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1.  Percutaneous balloon kyphoplasty for the treatment of vertebral compression fractures 
BMC Surgery  2014;14:3.
Vertebral compression fractures (VCFs) constitute a major health care problem, not only because of their high incidence but also because of their direct and indirect negative impacts on both patients’ health-related quality of life and costs to the health care system. Two minimally invasive surgical approaches were developed for the management of symptomatic VCFs: balloon kyphoplasty and vertebroplasty. The purpose of this study was to evaluate the effectiveness and safety of balloon kyphoplasty in the treatment of symptomatic VCFs.
Between July 2011 and June 2012, one hundred and eighty-seven patients with two hundred and fifty-one vertebras received balloon kyphoplasty in our hospital. There were sixty-five male and one hundred and twenty-two female patients with an average age of 74.5 (range, 61 to 95 years). The pain symptoms and quality of life, were measured before operation and at one day, three months, six months and one year following kyphoplasty. Radiographic data including restoration of kyphotic angle, anterior vertebral height, and any leakage of cement were defined.
The mean visual analog pain scale decreased from a preoperative value of 7.7 to 2.2 at one day (p < .05) following operation and the Oswestry Disability Index improved from 56.8 to 18.3 (p < .05). The kyphotic angle improved from a mean of 14.4° before surgery to 6.7° at one day after surgery (p < .05). The mean anterior vertebral height increased significantly from 52% before surgery to 74.5% at one day after surgery (p < .05) and 70.2% at one year follow-up. Minor cement extravasations were observed in twenty-nine out of two hundred and fifty-one procedures, including six leakage via basivertebral vein, three leakage via segmental vein and twenty leakage through a cortical defect. None of the leakages were associated with any clinical consequences.
Balloon kyphoplasty not only rapidly reduced pain and disability but also restored sagittal alignment in our patients at one-year follow-up. The treatment of osteoporotic vertebral compression fractures with balloon kyphoplasty is a safe, effective, and minimally invasive procedure that provides satisfactory clinical results.
PMCID: PMC3922728  PMID: 24423182
2.  High-Resolution Transcriptomic Analyses of Sinorhizobium sp. NGR234 Bacteroids in Determinate Nodules of Vigna unguiculata and Indeterminate Nodules of Leucaena leucocephala 
PLoS ONE  2013;8(8):e70531.
The rhizobium-legume symbiosis is a model system for studying mutualistic interactions between bacteria and eukaryotes. Sinorhizobium sp. NGR234 is distinguished by its ability to form either indeterminate nodules or determinate nodules with diverse legumes. Here, we presented a high-resolution RNA-seq transcriptomic analysis of NGR234 bacteroids in indeterminate nodules of Leucaena leucocephala and determinate nodules of Vigna unguiculata. In contrast to exponentially growing free-living bacteria, non-growing bacteroids from both legumes recruited several common cellular functions such as cbb3 oxidase, thiamine biosynthesis, nitrate reduction pathway (NO-producing), succinate metabolism, PHB (poly-3-hydroxybutyrate) biosynthesis and phosphate/phosphonate transporters. However, different transcription profiles between bacteroids from two legumes were also uncovered for genes involved in the biosynthesis of exopolysaccharides, lipopolysaccharides, T3SS (type three secretion system) and effector proteins, cytochrome bd ubiquinol oxidase, PQQ (pyrroloquinoline quinone), cytochrome c550, pseudoazurin, biotin, phasins and glycolate oxidase, and in the metabolism of glutamate and phenylalanine. Noteworthy were the distinct expression patterns of genes encoding phasins, which are thought to be involved in regulating the surface/volume ratio of PHB granules. These patterns are in good agreement with the observed granule size difference between bacteroids from L. leucocephala and V. unguiculata.
PMCID: PMC3732241  PMID: 23936444
3.  Robust Markers Reflecting Phylogeny and Taxonomy of Rhizobia 
PLoS ONE  2012;7(9):e44936.
Genomic ANI (Average Nucleotide Identity) has been found to be able to replace DNA-DNA hybridization in prokaryote taxonomy. The ANI of each of the core genes that has a phylogeny congruent with the reference species tree of rhizobia was compared to the genomic ANI. This allowed us to identify three housekeeping genes (SMc00019-truA-thrA) whose ANI reflected the intraspecies and interspecies genomic ANI among rhizobial strains, revealing an ANI gap (≥2%) between the inter- and intra-species comparisons. The intraspecies (96%) and interspecies (94%) ANI boundaries calculated from three genes (SMc00019-truA-thrA) provided a criterion for bacterial species definition and confirmed 621/629 of known interspecies relationships within Bradyrhizobium, Mesorhizobium, Sinorhizobium and Rhizobium. Some widely studied strains should be renamed. The SMc00019-truA-thrA ANI also correlates well with the genomic ANI of strains in Agrobacterium, Methylobacterium, Ralstonia, Rhodopseudomonas, Cupriavidus and Burkholderia, suggesting their wide applicability in other bacteria.
PMCID: PMC3444505  PMID: 23028691
4.  Biodiversity and Biogeography of Rhizobia Associated with Soybean Plants Grown in the North China Plain ▿ †  
Applied and Environmental Microbiology  2011;77(18):6331-6342.
As the putative center of origin for soybean and the second largest region of soybean production in China, the North China Plain covers temperate and subtropical regions with diverse soil characteristics. However, the soybean rhizobia in this plain have not been sufficiently studied. To investigate the biodiversity and biogeography of soybean rhizobia in this plain, a total of 309 isolates of symbiotic bacteria from the soybean nodules collected from 16 sampling sites were studied by molecular characterization. These isolates were classified into 10 genospecies belonging to the genera Sinorhizobium and Bradyrhizobium, including four novel groups, with S. fredii (68.28%) as the dominant group. The phylogeny of symbiotic genes nodC and nifH defined four lineages among the isolates associated with Sinorhizobium fredii, Bradyrhizobium elkanii, B. japonicum, and B. yuanmingense, demonstrating the different origins of symbiotic genes and their coevolution with the chromosome. The possible lateral transfer of symbiotic genes was detected in several cases. The association between soil factors (available N, P, and K and pH) and the distribution of genospecies suggest clear biogeographic patterns: Sinorhizobium spp. were superdominant in sampling sites with alkaline-saline soils, while Bradyrhizobium spp. were more abundant in neutral soils. This study clarified the biodiversity and biogeography of soybean rhizobia in the North China Plain.
PMCID: PMC3187167  PMID: 21784912
5.  The Compliance of Doctors with Viral Hepatitis B Screening and Antiviral Prophylaxis in Cancer Patients Receiving Cytotoxic Chemotherapy Using a Hospital-Based Screening Reminder System 
PLoS ONE  2015;10(2):e0116978.
Background and Aim
Screenings for hepatitis B surface antigen (HBsAg) and antiviral prophylaxis are recommended for HBsAg-positive patients before the start of cytotoxic chemotherapy; however, compliance with these recommendations varies among doctors. We investigated the compliance of doctors with these recommendations using a reminder system and assessed the outcomes of HBsAg-positive patients receiving cytotoxic chemotherapy.
Using a computer-assisted reminder system, doctors were alerted of both HBsAg screening and antiviral prophylaxis prior to prescribing chemotherapy. The compliance between different doctors and outcomes of patients were investigated during the period of execution of this system. The rates of compliance with both recommendations were compared among various cancer types.
A total of 1053 patients were enrolled, of which only 88 had previous data pertaining to HBsAg status. Using this reminder system, an overall screening rate of 85.5% (825/965) was achieved and did not significantly differ according to cancer type. However, the overall antiviral prophylactic rate was only 45.5% (61/134). The rates of antiviral prophylaxis were lower for doctors treating lung, breast and colorectal cancers than for those treating hematological malignancies (all p<0.05). Consequently, the rate of HBV reactivation was lower in patients who received antiviral prophylaxis than in those who did not (1.6% vs. 15.1%; p<0.01). Multivariate analysis revealed that male gender and antiviral prophylaxis were both related to reactivation of hepatitis B (p<0.05).
By using this reminder system, the overall screening rate for HBsAg was satisfactory, whereas the antiviral prophylaxis was inadequate in patients with solid tumors due to the varying compliance of the attending doctors. Further strategies to improve both screening and prophylaxis are needed to minimize HBV-related events during cytotoxic chemotherapy.
PMCID: PMC4319781  PMID: 25658926
6.  Is schizophrenia associated with an increased risk of chronic kidney disease? A nationwide matched-cohort study 
BMJ Open  2015;5(1):e006777.
The impact of schizophrenia on vital diseases, such as chronic kidney disease (CKD), has not as yet been verified. This study aims to establish whether there is an association between schizophrenia and CKD.
A nationwide matched cohort study.
Taiwan's National Health Insurance Research Database.
A total of 2338 patients with schizophrenia, and 7014 controls without schizophrenia (1:3), matched cohort for sex, age group, geography, urbanisation and monthly income, between 1 January 2003 and 31 December 2007, based on the International Classifications of Disease Ninth Edition (ICD-9), Clinical Modification codes.
Primary and secondary outcome measures
After making adjustments for confounding risk factors, a Cox proportional hazards model was used to compare the risk of developing CKD during a 3-year follow-up period from the index date.
Of the 2338-subject case cohort, 163 (6.97%) developed a CKD, as did 365 (5.20%) of the 7014 control participants. Cox proportional hazards regression analysis revealed that patients with schizophrenia were more likely to develop CKD (HR=1.36, 95% CI 1.13 to 1.63; p<0.001). After adjusting for gender, age group, hypertension, diabetes mellitus, hyperlipidaemia, heart disease and non-steroid anti-inflammatory drugs (NSAIDs) usage, the HR for patients with schizophrenia was 1.25 (95% CI 1.04 to 1.50; p<0.05). Neither typical nor atypical antipsychotics was associated an increased risk of CKD in patients with schizophrenia.
The findings from this population-based retrospective cohort study suggest that schizophrenia is associated with a 25% increase in the risk of developing CKD within only a 3-year follow-up period.
PMCID: PMC4316552  PMID: 25628048
Schizophrenia; chronic kidney diseases; National Health Insurance Research Dataset; non-steroid anti-inflammatory drugs
7.  Relationship between Time to Clinical Response and Outcomes among Pneumonia Outcomes Research Team (PORT) Risk Class III and IV Hospitalized Patients with Community-Acquired Pneumonia Who Received Ceftriaxone and Azithromycin 
Recent Food and Drug Administration (FDA) guidance endorses the use of an early clinical response endpoint as the primary outcome for community-acquired bacterial pneumonia (CABP) trials. While antibiotics will now be approved for CABP, in practice they will primarily be used to treat patients with community-acquired pneumonia (CAP). More importantly, it is unclear how achievement of the new FDA CABP early response endpoint translates into clinically applicable real-world outcomes for patients with CAP. To address this, a retrospective cohort study was conducted among adult patients who received ceftriaxone and azithromycin for CAP of Pneumonia Outcomes Research Team (PORT) risk class III and IV at an academic medical center. The clinical response was defined as clinical stability for 24 h with improvement in at least one pneumonia symptom and with no symptom worsening. A classification and regression tree (CART) was used to determine the delay in response time, measured in days, associated with the greatest risk of a prolonged hospital length of stay (LOS) and adverse outcomes (in-hospital mortality or 30-day CAP-related readmission). A total of 250 patients were included. On average, patients were discharged 2 days following the achievement of a clinical response. In the CART analysis, adverse clinical outcomes were higher among day 5 nonresponders than those who responded by day 5 (22.4% versus 6.9%, P = 0.001). The findings from this study indicate that time to clinical response, as defined by the recent FDA guidance, is a reasonable prognostic indictor of real-world effectiveness outcomes among hospitalized PORT risk class III and IV patients with CAP who received ceftriaxone and azithromycin.
PMCID: PMC4068528  PMID: 24752270
8.  TMEM14C is required for erythroid mitochondrial heme metabolism 
The Journal of Clinical Investigation  2014;124(10):4294-4304.
The transport and intracellular trafficking of heme biosynthesis intermediates are crucial for hemoglobin production, which is a critical process in developing red cells. Here, we profiled gene expression in terminally differentiating murine fetal liver-derived erythroid cells to identify regulators of heme metabolism. We determined that TMEM14C, an inner mitochondrial membrane protein that is enriched in vertebrate hematopoietic tissues, is essential for erythropoiesis and heme synthesis in vivo and in cultured erythroid cells. In mice, TMEM14C deficiency resulted in porphyrin accumulation in the fetal liver, erythroid maturation arrest, and embryonic lethality due to profound anemia. Protoporphyrin IX synthesis in TMEM14C-deficient erythroid cells was blocked, leading to an accumulation of porphyrin precursors. The heme synthesis defect in TMEM14C-deficient cells was ameliorated with a protoporphyrin IX analog, indicating that TMEM14C primarily functions in the terminal steps of the heme synthesis pathway. Together, our data demonstrate that TMEM14C facilitates the import of protoporphyrinogen IX into the mitochondrial matrix for heme synthesis and subsequent hemoglobin production. Furthermore, the identification of TMEM14C as a protoporphyrinogen IX importer provides a genetic tool for further exploring erythropoiesis and congenital anemias.
PMCID: PMC4191016  PMID: 25157825
9.  Fucoidan Supplementation Improves Exercise Performance and Exhibits Anti-Fatigue Action in Mice 
Nutrients  2014;7(1):239-252.
Fucoidan (FCD) is a well-known bioactive constituent of seaweed extract that possess a wide spectrum of activities in biological systems, including anti-cancer, anti-inflammation and modulation of immune systems. However, evidence on the effects of FCD on exercise performance and physical fatigue is limited. Therefore, we investigated the potential beneficial effects of FCD on ergogenic and anti-fatigue functions following physiological challenge. Male ICR mice from three groups (n = 8 per group) were orally administered FCD for 21 days at 0, 310 and 620 mg/kg/day, which were, respectively, designated the vehicle, FCD-1X and FCD-2X groups. The results indicated that the FCD supplementations increased the grip strength (p = 0.0002) and endurance swimming time (p = 0.0195) in a dose-depend manner. FCD treatments also produced dose-dependent decreases in serum levels of lactate (p < 0.0001) and ammonia (p = 0.0025), and also an increase in glucose level (p < 0.0001) after the 15-min swimming test. In addition, FCD supplementation had few subchronic toxic effects. Therefore, we suggest that long-term supplementation with FCD can have a wide spectrum of bioactivities on health promotion, performance improvement and anti-fatigue.
PMCID: PMC4303836  PMID: 25558908
brown seaweed extract; exercise performance; forelimb grip strength
10.  Reduced 5-Methylcytosine Level as a Potential Progression Predictor in Patients with T1 or Non-Invasive Urothelial Carcinoma 
This study aims to elucidate the level of DNA methylation in urothelial carcinomas (UCs) using 5-methylcytosine (5-MeC) immunohistochemistry (IHC). We examined the relationship among 5-MeC levels, DNA (cytosine-5)-methyltransferase 1 (DNMT1) immunostaining levels, and clinicopathologic features. Tissue samples included 23 normal urothelia and 150 urothelial neoplasia, which comprised 40 non-invasive and 110 invasive UCs. The levels of 5-MeC and DNMT1 were assessed based on their immunoreactivities and then divided into low and high levels. In addition, we collected information on clinical variables, pathologic features, and recurrent status from patient questionnaires and medical records. Chi-square test and multivariate logistic regression model were used for analyses. Results showed that 5-MeC levels were positively associated with DNMT1 levels in UC (p = 0.0288). Both 5-MeC and DNMT1 were low in approximately 50% (76/150) of UC. The percentage of low 5-MeC levels was higher in invasive UC (65/110; 59%) than in normal urothelia (2/23; 13%) and non-invasive UC (18/40; 45%). Clinical factors were independently associated with low 5-MeC levels after adjusting for age and sex, including cancer stages II–IV, presence of UC in situ, and marked inflammation. Low 5-MeC levels in stage I invasive UC were not significantly different from those of non-invasive tumors (p = 0.8478). Low DNMT1 levels were only associated with UC with squamous differentiation (p = 0.0365). Neither 5-MeC nor DNMT1 levels were associated with UC recurrence. In conclusion, a low 5-MeC level could predict the progression of UC invasion into muscle.
PMCID: PMC4307268  PMID: 25561224
5-methylcytosine; immunohistochemistry; urothelial carcinoma; DNA (cytosine-5)-methyltransferase 1
11.  Cloud Computing-Based TagSNP Selection Algorithm for Human Genome Data 
Single nucleotide polymorphisms (SNPs) play a fundamental role in human genetic variation and are used in medical diagnostics, phylogeny construction, and drug design. They provide the highest-resolution genetic fingerprint for identifying disease associations and human features. Haplotypes are regions of linked genetic variants that are closely spaced on the genome and tend to be inherited together. Genetics research has revealed SNPs within certain haplotype blocks that introduce few distinct common haplotypes into most of the population. Haplotype block structures are used in association-based methods to map disease genes. In this paper, we propose an efficient algorithm for identifying haplotype blocks in the genome. In chromosomal haplotype data retrieved from the HapMap project website, the proposed algorithm identified longer haplotype blocks than an existing algorithm. To enhance its performance, we extended the proposed algorithm into a parallel algorithm that copies data in parallel via the Hadoop MapReduce framework. The proposed MapReduce-paralleled combinatorial algorithm performed well on real-world data obtained from the HapMap dataset; the improvement in computational efficiency was proportional to the number of processors used.
PMCID: PMC4307292  PMID: 25569088
SNPs; haplotype; cloud computing; parallel processing; MapReduce
12.  Comparison of two-stage open versus percutaneous pedicle screw fixation in treating pyogenic spondylodiscitis 
Percutaneous pedicle screw instrumentation is a minimally invasive surgical technique; however, the effects of using percutaneous pedicle screw fixation in treating patients with spinal infections have not yet been well demonstrated. The aim of this study, therefore, was to determine whether percutaneous posterior pedicle screw instrumentation is superior to the traditional open approach in treating pyogenic spondylodiscitis.
We retrospectively reviewed data for 45 patients treated for pyogenic spondylodiscitis with anterior debridement and interbody fusion followed by a second-stage procedure involving either traditional open posterior pedicle screw fixation or percutaneous posterior pedicle screw fixation. Twenty patients underwent percutaneous fixation and 25 patients underwent open fixation. Demographic, operative, and perioperative data were collected and analyzed.
The average operative time for the percutaneous procedure was 102.5 minutes, while the average time for the open procedure was 129 minutes. The average blood loss for the percutaneous patients was 89 ml versus a 344.8 ml average for the patients in the open group. Patients who underwent the minimally invasive surgery had lower visual analogue scale scores and required significantly less analgesia afterwards. After two years of follow-up, neither recurrent infection nor intraoperative complications, such as wound infection or screw loosening, were found in the percutaneous group. Moreover, there was no significant difference in outcome between the two groups in terms of Oswestry Disability Index scores.
Anterior debridement and interbody fusion with bone grafting followed by minimally invasive percutaneous posterior instrumentation is an alternative treatment for pyogenic spondylodiscitis which can result in less intraoperative blood loss, shorter operative time, and reduced postoperative pain with no adverse effect on infection control.
PMCID: PMC4300775  PMID: 25519761
Minimally invasive surgery; Percutaneous pedicle screw; Pyogenic spondylodiscitis; Anterior interbody fusion
13.  Histone Acetylation Accompanied with Promoter Sequences Displaying Differential Expression Profiles of B-Class MADS-Box Genes for Phalaenopsis Floral Morphogenesis 
PLoS ONE  2014;9(12):e106033.
Five B-class MADS-box genes, including four APETALA3 (AP3)-like PeMADS2∼5 and one PISTILLATA (PI)-like PeMADS6, specify the spectacular flower morphology in orchids. The PI-like PeMADS6 ubiquitously expresses in all floral organs. The four AP3-like genes, resulted from two duplication events, express ubiquitously at floral primordia and early floral organ stages, but show distinct expression profiles at late floral organ primordia and floral bud stages. Here, we isolated the upstream sequences of PeMADS2∼6 and studied the regulatory mechanism for their distinct gene expression. Phylogenetic footprinting analysis of the 1.3-kb upstream sequences of AP3-like PeMADS2∼5 showed that their promoter regions have sufficiently diverged and contributed to their subfunctionalization. The amplified promoter sequences of PeMADS2∼6 could drive beta-glucuronidase (GUS) gene expression in all floral organs, similar to their expression at the floral primordia stage. The promoter sequence of PeMADS4, exclusively expressed in lip and column, showed a 1.6∼3-fold higher expression in lip/column than in sepal/petal. Furthermore, we noted a 4.9-fold increase in histone acetylation (H3K9K14ac) in the translation start region of PeMADS4 in lip as compared in petal. All these results suggest that the regulation via the upstream sequences and increased H3K9K14ac level may act synergistically to display distinct expression profiles of the AP3-like genes at late floral organ primordia stage for Phalaenopsis floral morphogenesis.
PMCID: PMC4263434  PMID: 25501842
14.  Prevalence of potentially traumatic events, depression, alcohol use, and social network supports among Chinese migrants: an epidemiological study in Guangzhou, China 
European Journal of Psychotraumatology  2014;5:10.3402/ejpt.v5.26529.
Addressing the health needs of Chinese migrants is a critical public health concern. Epidemiological studies are needed to establish the prevalence of potentially traumatic events (PTEs) and common mental disorders among Chinese migrants and identify protective community and social resources.
Utilizing random household sampling, we are in the process of recruiting a representative sample of Chinese adults (N=1,000) in two districts home to a large number of internal migrants. Data are collected using face-to-face interviews and participant self-report methods. Chinese versions of the Life Events Checklist, Alcohol Use Disorders Identification Test, Patient Health Questionnaire and the Social Support Rating Scale measured exposure to PTEs, alcohol use disorder, depression, and social support networks.
Preliminary results indicate a high proportion (68%) of the sample was exposed directly or indirectly to at least one PTE. The most commonly reported events were transportation accidents (43%), natural disasters (39%), and physical assault (26%). A total of 17% of the sample reported drinking consistent with having an alcohol use disorder. Moderate or severe depression was reported by 9% of the sample. The majority (75%) reported having three or more people to rely on for support, and 41% reported active participation in civic groups. Despite these strengths, only half the sample reported having trust in their community.
Preliminary evidence from this population-level survey indicates high exposure to PTEs and a high potential burden of alcohol use disorders. The role of social networks will be explored as potentially useful for community-based intervention development.
PMCID: PMC4265129  PMID: 25511733
depression; alcohol abuse; social resources; migration; China
15.  Upregulation of Stromal Cell–Derived Factor 1 (SDF-1) is Associated with Macrophage Infiltration in Renal Ischemia-Reperfusion Injury 
PLoS ONE  2014;9(12):e114564.
Stromal cell-derived factor-1(SDF-1) is a chemotactic and angiogenic factor that mediates the repair of various tissues. As macrophages are important contributors to ischemic kidney injury, we examine the role of SDF-1 in a rodent model of ischemia-reperfusion (I/R) injury.
Male wild-type (WT) (C57BL/6) mice were subjected to bilateral I/R injury or sham operation in the presence or absence of macrophage depletion (liposomal clodronate [0.2 ml/20–25 g body weight i.p.]). Macrophage accumulation was assessed by immunohistochemistry. Tissue levels of SDF-1 (ELISA) and SDF-1 mRNA expression (real-time PCR) were measured. The cellular location of SDF-1 was assessed using immunohistochemical staining.
Immunofluorescence staining of renal tissue sections confirmed macrophage depletion by liposomal clodronate. SDF-1 production was elevated in response to I/R injury and was significantly increased upon macrophage depletion. SDF-1 positive cells initially appeared initially in the cortex, and subsequently diffused to the outer medulla after I/R injury.
Our study demonstrates that SDF-1 is significantly upregulated during renal I/R. We hypothesize that SDF-1 upregulation may be an important macrophage effector mechanism during I/R injury.
PMCID: PMC4257711  PMID: 25478952
16.  A large inflammatory myofibroblastic tumor involving both stomach and spleen: A case report and review of the literature 
Oncology Letters  2014;9(2):811-815.
Inflammatory myofibroblastic tumor (IMT) is a rare, benign neoplasm that most commonly occurs in pediatric patients; it has been described as a pseudosarcomatous proliferation of spindled myofibroblasts mixed with lymphoplasmacytic cells. IMT has been reported in a number of locations throughout the body; however, cases occurring in the gastrointestinal tract are rare and to date, no case involving both the stomach and spleen has been reported. The current study presents a case of an extremely large IMT invading both the stomach and spleen in a 50-year-old female, presenting with a three-month history of left-sided abdominal distension without abdominal pain, fever or vomiting. As the tumor had invaded the stomach and spleen, it was completely excised and concomitantly, the entire stomach and spleen were removed. Histological examination of the biopsy revealed fascicles of spindle cells in a mixed inflammatory background, with inflammatory cells that were immunopositive for vimentin, smooth muscle actin, and negative for anaplastic lymphoma kinase and CD30, confirming the diagnosis of IMT. Four months following local excision of the mass, accompanied by a total gastrectomy and splenectomy, no abdominal distension, abdominal pain, fever or vomiting were observed and no IMT recurrence was identified.
PMCID: PMC4301536  PMID: 25624905
inflammatory myofibroblastic tumor; stomach; spleen; gastrointestinal stromal tumor
17.  Effect of Taxane-Based Neoadjuvant Chemotherapy on Fibroglandular Tissue Volume and Percent Breast Density in the Contralateral Normal Breast: Evaluated at 3T MR 
NMR in biomedicine  2013;26(12):10.1002/nbm.3006.
The aim of this study was to evaluate the change of breast density in the normal breast of patients receiving neoadjuvant chemotherapy (NAC). Forty-four breast cancer patients were studied. MRI acquisition was performed before treatment (baseline), and 4 and 12 weeks after treatment. A computer algorithm-based program was used to segment breast tissue and calculate breast volume (BV), fibroglandular tissue volume (FV) and percent density (PD) (the ratio of FV over BV x100%). The reduction of FV and PD after treatment was compared to baseline using paired t-tests with a Bonferroni-Holm correction. The association of density reduction with age was analyzed. FV and PD after NAC showed significant decreases compared to the baseline. FV was 110.0ml (67.2, 189.8) (geometric mean (interquartile range)) at baseline, 104.3ml (66.6, 164.4) after 4 weeks (p< 0.0001), and 94.7ml (60.2, 144.4) after 12 weeks (comparison to baseline, p<0.0001; comparison to 4 weeks, p=0.016). PD was 11.2% (6.4, 22.4) at baseline, 10.6% (6.6, 20.3) after 4 weeks (p< 0.0001), and 9.7% (6.2, 17.9) after 12 weeks (comparison to baseline, p=0.0001; comparison to 4 weeks, p =0.018). Younger patients tended to show a higher density reduction, but overall correlation with age was only moderate (r=0.28 for FV, p=0.07 and r=0.52 for PD, p=0.0003). Our study showed that breast density measured from MR images acquired at 3T MR can be accurately quantified using a robust computer-aided algorithm based on nonparametric nonuniformity normalization (N3) and an adaptive fuzzy C-means algorithm. Similar to doxorubicin and cyclophosphamide regimens, the taxane-based NAC regimen also caused density atrophy in the normal breast and showed reduction in FV and PD. The effect of breast density reduction was age-related and duration-related.
PMCID: PMC3838444  PMID: 23940080
breast density; normal breast; neoadjuvant chemotherapy; taxane; MRI; fibroglandular tissue volume; percent density; 3T MR
18.  Optimal Positive Cutoff Points for careHPV Testing of Clinician- and Self-Collected Specimens in Primary Cervical Cancer Screening: an Analysis from Rural China 
Journal of Clinical Microbiology  2014;52(6):1954-1961.
careHPV, a lower-cost DNA test for human papillomavirus (HPV), is being considered for cervical cancer screening in low- and middle-income countries. However, not a single large-scaled study exists to investigate the optimal positive cutoff point of careHPV test. We pooled data for 9,785 women participating in two individual studies conducted from 2007 to 2011 in rural China. Woman underwent multiple screening tests, including careHPV on clinician-collected specimens (careHPV-C) and self-collected specimens (careHPV-S), and Hybrid Capture 2 on clinician-collected specimens (HC2-C) as a reference standard. The primary endpoint was cervical intraepithelial neoplasia grade 3 or more severe (CIN3+) (n = 127), and secondary endpoint was CIN2+ (n = 213). The area under the curves (AUCs) for HC2-C and careHPV-C were similar (0.954 versus 0.948, P = 0.166), and better than careHPV-S (0.878; P < 0.001 versus both). The optimal positive cutoff points for HC2-C, careHPV-C, and careHPV-S were 1.40, 1.74, and 0.85, respectively. At the same cutoff point, careHPV-C was not significantly less sensitive and more specific for CIN3+ than HC2-C, and careHPV-S was significantly less sensitive for CIN3+ than careHPV-C and HC2-C. Raising the cutoff point of careHPV-C from 1.0 to 2.0 could result in nonsignificantly lower sensitivity but significantly higher specificity. Similar results were observed using CIN2+ endpoint. careHPV using either clinician- or self-collected specimens performed well in detecting cervical precancer and cancer. We found that the optimal cutoff points of careHPV were 2.0 on clinician-collected specimens and 1.0 on self-collected specimens.
PMCID: PMC4042749  PMID: 24671789
19.  Interleukin 13– and interleukin 17A–induced pulmonary hypertension phenotype due to inhalation of antigen and fine particles from air pollution 
Pulmonary Circulation  2014;4(4):654-668.
Pulmonary hypertension has a marked detrimental effect on quality of life and life expectancy. In a mouse model of antigen-induced pulmonary arterial remodeling, we have recently shown that coexposure to urban ambient particulate matter (PM) significantly increased the thickening of the pulmonary arteries and also resulted in significantly increased right ventricular systolic pressures. Here we interrogate the mechanism and show that combined neutralization of interleukin 13 (IL-13) and IL-17A significantly ameliorated the increase in right ventricular systolic pressure, the circumferential muscularization of pulmonary arteries, and the molecular change in the right ventricle. Surprisingly, our data revealed a protective role of IL-17A for the antigen- and PM-induced severe thickening of pulmonary arteries. This protection was due to the inhibition of the effects of IL-13, which drove this response, and the expression of metalloelastase and resistin-like molecule α. However, the latter was redundant for the arterial thickening response. Anti-IL-13 exacerbated airway neutrophilia, which was due to a resulting excess effect of IL-17A, confirming concurrent cross inhibition of IL-13- and IL-17A-dependent responses in the lungs of animals exposed to antigen and PM. Our experiments also identified IL-13/IL-17A-independent molecular reprogramming in the lungs induced by exposure to antigen and PM, which indicates a risk for arterial remodeling and protection from arterial constriction. Our study points to IL-13- and IL-17A-coinduced inflammation as a new template for biomarkers and therapeutic targeting for the management of immune response–induced pulmonary hypertension.
PMCID: PMC4278625  PMID: 25610601
pulmonary vasculature; particulate matter 2.5; air pollution; inhaled antigen
20.  Impact of dose calculation algorithm on radiation therapy 
World Journal of Radiology  2014;6(11):874-880.
The quality of radiation therapy depends on the ability to maximize the tumor control probability while minimize the normal tissue complication probability. Both of these two quantities are directly related to the accuracy of dose distributions calculated by treatment planning systems. The commonly used dose calculation algorithms in the treatment planning systems are reviewed in this work. The accuracy comparisons among these algorithms are illustrated by summarizing the highly cited research papers on this topic. Further, the correlation between the algorithms and tumor control probability/normal tissue complication probability values are manifested by several recent studies from different groups. All the cases demonstrate that dose calculation algorithms play a vital role in radiation therapy.
PMCID: PMC4241494  PMID: 25431642
Dose calculation; Algorithm; Radiation therapy; Tumor control probability; Normal tissue complication probability
21.  Manganese regulation of virulence factors and oxidative stress resistance in Neisseria gonorrhoeae 
Journal of proteomics  2009;73(5):899-916.
Neisseria gonorrhoeae has evolved a complex and novel network of oxidative stress responses, including defense mechanisms that are dependent on manganese (Mn). We performed systematic analyses at the transcriptomic and proteomic (1D SDS-PAGE and Isotope-Coded Affinity Tag [ICAT]) levels to investigate the global expression changes that take place in a high Mn environment, which results in a Mn-dependent oxidative stress resistance phenotype. These studies revealed that 97 proteins are regulated at the post-transcriptional level under conditions of increased Mn concentration, including proteins involved in virulence (eg. Pilin, a key adhesin), oxidative stress defence (eg. superoxide dismutase), cellular metabolism, protein synthesis, RNA processing and cell division. Mn regulation of inorganic pyrophosphatase (Ppa) indicated the potential involvement of phosphate metabolism in the Mn-dependent oxidative stress defense. A detailed analysis of the role of Ppa and polyphosphate kinase (Ppk) in the gonococcal oxidative stress response revealed that ppk and ppa mutant strains showed increased resistance to oxidative stress. Investigation of these mutants grown with high Mn suggests that phosphate and pyrophosphate are involved in Mn-dependent oxidative stress resistance.
PMCID: PMC4238106  PMID: 20004262
manganese; microarray; Neisseria gonorrhoeae; oxidative stress; pili; proteomics
22.  Quantitative Ultrasound Facilitates the Exploration of Morphological Association of the Long Head Biceps Tendon with Supraspinatus Tendon Full Thickness Tear 
PLoS ONE  2014;9(11):e113803.
Pathology of the long head biceps tendon (LHBT) is associated with rotator cuff tears but whether the LHBT texture changes following supraspinatus tendon full thickness tear (SSFT) can be detected at the extra-articular segment remains unknown. This cross-sectional study aimed to explore the morphological differences of the LHBT in shoulders with and without deficient rotator cuffs by using quantitative ultrasound.
Materials and Methods
We selected 145 cases with SSFT and 145 age-and- gender-matched controls. The width, thickness, flattening ratio, cross-sectional area, and echogenicity ratio of the LHBT were measured and a general linear model was used to clarify the relationship between rotator cuff pathology and LHBT morphology. The receiver operating characteristic curves of each parameter were constructed for SSFT discrimination and the maximal Youden indexes were used to define the best cut-off points.
We found increased thickness and cross-sectional area but decreased flattening ratio in shoulders with SSFT, and no between-group differences in the width and echogenicity ratio. The LHBT appearance was modified by biceps peritendinous effusion and medial subluxation, but not by the size of SSFT. The flattening ratio was the best discriminator for SSFT with an area under curve of 0.81 (95% confidence interval, 0.76–0.86). The cut-off values to differentiate between the non-tear and tear groups were 2.00 mm of the thickness, 1.73 of the flattening ratio and 10.53 mm2 of the cross-sectional area.
Quantitative ultrasound facilitated the detection of the LHBT morphological changes following SSFT and demonstrated its potential utility in discriminating rotator cuff deficiency.
PMCID: PMC4239113  PMID: 25412357
23.  Increased risk of ischemic stroke in patients with mild traumatic brain injury: a nationwide cohort study 
It is known that the risk of stroke in patients with traumatic brain injury might be increased. However, the relationship between mild traumatic brain injury and ischemic stroke has never been established. We conducted a study of patients in Taiwan with mild traumatic brain injury to evaluate if they had a higher risk of stroke compared with the general population.
We utilized a sampled National Health Insurance claims database containing one million beneficiaries. We followed all adult beneficiaries older than 18 years from January 1, 2007 to December 31, 2010 to determine if they were diagnosed with ischemic stroke. We further identified patients with mild traumatic brain injury and compared their risk of ischemic stroke with the general population.
We identified 24,905 patients with mild traumatic brain injury and 719,811 patients without mild traumatic brain injury. After controlling for age, gender, urbanization level, socioeconomic status, diabetes, hypertension, coronary artery disease, hyperlipidemia, history of alcohol intoxication, malignancies, heart failure, atrial fibrillation, smoking, obesity, epilepsy, peripheral artery disease and Charlson Comorbidity Index score, the adjusted hazard ratio for ischemic stroke was 1.46 (95% confidence interval, 1.33—1.62).
Mild traumatic brain injury is an independent significant risk factor for ischemic stroke.
PMCID: PMC4239396  PMID: 25406859
Stroke; Traumatic brain injury; National health insurance
24.  Lower cost strategies for triage of human papillomavirus DNA-positive women 
Using human papillomavirus (HPV) testing for cervical cancer screening in lower-resource settings (LRS) will result in a significant number of screen-positive women. This analysis compares different triage strategies for detecting cervical precancer and cancer among HPV-positive women in LRS. This was a population-based study of women aged 25–65 years living in China (n = 7,541). Each woman provided a self-collected and two clinician-collected specimens. The self-collected and one clinician-collected specimen were tested by two HPV DNA tests—careHPV™ and Hybrid Capture 2; the other clinician-collected specimen was tested for HPV16/18/45 E6 protein. CareHPV™-positive specimens were tested for HPV16/18/45 DNA. HPV DNA-positive women underwent visual inspection with acetic acid (VIA) and then colposcopic evaluation with biopsies. The performance for detection of cervical intraepithelial neoplasia grade 3 or cancer (CIN3+) among HPV DNA-positive women was assessed for different triage strategies: HPV16/18/45 E6 or DNA detection, VIA, colposcopic impression, or higher signal strength (≥10 relative light units/positive control [rlu/pc]). The percent triage positive ranges were 14.8–17.4% for VIA, 17.8–20.9% for an abnormal colposcopic impression; 7.9–10.5% for HPV16/18/45 E6; 23.4–28.4% for HPV16/18/45 DNA; and 48.0–62.6% for higher signal strength (≥10 rlu/pc), depending on the HPV test/specimen combination. The positivity for all triage tests increased with severity of diagnosis. HPV16/18/45 DNA detection was approximately 70% sensitive and had positive predictive values (PPV) of approximately 25% for CIN3+. HPV16/18/45 E6 detection was approximately 50% sensitive with a PPV of nearly 50% for CIN3+. Different triage strategies for HPV DNA-positive women provide important tradeoffs in colposcopy or treatment referral percentages and sensitivity for prevalent CIN3+.
What's new?
The careHPV™ test is a novel technology for primary cervical cancer screening of women from lower-resource settings. However, triage strategies are needed to identify which HPV-positive women are at highest risk of cervical precancer and cancer. Here, multiple viable and affordable strategies to manage HPV-positive women depending on local requirements and resources are identified, based on evaluation of the performance of different triage strategies for developing countries. The different strategies for women who test positive for HPV DNA provide important tradeoffs in colposcopy or treatment referral percentages and sensitivity for cervical intraepithelial neoplasia grade 3 or cancer (CIN3+).
PMCID: PMC4232922  PMID: 24248915
HPV; triage; cervical cancer; careHPV; developing countries; E6
25.  Mental health status and work environment among workers in small- and medium-sized enterprises in Guangdong, China-a cross-sectional survey 
BMC Public Health  2014;14(1):1162.
Small- and medium-sized enterprises (SMEs) generate nearly 80% of the jobs in China, but the dangerous work environment often found in these enterprises poses a major concern for public health. Psychosocial pressure and mental health problems among the workers are also common in SMEs. However, mental health of workers in SMEs is largely neglected in occupational health research and practice in China. The purpose of this study is to assess mental health of the workers and to explore the associations between physical and psychosocial work environment and workers’ mental health in SMEs in South China.
Data were collected in 2012 through a cross-sectional survey among 1200 workers working in small- and medium-sized enterprises (SMEs) in Guangdong, China. Mental health was measured by psychological well-being in the current study. Job Demand-Control-Support (JDCS) model was used as a theoretical framework to examine the psychosocial factors associated with workers’ psychological well-being. Data were analyzed using SPSS 20.0 and analysis was performed using bivariate analyses and multivariate logistic regression.
About three in ten workers (35.3%) in the sample had poor psychological well-being. Those who were men, younger in age, or migrant workers had worse psychological outcome in bivariate analyses. After controlling for individual variables (gender, age, marital status, and household registration), we found that longer weekly work hours (OR = 1.30, 95% CI: 1.13 ~ 1.50), more exposure to hazardous work environment (OR = 1.26, 95% CI: 1.10 ~ 1.44), higher job demands (OR = 1.29, 95% CI: 1.12 ~ 1.49), and lower job autonomy (OR = 0.70, 95% CI: 0.60 ~ 0.81) were significant associated with worse psychological well-being. The results were consistent with predictions of the JDCS model.
The results indicate that the JDCS model is a useful framework in predicting psychological well-being among Chinese workers in SMEs. Future mental health promotion should focus on young migrant male workers as they appear to be most vulnerable in their psychological well-being. Both physical and psychosocial aspects of the work environment should be taken into account in policy making to prevent mental disorder and promote psychological well-being among workers in SMEs.
PMCID: PMC4247769  PMID: 25387579
Chinese workers; Mental health; Psychological well-being; WHO (five) well-being index; Small- and medium-sized enterprises (SMEs); Job demand-control (JDC) model; Job demand-control-support (JDCS) model

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