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1.  Transcatheter arterial embolization with trisacryl gelatin microspheres (Embosphere®) leads to life-threatening tumor lysis syndrome in a rectal carcinoid patient with hepatic metastases 
Acta Radiologica Short Reports  2012;1(10):arsr.2012.110011.
The incidence of gastrointestinal carcinoids appears to be increasing, and the rectum is the third most common location. Transcatheter arterial embolization (TAE) with trisacryl gelatin microspheres (Embosphere®) has been reported as an effective method for hepatic metastases of rectal carcinoids. Complications are uncommon and usually of minor consequence. We report an unusual case of a 34-year-old man with tumor lysis syndrome following TAE with Embosphere® in a patient with multiple hepatic metastases of a rectal carcinoid. Early detection and effective treatment are essential for this rare but potentially catastrophic complication.
PMCID: PMC3738337  PMID: 23986828
Transcatheter arterial embolization; tumor lysis syndrome; trisacryl gelatin microspheres; rectal carcinoid tumors
2.  The Waveform Fluctuation and the Clinical Factors of the Initial and Sustained Erythropoietic Response to Continuous Erythropoietin Receptor Activator in Hemodialysis Patients 
The Scientific World Journal  2012;2012:157437.
Objectives. Erythropoiesis-stimulating agents (ESA) are the main treatment for anemia in hemodialysis (HD) patients. We evaluated factors determining the response after treatment of a new ESA (continuous erythropoietin erythropoietin receptor activator (CERA)). Methods. 61 HD patients were classified by their response at two different timings. First, patients whose hematocrit (Hct) increased 1.5% in the first week were defined as initial responders (IR, n = 16). We compared several parameters between IR and the rest of the study subjects (non-IR, n = 45). Second, patients whose Hct increased 2% in the 4th week were defined as sustained responders (SR, n = 12), and we did a similar comparison. Results. The Hct showed a waveform fluctuation. Compared with the rest, IR had significantly lower platelet counts and higher levels of ferritin, total protein, total bilirubin, and serum sodium, while SR had significantly lower levels of C-reactive protein and low-density lipoprotein (All P < 0.05). In comparison with the rest, higher Hct persisted for 10 weeks in SR but only for two separate weeks (the 1st and 7th week) in IR. Conclusions. The initial and sustained erythropoietic responses are independent from each other and are associated with different factors. Treatment focusing on these factors may improve the response.
PMCID: PMC3349104  PMID: 22619601
3.  Sequence Variants of ADIPOQ and Association with Type 2 Diabetes Mellitus in Taiwan Chinese Han Population 
The Scientific World Journal  2014;2014:650393.
Diabetes is a serious global health problem. Large-scale genome-wide association studies identified loci for type 2 diabetes mellitus (T2DM), including adiponectin (ADIPOQ) gene and transcription factor 7-like 2 (TCF7L2), but few studies clarified the effect of genetic polymorphisms of ADIPOQ and TCF7L2 on risk of T2DM. We attempted to elucidate association between T2DM and polymorphic variations of both in Taiwan's Chinese Han population, with our retrospective case-control study genotyping single nucleotide polymorphisms (SNPs) in ADIPOQ and TCF7L2 genes both in 149 T2DM patients and in 139 healthy controls from Taiwan. Statistical analysis gauged association of these polymorphisms with risk of T2DM to show ADIPOQ rs1501299 polymorphism variations strongly correlated with T2DM risk (P = 0.042), with rs2241766 polymorphism being not associated with T2DM (P = 0.967). However, both polymorphisms rs7903146 and rs12255372 of TCF7L2 were rarely detected in Taiwanese people. This study avers that ADIPOQ rs1501299 polymorphism contributes to risk of T2DM in the Taiwanese population.
PMCID: PMC4121223  PMID: 25121131
4.  Chronic Exposure to Rhodobacter Sphaeroides Extract Lycogen™ Prevents UVA-Induced Malondialdehyde Accumulation and Procollagen I Down-Regulation in Human Dermal Fibroblasts 
UVA contributes to the pathogenesis of skin aging by downregulation of procollagen I content and induction of matrix metalloproteinase (MMP)-associated responses. Application of antioxidants such as lycopene has been demonstrated as a convenient way to achieve protection against skin aging. Lycogen™, derived from the extracts of Rhodobacter sphaeroides, exerts several biological effects similar to that of lycopene whereas most of its anti-aging efficacy remains uncertain. In this study, we attempted to examine whether Lycogen™ could suppress malondialdehyde (MDA) accumulation and restore downregulated procollagen I expression induced by UVA exposure. In human dermal fibroblasts Hs68 cells, UVA repressed cell viability and decreased procollagen I protein content accompanied with the induction of MMP-1 and MDA accumulation. Remarkably, incubation with 50 μM Lycogen™ for 24 h ameliorated UVA-induced cell death and restored UVA-induced downregulation of procollagen in a dose-related manner. Lycogen™ treatment also prevented the UVA-induced MMP-1 upregulation and intracellular MDA generation in Hs68 cells. Activation of NFκB levels, one of the downstream events induced by UVA irradiation and MMP-1 induction, were also prevented by Lycogen™ administration. Taken together, our findings demonstrate that Lycogen™ may be an alternative agent that prevents UVA-induced skin aging and could be used in cosmetic and pharmaceutical applications.
PMCID: PMC3958816  PMID: 24463291
Lycogen™; skin aging; UVA; procollagen I; matrix metalloproteinase
5.  A Large Cohort Study Reveals the Association of Elevated Peripheral Blood Lymphocyte-to-Monocyte Ratio with Favorable Prognosis in Nasopharyngeal Carcinoma 
PLoS ONE  2013;8(12):e83069.
Nasopharyngeal carcinoma (NPC) is an endemic neoplasm in southern China. Although NPC sufferers are sensitive to radiotherapy, 20–30% of patients finally progress with recurrence and metastases. Elevated lymphocyte-to-monocyte ratio (LMR) has been reported to be associated with favorable prognosis in some hematology malignancies, but has not been studied in NPC. The aim of this study was to evaluate whether LMR could predict the prognosis of NPC patients.
A retrospective cohort of 1,547 non-metastatic NPC patients was recruited between January 2005 and June 2008. The counts for peripheral lymphocyte and monocyte were retrieved, and the LMR was calculated. Receiver operating characteristic curve analysis, univariate and multivariate COX proportional hazards analyses were applied to evaluate the associations of LMR with overall survival (OS), disease-free survival (DFS), distant metastasis-free survival (DMFS) and loco-regional recurrence-free survival (LRRFS), respectively.
Univariate analysis revealed that higher LMR level (≥5.220) was significantly associated with superior OS, DFS and DMFS (P values <0.001). The higher lymphocyte count (≥2.145×109/L) was significantly associated with better OS (P = 0.002) and DMFS (P = 0.031), respectively, while the lower monocyte count (<0.475×109/L) was associated with better OS (P = 0.012), DFS (P = 0.011) and DMFS (P = 0.003), respectively. Multivariate Cox proportional hazard analysis showed that higher LMR level was a significantly independent predictor for superior OS (hazard ratio or HR  = 0.558, 95% confidence interval or 95% CI  = 0.417–0.748; P<0.001), DFS (HR  = 0.669, 95% CI  = 0.535–0.838; P<0.001) and DMFS (HR = 0.543, 95% CI  = 0.403–0.732; P<0.001), respectively. The advanced T and N stages were also independent indicators for worse OS, DFS, and DMFS, except that T stage showed borderline statistical significance for DFS (P = 0.053) and DMFS (P = 0.080).
The elevated pretreatment peripheral LMR level was a significant favorable factor for NPC prognosis and this easily accessed variable may serve as a potent marker to predict the outcomes of NPC patients.
PMCID: PMC3873908  PMID: 24386144
6.  An Extract of Rhodobacter sphaeroides Reduces Cisplatin-Induced Nephrotoxicity in Mice 
Toxins  2013;5(12):2353-2365.
Cisplatin is used as a treatment for various types of solid tumors. Renal injury severely limits the use of cisplatin. Renal cell apoptosis, oxidative stress, and inflammation contribute to cisplatin-induced nephrotoxicity. Previously, we found that an extract of Rhodobacter sphaeroides (Lycogen™) inhibited proinflammatory cytokines and the production of nitric oxide in activated macrophages in a dextran sodium sulfate (DSS)-induced colitis model. Here, we evaluated the effect of Lycogen™, a potent anti-inflammatory agent, in mice with cisplatin-induced renal injury. We found that attenuated renal injury correlated with decreased apoptosis due to a reduction in caspase-3 expression in renal cells. Oral administration of Lycogen™ significantly reduced the expression of tumor necrosis factor-α and interleukin-1β in mice with renal injury. Lycogen™ reduces renal dysfunction in mice with cisplatin-induced renal injury. The protective effects of the treatment included blockage of the cisplatin-induced elevation in serum urea nitrogen and creatinine. Meanwhile, Lycogen™ attenuated body weight loss and significantly prolonged the survival of mice with renal injury. We propose that Lycogen™ exerts anti-inflammatory activities that represent a promising strategy for the treatment of cisplatin-induced renal injury.
PMCID: PMC3873690  PMID: 24335753
Rhodobacter sphaeroides; Lycogen™; cisplatin; nephrotoxicity
7.  Association of intercellular adhesion molecular-1 gene polymorphism in ischemic stroke patients 
Ischemic stroke (IS) is a prevalent disease causing a body disability, the third leading cause of death in Taiwan. It shows that the level of intercellular adhesion molecular-1 (ICAM-1) in IS patients is higher than control subjects.
This study is to investigate the possible association of ICAM-1 (G1548A) polymorphism in IS patients.
Materials and Methods:
A total of 646 subjects were enrolled in this study, including 312 IS patients, and 334 controls without a history of symptomatic IS. The ICAM-1 (G1548A) polymorphism was analyzed by polymerase chain reaction and restriction fragment length polymorphism. Clinical factors were also determined.
The frequencies of the ICAM-1 (G1548A) polymorphism for G/G, G/A, and A/A were 74.8%, 23.9%, and 0.3%, respectively, in healthy controls, and 62.8%, 32.1%, and 5.1%, respectively, in patients. The frequency of the ICAM-1 (G1548A) A allele (21.2% versus 13.2%, respectively; P = 0.007) and the carriers of the ICAM-1 (G1548A) A allele (37.2% versus 25.2%; P = 0.019, OR 1.76, 95% CI 1.1-2.83) are great in IS patients compared with healthy controls. There is a higher risk of IS associated with homozygosity for the ICAM-1 (G1548A) A allele (AA genotype) compared with the control population (5.1% vs. 0.3%, respectively, P = 0.04; OR 5.1, 95% CI 1.19-21.66). We also observed both hypertension and diabetes has shown a positive association with IS.
The ICAM-1 (G1548A) polymorphism was associated with independent risk factor for the development of IS.
PMCID: PMC3788285  PMID: 24101821
Allele; intercellular adhesion molecular-1; ischemic stroke; polymorphism
8.  The Extract of Rhodobacter sphaeroides Inhibits Melanogenesis through the MEK/ERK Signaling Pathway 
Marine Drugs  2013;11(6):1899-1908.
Reducing hyperpigmentation has been a big issue for years. Even though pigmentation is a normal mechanism protecting skin from UV-causing DNA damage and oxidative stress, it is still an aesthetic problem for many people. Bacteria can produce some compounds in response to their environment. These compounds are widely used in cosmetic and pharmaceutical applications. Some probiotics have immunomodulatory activities and modulate the symptoms of several diseases. Previously, we found that the extracts of Rhodobacter sphaeroides (Lycogen™) inhibited nitric oxide production and inducible nitric-oxide synthase expression in activated macrophages. In this study, we sought to investigate an anti-melanogenic signaling pathway in α-melanocyte stimulating hormone (α-MSH)-treated B16F10 melanoma cells and zebrafish. Treatment with Lycogen™ inhibited the cellular melanin contents and expression of melanogenesis-related protein, including microphthalmia-associated transcription factor (MITF) and tyrosinase in B16F10 cells. Moreover, Lycogen™ reduced phosphorylation of MEK/ERK without affecting phosphorylation of p38. Meanwhile, Lycogen™ decreased zebrafish melanin expression in a dose-dependent manner. These findings establish Lycogen™ as a new target in melanogenesis and suggest a mechanism of action through the ERK signaling pathway. Our results suggested that Lycogen™ may have potential cosmetic usage in the future.
PMCID: PMC3721212  PMID: 23736765
Rhodobacter sphaeroides; Lycogen™; melanogenesis
9.  Effect of add-on direct renin inhibitor aliskiren in patients with non-diabetes related chronic kidney disease 
BMC Nephrology  2012;13:89.
The renin-angiotensin-aldosterone system (RAAS) plays an important role in the progression of chronic kidney disease (CKD). Although dual RAAS inhibition results in worse renal outcomes than monotherapy in high risk type 2 diabetes patients, the effect of dual RAAS inhibition in patients with non-DM CKD is unclear. The aim of this study was to evaluate the potential renoprotective effect of add-on direct renin inhibitor in non-DM CKD patients.
We retrospectively enrolled 189 non-DM CKD patients who had been taking angiotensin II receptor blockers (ARBs) for more than six months. Patients were divided into an add-on aliskiren group and an ARB monotherapy group. The primary outcomes were a decline in glomerular filtration rate (GFR) and a reduction in urinary protein-to-creatinine ratio at six months.
The baseline characteristics of the two groups were similar. Aliskiren 150 mg daily reduced the urinary protein-to-creatinine ratio by 26% (95% confidence interval, 15 to 37%; p < 0.001). The decline in GFR was smaller in the add-on aliskiren group (−2.1 vs. -4.0 ml/min, p = 0.038). Add-on aliskiren had a neutral effect on serum potassium in the non-DM CKD patients. In subgroup analysis, the proteinuria-reducing effect of aliskiren was more prominent in patients with a GFR less than 60 ml/min, and in patients with a urinary protein-to-creatinine ratio greater than 1.8. The effect of aliskiren in retarding the decline in GFR was more prominent in patients with hypertensive nephropathy than in those with glomerulonephritis.
Add-on direct renin inhibitor aliskiren (150 mg daily) safely reduced proteinuria and attenuated the decline in GFR in the non-DM CKD patients who were receiving ARBs.
PMCID: PMC3509390  PMID: 22917002
Aliskiren; Direct renin inhibitor; Proteinuria; CKD
10.  Severe Proteinuria Secondary to Amyloidosis Requiring Bilateral Renal Artery Embolization 
In the case reported here, after prolonged medical therapy resistance, severe proteinuria subsided following bilateral renal artery embolization (RAE). Thereafter, respiratory distress, anasarca edema, muscle mass, and serum albumin level improved after regular hemodialysis. Although RAE is reported to be a safe and effective therapeutic procedure, it is rarely used for severe proteinuria with prolonged medical therapy resistance. The limited use of bilateral RAE for nephrological purposes may be partly related to its tendency to destroy renal function, which results in anuria and subsequent regular dialysis. However, delayed RAE could cause the patient to reach a life-threatening cachexic state and could increase the risk of morbidity and mortality due to severe proteinuria-induced hypoalbuminemia. Our case and selected previous reports reveal important information for physicians and patients while discussing prognoses and considering the pros and cons of bilateral RAE.
PMCID: PMC3482077  PMID: 23197960
Amyloidosis; Chronic kidney disease; Proteinuria; Renal artery embolization
11.  Interleukin-1 receptor antagonist gene polymorphism in patients with multidrug-resistant Acinetobacter baumannii-associated pneumonia 
Annals of Thoracic Medicine  2012;7(2):74-77.
Multidrug-resistant Acinetobacter baumannii (MDRAB)-associated pneumonia has been a common disease and a therapeutic problem in hospitals. Interleukin-1 receptor antagonist (IL-1ra) has been considered a required role for host immune defense in pneumonia disease. The aim of this study was to investigate whether the variable nucleotide tandem repeat polymorphism of the IL-1ra gene was associated with MDRAB-related pneumonia.
Sixty-six pneumonia patients were enrolled in the study: 36 subjects had MDRAB-related pneumonia and 30 controls had non-MDRAB pneumonia. Polymerase chain reaction, restriction fragment length polymorphism, and agarose gel electrophoresis techniques were used to determine the IL-1ra genotype.
The frequencies of the IL-1ra genotype in the MDRAB-related pneumonia cases were A1/A1, 0.889 and A1/A2, 0.111; the frequencies of the IL-1ra genotype in the controls were A1/A1, 0.333 and A1/A2, 0.667. A statistically significant difference was determined (P < 0.05). We also observed an increase in the frequency of IL-1ra A1 allele in the MDRAB-related pneumonia group. A statistically significant difference was determined (P<0.05).
We suggested that IL-1ra polymorphism was associated with the risk of MDRAB-related pneumonia.
PMCID: PMC3339207  PMID: 22558011
Acinetobacter baumannii; IL-1ra; pneumonia; polymorphism
12.  Ankle-Brachial Index Is a Powerful Predictor of Renal Outcome and Cardiovascular Events in Patients with Chronic Kidney Disease 
The Scientific World Journal  2012;2012:238494.
Ankle-brachial index (ABI) is an accurate tool to diagnose peripheral arterial disease. The aim of this study was to evaluate whether ABI is also a good predictor of renal outcome and cardiovascular events in patients with chronic kidney disease (CKD). We enrolled 436 patients with stage 3–5 CKD who had not been undergoing dialysis. Patients were stratified into two groups according to the ABI value with a cut point of 0.9. The composite renal outcome, including doubling of serum creatinine level and commencement of dialysis, and the incidence of cardiovascular events were compared between the two groups. After a median follow-up period of 13 months, the lower ABI group had a poorer composite renal outcome (OR = 2.719, P = 0.015) and a higher incidence of cardiovascular events (OR = 3.260, P = 0.001). Our findings illustrated that ABI is a powerful predictor of cardiovascular events and renal outcome in patients with CKD.
PMCID: PMC3259574  PMID: 22272169
13.  Sequencing of DC-SIGN promoter indicates an association between promoter variation and risk of nasopharyngeal carcinoma in cantonese 
BMC Medical Genetics  2010;11:161.
The dendritic cell-specific intercellular adhesion molecule 3 grabbing non-integrin (DC-SIGN) is an important pathogen recognition receptor of the innate immune system. DC-SIGN promoter variants play important role in the susceptibility to various infectious diseases. Nasopharyngeal carcinoma (NPC) is a malignancy that is common in southern China and whether DC-SIGN promoter variants have effects on susceptibility to NPC is still unknown. The aim of this study is to ascertain the potential involvement of DC-SIGN promoter single nucleotide polymorphisms (SNPs) in NPC susceptibility.
We conducted a case control study based on Cantonese population including 444 NPC patients and 464 controls matched on age and sex. The 1041 bp of DC-SIGN promoter region was directly sequenced for all samples. Sequence alignment and SNP search were inspected using DNAStar analysis programs and haplotype frequencies were estimated in Haploview V 4.0. The associations between the SNPs and the risk of NPC were analyzed using chi-square test and non-conditional logistic regression analysis with SPSS 13.0 software.
A total of six variants were observed in the DC-SIGN promoter region and DC-SIGN -139 GG and -939 AA were significantly associated with NPC risk with adjusted Odds Ratios (ORs) of 2.10 (95% confidence interval [CI] = 1.23-3.59; P = 0.006) and 2.52 (1.29-4.93; P = 0.007) respectively and subjects carrying the risk allele DC-SIGN -871 G had 1.47-fold (95% CI = 1.14-1.90) increased risks of developing NPC (P = 0.003). Haplotype analysis revealed that h1 'AAAG' was significantly associated with protection against NPC (OR = 0.69; P = 0.0002) and the association was still significant when using 1000 permutation test runs (P = 0.001).
Our study indicated that DC-SIGN promoter variants appear to be involved in the susceptibility to NPC and the detailed mechanism of this effect need further studies.
PMCID: PMC2989958  PMID: 21067616
14.  Traditional Cantonese diet and nasopharyngeal carcinoma risk: a large-scale case-control study in Guangdong, China 
BMC Cancer  2010;10:446.
Nasopharyngeal carcinoma (NPC) is rare in most parts of the world but is a common malignancy in southern China, especially in Guangdong. Dietary habit is regarded as an important modifier of NPC risk in several endemic areas and may partially explain the geographic distribution of NPC incidence. In China, rapid economic development during the past few decades has changed the predominant lifestyle and dietary habits of the Chinese considerably, requiring a reassessment of diet and its potential influence on NPC risk in this NPC-endemic area.
To evaluate the association between dietary factors and NPC risk in Guangdong, China, a large-scale, hospital-based case-control study was conducted. 1387 eligible cases and 1459 frequency matched controls were recruited. Odds ratios (ORs) and the corresponding 95% confidence intervals (CIs) were estimated using a logistic regression model, adjusting for age, sex, education, dialect, and habitation household type.
Observations made include the following: 1) consumption of canton-style salted fish, preserved vegetables and preserved/cured meat were significantly associated with increased risk of NPC, with enhanced odds ratios (OR) of 2.45 (95% CI: 2.03-2.94), 3.17(95% CI: 2.68-3.77) and 2.09 (95% CI: 1.22-3.60) respectively in the highest intake frequency stratum during childhood; 2) consumption of fresh fruit was associated with reduced risk with a dose-dependent relationship (p = 0.001); and 3) consumption of Canton-style herbal tea and herbal slow-cooked soup was associated with decreased risk, with ORs of 0.84 (95% CI: 0.68-1.03) and 0.58 (95% CI: 0.47-0.72) respectively in the highest intake frequency stratum. In multivariate analyses, these associations remained significant.
It can be inferred that previously established dietary risk factors in the Cantonese population are still stable and have contributed to the incidence of NPC.
PMCID: PMC2931495  PMID: 20727127
15.  Large Clones on Cliff Faces: Expanding by Rhizomes through Crevices 
Annals of Botany  2007;100(1):51-54.
Background and Aims
Large clones of rhizomatous plants are found in many habitats, but little is known about whether such clones also occur on cliff faces where environmental conditions are extremely harsh and heterogeneous.
Using molecular (intersimple sequence repeat, ISSR) markers, the genotypic composition of a cliff-face population of Oxyria sinensis in Sichuan, China, was investigated.
Key Results
The 98 O. sinensis ramets sampled belonged to 12 different genotypes (clones). The three most frequent clones were represented with 45, 22 and 12 ramets, respectively; the remaining nine were represented with only one to five ramets. The three largest clones spanned at least 2·7 m in the vertical direction and 4·6–6·9 m in the horizontal direction on the cliff face.
On the cliff face, large clones of O. sinensis are formed by rhizomes growing along the crevices. Expansion by rhizomes may help O. sinensis to exploit the patchy resources and support establishment and growth of new ramets. Moreover, rooted ramets connected by rhizomes may effectively reduce the susceptibility of O. sinensis to rock fall and erosion and thus greatly improve the chances for long-term survival. The multi-clone structure indicates that sexual reproduction is also important for the long-term persistence of O. sinensis populations on cliffs.
PMCID: PMC2735296  PMID: 17525100
Cliff ecology; clonal diversity; clonal growth; genet distribution; Oxyria sinensis; rhizomatous plants

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