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1.  Role of leptin receptor gene polymorphisms in susceptibility to the development of essential hypertension: a case–control association study in a Northern Han Chinese population 
Journal of human hypertension  2014;28(9):551-556.
In order to explore the potential association between the leptin receptor (LEPR) gene polymorphisms and essential hypertension (EH) risk in the Northern Han Chinese population, we recruited 823 hypertensive subjects and 491 healthy control subjects from the Northern Han Chinese. Genotyping was performed to identify the Lys109Arg, Gln223Arg and Lys656Asn polymorphisms of the LEPR gene. Significant associations were found in a dominant genetic model ([GG+AG] vs AA), P=0.007, odds ratio (OR)=3.697, 95% confidence interval (CI) 1.442–9.482), and in homozygote comparison (GG vs AA, P=0.005, OR=3.890, 95% CI 1.501–10.077) for the Gln223Arg polymorphism. No significant association could be found between Lys109Arg or Lys656Asn polymorphism and EH risk. Linkage disequilibrium was detected between the Lys109Arg and Gln223Arg polymorphisms, and haplotype analyses identified that the G-A haplotype was a protective haplotype for EH. Our studies demonstrated that the LEPR Gln223Arg polymorphism had an important role in a patient's susceptibility to EH in the Northern Han Chinese population.
PMCID: PMC4133281  PMID: 24522342
leptin receptor; polymorphism; essential hypertension; Chinese; linkage disequilibrium; haplotypes
2.  Should both iodised and non-iodised salt be made available in Chinese cities? A cross-sectional survey 
Yu, J | Liu, P | Liu, Y | Liu, S J | Sun, D J
BMJ Open  2014;4(7):e005397.
To contribute evidence relevant to the policy of supplying iodised salt (IS), non-iodised salt (NIS) or both in Chinese cities.
Subnational telephone interview survey.
Totally, 24 557 telephone numbers were dialled and 4833 citizens accepted the telephone interview. The telephone numbers were randomly selected by random digit dialling and a Mitofsky-Waksberg two-stage sampling method in 17 capital cities and 6 coastal cities from 17 iodine deficiency disorder (IDD)-eliminated provinces (municipalities).
The 4833 citizens finished the telephone interview. Among them, 3738 (77.3%) citizens chose IS, 481 (10%) citizens chose NIS, and the others chose both IS and NIS. The citizens’ awareness rates of IDD and IDD preventive measures were 68.7% and 62.5%, respectively.
It is not a suitable time to supply IS and NIS simultaneously in the developed cities of China, but a pilot project may be conducted in the cities where IDD has been sustainably eliminated, there is strong awareness of IDD and the population can make informed decisions regarding IS. IDD health education should be further strengthened, especially regarding the potential for IQ damage.
PMCID: PMC4120298  PMID: 25015474
telephone interview; iodized salt; non-iodized salt; knowledge-attitude-practice; iodine deficiency disorders
3.  LHX6 acts as a novel potential tumour suppressor with epigenetic inactivation in lung cancer 
Cell Death & Disease  2013;4(10):e882-.
LIM homeobox domain 6 (LHX6) is a putative transcriptional regulator that controls the differentiation and development of neural and lymphoid cells. However, the function of LHX6 in cancer development remains largely unclear. Recently, we found that LHX6 is hypermethylated in lung cancer. In this study, we analysed its epigenetic regulation, biological functions, and related molecular mechanisms in lung cancer. Methylation status was evaluated by methylation-specific PCR and bisulfite genomic sequencing. LHX6 mRNA levels were measured in relation to the methylation status. The effects of LHX6 expression on tumourigenesis were studied in vitro and in vivo. LHX6 was readily expressed in normal lung tissues without methylation, but was downregulated or silenced in lung cancer cell lines and tissues with hypermethylation status. Treatment of lung cancer cells with the demethylating agent 5-aza-2′-deoxycytidine restored LHX6 expression. Moreover, LHX6 hypermethylation was detected in 56% (52/93) of primary lung cancers compared with none (0/20) of the tested normal lung tissues. In lung cancer cell lines 95D and H358, forced expression of LHX6 suppressed cell viability, colony formation, and migration, induced apoptosis and G1/S arrest, and inhibited their tumorigenicity in nude mice. On the other hand, knockdown of LHX6 expression by RNA interference increased cell proliferation and inhibited apoptosis and cell cycle arrest. These effects were associated with upregulation of p21 and p53, and downregulation of Bcl-2, cyclinD1, c-myc, CD44, and MMP7. In conclusion, our results suggest that LHX6 is a putative tumour suppressor gene with epigenetic silencing in lung cancer.
PMCID: PMC3824675  PMID: 24157876
LHX6; DNA methylation; tumour suppressor; lung cancer; epigenetics
5.  Cardioprotective effects of peroxisome proliferator activated receptor γ activators on acute myocarditis: anti-inflammatory actions associated with nuclear factor κB blockade 
Heart  2005;91(9):1203-1208.
Objective: To test the hypothesis that activation of peroxisome proliferator activated receptor γ (PPAR-γ) reduces experimental autoimmune myocarditis (EAM) associated with inhibitor κB (IκB) α induction, blockade of nuclear factor κB (NF-κB), and inhibition of inflammatory cytokine expression.
Methods: EAM was induced in Lewis rats by immunisation with porcine cardiac myosin. PPAR-γ activators 15-deoxy-Δ12,14-prostaglandin J2 (15d-PGJ2) and pioglitazone (PIO) were administered to rats with EAM.
Results: Enhanced PPAR-γ expression was prominently stained in the nuclear and perinuclear regions of infiltrating inflammatory cells. Administration of 15d-PGJ2 and PIO greatly reduced the severity of myocarditis and suppressed myocardial mRNA and protein expression of inflammatory cytokines in rats with EAM. In addition, treatment with PPAR-γ activators enhanced IκB concentrations in the cytoplasmic fractions and nuclear fractions from inflammatory myocardium. Concurrently, NF-κB was greatly activated in myocarditis; this activation was blocked in the 15d-PGJ2 treated and PIO treated groups.
Conclusions: PPAR-γ may have a role in the pathophysiology of EAM. Because an increase in IκB expression and inhibition of translocation of the NF-κB subunit p65 to the nucleus in inflammatory cells correlated with the protective effects of PPAR-γ activators, these results suggest that PPAR-γ activators act sequentially through PPAR-γ activation, IκB induction, blockade of NF-κB activation, and inhibition of inflammatory cytokine expression. These results suggest that PPAR-γ activators such as 15d-PGJ2 and PIO may have the potential to modulate human inflammatory heart diseases such as myocarditis.
PMCID: PMC1769084  PMID: 15774612
myocarditis; immunity; PPAR-γ; NF-κB; cytokine; inflammation
6.  Torsional ultrasound modality for hard nucleus phacoemulsification cataract extraction 
Zeng, M | Liu, X | Liu, Y | Xia, Y | Luo, L | Yuan, Z | Zeng, Y | Liu, Y
The British Journal of Ophthalmology  2008;92(8):1092-1096.
To evaluate the efficacy and safety of phacoemulsification using torsional modality with different parameter settings for hard nucleus cataract extraction.
A prospective, randomised clinical study.
A clinical practice study conducted at the Cataract Service, Zhongshan Ophthalmic Center, Sun-Yat-Sen University, and Guangzhou. One eye each from 198 consecutive patients with cataract density grade IV according to the Emery–Little system classification system, requiring phacoemulsification and intraocular lens implantation, was included. Eyes were randomly assigned to the Linear Torsional combined with Ultrasound power group (Linear Tor+US group, n = 66), 100% Fixed Torsional group (Fixed Tor group, n = 65) and conventional Ultrasound burst group (US group, n = 67). All surgeries were performed by a single experienced surgeon and outcomes evaluated by another surgeon masked to treatment. Intraoperative parameters were Ultrasound Time (UST), Cumulative Dissipated Energy (CDE) and surgical complications. Patients were examined on post-op days 1, 7 and 30. Postoperative outcomes were final best corrected visual acuity (BCVA), average central and incisional corneal thickness and central endothelial cell counts.
The mean UST was lower in the Fixed Tor group than in the US group and in the Lin US+Tor group (p⩽0.0001). The mean CDE was lower in the Lin Tor+US group and in the Fixed Tor group than in the US group (p⩽0.0001). Comparing with the two Tor group, the US group had a lower average BCVA on post-op 1, 7 (p⩽0.0001) and 30 (p>0.01), greater average central corneal and incisional thickness on days 1, 7 (p⩽0.0001) and 30 (p>0.01), and higher average corneal endothelial cell losses on day 7 and 30 days (p⩽0.0001).
Torsional combined with ultrasound power or high fixed torsional amplitude can yield more effective hard nucleus phacoemulsification than conventional ultrasound modality.
PMCID: PMC2569137  PMID: 18567650
7.  A genome-wide linkage scan for bone mineral density in an extended sample: evidence for linkage on 11q23 and Xq27 
Journal of Medical Genetics  2004;41(10):743-751.
Background: Osteoporosis is a major public health problem, mainly quantified by low bone mineral density (BMD). The majority of BMD variation is determined by genetic effects. A pilot whole genome linkage scan (WGS) was previously reported in 53 white pedigrees with 630 subjects. Several genomic regions were suggested to be linked to BMD variation.
Objective: To substantiate these previous findings and detect new genomic regions.
Methods: A WGS was conducted on an extended sample where the size was almost tripled (1816 subjects from 79 pedigrees). All the subjects were genotyped with 451 microsatellite markers spaced ∼8.1 cM apart across the human genome. Two point and multipoint linkage analyses were carried out using the variance component method.
Results: The strongest linkage signal was obtained on Xq27 with two point LOD scores of 4.30 for wrist BMD, and 2.57 for hip BMD, respectively. Another important region was 11q23, which achieved a maximum LOD score of 3.13 for spine BMD in multipoint analyses, confirming the results on this region in two earlier independent studies. Suggestive linkage evidence was also found on 7p14 and 20p12.
Conclusions: Together with the findings from other studies, the current study has further delineated the genetic basis of bone mass and highlights the importance of increasing sample size to confirm linkage findings and to identify new regions of linkage.
PMCID: PMC1735607  PMID: 15466007
8.  Role of leptin receptor gene polymorphisms in susceptibility to the development of essential hypertension: a case–control association study in a Northern Han Chinese population 
Journal of Human Hypertension  2014;28(9):551-556.
In order to explore the potential association between the leptin receptor (LEPR) gene polymorphisms and essential hypertension (EH) risk in the Northern Han Chinese population, we recruited 823 hypertensive subjects and 491 healthy control subjects from the Northern Han Chinese. Genotyping was performed to identify the Lys109Arg, Gln223Arg and Lys656Asn polymorphisms of the LEPR gene. Significant associations were found in a dominant genetic model ([GG+AG] vs AA), P=0.007, odds ratio (OR)=3.697, 95% confidence interval (CI) 1.442–9.482), and in homozygote comparison (GG vs AA, P=0.005, OR=3.890, 95% CI 1.501–10.077) for the Gln223Arg polymorphism. No significant association could be found between Lys109Arg or Lys656Asn polymorphism and EH risk. Linkage disequilibrium was detected between the Lys109Arg and Gln223Arg polymorphisms, and haplotype analyses identified that the G-A haplotype was a protective haplotype for EH. Our studies demonstrated that the LEPR Gln223Arg polymorphism had an important role in a patient's susceptibility to EH in the Northern Han Chinese population.
PMCID: PMC4133281  PMID: 24522342
leptin receptor; polymorphism; essential hypertension; Chinese; linkage disequilibrium; haplotypes
9.  MicroRNA-29a promotes colorectal cancer metastasis by regulating matrix metalloproteinase 2 and E-cadherin via KLF4 
Tang, W | Zhu, Y | Gao, J | Fu, J | Liu, C | Liu, Y | Song, C | Zhu, S | Leng, Y | Wang, G | Chen, W | Du, P | Huang, S | Zhou, X | Kang, J | Cui, L
British Journal of Cancer  2013;110(2):450-458.
Growing evidence suggests that miR-29a has an important role in regulating tumourigenesis and development of various types of cancer. However, the role and the underlying mechanism of miR-29a in colorectal cancer (CRC) remain largely unknown.
MiR-29a targeted gene was identified by the luciferase assay and western blot. MiR-29a function was analysed by invasion assays and the orthotopic transplantation mouse model. The miR-29a pathway was assayed by real-time PCR, western blot and chip analysis.
KLF4 was identified as a direct target gene of miR-29a. MiR-29a promoted CRC cell invasion, which was blocked by re-expression of KLF4. In addition, MMP2 was identified as a novel direct target of KLF4. Both miR-29a overexpression and KLF4 knockdown promoted MMP2 expression but inhibited E-cadherin expression. Furthermore, clinical data indicated that both miR-29a high expression and KLF4 mRNA low expression were associated with metastasis and poor prognosis in CRC patients, and KLF4 protein expression was inversely correlated with MMP2 but positively correlated with E-cad protein expression.
Increased expression of miR-29a promoted CRC metastasis by regulating MMP2/E-cad through direct targeting KLF4, which highlights the potential of the miR-29a inhibitor as a novel agent against CRC metastasis.
PMCID: PMC3899762  PMID: 24281002
miR-29a; colorectal cancer; metastasis; KLF4
11.  IRF4 is a novel mediator for neuronal survival in ischaemic stroke 
Cell Death and Differentiation  2014;21(6):888-903.
Neuroprotection following ischaemic stroke is driven by the interplay between regulatory transcription factors and endogenous protective factors. IRF4, a member of the interferon regulatory factor (IRF) family, is implicated in the survival of tumour cells. However, its role in the survival of normal cells including neurons remains elusive. Using genetic approaches, we established a central role for IRF4 in protection against ischaemia/reperfusion (I/R)-induced neuronal death. IRF4 was expressed in neurons, and induced by ischaemic stroke. Neuron-specific IRF4 transgenic (IRF4-TG) mice exhibited reduced infarct lesions, and this effect was reversed in IRF4-knockout mice. Notably, we revealed that IRF4 rescues neurons from I/R-induced death both in vivo and in vitro. Integrative transcriptional and cell survival analyses showed that IRF4 functions mechanistically as a transcription activator of serum response factor (SRF) crucial to salvage neurons during stroke. Indeed, the expression of SRF and SRF-dependent molecules was significantly upregulated upon IRF4 overexpression and conversely inhibited upon IRF4 ablation. Similar results were observed in oxygen glucose deprivation (OGD)-treated primary cortical neurons. Furthermore, we identified the IRF4-binding site in the promoter region of the SRF gene essential for its transcription. To verify the IRF4–SRF axis in vivo, we generated neuron-specific SRF knockout mice, in which SRF exerted profound cerebroprotective effects similar to those of IRF4. More importantly, the phenotype observed in IRF4-TG mice was completely reversed by SRF ablation. Thus, we have shown that the IRF4–SRF axis is a novel signalling pathway critical for neuronal survival in the setting of ischaemic stroke.
PMCID: PMC4013523  PMID: 24510125
IRF4; SRF; ischaemic stroke; neuronal survival
12.  Tumor development is associated with decrease of TET gene expression and 5-methylcytosine hydroxylation 
Oncogene  2012;32(5):663-669.
The TET (ten–eleven translocation) family of α-ketoglutarate (α-KG)-dependent dioxygenases catalyzes the sequential oxidation of 5-methylcytosine (5mC) to 5-hydroxymethyl-cytosine (5hmC), 5-formylcytosine and 5-carboxylcytosine, leading to eventual DNA demethylation. The TET2 gene is a bona fide tumor suppressor frequently mutated in leukemia, and TET enzyme activity is inhibited in IDH1/2-mutated tumors by the oncometabolite 2-hydroxyglutarate, an antagonist of α-KG, linking 5mC oxidation to cancer development. We report here that the levels of 5hmC are dramatically reduced in human breast, liver, lung, pancreatic and prostate cancers when compared with the matched surrounding normal tissues. Associated with the 5hmC decrease is the substantial reduction of the expression of all three TET genes, revealing a possible mechanism for the reduced 5hmC in cancer cells. The decrease of 5hmC was also observed during tumor development in different genetically engineered mouse models. Together, our results identify 5hmC as a biomarker whose decrease is broadly and tightly associated with tumor development.
PMCID: PMC3897214  PMID: 22391558
TET; 5-hydroxymethylation; DNA methylation; cancer biomarker
13.  Histone demethylase Kdm4b functions as a co-factor of C/EBPβ to promote mitotic clonal expansion during differentiation of 3T3-L1 preadipocytes 
Cell Death and Differentiation  2012;19(12):1917-1927.
CCAAT/enhancer-binding protein (C/EBP) β is required for both mitotic clonal expansion (MCE) and terminal adipocyte differentiation of 3T3-L1 preadipocytes. Although the role of C/EBPβ in terminal adipocyte differentiation is well defined, its mechanism of action during MCE is not. In this report, histone demethylase Kdm4b, as well as cell cycle genes Cdc45l (cell division cycle 45 homolog), Mcm3 (mini-chromosome maintenance complex component 3), Gins1 (GINS complex subunit 1) and Cdc25c (cell division cycle 25 homolog c), were identified as potential C/EBPβ target genes during MCE by utilizing promoter-wide chromatin immunoprecipitation (ChIP)-on-chip analysis combined with gene expression microarrays. The expression of Kdm4b is induced during MCE and its induction is dependent on C/EBPβ. ChIP, Electrophoretic Mobility Shift Assay (EMSA) and luciferase assay confirmed that the promoter of Kdm4b is bound and activated by C/EBPβ. Knockdown of Kdm4b impaired MCE. Furthermore, Kdm4b interacted with C/EBPβ and was recruited to the promoters of C/EBPβ-regulated cell cycle genes, including Cdc45l, Mcm3, Gins1, and Cdc25c, demethylated H3K9me3 and activated their transcription. These findings suggest a novel feed forward mechanism involving a DNA binding transcription factor (C/EBPβ) and a chromatin regulator (Kdm4b) in the regulation of MCE by controlling cell cycle gene expression.
PMCID: PMC3504706  PMID: 22722334
3T3-L1 preadipocytes; adipocyte differentiation; mitotic clonal expansion; C/EBPβ; Kdm4b; ChIP-on-chip
14.  A modified bicanalicular intubation procedure to repair canalicular lacerations using silicone tubes 
Liang, X | Lin, Y | Wang, Z | Lin, L | Zeng, S | Liu, Z | Li, N | Wang, Z | Liu, Y
Eye  2012;26(12):1542-1547.
To explore a modified technique for silicone intubation for the repair of canalicular lacerations.
The surgery was performed on 35 eyes in 35 adult patients from October 2007 to September 2009. Using a modified soft probe, silicone tubes were inserted through the lacrimal punctum and left in the bicanaliculi for 3–10 months.
The surgery was performed successfully in all cases. The tubes were removed after 3–10 months (mean 5.3±1.8 months). The mean follow-up time after tube removal was 13.8 months (range, 6–22 months). Lower punctum splitting occurred in one case (2.86%) after the surgery. No other complications associated with the silicone tubes occurred. All the tubes were removed successfully without any difficulty. No iatrogenic injuries occurred during tube removal.
The modified bicanalicular intubation procedure described here is an effective and atraumatic procedure for the management of canalicular lacerations in adults, and it is associated with fewer complications than the traditional sutures of canalicular lacerations.
PMCID: PMC3522846  PMID: 23060024
modified; canalicular laceration; tube intubation
15.  Serial evaluation of high-resolution CT findings in patients with pneumonia in novel swine-origin influenza A (H1N1) virus infection 
The British Journal of Radiology  2012;85(1014):729-735.
The purpose of our study was to review the changes in the serial high-resolution CT (HRCT) findings from patients with novel swine-origin influenza A (H1N1) virus (S-OIV) infection.
HRCT findings of 70 patients with presumed or laboratory-confirmed novel S-OIV infection were reviewed. The pattern (consolidation, ground glass, fibrosis and air trapping), distribution and extent of abnormality of the lesions on the HRCT were evaluated at different time points. To assess changes that occurred over time, the CT scans in 56 patients were examined in sequence.
The most common CT findings in patients with S-OIV infection are ground-glass opacities with or without consolidation at the first week. The abnormalities peaked at the second week and resolved after that time, which resulted in substantial reduced residual disease at 4 weeks or later. The development of fibrosis was noted in the first week and peaked at the third week of illness (34.7%), then decreased slowly after that time. The mean time of air trapping being noted after the onset of symptoms was 55.5±20.6 days. Comparing the findings of initial CT, most results (96.4%) of follow-up chest CT findings showed improvement (p<0.01).
The abnormalities of ground-glass opacities and/or consolidation on initial CT scans tended to resolve to fibrosis, which then resolved completely or displayed substantially reduced residual disease. HRCT may show more changes in disease progression and play an important role in the evaluation of severe S-OIV.
PMCID: PMC3474108  PMID: 22167502
16.  Isoform-specific palmitoylation of JNK regulates axonal development 
Cell Death and Differentiation  2011;19(4):553-561.
The c-jun N-terminal kinase (JNK) proteins are encoded by three genes (Jnk1–3), giving rise to 10 isoforms in the mammalian brain. The differential roles of JNK isoforms in neuronal cell death and development have been noticed in several pathological and physiological contexts. However, the mechanisms underlying the regulation of different JNK isoforms to fulfill their specific roles are poorly understood. Here, we report an isoform-specific regulation of JNK3 by palmitoylation, a posttranslational modification, and the involvement of JNK3 palmitoylation in axonal development and morphogenesis. Two cysteine residues at the COOH-terminus of JNK3 are required for dynamic palmitoylation, which regulates JNK3's distribution on the actin cytoskeleton. Expression of palmitoylation-deficient JNK3 increases axonal branching and the motility of axonal filopodia in cultured hippocampal neurons. The Wnt family member Wnt7a, a known modulator of axonal branching and remodelling, regulates the palmitoylation and distribution of JNK3. Palmitoylation-deficient JNK3 mimics the effect of Wnt7a application on axonal branching, whereas constitutively palmitoylated JNK3 results in reduced axonal branches and blocked Wnt7a induction. Our results demonstrate that protein palmitoylation is a novel mechanism for isoform-specific regulation of JNK3 and suggests a potential role of JNK3 palmitoylation in modulating axonal branching.
PMCID: PMC3307970  PMID: 21941371
c-Jun N-terminal kinase/JNK; palmitoylation; axonal branching; isoform regulation; cytoskeleton; Wnt pathway
17.  TCF3, a novel positive regulator of osteogenesis, plays a crucial role in miR-17 modulating the diverse effect of canonical Wnt signaling in different microenvironments 
Liu, W | Liu, Y | Guo, T | Hu, C | Luo, H | Zhang, L | Shi, S | Cai, T | Ding, Y | Jin, Y
Cell Death & Disease  2013;4(3):e539-.
Wnt signaling pathways are a highly conserved pathway, which plays an important role from the embryonic development to bone formation. The effect of Wnt pathway on osteogenesis relies on their cellular environment and the expression of target genes. However, the molecular mechanism of that remains unclear. On the basis of the preliminary results, we observed the contrary effect of canonical Wnt signaling on osteogenic differentiation of periodontal ligament stem cells (PDLSCs) in the different culture environment. Furthermore, we found that the expression level of miR-17 was also varied with the change in the culture environment. Therefore, we hypothesized that miR-17 and canonical Wnt signaling may have potential interactions, particularly the inner regulation relationship in different microenvironments. In this paper, we observed that canonical Wnt signaling promoted osteogenesis of PDLSCs in the fully culture medium, while inhibited it in the osteogenic differentiation medium. Interestingly, alteration in the expression level of endogenous miR-17 could partially reverse the different effect of canonical Wnt signaling. Furthermore, the role of miR-17 was because of its target gene TCF3 (transcription factor 3), a key transcription factor of canonical Wnt pathway. Overexpression of TCF3 attenuated the effect of miR-17 on modulating canonical Wnt signaling. Finally, we elucidated that TCF3 enhanced osteogenesis both in vitro and in vivo. In brief, the different level of miR-17 was the main cause of the different effect of canonical Wnt signaling, and TCF3 was the crucial node of miR-17–canonial Wnt signaling regulation loop. This understanding of microRNAs regulating signaling pathways in different microenvironments may pave the way for fine-tuning the process of osteogenesis in bone-related disorders.
PMCID: PMC3613843  PMID: 23492770
transcription factor 3; miR-17; canonical Wnt signaling; osteogenesis; microenvironment
18.  Prevalence and risk factors for esophageal squamous cell cancer and precursor lesions in Anyang, China: a population-based endoscopic survey 
He, Z | Zhao, Y | Guo, C | Liu, Y | Sun, M | Liu, F | Wang, X | Guo, F | Chen, K | Gao, L | Ning, T | Pan, Y | Li, Y | Zhang, S | Lu, C | Wang, Z | Cai, H | Ke, Y
British Journal of Cancer  2010;103(7):1085-1088.
The etiology of esophageal squamous cell cancer (ESCC) in high prevalence regions of China remains unclear.
Endoscopic biopsies were conducted among 7381 inhabitants aged from 25 to 65 of Anyang, China.
In this study, 2.57, 0.20 and 0.16% of the participants had mild, moderate and severe squamous dysplasia, respectively; 0.19 and 0.08% showed squamous carcinoma in situ and invasive ESCC. Using deep well (depth >100 meters) as water source (odds ratio=0.72, 95% confidence interval: 0.54–0.96) was negatively associated with ESCC and its precursors, whereas tobacco and alcohol use were not significantly associated with ESCC.
Water source and other factors in this region need further evaluation by longitudinal studies.
PMCID: PMC2965859  PMID: 20700119
prevalence; risk factor; esophageal cancer; precursor lesion; China
19.  Cell-type-specific regulation of raft-associated Akt signaling 
Liu, Y | Yang, G | Bu, X | Liu, G | Ding, J | Li, P | Jia, W
Cell Death & Disease  2011;2(4):e145-.
20S-protopanaxadiol (aPPD) is a metabolite of ginseng saponins, which is reported to be pro-apoptotic in some cells but anti-apoptotic in neuronal cells by regulating Akt signaling. Owing to its cholesterol-like structure, we hypothesized that aPPD may regulate Akt signaling by interacting with lipid rafts. Here, we compared Akt signaling in glioblastoma U87MG and neuroblastoma Neuro-2a cells treated with aPPD. aPPD did not change Akt activity in the total plasma membranes of each cell type, but drastically altered the activity of raft-associated Akt. Strikingly, Akt activity was decreased in the rafts of U87MG cells but increased in N2a cells by aPPD through regulating raft-associated dephosphorylation. The bidirectional regulation of raft-associated Akt signaling by aPPD enhanced the chemotoxicity of Paclitaxel or Vinblastine in U87MG cells but attenuated the excitotoxicity of N-methyl--aspartate in N2a cells. Our results demonstrated that the activity of raft-associated but not total membrane Akt determines its cellular functions. Lipid rafts differ in different types of cells, which allows for the possibility of cell-type-specific targeting for which aPPD might prove to be a useful agent.
PMCID: PMC3122059  PMID: 21490677
20S-protopanaxadiol; Akt; apoptosis; lipid rafts
21.  P02-08. Enhancement of HIV-1 DNA vaccine immunogenicity by BCG-PSN, a novel adjuvant 
Sun, J | Liu, Y | Li, D | Hou, J | Xu, Z | Fan, W | Fu, J | Liu, Y | Shao, Y
Retrovirology  2009;6(Suppl 3):P13.
PMCID: PMC2767615
22.  ERCC1 mRNA levels and survival of advanced gastric cancer patients treated with a modified FOLFOX regimen 
Wei, J | Zou, Z | Qian, X | Ding, Y | Xie, L | Sanchez, J J | Zhao, Y | Feng, J | Ling, Y | Liu, Y | Yu, L | Rosell, R | Liu, B
British Journal of Cancer  2008;98(8):1398-1402.
Molecular markers involved in DNA repair can help to predict survival in gastric cancer patients treated with 5-FU plus platinum chemotherapy. Excision repair cross-complementing 1 (ERCC1) and thymidylate synthase (TS) mRNA expression levels were assessed in advanced gastric cancer tumour samples using real-time quantitative PCR in 76 patients treated with a modified FOLFOX (biweekly oxaliplatin plus 5-FU and folinic acid) regimen. Median survival time in patients with low ERCC1 levels was significantly longer than in those with high levels (15.8 vs 6.2 months; P<0.0001). Patients with high TS levels had longer survival than those with low levels (12.2 vs 10.1 months; P=0.01). Forty-eight patients with low ERCC1 and high TS levels had a median survival of 16.1 months (P<0.0001). The hazard ratio for patients with high ERCC1 expression was 9.4 (P<0.0001). In patients with high mRNA levels of ERCC1, alternative chemotherapy regimens should be considered.
PMCID: PMC2361707  PMID: 18362936
ERCC1; TS; advanced gastric cancer; FOLFOX
23.  A survey of haplotype variants at several disease candidate genes: the importance of rare variants for complex diseases 
Liu, P | Zhang, Y | Lu, Y | Long, J | Shen, H | Zhao, L. | Xu, F | Xiao, P | Xiong, D | Liu, Y | Recker, R | Deng, H
Journal of Medical Genetics  2005;42(3):221-227.
Background: The haplotype based association method offers a powerful approach to complex disease gene mapping. In this method, a few common haplotypes that account for the vast majority of chromosomes in the populations are usually examined for association with disease phenotypes. This brings us to a critical question of whether rare haplotypes play an important role in influencing disease susceptibility and thus should not be ignored in the design and execution of association studies.
Methods: To address this question we surveyed, in a large sample of 1873 white subjects, six candidate genes for osteoporosis (a common late onset bone disorder), which had 29 SNPs, an average marker density of 13 kb, and covered a total of 377 kb of the DNA sequence.
Results: Our empirical data demonstrated that two rare haplotypes of the parathyroid hormone (PTH)/PTH related peptide receptor type 1 and vitamin D receptor genes (PTHR1 and VDR) with frequencies of 1.1% and 2.9%, respectively, had significant effects on osteoporosis phenotypes (p = 4.2 x 10–6 and p = 1.6 x 10–4, respectively). Large phenotypic differences (4.0∼5.0%) were observed between carriers of these rare haplotypes and non-carriers. Carriers of the two rare haplotypes showed quantitatively continuous variation in the population and were derived from a wide spectrum rather than from one extreme tail of the population phenotype distribution.
Conclusions: These findings indicate that rare haplotypes/variants are important for disease susceptibility and cannot be ignored in genetics studies of complex diseases. The study has profound implications for association studies and applications of the HapMap project.
PMCID: PMC1736011  PMID: 15744035
24.  APOE and TGF-ß1 genes are associated with obesity phenotypes 
Long, J | Liu, P | Liu, Y | Lu, Y | Xiong, D | Elze, L | Recker, R | Deng, H
Journal of Medical Genetics  2003;40(12):918-924.
PMCID: PMC1735335  PMID: 14684691

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