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1.  Theoretical design of multi-colored semi-transparent organic solar cells with both efficient color filtering and light harvesting 
Scientific Reports  2014;4:7036.
Solar cells incorporated with multi-coloring capability not only offer an aesthetic solution to bridge the gap between solar modules and building decorations but also open up the possibility for self-powered colorful display. In this paper, we proposed a multi-colored semi-transparent organic solar cells (TOSCs) design containing metallic nanostructures with the both high color purity and efficiency based on theoretical considerations. By employing guided mode resonance effect, the multi-colored TOSC behave like an efficient color filter that selectively transmits light with the desired wavelengths and generates electricity with light of other wavelengths. Broad range of coloring and luminosity adjusting for the transmission light can be achieved by simply tuning the period and the duty cycle of the metallic nanostructures. Furthermore, accompanying with the efficient color filtering characteristics, the optical absorption of TOSCs was improved due to the marked suppression of transmission loss at the off-resonance wavelengths and the increased light trapping in TOSCs. The mechanisms of the light guiding in photoactive layer and broadband backward scattering from the metallic nanostructures were identified to make an essential contribution to the improved light-harvesting. By enabling efficient color control and high efficiency simultaneously, this approach holds great promise for future versatile photovoltaic energy utilization.
PMCID: PMC4229659  PMID: 25391756
2.  Association of HLA-DQA1 (rs9272219) with susceptibility to rheumatoid arthritis in a Han Chinese population 
HLA-DQA1 (rs9272219) has been previously reported that it is a susceptibility locus in rheumatoid arthritis (RA) of UK Caucasian population and North American; however, it has not reported in RA of Chinese population. Our study was to identify whether or not this relationship is reside between rs9272219 and RA in a Han Chinese population. 207 patients with RA and 199 control subjects were recruited. The single nucleotide polymorphism (SNP) of rs9272219 was tested in alleles and genotype frequencies and the data was analyzed by doing the statistic analysis of odds ratio (OR) and 95% confidence interval (CI) from multivariate unconditional logistic regression analyses after pairwise linkage disequilibrium (LD) was estimated. Finally, the Alleles and genotype frequencies distribution of rs9272219 locus among RA patients and control subjects were in accordance with Hardy-Weinberg equilibrium. We found significant association between rs9272219 and RA of Chinese population (OR 0.494, 95% confidence interval [95% CI] 0.354-0.688, P = 0 and OR 2.541, 95% CI 1.695-3.808, P = 0, respectively). In this study, we found that the SNP of rs9272219 in HLA-DQA1 is a potential susceptibility locus in RA of Han Chinese population; the results suggest that HLA-DQA1 may be related to the development of RA.
PMCID: PMC4270615  PMID: 25550865
Rheumatoid arthritis; HLA-DQA1; single nucleotide polymorphism
3.  Apo E Gene Polymorphism Affects Development of Type 2 Diabetic Nephropathy in Asian Populations, Especially in East Asians: An Updated Meta-Analysis 
Many studies have determined the correlation between the Apolipoprotein E (APO E) gene polymorphisms and diabetic nephropathy, but their results are inconclusive.
With the aim to confirm this correlation, we performed a meta-analysis of 16 studies. The dichotomous data are presented as the odds ratio (OR) with a 95% confidence interval (CI).
The results of our study indicate that APO ɛ2 allele among the pooled Asian populations were more likely to show high risk of DN development (2 allele vs. ɛ3 allele: pooled OR =1.629, 95% CI=1.010–2.628, P=0.045). For further analysis, the APO ɛ2 allele was associated with progress of DN in the group with duration >10 years, but not in the group with duration <10 years (ɛ2 allele vs. ɛ3 allele: pooled OR=1.920, 95% CI=1.338–2.754, P<0.001). The APO ɛ2 polymorphism increased the susceptibility to DN in Asian population compared with healthy people (ɛ2 allele vs. ɛ3 allele: pooled OR=1.629, 95% CI=1.010–2.628, P=0.045).
Development of DN is associated with APO E polymorphisms in Asian populations, especially in East Asians.
PMCID: PMC4166221  PMID: 25196797
Diabetic Nephropathies; Disease Susceptibility; Meta-Analysis
4.  The phytotoxin coronatine is a multifunctional component of the virulence armament of Pseudomonas syringae 
Planta  2014;240(6):1149-1165.
Plant pathogens deploy an array of virulence factors to suppress host defense and promote pathogenicity. Numerous strains of Pseudomonas syringae produce the phytotoxin coronatine (COR). A major aspect of COR function is its ability to mimic a bioactive jasmonic acid (JA) conjugate and thus target the JA-receptor COR-insensitive 1 (COI1). Biological activities of COR include stimulation of JA-signaling and consequent suppression of SA-dependent defense through antagonistic crosstalk, antagonism of stomatal closure to allow bacterial entry into the interior of plant leaves, contribution to chlorotic symptoms in infected plants, and suppression of plant cell wall defense through perturbation of secondary metabolism. Here, we review the virulence function of COR, including updates on these established activities as well as more recent findings revealing COI1-independent activity of COR and shedding light on cooperative or redundant defense suppression between COR and type III effector proteins.
PMCID: PMC4228168  PMID: 25156488
Phytotoxin; Coronatine; Plant hormones; Hormone crosstalk; Plant defense; Type III effectors
5.  The prevalence of transmitted HIV drug resistance among MSM in Anhui province, China 
To optimize treatment regimens, we assessed human immunodeficiency virus (HIV) diversity and the prevalence of transmitted drug resistance (TDR) among men who have sex with men (MSM) in Anhui province, China.
A total of 139 MSM who were newly diagnosed and antiretroviral treatment-naive were enrolled in Anhui in 2011. A partial pol fragment was amplified and sequenced, and HIV subtypes were determined by phylogenetic analyses. Surveillance/transmitted drug resistance mutations (SDRMs) were identified according to the 2009 World Health Organization (WHO) list.
A total of 133 (95.7%) samples were successfully amplified and sequenced. Based on phylogenetic analyses of the pol fragment, CRF01_AE accounted for 55.6% (74/133) of the infections, followed by CRF07_BC with 32.3% (43/133), B with 5.3% (7/133), and unique recombinant forms with 6.8% (9/133). A total of 3.0% (4/133) of the subjects were found to harbor HIV variants with SDRMs, including 1.5% with NRTI-related mutations and 1.5% with NNRTI-related mutations. PI-related mutations were absent. The SDRMs included L210W (1.5%), Y181C (0.8%), and G190A (0.8%).
In Anhui, CRF01_AE strains contributed to most of the HIV infections among MSM, and the prevalence of TDR was relatively low in this population. Further studies should be performed to evaluate the trend of TDR among MSM in Anhui and to inform first-line antiretroviral treatment.
PMCID: PMC4102087  PMID: 25035709
HIV; Prevalence; Transmitted drug resistance; Treatment-naive; MSM
6.  Clinical application of contrast enhanced ultrasound to diagnose benign prostatic hyperplasia 
Diagnostic Pathology  2014;9:133.
This study aimed to investigate the clinical significance of contrast enhanced ultrasound (CEUS) in diagnosis of benign prostatic hyperplasia (BPH) through comparing CEUS parameters between BPH and normal person.
A retrospective study of sixty BPH patients (aged 73.5 ± 20.5 years old) and thirty normal controls without prostate diseases (aged 75.3 ± 19.7 years old) who had accepted CEUS detection were performed. Time-intensity curves were obtained for all tests in regions of interest. Images were processed using ACQ software and the following parameters were obtained: arrival time (AT), peak intensity (P), time to peak (TP), area under the curve (AUC), mean transit time (MTT) and extinction time (ET). Differences in inner and outer gland of prostate between BPH and the normal tissue were evaluated.
There was a clear boundary between the inner and outer gland of BPH prostate. AT, TP, MTT, ET and P in BPH outer gland were significantly higher than the control group. In inner gland, MTT, ET, AUC and P were also significantly higher than the controls. The accurate rate to diagnose BPH using CEUS was 95.6%, and the sensitivity and specificity were 95.0% and 96.7%, respectively.
Among these significantly changed parameters, the increases of MTT, ET and AUC in inner gland and AT, TP in outer gland were most likely related to BPH. These parameters provide an objective visual assessment to diagnosis of BPH.
Virtual Slides
The virtual slide(s) for this article can be found here:
PMCID: PMC4108000  PMID: 24986664
Contrast enhanced ultrasound; Benign prostatic hyperplasia; Contrast agents
7.  Copy number changes of 4-gene set may predict early relapse in advanced epithelial ovarian cancer after initial platinum-paclitaxel chemotherapy 
For advanced epithelial ovarian cancer (EOC), time to recurrence (TTR) is an important indicator to gauge the therapeutic efficacy of postoperative adjuvant chemotherapy. Our objective was to determine the genes that could potentially distinguish patients with short versus long TTR after initial administration of platinum-paclitaxel combination chemotherapy in advanced EOC. Tumor samples of 159 patients were obtained during the primary cytoreduction. Array comparative genomic hybridization (CGH) was carried with genomic DNA from 17 EOC samples (8 with TTR > 15 months and 9 with TTR ≤ 6 months) to screen candidate gene set, copy-number changes (CNC) of which were significantly different between early and late relapse cases. Seventeen candidate genes were identified by array CGH. The analysis of consistency between real-time PCR and array CGH revealed that 4 genes displayed consistent results, namely GSTT1, ISG20L1, STARD5 and FREM1. In a 142-case validation set, CNC of 4 candidate genes was evaluated and verified by real-time PCR. Sixty five point five percent of the patients were correctly divided into early (TTR ≤ 10 months) and late (TTR > 10 months) recurrent group by CNC of the 4 genes using discriminant analysis. The results showed that CNC of 4-gene set could potentially determine early (TTR ≤ 10 months) or late relapse (TTR > 10 months) after initial platinum-paclitaxel combination chemotherapy in advanced EOC.
PMCID: PMC4065409  PMID: 24959383
Epithelial ovarian cancer; paclitaxel; platinum; recurrence; array comparative genomic hybridization
8.  The Epidemic Characteristics and Changing Trend of Hemorrhagic Fever with Renal Syndrome in Hubei Province, China 
PLoS ONE  2014;9(3):e92700.
Hemorrhagic fever with renal syndrome (HFRS) is caused by different hantaviruses within the Bunyaviridae family. HFRS is a fulminant, infectious disease that occurs worldwide and is endemic in all 31 provinces of China. Since the first HFRS case in Hubei Province was reported in 1957, the disease has spread across the province and Hubei has become one of the seriously affected areas in China with the greatest number of reported HFRS cases in the 1980's. However, the epidemic characteristics of HFRS in Hubei are still not entirely clear and long-term, systematic investigations of this epidemic area have been very limited.
The spatiotemporal distribution of HFRS was investigated using data spanning the years 1980 to 2009. The annual HFRS incidence, fatality rate and seasonal incidence between 1980 and 2009 were calculated and plotted. GIS-based spatial analyses were conducted to detect the spatial distribution and seasonal pattern of HFRS. A spatial statistical analysis, using Kulldorff's spatial scan statistic, was performed to identify clustering of HFRS.
A total of 104,467 HFRS cases were reported in Hubei Province between 1980 and 2009. Incidence of and mortality due to HFRS declined after the outbreak in 1980s and HFRS cases have been sporadic in recent years. The locations and scale of disease clusters have changed during the three decades. The seasonal epidemic pattern of HFRS was characterized by the shift from the unimodal type (autumn/winter peak) to the bimodal type.
Socioeconomic development has great influence on the transmission of hantaviruses to humans and new epidemic characteristics have emerged in Hubei Province. It is necessary to reinforce preventative measures against HFRS according to the newly-presented seasonal variation and to intensify these efforts especially in the urban areas of Hubei Province.
PMCID: PMC3962441  PMID: 24658382
9.  Beneficial soil bacterium Bacillus subtilis (GB03) augments salt tolerance of white clover 
Soil salinity is an increasingly serious problem worldwide that reduces agricultural output potential. Selected beneficial soil bacteria can promote plant growth and augment tolerance to biotic and abiotic stresses. Bacillus subtilis strain GB03 has been shown to confer growth promotion and abiotic stress tolerance in the model plant Arabidopsis thaliana. Here we examined the effect of this beneficial soil bacterium on salt tolerance in the legume forage crop, white clover. Plants of white clover (Trifolium repens L. cultivar Huia) were grown from seeds with or without soil inoculation of the beneficial soil bacterium Bacillus subtilis GB03 supplemented with 0, 50, 100, or 150 mM NaCl water into soil. Growth parameters, chlorophyll content, malondialdehyde (MDA) content and osmotic potential were monitored during the growth cycle. Endogenous Na+ and K+ contents were determined at the time of harvest. White clover plants grown in GB03-inoculated soil were significantly larger than non-inoculated controls with respect to shoot height, root length, plant biomass, leaf area and chlorophyll content; leaf MDA content under saline condition and leaf osmotic potential under severe salinity condition (150 mM NaCl) were significantly decreased. Furthermore, GB03 significantly decreased shoot and root Na+ accumulation and thereby improved K+/Na+ ratio when GB03-inoculated plants were grown under elevated salt conditions. The results indicate that soil inoculation with GB03 promotes white clover growth under both non-saline and saline conditions by directly or indirectly regulating plant chlorophyll content, leaf osmotic potential, cell membrane integrity and ion accumulation.
PMCID: PMC4189326  PMID: 25339966
Bacillus subtilis; white clover; salt tolerance; MDA; osmotic potential; Na+ accumulation
10.  Ultrastructural and physiological responses of potato (Solanum tuberosum L.) plantlets to gradient saline stress 
Salinity is one of the major abiotic stresses that impacts plant growth and reduces the productivity of field crops. Compared to field plants, test tube plantlets offer a direct and fast approach to investigate the mechanism of salt tolerance. Here we examined the ultrastructural and physiological responses of potato (Solanum tuberosum L. c.v. “Longshu No. 3”) plantlets to gradient saline stress (0, 25, 50, 100, and 200 mM NaCl) with two consequent observations (2 and 6 weeks, respectively). The results showed that, with the increase of external NaCl concentration and the duration of treatments, (1) the number of chloroplasts and cell intercellular spaces markedly decreased, (2) cell walls were thickened and even ruptured, (3) mesophyll cells and chloroplasts were gradually damaged to a complete disorganization containing more starch, (4) leaf Na and Cl contents increased while leaf K content decreased, (5) leaf proline content and the activities of catalase (CAT) and superoxide dismutase (SOD) increased significantly, and (6) leaf malondialdehyde (MDA) content increased significantly and stomatal area and chlorophyll content decline were also detected. Severe salt stress (200 mM NaCl) inhibited plantlet growth. These results indicated that potato plantlets adapt to salt stress to some extent through accumulating osmoprotectants, such as proline, increasing the activities of antioxidant enzymes, such as CAT and SOD. The outcomes of this study provide ultrastructural and physiological insights into characterizing potential damages induced by salt stress for selecting salt-tolerant potato cultivars.
PMCID: PMC4292236  PMID: 25628634
potato plantlets; saline stress; ultrastructure; antioxidant defense system; ion distribution
11.  Dominant resistance to Bt cotton and minor cross-resistance to Bt toxin Cry2Ab in cotton bollworm from China 
Evolutionary Applications  2013;6(8):1222-1235.
Evolution of resistance by insect pests threatens the long-term benefits of transgenic crops that produce insecticidal proteins from Bacillus thuringiensis (Bt). Previous work has detected increases in the frequency of resistance to Bt toxin Cry1Ac in populations of cotton bollworm, Helicoverpa armigera, from northern China where Bt cotton producing Cry1Ac has been grown extensively for more than a decade. Confirming that trend, we report evidence from 2011 showing that the percentage of individuals resistant to a diagnostic concentration of Cry1Ac was significantly higher in two populations from different provinces of northern China (1.4% and 2.3%) compared with previously tested susceptible field populations (0%). We isolated two resistant strains: one from each of the two field-selected populations. Relative to a susceptible strain, the two strains had 460- and 1200-fold resistance to Cry1Ac, respectively. Both strains had dominant resistance to a diagnostic concentration of Cry1Ac in diet and to Bt cotton leaves containing Cry1Ac. Both strains had low, but significant cross-resistance to Cry2Ab (4.2- and 5.9-fold), which is used widely as the second toxin in two-toxin Bt cotton. Compared with resistance in other strains of H. armigera, the resistance in the two strains characterized here may be especially difficult to suppress.
PMCID: PMC3901552  PMID: 24478804
dominant resistance; resistance evolution; resistance management
12.  Oligodendroglia metabolically support axons and contribute to neurodegeneration 
Nature  2012;487(7408):443-448.
Oligodendroglia support axon survival and function through mechanisms independent of myelination and their dysfunction leads to axon degeneration in several diseases. The cause of this degeneration has not been determined, but lack of energy metabolites such as glucose or lactate has been hypothesized. Lactate is transported exclusively by monocarboxylate transporters, and changes to these transporters alter lactate production and utilization. We show the most abundant lactate transporter in the CNS, monocarboxylate transporter 1 (MCT1), is highly enriched within oligodendroglia and that disruption of this transporter produces axon damage and neuron loss in animal and cell culture models. In addition, this same transporter is reduced in patients with, and mouse models of, amyotrophic lateral sclerosis (ALS), suggesting a role for oligodendroglial MCT1 in pathogenesis. The role of oligodendroglia in axon function and neuron survival has been elusive; this study defines a new fundamental mechanism by which oligodendroglia support neurons and axons.
PMCID: PMC3408792  PMID: 22801498
13.  New Emerging Recombinant HIV-1 Strains and Close Transmission Linkage of HIV-1 Strains in the Chinese MSM Population Indicate a New Epidemic Risk 
PLoS ONE  2013;8(1):e54322.
In recent years, the population of men who have sex with men (MSM) have become the most significant increasing group of HIV-1 transmission in China. To identify new recombinant strains and transmission patterns of HIV-1 in Chinese MSM population, a cross-sectional investigation of MSM in Anhui Province (in south-eastern China) was performed in 2011. The diagnosed AIDS case rate, CD4 T-cell counts, HIV subtypes, and origin of the recombinant strains were investigated in 138 collected samples. The phylogenetic and bootscan analyses demonstrated that, apart from three previously reported circulating strains (CRF07_BC, CRF01_AE, subtype B), various recombinant strains among subtype B, subtype C, CRF01_AE, and CRF07_BC were simultaneously identified in Chinese MSM for the first time. The introducing time of B subtype in Chinese MSM populations was estimated in 1985, CRF01_AE in 2000, and CRF07_BC in 2003; the latter two account for more than 85% of MSM infections. Notably, in comparison with B subtype infections in Anhui MSM, CRF01_AE, with the highest prevalence rate, may accelerate AIDS progression. Over half of patients (56%) infected with new recombinant strains infection are diagnosed as progression into AIDS. Both Bayes and phylogenetic analyses indicated that there was active HIV transmission among MSM nationwide, which may facilitate the transmission of the new 01B recombinant strains in MSM. In conclusion, new recombinant strains and active transmission were identified in the Chinese MSM population, which may lead to a new alarming HIV pandemic in this population due to the increased pathogenesis of the newly emerging strains.
PMCID: PMC3553145  PMID: 23372706
14.  Amelioration of influenza virus-induced reactive oxygen species formation by epigallocatechin gallate derived from green tea 
Acta Pharmacologica Sinica  2012;33(12):1533-1541.
To study whether epigallocatechin gallate (EGCG), a green tea-derived polyphenol, exerted anti-influenza A virus activity in vitro and in vivo.
Madin-Darby canine kidney (MDCK) cells were tested. The antiviral activity of EGCG in the cells was determined using hemagglutination assay and qPCR. Time of addition assay was performed to determine the kinetics of inhibition of influenza A by EGCG. The level of reactive oxygen species (ROS) were determined with confocal microscopy and flow cytometry. BALB/c mice were treated with EGCG (10, 20 or 40 mg·kg−1·d−1, po) for 5 d. On the 3rd d of the treatment, the mice were infected with influenza A virus. Histopathological changes, lung index and virus titers in the lungs were determined.
Treatment of influenza A-infected MDCK cells with EGCG (1.25–100 nmol/L) inhibited influenza A replication in a concentration-dependent manner (the ED50 value was 8.71±1.11 nmol/L). Treatment with EGCG (20 nmol/L) significantly suppressed the increased ROS level in MDCK cells following influenza A infection. In BALB/c mice infected with influenza virus, oral administration of EGCG (40 mg·kg−1·d−1) dramatically improved the survival rate, decreased the mean virus yields and mitigated viral pneumonia in the lungs, which was equivalent to oral administration of oseltamivir (40 mg·kg−1·d−1), a positive control drug.
The results provide a molecular basis for development of EGCG as a novel and safe chemopreventive agent for influenza A infection.
PMCID: PMC4001843  PMID: 22941291
influenza A virus; epigallocatechin gallate (EGCG); oseltamivir; antiviral agent; ROS
15.  CpG island methylator phenotype and Helicobacter pylori infection associated with gastric cancer 
AIM: To investigate the association between the CpG island methylator phenotype (CIMP) and serum Helicobacter pylori (H. pylori) levels for clinical prediction of gastric cancer (GC) progression.
METHODS: We analyzed the serum CIMP status of 75 patients with GC using a methylation marker panel and a methylation-specific polymerase chain reaction. Serum samples from 40 healthy persons were examined at the same time. The genes examined were APC, WIF-1, RUNX-3, DLC-1, SFRP-1, DKK and E-cad. H. pylori infection in serum was assayed with an anti-H. pylori immunoglobulin G antibody test and a rapid urease test.
RESULTS: The frequencies of high-level methylation in GC tissues for the seven genes were: 48% for APC, 57.33% for WIF-1, 56% for RUNX-3, 50.67% for DLC-1, 52% for SFRP-1, 54.67% for DKK, and 48% for E-cad. The frequencies in GC serum were 30.67% for APC, 34.67% for WIF-1, 37.33% for RUNX-3, 29.33% for DLC-1, 33.33% for SFRP-1, 32% for DKK, and 26.67% for E-cad. CIMP+ (defined as ≥ 3 methylated genes) was associated with 47 (62.67%) GC tissue samples and 44 (58.67%) GC serum samples. CIMP+ was not associated with non-neoplastic mucosal tissues or the serum of healthy persons. Of the 75 GC cases, 51 (68%) were H. pylori+, and 24 (32%) were H. pylori-. Of the 51 H. pylori+ cases, 36 were CIMP+ and 15 were CIMP-. In contrast, for the 24 H. pylori- cases, 11 were CIMP+, and 13 were CIMP-. The difference was significant between the H. pylori+ and H. pylori- groups (χ2 = 4.27, P < 0.05). Of the 51 H. pylori+ GC patients, 34 were CIMP+ and 17 were CIMP-, while among the 24 H. pylori- GC cases, 10 were CIMP+ and 14 were CIMP-. The difference was significant between the H. pylori+ and H. pylori- groups (χ2 = 4.21, P < 0.05). A 2-year follow-up showed significant difference in the rates of metastasis and recurrence between H. pylori+/CIMP+ cases and the H. pylori+/CIMP- cases or CIMP- cases associated with H. pylori assayed in serum (P < 0.05). However, there were no significant differences in survival rates between the two groups.
CONCLUSION: H. pylori+/CIMP+ cases are associated with higher rates of metastasis and recurrence than H. pylori+/CIMP- cases. Serum may be useful for examining CIMP status.
PMCID: PMC3460343  PMID: 23049225
CpG island methylator phenotype; Helicobacter pylori; Serum; Prognosis; Gastric cancer
16.  Intrathoracic displacement of the humeral head in a trauma patient 
Indian Journal of Orthopaedics  2012;46(5):596-598.
Fracture and intrathoracic displacement of the humeral head is the result of severe high energy trauma and are extremely rare. Because of the exceedingly limited number of cases, appropriate treatment modality remains unclear. Hitherto, we describe a unique case of thoracic aorta injury caused by fragmented humeral head. Purposeful medical examination and fast locating of the humeral head fragment are crucial for the selection of appropriate treatment modality. Early aggressive intervention, e.g., emergency thoracoscopy exploring, can be performed to treat potential thoracic complications.
PMCID: PMC3491799  PMID: 23162158
Shoulder dislocation; humeral head fracture; thoracic cavity
17.  Upper Gastrointestinal Endoscopy Detection of Synchronous Multiple Primary Cancers in Esophagus and Stomach: Single Center Experience from China 
The present study was undertaken to clarify the prevalence and clinicopathological features of synchronous multiple primary cancers (SMPCs) under upper gastrointestinal endoscopic examination. We enrolled 45,032 consecutive patients who underwent upper gastrointestinal endoscopic examination for digestive disease from January 2006 to December 2007 in our hospital and analyzed the clinicopathological features of SMPCs in esophagus and stomach. SMPCs are defined as two or over two different cancerous lesions developing in the same or other organs within 6 months. SMPCs were identified in 46 patients (0.1%). The gender ratio was 5.6 : 1 (male/female) and the mean age was 59.4 years. Synchronous esophageal and gastric cancers were the most frequent, being seen in 32 patients (0.07%). The most common histological types of SMPCs were squamous cell carcinoma in esophagus and adenocarcinoma in stomach, respectively. There were 27 (59%) SMPCs patients who had the history of simultaneous exposure to tobacco smoking and alcohol drinking. Additionally, 32 (78%) esophageal squamous cell cancers were associated with tobacco use. And 23 adenocarcinomas of the stomach were associated with Helicobacter pylori infection.
PMCID: PMC3320007  PMID: 22536217
18.  Molecular Comparison of GLT1+ and ALDH1L1+ Astrocytes In Vivo In Astroglial Reporter Mice 
Glia  2011;59(2):200-207.
Astrocyte heterogeneity remains largely unknown in the CNS due to lack of specific astroglial markers. In this study, molecular identity of in vivo astrocytes was characterized in BAC ALDH1L1 and BAC GLT1 eGFP promoter reporter transgenic mice. ALDH1L1 promoter is selectively activated in adult cortical and spinal cord astrocytes, indicated by the overlap of eGFP expression with ALDH1L1 and GFAP, but not with NeuN, APC, Olig2, IbaI, PDGFRα immunoreactivity in BAC ALDH1L1 eGFP reporter mice. Interestingly, ALDH1L1 expression levels (protein, mRNA, and promoter activity) in spinal cord were selectively decreased during postnatal maturation. In contrast, its expression was up-regulated in reactive astrocytes in both acute neural injury and chronic neurodegenerative (G93A mutant SOD1) conditions, similar to GFAP, but opposite of GLT1. ALDH1L1+ and GLT1+ cells isolated through fluorescence activated cell sorting (FACS) from BAC ALDH1L1 and BAC GLT1 eGFP mice share a highly similar gene expression profile, suggesting ALDH1L1 and GLT1 are co-expressed in the same population of astrocytes. This observation was further supported by overlap of the eGFP driven by the ALDH1L1 genomic promoter and the tdTomato driven by a 8.3kb EAAT2 promoter fragment in astrocytes of BAC ALDH1L1 eGFP X EAAT2-tdTomato mice. These studies support ALDH1L1 as a general CNS astroglial marker and investigated astrocyte heterogeneity in the CNS by comparing the molecular identity of the ALDH1L1+ and GLT1+ astrocytes from astroglial reporter mice. These astroglial reporter mice provide useful in vivo tools for the molecular analysis of astrocytes in physiological and pathological conditions.
PMCID: PMC3199134  PMID: 21046559
astroglia; BAC; ALDH1L1; GLT1; GFAP; oligodendroglia; ALS
19.  Early Warning of Cotton Bollworm Resistance Associated with Intensive Planting of Bt Cotton in China 
PLoS ONE  2011;6(8):e22874.
Transgenic crops producing Bacillus thuringiensis (Bt) toxins kill some key insect pests, but evolution of resistance by pests can reduce their efficacy. The predominant strategy for delaying pest resistance to Bt crops requires refuges of non-Bt host plants to promote survival of susceptible pests. To delay pest resistance to transgenic cotton producing Bt toxin Cry1Ac, farmers in the United States and Australia planted refuges of non-Bt cotton, while farmers in China have relied on “natural” refuges of non-Bt host plants other than cotton. Here we report data from a 2010 survey showing field-evolved resistance to Cry1Ac of the major target pest, cotton bollworm (Helicoverpa armigera), in northern China. Laboratory bioassay results show that susceptibility to Cry1Ac was significantly lower in 13 field populations from northern China, where Bt cotton has been planted intensively, than in two populations from sites in northwestern China where exposure to Bt cotton has been limited. Susceptibility to Bt toxin Cry2Ab did not differ between northern and northwestern China, demonstrating that resistance to Cry1Ac did not cause cross-resistance to Cry2Ab, and implying that resistance to Cry1Ac in northern China is a specific adaptation caused by exposure to this toxin in Bt cotton. Despite the resistance detected in laboratory bioassays, control failures of Bt cotton have not been reported in China. This early warning may spur proactive countermeasures, including a switch to transgenic cotton producing two or more toxins distinct from Cry1A toxins.
PMCID: PMC3153483  PMID: 21857961
20.  Complementarity-Determining Region 3 Size Spectratypes of T Cell Receptor β Chains in CD8+ T Cells following Antiviral Treatment of Chronic Hepatitis B▿  
An increased CD8+ T cell response to hepatitis B virus (HBV) peptides occurs between 12 and 24 weeks after starting antiviral therapy for chronic hepatitis B. It is not known whether these cells have antiviral function. The aim of this study was to determine whether clonal expansions of CD8+ T cells at these time points predict the virological response to therapy. Peripheral blood CD8+ T cells were obtained from 20 patients treated with lamivudine or telbivudine for chronic hepatitis B at baseline, 12 weeks, and 24 weeks. The CDR3 spectratype of each T cell receptor (TCR) β chain variable region (Vβ) gene family was analyzed, and the changes in the numbers of Vβ families with clonal expansions were compared in subjects with (n = 12) and without (n = 8) a virological response (52 week HBV DNA < 300 copies/ml). The number of CD8+ TCR Vβ families with clonal expansions at 12 weeks relative to baseline (median [10th to 90th percentile], +2.5 [0 to +7] versus +1 [0 to +2], P = 0.03) and at 24 weeks relative to 12 weeks (+1 [0 to +2] versus −1 [−3 to +4], P = 0.006) was higher in subjects with a virological response versus subjects without a virological response, as were interleukin-2 (IL-2) but not IL-21 mRNA levels in peripheral blood mononuclear cells. The duration of new expansions at 12 weeks was higher (P < 0.0001) in responders. Increased numbers of CD8+ T cell expansions after antiviral therapy are associated with a virological response to treatment. These CD8+ T cells are a potential target for a therapeutic vaccine for chronic hepatitis B.
PMCID: PMC3028785  PMID: 21098256
21.  Emergency surgery for perforated gastric malignancy: An institution’s experience and review of the literature 
The aim was to evaluate the outcome of patients who underwent surgery for perforated gastric malignancies.
A review of all patients who underwent surgery for perforated gastric malignancy was performed.
Twelve patients (nine gastric adenocarcinoma and three B-cell lymphoma) formed the study group. Ten (83.3%) had subtotal gastrectomy performed, while two (16.7%) underwent total gastrectomy. All eight patients with adenocarcinoma who survived the initial operation fared poorly. The two patients with lymphoma who survived the surgery underwent subsequent chemotherapy has no disease recurrence currently.
Surgery in perforated gastric malignancy is fraught with numerous challenges.
PMCID: PMC3397585  PMID: 22811822
emergency; surgery; perforation; treatment outcome; malignancy
22.  The alpha-fetoprotein enhancer region activates the albumin and alpha-fetoprotein promoters during liver development 
Developmental biology  2009;336(2):294-300.
The four members of the albumin gene family encode the serum transport proteins albumin, α-fetoprotein, α-albumin, and vitamin D-binding protein. These genes are transcribed primarily in the liver with each having a different pattern of developmental expression. The tight linkage of these genes, particularly that of albumin, α-fetoprotein and α-albumin, and their liver-specific expression, has led to the suggestion that these genes share common regulatory elements. To directly examine whether the α-fetoprotein enhancer region could regulate the albumin gene family, expression of these genes was monitored in mice in which this region was deleted by homologous recombination. Our data indicate that this enhancer region is required for α-fetoprotein and albumin activation early in liver development and α-fetoprotein reactivation during liver regeneration, but that albumin, α-albumin, and vitamin D-binding protein expression later in hepatic development is not affected by the absence of these enhancers. We also demonstrate that RNA polymerase II loading on the α-fetoprotein and albumin promoters is reduced in the absence of this enhancer region, indicating a direct role for these enhancers in the assembly of the RNA Polymerase II complex during liver development.
PMCID: PMC2783961  PMID: 19782060
albumin; alpha-fetoprotein; transcription; liver; mammalian development; enhancers; gene targeting; chromatin immunoprecipitation; RNA Polymerase II
23.  Intranasal Immunization with Chitosan/pCAGGS-flaA Nanoparticles Inhibits Campylobacter jejuni in a White Leghorn Model 
Campylobacter jejuni is the most common zoonotic bacterium associated with human diarrhea, and chickens are considered to be one of the most important sources for human infection, with no effective prophylactic treatment available. We describe here a prophylactic strategy using chitosan-DNA intranasal immunization to induce specific immune responses. The chitosan used for intranasal administration is a natural mucus absorption enhancer, which results in transgenic DNA expression in chicken nasopharynx. Chickens immunized with chitosan-DNA nanoparticles, which carried a gene for the major structural protein FlaA, produced significantly increased levels of serum anti-Campylobacter jejuni IgG and intestinal mucosal antibody (IgA), compared to those treated with chitosan-DNA (pCAGGS). Chitosan-pCAGGS-flaA intranasal immunization induced reductions of bacterial expellation by 2-3 log10 and 2 log10 in large intestine and cecum of chickens, respectively, when administered with the isolated C. jejuni strain. This study demonstrated that intranasal delivery of chitosan-DNA vaccine successfully induced effective immune response and might be a promising vaccine candidate against C. jejuni infection.
PMCID: PMC2948919  PMID: 20936115
24.  Patterns of managing chronic hepatitis B treatment-related drug resistance: a survey of physicians in Mainland China, South Korea, Taiwan, and Thailand 
Hepatology International  2009;3(3):453-460.
The emergence of antiviral resistance can negate the benefits of antiviral therapy in patients with chronic hepatitis B (CHB). This study aimed to assess how physicians in Asia manage suspected antiviral resistance.
Randomly selected CHB-treating physicians in Mainland China, South Korea, Taiwan, and Thailand underwent a face-to-face interview. A standardized questionnaire was used to assess how physicians identify, monitor, and manage suspected resistance and its associated medical costs.
We interviewed 575 physicians from January to May 2008. Most physicians preferred a “prevention-of-antiviral resistance” strategy over a “rescue-once-resistance-develops” strategy. Physicians had encountered lamivudine resistance most frequently (96–100% of respondents), followed by the resistance to adefovir (18–58%) and entecavir (3–7%). While physicians in South Korea and Taiwan have access to resistance testing, physicians in Mainland China and Thailand have limited access to resistance testing but rely on HBV DNA and alanine aminotransferase (ALT) tests to identify resistance. Once resistance is suspected, 60% of the physicians in Mainland China, South Korea, and Thailand monitored these patients quarterly and the remaining 40% opted for monthly follow-up. In comparison, 70% of the Taiwanese physicians monitored these patients monthly. The average total direct medical costs, excluding antiviral costs, to manage a patient during the first year after suspected resistance is identified ranged from USD $319 to USD $709.
Limited access to HBV resistance tests causes physicians in Asia to manage suspected resistance by various HBV DNA assays and ALT tests. This raises concerns that resistance may not be detected early enough to be rescued efficiently.
PMCID: PMC2748378  PMID: 19669246
Chronic hepatitis B; Nucleoside/nucleotide analogs; HBV DNA; ALT; Antiviral resistance; Asia
25.  T Cell Responses to Whole SARS Coronavirus in Humans1 
Effective vaccines should confer long-term protection against future outbreaks of severe acute respiratory syndrome (SARS) caused by a novel zoonotic coronavirus (SARS-CoV) with unknown animal reservoirs. We conducted a cohort study examining multiple parameters of immune responses to SARS-CoV infection, aiming to identify the immune correlates of protection. We used a matrix of overlapping peptides spanning whole SARS-CoV proteome to determine T cell responses from 128 SARS convalescent samples by ex vivo IFN-γ ELISPOT assays. Approximately 50% of convalescent SARS patients were positive for T cell responses, and 90% possessed strongly neutralizing Abs. Fifty-five novel T cell epitopes were identified, with spike protein dominating total T cell responses. CD8+ T cell responses were more frequent and of a greater magnitude than CD4+ T cell responses (p < 0.001). Polychromatic cytometry analysis indicated that the virus-specific T cells from the severe group tended to be a central memory phenotype (CD27+/CD45RO+) with a significantly higher frequency of polyfunctional CD4+ T cells producing IFN-γ, TNF-α, and IL-2, and CD8+ T cells producing IFN-γ, TNF-α, and CD107a (degranulation), as compared with the mild-moderate group. Strong T cell responses correlated significantly (p < 0.05) with higher neutralizing Ab. The serum cytokine profile during acute infection indicated a significant elevation of innate immune responses. Increased Th2 cytokines were observed in patients with fatal infection. Our study provides a roadmap for the immunogenicity of SARS-CoV and types of immune responses that may be responsible for the virus clearance, and should serve as a benchmark for SARS-CoV vaccine design and evaluation.
PMCID: PMC2683413  PMID: 18832706

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