RESUMO
BACKGROUND: Early diagnosis of hepatocellular carcinoma (HCC) can significantly improve patient survival. We aimed to develop a blood-based assay to aid in the diagnosis, detection and prognostic evaluation of HCC. METHODS: A three-phase multicentre study was conducted to screen, optimise and validate HCC-specific differentially methylated regions (DMRs) using next-generation sequencing and quantitative methylation-specific PCR (qMSP). RESULTS: Genome-wide methylation profiling was conducted to identify DMRs distinguishing HCC tumours from peritumoural tissues and healthy plasmas. The twenty most effective DMRs were verified and incorporated into a multilocus qMSP assay (HepaAiQ). The HepaAiQ model was trained to separate 293 HCC patients (Barcelona Clinic Liver Cancer (BCLC) stage 0/A, 224) from 266 controls including chronic hepatitis B (CHB) or liver cirrhosis (LC) (CHB/LC, 96), benign hepatic lesions (BHL, 23), and healthy controls (HC, 147). The model achieved an area under the curve (AUC) of 0.944 with a sensitivity of 86.0% in HCC and a specificity of 92.1% in controls. Blind validation of the HepaAiQ model in a cohort of 523 participants resulted in an AUC of 0.940 with a sensitivity of 84.4% in 205 HCC cases (BCLC stage 0/A, 167) and a specificity of 90.3% in 318 controls (CHB/LC, 100; BHL, 102; HC, 116). When evaluated in an independent test set, the HepaAiQ model exhibited a sensitivity of 70.8% in 65 HCC patients at BCLC stage 0/A and a specificity of 89.5% in 124 patients with CHB/LC. Moreover, HepaAiQ model was assessed in paired pre- and postoperative plasma samples from 103 HCC patients and correlated with 2-year patient outcomes. Patients with high postoperative HepaAiQ score showed a higher recurrence risk (Hazard ratio, 3.33, p < .001). CONCLUSIONS: HepaAiQ, a noninvasive qMSP assay, was developed to accurately measure HCC-specific DMRs and shows great potential for the diagnosis, detection and prognosis of HCC, benefiting at-risk populations.
Assuntos
Carcinoma Hepatocelular , Metilação de DNA , Detecção Precoce de Câncer , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/sangue , Carcinoma Hepatocelular/diagnóstico , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/sangue , Neoplasias Hepáticas/diagnóstico , Feminino , Masculino , Metilação de DNA/genética , Pessoa de Meia-Idade , Prognóstico , Detecção Precoce de Câncer/métodos , DNA Tumoral Circulante/sangue , DNA Tumoral Circulante/genética , Estudos de Coortes , Biomarcadores Tumorais/sangue , Biomarcadores Tumorais/genética , Idoso , AdultoRESUMO
OBJECTIVE: To investigate the clinical effect of NRD assisted Ilizarov technique in the treatment of infected bone and soft tissue defect of tibia. METHODS: All 48 patients with infected bone and soft tissue defect of tibia were randomly divided into study group and control group from March 2013 to December 2020. There were 34 males and 14 females, aged from 24 to 55 years old with an average of (40.54±11.64) years old. There were 25 patients in the study group, including 17 males and 8 females, aged from 31 to 55 years old with an average of (41.36±9.69) years old. The study group were treated with NRD assisted with Ilizarov bone transport technique. There were 23 patients in control group, including 17 males and 6 females, aged from 24 to 53 years old with an average of(38.61±8.76) years old. The control group were treated with traditional bone transport technique. The curative rate, recurrence rate, incidence rate of pin track infection, time of using antibiotics, time of wound healing, time of carrying external fixation, time of bone transport, time of bone healing and postoperative function were used to evaluate the therapeutic effect of the two groups. RESULTS: The follow-up period was from 12 to 62 months with an average of (33.0±7.2) months. At the final follow-up, there was no significant difference in the curative rate between the two groups (P>0.05). The recurrence rate in the study group was lower than that in the control group(P<0.05). The incidence of pin track infection in the study group was lower than that in the control group (P<0.05). The time of using antibiotics and wound healing in the study group was shorter than that in the control group(P<0.05). There was no significant difference in the time of bone transport and carrying of external fixation between the two groups(P>0.05). There was no significant difference in bone healing and postoperative function between the two groups(P>0.05). CONCLUSION: NRD assisted Ilizarov technique can achieve satisfactory results in the treatment of infected bone and soft tissue defect of tibia and shorten the treatment period and the time of using antibiotics. It is worthy of development in clinic.
Assuntos
Técnica de Ilizarov , Fraturas da Tíbia , Masculino , Feminino , Humanos , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Tíbia/cirurgia , Fraturas da Tíbia/cirurgia , Cicatrização , Antibacterianos , Resultado do Tratamento , Estudos Retrospectivos , Fixadores ExternosRESUMO
To investigate the effects of extended light/dark (L/D) cycle period (relative to the diurnal L/D cycle) on lettuce and explore potential advantages of abnormal L/D cycles, butter leaf lettuce were grown in a plant factory with artificial light (PFAL) and exposed to mixed red (R) and blue (B) LED light with different L/D cycles that were respectively 16 h light/8 h dark (L16/D8, as control), L24/D12, L48/D24, L96/D48 and L120/D60. The results showed that, all the abnormal L/D cycles increased shoot dry weight (DW) of lettuce (by 34-83%) compared with the control, and lettuce DW increased with the L/D cycle period prolonged. The contents of soluble sugar and crude fiber in lettuce showed an overall upward trend with the length of L/D cycle extended, and the highest vitamin C content as well as low nitrate content were both detected in lettuce treated with L120/D60. The light use efficiency (LUE) and electric use efficiency (EUE) of lettuce reached the maximum (respectively 5.37% and 1.76%) under L120/D60 treatment and so were DW, Assimilation rate (A), RC/CS, ABS/CS, TRo/CS and DIo/CS, indicating that longer L/D cycle period was beneficial for the assimilation efficiency and dry matter accumulation in lettuce leaves. The highest shoot fresh weight (FW) and nitrate content detected in lettuce subjected to L24/D12 may be related to the vigorous growth of root, specific L/D cycle seemed to strengthen root growth and water absorption of lettuce. The openness level of RC in PSII (Ψo), ETo/CS, and PIabs were all the highest in lettuce treated with L24/D12, implying that slightly extending the L/D cycle period might promote the energy flowing to the final electron transfer chain. In general, irradiation modes with extended L/D cycle period had the potential to improve energy use efficiency and biomass of lettuce in PFAL. No obvious stress or injury was detected in lettuce subjected to prolonged L/D cycles in terms of plant growth and production. From the perspective of shoot FW, the optimal treatment in this study was L24/D12, while L120/D60 was the recommended treatment as regards of the energy use efficiency and nutritional quality.
Assuntos
Lactuca , Fotossíntese , Manteiga , Luz , Nitratos/análise , Fotossíntese/efeitos da radiaçãoRESUMO
BACKGROUND: Lung cancer is the leading cause of cancer-related deaths worldwide, with non-small cell lung cancer (NSCLC) accounting for 85% of all lung cancer cases. Inflammation has been proven to be one of the characteristics of malignant tumors. Chronic inflammatory response mediated by cytokines in the tumor microenvironment is an important factor in tumorigenesis. The purpose of this study was to observe and evaluate the value of red blood cell distribution width (RDW), neutrophil-to-lymphocyte ratio (NLR), and hemoglobin-to-red blood cell distribution width ratio (HRR) in the progression of NSCLC. METHODS: A total of 245 patients with NSCLC, 97 patients with benign pulmonary nodules, and 94 healthy volunteers were included in this study. Factors, such as age, gender, smoking history, histological type, lymph node metastasis, distant metastasis, TNM stage, and differentiation degree were statistically analyzed. The correlation of RDW, NLR, and HRR of patients with NSCLC with other clinical experimental parameters were also analyzed. Then, the diagnostic value of RDW, NLR, and HRR in the progression of NSCLC was evaluated. RESULTS: RDW, NLR, and HRR could be used to distinguish patients with NSCLC from healthy controls (p < 0.05). In addition, only the RDW in the NSCLC group with III-IV stage was significantly different from that in the benign pulmonary nodules group (p = 0.033), while NLR and HRR could significantly distinguish patients with NSCLC and benign pulmonary nodules (p < 0.001). RDW and NLR were positively correlated with NSCLC stage, whereas HRR was negatively correlated with NSCLC stage. RDW, NLR, and HRR were also significantly associated with the differentiation degree of NSCLC (p < 0.05). The ROC curve analysis showed that the combination of RDW with NLR, HRR, and CEA could show significantly higher diagnostic value than any one marker alone (AUC = 0.925, 95% CI: 0.897-0.954, and sensitivity and specificity of 79.60% and 93.60%, respectively). CONCLUSION: RDW, NLR, and HRR can be utilized as simple and effective biomarkers for the diagnosis and evaluation of NSCLC progression.
Assuntos
Carcinoma Pulmonar de Células não Pequenas/imunologia , Progressão da Doença , Eritrócitos/citologia , Hemoglobinas/metabolismo , Neoplasias Pulmonares/imunologia , Linfócitos/citologia , Neutrófilos/citologia , Idoso , Carcinoma Pulmonar de Células não Pequenas/sangue , Carcinoma Pulmonar de Células não Pequenas/diagnóstico , Carcinoma Pulmonar de Células não Pequenas/patologia , Estudos de Casos e Controles , Contagem de Células , Feminino , Humanos , Neoplasias Pulmonares/sangue , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Estudos RetrospectivosRESUMO
The classification of the distinct group of mesenchymal neoplasms, first described as 'Xp11 translocation perivascular epithelioid cell tumor (PEComa)' and for which the term 'melanotic Xp11 neoplasm' or 'Xp11 neoplasm with melanocytic differentiation' has recently been proposed, remains challenging and controversial. We collected 27 melanotic Xp11 neoplasms, the largest series to date, for a comprehensive evaluation. Fourteen of the cases, together with eight alveolar soft part sarcomas (ASPS), nine conventional PEComas and a control group of seven normal tissues were submitted to RNA sequencing. Follow-up available in 22 patients showed 5-year overall survival and 5-year disease-free survival of 47.6 and 35.7%, respectively, which were similar to ASPS and significantly worse than conventional PEComa. Univariate analysis of location (occurring in the kidney versus not kidney), infiltrative growth pattern, nuclear pleomorphism, mitotic activity ≥2/50 high-power fields (HPF), necrosis and lymphovascular invasion were found to be associated with overall survival and/or disease-free survival. Multivariate analysis identified that location was the only factor found to independently correlate with disease-free survival. More importantly, RNA sequencing-based clustering analysis segregated melanotic Xp11 neoplasm and ASPS from other tumors, including conventional PEComa and Xp11 translocation renal cell carcinoma, and formed a compact cluster representative of the largely similar expression signature. Here we clearly define the true biologic nature of melanotic Xp11 neoplasms which are distinctive malignant mesenchymal tumors, rather than simply PEComa variants with occasionally unpredictable behavior. Meanwhile, melanotic Xp11 neoplasm and ASPS more likely represent phenotypic variants of the same entity, which is distinct from conventional PEComa and Xp11 translocation renal cell carcinoma. Based on these important findings, melanotic Xp11 neoplasm might be reclassified into a distinctive entity together with ASPS, independent from PEComa, in future revisions of the current WHO categories of tumors of soft tissue and bone for the improved reclassification. © 2020 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Assuntos
Carcinoma de Células Renais/classificação , Neoplasias Renais/classificação , Neoplasias de Células Epitelioides Perivasculares/classificação , Sarcoma Alveolar de Partes Moles/classificação , Translocação Genética , Adolescente , Adulto , Carcinoma de Células Renais/genética , Carcinoma de Células Renais/patologia , Criança , Pré-Escolar , Análise por Conglomerados , Estudos de Coortes , Feminino , Perfilação da Expressão Gênica , Humanos , Neoplasias Renais/genética , Neoplasias Renais/patologia , Masculino , Pessoa de Meia-Idade , Neoplasias de Células Epitelioides Perivasculares/genética , Neoplasias de Células Epitelioides Perivasculares/patologia , Sarcoma Alveolar de Partes Moles/genética , Sarcoma Alveolar de Partes Moles/patologia , Análise de Sequência de RNA , Análise de Sobrevida , Adulto JovemRESUMO
The present study evaluated the growth response and sugar accumulation of lettuce exposed to different lighting modes of red and blue LED light based on the same daily light integral (7.49 µmol·m-2). Six lighting treatments were performed, that were monochromatic red light (R), monochromatic blue light (B), simultaneous red and blue light as the control (RB, R:B = 1:1), mixed modes of R, B and RB (R/RB/B, 4 h R to 4 h RB and then 4 h B), and alternating red and blue light with alternating intervals of 4 h and 1 h respectively recorded as R/B(4 h) and R/B(1 h). The Results showed that different irradiation modes led to obvious morphological changes in lettuce. Among all the treatments, the highest fresh and dry weight of lettuce shoot were both detected with R/B(1 h), significantly higher than the other treatments. Compared with plants treated with RB, the contents of fructose, glucose, crude fiber as well as the total sweetness index (TSI) of lettuce were significantly enhanced by R treatment; meanwhile, monochromatic R significantly promoted the activities of sucrose degrading enzymes such as acid invertase (AI) and neutral invertase (NI), while obviously reduced the activity of sucrose synthesizing enzyme (SPS). Additionally. The highest contents of sucrose and starch accompanied with the strongest activity of SPS were detected in plants treated with R/B(1 h). The alternating treatments R/B(4 h) and R/B(1 h) inhibited the activity of SS, while enhanced that of SPS compared with the other treatments, indicating that different light environment might influence sugar compositions via regulating the activities of sucrose metabolism enzymes. On the whole, R/B(1 h) was the optimal lighting strategy in terms of lettuce yield, taste and energy use efficiency in the present study.
Assuntos
Lactuca/fisiologia , Lactuca/efeitos da radiação , Luz , Açúcares/metabolismo , Biomassa , Metabolismo dos Carboidratos/efeitos da radiação , Fibras na Dieta , Regulação Enzimológica da Expressão Gênica , Redes e Vias Metabólicas , Fenótipo , Pigmentos Biológicos , Amido/metabolismoRESUMO
In order to explore the mechanism of response of growth and development of tomato seedlings to the combination of red and blue light, the light-emitting-diodes (LEDs) as precision modulation light sources were used in this study with 7 treatments including red (R) light, blue (B) light and combination of R+B light (9R1B, 6R1B, 3R1B, 1R1B, 1R3B), white (W) light as control, and the effects of different proportions of R and B light on the growth, photosynthetic pigment content, photosynthetic characteristics, chlorophyll fluorescence and root activity of tomato seedlings with variety of 'SV0313TG' as experiment material were studied. The results showed that there were significant differences in growth of tomato seedlings under treatments of different proportions of R and B light. The plant height, specific leaf area and intercellular CO2 concentration of tomato seedlings were significantly promoted by R light, while Fv/Fm and χPS2 were decreased, the root growth was inhibited as the root activity declined, so that the seedling index was reduced. The seedling growth was significantly suppressed under B light and the chlorophyll content was decreased, while the chlorophyll a/b was enhanced. Furthermore, combination of R+B light was be-neficial to the growth and development of tomato seedlings, and the plant dry mass, chlorophyll content and photosynthetic performance were significantly increased under 3R1B. In addition, seedlings grew strongly and had the highest value of seedling index under this treatment. In conclusion, the combination of R+B light could promote photosynthetic pigment content and photosynthetic efficiency in leaves of tomato seedlings, as well as plant growth, especially for treatment of 3R1B.
Assuntos
Clorofila , Fotossíntese , Solanum lycopersicum , Clorofila A , Luz , Folhas de Planta , PlântulaRESUMO
Purple lettuce was grown hydroponically under six different nitrogen nutrition conditions, with NO(3-)-N:NH(4+)-N at 1:0, 4:1 and 1:1 combined with nitrogen application levels of 10 and 15 mmol · L(-1), for 25 days in solar greenhouse, then treated with short-term continuous lighting (SCL) before harvest to study the changes in contents of nutrients and analyze the effects of nitrogen nutrition conditions on the changes. Results showed that the shoot dry mass of all six nitrogen nutrition conditions were significantly improved under SCL treatment, by 35.1% at least, and the root dry mass increased greatly except for NO(3-)-N:NH(4+)-N 1:1 combined with nitrogen application level 15 mmol · L(-1) treatment and NO(3-)-N:NH(4+)-N 1:0 combined with nitrogen application level 10 mmol · L(-1) treatment. The relative contents of total phenols and flavonoid of different nitrogen nutrition conditions turned significantly different after treatment with SCL. The relative contents of total phenols and flavonoid were enhanced with the improvement of ammonium nitrogen ratio, while the relative content of anthocyanin increased and then decreased with the improvement of ammonium nitrogen ratio. The lighting treatment reduced the nitrate content of leaf blade of all six nitrogen nutrition conditions remarkably by 23.2% at least. The contents of ascorbic acid, soluble sugar and soluble protein rose significantly under SCL treatments. The study showed that the reduction of nitrate content speeded up with the enhancement of nitrogen application level and ammonium nitrogen ratio, and the advancement of ascorbic acid content slowed down with the increasing nitrogen application level. The soluble sugar improvement speed increased with the increasing ammonium nitrogen ratio, and SCL lifted the dry mass of the lettuce greatly. The results showed that SCL with LED lamps improved significantly the dry matter of lettuce under different nitrogen nutrition conditions, reduced the nitrate content and increased the ascorbic acid, soluble sugar and soluble protein contents greatly. In addition, nitrogen nutrition conditions affected the effectiveness of short-term continuous lighting on quality improvement rate of hydroponic lettuce remarkably.
Assuntos
Hidroponia , Lactuca/efeitos da radiação , Luz , Iluminação , Nitrogênio/química , Compostos de Amônio/química , Ácido Ascórbico/química , Carboidratos/química , Lactuca/crescimento & desenvolvimento , Nitratos/química , Folhas de Planta/química , Folhas de Planta/crescimento & desenvolvimento , Raízes de Plantas/crescimento & desenvolvimentoRESUMO
Phytochemicals in vegetables are important for human health, and their biosynthesis, metabolism and accumulation are affected by environmental factors. Light condition (light quality, light intensity and photoperiod) is one of the most important environmental variables in regulating vegetable growth, development and phytochemical accumulation, particularly for vegetables produced in controlled environments. With the development of light-emitting diode (LED) technology, the regulation of light environments has become increasingly feasible for the provision of ideal light quality, intensity and photoperiod for protected facilities. In this review, the effects of light quality regulation on phytochemical accumulation in vegetables produced in controlled environments are identified, highlighting the research progress and advantages of LED technology as a light environment regulation tool for modifying phytochemical accumulation in vegetables.
Assuntos
Ambiente Controlado , Qualidade dos Alimentos , Luz , Iluminação , Compostos Fitoquímicos/biossíntese , Verduras/efeitos da radiação , Luz/efeitos adversos , Iluminação/tendências , Fotoperíodo , Fotossíntese/efeitos da radiação , Verduras/química , Verduras/crescimento & desenvolvimento , Verduras/metabolismoRESUMO
The aim of the present study was to explore a disintegrin and metalloproteinase 17 (ADAM17) mRNA and protein expression in esophageal squamous cell carcinoma and its association with clinicopathological factors and prognosis. Through semiquantitative reverse transcription polymerase chain reaction, the ADAM17 mRNA expression in 50 cases of esophageal squamous cell carcinoma and corresponding normal esophageal mucosa were detected. Using streptavidin peroxidase conjugated immunohistochemistry, ADAM17 protein levels were detected in 80 cases of esophageal squamous cell carcinoma and corresponding normal esophageal mucosa. A log rank test and the Cox proportional hazards model were used for the esophageal cancer survival analysis. ADAM17 mRNA expression levels in esophageal squamous cell carcinoma and corresponding normal esophageal mucosa were 0.937±0.241 and 0.225±0.077, respectively (P<0.01). ADAM17 mRNA expression in esophageal squamous cell carcinoma was correlated with lymph node metastasis (P<0.01) and tumor, node and metastasis (TNM) staging (P<0.05), however, it was not correlated with gender, age or histological grade (P>0.05). ADAM17 protein expression rates in esophageal squamous cell carcinoma and corresponding normal esophageal mucosa were 66.25 and 6.25% respectively, a difference that was statistically significant (P<0.01). In addition, ADAM17 protein expression in esophageal squamous cells was correlated with lymph node metastasis and TNM stage (P<0.05), while it was not correlated with gender, age or histological grade (P>0.05). ADAM17 protein expression and epidermal growth factor receptor (EGFR) protein expression were positively correlated (P<0.01). Lymph node metastasis, TNM stage, ADAM17 and EGFR protein expression may be used as independent prognostic indicators of esophageal squamous cell carcinoma (all P<0.05). ADAM17 mRNA and protein were highly expressed in esophageal squamous cell carcinoma; they have important roles in invasion and metastasis and a certain value in judging the prognosis of patients with esophageal squamous cell carcinoma.
Assuntos
Proteínas ADAM/metabolismo , Carcinoma de Células Escamosas/diagnóstico , Carcinoma de Células Escamosas/genética , Neoplasias Esofágicas/diagnóstico , Neoplasias Esofágicas/genética , Proteínas ADAM/genética , Proteína ADAM17 , Idoso , Carcinoma de Células Escamosas/terapia , Receptores ErbB/genética , Receptores ErbB/metabolismo , Neoplasias Esofágicas/terapia , Carcinoma de Células Escamosas do Esôfago , Feminino , Humanos , Imuno-Histoquímica , Metástase Linfática/genética , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Modelos de Riscos Proporcionais , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Análise de Sobrevida , Taxa de SobrevidaRESUMO
OBJECTIVE: To investigate the expression of A disintegrin and metalloproteinase 17 (ADAM17) mRNA and ADAM17 protein in esophageal squamous cell carcinoma (ESCC), and to evaluate their correlation with clinicopathological features and prognosis. METHODS: The expression of ADAM17 mRNA in 50 ESCC and 50 normal esophageal tissues was detected by RT-PCR. The expression of ADAM17 protein in 80 ESCC and 80 normal esophageal tissues was detected with immunohistochemioal staining (SP). Log rank test and Cox proportional hazards analysis were used to analyze the prognosis of ESCC. RESULTS: The expression of ADAM17 mRNA in 50 ESCC and 50 normal esophageal tissues was 0.937 ± 0.241 and 0.225 ± 0.077, respectively. The positive expression rates of ADAM17 protein in 80 ESCC and 80 normal esophageal tissues was 66.2% and 6.2%, respectively. The expressions of ADAM17 mRNA and ADAM17 protein in the ESCC were significantly higher than those in normal esophageal tissues (P < 0.01). The expressions of ADAM17 mRNA and protein were positively correlated with lymph node metastasis and TNM staging (P < 0.05). There were no correlations between the expressions of ADAM17 mRNA and protein and sex, age and histological grade (P > 0.05) . The expression of ADAM17 protein was positively correlated with EGFR protein (P < 0.01). The lymph node metastasis, TNM staging and the expression of ADAM17 and EGFR protein were independent prognostic factors. CONCLUSIONS: ADAM17 mRNA and protein are highly expressed in ESCC than in normal esophageal tissues and may play an important role in the development, invasion and metastasis of ESCC. They may be used as prognostic factors of ESCC.
Assuntos
Proteínas ADAM/metabolismo , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/patologia , Neoplasias Esofágicas/metabolismo , Neoplasias Esofágicas/patologia , Proteínas ADAM/genética , Proteína ADAM17 , Idoso , Biomarcadores Tumorais/metabolismo , Carcinoma de Células Escamosas/cirurgia , Receptores ErbB/metabolismo , Neoplasias Esofágicas/cirurgia , Carcinoma de Células Escamosas do Esôfago , Feminino , Seguimentos , Humanos , Estimativa de Kaplan-Meier , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Modelos de Riscos Proporcionais , RNA Mensageiro/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Taxa de SobrevidaRESUMO
The purpose of this paper was to explore the immunohistochemistry (IHC) results for a cocktail of minichromosome maintenance protein 2 (MCM2) and topoisomerase IIï¡ (TOP2A), p16INK4a and Ki-67 as biomarkers for the diagnosis of cervical intraepithelial neoplasia (CIN), improving the routine interpretation of cervical histopathology. 133 cases of CIN were collected from the archival data. All routine hematoxylin and eosin (HE)-stained slides of the subjects were re-examined independently by three senior pathologists, to provide a "consensus diagnosis". Immunohistochemistry for the three biomarkers was performed, and the results were reviewed independently of the corresponding archival diagnosis to make a "diagnosis assisted by IHC" by the original pathological practitioners. The diagnosis accordance rate of the archival original diagnosis with the "consensus diagnosis" and the "diagnosis assisted by IHC" with the "consensus diagnosis" were verified by Fisher's exact test. The results showed that raw agreement between the original HE diagnosis and the "consensus diagnosis" was 88.55%, and raw agreement between the "diagnosis assisted by IHC" and the "consensus diagnosis" was 95.78%. The latter was significantly higher than the former (Fisher's exact test, p = 0.023). In conclusion, the three biomarkers had a high degree of sensitivity and specificity, and appear to be a useful and reliable diagnostic adjunct to improve the routine diagnosis, and reduce inter-observer variability in cervical biopsy specimens.
Assuntos
Biomarcadores Tumorais/metabolismo , Displasia do Colo do Útero/diagnóstico , Neoplasias do Colo do Útero/diagnóstico , Adulto , Idoso , Idoso de 80 Anos ou mais , Antígenos de Neoplasias/metabolismo , Colo do Útero/metabolismo , Colo do Útero/patologia , Inibidor p16 de Quinase Dependente de Ciclina/metabolismo , DNA Topoisomerases Tipo II/metabolismo , Proteínas de Ligação a DNA/metabolismo , Feminino , Humanos , Imuno-Histoquímica , Antígeno Ki-67/metabolismo , Pessoa de Meia-Idade , Componente 2 do Complexo de Manutenção de Minicromossomo/metabolismo , Proteínas de Ligação a Poli-ADP-Ribose , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Neoplasias do Colo do Útero/metabolismo , Adulto Jovem , Displasia do Colo do Útero/metabolismoAssuntos
Antígenos de Neoplasias/metabolismo , Proteínas de Ciclo Celular/metabolismo , Inibidor p16 de Quinase Dependente de Ciclina/metabolismo , DNA Topoisomerases Tipo II/metabolismo , Proteínas de Ligação a DNA/metabolismo , Antígeno Ki-67/metabolismo , Proteínas Nucleares/metabolismo , Displasia do Colo do Útero/diagnóstico , Neoplasias do Colo do Útero/diagnóstico , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Monoclonais/metabolismo , Antígenos de Neoplasias/imunologia , Biomarcadores Tumorais/metabolismo , Carcinoma de Células Escamosas/diagnóstico , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/patologia , Proteínas de Ciclo Celular/imunologia , DNA Topoisomerases Tipo II/imunologia , Proteínas de Ligação a DNA/imunologia , Feminino , Humanos , Imuno-Histoquímica , Pessoa de Meia-Idade , Componente 2 do Complexo de Manutenção de Minicromossomo , Proteínas Nucleares/imunologia , Neoplasias do Colo do Útero/metabolismo , Neoplasias do Colo do Útero/patologia , Adulto Jovem , Displasia do Colo do Útero/metabolismo , Displasia do Colo do Útero/patologiaRESUMO
OBJECTIVE: To determine novel predictors of ovarian interstitial fibrosis and microvascular injury associated with ovarian endometriotic cysts (OECs). DESIGN: Case-control study. SETTING: The gynecology unit of an affiliated hospital in China. POPULATION: Women <40 years of age with OECs or benign ovarian tumors (controls). METHODS: Transvaginal color Doppler sonography was performed preoperatively to detect ovarian interstitial flow. Postoperatively, expressions of transforming growth factor-ß1 (TGF-ß1) and thrombospondin-1 (TSP-1), as well as microvessel density in ovarian interstitial, were analyzed using immunohistochemistry. MAIN OUTCOME AND MEASURES: Ovarian interstitial flow and expressions of TGF-ß1, TSP-1, and microvessel density. RESULTS: Compared with controls, ovarian interstitial flow in the study group was decreased and arterial spectra indicated significantly higher resistance indices. Microvessel density was reduced, but TGF-ß1 and TSP-1 were elevated in the study group. There was a positive correlation between TGF-ß1 and TSP-1. There were negative correlations between TGF-ß1 and microvessel density, and between TSP-1 and microvessel density. Microvessel density and resistance indices were negatively correlated, whereas the correlations of TGF-ß1 and TSP-1 with resistance indices were positive. CONCLUSIONS: Resistance indices are consistent with pathological indices. Changes in resistance indices in ovaries with endometriosis are related to interstitial fibrosis and microvascular injury.
Assuntos
Endometriose/fisiopatologia , Microvasos/lesões , Cistos Ovarianos/fisiopatologia , Ovário/irrigação sanguínea , Ultrassonografia Doppler em Cores , Adulto , Estudos de Casos e Controles , Feminino , Fibrose/diagnóstico por imagem , Humanos , Imuno-Histoquímica , Microvasos/diagnóstico por imagem , Valor Preditivo dos Testes , Fluxo Sanguíneo Regional/fisiologia , Trombospondina 1/sangue , Fator de Crescimento Transformador beta1/sangue , Fator de Crescimento Transformador beta1/metabolismo , Vagina/diagnóstico por imagemRESUMO
PURPOSE: To evaluate the blood flow changes and their relationships to microvessel density (MVD) and thrombospondin-1 (TSP-1) by transvaginal colour Doppler sonography (TV-CDS) in the ovarian interstitium to predict ovarian interstitial microvascular injury in the pathological process of ovarian endometrial cysts (OEC). METHODS: TV-CDS was preoperatively performed to detect blood flow changes in 60 patients with 76 ovarian endometrioid cysts, and flow classification and resistance indices (RI) values were recorded for analysis. Ovarian interstitial specimens with blood flow signals were collected for postoperative pathologic examination. TSP-1 protein was evaluated by immunohistochemistry and Western blot, TSP-1 mRNA by reverse transcriptase polymerase chain reaction, microvessels by CD34 antibody, and MVD by image analysis. Thirty age-matched patients with benign ovarian tumours served as controls. RESULTS: Blood flow, most of star-shaped, within ovarian interstitial arteries in the OEC group was diminished; however, arterial spectra exhibited a high-resistance flow manifesting a significantly higher RI compared with that of the control group (P < 0.01). In ovarian interstitial specimens, there were significantly (P < 0.01) lower CD34-MVD and higher TSP-1 protein and mRNA in the OEC group than in the controls. CD34-MVD and TSP-1 showed remarkably negative correlation (rs = -0.76, P < 0.01). RI values correlated negatively with MVD values (rs = -0.91, P < 0.01), but positively with TSP-1 (rs = 0.81, P < 0.01), while flow classification correlated positively with MVD values (rs = 0.66, P < 0.01), but negatively with TSP-1 (rs = -0.54, P < 0.01). CONCLUSIONS: Changes in CD34-MVD and TSP-1 reflected ovarian interstitial microvascular injury of OEC, pathologically supported the findings of blood flow changes within ovarian interstitial arteries, and prospectively predicted OEC-induced ovarian interstitial vessel injury. This has important clinical value: early treatment, instead of allowing the cyst to become bigger, is of great importance for OEC patients, because a greater number of functional tissue blood vessels would be destroyed as the disease progresses.
Assuntos
Endometriose/complicações , Microvasos/lesões , Cistos Ovarianos/complicações , Ovário/irrigação sanguínea , Ovário/diagnóstico por imagem , Adulto , Anticorpos/metabolismo , Antígenos CD34/imunologia , Distribuição de Qui-Quadrado , Endometriose/cirurgia , Feminino , Humanos , Microcirculação , Microvasos/metabolismo , Microvasos/patologia , Cistos Ovarianos/cirurgia , Ovário/metabolismo , Valor Preditivo dos Testes , RNA Mensageiro/metabolismo , Fluxo Sanguíneo Regional , Estatísticas não Paramétricas , Trombospondina 1/genética , Trombospondina 1/metabolismo , Ultrassonografia Doppler em CoresAssuntos
Antígenos CD/imunologia , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Microvasos/imunologia , Receptores de Superfície Celular/imunologia , Neoplasias do Colo do Útero/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Endoglina , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Pessoa de Meia-Idade , Óxido Nítrico Sintase Tipo II/metabolismo , Neoplasias do Colo do Útero/genéticaAssuntos
Lipomatose Simétrica Múltipla/patologia , Pescoço/patologia , Adulto , Alcoolismo/complicações , Humanos , Lipomatose Simétrica Múltipla/diagnóstico por imagem , Lipomatose Simétrica Múltipla/etiologia , Lipomatose Simétrica Múltipla/cirurgia , Masculino , Pescoço/diagnóstico por imagem , Pescoço/cirurgia , Tomografia Computadorizada por Raios XRESUMO
OBJECTIVE: To investigate the effects of carvedilol on stabilizing atherosclerosis plaque. METHODS: Forty five male Japanese white rabbits were divided randomly into 5 groups with 9 for each. One group was fed up with normal diet as blank control. In other four groups, the common carotid artery of rabbits fed up with high cholesterol diet were injured by balloon. Three groups of them were transfected by wild-type p53 gene 8 weeks later, and then two groups of them were treated with carvedilol (3 mgxkg(-1)xd(-1)) and metoprolol (6 mgxkg(-1)xd(-1)) respectively, high cholesterol diet should be continued for other 4 weeks. Serum lipid, hypersensitive C-reaction protein (hsCRP), oxidized low density lipoprotein (oxLDL), superoxide dismutase (SOD), malondialdehyde (MDA) and glutathione peroxidase (GSH-PX) were measured in 0, 8, 12 weeks after experiment. The apoptosis rate of smooth muscle cell (SMC) in endomembrane and the local expression of p53, bcl-2, bax, alpha-actin were examined after experiment, and the carotid arteries were examined by light microscopy and transmission electron microscopy. RESULTS: The typical carotid atherosclerotic plaques were observed in balloon-injured groups. The local expression rates of p53 in groups transfected by wild type p53 gene were higher obviously than them in other two groups (P < 0.01). Compared with the rabbits received simple transfection, the thickness of the fibrous cap in rabbits received carvedilol and metoprolol were all increased, but the change could be observed significantly in carvedilol group (P < 0.05). Compared with metoprolol, carvedilol could reduce the level of serum hsCRP, oxLDL, MDA, and increase the concentration of SOD and GSH-PX significantly (P < 0.05 or 0.01), but two medicines had no obvious influence to serum lipid. The apoptosis rate of SMC in endomembrane, the local expression of bax gene and bax/bcl-2 ratio were decreased, the positive expression rates of alpha-actin and bcl-2 were enhanced in carvedilol group (P < 0.01). CONCLUSIONS: Both carvedilol and metoprolol can improve the stability of the plaque, but carvedilol is superior. Its mechanisms may lie in that carvedilol still has function of anti-inflammation, anti-oxidation, decreasing the apoptosis rate of SMC in addition to its function of blocking beta-receptor.
Assuntos
Apoptose/efeitos dos fármacos , Carbazóis/farmacologia , Doenças das Artérias Carótidas/patologia , Propanolaminas/farmacologia , Proteína Supressora de Tumor p53/metabolismo , Ração Animal , Animais , Doenças das Artérias Carótidas/genética , Carvedilol , Genes p53 , Humanos , Masculino , Metoprolol/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Coelhos , Transfecção , Proteína Supressora de Tumor p53/genéticaRESUMO
OBJECTIVE: To explore a simplified and reproducible approach for the diagnosis and morphologic prognostication of gastrointestinal stromal tumor (GIST). METHODS: Eighty-five cases of gastrointestinal mesenchymal tumors including 74 cases of GIST, 8 esophageal smooth muscle tumor, 1 rectal leiomyosarcoma, 1 Schwannoma, and 1 malignant fibrous histiocytoma were studied by histological evaluation along with an immunohistochemistry panel including vimentin, CD117 (c-kit), CD34, SMA, desmin and S-100. Clinicopathological correlation was performed in 31 cases of GIST that had accompanied with the available follow-up data. RESULTS: Among 74 GISTs, 34 arose principally from the stomach, 30 from the small intestine, and 10 other cases found in the esophagus, retroperitoneum, mesenterium and omentum. The patients' age ranged from 23 to 80 years (mean 52.5 years), with 45 males and 29 females. Histologically, the tumors composed of either spindle or oval to round cells arranged in interlacing fascicles forming whorls or cellular clusters, cytoplasm generally abundant and eosinophilic. There were 48 cases of spindle cell type, 10 cases of epithelioid cell type and 16 cases of mixed cell type. All 74 cases of GIST were positive for CD117 in a cell membranous pattern, however, some variable staining patterns of CD117 had been noticed in a few cases. In addition, 54 GISTs were also positive for CD34 (72.9%), 25 cases positive for SMA, 5 cases positive for S-100 and 5 cases positive for desmin. According to the Fletcher's scheme, GISTs in this study were divided into 4 subcategories including groups of very low risk of aggressive behavior (3 cases), of low risk (15 cases), of intermediate risk (36 cases) and of high risk (20 cases) respectively. Kaplan-Meier survival analysis of 31 GIST cases whom had been followed up for 16 to 72 months showed a statistically significant difference present among the subcategories (P < 0.01). CONCLUSIONS: GISTs predominantly occur in the middle and old age patients, more common in male, and positive CD117 staining is considered to be the defining marker to differentiate GIST from other mesenchymal tumors of the GI tract. Positive CD34 immun-staining, plus a CD117 positivity, strengthens further a diagnosis of GIST. Subclassification of GISTs using Fletcher's scheme appears to be simple, reproducible, and correlates well with the clinical behavior of the tumor.