Objective To investigate the expressions of survivin and Ki67 in cutaneous extranodal NK/T-cell lymphoma,nasal type and their significance.Methods Clinical data and laboratory test results were collected from 15 cases of cutaneous extranodal NK/T-cell lymphoma,nasal type with skin lesions as the initial manifestation.Immunohistochemical SP method was used to measure the expression of survivin and Ki67 in tissue sections from the lesions of these patients.To determine the percentage of survivin-or Ki67-positive cells,200 tumor cells were counted in a high power field (HPF) and 5 HPFs were observed in 1 section.Results There were 10 males and 5 females among the 15 patients,with the median age at diagnosis being 28.7 (range:9-62) years.Immunohistochemical study showed that the lesional tissue was positive for CD56 in 9 cases,CD3ε in 13 cases,T cell intracellular antigen (TIA)-1 in 15 cases,granzyme B in 10 cases,CD3 in 2 cases,βF1 in 1 case,but negative for CD4,CD5,CD8,CD20,and CD79α.All the 15 cases were positive for 1 or 2 T-cell associated antigens (CD2,CD7 or CD45RO).CD30 was observed in large tumor cells in 3 of the 15 cases.Monoclonal TCR-γ gene rearrangement was found in 3 of 14 cases.In situ hybridization for EBER1/2 was positive in all of the 15 cases.Survivin and Ki67 were expressed in 73.3％ (11/15) and 100％ (14/14,note:a tissue section was unavailable because of the detachment of tissue from the slide) of the specimens respectively,with the average percentage of positive cells being 23.97％ ± 18.35％ and 41.20％ ± 19.52％ for survivin and Ki67,respectively.Statistical differences were observed in the percentage of Ki67-expressing cells between the specimens with 0-2 mitotic figures per high power field from 9 cases and those with more than 2 mitotic figures from 6 cases (25.27％ ± 12.96％ vs.58.23％ ± 16.02％,F =19.14,P =0.001).No correlation was found between the expression of survivin and Ki67 in cutaneous extranodal NK/T-cell lymphoma,nasal type.Conclusion The high expressions of survivin and Ki67 may play a role in the occurrence and development of cutaneous extranodal NK/T-cell lymphoma,nasal type.

Background Arresting the overexpression of vascular endothelial growth factor (VEGF) will be a new approach to the inhibition of neovascularization.RNA interference (RNAi) can inhibit the expression of specific gene,and its application in eye has little interference to other gene expression.Objective This study was to investigate the effect of small interference RNA (siRNA) targeting VEGF on the expression of VEGF and retinal neovascularization in oxygen-induced retinopathy (OIR) model.Methods psi-HITM/enhanced green fluorescent protein (EGFP)/VEGF siRNA was designed and prepared in vitro.Mouse endothelioma (EOMA) were cultured in DMEM without antibiotic and divided into 5 groups.The cells were incubated in DMEM only in the blank control group;while 1 μl of LipofectamineTM 2000 + psi-HITM/EGFP,1 μl LipofectamineTM 2000 + 40,50 or 60 nmol/L of psi-HITM/EGFP/VEGF siRNA was added into DMEM in the negative control group and siRNA groups,respectively.The expression of VEGF mRNA and protein was detected by real time PCR (RT-PCR) and Western blot.The optimal effective concentration of VEGF siRNA was assessed.OIR models were established in 48 7-day-old C57BL/6J mice by raising them at an oxygen concentration of (75±2) ％ for 5 days and then to normal air.The mice were randomized into the model group,null vector group and VEGF siRNA group.1 μl of a mixture of psi-HITM/EGFP or VEGF siRNA (60 nmol/L) and LipofectamineTM 2000 was intravitreally injected,respectively,in the null vector group and VEGF siRNA group.The normal mice were used as the normal control group.Expression of VEGF mRNA and protein in the mouse retinas was detected by RT-PCR and Western blot,respectively,and FITC-dextran stretched retinal preparation was examined to evaluate the neovascularization,and retinal sections were examined to quantify the number of vascular endothelial cell nuclei extending beyond the internal limiting membrane (ILM).Results The in vitro transfection test showed that the expression of VEGF mRNA and protein in the EOMA cells was significantly different among the blank control group,negative control group and 40,50,60 nmol/L VEGF siRNA groups (F =148.890,P ＜ 0.001; F =306.960,P ＜ 0.001),and the expression of VEGF mRNA was lower in different concentrations of VEGF siRNA groups than that in the blank control group (t=73.950,119.890,156.480,all at P＜0.001).Also,the expression of VEGF protein was less in different concentrations of VEGF siRNA groups than that in the blank control group (t =15.452,23.344,42.119,all at P＜0.001).The optimal inhibitory concentration of VEGF siRNA was 60 nmol/L.In vivo study determined that compared to the model group and null vector group,the non-perfusion zones and neovascular net in the retina were decreased,and the number of vascular endothelial cell nuclei extending beyond the ILM was less in the VEGF siRNA group.The relative expression level of VEGF mRNA in the retinas was 1.23±0.18,4.02±0.16,3.98±0.19 and 1.98±0.12 in the normal control group,model group,null vector group and VEGF siRNA group,respectively,with a significant difference among them (F=369.780,P＜0.001),and the relative expression levels of VEGF mRNA in the model group and null vector group were higher than that in the normal control group (t=37.880,37.336,both P＜0.001),and the expression of VEGF mRNA in the VEGF siRNA group declined by 50.8％ (t=10.183,P＜0.001).The difference in the expression levels of VEGF protein also was assayed among the various groups (F=408.980,P＜0.001),and VEGF level in the retina was lowered by 68.0％ in the VEGF siRNA group compared to the model group (t =11.473,P＜0.001).However,VEGF level in the VEGF siRNA group remained at a high level in comparison with the normal control group (t =2.422,P＜0.001).Conclusions Intravitreal injection of VEGF siRNA can attenuate retinal neovascularization by effectively downregulate the expression VEGF mRNA and protein in the retina.

This study was purposed to investigate the effect of AML1-ETO fusion protein resulted from hematopoietic transcription factor (AML1) and acute myeloid leukemia M(2b)(AML-M(2b)) on transcription activity of nucleobindin 2 (nucb2) promoter, and to explore the role of AML1-ETO in molecular pathogenesis of AML-M(2b). The real-time RT-PCR was used to study the regulation of AML1-ETO on nucb2 at transcription level in AML1-ETO inducible leukemia cell line, the chromatin immunoprecipitation (ChIP)-based qPCR was used to investigate the direct in vivo interaction between the AML1, AML1-ETO and nucb2 promoter in AML1-ETO positive leukemia cell line, the luciferase report gene assay was used to detect the regulation of AML1, AML1-ETO on the transcription activity of nucb2 promoter. The results showed that the expression level of nucb2 was reduced with the increase of AML1-ETO. The promoter of nucb2 could be bound by both AML1 and AML1-ETO. The promoter of nucb2 was trans-repressed by AML1 and AML1-ETO respectively. It is concluded that the nucb2 is the direct target gene of AML1 and AML1-ETO, the transcription regulation of AML1, AML1-ETO on nucb2 is carried out via repressing its promoter activity.
Calcium-Binding Proteins ; genetics ; Cell Line, Tumor ; Core Binding Factor Alpha 2 Subunit ; genetics ; DNA-Binding Proteins ; genetics ; Gene Expression Regulation, Leukemic ; Humans ; Nerve Tissue Proteins ; Oncogene Proteins, Fusion ; genetics ; Promoter Regions, Genetic ; RUNX1 Translocation Partner 1 Protein ; Transcription Factors ; genetics ; Transcriptional Activation

INTRODUCTION: Surgical resection of the primary and metastatic tumour is increasingly recommended in suitable patients with metastatic colorectal cancer (CRC). While the role of metastasectomy is well studied and established in colorectal liver metastasis, evidence remains limited in pulmonary metastases. This systematic review was conducted to examine the current evidence on the role of lung metastasectomy (LUM) in CRC. METHODS: Three databases were systematically searched, to identify studies that compared survival outcomes of LUM, and factors that affected decision for LUM. RESULTS: From a total of 5,477 records, 6 studies were eventually identified. Two papers reported findings from one randomised controlled trial and 4 were retrospective reviews. There was no clear survival benefit in patients who underwent LUM compared to those who did not. When compared against patients who underwent liver metastasectomy, there was also no clear survival benefit. Patients who underwent LUM were also more likely to have a single pulmonary tumour, and metachronous disease. CONCLUSION The evidence suggests a role for LUM, but is limited by inherent selection bias in retrospective reviews, and the single randomised clinical trial performed was not completed. More prospective studies are required to understand the true effect of LUM on outcomes in metastatic CRC.
Colorectal Neoplasms/surgery* ; Humans ; Liver Neoplasms/surgery* ; Lung Neoplasms/surgery* ; Metastasectomy ; Pneumonectomy ; Prognosis ; Randomized Controlled Trials as Topic ; Retrospective Studies ; Survival Rate

BACKGROUNDThe mechanism of retinal neovascularization is not understood completely. Many growth factors are involved in the process of retinal neovascularization, such as vascular endothelial growth factor (VEGF) and pigment epithelium-deprived factor (PEDF), which are the representatives of angiogenic and antiangiogenic molecules respectively. Oxygen induced retinopathy (OIR) is a useful model to investigate retinal neovascularization. The present study was conducted to investigate the feasibility of small interference RNA (siRNA) targeting VEGF gene in attenuating oxygen induced retinopathy (OIR) by regulating VEGF to PEDF ratio (VEGF/PEDF).

METHODSIn vitro, cultured EOMA cells were transfected with VEGF-siRNA (psi-HI(TM)/EGFP/VEGF siRNA) and Lipofectamine(TM) 2000 for 24, 48, and 72 hours, respectively. Expression of VEGF mRNA was evaluated by real time polymerase chain reaction (PCR) and the level of VEGF protein was analyzed by Western blotting. In vivo, OIR model mice were established, the mice (C57BL/6J) received an intra-vitreal injection of 1 µl of mixture of psi-HI(TM)/EGFP/VEGF siRNA and Lipofectamine 2000. Expressions of retinal VEGF and PEDF protein were measured by Western blotting, retinal neovascularization was observed by fluorescein angiography, and quantified.

RESULTSIn vitro psi-HI(TM)/EGFP/VEGF siRNA treatment significantly reduced VEGF mRNA and protein expression. In vivo, with decreased VEGF and VEGF-PEDF ratio, significant attenuation of neovascular tufts, avascular regions, tortuous, and dilated blood vessels were observed in the interfered animals.

CONCLUSIONSVEGF plays an important role in OIR, and the transfection of VEGF-siRNA can effectively downregulate VEGF expression in vivo, accompanied by the downregulation of VEGF-PEDF ratio, and simultaneous attenuation of retinal neovascularization was also observed. These findings suggest that VEGF/PEDF may serve as a potential target in the treatment of retinal neovascularization and RNA interference targeting VEGF expression, which represents a possible therapeutic strategy.

Animals ; Eye Proteins ; analysis ; Mice ; Mice, Inbred C57BL ; Nerve Growth Factors ; analysis ; RNA, Small Interfering ; genetics ; Retinal Neovascularization ; therapy ; Serpins ; analysis ; Vascular Endothelial Growth Factor A ; analysis ; genetics ; physiology

BACKGROUNDExtranodal natural killer/T-cell (NK/T cell) lymphoma, nasal-type, is a rare lymphoma. Skin is the second most common site of involvement after the nasal cavity/nasalpharynx. The aim of this study was to investigate the clinicopathologic features, immunophenotype, T cell receptor (TCR) gene rearrangement, the association with Epstein-Barr virus (EBV) infection and p53 gene mutations of the lymphoma.

METHODSThe clinicopathologic analysis, immunohistochemistry, in situ hybridization for EBER1/2, TCR gene rearrangement by polymerase chain reaction (PCR), mutations of p53 gene analyzed by PCR and sequence analysis were employed in this study.

RESULTSIn the 19 cases, the tumor primarily involved the dermis and subcutaneous layer. Immunohistochemical staining showed that most of the cases expressed CD45RO, CD56, CD3ε, TIA-1 and GrB. Three cases were positive for CD3 and two cases were positive for CD30. Monoclonal TCRγ gene rearrangement was found in 7 of 18 cases. The positive rate of EBER1/2 was 100%. No p53 gene mutation was detected on the exon 4 - 9 in the 18 cases. Fifteen cases showed Pro (proline)/Arg (arginine) single nucleotide polymorphisms (SNPs) on the exon 4 at codon 72. The expression of p53 protein was 72% (13/18) immunohistochemically.

CONCLUSIONSCutaneous NK/T-cell lymphoma is a rare but highly aggressive lymphoma with poor prognosis. No p53 gene mutation was detected on the exon 4 - 9, and Pro/Arg SNPs on p53 codon 72 were detected in the cutaneous NK/T-cell lymphoma. The overexpression of p53 protein may not be the result of p53 gene mutation.

Adolescent ; Adult ; Aged ; Child ; Epstein-Barr Virus Infections ; diagnosis ; genetics ; metabolism ; Female ; Humans ; Immunohistochemistry ; Immunophenotyping ; In Situ Hybridization ; Lymphoma, T-Cell ; diagnosis ; genetics ; metabolism ; Male ; Middle Aged ; Mutation ; Receptors, Antigen, T-Cell ; genetics ; metabolism ; Skin Neoplasms ; diagnosis ; genetics ; metabolism ; Tumor Suppressor Protein p53 ; genetics ; Young Adult

OBJECTIVETo explore the diagnostic implication of immunophenotyping and gene rearrangement in subcutaneous panniculitis-like T-cell lymphoma (SPTL).

METHODSAccording to the selection criteria of 2005 WHO-EORTC classification for cutaneous lymphomas, 20 SPTL patients were enrolled in this study. A 10-antibody panel was used for immunophenotyping and in addition, polymerase chain reaction for TCR gamma and IgH gene rearrangement and in situ hybridization for EBER1/2 were also employed.

RESULTSThere were 9 males and 11 female with a mean age of 29.5 years. Immunophenotypic study showed that all the patients expressed one to three T-cell associated antigens (CD2, CD3 or CD45RO), 18 patients were positive for beta F1, 18 for CD8, 20 for TIA-1 and 16 for granzyme B. None of the patients expressed CD4, CD20 and CD56. TCR gamma gene rearrangement was found in 16 of 20 cases (80.0%) and none for IgH gene rearrangement. The positive rate of EBER1/2 was 25.0% (5/20).

CONCLUSIONSSince the majority of SPTL patients show clonal TCR gene rearrangements, correlations among clinical presentation, histological features, immunophenotype and gene rearrangement data are considered important in confirming a diagnosis of SPTL.

Adolescent ; Adult ; Antigens, CD20 ; immunology ; CD56 Antigen ; analysis ; immunology ; Child ; Female ; Gene Rearrangement ; genetics ; Humans ; Immunophenotyping ; methods ; In Situ Hybridization ; Lymphoma, T-Cell ; classification ; diagnosis ; genetics ; immunology ; Lymphoma, T-Cell, Cutaneous ; classification ; diagnosis ; genetics ; immunology ; Male ; Middle Aged ; Panniculitis ; RNA, Viral ; immunology ; isolation & purification ; Skin Neoplasms ; immunology ; Subcutaneous Tissue ; Young Adult

Objective:To investigate the predictive value of MRI radiomics model in assessing the early response to concurrent chemoradiotherapy for locally advanced cervical squamous cell carcinoma.Methods:A total of 367 patients with pathologically proven locally advanced cervical squamous cell carcinoma (International Federation of Gynecology and Obstetrics stage ⅡB-ⅣA) in Liaoning Cancer Hospital & Institute from January 2013 to June 2019 were retrospectively collected. The patients were unable to undergo surgery and received complete concurrent chemoradiotherapy. Pelvic plain MRI, DWI and dynamic contrast-enhanced MRI were performed within 2 weeks before treatment and at the end of the 4th week of treatment. Patients were divided into complete response (CR) group ( n=247) and non-CR group ( n=120) according to response evaluation criteria in solid tumors 1.1. The patients were divided into a training set ( n=256) and a validation set (n=111) via a randomized split method at a ratio of 7∶3. Two radiologists drew the region of interest on the DWI, T 2WI and contrast-enhanced T 1WI (delayed phase) images before treatment to form the volume of interest finally. Totally 1 906 radiomics features were extracted from 3 single sequence images, respectively. Feature correlation analysis and tree model were used for feature selection. Three classifier learning algorithms, namely logistic regression (LR), support vector machine and random forest, were used for machine learning and the best classifier was selected. Based on the best classifier, 3 single sequence radiomics models were built, and a multi-sequence combined model was obtained by multivariate LR analysis. The differences in the area under the receiver operating characteristic curve (AUC) of the 3 single sequence models and the multi-sequence combined model were compared by DeLong test. The clinical application value of the multi-sequence combined model was evaluated by decision analysis curve. Results:In the training set and validation set, the LR classifier model had the best performance. Based on the LR classifier, AUCs of DWI, T 2WI, contrast-enhanced T 1WI and combined sequences in the training set were 0.77, 0.74, 0.79 and 0.86, respectively, and AUCs in the validation set were 0.71, 0.66, 0.75 and 0.77, respectively. In the training set, the AUC of multi-sequence combined model was higher than those of DWI, T 2WI and contrast-enhanced T 1WI sequence models, and the differences were statistically significant ( Z=3.01, 3.56, 2.83; P=0.003, 0.001, 0.005). In the validation set, the AUC of multi-sequence combined model and T 2WI model had significant difference ( Z=2.46, P=0.015). The decision analysis curve showed that when the threshold probability was in the range of 0.44 to 0.88, the multi-sequence combined model yielded a net benefit. Conclusion:Based on the LR classifier, the combined model built by radiomics features of multi-sequence MRI images has predictive value for assessing the early response of concurrent chemoradiotherapy for locally advanced cervical squamous cell carcinoma.

A healthy full-term female neonate, aged 3 days and born by vaginal delivery (with a 1-minute Apgar score of 10 and a 5-minute Apgar score of 10), had unexpected cardiac and respiratory arrests in the early morning on day 3 after birth and recovered to spontaneous breathing and heartbeat after a 10-minute resuscitation. The child had poor response and convulsion after resuscitation. Blood gas analysis showed metabolic acidosis, and amplitude-integrated EEG showed a burst-suppression pattern. She was diagnosed with sudden unexpected postnatal collapse but improved after hypothermia and symptomatic/supportive treatment. This article reports the first case of sudden unexpected postnatal collapse in China and summarizes related risk factors, pathophysiological mechanisms, and preventive and treatment measures of this disorder.
Apgar Score ; Child ; Child, Preschool ; China ; Female ; Humans ; Infant, Newborn ; Pregnancy ; Resuscitation ; Risk Factors

OBJECTIVETo study how to perform the hearing screening on the infants in the rural area.

METHODSThree thousand nine hundreds and twenty-two infants, about 84% of them from rural, were born in the People Hospital of LaiZhou City from January to December in 2004. The infants were performed fast hearing screening by transient evoked otoacoustic emission (TEOAE) after the birth in 2-7 days. The fail cases were checked again after 4-6 weeks, and then were diagnosed if they still failed after following-up.

RESULTSThe infants (3612/3922, 92.1%) have been checked by TEOAE, and the examination was free in the poverty cases. The rate passed on the first check was 69.96% (2527/3922), but 1085 infants failed (30.4%), while 310 infants have not been checked (7.9%). In the 1085 cases that should be rechecked, there was only 633 cases (58.34%) accepted the check on time, while 452 cases (41.66%) missed. In the 163 cases with high-risk infants in 2004, 114 infants (69.96%) were checked, but 49 infants (29.04%) were not checked. Fourteen cases failed in the recheck, and 11 of them were checked by ABR. Two cases were found to be moderate and severe hearing loss in binaural respectively and 4 cases with mild hearing loss in monaural while 3 cases were normal.

CONCLUSIONSIt is necessary and viable for the infants on hearing screening in the rural area It should be set up and perfected the model for infants on hearing screening in rural area as soon as possible; it should be free for the poor infants to make sure everyone enjoy the health care.

China ; Hearing Tests ; Humans ; Infant, Newborn ; Neonatal Screening ; methods ; Otoacoustic Emissions, Spontaneous ; Rural Population