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1.  Intracardiac leiomyomatosis: a comprehensive analysis of 194 cases 
Intracardiac leiomyomatosis is rare but has been increasingly reported in recent years. Owing to its rarity, intracardiac leiomyomatosis has been reported only as isolated case reports and case series. This disorder is thought to be underestimated and easily overlooked in the clinic, while it is dangerous owing to the risk of sudden death caused by total outflow tract obstruction. We performed an electronic literature search for intracardiac leiomyomatosis and identified 194 cases that were reported in English from 1974 (the first reported case) to September 2012. Our aim is to provide a detailed and comprehensive review of the clinical presentation, diagnosis, histopathological characterization, treatment and prognosis of this disorder. According to our analysis, intracardiac leiomyomatosis is most common in the fifth decade, and the mean age of detection is ∼50 years. Most patients had undergone previous hysterectomy/myomectomy or had a coexisting uterine leiomyoma when admitted. The most common clinical presentations were dyspnoea, syncope, oedema of the lower extremities and palpitation. Transoesophageal echocardiography, computed tomography and magnetic resonance imaging are helpful in the preoperative diagnosis and to guide the surgical management. Complete removal guarantees an excellent outcome, with no recurrence or postoperative death, while incomplete removal leads to recurrence in one-third of patients. Anti-oestrogen therapy is not imperative after incomplete removal owing to its inability to prevent recurrence.
doi:10.1093/icvts/ivt117
PMCID: PMC3686387  PMID: 23563052
Intracardiac leiomyomatosis; Secondary cardiac tumours; Metastasectomy
2.  A genome wide association study of plasma uric acid levels in obese cases and never-overweight controls 
Obesity (Silver Spring, Md.)  2013;21(9):E490-E494.
Objective
To identify plasma uric acid related genes in extremely obese and normal weight individuals using genome wide association studies (GWAS).
Design and Methods
Using genotypes from a GWAS focusing on obesity and thinness, we performed quantitative trait association analyses (PLINK) for plasma uric acid levels in 1,060 extremely obese individuals [body mass index (BMI) >35 kg/m2] and normal-weight controls (BMI<25kg/m2). In 961 samples with uric acid data, 924 were females.
Results
Significant associations were found in SLC2A9 gene SNPs and plasma uric acid levels (rs6449213, P=3.15×10−12). DIP2C gene SNP rs877282 also reached genome wide significance(P=4,56×10−8). Weaker associations (P<1×10−5) were found in F5, PXDNL, FRAS1, LCORL, and MICAL2genes. Besides SLC2A9, 3 previously identified uric acid related genes ABCG2 (rs2622605, P=0.0026), SLC17A1 (rs3799344, P=0.0017), and RREB1 (rs1615495, P =0.00055) received marginal support in our study.
Conclusions
Two genes/chromosome regions reached genome wide association significance (P< 1× 10−7, 550K SNPs) in our GWAS : SLC2A9, the chromosome 2 60.1 Mb region (rs6723995), and the DIP2C gene region. Five other genes (F5, PXDNL, FRAS1, LCORL, and MICAL2) yielded P<1× 10−5. Four previous reported associations were replicated in our study, including SLC2A9, ABCG2, RREB, and SLC17A1.
doi:10.1002/oby.20303
PMCID: PMC3762924  PMID: 23703922
uric acid; genome wide association study; obesity
3.  Surveillance of Intra-Abdominal Pressure and Intestinal Barrier Function in a Rat Model of Acute Necrotizing Pancreatitis and Its Potential Early Therapeutic Window 
PLoS ONE  2013;8(11):e78975.
Objectives
To monitor intra-abdominal pressure (IAP) and intestinal barrier function in a rat model of acute necrotizing pancreatitis (ANP) to elucidate a potential relevant therapeutic window.
Methods
Sprague-Dawley rats were randomly divided into experimental or control groups. The ANP group (n = 40) was injected with 4.5% sodium taurocholate into the pancreatic duct to induce ANP. The controls received only abdominal opening surgery (sham-operated, SO; n = 40) or no treatment or surgery (baseline; 0 h, n = 20). The SO and ANP groups were then randomly subdivided into 3, 6, 12 and 24 h groups (n = 10 each). IAP was measured at each time point and the rats were sacrificed to measure the weight of accumulated ascites fluid and the amylase, endogenous creatinine (Cr), total bilirubin (TB), tumor necrosis factor- alpha (TNF-alpha), diamine oxidase (DAO), and D-lactate. Mortality and the development of pathological changes in the pancreas and intestines were also monitored.
Results
IAP showed a continuous upward trend in the ANP group, with values 2 to 3 times higher than those in the SO group at the corresponding time points and the rising rate was peaking at 6 h. The levels of plasma amylase, TNF-alpha, Cr, TB, DAO, and D-lactate also gradually increased in the ANP group over time and were significantly higher than in the SO group at 3, 6, 12 and 24 h (all P<0.05). Moreover, the rising rate of TNF-alpha, DAO, and D-lactate also peaked at 6 h.
Conclusions
The ANP-induced changes in IAP, inflammatory factors and intestinal barrier that we observed in the rat model were especially obvious at 6 h post-induction, suggesting an early therapeutic window for the treatment of ANP in humans.
doi:10.1371/journal.pone.0078975
PMCID: PMC3828342  PMID: 24244397
4.  Ganoderma lucidum polysaccharides counteract inhibition on CD71 and FasL expression by culture supernatant of B16F10 cells upon lymphocyte activation 
Immune responses to tumor-associated antigens are often detectable in tumor-bearing hosts, but they fail to eliminate malignant cells or prevent development of metastases. Tumor cells produce factors such as interleukin-10, transforming growth factor-β1 and vascular endothelial growth factor (VEGF) that suppress the function of immune cells or induce apoptosis of immune cells. Culture supernatant of tumor cells may contain these immunosuppressive factors which suppress lymphocyte activation. CD71 and FasL are two important molecules that are expressed upon lymphocyte activation. Counteraction against suppression CD71 and FasL expression upon lymphocyte activation may benefit tumor control. A potential component with this effect is Ganoderma lucidum polysaccharides (Gl-PS). In this study, Gl-PS was used on lymphocytes incubating with culture supernatant of B16F10 melanoma cells (B16F10-CS) in the presence of phytohemagglutinin. Following induction with phytohemagglutinin, B16F10-CS suppressed CD71 expression in lymphocytes (as detected by immunofluorescence and flow cytometry), proliferation in lymphocytes (as detected by MTT assay), and FasL expression in lymphocytes (as detected by immunocytochemistry and western blot analysis), while Gl-PS fully or partially counteracted these suppressions. Gl-PS showed counteractive effects against suppression induced by B16F10-CS on CD71 and FasL expression upon lymphocyte activation, suggesting the potential of Gl-PS to facilitate cancer immunotherapy.
doi:10.3892/etm.2013.931
PMCID: PMC3628224  PMID: 23596479
tumor; lymphocyte activation; Ganoderma lucidum; polysaccharides; FasL; CD71
5.  Accessory Breast Cancer Occurring Concurrently with Bilateral Primary Invasive Breast Carcinomas: A Report of Two Cases and Literature Review 
Cancer Biology & Medicine  2012;9(3):197-201.
The development of accessory breast tissue, which is found anywhere along the milk line, is attributed to the failure of milk line remnants to regress during embryogenesis. Primary tumors may arise from any ectopic breast tissue. Accessory breast cancer occurring concurrently with primary invasive breast cancer is extremely rare. Two such cases were reported in this article. One was a 43-year-old Chinese female who exhibited bilateral breast cancer (invasive ductal carcinoma, not otherwise specified, IDC-NOS) and an accessory breast carcinoma (IDC-NOS) incidentally identified in her left axilla. The ectopic breast tissue in her right axilla presented with adenosis. The patient was surgically treated, followed by postoperative docetaxel epirubicin (TE) chemotherapy. The second case was a 53-year-old Chinese female with bilateral breast cancer (apocrine carcinoma) accompanied by an accessory breast carcinoma (IDC-NOS) in her right axilla that was also incidentally identified. The patient was surgically treated after three doses of cyclophosphamide epirubicin docetaxel (CET) neoadjuvant chemotherapy, followed by adjuvant chemotherapy of the same regimen.
doi:10.7497/j.issn.2095-3941.2012.03.008
PMCID: PMC3643663  PMID: 23691479
invasive breast cancer; bilateral; primary; accessory breast cancer; occurring concurrently
6.  Spatial correlation between malaria cases and water-bodies in Anopheles sinensis dominated areas of Huang-Huai plain, China 
Parasites & Vectors  2012;5:106.
Background
Malaria re-emerged in the Huang-Huai Plain of central China during 2006–2008, dominated with Anopheles sinensis as a vector. However, there is no information on strategies based on multi-factor analysis to effectively control the re-emergence of malaria in these areas. Previous experience indicates some relationship between the distribution of water bodies and malaria cases, but more detailed data are not available and in-depth studies have not been conducted up to now. The objective of this study was to identify the relationship between the distribution of water bodies and presentation of malaria cases using spatial analysis tools in order to provide guidance to help formulate effective strategies for use in controlling the sources of malaria infection, based on the identification of risk areas and population.
Methods
The geographic information of malaria cases and their surrounding water bodies were collected from Suixi, Guoyang, Guzhen, Yingshang, Fengyang and Yongqiao County in Anhui province, Yongcheng and Tongbai County in Henan province. All malaria cases distributed in 113 villages in these 8 counties were collected from the China Information System for Disease Control and Prevention and confirmed by household investigation. Data on GIS and malaria cases were mapped and analyzed with the software of ArcGIS 9.2 to identify the spatial correlation between malaria cases and water bodies. The distance from households with malaria cases to the nearest water bodies was used to calculate the OR value by Chi-square test. The risk area was identified through the comparison of OR values in different distances.
Results
357 malaria cases and their GPS data as well as surrounding water bodies were collected and analyzed. 74% of malaria cases were located within the extent of 60 m proximity to the water bodies. The risk rate of people living there and presenting with malaria was significantly higher than others (OR = 1.6,95%CI (1.042, 2.463),P < 0.05).
Conclusions
The results revealed that distribution of water bodies is an important factor influencing the occurrence and distribution of malaria cases in the An.sinensis areas, and implies that the scope and population within 60 m around water bodies are at risk and could be a targeted population for case management of malaria.
doi:10.1186/1756-3305-5-106
PMCID: PMC3414776  PMID: 22650153
7.  Promotion of Myelopoiesis in Myelosuppressed Mice by Ganoderma lucidum Polysaccharides 
Our previous studies demonstrated that Ganoderma lucidum polysaccharides (Gl-PS) exhibit potent immunomodulating effects. Immunomodulation plays an important role in hematopoiesis. To investigate the possible mechanism by which Gl-PS promote myelopoiesis during myelosuppression induced by cyclophosphamide, mice were injected intraperitoneally (i.p.) once daily with 2.5 mg/kg of Gl-PS for 10 days and were treated i.p. once daily with cyclophosphamide (100 mg/kg) on days 2 through 4. In the present study in vivo and in vitro, we find that Gl-PS selectively bind to bone marrow stromal cells, stimulate the secretion of hematopoietic growth factors, and enhance the clonogenic activities of hematopoietic and stromal cells to promote hematopoiesis in myelosuppressed mice.
doi:10.3389/fphar.2012.00020
PMCID: PMC3288721  PMID: 22403542
Ganoderma lucidum polysaccharides; myelosuppression; hematopoiesis
8.  Correction: A Genome-Wide Association Study on Obesity and Obesity-Related Traits 
PLoS ONE  2012;7(2):10.1371/annotation/a34ee94e-3e6a-48bd-a19e-398a4bb88580.
doi:10.1371/annotation/a34ee94e-3e6a-48bd-a19e-398a4bb88580
PMCID: PMC3293772
9.  Metachronous pulmonary and adrenal metastases after liver transplantation for hepatocarcinoma 
Background
The worldwide experience of surgical resection for isolated metastasis following liver transplantation (LT) for hepatocellular carcinoma (HCC) is limited.
Methods
The case of a 60-year-old patient performed successful surgical management for metachronous pulmonary and adrenal metastases from HCC after LT.
Results
Eighty months after LT, he was presently alive and disease-free with a normal AFP value.
Conclusion
The case is an interesting report on a somehow indolent metastatic spread of HCC after LT. It should be considered that metachronous metastatic resectable disease, with no data of recurrence at the primary site in an operable patient, is an indication to perform a surgical resection.
doi:10.1186/1477-7819-9-156
PMCID: PMC3286431  PMID: 22123282
liver transplantation; metachronous; metastasis; surgical management
10.  Lipopolysaccharide pretreatment protects against ischemia/reperfusion injury via increase of HSP70 and inhibition of NF-κB 
Cell Stress & Chaperones  2010;16(3):287-296.
It has been reported that pretreatment of rats with lipopolysaccharide (LPS) increases myocardial functional recovery in ischemia/reperfusion (I/R) hearts. However, the mechanisms by which LPS induces cardioprotection against I/R injury have not been fully elucidated. In this study, we pretreated rats with LPS (1.0 mg/kg) 24 h before they were subjected to I/R injury, and then examined the roles of heat shock protein-70 (HSP70) and nucleus factor-κB (NF-κB) in LPS-induced cardioprotection. We observed that pretreatment with low-dose LPS resulted in significantly increased levels of HSP70 in the myocardium, which could dramatically inhibit NF-κB translocation and reduce degradation of inhibitory κB. Inhibition of NF-κB, in turn, attenuated release of inflammatory cytokines (tumor necrosis factor-α, interleukin (IL)-1β, and IL-6) and reduced apoptosis of myocardium and infarct area following I/R injury. Moreover, HSP70 could ameliorate oxidative stress following I/R injury. To further investigate whether increase of HSP70 might be responsible for protection of the myocardium against I/R injury, we co-administered the HSP70 inhibitor, quercetin, with LPS before I/R injury. We found that LPS-induced cardioprotection was attenuated by co-administration with quercetin. Herein, we concluded that increased levels of HSP70 through LPS pretreatment led to inhibition of NF-κB activity in the myocardium after I/R injury. Our results indicated that LPS-induced cardioprotection was mediated partly through inhibition of NF-κB via increase of HSP70, and LPS pretreatment could provide a means of reducing myocardial I/R injury.
doi:10.1007/s12192-010-0242-6
PMCID: PMC3077230  PMID: 21080136
Lipopolysaccharide; Heat shock protein 70; NF-κB; Ischemia/reperfusion injury
11.  Large Copy-Number Variations Are Enriched in Cases With Moderate to Extreme Obesity 
Diabetes  2010;59(10):2690-2694.
OBJECTIVE
Obesity is an increasingly common disorder that predisposes to several medical conditions, including type 2 diabetes. We investigated whether large and rare copy-number variations (CNVs) differentiate moderate to extreme obesity from never-overweight control subjects.
RESEARCH DESIGN AND METHODS
Using single nucleotide polymorphism (SNP) arrays, we performed a genome-wide CNV survey on 430 obese case subjects (BMI >35 kg/m2) and 379 never-overweight control subjects (BMI <25 kg/m2). All subjects were of European ancestry and were genotyped on the Illumina HumanHap550 arrays with ∼550,000 SNP markers. The CNV calls were generated by PennCNV software.
RESULTS
CNVs >1 Mb were found to be overrepresented in case versus control subjects (odds ratio [OR] = 1.5 [95% CI 0.5–5]), and CNVs >2 Mb were present in 1.3% of the case subjects but were absent in control subjects (OR = infinity [95% CI 1.2–infinity]). When focusing on rare deletions that disrupt genes, even more pronounced effect sizes are observed (OR = 2.7 [95% CI 0.5–27.1] for CNVs >1 Mb). Interestingly, obese case subjects who carry these large CNVs have moderately high BMI and do not appear to be extreme cases. Several CNVs disrupt known candidate genes for obesity, such as a 3.3-Mb deletion disrupting NAP1L5 and a 2.1-Mb deletion disrupting UCP1 and IL15.
CONCLUSIONS
Our results suggest that large CNVs, especially rare deletions, confer risk of obesity in patients with moderate obesity and that genes impacted by large CNVs represent intriguing candidates for obesity that warrant further study.
doi:10.2337/db10-0192
PMCID: PMC3279563  PMID: 20622171
12.  A Genome-Wide Association Study on Obesity and Obesity-Related Traits 
PLoS ONE  2011;6(4):e18939.
Large-scale genome-wide association studies (GWAS) have identified many loci associated with body mass index (BMI), but few studies focused on obesity as a binary trait. Here we report the results of a GWAS and candidate SNP genotyping study of obesity, including extremely obese cases and never overweight controls as well as families segregating extreme obesity and thinness. We first performed a GWAS on 520 cases (BMI>35 kg/m2) and 540 control subjects (BMI<25 kg/m2), on measures of obesity and obesity-related traits. We subsequently followed up obesity-associated signals by genotyping the top ∼500 SNPs from GWAS in the combined sample of cases, controls and family members totaling 2,256 individuals. For the binary trait of obesity, we found 16 genome-wide significant signals within the FTO gene (strongest signal at rs17817449, P = 2.5×10−12). We next examined obesity-related quantitative traits (such as total body weight, waist circumference and waist to hip ratio), and detected genome-wide significant signals between waist to hip ratio and NRXN3 (rs11624704, P = 2.67×10−9), previously associated with body weight and fat distribution. Our study demonstrated how a relatively small sample ascertained through extreme phenotypes can detect genuine associations in a GWAS.
doi:10.1371/journal.pone.0018939
PMCID: PMC3084240  PMID: 21552555
13.  FTO gene SNPs associated with extreme obesity in cases, controls and extremely discordant sister pairs 
Background
FTO is a gene located in chromosome region 16q12.2. Recently two studies have found associations of several single nucleotide polymorphisms (SNPs) in FTO with body mass index (BMI) and obesity, particularly rs1421085, rs17817449, and rs9939609.
Methods
We examined these three SNPs in 583 extremely obese women with current BMI greater than 35 kg/m2 and lifetime BMI greater than 40 kg/m2, and 544 controls who were currently normal weight (BMI<25 kg/m2) and had never been overweight during their lifetimes.
Results
We detected highly significant associations of obesity with alleles in all three SNPs (p < 10-9). The strongest association was with rs1421085 (p = 3.04 × 10-10, OR = 1.75, CI = 1.47–2.08). A subset of 99 cases had extremely discordant sisters with BMI<25 kg/m2. The discordant sisters differed in allele and genotype frequencies in parallel with the overall case and control sample. The strongest association was with rs17817449 (z = 3.57, p = 3.6 × 10-4).
Conclusion
These results suggest common variability in FTO is associated with increased obesity risk or resistance and may in part account for differences between closely related individuals.
doi:10.1186/1471-2350-9-4
PMCID: PMC2254593  PMID: 18218107
14.  Proteasome Inhibitors Block Development of Plasmodium spp. 
Antimicrobial Agents and Chemotherapy  1998;42(10):2731-2738.
Proteasomes degrade most of the proteins inside eukaryotic cells, including transcription factors and regulators of cell cycle progression. Here we show that nanomolar concentrations of lactacystin, a specific irreversible inhibitor of the 20S proteasome, inhibit development of the exoerythrocytic and erythrocytic stages of the malaria parasite. Although lactacystin-treated Plasmodium berghei sporozoites are still invasive, their development into exoerythrocytic forms (EEF) is inhibited in vitro and in vivo. Erythrocytic schizogony of P. falciparum in vitro is also profoundly inhibited when drug treatment of the synchronized parasites is prior, but not subsequent, to the initiation of DNA synthesis, suggesting that the inhibitory effect of lactacystin is cell cycle specific. Lactacystin reduces P. berghei parasitemia in rats, but the therapeutic index is very low. Along with other studies showing that lactacystin inhibits stage-specific transformation in Trypanosoma and Entamoeba spp., these findings highlight the potential of proteasome inhibitors as drugs for the treatment of diseases caused by protozoan parasites.
PMCID: PMC105928  PMID: 9756786
15.  GTP Cyclohydrolase I and Tyrosine Hydroxylase Gene Mutations in Familial and Sporadic Dopa-Responsive Dystonia Patients 
PLoS ONE  2013;8(6):e65215.
Dopa-responsive dystonia (DRD) is a rare inherited dystonia that responds very well to levodopa treatment. Genetic mutations of GTP cyclohydrolase I (GCH1) or tyrosine hydroxylase (TH) are disease-causing mutations in DRD. To evaluate the genotype-phenotype correlations and diagnostic values of GCH1 and TH mutation screening in DRD patients, we carried out a combined study of familial and sporadic cases in Chinese Han subjects. We collected 23 subjects, 8 patients with DRD, 5 unaffected family members, and 10 sporadic cases. We used PCR to sequence all exons and splicing sites of the GCH1 and TH genes. Three novel heterozygous GCH1 mutations (Tyr75Cys, Ala98Val, and Ile135Thr) were identified in three DRD pedigrees. We failed to identify any GCH1 or TH mutation in two affected sisters. Three symptom-free male GCH1 mutation carriers were found in two DRD pedigrees. For those DRD siblings that shared the same GCH1 mutation, symptoms and age of onset varied. In 10 sporadic cases, only two heterozygous TH mutations (Ser19Cys and Gly397Arg) were found in two subjects with unknown pathogenicity. No GCH1 and TH mutation was found in 40 unrelated normal Han Chinese controls. GCH1 mutation is the main etiology of familial DRD. Three novel GCH1 mutations were identified in this study. Genetic heterogeneity and incomplete penetrance were quite common in DRD patients, especially in sporadic cases. Genetic screening may help establish the diagnosis of DRD; however, a negative GCH1 and TH mutation test would not exclude the diagnosis.
doi:10.1371/journal.pone.0065215
PMCID: PMC3675154  PMID: 23762320
16.  Syndecan Binding Protein (SDCBP) Is Overexpressed in Estrogen Receptor Negative Breast Cancers, and Is a Potential Promoter for Tumor Proliferation 
PLoS ONE  2013;8(3):e60046.
Background
Syndecan binding protein (SDCBP), an adapter protein containing PDZ domains, contributes to the tumorigenicity and metastasis of many malignant tumors, such as malignant melanoma. Our study aimed in revealing the expression profile of SDCBP in breast cancer (BCa) and its role in tumor cell proliferation, and then exploring its value in the targeted treatment of BCa.
Methodology/Principal Findings
We first evaluated the SDCBP expression by immunohistochemistry in normal breast and BCa tissues. Then we explored the expression profile of SDCBP in different BCa cell lines. By constructing SDCBP-silenced BCa cell clones, we further assessed the effects of SDCBP suppression on tumor cells in vitro by cell culture and in vivo by tumorigenicity. SDCBP expression was detected in 80.6% (n = 160) of BCa tissues, in contrast to its expression in 13% (n = 23) of normal breast tissues (P<0.001). Among the tumors, the level of its expression was positively correlated with histological grade and tumor staging while negatively correlated with the estrogen receptor (ER) expression. Higher expression of SDCBP was also noted in ER-negative BCa cell lines. It was also identified that SDCBP expression was down-regulated in a dose-dependent mode by 17-β estradiol in estrogen-responsive MCF-7. Furthermore, SDCBP silence inhibited ER-negative tumor cell growth in vivo and in vitro. Cell cycle studies showed that SDCBP silence increased G1 cell population and resulted in related cell-cycle-regulator changes: up-regulation of p21 and p27 while down-regulation of cyclin E.
Conclusion/Significance
Our results suggested that SDCBP played an important role in tumor growth of ER-negative BCas. In these tumors where the estrogen signaling pathway is not available, SDCBP probably contribute to tumor growth through an alternative signaling pathway by promoting tumor cells passing the G1/S checkpoint into the cell cycle. Suppression of SDCBP expression may have its potential to become a targeted therapy for ER-negative BCas.
doi:10.1371/journal.pone.0060046
PMCID: PMC3606191  PMID: 23533663

Results 1-16 (16)