Clinical and cytological characteristics of serous effusions in 69 cases of lymphoma patients.

BACKGROUND: To explore the value of cell morphology, immunophenotype, and gene alterations of serosal effusion in the diagnosis of lymphoma. METHODS: Serosal effusion of 69 cases of lymphoma patients were collected, including 36 cases with malignant effusion and 33 cases with nonmalignant effusion. Ordinary cytology, liquid-based cytology, cellblock, and immunocytochemical staining were performed in each case, some cases were detected by fluorescence in situ hybridization for C-MYC, BCL2, and BCL6 gene translocations. T/B cell ratio in malignant and nonmalignant serosal effusions was analyzed and compared by flow cytometry (FCM) and immunohistochemical (IHC), respectively. The prognostic value of serous effusion in diffuse large B-cell lymphoma (DLBCL) was investigated and another 20 DLBCL cases without effusion were successively selected as control. RESULTS: The number of naive lymphocytes, apoptotic bodies, and mitotic figures were more common in malignant effusions compared with nonmalignant effusions (p < .01). The top three lymphomas in malignant effusion were DLBCL (19/36, 52.8%), mantle cell lymphoma (MCL) (4/36, 11.1%, 3 blastoid variant) and high-grade B-cell lymphoma (HGBL) (4/36, 11.1%). T/B cell ratio by FCM analysis ranged from 0.00 to 0.55 (mean 0.084) in malignant effusion, and 2.58 to 984.00 (mean 249.9) in nonmalignant effusion. The difference was significant (p = .017). The T/B cell ratio by IHC analysis ranged from 0.02 to 3.00 (mean 0.200) in malignant effusion, and 2.00-100.00 (mean 34.10) in nonmalignant effusion. The difference was significant (p = .017). In the effusions involving DLBCL, most effusions were present at the time of diagnosis (57.9%); single pleural effusions were more common (36.8%). The median overall survival times of patients with malignant effusion, nonmalignant effusion and DLBCL without serous effusion were 11, 17, and 23 months respectively (p = .04). Three patients of HGBL died, and the overall survival times were 5, 8, and 9 months, respectively. CONCLUSIONS: The cytomorphological characteristics combined with immunophenotype, FCM, gene rearrangement, and other tests can diagnose and classify patients with effusion as the first symptom. The T/B cell ratio is less than 1 by FCM or IHC suggesting a malignant serosal effusion. The presence of malignant effusion in DLBCL patients is an important clue for poor prognosis.

PDP1 Promotes Cell Malignant Behavior and Is Associated with Worse Clinical Features in Ovarian Cancer Patients: Evidence from Bioinformatics and In Vitro Level.

PDP1 has been reported in multiple diseases. However, it has not been fully explored in ovarian cancer (OC). The public data was downloaded from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. Differentially expressed gene analysis was conducted out using the limma package. Prognosis analysis was performed using the survival package. Gene Set Enrichment Analysis (GSEA) was performed using the fgsea package. Immune infiltration analysis was performed based on the CIBERSORT algorithm. CCK8 assay was used to evaluate the cell proliferation ability of cancer cells. Transwell assay was used for the invasion and migration ability. Our result showed that PDP1 was overexpressed in OC tissue in RNA and protein level based on multiple databases (TCGA, GSE18520, GSE27651, and GSE54388). At the same time, we found PDP1 was correlated with poor prognosis and worse clinical parameters. In vitro experiment showed that PDP1 could significantly promote proliferation, invasion, and migration ability of OC cells. GSEA analysis showed that in the OC patients with high PDP1 expression, the pathway of IL6/JAK/STAT3 signaling, interferon-alpha response, apoptosis, adipogenesis, KRAS signaling, and IL2/STAT5 signaling was activated, which might be responsible for its oncogenic effect in OC. Immune infiltration analysis indicated that PDP1 was positively correlated with activated myeloid dendritic cells, resting CD4 memory T cells, neutrophil, and M1 and M2 macrophages, yet negatively correlated with M0 macrophages, plasma B cells, γδT cells, and activated CD4 memory T cells. Drug sensitivity analysis showed a negative correlation between PDP1 expression and the IC50 of bleomycin and gemcitabine, yet a positive correlation of cisplatin, indicating that the OC patients with high PDP1 expression might be more sensitive to bleomycin and gemcitabine and more resistant to cisplatin. PDP1 could facilitate OC progression and is associated with patient prognosis and chemosensitivity, making it an underlying biomarker of OC.

Aberrant expression of polo-like kinase 4 in renal cell carcinoma: Association with clinicopathological characteristics and long-term survival.

Polo-like kinase 4 (PLK4) promotes tumorigenesis and is associated with the prognosis of several solid tumors, while its clinical role in patients with renal cell carcinoma (RCC) remains unidentified. The present study aimed to analyze the association of PLK4 with clinicopathological characteristics and long-term prognosis in patients with RCC. The present study detected PLK4 protein and mRNA expression using immunohistochemical and reverse transcription-quantitative PCR assays in 120 patients with RCC. Disease-free survival (DFS) and overall survival (OS) time were calculated based on a median follow-up duration of 6.9 years (range, 1.2-9.9 years). PLK4 protein expression was elevated in tumor tissues compared with adjacent tissues (P<0.001). Upregulation of PLK4 protein was associated with increased T stage (P=0.023), N stage (P=0.014) and TNM stage (P=0.007). Additionally, elevated tumor PLK4 protein expression exhibited an associating trend (without statistical significance) with reduced DFS rate (P=0.066) and was associated with decreased OS rate (P=0.036). However, univariate Cox's regression analysis indicated that high PLK4 protein expression (compared with low PLK4 protein expression) was associated with reduced OS rate (P=0.040) but not with PFS rate (P=0.070). Following adjustment by multivariate Cox's regression analysis, PLK4 protein expression was associated with neither DFS nor OS rate (both P>0.050). Additionally, PLK4 mRNA expression was further detected in some patients (for which fresh specimens frozen in liquid nitrogen were available) to validate the aforementioned observations, and the expression was elevated in tumor tissues compared with adjacent tissues. Furthermore, increased PLK4 mRNA expression was associated with tumor size ≥7 cm, high TNM stage and reduced DFS rate (all P<0.050). PLK4 possesses a certain clinical utility in monitoring the clinical stage of patients with RCC, while its prognostic value requires further validation.

Microscopic phase reconstruction of cervical exfoliated cell under partially coherent illumination.

Basic coherent diffraction imaging methods strongly rely on having a highly coherent illumination in order to reconstruct the phase accurately. However, regardless of considering the turbulent transport medium, the instability of the system or the generation mechanism of the light source, partially coherent illumination is more common in real case. In this paper, we proposed an efficient microscopic phase imaging method to study normal and abnormal cervical exfoliated cells. By applying three phase modulations in a single point of the sample's transmitted field, the phase can be retrieved with correspoding three intensities under partially coherent illumination. Compared with intensity map, we can efficiently and clearly judge the proportion of high density shrinking abnormal cells from the phase distributions, which provides a confident analysis and evaluation basis for early medical diagnosis of cervical cancer. This study also has potential applications in noninvasive optical imaging of dynamic biological tissues.

Performance Evaluation of SHOX2 and RASSF1A Methylation for the Aid in Diagnosis of Lung Cancer Based on the Analysis of FFPE Specimen.

Emerging molecular diagnostic methods are more sensitive and objective, which can overcome the intrinsic failings of morphological diagnosis. Here, a RT-PCR-based in vitro diagnostic test kit (LungMe®) was developed and characterized to simultaneously quantify the DNA methylation of SHOX2 and RASSF1A in FFPE tissue specimens. The clinical manifestations were evaluated in 251 FFPE samples with specificity and sensitivity of 90.4 and 89.8%, respectively. Furthermore, the quantitative analysis shows that the degree of SHOX2 methylation was correlated with the stages of lung cancer, but not in the case of RASSF1A. Our observation indicated that the DNA methylation of SHOX2 and RASSF1A may play different roles in cancer development. Comparison of the methylation levels of SHOX2 and RASSF1A between cancer and cancer-adjacent specimens (n = 30), showed they have "epigenetic field defect". As additional clinical validation, the hypermethylation of SHOX2 and RASSF1A was detected not only in surgical operative specimens, but also in histopathological negative puncture biopsies. SHOX2 and RASSF1A methylation detection can be used to increase sensitivity and NPV, which provide us with a more accurate method of differential diagnosis and are likely to be rapidly applied in clinical examinations.

Clinicopathological and predictive significance of SIRT1 and peroxisome proliferator-activated receptor gamma in esophageal squamous cell carcinoma: The correlation with EGFR and Survivin.

SIRT1 (silent mating type information regulation 2 homolog 1) is an enzyme that deacetylates proteins that contributes to cell survival and angiogenesis. Peroxisome proliferator-activated receptor Ƴ (PPAR Ƴ) is a member of the nuclear steroid hormone receptor superfamily and regulates cell apoptosis and proliferation. The functional roles of SIRT1 and PPAR Ƴ in tumor progression remain controversy. This study aims to investigate the roles of SIRT1 and PPAR Ƴ in esophageal squamous cell carcinoma (ESCC), as well as correlation with expression of EGFR and Survivin. Here, we analyzed the protein expression of SIRT1 and PPAR Ƴ in tumor microarray with ESCC and its associations with clinicopathological parameters and overall survival. Both SIRT1 and PPAR Ƴ were highly expressed in tumor tissues comparing with non-cancerous epithelium. High expression of SIRT1 was positively correlated with advanced TNM stage and poor outcome, while high expression of PPAR Ƴ was positively related with tumor grading, not with patients' prognosis. In addition, the high expression of SIRT1 was positively correlated with overexpression of EGFR, not related with PPAR Ƴ or Survivin expression status. These data suggests SIRT1 may serve as a predictor of poor prognosis in ESCC, and its mediated tumor-promoting role might be associated with the overexpression of EGFR protein in ESCC.

Safety assessment of vitacoxib: 180-day chronic oral toxicity studies.

Vitacoxib, a selective COX-2 inhibitor, is approved for the relief of pain and inflammation associated with orthopedic surgery and osteoarthritis in dogs. In the current study, a chronic toxicity research was performed to evaluate the safety of vitacoxib in male and female rats for long-term. Vitacoxib was dosed orally to groups of rats for 180 days at 1.2, 6, 30 mg/kg bw/day by gavage. The chronic study oral administration of vitacoxib did not show observational or toxicological effects on the body or organ weights, food consumption, hematology and biochemistry at dose 6 mg/kg bw. However, vitacoxib (30 mg/kg) showed minor alterations to histopathology of liver, kidney and stomach related to treatment. These results provide further indication that vitacoxib is safe and well-tolerated in rats after 180 days of daily oral administration at 6 mg/kg bw and the NOAEL for both sexes was 6 mg/kg bw for 180 consecutive days.

Simple, high efficiency detection of microcystins and nodularin-R in water by fluorescence polarization immunoassay.

This manuscript describes the development of a sensitive, fast and easily-performed fluorescence polarization immunoassay (FPIA) for detection of microcystins (MCs) and nodularin-R (NOD) in water. MCs and NOD, the most widespread cyanobacterial toxin are hepatotoxins and tumor promoters, and their acute exposure may result in severe health problems in animals and humans. The fluorescein-based tracers were synthesized, and for the first time preparative high performance liquid chromatography (HPLC) was employed for their purification. Optimal tracers for the analysis were selected by evaluating the immunochemical activity. Under the optimal conditions, the achieved limits of detection (LODs) for MC-LR and NOD were 0.86 and 0.95 µg L-1, respectively, providing a sufficient sensitivity to meet the provisional guideline value recommended by the World Health Organization (WHO). An ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method was developed to confirm the accuracy and precision of the FPIA, and no obvious difference in recovery between these two methods was found. The correlation coefficients (R2) were higher than 0.968. The developed FPIA was easy-to-operate and could be completed within 10 min after simple filtration and adjustment of pH for water samples. The method can be easily extended for screening of other cyanotoxins, representing a versatile strategy for environmental sample analysis.

The overexpression and predictive significance of MMP-12 in esophageal squamous cell carcinoma.

Matrix metalloproteinase (MMP)-mediated degradation of the extracellular matrix is a major factor for tumor invasion and metastasis. MMP-12, as metalloelastase, its function in tumor progression remains contradictory. This study was undertaken to investigate the role of MMP-12 in esophageal squamous cell carcinoma (ESCC). We analyzed the protein expression of MMP-12 and its association with clinicopatholigical parameters, as well as survival analysis. MMP-12 was highly expressed in tumor cells comparing with normal epithelial cells. The high expression of MMP-12 was significantly correlated with tumor grade and stage, nodal metastasis and poor survival of ESCC. Cox multivariate analysis revealed that MMP-12 was an independent prognostic factor in ESCC. Our results suggest that MMP-12 might act as a potential target for the development of novel therapeutics of esophageal squamous cell carcinoma.

MiR-101 reduces cell proliferation and invasion and enhances apoptosis in endometrial cancer via regulating PI3K/Akt/mTOR.

PI3K/Akt/mTOR signaling pathway plays an important role in tumor development. mTOR overexpression and PI3K/ Akt/mTOR signaling pathway enhancement were found in endometrial cancer (EC). MiR-101 was found downregulated in EC. Bioinformatics analysis showed the binding site between miR-101 and the 3'-UTR of mTOR mRNA. This study investigated the role of miR-101 in affecting EC proliferation, apoptosis, and invasion, and mediating mTOR expression. EC tumor tissue and normal endometrial tissue were collected from Jinan maternity and child care hospital. MiR-101 and mTOR expressions were detected. The targeted relationship between miR-101 and mTOR was tested by dual-luciferase reporter gene assay. MiR-101, mTOR, p-mTOR, and p-4EBP1 expressions between HEEC and HEC-1A cells were compared. HEC-1A cells were cultured in vitro and divided into five groups, including miR-NC, miR-101 mimic, si-NC, si-mTOR, and miR-101 + si-mTOR. mTOR, p-mTOR, and p-4EBP1 expressions were compared. Cell apoptosis was evaluated by flow cytometry. Cell malignant proliferation was evaluated by colony formation assay. Cell invasion was determined by Transwell assay. MiR-101 and mTOR expressions significantly declined in EC tissue compared with normal endometrium. MiR-101 showed targeted relationship with mTOR. MiR-101 reduced, while mTOR, p-mTOR, and p-4EBP1 levels elevated in HEC-1 cells compared with HEEC cells. MiR-101 mimic and/or si-mTOR transfection obviously reduced mTOR, p-mTOR, and p-4EBP1 expressions, decreased colony formation, decreased invasion, and enhanced apoptosis in HEC-1A cells. MiR-101 downregulated and mTOR elevated in EC tissue. MiR-101 decreased HEC-1A cell proliferation and invasion, and upregulated apoptosis through targeting mTOR to attenuate PI3K/Akt/ mTOR signaling pathway activity.

Mucoepidermoid carcinoma of the transverse colon: A rare tumor entity with literature review.

Mucoepidermoid carcinoma of the gastrointestinal tract is a rare entity. Here, we report a case of mucoepidermoid carcinoma of the transverse colon in a 77-year-old woman who presented with a 2-month history of epigastrium pain, diarrhea and melena. A giant tumor with apparently invading gallbladder was found by enhanced CT scan, then the extended resection of transverse colon was performed for the patient 2 weeks later. Microscopically, the tumor was composed of solid nests of epidermoid and Periodic Acid-Schiff (PAS)-positive mucin-producing cells with desmoplastic stroma. The epidermoid component of the tumor contained intercellular bridges and individual cell keratinization. Thus, the case was diagnosed as mucoepidermoid carcinoma of the transverse colon. Unfortunately, despite chemotherapy, the patient developed systemic failure and died 7 months postoperatively.

The expression and clinical relevance of PD-1, PD-L1, and TP63 in patients with diffuse large B-cell lymphoma.

Latest study showed that a novel translocation between programmed cell death ligand 1 (PD-L1) (cluster of differentiation 274) and TP63 (tumor protein 63) can be found in diffuse large B-cell lymphoma (DLBCL), resulting in their conjunct overexpression in tumor cells at RNA level. However, the expressed pattern of these 2 genes at protein level in DLBCL remains largely unknown, and the clinical relevance of PD-L1 and TP63 expression in DLBCL are also unclear.Tumor tissues from 76 Chinese DLBCL patients were immunostained for programmed cell death 1 (PD-1), PD-L1, and TP63 using the EnVision system. Clinical relevance of PD-1, PD-L1, and TP63 in 74 DLBCL were analyzed by chi-square test, the Kaplan-Meier curves with log rank test, and Cox's proportional hazards regression model.PD-1 was mainly expressed in tumor-infiltrating lymphocytes (TILs) of 39.5% patients. PD-L1 was expressed in tumor cells of 26.3% patients, and TP63 was immunostained in nucleoli of tumor cells of 31.6% cases. PD-1 expression was significantly associated with the patients' gender and B symptoms (P = 0.032, P = 0.026). DLBCL with PD-L1 or TP63 expression in tumor cells showed low International Prognostic Index (IPI) score (P = 0.007, P = 0.009). PD-1 TILs was related to prolonged overall survival rate (OS) of DLBCL patients (P = 0.02), whereas PD-L1 expression was associated with worse clinical outcome of patients (P = 0.049). Immunoreactivity of TP63 was not correlated with patients' survival time. Besides, PD-1 expression, patients' age, Ann Arbor stage, and IPI score were significant prognostic markers for OS, but PD-L1 and TP63 had no prognostic significance.PD-1, PD-L1, and TP63 are frequently expressed in DLBCL. PD-1/PD-L1/TP63 blockade may be a potential therapeutic strategy for some patients.

Correlation between high perfusion syndrome and stent restenosis after stent implantation.

The present study was conducted to determine the correlation between high perfusion syndrome and stent restenosis after cerebral vascular stent implantation. A total of 146 patients diagnosed with cerebral vascular stenosis and stent implantation were selected. A total of 55 cases (37.67%) of cerebral hyperperfusion syndrome patients were diagnosed by xenon-enhanced computer tomography (Xe-CT) examination and clinical symptoms within 3 days after surgery and were chosen as the observation group. A total of 91 cases were selected as the control group. After treatment, blood flow of the anterior cerebral artery, middle cerebral artery, posterior cerebral artery, anterior border zone, posterior border zone and the inner border zone of the two groups increased, with values in the observation group increasing more significantly, and the differences were statistically significant (P<0.05). The rate of restenosis and target lesion diameter one month and one year after operation in the observation group were significantly higher than those in the control group (P<0.05). Multivariate logistic regression analysis showed that the mean systolic blood pressure (mSBP), mean diastolic blood pressure (mDBP), stenosis rate of cerebral vascular diameter and high perfusion syndrome were independent risk factors for restenosis (P<0.05). The application of Xe-CT examination is important for early diagnosis of hyperperfusion syndrome. Hyperperfusion syndrome and the occurrence of stent restenosis are closely related. mSBP, mDBP, cerebral blood vessel diameter stenosis rate and high perfusion comprehensive syndrome are the independent risk factors of restenosis.

Induced sputum deposition improves diagnostic yields of pulmonary alveolar proteinosis: A clinicopathological and methodological study of 17 cases.

Pulmonary alveolar proteinosis (PAP) is a rare diffuse lung disease characterized by the accumulation of intra-alveolar lipoprotein-like surfactants. Lung core biopsy and bronchoalveolar lavage (BAL) fluid are currently the two major sources of sampling for diagnosis. In the present study, we assessed the value of induced sputum in diagnosing PAP by transmission electron microscopy and examined the PAP 2-year death rate in Asians. Transmission electron microscopy was performed on the samples from 17 patients with PAP, 13 patients with inflammatory lung diseases, and 13 healthy adults. The PAP patients were followed up for 3-156 months, and inflammatory lung diseases patients or healthy adults for 12-36 months. The ultrastructural features including diagnostic lamellar bodies of induced sputum deposition (ISD) samples were similar to that of the BAL fluid sediment. However, the rates of lamellar bodies were 73.7% in the ISD group, significantly higher than the spontaneous sputum deposition (SSD) group (42.1%, P < .0487) and similar to the BAL sediment (76.2%) and the lung biopsy (54.5%) groups. The overall 2-year death rate of our PAP patients was 17.6% (3/17), not statistically different from the healthy adults and patients with inflammatory diseases (0/13, P = .237 for both). ISD may be the preferred non-invasive sampling method for diagnosing PAP by electronic microscopy because of the higher diagnostic yield than SSD. The diagnostic yields of this noninvasive method were similar to that of lung core biopsy and BAL.

Occult oncocytic papillary thyroid carcinoma with lymphoid stroma (Warthin-like tumor): report of a case with concomitant mutations of BRAF V600E and V600K.

Warthin-Like tumor of the thyroid is a recently described rare variant of papillary thyroid cancer. The distinct histological feature of this variant is papillary architecture lining oncocytic epithelial cells with nuclear characteristics of papillary carcinoma, accompanied by prominent lymphocytic infiltration in the papillary stalks. Here, we present a case of occult Warthin-like papillary thyroid carcinoma, 0.5-cm in maximum dimension, underwent left thyroid lobectomy in a 65 years old Chinese woman. In this case, there was no extrathyroid extension, vascular invasion and lymphatic metastasis, as well as no complication of lymphocytic thyroiditis. Immunohistochemistry staining revealed that the tumor cells were positive for Leu-M1, HBME-1, 34ßE12, and MIB-1 labeling index was low. RET/PTC expression was absent in tumor cells. Furthermore, activated point mutations of BRAF V600E and V600K were concurrently detected by DNA sequencing. Further studies are needed to elucidate the prevalence and role of BRAF(V600K) mutation in papillary thyroid carcinoma, and long-term follow-up for the patient is needed to clarify the biological behavior of this variant with dual BRAF mutations.

Comparative metabolism of Lappaconitine in rat and human liver microsomes and in vivo of rat using ultra high-performance liquid chromatography-quadrupole/time-of-flight mass spectrometry.

Lappaconitine (LAP), a non-addictive potent analgesic drug, is broadly used to treat cancer and postoperative pain in many countries, and it also has antibiotic activity against Pseudomonas aeruginosa and Salmonella Typhi. Despite its widespread usage and potential for expanded use, its metabolism was poorly investigated. In this work, the metabolic fate of LAP in liver microsomes of the rat and human was compared, and after oral administration, the metabolites in the rat were investigated using ultra high-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UHPLC-Q/TOF-MS). As a result, a total of 51 metabolites were identified, including 48 metabolites that were reported here for the first time. Based on accurate MS/MS spectra and the known structure of LAP, the metabolites structures and their fragment ions were readily characterized. The biotransformations of LAP in vitro and in vivo were shown to involve hydroxylation, N-deacetylation, O-demethylation, N-deethylation, and hydrolysis. Furthermore, the results indicated a quantitative species difference in the metabolites for LAP between the rat and human. However, 16-DMLAP, DAL and 5'-OH-DAL were the main in vitro and in vivo metabolites. This work provides the LAP metabolite profiles in rat and human, which will help better understand the pharmacological and toxicological activities of LAP.

In vitro and in vivo metabolism of ochratoxin A: a comparative study using ultra-performance liquid chromatography-quadrupole/time-of-flight hybrid mass spectrometry.

Ochratoxin A (OTA) is a mycotoxin that frequently contaminates a wide variety of food and feedstuffs. The metabolism of OTA greatly affects fate and toxicity in humans and animals, because of its possible carcinogenic character (International Agency for Research on Cancer (IARC), group 2B). To completely characterize the metabolites of OTA, the metabolism of OTA in liver microsomes of rats, chickens, swine, goats, cows, and humans was investigated using ultra-performance liquid chromatography-quadrupole/time-of-flight hybrid mass spectrometry (UPLC-Q/TOF-MS). In addition, an in vivo comparative metabolism study of OTA was performed among rats and chickens after oral administration of OTA. As a result, a clear metabolic profile of OTA in different species was proposed, and a total of eight metabolites were identified, of which three hydroxylated metabolites at the phenylalanine moiety were discovered for the first time (preliminarily identified as 9'-OH-OTA, 7'-OH-OTA, and 5'-OH-OTA). Considerable amounts of 7'-OH-OTA were detected in different species' liver microsomes, especially in chickens and humans. Moreover, the metabolism of OTA in chickens was elucidated for the first time in the present study. The 7'-OH-OTA proved to be the main metabolite in vitro and in vivo in chickens. Furthermore, the 4(S)-OH-OTA isomer was the major one, and 4(R)-OH-OTA the minor metabolite in chickens, which was different from others where 4R was the major. OTA undergoes metabolism via three different pathways, namely hydroxylation, dechlorination, and conjugation. The proposed metabolic pathways of OTA in various species provide the scientific community useful data for the toxicological safety evaluation of OTA among different species, and will further facilitate the food safety evaluation of OTA.

Histology subtypes and polyp size are associated with synchronous colorectal carcinoma of colorectal serrated polyps: a study of 499 serrated polyps.

Sessile serrated adenomas (SSA) and traditional serrated adenomas (TSA) are considered as precursors of colorectal cancer, and are often diagnostic challenges. Their true prevalence is masked by significant inter-observer variations. To investigate the true prevalence and synchronous colorectal carcinoma (sCRC) of colorectal serrated polyps (CSP) and their associated factors, we first retrospectively identified all colorectal polyps collected at our institution between June 1995 and May 2013. After centrally reclassifying all CSP to reduce inter-observer variations, Chi-square tests and logistic regression analyses were used to analyze the potential factors. Among the included 5501 colorectal polyps, 499 CSP of 428 patients were identified and studied, including 353 hyperplastic polyps (HP, 70.7%), 80 SSA (16.0%), 61 TSA (12.2%) and 5 mixed polyp (1.0%). Diagnostic disagreements were found in 68 CSP (13.63% of CSP). SSA and TSA were more often larger than 5 mm and in proximal colon than HP. SSA were also more likely associated with older age (p=0.005), size ≥5 mm (p<0.001) and ≥3 polyps (p=0.004) than HP in distal colon, but only more likely associated with older age (p=0.006) in proximal colon. Multivariate regression analysis demonstrated that CSP with sCRC, compared with CSP without sCRC, were linked to CSP size ≥1 cm (vs <1 cm, odds ratio [OR] 4.412, 95% confidence interval [CI] 1.684-11.556, P=0.003) and a diagnosis of SSA or TSA (vs HP, OR 6.194, 95% CI 1.870-20.513, P=0.003 and OR 6.754, 95% CI 1.981-23.028, P=0.002, respectively), but not age, gender, polyp number and polyp shape. SSA and TSA are similarly often associated with sCRC (P=0.460). In conclusion, histology subtypes and polyp size may serve as markers for sCRC of CSP. SSA and TSA may warrant careful endoscopic examinations and similar follow-up intervals.

[The expressions and meanings of BMP-7 and TGF-ß in idiopathic pulmonary fibrosis and idiopathic nonspecific interstitial pneumonia].

OBJECTIVE: To investigate the expressions of cytokines in idiopathic pulmonary fibrosis (IPF) and in idiopathic nonspecific interstitial pneumonia (INSIP); To discuss expressions and meanings of bone morphogenetic protein 7 (BMP-7) and transforming growth factor beta (TGF-ß) in IPF and IPF. METHODS: Selected 47 cases of idiopathic interstitial pneumonia (IIP), which were diagnosed by clinical-radiologic-pathologic (CRP), and classified into two groups which were group IPF (25 IPF) and group INSIP (22 INSIP, including 6 cellular pattern and 16 fibrosing pattern). The normal lung tissues were collected as the control group: The fresh tissues were made to detect more than 114 kinds of cytokines' expressions via Oligo GEArray gene microarray technology. Made a tissue microarray which applied EnVision immunohistochemistry technology to detect the expressions of BMP-7 and TGF-ß in both kinds of IIPs. The two groups of patients were followed-up visited around 5 to 8 years and the survival curves were evaluated by Kaplan-Meier method. RESULTS: According to gene microarray results, these two groups were up-expression in TGF family,IL family and TNF family. Most of BMP members were down-expression, in comparison with the control group, except BMP-5,BMP-8B and BMP-15. As the tissue microarray results demonstrated, compared with normal lung tissues,BMP-7 expressed decreasingly in IPF and INSIP groups (t1 = 27.618, P < 0.001; t2 = -12.404, P < 0.001). The expression of IPF were lower than INSIP (t = 5.387, P < 0.05); In INSIP group, patients of cellular pattern expressed BMP-7 more than fibrosing pattern's (t = -5.341, P < 0.001). There were dramatically increasing expressions of TGF-ß in IPF and INSIP, when compared with the control group (t1 = 23.393, P < 0.001; t2 = -13.445, P < 0.001) and it presented negative correlation with BMP-7(group IPF: r = -0.771, P < 0.001; group INSIP: r = -0.729, P < 0.001). (3) Clinical follow-up data showed, the stability(improvement), deterioration and death rates of the group IPF and the group INSIP were, respectively, 0(0%), 2 (8%), 23 (92%) and 15 (68.1%), 3 (13.6%), 4 (18.2%). The results were statistically significant (all P < 0.05). The median survival time of the part with higher BMP-7 expression and the part with relatively lower BMP-7 expression, in the group IPF, were 110.8 and 66.4 months (t = -2.686, P < 0.05); In the group INSIP, were 146.4 and 74.9 months (t = -3.037, P < 0.05). CONCLUSIONS: Cellular cytokines presented different expression profiles in IPF and INSIP patients. Differently with highly activated TGF-ß, BMP-7 was inhibited in IIP patients, which would remind the degree of fibrosis and prognosis of IIP. BMP-7 would be expected to be a novel target for IIP pathogenesis and prognostic research.