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1.  Association of Clinical Symptomatic Hypoglycemia With Cardiovascular Events and Total Mortality in Type 2 Diabetes 
Diabetes Care  2013;36(4):894-900.
OBJECTIVE
Hypoglycemia is associated with serious health outcomes for patients treated for diabetes. However, the outcome of outpatients with type 2 diabetes who have experienced hypoglycemia episodes is largely unknown.
RESEARCH DESIGN AND METHODS
The study population, derived from the National Health Insurance Research Database released by the Taiwan National Health Research Institutes during 1998–2009, comprised 77,611 patients with newly diagnosed type 2 diabetes. We designed a prospective study consisting of randomly selected hypoglycemic type 2 diabetic patients and matched type 2 diabetic patients without hypoglycemia. We investigated the relationships of hypoglycemia with total mortality and cardiovascular events, including stroke, coronary heart disease, cardiovascular diseases, and all-cause hospitalization.
RESULTS
There were 1,844 hypoglycemic events (500 inpatients and 1,344 outpatients) among the 77,611 patients. Both mild (outpatient) and severe (inpatient) hypoglycemia cases had a higher percentage of comorbidities, including hypertension, renal diseases, cancer, stroke, and heart disease. In multivariate Cox regression models, including diabetes treatment adjustment, diabetic patients with hypoglycemia had a significantly higher risk of cardiovascular events during clinical treatment periods. After constructing a model adjusted with propensity scores, mild and severe hypoglycemia still demonstrated higher hazard ratios (HRs) for cardiovascular diseases (HR 2.09 [95% CI 1.63–2.67]), all-cause hospitalization (2.51 [2.00–3.16]), and total mortality (2.48 [1.41–4.38]).
CONCLUSIONS
Symptomatic hypoglycemia, whether clinically mild or severe, is associated with an increased risk of cardiovascular events, all-cause hospitalization, and all-cause mortality. More attention may be needed for diabetic patients with hypoglycemic episodes.
doi:10.2337/dc12-0916
PMCID: PMC3609481  PMID: 23223349
2.  FRET-Based System for Probing Protein-Protein Interactions between σR and RsrA from Streptomyces Coelicolor in Response to the Redox Environment 
PLoS ONE  2014;9(3):e92330.
Protein-protein interactions between sigma factor σR and its corresponding zinc-binding anti-sigma (ZAS) protein RsrA trigger the thioredoxin system for maintaining cellular redox homeostasis in S. coelicolor. RsrA bound to zinc associates with σR, inhibiting its transcriptional activity in a reducing environment. During disulfide stress it forms intramolecular disulfide bonds, leading to zinc release and dissociation from σR, which initiates transcription to produce reductase and thioredoxin. We designed a fluorescence resonance energy transfer (FRET) based system for monitoring protein-protein interactions between σR and RsrA to further understand how this redox switch regulates the thioredoxin system in S. coelicolor in response to its redox environment, especially various reactive oxygen species (ROS) derived from different metabolic pathways, and clarify the different response mechanisms between Zn-RsrA and apo-RsrA. By the use of the FRET approach described here, we showed that zinc protected thiols in RsrA and causes the σR-RsrA complex to form a more compact structure. This system was also utilized to detect changes in redox status induced by ROS and diamide in real time in E. coli cells.
doi:10.1371/journal.pone.0092330
PMCID: PMC3961337  PMID: 24651617
3.  Overcoming the chromatin barrier to end resection 
Cell Research  2012;23(3):317-319.
Repair of double-strand breaks by homologous recombination requires Repair of double-strand breaks by homologous recombination requires 5′-3′ resection of the DNA ends to create 3′ single-stranded DNA tails. While much progress has been made in identifying the proteins that directly participate in end resection, how this process occurs in the context of chromatin is not well understood. Two papers in Nature report that Fun30, a poorly characterized member of the Swi2/Snf2 family of chromatin remodelers, plays a role in end processing by facilitating the Exo1 and Sgs1-Dna2 resection pathways.
doi:10.1038/cr.2012.148
PMCID: PMC3587700  PMID: 23147792
4.  The clinical value of the quantitative detection of four cancer-testis antigen genes in multiple myeloma 
Molecular Cancer  2014;13:25.
Background
Cancer-testis (CT) antigen genes might promote the progression of multiple myeloma (MM). CT antigens may act as diagnostic and prognostic markers in MM, but their expression levels and clinical implications in this disease are not fully understood. This study measured the expression levels of four CT antigen genes in Chinese patients with MM and explored their clinical implications.
Methods
Real-time quantitative polymerase chain reaction (qPCR) was used to quantify the expression of MAGE-C1/CT7, MAGE-A3, MAGE-C2/CT10 and SSX-2 mRNA in 256 bone marrow samples from 144 MM patients.
Results
In the newly diagnosed patients, the positive expression rates were 88.5% for MAGE-C1/CT7, 82.1% for MAGE-C2/CT10, 76.9% for MAGE-A3 and 25.6% for SSX-2. The expression levels and the number of co-expressed CT antigens correlated significantly with several clinical indicators, including the percentage of plasma cells infiltrating the bone marrow, abnormal chromosome karyotypes and the clinical course.
Conclusion
MAGE-C1/CT7, MAGE-A3, MAGE-C2/CT10 and SSX-2 expression levels provide potentially effective clinical indicators for the auxiliary diagnosis and monitoring of treatment efficacy in MM.
doi:10.1186/1476-4598-13-25
PMCID: PMC3922338  PMID: 24499297
Cancer-testis antigen gene; Multiple myeloma; Real-time quantitative polymerase chain reaction
5.  Effects of Preventive Acupuncture and Moxibustion on Fat Accumulation, Blood Lipid, and Uterus E2 of Menopause Rats 
Objective. To observe the effect of preventive acupuncture and moxibustion on blood lipid of menopause rats. Methods. Seventy 10-month-old SD rats with estrous cycle disorders were divided into three control groups and four treatment groups (n = 10/group) and another ten 3.5-month-old female SD rats were chosen as young control group. Preventive acupuncture and moxibustion were applied at Guanyuan (CV 4). Body weight growth rate has been recorded. Plasma total cholesterol (TC), triglyceride (TG), low density lipoprotein (LDL), and high density lipoprotein (HDL) levels and uterus E2 level were measured. Results. Compared to young control group, plasma TC and LDL increased and uterus E2 reduced significantly in 12-month-old control group. Compared to 12-month-old control group, plasma TC and LDL level and body weight growth rate decreased while HDL level increased remarkably in preventive acupuncture 12-month-old group. Compared to 14-month-old control group, plasma TC level and body weight growth rate decreased remarkably in preventive moxibustion 14-month-old group. Conclusions. Preventive acupuncture and moxibustion can significantly decrease the plasma TG and LDL, increase the plasma HDL, and prevent fat accumulation. Our finding suggests that preventive acupuncture and moxibustion have beneficial effects on blood lipid. Different treatment effects were found between preventive acupuncture and preventive moxibustion.
doi:10.1155/2014/621975
PMCID: PMC3930127  PMID: 24639882
6.  Autocrine CCL3 and CCL4 Induced by the Oncoprotein LMP1 Promote Epstein-Barr Virus-Triggered B Cell Proliferation 
Journal of Virology  2013;87(16):9041-9052.
Epstein-Barr virus (EBV) alters the regulation and expression of a variety of cytokines in its host cells to modulate host immune surveillance and facilitate viral persistence. Using cytokine antibody arrays, we found that, in addition to the cytokines reported previously, two chemotactic cytokines, CCL3 and CCL4, were induced in EBV-infected B cells and were expressed at high levels in all EBV-immortalized lymphoblastoid cell lines (LCLs). Furthermore, EBV latent membrane protein 1 (LMP1)-mediated Jun N-terminal protein kinase activation was responsible for upregulation of CCL3 and CCL4. Inhibition of CCL3 and CCL4 in LCLs using a short hairpin RNA approach or by neutralizing antibodies suppressed cell proliferation and caused apoptosis, indicating that autocrine CCL3 and CCL4 are required for LCL survival and growth. Importantly, significant amounts of CCL3 were detected in EBV-positive plasma from immunocompromised patients, suggesting that EBV modulates this chemokine in vivo. This study reveals the regulatory mechanism and a novel function of CCL3 and CCL4 in EBV-infected B cells. CCL3 might be useful as a therapeutic target in EBV-associated lymphoproliferative diseases and malignancies.
doi:10.1128/JVI.00541-13
PMCID: PMC3754032  PMID: 23760235
7.  Video-assisted thoracic surgery for lung carcinoma 
Journal of Thoracic Disease  2013;5(6):912-913.
doi:10.3978/j.issn.2072-1439.2013.12.20
PMCID: PMC3886878  PMID: 24416514
8.  Role of stress-inducible protein-1 in recruitment of bone marrow derived cells into the ischemic brains 
EMBO Molecular Medicine  2013;5(8):1227-1246.
Stress-inducible protein-1 (STI-1) is the proposed ligand for the cellular prion protein (PrPC), which is thought to facilitate recovery following stroke. Whether STI-1 expression is affected by stroke and how its signalling facilitates recovery remain elusive. Brain slices from patients that died of ischemic stroke were collected for STI-1 immunohistochemistry. These findings were compared to results from cell cultures, mice with or without the PrPC knockout, and rats. Based on these findings, molecular and pharmacological interventions were administered to investigate the underlying mechanisms and to test the possibility for therapy in experimental stroke models. STI-1 was upregulated in the ischemic brains from humans and rodents. The increase in STI-1 expression in vivo was not cell-type specific, as it was found in neurons, glia and endothelial cells. Likewise, this increase in STI-1 expression can be mimicked by sublethal hypoxia in primary cortical cultures (PCCs) in vitro, and appear to have resulted from the direct binding of the hypoxia inducible factor-1α (HIF-1α) to the STI-1 promoter. Importantly, this STI-1 signalling promoted bone marrow derived cells (BMDCs) proliferation and migration in vitro and recruitment to the ischemic brain in vivo, and augmenting its signalling facilitated neurological recovery in part by recruiting BMDCs to the ischemic brain. Our results thus identified a novel mechanism by which ischemic insults can trigger a self-protective mechanism to facilitate recovery.
This work identifies HIF-1α-mediated transcription of STI-1 and PrPc interaction as leading to BMDCs recruitment into ischemic brains following stroke in both patients and animal models of stroke, highlighting novel neuroprotective possibilities.
doi:10.1002/emmm.201202258
PMCID: PMC3944463  PMID: 23836498
bone marrow derived cells (BMDCs); cell trafficking; hypoxia inducible factor 1α (HIF-1α); stress inducible protein type 1 (STI-1); stroke
9.  A small core predatory genome in the divergent marine Bacteriovorax marinus SJ and the terrestrial Bdellovibrio bacteriovorus 
The ISME journal  2012;7(1):148-160.
Bacteriovorax marinus SJ is a predatory delta-proteobacterium isolated from a marine environment. The genome sequence of this strain provides an interesting contrast to that of the terrestrial predatory bacterium B. bacteriovorus HD100. Based on their predatory lifestyle, Bacteriovorax were originally designated members of the genus Bdellovibrio but subsequently were re-assigned to a new genus and family based on genetic and phenotypic differences. B. marinus attaches to Gram negative bacteria, attaches, penetrates through the cell wall to form a bdelloplast, in which it replicates, as shown using microscopy.
Bacteriovorax is distinct, since it shares only 30% of its gene products with its closest sequenced relatives. Remarkably, 34% of predicted genes over 500 nt in length were completely unique with no significant matches in the databases. As expected Bacteriovorax shares several characteristic loci with the other delta-proteobacteria.
A shared geneset Bacteriovorax and Bdellovibrio that is not conserved amongst other delta-proteobacteria such as Myxobacteria (which destroy prey bacteria externally via lysis), or the non-predatory Desulfo-bacteria and Geobacter species was identified. These 291 gene orthologues common to both Bacteriovorax and Bdellovibrio may be key indicators of predatory-specific processes required for prey entry. The hit locus from Bd. bacteriovorus is implicated in the switch from predatory to prey/host-independent (HI) growth. Although the locus is conserved in B. marinus, the sequence has only limited similarity. The results of this study advance understanding of both the similarities and differences between Bdellovibrio and Bacteriovorax and confirm the distant relationship between the two and their separation into different genera.
doi:10.1038/ismej.2012.90
PMCID: PMC3526173  PMID: 22955231
10.  Comparative transcriptome analysis of microsclerotia development in Nomuraea rileyi 
BMC Genomics  2013;14:411.
Background
Nomuraea rileyi is used as an environmental-friendly biopesticide. However, mass production and commercialization of this organism are limited due to its fastidious growth and sporulation requirements. When cultured in amended medium, we found that N. rileyi could produce microsclerotia bodies, replacing conidiophores as the infectious agent. However, little is known about the genes involved in microsclerotia development. In the present study, the transcriptomes were analyzed using next-generation sequencing technology to find the genes involved in microsclerotia development.
Results
A total of 4.69 Gb of clean nucleotides comprising 32,061 sequences was obtained, and 20,919 sequences were annotated (about 65%). Among the annotated sequences, only 5928 were annotated with 34 gene ontology (GO) functional categories, and 12,778 sequences were mapped to 165 pathways by searching against the Kyoto Encyclopedia of Genes and Genomes pathway (KEGG) database. Furthermore, we assessed the transcriptomic differences between cultures grown in minimal and amended medium. In total, 4808 sequences were found to be differentially expressed; 719 differentially expressed unigenes were assigned to 25 GO classes and 1888 differentially expressed unigenes were assigned to 161 KEGG pathways, including 25 enrichment pathways. Subsequently, we examined the up-regulation or uniquely expressed genes following amended medium treatment, which were also expressed on the enrichment pathway, and found that most of them participated in mediating oxidative stress homeostasis. To elucidate the role of oxidative stress in microsclerotia development, we analyzed the diversification of unigenes using quantitative reverse transcription-PCR (RT-qPCR).
Conclusion
Our findings suggest that oxidative stress occurs during microsclerotia development, along with a broad metabolic activity change. Our data provide the most comprehensive sequence resource available for the study of N. rileyi. We believe that the transcriptome datasets will serve as an important public information platform to accelerate studies on N. rileyi microsclerotia.
doi:10.1186/1471-2164-14-411
PMCID: PMC3698084  PMID: 23777366
Transcriptome; Oxidative Stress; Microsclerotia; Nomuraea Rileyi
11.  Deficits in the Mitochondrial Enzyme α-Ketoglutarate Dehydrogenase Lead to Alzheimer’s Disease-like Calcium Dysregulation 
Neurobiology of Aging  2011;33(6):1121.e13-1121.e24.
Understanding the molecular sequence of events that culminate in multiple abnormalities in brains from patients that died with Alzheimer’s Disease (AD) will help to reveal the mechanisms of the disease and identify upstream events as therapeutic targets. The activity of the mitochondrial α-ketoglutarate dehydrogenase complex (KGDHC) in homogenates from autopsy brain declines with AD. Experimental reductions in KGDHC in mouse models of AD promote plaque and tangle formation, the hallmark pathologies of AD. We hypothesize that deficits in KGDHC also lead to the abnormalities in endoplasmic reticulum (ER) calcium stores and cytosolic calcium following K+ -depolarization that occur in cells from AD patients and transgenic models of AD. The activity of the mitochondrial enzyme KGDHC was diminished acutely (minutes), long term (days) or chronically (weeks). Acute inhibition of KGDHC produced effects on calcium opposite to those in AD, while the chronic or long term inhibition of KGDHC mimicked the AD-related changes in calcium. Divergent changes in proteins released from the mitochondria that effect ER calcium channels may underlie the selective cellular consequences of acute versus longer term inhibition of KGDHC. The results suggest that the mitochondrial abnormalities in AD can be upstream of those in calcium.
doi:10.1016/j.neurobiolaging.2011.11.003
PMCID: PMC3321099  PMID: 22169199
Calcium; Endoplasmic reticulum; Mitochondria; Ketoglutarate dehydrogenase
12.  Galectin-3 regulates intracellular trafficking of epidermal growth factor receptor through Alix and promotes keratinocyte migration 
The epidermal growth factor receptor (EGFR)-mediated signaling pathways are important in a variety of cellular processes, including cell migration and wound re-epithelialization. Intracellular trafficking of EGFR is critical for maintaining EGFR surface expression. Galectin-3, a member of an animal lectin family, has been implicated in a number of physiological and pathological processes. Through studies of galectin-3-deficient mice and cells isolated from these mice, we demonstrated that absence of galectin-3 impairs keratinocyte migration and skin wound re-epithelialization. We have linked this pro-migratory function to a crucial role of cytosolic galectin-3 in controlling intracellular trafficking and cell surface expression of EGFR after EGF stimulation. Without galectin-3, the surface levels of EGFR are dramatically reduced and the receptor accumulates diffusely in the cytoplasm. This is associated with reduced rates of both endocytosis and recycling of the receptor. We have provided evidence that this novel function of galectin-3 may be mediated through interaction with its binding partner Alix, which is a protein component of the endosomal sorting complex required for transport (ESCRT) machinery. Our results suggest that galectin-3 is potentially a critical regulator of a number of important cellular responses through its intracellular control of trafficking of cell surface receptors.
doi:10.1038/jid.2012.211
PMCID: PMC3496033  PMID: 22785133
13.  A Novel Bat Algorithm Based on Differential Operator and Lévy Flights Trajectory 
Aiming at the phenomenon of slow convergence rate and low accuracy of bat algorithm, a novel bat algorithm based on differential operator and Lévy flights trajectory is proposed. In this paper, a differential operator is introduced to accelerate the convergence speed of proposed algorithm, which is similar to mutation strategy “DE/best/2” in differential algorithm. Lévy flights trajectory can ensure the diversity of the population against premature convergence and make the algorithm effectively jump out of local minima. 14 typical benchmark functions and an instance of nonlinear equations are tested; the simulation results not only show that the proposed algorithm is feasible and effective, but also demonstrate that this proposed algorithm has superior approximation capabilities in high-dimensional space.
doi:10.1155/2013/453812
PMCID: PMC3628216  PMID: 23606827
14.  Overexpression of Arabidopsis Dehydration-Responsive Element-Binding Protein 2C Confers Tolerance to Oxidative Stress 
Molecules and Cells  2012;33(2):135-140.
Dehydration-responsive element-binding proteins (DREBs) regulate plant responses to environmental stresses. In the current study, transcription of DREB2C, a class 2 Arabidopsis DREB, was induced by a superoxide anion propagator, methyl viologen (MV). The oxidative stress tolerance of DREB2C-overexpressing transgenic plants was significantly greater than that of wild-type plants, as measured by ion leakage and chlorophyll fluorescence under light conditions. The transcriptional activity of several ascorbate peroxidase (APX) genes as well as APX protein activity was induced in DREB2C overexpressors. Additionally, the level of H2O2 in the overexpressors was lower than in wt plants under similar oxidative stress conditions. An electrophoretic mobility shift assay and transient activator-reporter assay showed that APX2 expression was regulated by heat shock factor A3 (HsfA3) and that HsfA3 is regulated at the transcriptional level by DREB2C. These results suggest that DREB2C plays an important role in promoting oxidative stress tolerance in Arabidopsis.
doi:10.1007/s10059-012-2188-2
PMCID: PMC3887724  PMID: 22286229
gene expression; signaling; transcription factor; transgenic plant
15.  Transcriptome Exploration in Leymus chinensis under Saline-Alkaline Treatment Using 454 Pyrosequencing 
PLoS ONE  2013;8(1):e53632.
Background
Leymus chinensis (Trin.) Tzvel. is a high saline-alkaline tolerant forage grass genus of the tribe Gramineae family, which also plays an important role in protection of natural environment. To date, little is known about the saline-alkaline tolerance of L. chinensis on the molecular level. To better understand the molecular mechanism of saline-alkaline tolerance in L. chinensis, 454 pyrosequencing was used for the transcriptome study.
Results
We used Roche-454 massive parallel pyrosequencing technology to sequence two different cDNA libraries that were built from the two samples of control and under saline-alkaline treatment (optimal stress concentration-Hoagland solution with 100 mM NaCl and 200 mM NaHCO3). A total of 363,734 reads in control group and 526,267 reads in treatment group with an average length of 489 bp and 493 bp were obtained, respectively. The reads were assembled into 104,105 unigenes with MIRA sequence assemable software, among which, 73,665 unigenes were in control group, 88,016 unigenes in treatment group and 57,576 unigenes in both groups. According to the comparative expression analysis between the two groups with the threshold of “log2 Ratio ≥1”, there were 36,497 up-regulated unegenes and 18,218 down-regulated unigenes predicted to be the differentially expressed genes. After gene annotation and pathway enrichment analysis, most of them were involved in stress and tolerant function, signal transduction, energy production and conversion, and inorganic ion transport. Furthermore, 16 of these differentially expressed genes were selected for real-time PCR validation, and they were successfully confirmed with the results of 454 pyrosequencing.
Conclusions
This work is the first time to study the transcriptome of L. chinensis under saline-alkaline treatment based on the 454-FLX massively parallel DNA sequencing platform. It also deepened studies on molecular mechanisms of saline-alkaline in L. chinensis, and constituted a database for future studies.
doi:10.1371/journal.pone.0053632
PMCID: PMC3554714  PMID: 23365637
16.  Prunus pananensis (Rosaceae), a New Species from Pan'an of Central Zhejiang, China 
PLoS ONE  2013;8(1):e54030.
Prunus pananensis Z. L. Chen, W. J. Chen & X. F. Jin, a new species of Rosaceae from central Zhejiang, China is described and illustrated. Micromorphological characters of the indumentum on young shoots, leaves, petioles and peduncles, including scanning electron microscope [SEM] images, are provided. This new species is morphologically similar to P. schneiderianae Koehne in having its young shoots, petioles and pedicels all densely villose, but differs in having bracts persistent, styles glabrous, stipules 8–9 mm long, stamens 28–30 of per flower, and drupes glabrous. The new species is also similar to P. discoidea (Yü & C. L. Li) Yü & C. L. Li ex Z. Wei & Y. B. Chang in having 2 or 3 flowers in an umbellate inflorescence, and bracts persistent and marginally glandular, but it differs in having young shoots and petioles densely covered with yellowish-brown villose trichomes; leaves rounded or slightly cordate at base, the mid-ribs and lateral veins abaxially densely covered with yellowish-brown villose trichomes; and hypanthium ca. 3 mm long, shorter than sepals. The atpB-rbcL and trnL-F intergenic chloroplast spacers are selected for identification of the new and its similar species.
doi:10.1371/journal.pone.0054030
PMCID: PMC3548807  PMID: 23349780
17.  A small predatory core genome in the divergent marine Bacteriovorax marinus SJ and the terrestrial Bdellovibrio bacteriovorus 
The ISME Journal  2012;7(1):148-160.
Bacteriovorax marinus SJ is a predatory delta-proteobacterium isolated from a marine environment. The genome sequence of this strain provides an interesting contrast to that of the terrestrial predatory bacterium Bdellovibrio bacteriovorus HD100. Based on their predatory lifestyle, Bacteriovorax were originally designated as members of the genus Bdellovibrio but subsequently were re-assigned to a new genus and family based on genetic and phenotypic differences. B. marinus attaches to Gram-negative bacteria, penetrates through the cell wall to form a bdelloplast, in which it replicates, as shown using microscopy. Bacteriovorax is distinct, as it shares only 30% of its gene products with its closest sequenced relatives. Remarkably, 34% of predicted genes over 500 nt in length were completely unique with no significant matches in the databases. As expected, Bacteriovorax shares several characteristic loci with the other delta-proteobacteria. A geneset shared between Bacteriovorax and Bdellovibrio that is not conserved among other delta-proteobacteria such as Myxobacteria (which destroy prey bacteria externally via lysis), or the non-predatory Desulfo-bacteria and Geobacter species was identified. These 291 gene orthologues common to both Bacteriovorax and Bdellovibrio may be the key indicators of host-interaction predatory-specific processes required for prey entry. The locus from Bdellovibrio bacteriovorus is implicated in the switch from predatory to prey/host-independent growth. Although the locus is conserved in B. marinus, the sequence has only limited similarity. The results of this study advance understanding of both the similarities and differences between Bdellovibrio and Bacteriovorax and confirm the distant relationship between the two and their separation into different families.
doi:10.1038/ismej.2012.90
PMCID: PMC3526173  PMID: 22955231
Bacteriovorax; Bdellovibrio; genome sequence; BALO; subtractive hybridization; host-interaction locus
18.  Mesenteric Vascular Occlusion: Comparison of Ancillary CT Findings between Arterial and Venous Occlusions and Independent CT Findings Suggesting Life-Threatening Events 
Korean Journal of Radiology  2012;14(1):38-44.
Objective
To compare the ancillary CT findings between superior mesenteric artery thromboembolism (SMAT) and superior mesenteric vein thrombosis (SMVT), and to determine the independent CT findings of life-threatening mesenteric occlusion.
Materials and Methods
Our study was approved by the institution review board. We included 43 patients (21 SMAT and 22 SMVT between 1999 and 2008) of their median age of 60.0 years, and retrospectively analyzed their CT scans. Medical records were reviewed for demographics, management, surgical pathology diagnosis, and outcome. We compared CT findings between SMAT and SMVT groups. Multivariate analysis was conducted to determine the independent CT findings of life-threatening mesenteric occlusion.
Results
Of 43 patients, 24 had life-threatening mesenteric occlusion. Death related to mesenteric occlusion was 32.6%. A thick bowel wall (p < 0.001), mesenteric edema (p < 0.001), and ascites (p = 0.009) were more frequently associated with SMVT, whereas diminished bowel enhancement (p = 0.003) and paralytic ileus (p = 0.039) were more frequent in SMAT. Diminished bowel enhancement (OR = 20; p = 0.007) and paralytic ileus (OR = 16; p = 0.033) were independent findings suggesting life-threatening mesenteric occlusion.
Conclusion
The ancillary CT findings occur with different frequencies in SMAT and SMVT. However, the independent findings indicating life-threatening mesenteric occlusion are diminished bowel wall enhancement and paralytic ileus.
doi:10.3348/kjr.2013.14.1.38
PMCID: PMC3542301  PMID: 23323029
CT; Superior mesenteric artery thromboembolism; Superior mesenteric vein thrombosis; Life-threatening mesenteric occlusion; Independent finding
19.  Enteroenteroanastomosis near adjacent ileocecal valve in infants 
AIM: To investigate the feasibility and the effectiveness of ileoileostomy in the region adjacent to the ileocecal valve, which can retain the ileocecal valve in infants.
METHODS: This is a retrospective review of 48 patients who underwent ileoileostomy in the region adjacent to the ileocecal valve (group 1) and 34 patients who underwent ileocecal resections and ileotransversanastomosis (group 2). Patients were monitored for the time to flatus, resumption of eating, length of hospital stay after surgery, serum total bile acid, vitamin B12 and postoperative complications.
RESULTS: The time to flatus, time until resumption of eating and post-operative length of hospital stay showed no statistically significant differences between the two groups. Serum total bile acid and vitamin B12 were not significantly different between the two groups at post-operative day 1 and day 3, but were significantly decreased at 1 wk after operation in group 2. None of the patients died or suffered from stomal leak in these two groups. However, the incidence of diarrhea, intestinal infection, disturbance of acid-base balance and water-electrolytes in group 1 was lower than in group 2.
CONCLUSION: Ileoileostomy in the region adjacent to the ileocecal valve is safe and results in fewer complications than ileotransversanastomosis in infants.
doi:10.3748/wjg.v18.i48.7314
PMCID: PMC3544036  PMID: 23326139
Ileocecal valve; Ileoileostomy; Infants
20.  Engineered Nanostructures of Antigen Provide an Effective Means for Regulating Mast Cell Activation 
ACS nano  2011;5(11):8672-8683.
Nanostructures containing 2,4-Dinitrophenyl (DNP) as antigen were designed and produced to investigate antibody-mediated activation of mast cells. The design consists of nanogrids of DNP termini inlaid in alkanethiol self-assembled monolayers (SAMs). Using scanning probe-based nanografting, nanometer precision was attained for designed geometry, size and periodicity. Rat basophilic leukemia (RBL) cells exhibited high sensitivity to the geometry and local environment of DNP presented on these nanostructures. The impact included cellular adherence, spreading, membrane morphology, cytoskeleton structure, and activation. The highest level of spreading and activation was induced by nanogrids of 17 nm line width and 40 nm periodicity, with DNP haptens 1.4 nm above the surroundings. The high efficacy is attributed to two main factors. First, DNP sites in the nanostructure are highly accessible by anti-DNP-IgE during recognition. Second, the arrangement or geometry of DNP termini in nanostructures promotes clustering of FcεRI receptors that are pre-linked to IgE. The clustering effectively initiates Lyn-mediated signaling cascades, ultimately leading to the degranulation of RBL cells. This work demonstrates an important concept, that nanostructures of ligands provide new and effective cues for directing cellular signaling processes.
doi:10.1021/nn202510n
PMCID: PMC3228856  PMID: 21999491
atomic force microscopy; engineered nanostructures; self-assembled monolayers; mast cells; antibody-mediated activation; nanografting
21.  Galectin-3 and the Skin 
Galectin-3 is highly expressed in epithelial cells including keratinocytes and is involved in the pathogenesis of inflammatory skin diseases by affecting the functions of immune cells. For example, galectin-3 can contribute to atopic dermatitis (AD) by promoting polarization toward a Th2 immune response by regulating dendritic cell (DC) and T cell functions. In addition, galectin-3 may be involved in the development of contact hypersensitivity by regulating the migratory capacity of antigen presenting cells. Galectin-3 may act as a regulator of epithelial tumor progression and development through various signaling pathways, such as inhibiting keratinocyte apoptosis through regulation of the activation status of extracellular signal-regulated kinase (ERK) and activated protein kinase B (AKT). Galectin-3 is detected at different stages of melanoma development. In contrast, a marked decrease in the expression of galectin-3 is observed in non-melanoma skin cancers, such as squamous cell carcinoma (SCC) and basal cell carcinoma (BCC). Galectin-3 may play an important role in tumor cell growth, apoptosis, cell motility, invasion, and metastasis. Galectin-3 may be a novel therapeutic target for a variety of skin diseases.
doi:10.1016/j.jdermsci.2011.07.008
PMCID: PMC3192432  PMID: 21889881
22.  Synchronous right hepatectomy and cesarean section in a pregnant lady with hepatocellular carcinoma 
INTRODUCTION
Cancer in pregnancy is rare and hepatocellular carcinoma (HCC) during pregnancy is even rarer. Due to limited experience, management of these patients remains challenging.
PRESENTATION OF CASE
A 33-year old pregnant lady presented with HCC at 28 weeks of gestation. She underwent synchronous cesarean section and right hepatectomy at 32 weeks of gestation. The post-operative course was uneventful. She was discharged home on day 10 after surgery. Histolopathology confirmed HCC. The surgical resection margins were clear. At a follow-up of 3 months after surgery, the mother was disease free and the infant was well.
DISCUSSION
HCC during pregnancy is extremely rare. The experience in its management and outcomes are lacking. In managing any patient diagnosed with a malignant neoplasm in pregnancy, both the mother and the fetus have to be considered.
CONCLUSION
With adequate preoperative assessment and a good management strategy, good results can be obtained for both the mother and the baby for a pregnant patient with HCC.
doi:10.1016/j.ijscr.2012.10.014
PMCID: PMC3537950  PMID: 23159911
Hepatocellular carcinoma; Hepatectomy; Pregnancy; Cesarean section
23.  Cardiovascular determinants of prognosis in normotensive hemodialysis patients 
BMC Nephrology  2012;13:115.
Background
Normotension has been hold to be the goal of hemodialysis. It remains obscure which cardiovascular parameter determines the prognosis in these normotensive hemodialysis patients.
Methods
We prospectively enrolled 145 hemodialysis patients, who had attained normotension without anti-hypertensive medications, and followed them for 72.6 ± 28.5 months. Important cardiovascular parameters were obtained at enrollment. Predictors for all-cause and cardiovascular mortalities were identified with the Cox model.
Results
There were 45 (18 cardiovascular/27 non-cardiovascular) deaths occurred during follow-up. Age, diabetes, left ventricular mass index (LVMI), left ventricular ejection fraction (LVEF), carotid intima-media thickness (CIMT), and aortic pulse wave velocity (PWV) were significant predictors for all-cause and cardiovascular mortalities. After adjustment for age and diabetes, only LVEF was significantly associated with all-cause mortality. LVEF was significantly associated with cardiovascular mortality. LVEF remained as a significant independent predictor of cardiovascular death after adjusting for age, diabetes, LVMI, CIMT, or PWV, respectively.
Conclusion
LVEF is the independent predictor for all-cause and cardiovascular mortalities in the normotensive hemodialysis patients.
doi:10.1186/1471-2369-13-115
PMCID: PMC3504582  PMID: 22994452
Arterial stiffness; End-stage renal disease; Hypertension; Left ventricular function; Mortality
24.  A Micromechanics Finite-Strain Constitutive Model of Fibrous Tissue 
Biological tissues have unique mechanical properties due to the wavy fibrous collagen and elastin microstructure. In inflation, a vessel easily distends under low pressure but becomes stiffer when the fibers are straightened to take up the load. The current microstructural models of blood vessels assume affine deformation; i.e., the deformation of each fiber is assumed to be identical to the macroscopic deformation of the tissue. This uniform-field (UF) assumption leads to the macroscopic (or effective) strain energy of the tissue that is the volumetric sum of the contributions of the tissue components. Here, a micromechanics-based constitutive model of fibrous tissue is developed to remove the affine assumption and to take into consideration the heterogeneous interactions between the fibers and the ground substance. The development is based on the framework of a recently developed second-order homogenization theory, and takes into account the waviness, orientations, and spatial distribution of the fibers, as well as the material nonlinearity at finite-strain deformation. In an illustrative simulation, the predictions of the macroscopic stress-strain relation, and the statistical deformation of the fibers are compared to the UF model, as well as finite-element (FE) simulation. Our predictions agree well with the FE results, while the UF predictions significantly overestimate. The effects of fiber distribution and waviness on the macroscopic stress-strain relation are also investigated. The present mathematical model may serves as a foundation for native as well as for engineered tissues and biomaterials.
doi:10.1016/j.jmps.2011.05.012
PMCID: PMC3171755  PMID: 21927506
Tissue; Fibers; Collagen; Microstructure; Vessel
25.  Prey bacteria shape the community structure of their predators 
The ISME Journal  2011;5(8):1314-1322.
Although predator–prey interactions among higher organisms have been studied extensively, only few examples are known for microbes other than protists and viruses. Among the bacteria, the most studied obligate predators are the Bdellovibrio and like organisms (BALOs) that prey on many other bacteria. In the macroscopical world, both predator and prey influence the population size of the other's community, and may have a role in selection. However, selective pressures among prey and predatory bacteria have been rarely investigated. In this study, Bacteriovorax, a predator within the group of BALOs, in environmental waters were fed two prey bacteria, Vibrio vulnificus and Vibrio parahaemolyticus. The two prey species yielded distinct Bacteriovorax populations, evidence that selective pressures shaped the predator community and diversity. The results of laboratory experiments confirmed the differential predation of Bacteriovorax phylotypes on the two bacteria species. Not only did Bacteriovorax Cluster IX exhibit the versatility to be the exclusive efficient predator on Vibrio vulnificus, thereby, behaving as a specialist, but was also able to prey with similar efficiency on Vibrio parahaemolyticus, indicative of a generalist. Therefore, we proposed a designation of versatilist for this predator. This initiative should provide a basis for further efforts to characterize the predatory patterns of bacterial predators. The results of this study have revealed impacts of the prey on Bacteriovorax predation and in structuring the predator community, and advanced understanding of predation behavior in the microbial world.
doi:10.1038/ismej.2011.4
PMCID: PMC3146273  PMID: 21326335
Bdellovibrio and like organisms (BALOs); predator–prey interaction; Vibrio spp.; Bacteriovorax; microbial community structure

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