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1.  Anatomical Characteristics of Pulmonary Veins for the Prediction of Postoperative Recurrence after Radiofrequency Catheter Ablation of Atrial Fibrillation 
PLoS ONE  2014;9(4):e93817.
The relationship between focal pulmonary vein potential and atrial fibrillation (AF) has been confirmed. Pulmonary vein (PV) isolation and circumferential pulmonary vein ablation have been the most commonly used procedures of radiofrequency ablation. However, few studies have investigated the relationship between anatomical characteristics of PV and AF recurrences after radiofrequency ablation.
For 267 AF patients treated by radiofrequency catheter ablation, the anatomic structure characteristics of pulmonary veins were assessed by multi-slice spiral computed tomography while the values of left atrial diameter (LAD) were measured with transesophageal ultrasonic cardiogram. After radiofrequency catheter ablation, postoperative recurrence was evaluated during a 10-month term follow-up.
Principal Findings
During follow-up, postoperative recurrence occurred in 44 patients. The mean diameters of LAD, left superior PV, right superior PV, all left PV, and all superior PV were significantly larger in patients with postoperative recurrence (Recurrence vs. Non-recurrence group; 43.9 ± 6.4 mm vs. 40.7 ± 5.6 mm; 18.4 ± 2.1 mm vs. 17.1 ± 3.1 mm; 18.2 ± 2.8 mm vs. 17.2 mm ± 3.9 mm; 16.4 ± 1.5 mm vs. 15.6 ± 2.5 mm; 18.3 ± 2.1 mm vs. 17.1 ± 3.0 mm; respectively; all P < 0.05). Multivariable survival analysis showed that the type and the course of AF, LAD, and the diameters of all superior PV were the independent risk factors for the postoperative recurrence after radiofrequency catheter ablation.
The enlargements of all superior PV and LAD, long course of diseases, and persistent AF were the independent risk factors for the postoperative recurrence after radiofrequency catheter ablation.
PMCID: PMC3976314  PMID: 24705909
2.  Can Fresh Osteochondral Allografts Restore Function in Juveniles With Osteochondritis Dissecans of the Knee? 
Failure of initial treatment for juvenile osteochondritis dissecans (OCD) may require further surgical intervention, including microfracture, autograft chondrocyte implantation, osteochondral autografting, and fresh osteochondral allografting. Although allografts and autografts will restore function in most adults, it is unclear whether fresh osteochondral allograft transplantations similarly restore function in skeletally immature patients who failed conventional treatment.
Therefore, we determined function in (1) daily activity; (2) sports participation; and (3) healing (by imaging) in children with juvenile OCD who failed conventional therapy and underwent fresh osteochondral allograft transplantation.
We retrospectively reviewed 11 children with OCD of the knee treated with a fresh stored osteochondral allograft between 2004 and 2009 (six males and five females). The average age of the children at the time of their allograft surgery was 15.2 years (range, 13–20 years). The clinical assessments included physical examination, radiography, MRI, and a modified Merle D’Aubigné-Postel score. The size of the allograft was an average of 5.11 cm2. The minimum followup was 12 months (average, 24 months; range, 12–41 months).
All patients had returned to activities of daily living without difficulties at 6 months and returned to full sports activities between 9 and 12 months after surgery. The modified Merle D’Aubigné-Postel score improved from an average of 12.7 preoperatively to 16.3 at 24 months postoperatively. Followup radiographs at 2 years showed full graft incorporation and no demarcation between the host and graft bone.
Our observations suggested fresh osteochondral allografts restored short-term function in patients with juvenile OCD who failed standard treatments.
Level of Evidence
Level IV, case series. See Guidelines for Authors for a complete description of levels of evidence.
PMCID: PMC3586015  PMID: 22972653
3.  Does Extracorporeal Shock Wave Therapy Enhance Healing of Osteochondritis Dissecans of the Rabbit Knee?: A Pilot Study 
Severe osteochondritis dissecans (OCD) in children and adolescents often necessitates surgical interventions (ie, drilling, excision, or débridement). Since extracorporeal shock wave therapy (ESWT) enhances healing of long-bone nonunion fractures, we speculated ESWT would reactivate the healing process in OCD lesions.
We asked whether ESWT would enhance articular cartilage quality, bone and cartilage density, and histopathology of osteochondral lesions compared to nontreated controls in an OCD rabbit model.
We harvested a 4-mm-diameter plug of the weightbearing osteochondral surface on the medial femoral condyle of each knee in 20 skeletally immature (8-week-old) female rabbits. We placed a piece of acellular collagen-glycosaminoglycan matrix into the cavity and then replaced the plug. Two weeks after surgery, we sedated each rabbit and treated the right knee in a single setting with shock waves: 4000 impulses at 4 Hz and 18 kV. The left knee was a sham control. Ten weeks after surgery, we assessed cartilage morphology of the lesion using a modified Outerbridge Grading System, bone and cartilage density using histologic imaging, bone and cartilage morphology using the histopathology assessment system, and radiographic bone density and union and compared these parameters between ESWT-treated and control knees.
Histologically, we observed more mature bone formation and better healing (1.1 versus 3.4) and density of the cartilage (60 versus 49) on the treated side. Radiographically, we noted an increase in bony density (154 versus 138) after ESWT.
ESWT accelerated the healing rate and improved cartilage and subchondral bone quality in the OCD rabbit model.
Clinical Relevance
This therapeutic modality may be applicable in OCD treatment in the pediatric population. Future research will be necessary to determine whether it may play a role in healing of human osteochondral defects.
PMCID: PMC3586044  PMID: 22669551
4.  In Vitro Interaction of Pseudomonas aeruginosa with Human Middle Ear Epithelial Cells 
PLoS ONE  2014;9(3):e91885.
Otitis media (OM) is an inflammation of the middle ear which can be acute or chronic. Acute OM is caused by Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis whereas Pseudomonas aeruginosa is a leading cause of chronic suppurative otitis media (CSOM). CSOM is a chronic inflammatory disorder of the middle ear characterized by infection and discharge. The survivors often suffer from hearing loss and neurological sequelae. However, no information is available regarding the interaction of P. aeruginosa with human middle ear epithelial cells (HMEECs).
Methodology and Findings
In the present investigation, we demonstrate that P. aeruginosa is able to enter and survive inside HMEECs via an uptake mechanism that is dependent on microtubule and actin microfilaments. The actin microfilament disrupting agent as well as microtubule inhibitors exhibited significant decrease in invasion of HMEECs by P. aeruginosa. Confocal microscopy demonstrated F-actin condensation associated with bacterial entry. This recruitment of F-actin was transient and returned to normal distribution after bacterial internalization. Scanning electron microscopy demonstrated the presence of bacteria on the surface of HMEECs, and transmission electron microscopy confirmed the internalization of P. aeruginosa located in the plasma membrane-bound vacuoles. We observed a significant decrease in cell invasion of OprF mutant compared to the wild-type strain. P. aeruginosa induced cytotoxicity, as demonstrated by the determination of lactate dehydrogenase levels in culture supernatants of infected HMEECs and by a fluorescent dye-based assay. Interestingly, OprF mutant showed little cell damage compared to wild-type P. aeruginosa.
Conclusions and Significance
This study deciphered the key events in the interaction of P. aeruginosa with HMEECs in vitro and highlighted the role of bacterial outer membrane protein, OprF, in this process. Understanding the molecular mechanisms in the pathogenesis of CSOM will help in identifying novel targets to design effective therapeutic strategies and to prevent hearing loss.
PMCID: PMC3954863  PMID: 24632826
5.  Congenital Malaria in China 
Congenital malaria, in which infants are directly infected with malaria parasites from their mother prior to or during birth, is a potentially life-threatening condition that occurs at relatively low rates in malaria-endemic regions. It is recognized as a serious problem in Plasmodium falciparum–endemic sub-Saharan Africa, where recent data suggests that it is more common than previously believed. In such regions where malaria transmission is high, neonates may be protected from disease caused by congenital malaria through the transfer of maternal antibodies against the parasite. However, in low P. vivax–endemic regions, immunity to vivax malaria is low; thus, there is the likelihood that congenital vivax malaria poses a more significant threat to newborn health. Malaria had previously been a major parasitic disease in China, and congenital malaria case reports in Chinese offer valuable information for understanding the risks posed by congenital malaria to neonatal health. As most of the literature documenting congenital malaria cases in China are written in Chinese and therefore are not easily accessible to the global malaria research community, we have undertaken an extensive review of the Chinese literature on this subject.
Methods/Principal Findings
Here, we reviewed congenital malaria cases from three major searchable Chinese journal databases, concentrating on data from 1915 through 2011. Following extensive screening, a total of 104 cases of congenital malaria were identified. These cases were distributed mainly in the eastern, central, and southern regions of China, as well as in the low-lying region of southwest China. The dominant species was P. vivax (92.50%), reflecting the malaria parasite species distribution in China. The leading clinical presentation was fever, and other clinical presentations were anaemia, jaundice, paleness, diarrhoea, vomiting, and general weakness. With the exception of two cases, all patients were cured with antimalarial drugs such as chloroquine, quinine, artemether, and artesunate.
The symptoms of congenital malaria vary significantly between cases, so clear and early diagnosis is difficult. We suggest that active surveillance might be necessary for neonates born to mothers with a history of malaria.
PMCID: PMC3953009  PMID: 24626148
6.  Regulation of matrix metalloproteinase-9 protein expression by 1α,25-(OH)2D3 during osteoclast differentiation 
Journal of Veterinary Science  2014;15(1):133-140.
To investigate 1α,25-(OH)2D3 regulation of matrix metalloproteinase-9 (MMP-9) protein expression during osteoclast formation and differentiation, receptor activator of nuclear factor κB ligand (RANKL) and macrophage colony-stimulating factor (M-CSF) were administered to induce the differentiation of RAW264.7 cells into osteoclasts. The cells were incubated with different concentrations of 1α,25-(OH)2D3 during culturing, and cell proliferation was measured using the methylthiazol tetrazolium method. Osteoclast formation was confirmed using tartrate-resistant acid phosphatase (TRAP) staining and assessing bone lacunar resorption. MMP-9 protein expression levels were measured with Western blotting. We showed that 1α,25-(OH)2D3 inhibited RAW264.7 cell proliferation induced by RANKL and M-CSF, increased the numbers of TRAP-positive osteoclasts and their nuclei, enhanced osteoclast bone resorption, and promoted MMP-9 protein expression in a concentration-dependent manner. These findings indicate that 1α,25-(OH)2D3 administered at a physiological relevant concentration promoted osteoclast formation and could regulate osteoclast bone metabolism by increasing MMP-9 protein expression during osteoclast differentiation.
PMCID: PMC3973756  PMID: 24136216
1α,25-(OH)2D3; bone lacunar resorption; MMP-9; osteoclast; TRAP
7.  Microbleeds in Late-Life Depression: Comparison of Early- and Late-Onset Depression 
BioMed Research International  2014;2014:682092.
Late-life depression could be classified roughly as early-onset depression (EOD) and late-onset depression (LOD). LOD was proved to be associated with cerebral lesions including white matter hyperintensities (WMH) and silent brain infarctions (SBI), differently from EOD. However, it is unclear whether similar association is present between LOD and microbleeds which are also silent lesions. In this study, 195 patients of late-life depression were evaluated and divided into EOD, presenile-onset depression (POD), and LOD groups; 85 healthy elderly controls were enrolled as controls. Subjects were scanned by MRI including susceptibility weighted images to evaluate white matter hyperintensities (WMH), silent brain infarctions (SBI), and microbleeds. The severity of depression was evaluated with 15-item Geriatric Depression Scale. Psychosocial factors were investigated with Scale of Life Events and Lubben Social Network Scale. Logistic regression and linear regression were performed to identify the independent risk factors for depression. Results showed that LOD patients had higher prevalence of microbleeds than EOD, POD, and control patients. The prevalence of lobar microbleeds and microbleeds in the left hemisphere was the independent risk factor for the occurrence of LOD; a high number of microbleeds were associated with severe state of LOD, whereas life events and lack of social support were more important for EOD and POD. All these results indicated that Microbleeds especially lobar microbleeds and microbleeds in the left hemisphere were associated with LOD but not with EOD.
PMCID: PMC3955674  PMID: 24719883
8.  Synchronous double primary lung cancer: a report of three cases 
The incidence of synchronous multiple primary lung cancers is on the rise due to improvements in computed tomography (CT) scanning and increasing use of positron emission tomography scanning and other diagnostic modalities. We report three cases of synchronous double primary lung cancer (DPLC) diagnosed based on CT findings, results of bronchoscopy and histological study. All patients had a long-term history of heavy smoking. Squamous cell carcinoma and small cell carcinoma were the most common histological types in these cases. DPLC frequently involves the upper lobes of left or right lung. Future molecular biological studies on DPLC should be warranted to shed light on the mechanisms underlying the pathogenesis of DPLC and the role of targeted therapy in this condition.
PMCID: PMC3937752  PMID: 24653639
Synchronous double primary lung cancer; diagnosis; pathology
9.  Feature Optimization for Long-Range Visual Homing in Changing Environments 
Sensors (Basel, Switzerland)  2014;14(2):3342-3361.
This paper introduces a feature optimization method for robot long-range feature-based visual homing in changing environments. To cope with the changing environmental appearance, the optimization procedure is introduced to distinguish the most relevant features for feature-based visual homing, including the spatial distribution, selection and updating. In the previous research on feature-based visual homing, less effort has been spent on the way to improve the feature distribution to get uniformly distributed features, which are closely related to homing performance. This paper presents a modified feature extraction algorithm to decrease the influence of anisotropic feature distribution. In addition, the feature selection and updating mechanisms, which have hardly drawn any attention in the domain of feature-based visual homing, are crucial in improving homing accuracy and in maintaining the representation of changing environments. To verify the feasibility of the proposal, several comprehensive evaluations are conducted. The results indicate that the feature optimization method can find optimal feature sets for feature-based visual homing, and adapt the appearance representation to the changing environments as well.
PMCID: PMC3958223  PMID: 24556671
long-range visual homing; uniform distribution; feature selection; feature updating; changing environments
10.  Impact of Cigarette Smoking on Outcome of Hepatocellular Carcinoma after Surgery in Patients with Hepatitis B 
PLoS ONE  2014;9(1):e85077.
Background and Objectives
Cigarette smoking is a potential risk factor for hepatocellular carcinoma (HCC) initiation, partially through interaction with hepatitis B virus (HBV). We examined the hypothesis that cigarette smoking might be associated with HBV-related HCC recurrence and patient survival after curative surgery.
Patients and Methods
Data of 302 patients with HBV infection who had undergone curative resection for HCC were prospectively collected from 2008 to 2011. Smoking status and smoking quantity (pack-years, PY) were asked at admission. Factors affecting recurrence-free survival (RFS) were examined. RFS and liver-specific mortality (LSM) stratified by risk factors were compared with log-rank test.
109 were current smokers. Current smokers were not different from non-smokers in tumor burden and surgical procedure. Univariate and multivariate analysis identified that heavy smoking (PY ≥20) was the most significant factor associated with HBV-related HCC recurrence after curative surgical resection (p = 0.001), followed by anti-HBV treatment (p<0.01), current smoking (p = 0.028), surgical margin <1 cm (p = 0.048) and blood transfusion >600 ml (p = 0.028). The median RFS in non-smokers, ex-smokers and current smokers was 34 months, 24 months and 26 months, respectively (p = 0.033). Current smokers had significantly worse RFS rate and increased 5-year cumulative LSM than non-smokers (p = 0.024, and p<0.001, respectively). Heavy smokers had significantly worse RFS than non- and light smokers (0
Smoking history and quantity appears to be risk factors for HBV-related HCC recurrence and LSM of patients after surgery. For smokers, continued smoking postoperatively might accelerate tumor recurrence and patient death. Therefore, smoking abstinence should be strongly recommended to patients pre- and postoperatively.
PMCID: PMC3893178  PMID: 24454795
The Scientific World Journal  2014;2014:412534.
We obtain some equivalent conditions of (strictly) pseudoconvex and quasiconvex fuzzy mappings. These results will be useful to present some characterizations of solutions for fuzzy mathematical programming.
PMCID: PMC3910391  PMID: 24511284
The Scientific World Journal  2013;2013:459692.
microRNAs (miRNA), a sort of noncoding RNAs widely distributed in eukaryotic cells, could regulate gene expression by inhibiting transcription or translation. They were involved in important physiological and pathological processes including growth, development, and occurrence and progression of diseases. miRNAs are crucial for the development of the nervous system. Recent studies have demonstrated that some miRNAs play important roles in the occurrence and development of ischemic cerebrovascular diseases such as stroke and were also involved in the occurrence and development of poststroke depression (PSD). Herein, studies on the role of miRNAs in the cerebral ischemia and PSD were reviewed, and results may be helpful for the diagnosis and prognosis of cerebral ischemia and PSD with miRNAs in clinical practice.
PMCID: PMC3865697  PMID: 24363618
Indian Journal of Microbiology  2012;52(4):565-568.
One isolate from bark beetle galleries was identified and characterized using morphological and molecular methodology, and described and illustrated based on these data. These results identified a new species distribution record in China for Neoscytalidium novaehollandiae. Species morphology and micrographs are provided in this paper. The specimens are stored in Northeast Forestry University.
PMCID: PMC3516645  PMID: 24293711
Neoscytalidium novaehollandiae; Ulmus densa; New record; China
To investigate the prevalence of subclinical thyroid dysfunction and the relationship between thyrotropin levels and cardiovascular risk factors in residents of the coastal area of China.
Atotalof4256individuals(mean[±SD]age50.51±14.24years; 2079 males, 2177 females,) were enrolled in the present study. Sex, blood pressure, body mass index, waist-to-hip ratio, serum levels of fasting glucose, total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglycerides, uric acid and smoking status were measured. The relationship between thyrotropin levels and cardiovascular risk factors was analyzed.
The overall prevalence of thyroid dysfunction was 11.07%. The prevalence of subclinical hypothyroidism (6.32%) was higher than that of hyperthyroidism (1.53%). The prevalence of thyroid dysfunction among female subjects was higher than that among male subjects (16.54% versus 5.34%, respectively; P<0.001). Significant differences were detected with respect to body mass index (P=0.026), waist-to-hip ratio (P<0.001), fasting glucose levels (P=0.001), total cholesterol levels (P=0.013), triglyceride levels (P=0.003) and smoking status according to different thyrotropin levels.
The prevalence of thyroid dysfunction was high in residents of China’s coastal area. Significant differences were detected with regard to body mass index, waist-to-hip ratio, fasting glucose levels, total cholesterol levels, triglyceride levels and smoking status according to different thyrotropin levels.
PMCID: PMC3716495  PMID: 24294042
Cardiovascular risk factors; Coronary heart disease; Thyroid dysfunction
Journal of Veterinary Science  2013;14(4):405-412.
The purpose of this study was to determine whether osteoprotegerin (OPG) could affect osteoclat differentiation and activation under serum-free conditions. Both duck embryo bone marrow cells and RAW264.7 cells were incubated with macrophage colony stimulatory factor (M-CSF) and receptor activator for nuclear factor κB ligand (RANKL) in serum-free medium to promote osteoclastogenesis. During cultivation, 0, 10, 20, 50, and 100 ng/mL OPG were added to various groups of cells. Osteoclast differentiation and activation were monitored via tartrate-resistant acid phosphatase (TRAP) staining, filamentous-actin rings analysis, and a bone resorption assay. Furthermore, the expression osteoclast-related genes, such as TRAP and receptor activator for nuclear factor κB (RANK), that was influenced by OPG in RAW264.7 cells was examined using real-time polymerase chain reaction. In summary, findings from the present study suggested that M-CSF with RANKL can promote osteoclast differentiation and activation, and enhance the expression of TRAP and RANK mRNA in osteoclasts. In contrast, OPG inhibited these activities under serum-free conditions.
PMCID: PMC3885733  PMID: 23820214
activation; differentiation; osteoclast; osteoprotegerin; serum-free
PLoS ONE  2013;8(11):e81368.
Lung alveolar development in late gestation is a process important to postnatal survival. Follistatin-like 1 (Fstl1) is a matricellular protein of the Bmp antagonist class, which is involved in the differentiation/maturation of alveolar epithelial cells during saccular stage of lung development. This study investigates the role of Fstl1 on elastin deposition in mesenchyme and subsequent secondary septation in the late gestation stage of terminal saccular formation. To this aim, we modified the renal capsule allograft model for lung organ culture by grafting diced E15.5 distal lung underneath the renal capsule of syngeneic host and cultured up to 7 days. The saccular development of the diced lung allografts, as indicated by the morphology, epithelial and vascular developments, occurred in a manner similar to that in utero. Fstl1 deficiency caused atelectatic phenotype companied by impaired epithelial differentiation in D3 Fstl1−/− lung allografts, which is similar to that of E18.5 Fstl1−/− lungs, supporting the role of Fstl1 during saccular stage. Inhibition of Bmp signaling by intraperitoneal injection of dorsomorphin in the host mice rescued the pulmonary atelectasis of D3 Fstl1−/− allografts. Furthermore, a marked reduction in elastin expression and deposition was observed in walls of air sacs of E18.5 Fstl1−/− lungs and at the tips of the developing alveolar septae of D7 Fstl1−/− allografts. Thus, in addition to its role on alveolar epithelium, Fstl1 is crucial for elastin expression and deposition in mesenchyme during lung alveologenesis. Our data demonstrates that the modified renal capsule allograft model for lung organ culture is a robust and efficient technique to increase our understanding of saccular stage of lung development.
PMCID: PMC3839892  PMID: 24282586
PLoS ONE  2013;8(9):e72985.
Estrogen deficiency is associated with increased incidence of cardiovascular diseases. But merely estrogen supplementary treatment can induce many severe complications such as breast cancer. The present study was designed to elucidate molecular mechanisms underlying increased susceptibility of arrhythmogenesis during myocardial infarction with estrogen deprivation, which provides us a new target to cure cardiac disease accompanied with estrogen deprivation. We successfully established a rat model of myocardial ischemia (MI) accompanied with estrogen deprivation by coronary artery ligation and ovariectomy (OVX). Vulnerability and mortality of ventricular arrhythmias increased in estrogen deficiency rats compared to non estrogen deficiency rats when suffered MI, which was associated with down-regulation of microRNA-151-5p (miR-151-5p). Luciferase Reporter Assay demonstrated that miR-151-5p can bind to the 3′-UTR of FXYD1 (coding gene of phospholemman, PLM) and inhibit its expression. We found that the expression of PLM was increased in (OVX+MI) group compared with MI group. More changes such as down-regulation of Kir2.1/IK1, calcium overload had emerged in (OVX+MI) group compared to MI group merely. Transfection of miR-151-5p into primary cultured myocytes decreased PLM levels and [Ca2+]i, however, increased Kir2.1 levels. These effects were abolished by the antisense oligonucleotides against miR-151-5p. Co-immunoprecipitation and immunofluorescent experiments confirmed the co-localization between Kir2.1 and PLM in rat ventricular tissue. We conclude that the increased ventricular arrhythmias vulnerability in response to acute myocardial ischemia in rat is critically dependent upon down-regulation of miR-151-5p. These findings support the proposal that miR-151-5p could be a potential therapeutic target for the prevention of ischemic arrhythmias in the subjects with estrogen deficiency.
PMCID: PMC3767733  PMID: 24039836
Obesity (Silver Spring, Md.)  2009;17(8):1581-1587.
The increasing prevalence of metabolic syndrome (MS) poses a serious public health problem worldwide. Effective prevention and intervention require improved understanding of the factors that contribute to MS. We analyzed data on a large twin cohort to estimate genetic and environmental contributions to MS and to major MS components and their inter-correlations: waist circumference, systolic and diastolic blood pressure, fasting plasma glucose, triglycerides, and high density lipoprotein cholesterol. We applied structural equation modeling to determine genetic and environmental structure of MS and its major components, using 1,617 adult female twin pairs recruited from rural China. The heritability estimate for MS was 0.42 (95% CI: 0.00–0.83) in this sample with low MS prevalence (4.4%). For MS components, heritability estimates were statistically significant and ranged from 0.13 to 0.64 highest for WC, followed by TG, SBP, DBP, HDL-C, and FPG. HDL-C was mainly influenced by common environmental factors (0.62, 95%CI: 0.58–0.62), while the other five MS components were largely influenced by unique environmental factors (0.32–0.44). Bivariate Cholesky decomposition analysis indicated that the clinical clustering of MS components may be explained by shared genetic and/or environmental factors. Our study underscores the importance of examining MS components as inter-correlated traits, and to carefully consider environmental and genetic factors in studying MS etiology.
PMCID: PMC3766632  PMID: 19407809
metabolic syndrome; twin study; heritability; Chinese
Vitamin nutritional status may influence some xenobiotic metabolism or vice versa.
This analysis examines the relationship between B-vitamin concentrations and 1,1-dichloro-2,2-bis(p-chlorophenyl)ethylene (DDT) isomers and metabolites in healthy women. Serum pp′DDT, pp′DDE, pp′DDD, op′DDT, op′DDE, and serum folate, cysteine, and vitamins B6 and B12 were measured in 296 nonsmoking female textile workers (21–34 yr) in Anhui, China. Mean (SD) age and body mass index of this cohort were 24.9 (1.5) y and 19.7 (2.0) kg/m2, respectively.
Median pp′DDT, pp′DDE, pp′DDD, op′DDT, and op′DDE were 1.5, 29.2, 0.22, 0.17, and 0.09 ng/g, respectively. Median folate and cysteine were 9.2 and 200.0 nmol/L, respectively. Folate was significantly inversely associated with pp′DDT and pp′DDE: β (95% confidence interval [CI]) = −0.23 (−0.39, −0.07) and −0.20 (−0.36, −0.05), respectively, and it was marginally associated with pp′DDD. Cysteine was significantly inversely associated with pp′DDT, β (95% CI) = −0.69 (−1.00, −0.37); pp′DDE, β (95% CI) = −0.32 (−0.62, −0.02); pp′DDD, β (95% CI) = −0.31 (−0.59, −0.03); and op′DDT, β (95% CI) = −0.35 (−0.68, −0.02).
Folate and cysteine are independently inversely associated with DDT isomers, adjusting for vitamins B6 and B12, age, and body mass index. These nutrients may play a role in DDT metabolism; however, it is also possible that DDT may exert a negative impact on folate and cysteine levels. Longitudinal studies are needed to ascertain the direction of this association.
PMCID: PMC3763738  PMID: 20368376
DDT isomers/metabolites; folate; cysteine; vitamin B6; vitamin B12
Deafness is a heterogeneous trait with many known genetic and environmental causes. Hereditary hearing loss is an extremely common disorder in the general population. Mutations in mitochondrial DNA (mtDNA) are known to be associated with nonsyndromic deafness (NSD) and syndromic deafness. The objective of this article is to investigate the frequency of common mitochondrial mutations (A1555G, G7444A, and A3243G) in an ethnically diverse cohort of probands with NSD from South Florida. These patients were ascertained at the University of Miami. Polymerase chain reaction–restriction fragment length polymorphism analysis and direct sequencing methods were used for mutation screening in a cohort of 217 patients with NSD. The frequency of common mitochondrial mutations is 1.84% (4/217) in this cohort. A1555G and G7444A accounted for four patients with NSD. Our mutation frequencies are comparable with those previously reported in other populations, indicating that mutations in mtDNA are an important cause of NSD in our patient cohort.
PMCID: PMC3438807  PMID: 22853457
Sleep medicine  2011;12(7):693-699.
There are limited data about the role of gender on the relationship between sleep duration and blood pressure (BP) from rural populations.
We conducted a cross-sectional rural population-based study. This report includes 1,033 men and 783 women aged 18–65 years from a cohort of twins enrolled in Anhui, China, between 2005 and 2008. Sleep duration was derived from typical bedtime, wake-up time, and sleep latency as reported on a standard sleep questionnaire. Primary outcomes included measured systolic blood pressure (SBP) and diastolic blood pressure (DBP). High blood pressure (HBP) was defined as SBP≥130 mmHg, DBP ≥85 mmHg, or physician diagnosed hypertension. Linear and logistic regression models were used to assess gender-specific associations between sleep duration and BP or HBP, respectively, with adjustment for known risk factors including adiposity and sleep-related disorder risk from the questionnaires. Generalized estimating equations were used to account for intra-twin pair correlations.
Compared with those sleeping 7 to less than 9 hours, women sleeping <7 hours had a higher risk of HBP (odds ratios [ORs] 3.0, 95% confidence interval [CI], 1.4–6.6); men sleeping ≥9 hours had a higher risk of HBP (ORs=1.5, 95%CI: 1.1–2.2).
Among rural Chinese adults, a gender-specific association of sleep duration with BP exists such that HBP is associated with short sleep duration in women and long sleep duration in men. Longitudinal studies are needed to further examine the temporal relationship and biological mechanisms underlying sleep duration and BP in this population. Our findings underscore the potential importance of appropriate sleep duration for optimal blood pressure.
PMCID: PMC3755492  PMID: 21764369
sleep duration; high blood pressure; gender difference; rural Chinese
To explore the effects and potential mechanisms of curcumin on retinal Müller cell in early diabetic rats.
Diabetic rats were induced by a single intraperitoneal injection of streptozotocin (STZ). Male Sprague-Dawley (SD) rats were randomly assigned into 4 groups: control group (naïve SD rats administered with a single intraperitoneal injection of citric buffer), diabetic group (STZ-diabetic rats), dimethyl sulfoxide (DMSO) group (diabetic rats intraperitoneally administered with mixture of DMSO and normal saline, once a day) and curcumin group (diabetic rats intraperitoneally administered with curcumin, 80mg/kg, once a day). Three months after diabetes onset, malondialdehyde (MDA, indication of oxidative stress level) and reduced glutathione (GSH) in retina were detected with kits, glial fibrillary acidic protein (GFAP) in retina was revealed by immunohistochemistry and Western blot, and retinal glutamine synthetase (GS) were observed by Western blot.
Compared with control group, retinal MDA was increased, and GSH was decreased in diabetic and DMSO groups (P<0.05, respectively). While, retinal MDA and GSH in curcumin group showed no difference compared with control group (P>0.05). Furthermore, up-regulation of retinal GFAP and down-regulation of retinal GS were detected in diabetic and DMSO groups, and no alteration could be observed in curcumin group revealed with Western blot. Compared with control group, retinal Müller cells showed significant increase in GFAP immunochemistry staining in diabetic and DMSO groups. Moreover, GFAP-positive staining was decreased in curcumin group compared with diabetic group.
Curcumin inhibits diabetic retinal oxidative stress, protects Müller cell, and prevents the down-regulation of GS in diabetic retina. Therefore, curcumin has a therapeutic potential in the treatment of diabetic retinopathy (DR).
PMCID: PMC3755296  PMID: 23991371
diabetic retinopathy; curcumin; oxidative stress; Müller cell
Science translational medicine  2011;3(92):92ra65.
A glycosylated polypeptide, β-defensin 126 (DEFB126), derived from the epididymis and adsorbed onto the sperm surface, has been implicated in immunoprotection and efficient movement of sperm in mucosal fluids of the female reproductive tract. Here, we report a sequence variant in DEFB126 that has a 2-nucleotide deletion in the open reading frame, which generates a non-stop mRNA. The allele frequency of this variant sequence is high in both a European (0.47) and a Chinese (0.45) population cohort. Binding of the Agaricus bisporus lectin to the sperm surface glycocalyx was significantly lower in men with the homozygous variant (del/del) genotype than in those with either a del/wt or wt/wt genotype, suggesting an altered sperm glycocalyx with fewer O-linked oligosaccharides in del/del men. Moreover, sperm from the del/del donors exhibited an 84% reduction in the rate of penetration of a hyaluronic acid (HA) gel, a surrogate for cervical mucus, compared to the other genotypes. This reduction in sperm performance in HA gels was not a result of decreased progressive motility (average curvilinear velocity) or morphological deficits. However, DEFB126 genotype and lectin binding were highly correlated with performance in the penetration assays. In a prospective cohort study of newly married couples who were trying to conceive by natural means, couples were less likely to become pregnant and took longer to achieve a live birth if the male partner was homozygous for the variant sequence. This common sequence variation in DEFB126, and its apparent cause of impaired reproductive function, provides an opportunity to better understand, clinically evaluate, and possibly treat human infertility.
PMCID: PMC3736313  PMID: 21775668
Cell Research  2013;23(8):1043-1054.
Abscisic acid (ABA) is the most important hormone for plants to resist drought and other abiotic stresses. ABA binds directly to the PYR/PYL family of ABA receptors, resulting in inhibition of type 2C phosphatases (PP2C) and activation of downstream ABA signaling. It is envisioned that intervention of ABA signaling by small molecules could help plants to overcome abiotic stresses such as drought, cold and soil salinity. However, chemical instability and rapid catabolism by plant enzymes limit the practical application of ABA itself. Here we report the identification of a small molecule ABA mimic (AM1) that acts as a potent activator of multiple members of the family of ABA receptors. In Arabidopsis, AM1 activates a gene network that is highly similar to that induced by ABA. Treatments with AM1 inhibit seed germination, prevent leaf water loss, and promote drought resistance. We solved the crystal structure of AM1 in complex with the PYL2 ABA receptor and the HAB1 PP2C, which revealed that AM1 mediates a gate-latch-lock interacting network, a structural feature that is conserved in the ABA-bound receptor/PP2C complex. Together, these results demonstrate that a single small molecule ABA mimic can activate multiple ABA receptors and protect plants from water loss and drought stress. Moreover, the AM1 complex crystal structure provides a structural basis for designing the next generation of ABA-mimicking small molecules.
PMCID: PMC3731570  PMID: 23835477
abscisic acid; plant hormone; drought resistance; crystal structure; ABA-mimicking ligand
Clinics  2013;68(7):968-973.
To investigate the effect of obstructive sleep apnea and continuous positive airway pressure treatment on serum butyrylcholinesterase activity and ischemia-modified albumin levels.
Thirty-two patients with obstructive sleep apnea and 30 age- and sex-matched controls were enrolled and underwent a diagnostic polysomnogram. The serum butyrylcholinesterase activity, ischemia-modified albumin levels, metabolic parameters, and polysomnography scores were detected and evaluated. Nine patients were studied before and after treatment with continuous positive airway pressure.
The serum ischemia-modified albumin levels were significantly higher and the butyrylcholinesterase activity was significantly lower in patients with obstructive sleep apnea than in the controls (p<0.001). The continuous positive airway pressure treatment decreased the modified albumin levels and elevated the buthrylcholinesterase activity (p = 0.019 and p = 0.023, respectively). The modified albumin levels were positively correlated with the apnea-hypopnea index (r = 0.462, p = 0.008) at baseline. Elevated ischemia-modified albumin levels can be more accurate than butyrylcholinesterase activity at reflecting the presence of obstructive sleep apnea. Receiver operating characteristic curves revealed a significant difference between the areas under the curve 0.916 for ischemia-modified albumin and 0.777 for butyrylcholinesterase (z = 2.154, p = 0.031).
The elevated ischemia-modified albumin level was significantly associated with obstructive sleep apnea and was more sensitive than butyrylcholinesterase activity in reflecting obstructive sleep apnea. The continuous positive airway pressure treatment helped to ameliorate the imbalance.
PMCID: PMC3714914  PMID: 23917661
Ischemia-Modified Albumin; Butyrylcholinesterase; Obstructive Sleep Apnea; Biomarker

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