients of 216 qualified patients suffered from recurrence. Similar recurrence-free and long-term survival rates were observed between living donor liver transplant recipients (N = 60) and deceased donor liver transplant recipients (N = 156). Total tumour volume (TTV) and preoperative percentage of lymphocytes (L%) were two independent risk factors in the multivariate analysis. We propose a prognostic score model based on these two risk factors. Patients within our criteria achieved a similar recurrence-free survival to patients within the Milan criteria. Seventy-one patients who were beyond the Milan criteria but within our criteria also had comparable survival to patients within the Milan criteria.
TTV and L% are two risk factors that contribute to posttransplant recurrence. Selection criteria based on these two factors, which are proposed by our study, expanded the Milan criteria without increasing the risk of posttransplant recurrence.
AIM: Our study aimed to compare the results of liver transplantation (LT) and liver resection (LR) in patients with hepatocellular carcinoma (HCC) that met the Milan criteria after successful downstaging therapy.
METHODS: From February 2004 to August 2010, a consecutive series of 102 patients were diagnosed with advanced-stage HCC that met the modified UCSF down-staging protocol inclusion criteria. All of the patients accepted various down-staging therapies. The types and numbers of treatments were tailored to each patient according to the tumor characteristics, location, liver function and response. After various downstaging therapies, 66 patients had tumor characteristics that met the Milan criteria; 31 patients accepted LT in our center, and 35 patients accepted LR. The baseline characteristics, down-staging protocols, postoperative complications, overall survival and tumor free survival rate, and tumor recurrence rate were compared between the two groups. Kaplan-Meier analyses were used to estimate the long-term overall survival and tumor-free survival rate. Meanwhile, a Cox proportional hazards model was used for the multivariate analyses of overall survival and disease-free survival rate.
RESULTS: No significant difference was observed between the LT and LR groups with respect to the down-staging protocol, target tumor characteristics, and baseline patient characteristics. Fifteen patients suffered various complications after LT, and 8 patients had complications after LR. The overall complication rate for the LT group was 48.4%, which was significantly higher than the LR group (22.9%) (P = 0.031). The overall in-hospital mortality in hospital for the LT group was 12.9% vs 2.9% for the LR group (P = 0.172). The overall patient survival rates at 1-, 3- and 5-years were 87.1%, 80.6% and 77.4%, respectively, after LT and 91.4%, 77.1% and 68.6%, respectively, after LR (P = 0.498). The overall 1-, 3- and 5-year tumor recurrence-free rates were also comparable (P = 0.656). Poorer tumor differentiation (P = 0.041) and a higher post-downstage alpha-fetoprotein (AFP) level (> 400 ng/mL) (P = 0.015) were the two independent risk factors for tumor recurrence in the LT and LR patients who accepted successful down-staging therapy.
CONCLUSION: Due to the higher postoperative morbidity and similar survival and tumor recurrence-free rates, LR might offer better or similar outcome over LT, but a larger number and further randomized studies may be needed in the future for drawing any positive conclusions.
Liver; Resection; Transplantation; Down-stage; Survival; Complication; Recurrence; Comparison
AIM: To investigate the metabolic profiles of xenograft pancreatic cancer before and after radiotherapy by high-resolution magic angle spinning proton magnetic resonance spectroscopy (HRMAS 1H NMR) combined with principal components analysis (PCA) and evaluate the radiotherapeutic effect.
METHODS: The nude mouse xenograft model of human pancreatic cancer was established by injecting human pancreatic cancer cell SW1990 subcutaneously into the nude mice. When the tumors volume reached 800 mm3, the mice received various radiation doses. Two weeks later, tumor tissue sections were prepared for running the NMR measurements. 1H NMR and PCA were used to determine the changes in the metabolic profiles of tumor tissues after radiotherapy. Metabolic profiles of normal pancreas, pancreatic tumor tissues, and radiation- treated pancreatic tumor tissues were compared.
RESULTS: Compared with 1H NMR spectra of the normal nude mouse pancreas, the levels of choline, taurine, alanine, isoleucine, leucine, valine, lactate, and glutamic acid of the pancreatic cancer group were increased, whereas an opposite trend for phosphocholine, glycerophosphocholine, and betaine was observed. The ratio of phosphocholine to creatine, and glycerophosphocholine to creatine showed noticeable decrease in the pancreatic cancer group. After further evaluation of the tissue metabolic profile after treatment with three different radiation doses, no significant change in metabolites was observed in the 1H NMR spectra, while the inhibition of tumor growth was in proportion to the radiation doses. However, PCA results showed that the levels of choline and betaine were decreased with the increased radiation dose, and conversely, the level of acetic acid was dramatically increased.
CONCLUSION: The combined methods were demonstrated to have the potential for allowing early diagnosis and assessment of pancreatic cancer response to radiotherapy.
High-resolution magic angle spinning proton magnetic resonance spectroscopy; Principal components analysis; Pancreatic cancer; Radiotherapy
A common hypothesis to explain the effect of litter mixing is based on the difference in litter N content between mixed species. Although many studies have shown that litter of invasive non-native plants typically has higher N content than that of native plants in the communities they invade, there has been surprisingly little study of mixing effects during plant invasions. We address this question in south China where Mikania micrantha H.B.K., a non-native vine, with high litter N content, has invaded many forested ecosystems. We were specifically interested in whether this invader accelerated decomposition and how the strength of the litter mixing effect changes with the degree of invasion and over time during litter decomposition. Using litterbags, we evaluated the effect of mixing litter of M. micrantha with the litter of 7 native resident plants, at 3 ratios: M1 (1∶4, = exotic:native litter), M2 (1∶1) and M3 (4∶1, = exotic:native litter) over three incubation periods. We compared mixed litter with unmixed litter of the native species to identify if a non-additive effect of mixing litter existed. We found that there were positive significant non-additive effects of litter mixing on both mass loss and nutrient release. These effects changed with native species identity, mixture ratio and decay times. Overall the greatest accelerations of mixture decay and N release tended to be in the highest degree of invasion (mix ratio M3) and during the middle and final measured stages of decomposition. Contrary to expectations, the initial difference in litter N did not explain species differences in the effect of mixing but overall it appears that invasion by M. micrantha is accelerating the decomposition of native species litter. This effect on a fundamental ecosystem process could contribute to higher rates of nutrient turnover in invaded ecosystems.
Autosomal recessive retinitis pigmentosa (RP), a heterogeneous group of degenerations of the retina, can be due to mutations in the MFRP (membrane-type frizzled-related protein) gene. A patient with RP with MFRP mutations, one of which is novel and the first splice site mutation reported, was characterized by noninvasive retinal and visual studies. The phenotype, albeit complex, suggested that this retinal degeneration may be a candidate for gene-based therapy. Proof-of-concept studies were performed in the rd6 Mfrp mutant mouse model. The fast-acting tyrosine-capsid mutant AAV8 (Y733F) vector containing the small chicken β-actin promoter driving the wild-type mouse Mfrp gene was used. Subretinal vector delivery on postnatal day 14 prevented retinal degeneration. Treatment rescued rod and cone photoreceptors, as assessed by electroretinography and retinal histology at 2 months of age. This AAV-mediated gene delivery also resulted in robust MFRP expression predominantly in its normal location within the retinal pigment epithelium apical membrane and its microvilli. The clinical features of MFRP-RP and our preliminary data indicating a response to gene therapy in the rd6 mouse suggest that this form of RP is a potential target for gene-based therapy.
In this proof-of-concept study, Dinculescu and colleagues demonstrate that subretinal delivery of a self-complementary tyrosine-capsid mutant AAV serotype 8 (AAV8) (Y733F) vector carrying the mouse Mfrp gene prevents retinal degeneration and rescues rod and cone photoreceptors in a mouse model of autosomal recessive retinitis pigmentosa.
AIM: To explore the relationship between α-fetoprotein (AFP) and various clinicopathological variables and different staging system of hepatocellular carcinoma (HCC) thoroughly.
METHODS: A retrospective cohort study of consecutive patients diagnosed with HCC between January 2008 and December 2009 in West China Hospital was enrolled in our study. The association of serum AFP values with the HCC clinicopathological features was analysed by univariate and multivariate analysis, such as status of hepatitis B virus (HBV) infection, tumor size, tumor number, vascular invasion and degree of tumor differentiation. Also, patients were divided into four groups at the time of enrollment according to different cutoff values for serum value of AFP (≤ 20 μg/L, 21-400 μg/L, 401-800 μg/L, and ≥ 801 μg/L), to compare the positive rate of patient among four groups stratified by various clinicopathological variables. And the correlation of different kinds of tumor staging systems, such as TNM, Barcelona Clinic Liver Cancer (BCLC) staging classification and China staging, were compared with the serum concentration of AFP.
RESULTS: A total of 2304 HCC patients were enrolled in this study totally; the mean serum level of AFP was 555.3 ± 546.6 μg/L. AFP levels were within the normal range (< 20 μg/L) in 27.4% (n = 631) of all the cases. 81.4% (n = 1875) patients were infected with HBV, and those patients had much higher serum AFP level compared with non-HBV infection ones (573.9 ± 547.7 μg/L vs 398.4 ± 522.3 μg/L, P < 0.001). The AFP level in tumors ≥ 10 cm (808.4 ± 529.2 μg/L) was significantly higher (P < 0.001) than those with tumor size 5-10 cm (499.5 ± 536.4 μg/L) and with tumor size ≤ 5 cm (444.9 ± 514.2 μg/L). AFP levels increased significantly in patients with vascular invasion (694.1 ± 546.9 μg/L vs 502.1 ± 543.1 μg/L, P < 0.001). Patients with low tumor cell differentiation (559.2 ± 545.7 μg/L) had the significantly (P = 0.007) highest AFP level compared with high differentiation (207.3 ± 420.8 μg/L) and intermediate differentiation (527.9 ± 538.4 μg/L). In the multiple variables analysis, low tumor cell differentiation [OR 6.362, 95%CI: 2.891-15.382, P = 0.006] and tumor size (≥ 10 cm) (OR 5.215, 95%CI: 1.426-13.151, P = 0.012) were independent predictors of elevated AFP concentrations (AFP > 400 μg/L). Serum AFP levels differed significantly (P < 0.001) in the D stage of BCLC (625.7 ± 529.8 μg/L) compared with stage A (506.2 ± 537.4 μg/L) and B (590.1 ± 551.1 μg/L).
CONCLUSION: HCC differentiation, size and vascular invasion have strong relationships with AFP, poor differentiation and HCC size ≥ 10 cm are independent predictors of elevated AFP. BCLC shows better relationship with AFP
α-fetoprotein; Hepatocellular carcinoma; Tumor markers; Clinical features; Pathological features
Kawasaki disease (KD) is a complex disease, leading to the damage of multisystems. The pathogen that triggers this sophisticated disease is still unknown since it was first reported in 1967. To increase our knowledge on the effects of genes in KD, we extracted statistically significant genes so far associated with this mysterious illness from candidate gene studies and genome-wide association studies. These genes contributed to susceptibility to KD, coronary artery lesions, resistance to initial IVIG treatment, incomplete KD, and so on. Gene ontology category and pathways were analyzed for relationships among these statistically significant genes. These genes were represented in a variety of functional categories, including immune response, inflammatory response, and cellular calcium ion homeostasis. They were mainly enriched in the pathway of immune response. We further highlighted the compelling immune pathway of NF-AT signal and leukocyte interactions combined with another transcription factor NF-κB in the pathogenesis of KD. STRING analysis, a network analysis focusing on protein interactions, validated close contact between these genes and implied the importance of this pathway. This data will contribute to understanding pathogenesis of KD.
Squamous cell carcinoma is the major pathology type of esophageal cancer in China, where adenocarcinoma is rare and adenoid cystic carcinoma (ACC) is more rare comparing to the western countries. We report the surgical and pathologic findings of two cases of primary ACC of the esophagus, and review of the Chinese literature of this tumor.
The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1507582238843246
Adenoid cystic carcinoma; Esophagus; Surgery
In our previous study, significantly high expression levels of matrix-remodeling associated 5 (MXRA5) were identified in fresh-cultured colorectal cancer (CRC) tissues compared with their normal adjacent mucosa by differential secretome analysis. Whether MXRA5 is a potential serum biomarker of CRC has not been evaluated. The aim of this study was to investigate the association between MXRA5 expression and clinicopathological characteristics of CRC patients. The MXRA5 expression levels were determined by quantitative real-time PCR (qRT-PCR) and immunohistochemistry (IHC) in 20 colorectal adenoma tissues, 156 CRC tissues and their corresponding adjacent normal mucosa. Relative quantity (RQ) value and immunoreactive score (IRS) were used for quantitative assessment. The staining for MXRA5 protein was mainly located in the cytoplasm of CRC cells. All CRC tissues were positively stained, with a higher expression rate (IRS>4) of 67% (105/156), and a lower expression rate (IRS≤4) of 33% (51/156). Meanwhile, their corresponding normal tissues exhibited little positive staining; the higher expression rate was 0% (0/156) and the lower expression rate was 25% (16/156). Additionally, more than half of the adenoma tissues were positively stained; the higher expression rate was 15% (3/20) and the lower expression rate was 50% (10/20). The MXRA5 protein positive staining rates were significantly correlated with the lesion sites (colon vs. rectum, 76 vs. 59%), TNM staging (I+II vs. III+IV, 56 vs. 73%) and metastasis (present vs. absent; 76 vs. 61%) with the most high positive staining rate observable in omental metastasis (82%). However, MXRA5 mRNA expression levels showed no significant differences between CRC tissues and their corresponding normal tissues, and no significant correlation between IRS and corresponding RQ value was observed. In this study, we present the first evaluation of MXRA5 protein expression in CRC tissue. Our results revealed that MXRA5 protein is aberrantly expressed in CRC tissues, and has potential value in early detection of CRC and prediction of omental metastasis.
MXRA5; colorectal cancer; proteomics; omental metastasis
AIM: To investigate health-related quality of life (HRQoL) and psychological outcomes in 256 adults who had undergone liver transplantation (LT).
METHODS: A stratified random sampling method was used in this follow-up multicenter study to select a representative sample of recipients undergoing either living donor liver transplantation (LDLT) or deceased donor liver transplantation (DDLT). HRQoL was measured by using the Chinese version of Medical Outcome Study Short Form-36 (SF-36), and psychological outcomes by using the beck anxiety inventory (BAI) and the self-rating depression scale (SDS). Clinical and demographic data were collected from the records of the Chinese Liver Transplant Registry and via questionnaires.
RESULTS: A total of 256 patients were sampled, including 66 (25.8%) receiving LDLT and 190 (74.2%) undergoing DDLT; 15 (5.9%) recipients had anxiety and four (1.6%) developed severe depression after the operation. Compared with LDLT recipients, DDLT patients had higher scores in general health (60.33 ± 16.97 vs 66.86 ± 18.42, P = 0.012), role-physical (63.64 ± 42.55 vs 74.47 ± 36.46, P = 0.048), role-emotional (61.11 ± 44.37 vs 78.95 ± 34.31, P = 0.001), social functioning (78.60 ± 22.76 vs 88.16 ± 21.85, P = 0.003), vitality (70.30 ± 15.76 vs 75.95 ± 16.40, P = 0.016), mental health (65.88 ± 12.94 vs 71.85 ± 15.45, P = 0.005), physical component summary scale (PCS, 60.07 ± 7.36 vs 62.58 ± 6.88, P = 0.013) and mental component summary scale (MCS, 52.65 ± 7.66 vs 55.95 ± 10.14, P = 0.016). Recipients > 45 years old at the time of transplant scored higher in vitality (77.33 ± 15.64 vs 72.52 ± 16.66, P = 0.020), mental health (73.64 ± 15.06 vs 68.00 ± 14.65, P = 0.003) and MCS (56.61 ± 10.00 vs 54.05 ± 9.30, P = 0.037) than those aged ≤ 45 years. MCS was poorer in recipients with than in those without complications (52.92 ± 12.21 vs 56.06 ± 8.16, P = 0.017). Regarding MCS (55.10 ± 9.66 vs 50.0 ± 10.0, P < 0.05) and PCS (61.93 ± 7.08 vs 50.0 ± 10.0, P < 0.05), recipients scored better than the Sichuan general and had improved overall QoL compared to patients with chronic diseases. MCS and PCS significantly correlated with scores of the BAI (P < 0.001) and the SDS (P < 0.001).
CONCLUSION: Age > 45 years at time of transplant, DDLT, full-time working, no complications, anxiety and depression were possible factors influencing postoperative HRQoL in liver recipients.
Liver transplantation; Living donor liver transplantation; Deceased donor liver transplantation; Psychology; Health-related quality of life
Glycogen synthase kinase 3β(GSK3β) is a ubiquitous serine-threonine protein kinase that participates in numerous cellular processes and disease pathophysiology. We aimed to determine therapeutic potential of GSK3β inhibition and its mechanism in a well-characterized model of lipopolysaccharide (LPS)-induced model of acute liver failure (ALF).
In a murine ALF model induced by D-GalN(700 mg/kg)/LPS(10 µg/kg), we analyzed GSK3β mechanisms using a specific chemical inhibitor, SB216763, and detected the role of endoplasmic reticulum stress (ERS). Mice were administered SB216763 at 2 h before or after D-GalN/LPS injection, respectively, and then sacrificed 6 h after D-GalN/LPS treatment to evaluate its prophylactic and therapeutic function. The lethality rate, liver damage, ERS, cytokine expression, MAP kinase, hepatocyte apoptosis and expression of TLR 4 were evaluated, respectively. Whether the inhibition of GSK3β activation protected hepatocyte from ERS-induced apoptosis was investigated in vitro.
GSK3β became quickly activated (dephosphorylated) upon D-GalN/LPS exposure. Administration of SB216763 not only ameliorated liver injury, as evidenced by reduced transaminase levels, and well-preserved liver architecture, but also decreased lethality. Moreover, GSK3β inhibition resulted in down-regulation of pro-apoptotic proteins C/EBP–homologous protein(CHOP) and caspase-12, which are related to ERS. To further demonstrate the role of ERS, we found that GSK3β inhibition protected hepatocyte from ERS-induced cell death. GSK3β inhibition down-regulated the MAPK pathways, reduced expression of inflammatory cytokines and decreased expression of TLR4.
Our findings demonstrate the key function of GSK3β signaling in the pathophysiology of ALF, especially in regulating the ERS, and provide a rationale for targeting GSK3β as a potential therapeutic strategy to ameliorate ALF.
The recombinant xylose-fermenting Saccharomyces cerevisiae strain harboring xylose reductase (XR) and xylitol dehydrogenase (XDH) from Scheffersomyces stipitis requires NADPH and NAD+, creates cofactor imbalance, and causes xylitol accumulation during growth on d-xylose. To solve this problem, noxE, encoding a water-forming NADH oxidase from Lactococcus lactis driven by the PGK1 promoter, was introduced into the xylose-utilizing yeast strain KAM-3X. A cofactor microcycle was set up between the utilization of NAD+ by XDH and the formation of NAD+ by water-forming NADH oxidase. Overexpression of noxE significantly decreased xylitol formation and increased final ethanol production during xylose fermentation. Under xylose fermentation conditions with an initial d-xylose concentration of 50 g/liter, the xylitol yields for of KAM-3X(pPGK1-noxE) and control strain KAM-3X were 0.058 g/g xylose and 0.191 g/g, respectively, which showed a 69.63% decrease owing to noxE overexpression; the ethanol yields were 0.294 g/g for KAM-3X(pPGK1-noxE) and 0.211 g/g for the control strain KAM-3X, which indicated a 39.33% increase due to noxE overexpression. At the same time, the glycerol yield also was reduced by 53.85% on account of the decrease in the NADH pool caused by overexpression of noxE.
AIM: To evaluate whether total splenic artery embolization (TSAE) for patients with hypersplenism delivers better long-term outcomes than partial splenic embolization (PSE).
METHODS: Sixty-one patients with hypersplenism eligible for TSAE (n = 27, group A) or PSE (n = 34, group B) were enrolled into the trial, which included clinical and computed tomography follow-up. Data on technical success, length of hospital stay, white blood cell (WBC) and platelet (PLT) counts, splenic volume and complications were collected at 2 wk, 6 mo, and 1, 2, 3, 4 years postoperatively.
RESULTS: Both TSAE and PSE were technically successful in all patients. Complications were significantly fewer (P = 0.001), and hospital stay significantly shorter (P = 0.007), in group A than in group B. Post-procedure WBC and PLT counts in group A were significantly higher than those in group B from 6 mo to 4 years (P = 0.001), and post-procedure residual splenic volume in group A was significantly less than that observed in group B at 1, 2, 3 and 4 years post-procedure (P = 0.001). No significant differences were observed in red blood cell counts and liver function parameters between the two groups following the procedure.
CONCLUSION: Our results indicate that TSAE for patients with hypersplenism not only delivers a better long-term outcome, but is also associated with lower complication rates and a shorter hospital stay than PSE.
Embolization; Hypersplenism; Complications; White cell counts; Platelet counts
Achromatopsia is a rare autosomal recessive disorder which shows color blindness, severely impaired visual acuity, and extreme sensitivity to bright light. Mutations in the alpha subunits of the cone cyclic nucleotide-gated channels (CNGA3) are responsible for about 1/4 of achromatopsia in the U.S. and Europe. Here, we test whether gene replacement therapy using an AAV5 vector could restore cone-mediated function and arrest cone degeneration in the cpfl5 mouse, a naturally occurring mouse model of achromatopsia with a CNGA3 mutation. We show that gene therapy leads to significant rescue of cone-mediated ERGs, normal visual acuities and contrast sensitivities. Normal expression and outer segment localization of both M- and S-opsins were maintained in treated retinas. The therapeutic effect of treatment lasted for at least 5 months post-injection. This study is the first demonstration of substantial, relatively long-term restoration of cone-mediated light responsiveness and visual behavior in a naturally occurring mouse model of CNGA3 achromatopsia. The results provide the foundation for development of an AAV5-based gene therapy trial for human CNGA3 achromatopsia.
AIM: To evaluate the prophylaxis of chronic kidney disease (CKD) after liver transplantation (LT) with low-dose calcineurin inhibitor (CNI) and mycophenolate mofetil (MMF).
METHODS: From March 1999 to December 2009, a total of 572 patients (478 males and 94 females) underwent LT enrolled in the study. Initial immunosuppression was by triple-drug regimens that included a CNI, MMF, and prednisone. The initial dose of CNI was 0.05-0.10 mg/kg per day for tacrolimus (TAC) and 5-10 mg/kg per d for cyclosporine A (CSA) respectively, and was gradually reduced based on a stable graft function. The serum trough level of CNI was 6-8 ng/mL for TAC and 120-150 ng/mL for CSA 3-mo post-operation, 4-6 ng/mL for TAC and 80-120 ng/mL for CSA 1-year after transplantation was expected with stable liver function. MMF was personalized between 1.0-1.5 g/d. Glomerular filtration rate (GFR) was estimated by an abbreviated Modification of Diet in Renal Disease formula. Risk factors of CKD were examined by univariate and multivariate logistic regression.
RESULTS: With a definition of GFR < 60 mL/min per 1.73 m2, the incidence of CKD was 17.3% 5-year after LT. There were 68.3% (293 of 429 cases) patients managed to control their TAC trough concentrations within 8 ng/mL and 58.0% (83 of 143 cases) patients’ CSA trough concentrations within 150 ng/mL. Of the 450 recipients followed-up over 1 year, 55.5% (183 of 330 cases) of which were treated with TAC had a trough concentration ≤ 6 ng/mL while 65.8% (79 of 120 cases) of which were treated with CSA had a concentration ≤ 120 ng/mL. The incidence of CKD in the groups of lower CNI trough concentrations was significantly lower than the groups with CNI concentrations above the ideal range. Patients with CKD had much higher CNI trough concentrations than that of patients without CKD. MMF was adopted in 359 patients (62.8%). Patients administrated with MMF had a relatively low CNI trough concentrations but with no significant difference. The graft function remained stable during follow-up. No difference was found between different groups of CNI trough concentrations. Pre-LT renal dysfunction, ages, acute kidney injury, high blood trough concentrations of CNI in 3 mo (TAC > 8 ng/mL, CSA > 150 ng/mL) and hypertension after operation were associated with CKD progression, while male gender and adoption of MMF were protection factors.
CONCLUSION: Low dose of CNI combined with MMF managed to prevent CKD after LT with stable graft function.
Liver transplantation; Chronic kidney disease; Calcineurin inhibitor; Mycophenolate mofetil; Risk factor
Targeted delivery is a highly desirable strategy for diagnostic imaging due to enhanced efficacy and reduced dosage/toxicity. The need to develop target-specific magnetic resonance imaging (MRI) contrast agents to aid in disease characterization is highly essential. In this study, a specific contrast agent, Gd-DTPA-poly-L-lysine (PL-Gd-DTPA)-folate, was synthesized and evaluated for its efficacy as a targeted agent for the imaging of tumors that overexpress the folate receptor. Folic acid was conjugated to PL-Gd-DTPA via the ε-amino groups. The receptor binding properties of folate-PL-Gd-DTPA were studied in cultured tumor cells that overexpressed the folate receptor. The tumor-selecting properties of folate-PL-Gd-DTPA were then evaluated in BALB/c mice bearing subcutaneously implanted folate receptor-positive tumors. Tissue MR signal intensities were measured at six different time-points. In the in vitro study, the folate-PL-Gd-DTPA was able to bind to these cells, which overexpressed the folate receptor, as with free folic acid. Excellent tumor selectivity was also shown in the animal model; after the success of injection of folate-PL-Gd-DTPA, a maximum intensity increase of 125.4% was observed from pre-injection compared to post-injection images of the tumor at the 48 h time-point. The liver enhancement was non-specific and the muscle signal intensity at any time-point after injection showed no statistical difference with that observed before injection. Folate-PL-Gd-DTPA is a promising, novel receptor-specific MRI contrast agent with potential applications in the imaging of human folate receptor-positive tumors.
folate receptor; pulmonary tumor; targeted contrast agents; magnetic resonance imaging; gadolinium-DTPA
AIM: To investigate the association between interleukin (IL)-10-1082 (G/A) promoter polymorphism and acute rejection (AR) in liver transplant (LT) recipients.
METHODS: Two investigators independently searched the Medline, Embase, China National Knowledge Infrastructure, and Chinese Biomedicine Databases. Summary odds ratios (ORs) and 95% CIs for IL-10-1082 G/A polymorphism and AR were calculated in a ﬁxed- and a random-effects model as appropriate.
RESULTS: This meta-analysis included seven case-control studies, which comprised 652 cases of LT recipients in which 241 cases developed AR and 411 cases did not develop AR. Overall, the variant A allele was not associated with AR risk when compared with the wild-type G allele (OR = 0.94, 95% CI: 0.64-1.39). Moreover, similar results were observed when the AA genotype was compared with the AG/GG genotype (OR = 1.05, 95% CI: 0.55-2.02). When stratifying for ethnicity, no signiﬁcant association was observed among either Caucasians or Asians. Because only one study was performed in Asian patients, the result of subgroup analysis by ethnicity would not be reliable for Asians. Limiting the analysis to the studies with controls in the Hardy-Weinberg equilibrium, the results were persistent and robust. No publication bias was found in the present study.
CONCLUSION: This meta-analysis suggests that IL-10-1082 G/A polymorphism may be not associated with AR risk in LT recipients among Caucasians.
Liver transplantation; Acute rejection; Interleukin-10; Gene polymorphism; Meta-analysis
The complete molecule of the title compound, C28H28B2Br4O4, is generated by the application of a centre of inversion. In the molecule, the BO2 plane is perpendicular to that through the pyrene ring [dihedral angle = 86.27 (13)°]. In the crystal, molecules stack into columns along the b axis, the closest contact between these being of the type C—Br⋯π.
AIM: To investigate the health related quality of life (HRQoL) and psychological outcome of donors after living donor liver transplantation.
METHODS: Participants were 92 consecutive liver transplant donors who underwent hepatectomy without middle hepatic vein at West China Hospital of Sichuan University between January 2007 and September 2010. HRQoL was measured using the Chinese version of the Medical Outcomes Study Short Form-36 (SF-36), and psychological symptoms were measured using the Symptom Checklist-90-Revised (SCL-90-R). Data collected from donors were compared to previously published data from the general population. Clinical and demographic data were collected from medical records and questionnaires.
RESULTS: The general health score of the SF-36 was significantly lower in females (59.78 ± 12.25) than in males (75.83 ± 22.09). Donors more than 40 years old scored higher in social functioning (85.71 ± 14.59) and mental health (82.61 ± 20.00) than those younger than 40 (75.00 ± 12.13, 68.89 ± 12.98; social functioning and mental health, respectively). Donors who had surgery more than two years prior to the study scored highest in physical functioning (P = 0.001) and bodily pain (P = 0.042) while those less than one year from surgery scored lowest. The health of the liver recipient significantly influenced the general health (P = 0.042), social functioning (P = 0.010), and role-emotional (P = 0.028) of donors. Donors with full-time employment scored highest in role-physical (P = 0.005), vitality (P = 0.001), social functioning (P = 0.016), mental health (P < 0.001), the physical component summary scale (P < 0.001), and the mental component summary scale (MCS) (P < 0.001). Psychological measures indicated that donors were healthier than the general population in obsessive-compulsive behavior, interpersonal sensitivity, phobic anxiety, and paranoid ideation. The MCS of the SF-36 was significantly correlated with most symptom scores of the SCL-90-R.
CONCLUSION: HRQoL and psychological outcome were favorable in living liver transplant donors after donation. Specifically, gender, age, time since operation, recipient health condition, and employment after donation, influenced postoperative quality of life.
Health related quality of life; Psychology; Living donor liver transplantation; Donor
The number of people undergoing living donor liver transplantation (LDLT) has increased rapidly in many transplant centres. Patients considering LDLT need to know whether LDLT is riskier than deceased donor liver transplantation (DDLT). The aim of this study was to compare the outcomes of patients undergoing LDLT versus DDLT.
A total of 349 patients with benign liver diseases were recruited from 2005 to 2011 for this study. LDLT was performed in 128 patients, and DDLT was performed in 221 patients. Pre- and intra-operative variables for the two groups were compared. Statistically analysed post-operative outcomes include the postoperative incidence of complication, biliary and vascular complication, hepatitis B virus (HBV) recurrence, long-term survival rate and outcomes of emergency transplantation.
The waiting times were 22.10±15.31 days for the patients undergoing LDLT versus 35.81±29.18 days for the patients undergoing DDLT. The cold ischemia time (CIT) was 119.34±19.75 minutes for the LDLT group and 346±154.18 for DDLT group. LDLT group had higher intraoperative blood loss, but red blood cell (RBC) transfusion was not different. Similar ≥ Clavien III complications, vascular complications, hepatitis B virus (HBV) recurrence and long-term survival rates were noted. LDLT patients suffered a higher incidence of biliary complications in the early postoperative days. However, during the long-term follow-up period, biliary complication rates were similar between the two groups. The long-term survival rate of patients undergoing emergency transplantation was lower than of patients undergoing elective transplantation. However, no significant difference was observed between emergency LDLT and emergency DDLT.
Patients undergoing LDLT achieved similar outcomes to patients undergoing DDLT. Although LDLT patients may suffer a higher incidence of early biliary complications, the total biliary complication rate was similar during the long-term follow-up period.
Confocal light absorption and scattering spectroscopic (CLASS) microscopy can detect changes in biochemicals and the morphology of cells. It is therefore used to detect high-grade cervical squamous intraepithelial lesion (HSIL) cells in the diagnosis of premalignant cervical lesions. Forty cervical samples from women with abnormal Pap smear test results were collected, and twenty cases were diagnosed as HSIL; the rest were normal or low-grade cervical squamous intraepithelial lesion (LSIL). The enlarged and condensed nuclei of HSIL cells as viewed under CLASS microscopy were much brighter and bigger than those of non-HSIL cells. Cytological elastic scattered light data was then collected at wavelengths between 400 and 1000 nm. Between 600 nm to 800 nm, the relative elastic scattered light intensity of HSIL cells was higher than that of the non-HSIL. Relative intensity peaks occurred at 700 nm and 800 nm. CLASS sensitivity and specificity results for HSIL and non-HSIL compared to cytology diagnoses were 80% and 90%, respectively. This study demonstrated that CLASS microscopy could effectively detect cervical precancerous lesions. Further study will verify this conclusion before the method is used in clinic for early detection of cervical cancer.
AIM: To assess the association between Interleukin-10 (IL-10) gene IL-10-1082 (G/A), IL-10-592(C/A), IL-10-819 (T/C) polymorphisms and hepatocellular carcinoma (HCC) susceptibility.
METHODS: Two investigators independently searched the Medline, Embase, China National Knowledge Infrastructure, and Chinese Biomedicine Database. Summary odds ratios (ORs) and 95% confidence intervals (95% CIs) for IL-10 polymorphisms and HCC were calculated in a ﬁxed-effects model (the Mantel-Haenszel method) and a random-effects model (the DerSimonian and Laird method) when appropriate.
RESULTS: This meta-analysis included seven eligible studies, which included 1012 HCC cases and 2308 controls. Overall, IL-10-1082 G/A polymorphism was not associated with the risk of HCC (AA vs AG + GG, OR = 1.11, 95% CI = 0.90-1.37). When stratifying for ethnicity, the results were similar (Asian, OR = 1.12, 95% CI = 0.87-1.44; non-Asian, OR = 1.10, 95% CI = 0.75-1.60). In the overall analysis, the IL-10 polymorphism at position -592 (C/A) was identiﬁed as a genetic risk factor for HCC among Asians; patients carrying the IL-10-592*C allele had an increased risk of HCC (OR = 1.29, 95% CI = 1.12-1.49). No association was observed between the IL-10-819 T/C polymorphism and HCC susceptibility (TT vs TC + CC, OR = 1.02, 95% CI = 0.79-1.32).
CONCLUSION: This meta-analysis suggests that IL-10-592 A/C polymorphism may be associated with HCC among Asians. IL-10-1082 G/A and IL-10-819 T/C polymorphisms were not detected to be related to the risk for HCC.
Hepatocellular carcinoma; Interleukin-10; Gene polymorphism; Meta-analysis
AIM: To study the safety and feasibility of total embolization of the main splenic artery as a supplemental treatment modality for hypersplenism with thrombocytopenia or leukocytopenia accompanying liver cirrhosis.
METHODS: Fifteen consecutive patients with hypersplenism due to cirrhosis were enrolled in this study from January 2006 to June 2010. All patients underwent total embolization of the main splenic artery. Clinical symptoms, white blood cell (WBC) and platelet (PLT) counts, splenic volume, and complications of the patients were recorded. The patients were followed up for 1 and 6 mo, and 1, 2, 3 years, respectively, after operation.
RESULTS: Total embolization of the main splenic artery was technically successful in all patients. Minor complications occurred in 13 patients after the procedure, but no major complications were found. The WBC and PLT counts were significantly higher and the residual splenic volume was significantly lower 1 and 6 mo, and 1, 2, 3 years after the procedure than before the procedure (P < 0.01). Moreover, the residual splenic volume increased very slowly with the time after embolization. All patients were alive during the follow-up period.
CONCLUSION: Total embolization of the main splenic artery is a safe and feasible procedure and may serve as a supplemental treatment modality for hypersplenism with thrombocytopenia or leukocytopenia accompanying liver cirrhosis.
Liver cirrhosis; Hypersplenism; Coil embolization; Splenic artery