Publications by authors named "Wenbin Guan"

38 Publications

Expanding mutational spectrum of HRAS by a patient with Schimmelpenning-Feuerstein-Mims syndrome.

J Dermatol 2021 Jun 9. Epub 2021 Jun 9.

Department of Pediatric Hematology-Oncology, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

As one of the epidermal nevus syndromes, Schimmelpenning-Feuerstein-Mims (SFM) is characterized by craniofacial nevus sebaceous (NS) and extracutaneous abnormalities (e.g., brain, eyes, and bone). Here, we report a case of a 4-year-old boy who presented with significant skin abnormalities (NS in the scalp, extensive epidermal nevus along Blaschko's lines), ocular abnormalities (strabismus), central nervous system abnormalities (seizure and mental retardation), lymphatic dysplasia (chylous pleural and pericardial effusion), cardiac abnormalities (patent foramen ovale), urogenital system abnormalities (cryptorchidism, hypospadias), and a tumor predisposition (embryonal rhabdomyosarcoma). DNA samples from NS, rhabdomyosarcoma, and peripheral blood leukocytes were analyzed by next-generation sequencing. A novel mutation in the HRAS gene (c.38G>T; p.Gly13Val) was detected in a mosaic state in NS, rhabdomyosarcoma, and peripheral blood leukocytes, with different ratio of heterozygous mutation (HRAS c.38G>T) of 39.90% (9412/23 588 reads), 73.03% (205 562/281 468 reads), and 14.16% (15 837/111 842 reads), respectively. By predicting the impact of the mutation on the biological function of protein, we found that the novel HRAS mutation (c.38G>T; p.Gly13Val) had the highest damaging scores among other HRAS mutations reported so far. This is the first reported SFM syndrome patient with novel mosaic HRAS mutation, which may help to expand the mutational spectrum of HRAS and better understand the role of HRAS in the disease.
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http://dx.doi.org/10.1111/1346-8138.15922DOI Listing
June 2021

Diagnosis of chronic prostatitis by noninvasive methods in elderly patients with benign prostatic hyperplasia in China.

Andrologia 2021 Jul 2;53(6):e14055. Epub 2021 Apr 2.

Department of Urology, School of Medicine, Xinhua Hospital, Shanghai Jiao Tong University, Shanghai, China.

Chronic prostatitis is hard to be identified in BPH patients in clinical works. This study aimed to diagnose chronic prostatitis in BPH patients by noninvasive methods. BPH patients who received transurethral resection of prostate from January 2014 to July 2015 were enrolled in current study. Patients were received examinations of PSA, sex hormones, inflammatory cytokines, metabolic panel and transrectal ultrasonography. According to histological results, patients were divided into two group of BPH with/without prostatitis. Logistic regression was used to find risk factors of chronic prostatitis. As a result, 181 men with an average age of 72.15 ± 8.41 years were enrolled in this study, including 116 patients with prostatitis and 65 patients without prostatitis. The storage sub-score, PSA and IL-2R were significantly higher in patients with prostatitis than those without prostatitis. Based on logistic regression analysis, the above three parameters were also the risk factors of BPH with prostatitis. The diagnostic model was calculated as: 0.317 × storage sub-score + 0.092 × PSA + 0.003 × IL-2R - 4.296. The AUC was 0.725. Histological prostatitis in BPH patients can be diagnosed by the combination of serum IL-2R, PSA and storage sub-score. Identification of chronic prostatitis in BPH patients could more efficiently alleviate urinary symptoms and reduce the risk of disease progression.
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http://dx.doi.org/10.1111/and.14055DOI Listing
July 2021

Resveratrol could attenuate prostatic inflammation in rats with Oestradiol-induced chronic prostatitis.

Andrologia 2021 May 7;53(4):e14004. Epub 2021 Feb 7.

Department of Urology, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.

To evaluate the effect of resveratrol in rats with chronic prostatitis, 24 rats were randomly divided into the negative control, vehicle-treated and resveratrol groups. The rats in the vehicle-treated group and the resveratrol group were injected subcutaneously with 17-β-oestradiol (0.25 mg/kg) daily for 6 weeks while the rats in the control group were injected with equivalent normal saline. From the 45th day, the rats in the resveratrol group were given resveratrol (10 mg/kg) by gavage per day while the rest rats were given normal saline. After 55 days, all the rats were sacrificed and the prostatic tissue was removed. Morphological changes were examined by light microscope after H&E staining. The expressions of IL-6, IL-8 and TNF-α were determined through ELISA and immunohistochemical staining. As a result, significant inflammatory cell infiltration and fibroblastic hyperplasia were observed in prostatic stroma in the vehicle-treated group compared with the negative control group, as well as the high expression of IL-6, IL-8 and TNF-α. After resveratrol treatment, inflammatory cell infiltration and fibroblastic hyperplasia were shown prominently reduced. Meanwhile, the expression of IL-6, IL-8 and TNF-α was significantly suppressed. For conclusion, resveratrol could attenuate the prostatic inflammation and downregulate the expression of IL-6, IL-8 and TNF-α in rat with oestradiol-induced chronic prostatitis.
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http://dx.doi.org/10.1111/and.14004DOI Listing
May 2021

The Adrenal Cortex, an Underestimated Site of SARS-CoV-2 Infection.

Front Endocrinol (Lausanne) 2020 8;11:593179. Epub 2021 Jan 8.

Department of Anesthesiology and Surgical Intensive Care Unit, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.

Background: The majority of the critically ill patients may have critical illness-related corticosteroid insufficiency (CIRCI). The therapeutic effect of dexamethasone may be related to its ability to improve cortical function. Recent study showed that dexamethasone can reduce COVID-19 deaths by up to one third in critically ill patients. The aim of this article is to investigate whether SARS-CoV-2 can attack the adrenal cortex to aggravate the relative adrenal insufficiency.

Methods: We summarized the clinical features of COVID-19 reported in currently available observational studies. ACE2 and TMPRSS2 expression was examined in human adrenal glands by immunohistochemical staining. We retrospectively analyzed serum cortisol levels in critically ill patients with or without COVID-19.

Results: High percentage of critically ill patients with SARS-COV-2 infection in the study were treated with vasopressors. ACE2 receptor and TMPRSS2 serine protease were colocalized in adrenocortical cells in zona fasciculata and zona reticularis. We collected plasma cortisol concentrations in nine critically ill patients with COVID-19. The cortisol levels of critically ill patients with COVID-19 were lower than those in non-COVID-19 critically ill group. Six of the nine COVID-19 critically ill patients had random plasma cortisol concentrations below 10 µg/dl, which met the criteria for the diagnosis of CIRCI.

Conclusion: We demonstrate that ACE2 and TMPRSS2 are colocalized in adrenocortical cells, and that the cortisol levels are lower in critically ill patients with COVID-19 as compared to those of non-COVID-19 critically ill patients. Based on our findings, we recommend measuring plasma cortisol level to guide hormonal therapy.
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http://dx.doi.org/10.3389/fendo.2020.593179DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7820749PMC
January 2021

Magnetic polymeric nanobubbles with optimized core size for MRI/ultrasound bimodal molecular imaging of prostate cancer.

Nanomedicine (Lond) 2020 12 10;15(30):2901-2916. Epub 2020 Dec 10.

Department of Ultrasound in Medicine, Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine, 1665 Kongjiang Road, Shanghai 200092, PR China.

To design MRI/ultrasound (US) dual modality imaging probes with optimized size for prostate cancer imaging by targeting prostate-specific membrane antigen (PSMA). The PSMA-targeting polypeptide-nanobubbles (PP-NBs) with core size of 400 and 700 nm were fabricated and evaluated. With excellent physical property and specificity, PP-NBs of both core size could image PSMA expression in prostate cancer xenografts. Particularly, 400 nm PP-NBs generated higher PSMA-specific MRI/US dual modality contrast enhancement than 700 nm PP-NBs in correlation with histopathologic findings. Benefit from the smaller core size, 400 nm PP-NBs had higher permeability and specificity than 700 nm PP-NBs, hence producing better PSMA-specific MRI/US dual modality imaging.
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http://dx.doi.org/10.2217/nnm-2020-0188DOI Listing
December 2020

Radiogenomics of neuroblastoma in pediatric patients: CT-based radiomics signature in predicting MYCN amplification.

Eur Radiol 2021 May 29;31(5):3080-3089. Epub 2020 Oct 29.

Department of Radiology, Xinhua Hospital affiliated of Shanghai Jiao Tong University School of Medicine, No.1665 Kongjiang Road, Yangpu District, Shanghai City, 200082, China.

Objectives: To construct a CT-based radiomics signature and assess its performance in predicting MYCN amplification (MNA) in pediatric patients with neuroblastoma.

Methods: Seventy-eight pediatric patients with neuroblastoma were recruited (55 in training cohort and 23 in test cohort). Radiomics features were extracted automatically from the region of interest (ROI) manually delineated on the three-phase computed tomography (CT) images. Selected radiomics features were retained to construct radiomics signature and a radiomics score (rad-score) was calculated by using the radiomics signature-based formula. A clinical model was established with clinical factors, including clinicopathological data, and CT image features. A combined nomogram was developed with the incorporation of a radiomics signature and clinical factors. The predictive performance was assessed by receiver operating characteristics curve (ROC) analysis and decision curve analysis (DCA).

Results: The radiomics signature was constructed using 7 selected radiomics features. The clinical radiomics nomogram, which was based on the radiomics signature and two clinical factors, showed superior predictive performance compared with the clinical model alone (area under the curve (AUC) in the training cohort: 0.95 vs. 0.82, the test cohort: 0.91 vs. 0.70). The clinical utility of clinical radiomics nomogram was confirmed by DCA.

Conclusions: This proposed CT-based radiomics signature was able to predict MNA. Combining the radiomics signature with clinical factors outperformed using clinical model alone for MNA prediction.

Key Points: • A CT-based radiomics signature has the ability to predict MYCN amplification (MNA) in neuroblastoma. • Both pre- and post-contrast CT images are valuable in predicting MNA. • Associating the radiomics signature with clinical factors improved the predictive performance of MNA, compared with clinical model alone.
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http://dx.doi.org/10.1007/s00330-020-07246-1DOI Listing
May 2021

The effect of slope aspect on vegetation attributes in a mountainous dry valley, Southwest China.

Sci Rep 2020 10 5;10(1):16465. Epub 2020 Oct 5.

School of Ecology and Nature Conservation, Beijing Forestry University, Beijing, China.

Slope aspect plays a critical role in influencing vegetation pattern in semiarid area. The dry valleys of the Hengduan Mountains Region, southwestern China, are striking geographical landscape, suffering from severe ecological degradation. Here, we comprehensively investigated how slope aspect affects vegetation attributes in one of these valleys- the dry valley in the upper reaches of Min River. Three sites were selected along the valley and we quantitively examined the vegetation difference between slope aspects at the whole valley scale and each site level. We found significant vegetation differences between slope aspects in species composition, vegetative structure, and biodiversity pattern, which were in accordance with the observed significant difference in soil nutrient. Generally, north-facing slopes are associated with higher biomass, coverage and height, and species diversity than south-facing slopes. We also found between-aspect differences varied among the study sites, resulting in increased biomass, height, and β diversity differences, decreased density and coverage differences, and opposite trend observed in α diversity at relatively wet site. In conclusion, slope aspect had significant effect on vegetation attributes, which was significantly influenced by local climate (aridity) in terms of both strength and direction depending on the specific attributes investigated.
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http://dx.doi.org/10.1038/s41598-020-73496-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7536199PMC
October 2020

A novel definition of microvessel density in renal cell carcinoma: Angiogenesis plus vasculogenic mimicry.

Oncol Lett 2020 Nov 3;20(5):192. Epub 2020 Sep 3.

Department of Urology, Xin Hua Hospital Affiliated to Shanghai Jiao Tong University, School of Medicine, Shanghai 200092, P.R. China.

The present study proposed the novel concept of total microvessel density (TMVD), which is the combination of the MVD and the vasculogenic mimicry (VM) status, and evaluated its clinical significance in patients with renal cell carcinoma (RCC). For that purpose, tumor samples from 183 patients with primary RCC were examined by CD34 single or periodic acid Schiff (PAS)/CD34 dual histology staining. MVD and VM were determined according to previous literature. Clinical information (tumor stage and grade, and duration of survival) was retrieved and analyzed. Survival information and VM-associated gene expression data of patients with RCC were also retrieved from The Cancer Genome Atlas (TCGA) database and the clinical significance of each individual gene was analyzed. The results indicated that MVD exhibited obvious differences among patients with RCC; however, it was not correlated with the stage/grade or length of survival in patients with RCC. In total, 81 patients (44.3%) were CD34(-)/PAS(+) and defined as VM(+), and they had a significantly shorter survival compared with that of VM(-) patients (P=0.0002). VM was not associated with MVD. TMVD was able to distinguish between patients with high and low MVD in terms of survival, thus TMVD was better compared with MVD alone at distinguishing between patients with different survival prognoses. TCGA data analysis revealed that among the VM-associated genes, nodal growth differentiation factor, caspase-3, matrix metalloproteinase-9 and galectin-3 had a statistically significant impact on the overall/disease-free survival of patients with RCC. In conclusion, the TMVD concept may be more appropriate and sensitive compared with the MVD or VM alone in predicting tumor aggressiveness and patient survival, particularly in RCC, which is a highly vascularized, VM-rich neoplasm, and certain VM formation-associated genes are negatively associated with the survival of patients with RCC.
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http://dx.doi.org/10.3892/ol.2020.12054DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7479517PMC
November 2020

The Better Survival of MSI Subtype Is Associated With the Oxidative Stress Related Pathways in Gastric Cancer.

Front Oncol 2020 28;10:1269. Epub 2020 Jul 28.

Department of Pathology, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.

Gastric cancer (GC) is the third leading fatal cancer in the world and its incidence ranked second among all malignant tumors in China. The molecular classification of GC, proposed by the The Cancer Genome Atlas (TCGA), was added to the updated edition (2019) of WHO classification for digestive system tumor. Although MSI and EBV subtypes appeared as ever-increasingly significant roles in immune checkpoint inhibitor therapy, the underlying mechanisms are still unclear. We systematically summarized the relationship between EBV, d-MMR/MSI-H subtypes and clinicopathological parameters in 271 GC cases. Furthermore, GSE62254/ACRG and TCGA-STAD datasets, originated from Gene Expression Omnibus (GEO) and TCGA respectively, were analyzed to figure out the prognosis related molecular characteristics by bioinformatics methods. Patients with MSI subtype had better prognosis than the MSS subtype ( = 0.013) and considered as an independent biomarker by the univariate analysis ( = 0.017) and multivariate analysis ( = 0.050). While there was no significant difference between EBV positive and negative tissues ( = 0.533). The positive prognostic value conferred by MSI in different cohorts was revalidated via the clinical analysis of GSE62254/ACRG and TCGA-STAD datasets regardless of race. Then key gene module that tightly associated with better status and longer OS time for MSI cases was obtained from weighted gene co-expression network analysis(WGCNA). and were screened from the gene cluster and oxidative phosphorylation, reactive oxygen species(ROS) and glutathione metabolism were analyzed to be the differential pathways in their highly expressed groups. Our results manifested the significant prognostic value of MSI in Chinese GC cohort and comparisons with other populations. More opportunities to induce apoptosis of cancer cells, led by the unbalance between antioxidant system and ROS accumulation, lay foundations for unveiling the better prognosis in MSI phenotype through the bioinformatics analysis.
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http://dx.doi.org/10.3389/fonc.2020.01269DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7399340PMC
July 2020

Pure dysgerminoma of the ovary: CT and MRI features with pathological correlation in 13 tumors.

J Ovarian Res 2020 Jun 17;13(1):71. Epub 2020 Jun 17.

Department of Radiology, Xinhua Hospital affiliated to Shanghai Jiaotong University School of Medicine, 1665 Kongjiang Road, Shanghai, 200092, China.

Background: To investigate the spectrum of CT and MRI findings of dysgerminoma of the ovary.

Methods: CT and MRI imaging of 12 patients with 13 histologically proven dysgerminomas of the ovary were retrospectively reviewed. Patients ages ranged from 6 ~ 27 years (mean, 17.2 years). Two observers evaluated the following CT and MRI features of the tumor by consensus: (i) location, shape, and size; (ii) attenuation, T2 signal intensity, and ADC value; (iii) patterns of contrast enhancement; (iv) presence of fibrovascular septa; (v) presence of necrosis, hemorrhage, and calcification; (vi) presence of "ovarian vascular pedicle" sign. We also noted the extent or stage of the tumors.

Results: 75% lesions arised in the right ovary. Bilateral ovaries were involved in one case. Tumors displayed as a purely or predominantly solid mass (mean size, 17.0 ± 7.8 cm). Ten tumors were shaped multilobulated. The mean ADC value of lesions was 0.830 ± 0.154 × 10 mm/s. Characteristic fibrovascular septa were observed in all lesions. Among them, classic septa were present in 69% lesions. They were thin, hypointense on T2WI with a linear intense enhancement indicating the blood vessels in septa. Due to the stromal edema, fibrovascular septa may become thick even amorphous in shape, hyperintense on T2WI and even low attenuation on CT with a slight enhancement except for a bright blood vessel on the edge. Massive necrosis was observed only in one lesion. Calcification was present in 3 of the 5 tumors on CT. "Ovarian vascular pedicle" sign was present in 12 lesions. Lymphadenopathy, retroperitoneal spread, and distant metastases combined with an implantation in Douglas' cul-de-sac were present in one patient respectively.

Conclusion: On CT and MR images, ovarian dysgerminoma often appears as a large solid mass. The edematous condition of characteristic fibrovascular septa can be well displayed by imaging which then can guide the radiologists to make an accurate diagnosis. Calcifications often occur in the tumor. Nonspecific low ADC value and "ovarian vascular pedicle" sign may narrow the differential diagnosis.
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http://dx.doi.org/10.1186/s13048-020-00674-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7301981PMC
June 2020

Drought affects the coordination of belowground and aboveground resource-related traits in in China.

Ecol Evol 2019 Sep 19;9(17):9948-9960. Epub 2019 Aug 19.

State Environmental Protection Key Laboratory of Regional Ecological Processes and Functions Assessment Chinese Research Academy of Environmental Sciences Beijing China.

Quantifying patterns of variation and coordination of plant functional traits can help to understand the mechanisms underlying both invasiveness and adaptation of plants. Little is known about the coordinated variations of performance and functional traits of different organs in invasive plants, especially in response to their adaptation to environmental stressors. To identify the responses of the invasive species to drought, 180 individuals were randomly collected from 15 populations and 212 ramets were replanted in a greenhouse to investigate both the response and coordination between root and leaf functional traits. Drought significantly decreased plant growth and most of the root and leaf functional traits, that is, root length, surface area, volume and leaf size, number, and mass fraction, except for the root length ratio and root mass fraction. Phenotypic plasticity was higher in root traits than in leaf traits in response to drought, and populations did not differ significantly. The plasticity of most root functional traits, that is, root length (RL), root surface area (RSA), root volume (RV), and root mass fraction (RMF), were significantly positively correlated with biomass between control and drought. However, the opposite was found for leaf functional traits, that is, specific leaf area (SLA), leaf area ratio (LAR), and leaf mass fraction (LMF). Drought enhanced the relationship between root and leaf, that is, 26 pairwise root-leaf traits were significantly correlated under drought, while only 15 pairwise root-leaf traits were significantly correlated under control conditions. Significant correlations were found between biomass and all measured functional traits except for leaf size. RV, root length ratio, RMF, total area of leaves, and LMF responded differently to water availability. These responses enable to cope with drought conditions and may help to explain the reason of the vast ecological amplitude of this species.
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http://dx.doi.org/10.1002/ece3.5536DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6745655PMC
September 2019

Integrated assessment of PD-L1 expression and molecular classification facilitates therapy selection and prognosis prediction in gastric cancer.

Cancer Manag Res 2019 10;11:6397-6410. Epub 2019 Jul 10.

Department of Pathology, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200092, People's Republic of China.

Purpose: Targeting the PD-1/PD-L1 pathway has emerged as a novel therapy for cancer. To identify rational candidates for anti-PD-1/PD-L1 immunotherapy in gastric cancer (GC), the abundance of PD-L1 expression was evaluated on a kind of biomarker-based molecular classification for shaping prognosis and treatment planning.

Methods: One hundred and sixty-five GCs were classified into five subgroups using immunohistochemistry (IHC) and in situ hybridization (ISH) methods, based on a panel of seven markers (MLH1, PMS2, MSH2, MSH6, E-cadherin, P53, and Epstein-Barr virus mRNA). The expression of PD-L1 in GC tissues was analyzed immunohistochemically.

Results: The five categories (Epstein-Barr virus positivity, microsatellite instability, aberrant E-cadherin, aberrant P53 expression, and normal P53 expression) correspond to the reported molecular subgroups for similar proportions and clinicopathologic characteristics. Survival analysis indicated that subgroups with aberrant E-cadherin expression independently predicted a worse prognosis in GC patients (HR=2.51, =0.010). The clinical and prognostic profiles produced by this stratification in nonintestinal-type GC were distinguishable from those in intestinal-type. Although PD-L1 was not a significant prognostic factor, that more frequent presence of PD-L1-positive in microsatellite instability tumors than other subtypes (<0.010) hinted at a prolonged clinical course. Moreover, the lowest level of PD-L1 but the highest of Her2 was observed in the group of aberrant P53, namely it was suggested that there was a negative correlation between PD-L1 and Her2 overexpression.

Conclusion: Different molecular subtypes in GC may have a tendency to react differently to anti-PD-L1/PD-1 immunotherapy or anti-Her2 therapy. A combination of PD-L1 expression and this cost-effective classification strategy would be helpful for predicting prognosis and promoting personalized therapy in clinical practice.
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http://dx.doi.org/10.2147/CMAR.S206189DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6630096PMC
July 2019

Genome sequence of Malania oleifera, a tree with great value for nervonic acid production.

Gigascience 2019 02;8(2)

Beijing Advanced Innovation Center for Tree Breeding by Molecular Design, National Engineering Laboratory for Tree Breeding, School of Nature Conservation, College of Biological Sciences and Technology, Beijing Forestry University, Beijing, 100083, China.

Background: Malania oleifera, a member of the Olacaceae family, is an IUCN red listed tree, endemic and restricted to the Karst region of southwest China. This tree's seed is valued for its high content of precious fatty acids (especially nervonic acid). However, studies on its genetic makeup and fatty acid biogenesis are severely hampered by a lack of molecular and genetic tools.

Findings: We generated 51 Gb and 135 Gb of raw DNA sequences, using Pacific Biosciences (PacBio) single-molecule real-time and 10× Genomics sequencing, respectively. A final genome assembly, with a scaffold N50 size of 4.65 Mb and a total length of 1.51 Gb, was obtained by primary assembly based on PacBio long reads plus scaffolding with 10× Genomics reads. Identified repeats constituted ∼82% of the genome, and 24,064 protein-coding genes were predicted with high support. The genome has low heterozygosity and shows no evidence for recent whole genome duplication. Metabolic pathway genes relating to the accumulation of long-chain fatty acid were identified and studied in detail.

Conclusions: Here, we provide the first genome assembly and gene annotation for M. oleifera. The availability of these resources will be of great importance for conservation biology and for the functional genomics of nervonic acid biosynthesis.
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http://dx.doi.org/10.1093/gigascience/giy164DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6377399PMC
February 2019

Downregulation of miRNA-214 in cancer-associated fibroblasts contributes to migration and invasion of gastric cancer cells through targeting FGF9 and inducing EMT.

J Exp Clin Cancer Res 2019 Jan 15;38(1):20. Epub 2019 Jan 15.

Department of Pathology, School of Medicine, Xinhua Hospital, Shanghai Jiao Tong University, Shanghai, 200092, China.

Background: Cancer-associated fibroblasts (CAFs), one of the principal constituents of the tumor microenvironment, have a pivotal role in tumor progression. Dysregulation of microRNAs (miRNAs) in CAFs contributes to the tumor-promoting ability of CAFs. However, the mechanism underlying the involvement of miRNAs in CAFs of gastric cancer (GC) is not fully understood. This study aimed to explore the effects of miRNA-214 in CAFs on GC migration and invasion.

Methods: The primary CAFs and corresponding normal fibroblasts (NFs) were isolated. Cell counting kit-8, EdU cell proliferation staining and Transwell assays were used to determine the role of miRNA-214 in GC progression. Real-time polymerase chain reaction, Western blot analysis, and dual-luciferase reporter assay were performed to verify the target genes of miRNA-214. Immunofluorescence and Western blot analysis were applied to detect the expression of epithelial-mesenchymal transition (EMT) markers. Immunohistochemistry and in situ hybridization were implemented to analyze the fibroblast growth factor 9 (FGF9) and miRNA-214 expression in human GC tissues, respectively. Finally, to assess its prognostic relevance, Kaplan-Meier survival analysis was conducted.

Results: MiRNA-214 was significantly downregulated in CAFs of GC compared with NFs. The upregulation of miRNA-214 in CAFs inhibited GC cell migration and invasion in vitro but failed to affect proliferation. Moreover, GC cells cultured with conditioned medium from CAFs transfected with miR-214 mimic showed increased expression of E-cadherin and decreased expression of Vimentin, N-cadherin and Snail, indicating the suppression of EMT of GC cells. Furthermore, FGF9 was proved to be a direct target gene of miR-214. The expression of FGF9 was higher in CAFs than that in tumor cells not only in primary tumor but also in lymph node metastatic sites (30.0% vs 11.9%, P < 0.01 and 32.1% vs 12.3%, P < 0.01, respectively). Abnormal expression of FGF9 in CAFs of lymph node metastatic sites was significantly associated with poor prognosis in patients with GC (P < 0.05).

Conclusions: This study showed that miR-214 inhibited the tumor-promoting effect of CAFs on GC through targeting FGF9 in CAFs and regulating the EMT process in GC cells, suggesting miRNA-214/FGF9 in CAFs as a potential target for therapeutic approaches in GC.
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http://dx.doi.org/10.1186/s13046-018-0995-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6334467PMC
January 2019

Comparison of contrast-enhanced ultrasound targeted biopsy versus standard systematic biopsy for clinically significant prostate cancer detection: results of a prospective cohort study with 1024 patients.

World J Urol 2019 May 5;37(5):805-811. Epub 2018 Sep 5.

Department of Urology, Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine, 1665 Kongjiang Road, Shanghai, 200092, People's Republic of China.

Purpose: To assess contrast-enhanced ultrasound (CEUS) targeted biopsy (TB) for clinically significant prostate cancer (PCa) detection compared with systematic biopsy (SB).

Methods: A total of 1024 consecutive patients scheduled for prostate biopsy were enrolled in this prospective study. CEUS was performed by an experienced radiologist blinded to all clinical data. Suspicious lesions on postcontrast images were sampled in addition to standard 12-core SB. The clinically significant PCa detection rate by CEUS-TB was evaluated in comparison with SB in the total cohort and in different subgroups.

Results: In 378 of 1024 patients (36.9%), the diagnosis of PCa was histologically confirmed. PCa was detected by CEUS-TB in 306 patients (29.9%, 306/1024) and SB in 317 patients (31.0%, 317/1024, P = 0.340). Among 378 PCa patients, 326 (86.2%, 326/378) were diagnosed with significant PCa using Epstein criteria. The significant PCa detection rate of CEUS-TB was 28.7% (294/1024), which was higher than that of SB (25.3%, 259/1024, P = 0.000). CEUS-TB resulted in 67 additional cases of clinically significant PCa, including 51 patients missed by SB and 16 patients under-graded by SB. Conversely, SB detected 32 additional significant PCa missed by TB. In the subgroup analysis, CEUS-TB yielded a higher significant cancer detection rate than SB in patients with a PSA level ≤ 10.0 ng/ml or prostate volume from 30 to 60 ml.

Conclusion: The clinically significant PCa detection rate could be improved by the extra sampling of abnormalities on postcontrast images, especially in patients with a PSA level ≤ 10.0 ng/ml or prostate volume from 30 to 60 ml.
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http://dx.doi.org/10.1007/s00345-018-2441-1DOI Listing
May 2019

Testicular germ cell tumors: a clinicopathological and immunohistochemical analysis of 145 cases.

Int J Clin Exp Pathol 2018 1;11(9):4622-4629. Epub 2018 Sep 1.

Department of Assisted Reproduction, Xin Hua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine Shanghai, China.

Testicular germ cell tumor (TGCT) is the most common tumor usually occuring in males between 20-40 years old. In recentyears, the incidence of TGCTs has risen markedly. The outcome depends on its pathologic type and tumor stage. This study was a retrospective analysis of the clinicopathological and immunohistochemical of 145 TGCTs. According to our findings, teratoma, both mature and immature, mostly involved children, as did yolk sac tumor. Patients under 18 years old all survived for at least five years, while the mortality rate was 87.8% after five years since surgery and 96.5% in adults after three years. There was no difference between the survival rate of seminomatous tumor and non-seminomatous tumor. We also analyzed two routine diagnostic markers-PLAP and OCT4 on all TGCT tissues. Results showed that OCT4 may be a better predictive marker than PLAP to distinguish the TGCTS. Our finding suggested that TGCTs mostly occurred in young adult, and the mortality of those who under 18 years old is lower than the adult patients. However in distinguishing the seminoma tumor from non-seminoma tumor, new marker should be further study.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6962990PMC
September 2018

Meconium peritonitis due to fetal appendiceal perforation: two case reports and a brief review of the literature.

BMC Pediatr 2018 05 11;18(1):162. Epub 2018 May 11.

Department of Pediatric Surgery, Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine, No 1665, Kongjiang Road, Shanghai, 200092, People's Republic of China.

Background: Meconium peritonitis is an infrequent congenital disease usually caused by perforation of the fetal digestive tract. Meconium peritonitis resulting from intrauterine appendiceal perforation has been rarely reported and is often overlooked during pregnancy. We herein report two cases of fetal appendiceal perforation.

Case Presentation: Two neonates were found to have intestinal distension and gradually increasing ascites antenatally. After birth, diagnostic abdominal punctures revealed meconium peritonitis. Urgent surgery showed both neonates had developed gangrenous appendicitis in utero. Pathological examination supported the diagnosis of fetal appendiceal perforation in both neonates, and one also had deformity of cecal duplication. In the present report, we also review the presentation, diagnosis, pathology, management, and recent literature of fetal appendiceal perforation.

Conclusion: Meconium peritonitis due to fetal appendiceal perforation is extremely rare, and preoperative diagnosis is almost impossible. However, clinicians should be aware of abnormal gastrointestinal manifestations in the fetus during the antenatal examination. For neonates with severe meconium peritonitis, an early operation with careful intraoperative exploration is necessary.
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http://dx.doi.org/10.1186/s12887-018-1133-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5948796PMC
May 2018

Cancer associated fibroblasts tailored tumor microenvironment of therapy resistance in gastrointestinal cancers.

J Cell Physiol 2018 09 25;233(9):6359-6369. Epub 2018 Mar 25.

Department of Pathology, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.

Gastrointestinal cancers (GI), are a group of highly aggressive malignancies with heavy cancer-related mortalities. Even if continued development of therapy methods, therapy resistance has been a great obstruction for cancer treatment and thereby inevitably leads to depressed final mortality. Peritumoral cancer associated fibroblasts (CAFs), a versatile population assisting cancer cells to build a facilitated tumor microenvironment (TME), has been demonstrated exerting a promotion influence on cancer proliferation, migration, invasion, metastasis, and also therapy resistance. In this review, we provide an update progress in describing how CAFs mediate therapy resistance in GI by various means, meanwhile highlight the crosstalk between CAFs and cancer cells and present some vital signaling pathways activated by CAFs in this resistant process. Furthermore, we discuss the current advances in adopting novel drugs against CAFs and how the knowledge contributing to improved therapy efficacy in clinical practice. In sum, CAFs create a therapy-resistant TME in several aspects of GI progression, although some key problems about distinguishing CAFs subpopulations and controversial issues on pleiotropic CAFs in medication need to be solved for subsequent clinical application. Predictably, targeting therapy-resistant CAFs is a promising adjunctive treatment to benefit GI patients.
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http://dx.doi.org/10.1002/jcp.26433DOI Listing
September 2018

Primary malignant melanoma of the lung: A case report and literature review.

Medicine (Baltimore) 2017 Nov;96(46):e8772

aDepartment of Respiratory Medicine bDepartment of Pathology, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, PR China.

Rationale: Primary malignant melanoma of the lung (PMML) is an extremely rare neoplasm with a dismal prognosis. The diagnosis of PMML is very difficult and is based on several clinical, radiological, and histopathological criteria.

Patient Concerns: A 61-year-old women was admitted with a 2-month history of a productive cough and chest pain provoked by breathing and coughing. Computed tomography (CT) scans of the chest showed a large, solid tumor in the right middle lobe of the lung. Puncture biopsy of the right lung lesion was performed using B-ultrasound guidance, and immunohistochemical tests were performed.

Diagnoses: The diagnosis of PMML was histopathologically confirmed by puncture biopsy with B-ultrasound guidance of the right lung lesion.

Interventions: The patient refused to receive surgery, adjuvant chemotherapy, or radiation therapy.

Outcomes: The patient died 6 months after the diagnosis.

Lessons: The clinical manifestation and imaging features of PMML are not specific, and it does not differ from the more common primary bronchogenic carcinoma. In addition, it cannot be discriminated from other forms of primary melanoma according to its histology and immunohistochemistry. The treatment of choice is an aggressive surgical approach, combined with radiation therapy, chemotherapy, and immunotherapy.
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http://dx.doi.org/10.1097/MD.0000000000008772DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5704877PMC
November 2017

THSD7A-associated membranous nephropathy in a patient with neurofibromatosis type 1.

Eur J Med Genet 2018 Feb 25;61(2):84-88. Epub 2017 Oct 25.

Renal Division, Department of Internal Medicine, Xin Hua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China. Electronic address:

Target antigens in idiopathic membranous nephropathy (MN) include the phospholipase A2 receptor (PLAR), and in some cases, the thrombospondin type 1 domain-containing 7A (THSD7A). A notable phenomenon is the high rate of cancer (reported to be as high as 20%) in patients with THSD7A-associated MN. Neurofibromatosis type 1 (NF1) is an autosomal dominant disease caused by NF1 gene mutation, and clinically characterized by multiple cutaneous neurofibromas and café-au-lait spots. In this article, we report a patient with NF1 who developed THSD7A-associated MN when the NF1 skin lesions deteriorated. The patient, a 62-year-old male, was referred to us for nephrotic syndrome for 6 months. Physical examination revealed multiple cutaneous nodules throughout the entire body, and the patient noted recent increase in the numbers of these skin lesions. Cutaneous nodules excisional biopsy suggested NF1 and Sanger sequencing using genomic DNA extracted from peripheral blood revealed a previously reported heterozygous frameshift NF1 mutation (c.1541_1542delAG, p. Gln514fs). Renal biopsy revealed MN and immunohistochemistry (IHC) showed enhanced staining of THSD7A as well as PLAR along the glomerular basement membrane whereas the serum level of THSD7A and PLAR were both within normal range. The neurofibroma tissues were positive for THSD7A but not for PLAR on IHC. The patient did not respond to 6-month treatment with glucocorticosteroid and cyclophosphamide. In this exceptional case, strong positive staining of THSD7A in both skin and renal biopsy samples, together with the temporal association between nephrotic syndrome and skin lesions and lack of treatment response, suggested the possibility that MN could be the result of immune response to THSD7A in NF1. This report may improve understanding of the mechanistic link between MN and cancer.
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http://dx.doi.org/10.1016/j.ejmg.2017.10.014DOI Listing
February 2018

Roles of microRNAs in cancer associated fibroblasts of gastric cancer.

Pathol Res Pract 2017 Jul 8;213(7):730-736. Epub 2017 Mar 8.

Department of Pathology, Xin Hua Hospital Affiliated to Shanghai JiaoTong University School of Medicine, Shanghai 200092, China. Electronic address:

Cancer associated fibroblasts (CAFs) are a key component of the tumor microenvironment (TME). They play critical roles in the occurrence and development of gastric cancer (GC) through controlling various cytokines secretion and direct cell-to-cell interaction. However, the underlying mechanism of CAFs in tumor progression has not been entirely elucidated. MicroRNAs (miRNAs) as important factors have a central role in the interplay between tumor cell and TME. Recent studies also highlight that the aberrant expression of miRNAs in CAFs is involved in multiple functions in tumorigenesis and malignant process of GC. In this article, we shortly introduce the miRNAs biogenesis and provide an overview of the mechanisms and emerging roles of CAFs-related miRNAs. Focusing on these miRNAs as potential therapeutic targets may bring better treatment effect on GC and other diseases.
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http://dx.doi.org/10.1016/j.prp.2017.02.020DOI Listing
July 2017

Pathologically assessed grade of Hirschsprung-associated enterocolitis in resected colon in children with Hirschsprung's disease predicts postoperative bowel function.

J Pediatr Surg 2017 Nov 28;52(11):1776-1781. Epub 2017 Mar 28.

Department of Pediatric Surgery, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, No. 1665, Kongjiang Road, Shanghai, 200092, China; Shanghai Key Laboratory of Pediatric Gastroenterology and Nutrition, No. 1665, Kongjiang Road, Shanghai, 200092, China; Shanghai Institute for Pediatric Research, No. 1665, Kongjiang Road, Shanghai, 200092, China. Electronic address:

Purpose: The aim of this study was to investigate the relationship between the grade of enterocolitis on pathological assessment of resected colon and postoperative bowel function in children with Hirschsprung's disease (HD).

Methods: Children with HD who were seen at a large tertiary center from January 2012 to December 2013 were enrolled into this study. Resected colon was assessed using the histopathologic grade scoring system for Hirschsprung-associated enterocolitis (HAEC), and the relationship of these scores to postoperative bowel function was assessed. Time of recovery to normal defecation was the primary outcome measure. The t-test, analysis of variance, and Kaplan-Meier, univariate, and multiple regression analyses were performed.

Results: Eighty children with HD (median age at repair 7.9months; range 1.3months to 9years) were included in the study. Nineteen children dropped out of the study and were considered as providing censored data, giving a follow-up rate of 76.3%. A total of 21 children (34.4%) were admitted to hospital with at least one episode of enterocolitis. Multivariate Cox proportional hazards models showed that compared with patients with a normal proximal colon, those with an inflamed proximal segment had a 1.5-fold higher risk of a poor recovery. Logistic regression analyses suggested that postoperative HAEC admissions increased by 57% with each HAEC pathological grade of the transitional segment and by 50% with each grade of the overall segment. Compared with normal bowel in the transitional segment, the detection of grade ≥3 HAEC in the transitional area increased the incidence of postoperative HAEC by 4.75-fold.

Conclusions: Children whose resected proximal colon showed inflammation on pathological assessment were at risk of poor recovery after surgery. A higher pathological HAEC score for the sum of the overall three segments suggested an increased risk for the subsequent development of enterocolitis. Among three segments, the severity of enterocolitis in the transitional segment was the most significant factor in predicting postoperative HAEC.

Type Of Study: Clinical study.

Level Of Evidence: Moderate.
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http://dx.doi.org/10.1016/j.jpedsurg.2017.03.056DOI Listing
November 2017

Ossifying renal tumor of infancy (ORIT): The clinicopathological and cytogenetic feature of two cases and literature review.

Pathol Res Pract 2016 Nov 2;212(11):1004-1009. Epub 2016 Sep 2.

Department of Pathology, Xin Hua Hospital Affiliated to Shanghai JiaoTong University School of Medicine, Shanghai 200092, China. Electronic address:

Ossifying renal tumor of infancy (ORTI) is a rare benign pediatric renal tumor, which has typical clinical and pathological features. In this article, the histological features, immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) assay of two cases of ORTI were performed and the literatures were reviewed. Both of the patients presented to hospital with painless gross hematuria without other symptoms. One is 6 months old male, another is 5-month-old. After several diagnostic procedures, they underwent surgery and the histological diagnosis of ORTI was finally made. Grossly, the tumor had a nodular or irregular appearance, often partially calcified and located in the renal pelvis and calyces. The cut surface of this mass was grey-white, solid and firm. Histologically, the tumor was composed of three major histologic components: osteoblast-like cells, spindle cells, and an osteoid core. Immunohistochemistry staining revealed that osteoblast-like cells were positive for EMA, Vimentin and STAB2. Spindle cells were strongly immunoreactive for Vimentin, WT-1 and focally positive for SMA, but were negative for CK, PAX8 and PAX2. The FISH studies with CEP4 probe on interphase nuclei from the two ORTIs, revealed trisomy 4 were 8.97% (case 1) and 12.23% (case 2). Our study showed that clonal trisomy 4 may be considered as a cytogenetic feature of ORTI, which makes it distinct from other pediatric renal tumor.
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http://dx.doi.org/10.1016/j.prp.2016.08.008DOI Listing
November 2016

Latitudinal and longitudinal clines of phenotypic plasticity in the invasive herb Solidago canadensis in China.

Oecologia 2016 11 13;182(3):755-64. Epub 2016 Aug 13.

Department of Biology, University of Konstanz, Universitätsstrasse 10, 78457, Constance, Germany.

Phenotypic plasticity is thought to be important for plants in variable environments. The climatic variability hypothesis poses that populations at higher latitudes, due to the stronger variation in temperature, there should be more plastic in response to temperature than populations at lower latitudes. Similarly, populations at locations with stronger precipitation fluctuations should be more plastic in response to water availability than populations at locations with less variable precipitation. We sampled seven and nine populations of Solidago canadensis, a North American native that is invasive in China, along a latitudinal (temperature variability) and a longitudinal (precipitation variability) gradient, respectively, in China, and grew them under two temperature treatments and two water-availability treatments, respectively. Among the four traits with significant variation in plasticity among populations in response to temperature, plasticity of leaf length-to-width ratio was significantly positively correlated with latitude and temperature seasonality of the populations. In addition, root/shoot ratio and water-use efficiency showed significant variation in plasticity among populations in response to water availability, and plasticities of these two traits were significantly negatively correlated with longitude and positively correlated with precipitation seasonality. The observed geographic clines in plasticity suggest that phenotypic plasticity of S. canadensis may have evolved rapidly in regions with different climatic conditions, and this may have contributed to the spread of this invasive species.
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http://dx.doi.org/10.1007/s00442-016-3699-xDOI Listing
November 2016

Expression of Notch 1 receptor associated with tumor aggressiveness in papillary thyroid carcinoma.

Onco Targets Ther 2016 15;9:1519-23. Epub 2016 Mar 15.

Department of Nuclear Medicine, Shanghai Jiao Tong University, School of Medicine, Shanghai, People's Republic of China.

Aim: The aim of this study was to assess if the expression of Notch 1 receptor is associated with tumor aggressiveness in papillary thyroid carcinomas (PTCs).

Patients And Methods: By searching the electronic medical record system of Xin Hua Hospital, all cases of PTC patients who underwent thyroidectomy in the hospital between 2013 and 2014 were retrieved. Then, the cases of patients who had a history of any other malignancy or whose thyroid tumor specimen was not available for assay were rejected. Finally, 68 cases of PTC patients were obtained. Formalin-fixed paraffin-embedded tissue blocks of these patients were studied by immunohistochemistry to learn the expression of Notch 1 receptor. Meanwhile, the clinical data of these patients including sex, age, size of the tumor, presence of node metastasis or distant metastasis, and presence of capsule invasion and tumor multicentricity were collected. Pearson's chi-square test or Fisher's exact test was used for measuring statistical differences in categorical variables. All the statistical tests were two-sided. A P-value <0.05 was considered to be statistically significant.

Results: A total of 19 male and 49 female PTC patients with a mean age of 44.8±13.6 years (range 18-78 years) were studied. Notch 1 receptor expression was found in 15/68 (22%) samples of PTC. The expression of Notch 1 receptor was significantly associated with tumor size (P=0.021), distant metastasis (P=0.008), capsule invasion (P=0.001), tumor multicentricity (P=0.018), and age (P=0.033). However, the expression of Notch 1 receptor was not significantly correlated with node metastasis (P=0.096) and sex (P=0.901).

Conclusion: The expression of Notch 1 receptor is associated with tumor aggressiveness in PTC, and may be used as a molecular marker of tumor invasiveness in PTC. PTC patients who show positive expression of Notch 1 receptor may benefit from radioiodine remnant ablation.
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http://dx.doi.org/10.2147/OTT.S98239DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4801130PMC
April 2016

Optimal treatment for primary benign intratracheal schwannoma: A case report and review of the literature.

Oncol Lett 2015 Oct 21;10(4):2273-2276. Epub 2015 Jul 21.

Department of Respiratory Medicine, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200092, P.R. China.

A 53-year-old male was admitted to Xinhua Hospital (Shanghai, China) due to coughing and dyspnea that had persisted for half a year, with aggravation of chest tightness and dyspnea for 1 week. Chest computed tomography (CT) revealed a mass within the distal third of the trachea. Flexible bronchoscopy confirmed an ~2.0 cm, smooth, tan-colored mass in the trachea, 2 cm above the carina. Endoscopic resection by argon plasma coagulation combined with electronic snaring was applied, however, recurrence was found 2 weeks later. Finally, the tumor was completely removed by surgery and the post-operative course was uneventful. Since schwannoma is rare in the intrapulmonary region and extremely rare in the trachea, a review of 51 cases of primary tracheal schwannoma previously reported in the English literature was performed. The majority of cases occurred in adults and were usually located in the distal third of the trachea. The predominant tumor size was 1-3 cm and airway obstruction symptoms were common. Half of the patients were misdiagnosed with asthma, and CT scan and bronchoscopy were contributory to the correct diagnosis. The treatment of choice depended on the patient's condition, however, surgery should be chosen in the event of local recurrence following endoscopic treatment.
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http://dx.doi.org/10.3892/ol.2015.3521DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4579820PMC
October 2015

Development of 23 novel polymorphic EST-SSR markers for the endangered relict conifer Metasequoia glyptostroboides.

Appl Plant Sci 2015 Sep 11;3(9). Epub 2015 Sep 11.

National Engineering Laboratory for Tree Breeding, College of Biological Sciences and Technology, Beijing Forestry University, Beijing 100083, People's Republic of China.

Premise Of The Study: Metasequoia glyptostroboides is an endangered relict conifer species endemic to China. In this study, expressed sequence tag-simple sequence repeat (EST-SSR) markers were developed using transcriptome mining for future genetic and functional studies.

Methods And Results: We collected 97,565 unigene sequences generated by 454 pyrosequencing. A bioinformatics analysis identified 2087 unique and putative microsatellites, from which 96 novel microsatellite markers were developed. Fifty-three of the 96 primer sets successfully amplified clear fragments of the expected sizes; 23 of those loci were polymorphic. The number of alleles per locus ranged from two to eight, with an average of three, and the observed and expected heterozygosity values ranged from 0 to 1.0 and 0.117 to 0.813, respectively.

Conclusions: These microsatellite loci will enrich the genetic resources to develop functional studies and conservation strategies for this endangered relict species.
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http://dx.doi.org/10.3732/apps.1500038DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4578375PMC
September 2015

Comparison of Endobronchial Ultrasound-Guided Fine Needle Aspiration and Video-Assisted Mediastinoscopy for Mediastinal Staging of Lung Cancer.

Lung 2015 Oct 18;193(5):757-66. Epub 2015 Jul 18.

Department of Health Statistics, Second Military Medical University, 800 Xiang Yin Road, Shanghai, 200433, People's Republic of China.

Video-assisted mediastinoscopy (VAM) and endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) are the two most commonly used invasive methods for mediastinal staging of lung cancer. The objective of this review is to assess and compare the overall diagnostic values of VAM and EBUS-TBNA. PubMed, Embase, Web of Science and the Cochrane Library were searched for studies that evaluated EBUS-TBNA or VAM accuracy. Quantitative meta-analysis was used to pool sensitivity and specificity, and study quality was evaluated. Meta-regression was applied to indirectly compare EBUS-TBNA and VAM after adjusting quality score, study design, and station number. A total of ten studies with 999 EBUS-TBNA patients and seven studies with 915 VAM patients were included. Since the pooled specificity was 100% for both modalities, sensitivity was mainly analyzed. The pooled sensitivities for EBUS-TBNA and VAM were 0.84 (95% CI 0.79-0.88) and 0.86 (95% CI 0.82-0.90), respectively. Subgroup analyses of quality score, study design, station number and rapid on-site cytologic evaluation showed no significant influence on the overall sensitivity of the two modalities. After adjusting quality score, study design, and station number, the pooled sensitivities of VAM and EBUS-TBNA were not significantly different. However, more procedural complications and fewer false negatives (FN) were found with VAM than EBUS-TBNA. VAM and EBUS exhibited equally high diagnostic accuracy for mediastinal staging of lung cancer. Due to lower morbidity with EBUS-TBNA and fewer FN with VAM, EBUS-TBNA should be performed first, followed by VAM in the case of a negative needle result.
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http://dx.doi.org/10.1007/s00408-015-9761-3DOI Listing
October 2015

In Vivo Molecular MRI Imaging of Prostate Cancer by Targeting PSMA with Polypeptide-Labeled Superparamagnetic Iron Oxide Nanoparticles.

Int J Mol Sci 2015 Apr 28;16(5):9573-87. Epub 2015 Apr 28.

State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine, Shanghai 200032, China.

The prostate specific membrane antigen (PSMA) is broadly overexpressed on prostate cancer (PCa) cell surfaces. In this study, we report the synthesis, characterization, in vitro binding assay, and in vivo magnetic resonance imaging (MRI) evaluation of PSMA targeting superparamagnetic iron oxide nanoparticles (SPIONs). PSMA-targeting polypeptide CQKHHNYLC was conjugated to SPIONs to form PSMA-targeting molecular MRI contrast agents. In vitro studies demonstrated specific uptake of polypeptide-SPIONs by PSMA expressing cells. In vivo MRI studies found that MRI signals in PSMA-expressing tumors could be specifically enhanced with polypeptide-SPION, and further Prussian blue staining showed heterogeneous deposition of SPIONs in the tumor tissues. Taken altogether, we have developed PSMA-targeting polypeptide-SPIONs that could specifically enhance MRI signal in tumor-bearing mice, which might provide a new strategy for the molecular imaging of PCa.
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http://dx.doi.org/10.3390/ijms16059573DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4463605PMC
April 2015

Low doses of CMV induce autoimmune-mediated and inflammatory responses in bile duct epithelia of regulatory T cell-depleted neonatal mice.

Lab Invest 2015 Feb 22;95(2):180-92. Epub 2014 Dec 22.

1] Department of Pediatric Surgery, Xin Hua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China [2] Shanghai Key Laboratory of Pediatric Gastroenterology and Nutrition, Shanghai, China [3] Shanghai Institute for Pediatric Research, Shanghai, China.

Recent studies have indicated that perinatal infection with cytomegalovirus (CMV) may promote bile duct damage in biliary atresia (BA) and that the decreased regulatory T cell (Treg) percentage associated with BA may further amplify the bile duct damage. Although a majority of BA patients have had previous CMV infections and lower percentages of Tregs, it is unknown whether an initial exposure to a low dose of CMV could induce exaggerated and progressive biliary injury. A Treg-depleted neonatal mouse was infected with low-dose CMV (LD-CMV) as a model to study BA patients. LD-CMV infection in Treg-depleted mice induced extensive inflammation in both the intrahepatic and extrahepatic bile ducts, accompanied with injury to and atresia of intrahepatic bile ducts and partial obstruction of the extrahepatic bile ducts. Serum total and direct bilirubin amounts were also elevated. Evidence for the involvement of cellular and humoral autoimmune responses in LD-CMV-infection of Treg-depleted mice was also obtained through detection of increased percentages of CD3 and CD8 mononuclear cells and serum autoantibodies reactive to bile duct epithelial proteins, one of which was identified as α-enolase. Depletion of Tregs that can lead to the decreased inhibition of aberrantly activated hepatic T-lymphocytes and generation of autoantibodies may lead to further injury. Increased hepatic expression of Th1-related genes (TNF-α), IFN-γ-activated genes (STAT-1) and Th1 cytokines (TNF-α, lymphotactin, IL-12p40 and MIP -1γ) were also identified. In conclusion, autoimmune-mediated and inflammatory responses induced by LD-CMV infection in Treg-depleted mice results in increased intrahepatic and extrahepatic bile duct injury and contributed to disease progression.
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http://dx.doi.org/10.1038/labinvest.2014.148DOI Listing
February 2015
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