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1.  Comparison of Long-Term Survival of Patients with Solitary Large Hepatocellular Carcinoma of BCLC Stage A after Liver Resection or Transarterial Chemoembolization: A Propensity Score Analysis 
PLoS ONE  2014;9(12):e115834.
The aim of this study was to compare the long-term outcome of patients with a solitary large (>5 cm) hepatocellular carcinoma (HCC) in Barcelona Clinic Liver Cancer (BCLC) stage A who received liver resection (LR) or transarterial chemoembolization (TACE).
Our study examined 128 patients treated by LR and 90 treated by TACE. To reduce bias in patient selection, we conducted propensity score analysis in the present study and 54 pairs of patients after propensity score matching were generated, their long-term survival was compared using the Kaplan–Meier method. Independent predictors of survival were identified by multivariate analysis.
Long-term survival was significantly better for the LR group by log-rank test (P<0.001). In multivariate analysis, tumor size, serum ALT level and TACE independently predicted survival. Despite similar baseline characteristics after propensity score matching, LR group still had significantly better survival (1 year, 68.5 vs. 55.0%; 3 years, 47.6 vs. 21.2%; 5 years, 41.3 vs. 18.5%; P = 0.007) than TACE group. The LR and TACE groups had comparable 30- and 90-day post-treatment mortality. Multivariate analysis showed that serum ALT level, serum AFP level and TACE independently predicted survival by multivariate analysis after propensity score matching.
Our propensity-score-matched study suggested that LR provided significantly better long-term survival than TACE for a solitary large HCC of the BCLC stage A, regardless of tumor size.
PMCID: PMC4277403  PMID: 25541684
2.  Appropriate treatment strategies improve survival of hepatocellular carcinoma patients with portal vein tumor thrombus 
World Journal of Gastroenterology : WJG  2014;20(45):17141-17147.
AIM: To evaluate the survival benefits of different treatment strategies for hepatocellular carcinoma (HCC) patients with portal vein tumor thrombus (PVTT) and to determine the prognosis factors.
METHODS: Between 2007 and 2009, 338 HCC patients treated for PVTT were retrospectively studied. The patients were divided into 4 groups that underwent different treatments: the conservative treatment group (n = 75), the transarterial chemoembolization (TACE) group (n = 86), the hepatic resection group (n = 90), and the hepatic resection associated with postoperative TACE group (n = 87). Survival rates were determined using the Kaplan-Meier method and differences between the groups were identified through log-rank analysis. Cox’s proportional hazard model was used to identify the risk factors for survival.
RESULTS: The mean survival periods for patients in the conservative treatment, TACE, hepatic resection and hepatic resection associated with postoperative TACE groups were 3.8, 7, 8.2 and 15.1 mo, respectively. Significant differences were observed in the survival rates. For the surgical resection associated with postoperative TACE group, the survival rates after 1, 2 and 3 years were 49%, 37% and 19%, respectively. These results were significantly higher than those of the other groups (P < 0.05). Meanwhile, the 1, 2 and 3 year survival rates for the surgical resection group were 28%, 20% and 15%, whereas those for the TACE group were 17.5%, 0% and 0%, respectively. These values significantly increased after hepatic resection compared with those after TACE (P < 0.05).
CONCLUSION: Surgical resection is the most effective therapeutic strategy for HCC patients with PVTT and results in high hepatic functional reserve. For patients who can tolerate the procedure, postoperative TACE is necessary to prevent recurrence and prolong the survival period.
PMCID: PMC4258584  PMID: 25493028
Hepatocellular carcinoma; Portal vein tumor thrombosis; Conservative treatment; Transarterial chemoembolization; Surgical resection; Postoperative transarterial chemoembolization
3.  Impact of Diabetes Mellitus on the Prognosis of Patients with Hepatocellular Carcinoma after Curative Hepatectomy 
PLoS ONE  2014;9(12):e113858.
Background: The influence of diabetes mellitus (DM) on the prognosis of patients with hepatocellular carcinoma (HCC) remains controversial. Here we investigated the impact of DM on the prognosis of such patients after curative hepatectomy.
Methods: A consecutive cohort of 505 patients with HCC (134 with DM, 371 without) underwent curative hepatectomy were retrospectively evaluated. Postoperative morbidity and mortality, overall survival (OS) and disease-free survival (DFS) were compared between patients with or without DM. Independent prognostic predictors were identified using the Cox proportional hazards model.
Results: Patients with or without DM showed similar morbidity and 30- and 90- day mortality after curative hepatectomy (all P>0.05), as well as similar DFS at 1, 3, 5 years (P = 0.781). However, the group of patients with DM showed significantly lower OS at 1, 3, 5 years than the group without DM (P = 0.038). Similar results were obtained in the propensity-matched cohort. Cox multivariate analysis identified DM as an independent predictor of poor OS, but not of poor DFS. We repeat compared OS and DFS for DM and non-DM subgroups defined according to the presence or absence of hepatitis B virus infection and cirrhosis. Similar results were obtained in all subgroups except the non-cirrhotic subgroup which showed patients with and without DM had similar OS.
Conclusions: DM does not significantly affect the postoperative morbidity or mortality or the DFS of patients with HCC after curative hepatectomy. It is, however, associated with significantly lower OS, especially in patients with cirrhosis.
PMCID: PMC4250061  PMID: 25436613
4.  Mouse dead end 1-β interacts with c-Jun and stimulates activator protein 1 transactivation 
Molecular Medicine Reports  2014;11(3):1701-1707.
Dead end 1 (DND1), important for maintaining the viability of primordial germ cells, is the first protein containing an RNA recognition motif that has been directly implicated as a heritable cause of spontaneous tumorigenesis. In the present study, c-Jun was identified through yeast two-hybrid screening of a 10.5-day old mouse embryo cDNA library as one of the proteins which interact with DND1-β. The interaction between DND1-β and c-Jun was demonstrated to occur by glutathione S-transferase pull-down and co-immunoprecipitation. Using confocal microscopy, DND1-β was found to be specifically expressed in GC-1 spermatogonia cells, mainly in the nuclei. When transfected into GC-1 cells, DND1-β and c-Jun were demonstrated to be co-localized principally in the nuclei. Furthermore, in a dual luciferase reporter assay, the transcriptional activity of activator protein 1 was demonstrated to be significantly increased by co-transfection with DND1-β and c-Jun plasmids in GC-1 cells. The identification and confirmation of an additional protein interacting with DND1-β facilitates the investigation of the functions and molecular mechanisms of DND1.
PMCID: PMC4270339  PMID: 25405725
dead end 1-β; c-Jun; activator protein-1; yeast two-hybrid; interaction; immunoprecipitation; glutathione 3-transferase pull-down
5.  Primary hepatic non-Hodgkin’s lymphoma with rectal cancer: A case report 
Oncology Letters  2014;9(1):324-326.
Primary hepatic non-Hodgkin’s lymphoma (NHL) is an extremely rare disease that is commonly neglected as a possible diagnosis. The present study reports the case of a middle-aged male with chronic hepatitis B in which primary hepatic NHL and rectal cancer occurred simultaneously. A large solitary tumor in the left lobe of the liver was incidentally detected on routine examination prior to the laparoscopic resection of the rectal cancer. Laparoscopic resection of the rectal cancer and a liver biopsy were performed simultaneously. The pathology revealed that the hepatic tumor was NHL and that the rectal cancer was adenocarcinoma. Systemic staging revealed no evidence of nodal or bone marrow involvement, therefore, primary hepatic lymphoma (PHL) was diagnosed. PHL associated with rectal adenocarcinoma is extremely rare and to the best of our knowledge, has never been reported. At present, the cause and most effective therapy for the condition remain unclear.
PMCID: PMC4247066  PMID: 25435985
non-Hodgkin’s lymphoma; liver; primary liver lymphoma; rectal cancer
6.  Rapid Response of Hydrological Loss of DOC to Water Table Drawdown and Warming in Zoige Peatland: Results from a Mesocosm Experiment 
PLoS ONE  2014;9(11):e109861.
A large portion of the global carbon pool is stored in peatlands, which are sensitive to a changing environment conditions. The hydrological loss of dissolved organic carbon (DOC) is believed to play a key role in determining the carbon balance in peatlands. Zoige peatland, the largest peat store in China, is experiencing climatic warming and drying as well as experiencing severe artificial drainage. Using a fully crossed factorial design, we experimentally manipulated temperature and controlled the water tables in large mesocosms containing intact peat monoliths. Specifically, we determined the impact of warming and water table position on the hydrological loss of DOC, the exported amounts, concentrations and qualities of DOC, and the discharge volume in Zoige peatland. Our results revealed that of the water table position had a greater impact on DOC export than the warming treatment, which showed no interactive effects with the water table treatment. Both DOC concentration and discharge volume were significantly increased when water table drawdown, while only the DOC concentration was significantly promoted by warming treatment. Annual DOC export was increased by 69% and 102% when the water table, controlled at 0 cm, was experimentally lowered by −10 cm and −20 cm. Increases in colored and aromatic constituents of DOC (measured by Abs254 nm, SUVA254 nm, Abs400 nm, and SUVA400 nm) were observed under the lower water tables and at the higher peat temperature. Our results provide an indication of the potential impacts of climatic change and anthropogenic drainage on the carbon cycle and/or water storage in a peatland and simultaneously imply the likelihood of potential damage to downstream ecosystems. Furthermore, our results highlight the need for local protection and sustainable development, as well as suggest that more research is required to better understand the impacts of climatic change and artificial disturbances on peatland degradation.
PMCID: PMC4219674  PMID: 25369065
7.  Hepatic Resection Is Safe and Effective for Patients with Hepatocellular Carcinoma and Portal Hypertension 
PLoS ONE  2014;9(9):e108755.
Background & Aims
Official guidelines do not recommend hepatic resection (HR) for patients with hepatocellular carcinoma (HCC) and portal hypertension (PHT). This study aims to investigate the safety and efficacy of HR for patients with HCC and PHT.
Mortality and survival after HR were analyzed retrospectively in a consecutive sample of 1738 HCC patients with PHT (n = 386) or without it (n = 1352). To assess the robustness of findings, we repeated the analysis using propensity score-matched analysis. We also comprehensively searched the PubMed database for studies evaluating the efficacy and safety of HR for patients with HCC and PHT.
The 90-day mortality rate was 6.7% among those with PHT and 2.1% among those without it (P<.001). Patients without PHT had a survival benefit over those with PHT at 1, 3, and 5 years (96% vs 90%, 75% vs 67%, 54% vs 45%, respectively; P = .001). In contrast, PHT was not associated with worse short- or long-term survival when only propensity score-matched pairs of patients and those with early-stage HCC or those who underwent minor hepatectomy were included in the analysis (all P>.05). Moreover, the recurrence rates were similar between the two groups. Consistent with our findings, all 9 studies identified in our literature search reported HR to be safe and effective for patients with HCC and PHT.
HR is safe and effective in HCC patients with PHT and preserved liver function. This is especially true for patients who have early-stage HCC or who undergo minor hepatectomy.
PMCID: PMC4182657  PMID: 25268959
8.  Nucleos(t)ide analogues to treat hepatitis B virus-related hepatocellular carcinoma after radical resection 
World Journal of Hepatology  2014;6(9):652-659.
Significant advances have been made in nucleos(t)ide analogue (NA) therapy to treat chronic hepatitis B, and this therapy reduces the risk of hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) in some patients. However, whether NAs can also prevent recurrence after radical resection of HBV-related HCC remains controversial and is an important question, given that most patients will experience recurrence within a few years of curative surgery. Here we systematically reviewed the literature since 2004 on outcomes after administering NAs to patients with HBV-related HCC following radical resection. We focused on treatment indications, duration, effects on recurrence-free survival and overall survival, and the management of NA resistance. We find that patients with HCC should strongly consider NA therapy if they are positive for HBV-DNA, and that the available evidence suggests that postoperative NA therapy can increase both recurrence-free and overall survival. To minimize drug resistance, clinicians should opt for potent analogues with higher resistance barriers, and they should monitor the patient carefully for emergence of NA-resistant HBV.
PMCID: PMC4179144  PMID: 25276281
Antiviral therapy; Hepatitis B virus; Hepatocellular carcinoma; Liver resection; Nucleos(t)ide analogue; Survival rate
9.  Virtual reality training improves balance function 
Neural Regeneration Research  2014;9(17):1628-1634.
Virtual reality is a new technology that simulates a three-dimensional virtual world on a computer and enables the generation of visual, audio, and haptic feedback for the full immersion of users. Users can interact with and observe objects in three-dimensional visual space without limitation. At present, virtual reality training has been widely used in rehabilitation therapy for balance dysfunction. This paper summarizes related articles and other articles suggesting that virtual reality training can improve balance dysfunction in patients after neurological diseases. When patients perform virtual reality training, the prefrontal, parietal cortical areas and other motor cortical networks are activated. These activations may be involved in the reconstruction of neurons in the cerebral cortex. Growing evidence from clinical studies reveals that virtual reality training improves the neurological function of patients with spinal cord injury, cerebral palsy and other neurological impairments. These findings suggest that virtual reality training can activate the cerebral cortex and improve the spatial orientation capacity of patients, thus facilitating the cortex to control balance and increase motion function.
PMCID: PMC4211206  PMID: 25368651
nerve regeneration; brain injury; spinal cord injury; stroke; virtual reality; balance dysfunction; mechanism; sensorimotor function; neural plasticity; vision; vestibule; proprioception; somatosensory; balance; reviews; rehabilitation; NSFC grant; neural regeneration
10.  Vitamin-responsive Mesoporous Nanocarrier with DNA Aptamer-mediated Cell Targeting 
A smart drug delivery system with cancer cell targeting and bioresponsive controlled drug release has been constructed by taking advantage of the protein-capped mesoporous nanovalve and a DNA aptamer.
PMCID: PMC3676747  PMID: 23589821
11.  Progress of cancer research on astrocyte elevated gene-1/Metadherin (Review) 
Oncology Letters  2014;8(2):493-501.
Tumor development is initiated by an accumulation of numerous genetic and epigenetic alterations that promote tumor initiation, invasion and metastasis. Astrocyte elevated gene-1 [AEG-1; also known as Metadherin (MTDH) and Lysine-rich CEACAM1 co-isolated (LYRIC)] has emerged in recent years as a potentially crucial mediator of tumor malignancy, and a key converging point of a complex network of oncogenic signaling pathways. AEG-1/MTDH has a multifunctional role in tumor development that has been found to be involved in the following signaling cascades: i) The Ha-Ras and PI3K/Akt pathways; ii) the nuclear factor-κB signaling pathway; iii) the ERK/mitogen-activated protein kinase and Wnt/β-catenin pathways; and iv) the Aurora-A kinase signaling pathway. Studies have established that AEG-1/MTDH is crucial in tumor progression, including transformation, the evasion of apoptosis, invasion, angiogenesis and metastasis. In addition, recent clinical studies have convincingly associated AEG-1/MTDH with tumor progression and poor prognosis in a number of cancer types, including hepatocellular, esophageal squamous cell, gallbladder and renal cell carcinomas, breast, non-small cell lung, prostate, gastric and colorectal cancers, and glioma, melanoma, neuroblastoma and osteosarcoma. AEG-1/MTDH may be used as a biomarker to identify subgroups of patients who require more intensive treatments and who are likely to benefit from AEG-1/MTDH-targeted therapies. The therapeutic targeting of AEG-1/MTDH may simultaneously block metastasis, suppress tumor growth and enhance the efficacy of chemotherapeutic treatments.
PMCID: PMC4081432  PMID: 25009642
astrocyte elevated gene-1; metadherin; neoplasms; metastasis; chemoresistance
12.  MADS-Box Transcription Factor SsMADS Is Involved in Regulating Growth and Virulence in Sclerotinia sclerotiorum 
MADS-box proteins, a well-conserved family of transcription factors in eukaryotic organisms, specifically regulate a wide range of cellular functions, including primary metabolism, cell cycle, and cell identity. However, little is known about roles of the MADS-box protein family in the fungal pathogen Sclerotinia sclerotiorum. In this research, the S. sclerotiorum MADS-box gene SsMADS was cloned; it encodes a protein that is highly similar to Mcm1 orthologs from Saccharomyces cerevisiae and other fungi, and includes a highly conserved DNA-binding domain. MADS is a member of the MADS box protein SRF (serum response factor) lineage. SsMADS function was investigated using RNA interference. Silenced strains were obtained using genetic transformation of the RNA interference vectors pS1-SsMADS and pSD-SsMADS. SsMADS expression levels in silenced strains were analyzed using RT-PCR. The results showed that SsMADS mRNA expression in these silenced strains was reduced to different degrees, and growth rate in these silenced strains was significantly decreased. Infecting tomato leaflets with silenced strains indicated that SsMADS was required for leaf pathogenesis in a susceptible host. Our results suggest that the MADS-box transcription factor SsMADS is involved in S. sclerotiorum growth and virulence.
PMCID: PMC4057718  PMID: 24815067
Sclerotinia sclerotiorum; RNA interference; transcription factor; MADS-box
13.  Change of Muscle Architecture following Body Weight Support Treadmill Training for Persons after Subacute Stroke: Evidence from Ultrasonography 
BioMed Research International  2014;2014:270676.
Although the body weight support treadmill training (BWSTT) in rehabilitation therapy has been appreciated for a long time, the biomechanical effects of this training on muscular system remain unclear. Ultrasonography has been suggested to be a feasible method to measure muscle morphological changes after neurological diseases such as stroke, which may help to enhance the understanding of the mechanism underlying the impaired motor function. This study investigated the muscle architectural changes of tibialis anterior and medial gastrocnemius in patients after subacute stroke by ultrasound. As expected, we found the effect of BWSTT on the muscular system. Specifically, the results showed larger pennation angle and muscle thickness of tibialis anterior and longer fascicle length of medial gastrocnemius after the training. The findings of this study suggest that the early rehabilitation training of BWSTT in subacute stage of stroke provides positive changes of the muscle architecture, leading to the potential improvement of the force generation of the muscle. This may not only help us understand changes of subacute stroke in muscular system but also have clinical implications in the evaluation of rehabilitation training after neurological insults.
PMCID: PMC3982255  PMID: 24783198
14.  Cancer stem cell markers correlate with early recurrence and survival in hepatocellular carcinoma 
AIM: To investigate whether expression of cancer stem cell (CSC) markers is associated with recurrence and survival in hepatocellular carcinoma (HCC) patients.
METHODS: A consecutive series of 90 HCC patients who underwent curative hepatectomy between April 2007 and April 2009 were analyzed. Of the 90 patients, 38 (42%) experienced recurrence within two years of surgery. To adjust for baseline differences between this early recurrence group and the other patients, propensity-score matching was used to generate 25 pairs of patients. Immunohistochemistry was used to compare expression of CD133, CD90, and epithelial cell adhesion molecule (EpCAM) in liver tissues from propensity score-matched patients and from 10 healthy adults. Associations of the three markers with HCC, clinicopathological characteristics, early recurrence, and survival time were explored.
RESULTS: The expression of all three CSC markers was significantly higher in HCC tissue than in healthy liver tissue (P < 0.001 for all). Among the HCC clinicopathology characteristics examined, the absence of tumor capsule was associated with CD133 expression (P = 0.005); higher histopathology grade and larger tumor size were associated with CD90 expression (P = 0.010 and 0.034, respectively); and elevated serum alpha-fetoprotein levels were associated with EpCAM expression (P = 0.021). Expression of CD90 and EpCAM was significantly higher in the early recurrence group than in other patients (P = 0.001 and 0.045, respectively), whereas CD133 expression was not significantly different between the two groups (P = 0.440). Multivariate analysis identified only CD90 expression as significantly associated with early recurrence. Log-rank analysis identified expression of both CD90 and EpCAM as significantly associated with survival time of HCC patients. Cox regression identified EpCAM expression as an independent predictor of survival time.
CONCLUSION: Expression of CD133, CD90, and EpCAM CSC markers may be linked to HCC tumor onset and/or progression. In addition, EpCAM expression is associated with shorter survival time, while CD90 expression is associated with early HCC recurrence.
PMCID: PMC3934481  PMID: 24616575
Hepatocellular carcinoma; Cancer stem cells; CD133; CD90; Epithelial cell adhesion molecule
15.  An Exceptionally Simple Strategy for DNA-Functionalized Up-conversion Nanoparticles as Biocompatible Agents for Nano-Assembly, DNA Delivery and Imaging 
Lanthanide-doped upconversion nanoparticles (UCNPs) have shown promise in biomedical applications. However, as the UCNPs are normally capped with hydrophobic ligands, it remains challenging to prepare biocompatible UCNPs with specific molecular recognition capabilities. We herein report an exceptionally simple strategy to prepare uniform DNA-modified upconversion nanoparticles (DNA-UCNPs) as versatile bioprobes. The approach can directly convert as-prepared hydrophobic UCNPs into water-soluble DNA-UCNPs without any chemical modification of UCNPs or oligonucleotides. Furthermore, DNA molecules on the DNA-UCNPs retain their biorecognition ability, allowing programmable assembly of hybrid nanostructures. More importantly, we show that these DNA-UCNPs are capable of crossing cell membranes without the need of transfection agents, and their use as agents for bioimaging and DNA delivery are also demonstrated. Finally, DNA aptamer-conjugated UCNPs can be readily used for targeted imaging of cancer cells.
PMCID: PMC3608408  PMID: 23356394
16.  Earlier-Season Vegetation Has Greater Temperature Sensitivity of Spring Phenology in Northern Hemisphere 
PLoS ONE  2014;9(2):e88178.
In recent decades, satellite-derived start of vegetation growing season (SOS) has advanced in many northern temperate and boreal regions. Both the magnitude of temperature increase and the sensitivity of the greenness phenology to temperature–the phenological change per unit temperature–can contribute the advancement. To determine the temperature-sensitivity, we examined the satellite-derived SOS and the potentially effective pre-season temperature (Teff) from 1982 to 2008 for vegetated land between 30°N and 80°N. Earlier season vegetation types, i.e., the vegetation types with earlier SOSmean (mean SOS for 1982–2008), showed greater advancement of SOS during 1982–2008. The advancing rate of SOS against year was also greater in the vegetation with earlier SOSmean even the Teff increase was the same. These results suggest that the spring phenology of vegetation may have high temperature sensitivity in a warmer area. Therefore it is important to consider temperature-sensitivity in assessing broad-scale phenological responses to climatic warming. Further studies are needed to explore the mechanisms and ecological consequences of the temperature-sensitivity of start of growing season in a warming climate.
PMCID: PMC3914920  PMID: 24505418
17.  Dynamics and Sources of Soil Organic C Following Afforestation of Croplands with Poplar in a Semi-Arid Region in Northeast China 
PLoS ONE  2014;9(1):e86640.
Afforestation of former croplands has been proposed as a promising way to mitigate rising atmospheric CO2 concentration in view of the commitment to the Kyoto Protocol. Central to this C sequestration is the dynamics of soil organic C (SOC) storage and stability with the development of afforested plantations. Our previous study showed that SOC storage was not changed after afforestation except for the 0–10 cm layer in a semi-arid region of Keerqin Sandy Lands, northeast China. In this study, soil organic C was further separated into light and heavy fractions using the density fractionation method, and their organic C concentration and 13C signature were analyzed to investigate the turnover of old vs. new SOC in the afforested soils. Surface layer (0–10 cm) soil samples were collected from 14 paired plots of poplar (Populus × xiaozhuanica W. Y. Hsu & Liang) plantations with different stand basal areas (the sum of the cross-sectional area of all live trees in a stand), ranging from 0.2 to 32.6 m2 ha−1, and reference maize (Zea mays L.) croplands at the same sites as our previous study. Soil ΔC stocks (ΔC refers to the difference in SOC content between a poplar plantation and the paired cropland) in bulk soil and light fraction were positively correlated with stand basal area (R2 = 0.48, p<0.01 and R2 = 0.40, p = 0.02, respectively), but not for the heavy fraction. SOCcrop (SOC derived from crops) contents in the light and heavy fractions in poplar plantations were significantly lower as compared with SOC contents in croplands, but tree-derived C in bulk soil, light and heavy fraction pools increased gradually with increasing stand basal area after afforestation. Our study indicated that cropland afforestation could sequester new C derived from trees into surface mineral soil, but did not enhance the stability of SOC due to a fast turnover of SOC in this semi-arid region.
PMCID: PMC3900571  PMID: 24466183
18.  Correction: Comparison of Long-Term Survival of Patients with BCLC Stage B Hepatocellular Carcinoma after Liver Resection or Transarterial Chemoembolization 
PLoS ONE  2014;9(1):10.1371/annotation/32a8c7e3-5efc-478b-b374-c8cbfd1d3968.
PMCID: PMC3897329
19.  Distribution and location of Daxx in cervical epithelial cells with high risk human papillomavirus positive 
To provide the basis for further exploring the effect and its mechanism of Death domain associated protein (Daxx) on the progress of cervical carcinoma induced by human papillomavirus (HPV), the distribution and location of Daxx in cervical carcinoma with high risk HPV(HR-HPV) positive was analyzed.
The samples of normal cervical epithelial cells, cervical intraepithelial neoplasia grade I (CINI), CINII CINIII and cervical cancers were collected. Immunohistochemistry assay was used to analyze the distributions and locations of Daxx in the cervical tissue. Indirect immunoinfluorescence test was utilized to observe the locations of Daxx in Caski cells with HPV16 positive.
Under the light microscopy, the brown signals of Daxx distributed in the nuclei of normal cervical epithelial cells; Daxx mainly distributed in nuclear membrane and there were a small amount of Daxx in the nuclei in CINI. Daxx intensively distributed in the cytoplasm and cell membrane in CINII, CINIII and cervical cancer. Under fluorescent microscopy, the distribution and location of Daxx in Caski cells was similarly to that in cervical cells of CINII, CINIII and cervical cancer.
In the progress of the cervical cancer, Daxx gradually translocates from nucleus into nuclear membrane, cytoplasm and cell membrane. Daxx locates in the cytoplasm and cell membrane in CINII, CINIII and cervical cancer.
Virtual slides
The virtual slide(s) for this article can be found here:
PMCID: PMC3933295  PMID: 24398161
Human papillomavirus; Daxx; Cervical cancer; Intraepithelial neoplasia grade
20.  Genome-Wide and Differential Proteomic Analysis of Hepatitis B Virus and Aflatoxin B1 Related Hepatocellular Carcinoma in Guangxi, China 
PLoS ONE  2013;8(12):e83465.
Both hepatitis B virus (HBV) and aflatoxin B1 (AFB1) exposure can cause liver damage as well as increase the probability of hepatocellular carcinoma (HCC). To investigate the underlying genetic changes that may influence development of HCC associated with HBV infection and AFB1 exposure, HCC patients were subdivided into 4 groups depending upon HBV and AFB1 exposure status: (HBV(+)/AFB1(+), HBV(+)/AFB1(-), HBV(-)/AFB1(+), HBV(-)/AFB1(-)). Genetic abnormalities and protein expression profiles were analyzed by array-based comparative genomic hybridization and isobaric tagging for quantitation. A total of 573 chromosomal aberrations (CNAs) including 184 increased and 389 decreased were detected in our study population. Twenty-five recurrently altered regions (RARs; chromosomal alterations observed in ≥10 patients) in chromosomes were identified. Loss of 4q13.3-q35.2, 13q12.1-q21.2 and gain of 7q11.2-q35 were observed with a higher frequency in the HBV(+)/AFB1(+), HBV(+)/AFB1(-) and HBV(-)/AFB1(+) groups compared to the HBV(-)/AFB(-) group. Loss of 8p12-p23.2 was associated with high TNM stage tumors (P = 0.038) and was an unfavorable prognostic factor for tumor-free survival (P =0.045). A total of 133 differentially expressed proteins were identified in iTRAQ proteomics analysis, 69 (51.8%) of which mapped within identified RARs. The most common biological processes affected by HBV and AFB1 status in HCC tumorigenesis were detoxification and drug metabolism pathways, antigen processing and anti-apoptosis pathways. Expression of AKR1B10 was increased significantly in the HBV(+)/AFB1(+) and HBV(-)/AFB1(+) groups. A significant correlation between the expression of AKR1B10 mRNA and protein levels as well as AKR1B10 copy number was observered, which suggest that AKR1B10 may play a role in AFB1-related hepatocarcinogenesis. In summary, a number of genetic and gene expression alterations were found to be associated with HBV and AFB1- related HCC. The possible synergistic effects of HBV and AFB1 in hepatocarcinogenesis warrant further investigations.
PMCID: PMC3877066  PMID: 24391771
21.  Mechanism of Kinect-based virtual reality training for motor functional recovery of upper limbs after subacute stroke 
Neural Regeneration Research  2013;8(31):2904-2913.
The Kinect-based virtual reality system for the Xbox 360 enables users to control and interact with the game console without the need to touch a game controller, and provides rehabilitation training for stroke patients with lower limb dysfunctions. However, the underlying mechanism remains unclear. In this study, 18 healthy subjects and five patients after subacute stroke were included. The five patients were scanned using functional MRI prior to training, 3 weeks after training and at a 12-week follow-up, and then compared with healthy subjects. The Fugl-Meyer Assessment and Wolf Motor Function Test scores of the hemiplegic upper limbs of stroke patients were significantly increased 3 weeks after training and at the 12-week follow-up. Functional MRI results showed that contralateral primary sensorimotor cortex was activated after Kinect-based virtual reality training in the stroke patients compared with the healthy subjects. Contralateral primary sensorimotor cortex, the bilateral supplementary motor area and the ipsilateral cerebellum were also activated during hand-clenching in all 18 healthy subjects. Our findings indicate that Kinect-based virtual reality training could promote the recovery of upper limb motor function in subacute stroke patients, and brain reorganization by Kinect-based virtual reality training may be linked to the contralateral sensorimotor cortex.
PMCID: PMC4146174  PMID: 25206611
neural regeneration; neurological rehabilitation; rehabilitation training; neural plasticity; virtual reality; functional MRI; stroke; Kinect-based virtual reality training; upper limb; cerebral cortex; brain activation; region of interest; grants-supported paper; neuroregeneration
22.  Neuroprotective Effect of Ginkgolide B on Bupivacaine-Induced Apoptosis in SH-SY5Y Cells 
Local anesthetics are used routinely and effectively. However, many are also known to activate neurotoxic pathways. We tested the neuroprotective efficacy of ginkgolide B (GB), an active component of Ginkgo biloba, against ROS-mediated neurotoxicity caused by the local anesthetic bupivacaine. SH-SY5Y cells were treated with different concentrations of bupivacaine alone or following preincubation with GB. Pretreatment with GB increased SH-SY5Y cell viability and attenuated intracellular ROS accumulation, apoptosis, mitochondrial dysfunction, and ER stress. GB suppressed bupivacaine-induced mitochondrial depolarization and mitochondria complex I and III inhibition and increased cleaved caspase-3 and Htra2 expression, which was strongly indicative of activation of mitochondria-dependent apoptosis with concomitantly enhanced expressions of Grp78, caspase-12 mRNA, protein, and ER stress. GB also improved ultrastructural changes indicative of mitochondrial and ER damage induced by bupivacaine. These results implicate bupivacaine-induced ROS-dependent mitochondria, ER dysfunction, and apoptosis, which can be attenuated by GB through its antioxidant property.
PMCID: PMC3818975  PMID: 24228138
23.  Direct Detection of Adenosine in Undiluted Serum Using a Luminescent Aptamer Sensor Attached to a Terbium Complex 
Analytical chemistry  2012;84(18):7852-7856.
Aptamers, single-stranded nucleic acids that can selectively bind to various target molecules, have been widely used for constructing biosensors. A major challenge in this field, however, is direct sensing of analytes in complex biological media such as undiluted serum. While progress has been made in developing inhomogeneous assay by using a pre-separation step to wash away the interferences within serum, a facile strategy for direct detection of targets in homogenous unprocessed serum is highly desired. We herein report a turn-on luminescent aptamer biosensor for the direct detection of adenosine in undiluted and unprocessed serum, by taking advantage of a terbium chelate complex with long luminescence lifetime to achieve time-resolved detection. The sensor exhibits a detection limit of 60 µM adenosine while marinating excellent selectivity that is comparable to those in buffer. The approach demonstrated here can be applied for direct detection and quantification of a broad range of analytes in biological media by using other aptamers.
PMCID: PMC3461325  PMID: 22894546
Aptamer; sensor; serum; luminescence; terbium complex
24.  Methylenetetrahydrofolate Reductase Gene Polymorphism and Risk of Type 2 Diabetes Mellitus 
PLoS ONE  2013;8(9):e74521.
This review aimed to comprehensively assess the literature examining a possible link between the rs1801133 polymorphism (677C→T) in the gene encoding the methylenetetrahydrofolate reductase (MTHFR) gene and risk of type 2 diabetes mellitus (DM).
Research Design and Methods
Several research databases were systematically searched for studies examining the genotype at the rs1801133 polymorphism in healthy control individuals and individuals with type 2 DM. Genotype frequency data were examined across all studies and across subsets of studies according to ethnicity and presence of serious DM-related complications. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated.
A total of 4855 individuals with type 2 DM and 5242 healthy controls from 15 countries comprising Asian, Caucasian and African ethnicities were found to satisfy the inclusion criteria and included in the review. Genotype at the rs1801133 polymorphism was not consistently associated with either increased or reduced risk of type 2 DM; the OR across all studies was 0.91 (95%CI 0.82 to 1.00) for the C- vs. T-allele, 0.88 (0.75 to 1.03) for CC vs. CT+TT, 0.82 (0.71 to 0.95) for CC vs. TT, and 1.15 (1.03 to 1.29) for TT vs. CC+CT. Similar results were found when the meta-analysis was repeated separately for each ethnic subgroup, and for subgroups with or without serious DM-related complications.
There does not appear to be compelling evidence of an association between the genotype at the rs1801133 polymorphism of the MTHFR gene and risk of type 2 DM.
PMCID: PMC3762795  PMID: 24023947
25.  Antiviral therapy for hepatitis B virus-related hepatocellular carcinoma after radical hepatectomy 
Cancer Biology & Medicine  2013;10(3):158-164.
To assess the effect of antiviral therapy for hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) after radical hepatectomy.
A total of 478 HBV-related HCC patients treated by radical hepatectomy were retrospectively collected. Patients in the treatment group (n=141) received postoperative lamivudine treatment (100 mg/d), whereas patients in the control group (n=337) did not. Recurrence-free survival (RFS) rates, overall survival (OS) rates, treatments for recurrent HCC and cause of death were compared between the two groups. Propensity score matching (PSM) analysis was also conducted to reduce confounding bias between the two groups.
The 1-, 3-, and 5-year RFS rates didn't significantly differ between the two groups (P=0.778); however, the 1-, 3-, and 5-year OS rates in the treatment group were significantly higher than those in the control group (P=0.002). Similar results were observed in the matched data. Subgroup analysis showed that antiviral treatment conferred a significant survival benefit for Barcelona Clinical Liver Cancer stage A/B patients. Following HCC recurrence, more people in the treatment group were able to choose curative treatments than those in the control group (P=0.031). For cause of death, fewer people in the treatment group died of liver failure than those in the control group (P=0.041).
Postoperative antiviral therapy increases chances of receiving curative treatments for recurrent HCC and prevents death because of liver failure, thereby significantly prolonging OS, especially in early- or intermedian-stage tumors.
PMCID: PMC3860342  PMID: 24379991
Antiviral therapy; hepatocellular carcinoma; propensity score matching; recurrence-free survival rate

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