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OBJECTIVE: The aim of the study was to create two consensus nomograms for predicting Overall Survival (OS) and Cancer-Specific Survival (CSS) in adults with papillary Renal Cell Carcinoma (pRCC). METHODS: Using the Surveillance, Epidemiology, and End Results databases, a retrospective analysis of 1,074 adults with pRCC from 2004 to 2015 was performed. These patients were then randomly divided into two independent cohorts with a ratio of 7:3 (training cohort: 752; validation cohort: 322). In a retrospective analysis of 752 patients from the training cohort, independent prognostic variables affecting OS and CSS were found. R software was used to create prognostic nomograms based on the findings of Cox regression analysis. The performance of the nomograms was assessed using the Concordance Index (C-index), the Area Under Curve (AUC), a calibration curve, and Decision Curve Analysis (DCA). Data from the 107 postoperative pRCC patients at the Affiliated Hospital of Xuzhou Medical University were used for external validation of the nomogram. RESULTS: For OS and CSS, the C-indices and AUCs of the training cohort and the validation cohort indicated that the model had excellent discrimination. The DCA demonstrated that the model was clinically applicable, and the calibration curves in the internal and external validations showed that the model's accuracy was high. CONCLUSION: The authors developed and validated a prognostic nomogram that accurately predicted the 3-, 5-, and 8-year OS and CSS of adults with pRCC. Clinicians can use this knowledge to direct the clinical management and counseling of patients with pRCC.
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Carcinoma de Células Renais , Neoplasias Renais , Nomogramas , Humanos , Masculino , Carcinoma de Células Renais/mortalidade , Carcinoma de Células Renais/patologia , Carcinoma de Células Renais/cirurgia , Estudos Retrospectivos , Feminino , Pessoa de Meia-Idade , Neoplasias Renais/mortalidade , Neoplasias Renais/patologia , Neoplasias Renais/cirurgia , Prognóstico , Adulto , Idoso , Reprodutibilidade dos Testes , Estadiamento de Neoplasias , Programa de SEERRESUMO
Abstract Objective The aim of the study was to create two consensus nomograms for predicting Overall Survival (OS) and Cancer-Specific Survival (CSS) in adults with papillary Renal Cell Carcinoma (pRCC). Methods Using the Surveillance, Epidemiology, and End Results databases, a retrospective analysis of 1,074 adults with pRCC from 2004 to 2015 was performed. These patients were then randomly divided into two independent cohorts with a ratio of 7:3 (training cohort: 752; validation cohort: 322). In a retrospective analysis of 752 patients from the training cohort, independent prognostic variables affecting OS and CSS were found. R software was used to create prognostic nomograms based on the findings of Cox regression analysis. The performance of the nomograms was assessed using the Concordance Index (C-index), the Area Under Curve (AUC), a calibration curve, and Decision Curve Analysis (DCA). Data from the 107 postoperative pRCC patients at the Affiliated Hospital of Xuzhou Medical University were used for external validation of the nomogram. Results For OS and CSS, the C-indices and AUCs of the training cohort and the validation cohort indicated that the model had excellent discrimination. The DCA demonstrated that the model was clinically applicable, and the calibration curves in the internal and external validations showed that the model's accuracy was high. Conclusion The authors developed and validated a prognostic nomogram that accurately predicted the 3-, 5-, and 8-year OS and CSS of adults with pRCC. Clinicians can use this knowledge to direct the clinical management and counseling of patients with pRCC.
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BACKGROUND: Gliomas is a major challenge of current medical system, and thousands of people are struggling in the pain of this disease worldwide. In the last decade, the functions of miRNAs have been revealed by many studies, and the intervention on miRNA dysfunctions has been thought as a promising way to counter cancer. MiR-493-5p has been identified as a tumor inhibitor to suppress the progressions of several tumors while its role in gliomas remains unknown. Hence, the study investigated the expression levels of miR-493-5p in glioma tissues and cell lines. METHODS: CCK-8 assay, transwell assay and flow cytometry assay were used to observe the effects of miR-493-5p on tumor cells. The downstream targets of miR-493-5p were also searched and verified with online databases and dual-luciferase reporter assay. Moreover, the activities of P53 and PI3K/AKT pathways were also explored by western blot to illustrate the regulation mechanism of miR-493-5p on glioma development. RESULTS: The results showed that miR-493-5p was significantly downregulated in pathological tissues and glioma cell lines, and the increased miR-493-5p effectively inhibited the malignant behavior and promoted the apoptosis of glioma cells. CONCLUSIONS: E2F3 was confirmed as a target of miR-493-5p, and the effects of miR-493-5p on the phenotype of glioma cells could be partly reversed by E2F3. Besides, it was also found that miR-493-5p could effectively suppress the expression of E2F3 and then improve the dysfunctions of the P53 and PI3K/AKT pathways.
Assuntos
Neoplasias Encefálicas/etiologia , Fator de Transcrição E2F3/fisiologia , Glioma/etiologia , MicroRNAs/fisiologia , Fosfatidilinositol 3-Quinases/fisiologia , Proteínas Proto-Oncogênicas c-akt/fisiologia , Proteína Supressora de Tumor p53/fisiologia , Linhagem Celular Tumoral , Humanos , Transdução de SinaisRESUMO
OBJECTIVES: This study aims to compare the clinical efficacy of an integrated approach to prevent and treat the recurrence of moderate-to-severe intrauterine adhesions (IUA) after hysteroscopic transcervical resection of adhesion (TCRA). METHODS: The study included a total of 70 patients with moderate-to-severe IUAs who underwent TCRA. Patients were randomly divided into two groups: treatment group (n=35) and control group n=35). In the treatment group, patients underwent balloon uterine stent placement and artificial cycle as well as received intrauterine perfusion of Danshen injection and oral Chinese medicine. In the control group, patients underwent balloon uterine stent placement and artificial cycle as well as received hyaluronic acid sodium and intrauterine device (IUD). Follow-up was performed after treatment of uterine cavity, menstruation and pregnancy. RESULTS: After 3 months of treatment, we observed a significantly lower rate of intrauterine re-adhesion (45.71% versus 77.14%, p=0.044) and significantly higher clinical efficiency (82.86% versus 77.14%, p=0.025) in the treatment group than those in the control group. After 6 months of treatment, we observed a significantly higher clinical efficiency in the treatment group than that in the control group (88.57% versus 68.57%, p=0.039). During the follow-up period, the pregnancy rate was 45.71% and 37.14% in the treatment group and control group, respectively, although the difference was not statistically significant (p=0.628). CONCLUSIONS: After surgical management of IUA, the integrated treatment combining a uterus stent placement and artificial cycle with Danshen injection and oral Chinese medicine can improve the condition of menstruation, and prevent and treat recurrence of IUA.
Assuntos
Dispositivos Intrauterinos , Doenças Uterinas , Feminino , Humanos , Ácido Hialurônico/uso terapêutico , Histeroscopia , Gravidez , Aderências Teciduais/prevenção & controle , Doenças Uterinas/prevenção & controle , Doenças Uterinas/cirurgiaRESUMO
OBJECTIVES: This study aims to compare the clinical efficacy of an integrated approach to prevent and treat the recurrence of moderate-to-severe intrauterine adhesions (IUA) after hysteroscopic transcervical resection of adhesion (TCRA). METHODS: The study included a total of 70 patients with moderate-to-severe IUAs who underwent TCRA. Patients were randomly divided into two groups: treatment group (n=35) and control group n=35). In the treatment group, patients underwent balloon uterine stent placement and artificial cycle as well as received intrauterine perfusion of Danshen injection and oral Chinese medicine. In the control group, patients underwent balloon uterine stent placement and artificial cycle as well as received hyaluronic acid sodium and intrauterine device (IUD). Follow-up was performed after treatment of uterine cavity, menstruation and pregnancy. RESULTS: After 3 months of treatment, we observed a significantly lower rate of intrauterine re-adhesion (45.71% versus 77.14%, p=0.044) and significantly higher clinical efficiency (82.86% versus 77.14%, p=0.025) in the treatment group than those in the control group. After 6 months of treatment, we observed a significantly higher clinical efficiency in the treatment group than that in the control group (88.57% versus 68.57%, p=0.039). During the follow-up period, the pregnancy rate was 45.71% and 37.14% in the treatment group and control group, respectively, although the difference was not statistically significant (p=0.628). CONCLUSIONS: After surgical management of IUA, the integrated treatment combining a uterus stent placement and artificial cycle with Danshen injection and oral Chinese medicine can improve the condition of menstruation, and prevent and treat recurrence of IUA.
Assuntos
Humanos , Feminino , Gravidez , Doenças Uterinas/cirurgia , Doenças Uterinas/prevenção & controle , Dispositivos Intrauterinos , Histeroscopia , Aderências Teciduais/prevenção & controle , Ácido Hialurônico/uso terapêuticoRESUMO
BACKGROUND: Recent studies have confirmed that RASAL1 has an antitumor effect in many cancers, but its functional role and the molecular mechanism underlying in colon cancer has not been investigated. RESULTS: We collected human colon cancer tissues and adjacent non-tumor tissues, human colon cancer cell lines LoVo, CaCo2, SW1116, SW480 and HCT-116, and normal colonic mucosa cell line NCM460. RT-qPCR was used to detect the RASAL1 level in the clinical tissues and cell lines. In LoVo and HCT-116, RASAL1 was artificially overexpressed. Cell viability and proliferation were measured using CCK-8 assays, and cell cycle was detected via PI staining and flow cytometry analysis. RASAL1 significantly inhibited the cell proliferation via inducing cell cycle arrest, suppressed cell cycle associated protein expression, and decreased the lipid content and inhibited the SCD1 expression. Moreover, SCD1 overexpression induced and downregulation repressed cell proliferation by causing cell cycle arrest. Additionally, luciferase reporter assays were performed to confirm the direct binding between SREBP1c, LXRα and SCD1 promoter, we also demonstrated that RASAL1 inhibit SCD1 3'-UTR activity. RASAL1 inhibited tumor growth in xenograft nude mice models and shows inhibitory effect of SCD1 expression in vivo. CONCLUSION: Taken together, we concluded that RASAL1 inhibited colon cancer cell proliferation via modulating SCD1 activity through LXRα/SREBP1c pathway.
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Proliferação de Células/fisiologia , Neoplasias do Colo/patologia , Proteínas Ativadoras de GTPase/metabolismo , Receptores X do Fígado/metabolismo , Estearoil-CoA Dessaturase/metabolismo , Proteína de Ligação a Elemento Regulador de Esterol 1/metabolismo , Animais , Linhagem Celular Tumoral , Regulação para Baixo , Proteínas Ativadoras de GTPase/genética , Humanos , Receptores X do Fígado/genética , Camundongos , Estearoil-CoA Dessaturase/genética , Proteína de Ligação a Elemento Regulador de Esterol 1/genéticaRESUMO
Alligatorweed, Alternanthera philoxeroide (Mart.) Griseb. (Amaranthaceae) is an invasive weed in China that is often kept under control by the alligatorweed flea beetle, Agasicles hygrophila Selman and Vogt (Coleoptera: Chrysomelidae) introduced into China from Argentina in the 1980s. Elevated CO2 levels have been shown to have a direct effect on Ag. hygrophila. In order to fully evaluate the indirect effects of three different atmospheric concentrations of CO2 (420, 550, and 750 ppm) on the population parameters of Ag. hygrophila reared on Al. philoxeroides, we collected life table data for Ag. hygrophila using the age-stage, two-sex life table method. In general, there were no significant differences in the lengths of the preadult parameters among the three treatments. The adult duration and total longevity of males, however, did increase as CO2 increased in concentration. Although the adult preoviposition and total preoviposition periods decreased, the fecundity, oviposition days, eggs per oviposition day, net reproductive rate, intrinsic rate of increase, and finite rate of increase all increased significantly at the high CO2 concentration. Consequently, we determined that the Ag. hygrophila population size will potentially increase rapidly over a short period of time at elevated CO2 concentrations. Our results suggest that 550 and 750 ppm CO2 may also cause physiological changes in Al. philoxeroides that, in turn, provide enhanced nutrition for increasing reproduction in Ag. hygrophila by accelerating maturation of their reproductive system. These results indicate that the efficacy of Ag. hygrophila as a biological control agent against Al. philoxeroides will likely be increased at 550 and 750 ppm CO2.
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Acanthaceae , Amaranthaceae , Besouros , Animais , Argentina , Dióxido de Carbono , China , Feminino , MasculinoRESUMO
BACKGROUND: Recent studies have confirmed that RASAL1 has an antitumor effect in many cancers, but its functional role and the molecular mechanism underlying in colon cancer has not been investigated. RESULTS: We collected human colon cancer tissues and adjacent non-tumor tissues, human colon cancer cell lines LoVo, CaCo2, SW1116, SW480 and HCT-116, and normal colonic mucosa cell line NCM460. RT-qPCR was used to detect the RASAL1 level in the clinical tissues and cell lines. In LoVo and HCT-116, RASAL1 was artificially overexpressed. Cell viability and proliferation were measured using CCK-8 assays, and cell cycle was detected via PI staining and flow cytometry analysis. RASAL1 significantly inhibited the cell proliferation via inducing cell cycle arrest, suppressed cell cycle associated protein expression, and decreased the lipid content and inhibited the SCD1 expression. Moreover, SCD1 overexpression induced and downregulation repressed cell proliferation by causing cell cycle arrest. Additionally, luciferase reporter assays were performed to confirm the direct binding between SREBP1c, LXRα; and SCD1 promoter, we also demonstrated that RASAL1 inhibit SCD1 3'-UTR activity. RASAL1 inhibited tumor growth in xenograft nude mice models and shows inhibitory effect of SCD1 expression in vivo. CONCLUSION: Taken together, we concluded that RASAL1 inhibited colon cancer cell proliferation via modulating SCD1 activity through LXRα/SREBP1c pathway.
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Humanos , Animais , Camundongos , Estearoil-CoA Dessaturase/metabolismo , Neoplasias do Colo/patologia , Proteínas Ativadoras de GTPase/metabolismo , Proliferação de Células/fisiologia , Proteína de Ligação a Elemento Regulador de Esterol 1/metabolismo , Receptores X do Fígado/metabolismo , Estearoil-CoA Dessaturase/genética , Regulação para Baixo , Proteínas Ativadoras de GTPase/genética , Linhagem Celular Tumoral , Proteína de Ligação a Elemento Regulador de Esterol 1/genética , Receptores X do Fígado/genéticaRESUMO
ABSTRACT This study aimed to describe a Bacillus subtilis expression system based on genetically modified B. subtilis. Abaecin, an antimicrobial peptide obtained from Apis mellifera, can enhance the effect of pore-forming peptides from other species on the inhibition of bacterial growth. For the exogenous expression, the abaecin gene was fused with a tobacco etch virus protease cleavage site, a promoter Pglv, and a mature beta-glucanase signal peptide. Also, a B. subtilis expression system was constructed. The recombinant abaecin gene was expressed and purified as a recombinant protein in the culture supernatant. The purified abaecin did not inhibit the growth of Escherichia coli strain K88. Cecropin A and hymenoptaecin exhibited potent bactericidal activities at concentrations of 1 and 1.5 µM. Combinatorial assays revealed that cecropin A and hymenoptaecin had sublethal concentrations of 0.3 and 0.5 µM. This potentiating functional interaction represents a promising therapeutic strategy. It provides an opportunity to address the rising threat of multidrug-resistant pathogens that are recalcitrant to conventional antibiotics.
Assuntos
Bacillus subtilis/genética , Proteínas de Insetos/genética , Proteínas de Insetos/metabolismo , Peptídeos Catiônicos Antimicrobianos/genética , Peptídeos Catiônicos Antimicrobianos/metabolismo , Vetores Genéticos/genética , Bacillus subtilis/metabolismo , Proteínas Recombinantes/isolamento & purificação , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo , Proteínas Recombinantes/farmacologia , Engenharia de Proteínas , Expressão Gênica , Proteínas de Insetos/isolamento & purificação , Proteínas de Insetos/farmacologia , Peptídeos Catiônicos Antimicrobianos/isolamento & purificação , Peptídeos Catiônicos Antimicrobianos/farmacologia , Transporte Proteico , Escherichia coli/crescimento & desenvolvimento , Escherichia coli/efeitos dos fármacos , Vetores Genéticos/metabolismo , Antibacterianos/isolamento & purificação , Antibacterianos/metabolismo , Antibacterianos/farmacologiaRESUMO
PURPOSE:: To investigate the effect of intravascular cooling on renal function after resuscitation. METHODS:: Twenty four pigs were randomized into three groups (n=8 in each group): therapeutic hypothermia group (TH group), normothermia group (NH group) and sham operation group (SHAM group). After 6 minutes of untreated VF, CPR was performed. Upon ROSC, the TH group received the intravascular cooling. The NH and SHAM group did not undergo therapeutic hypothermia. Haemodynamic parameters were recorded. The bloods were analyzed for serum creatinine (sCr), CysC and NGAL. The kidney was surgically removed observe pathologic changes under a light microscope. RESULTS:: The sCr increased in both TH and NH groups after ROSC, compared to baseline. Between two groups, the sCr and creatinine clearance (Cc) showed lower level in the TH group. The urine volume per hour in the TH group were higher during cooling. After resuscitation, NGAL and CysC in the NH group were higher than in the TH group. Under the light microscope, compared with the TH group, the renal injury was prominent in the NH group. CONCLUSION:: Mild hypothermia had a protection to renal ischemia reperfusion injury after resuscitation.
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Reanimação Cardiopulmonar/efeitos adversos , Hipotermia Induzida/métodos , Rim/fisiopatologia , Traumatismo por Reperfusão/terapia , Animais , Modelos Animais de Doenças , Masculino , Distribuição Aleatória , Traumatismo por Reperfusão/etiologia , Traumatismo por Reperfusão/fisiopatologia , SuínosRESUMO
Abstract Purpose: To investigate the effect of intravascular cooling on renal function after resuscitation. Methods: Twenty four pigs were randomized into three groups (n=8 in each group): therapeutic hypothermia group (TH group), normothermia group (NH group) and sham operation group (SHAM group). After 6 minutes of untreated VF, CPR was performed. Upon ROSC, the TH group received the intravascular cooling. The NH and SHAM group did not undergo therapeutic hypothermia. Haemodynamic parameters were recorded. The bloods were analyzed for serum creatinine (sCr), CysC and NGAL. The kidney was surgically removed observe pathologic changes under a light microscope. Results: The sCr increased in both TH and NH groups after ROSC, compared to baseline. Between two groups, the sCr and creatinine clearance (Cc) showed lower level in the TH group. The urine volume per hour in the TH group were higher during cooling. After resuscitation, NGAL and CysC in the NH group were higher than in the TH group. Under the light microscope, compared with the TH group, the renal injury was prominent in the NH group. Conclusion: Mild hypothermia had a protection to renal ischemia reperfusion injury after resuscitation.
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Animais , Masculino , Traumatismo por Reperfusão/terapia , Reanimação Cardiopulmonar/efeitos adversos , Hipotermia Induzida/métodos , Rim/fisiopatologia , Suínos , Traumatismo por Reperfusão/etiologia , Traumatismo por Reperfusão/fisiopatologia , Distribuição Aleatória , Modelos Animais de DoençasRESUMO
This study aimed to describe a Bacillus subtilis expression system based on genetically modified B. subtilis. Abaecin, an antimicrobial peptide obtained from Apis mellifera, can enhance the effect of pore-forming peptides from other species on the inhibition of bacterial growth. For the exogenous expression, the abaecin gene was fused with a tobacco etch virus protease cleavage site, a promoter Pglv, and a mature beta-glucanase signal peptide. Also, a B. subtilis expression system was constructed. The recombinant abaecin gene was expressed and purified as a recombinant protein in the culture supernatant. The purified abaecin did not inhibit the growth of Escherichia coli strain K88. Cecropin A and hymenoptaecin exhibited potent bactericidal activities at concentrations of 1 and 1.5µM. Combinatorial assays revealed that cecropin A and hymenoptaecin had sublethal concentrations of 0.3 and 0.5µM. This potentiating functional interaction represents a promising therapeutic strategy. It provides an opportunity to address the rising threat of multidrug-resistant pathogens that are recalcitrant to conventional antibiotics.
Assuntos
Peptídeos Catiônicos Antimicrobianos/genética , Peptídeos Catiônicos Antimicrobianos/metabolismo , Bacillus subtilis/genética , Vetores Genéticos/genética , Proteínas de Insetos/genética , Proteínas de Insetos/metabolismo , Antibacterianos/isolamento & purificação , Antibacterianos/metabolismo , Antibacterianos/farmacologia , Peptídeos Catiônicos Antimicrobianos/isolamento & purificação , Peptídeos Catiônicos Antimicrobianos/farmacologia , Bacillus subtilis/metabolismo , Escherichia coli/efeitos dos fármacos , Escherichia coli/crescimento & desenvolvimento , Expressão Gênica , Vetores Genéticos/metabolismo , Proteínas de Insetos/isolamento & purificação , Proteínas de Insetos/farmacologia , Engenharia de Proteínas , Transporte Proteico , Proteínas Recombinantes/genética , Proteínas Recombinantes/isolamento & purificação , Proteínas Recombinantes/metabolismo , Proteínas Recombinantes/farmacologiaRESUMO
Objective: Recent genome-wide association studies have identified a significant relationship between the NT5C2 variant rs11191580 and schizophrenia (SCZ) in European populations. This study aimed to validate the association of rs11191580 polymorphism with SCZ risk in a South Chinese Han population. The relationship of this polymorphism with the severity of SCZ clinical symptoms was also explored. Methods: A case-control study was performed in 462 patients with SCZ and 598 healthy controls. Rs11191580 was genotyped by the Sequenom MassARRAY iPLEX platform. A total of 459 SCZ patients completed the Positive and Negative Syndrome Scale (PANSS) evaluation. Data were analyzed by PLINK software. Results: We confirmed an association of the rs11191580 polymorphism with SCZ risk in South Chinese Han under a dominant genetic model (ORadj = 0.769; 95%CIadj = 0.600-0.984; padj = 0.037). PANSS scores showed a significant association between variant rs11191580 and total score (padj = 0.032), lack of response scale score (padj = 0.022), and negative scale score (additive: padj = 0.004; dominant: padj = 0.016; recessive: padj = 0.021) after data were adjusted for age and sex. Conclusion: NT5C2 variant rs11191580 conferred susceptibility to SCZ and affected the clinical symptoms of SCZ in a South Chinese Han population.
Assuntos
Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Adulto Jovem , Esquizofrenia/genética , Polimorfismo de Nucleotídeo Único/genética , Estudo de Associação Genômica Ampla/métodos , Escalas de Graduação Psiquiátrica , Valores de Referência , Índice de Gravidade de Doença , Estudos de Casos e Controles , Modelos Lineares , China , Fatores de Risco , /genética , Técnicas de Genotipagem , Frequência do GeneRESUMO
OBJECTIVE:: Recent genome-wide association studies have identified a significant relationship between the NT5C2 variant rs11191580 and schizophrenia (SCZ) in European populations. This study aimed to validate the association of rs11191580 polymorphism with SCZ risk in a South Chinese Han population. The relationship of this polymorphism with the severity of SCZ clinical symptoms was also explored. METHODS:: A case-control study was performed in 462 patients with SCZ and 598 healthy controls. Rs11191580 was genotyped by the Sequenom MassARRAY iPLEX platform. A total of 459 SCZ patients completed the Positive and Negative Syndrome Scale (PANSS) evaluation. Data were analyzed by PLINK software. RESULTS:: We confirmed an association of the rs11191580 polymorphism with SCZ risk in South Chinese Han under a dominant genetic model (ORadj = 0.769; 95%CIadj = 0.600-0.984; padj = 0.037). PANSS scores showed a significant association between variant rs11191580 and total score (padj = 0.032), lack of response scale score (padj = 0.022), and negative scale score (additive: padj = 0.004; dominant: padj = 0.016; recessive: padj = 0.021) after data were adjusted for age and sex. CONCLUSION:: NT5C2 variant rs11191580 conferred susceptibility to SCZ and affected the clinical symptoms of SCZ in a South Chinese Han population.
Assuntos
5'-Nucleotidase/genética , Estudo de Associação Genômica Ampla/métodos , Polimorfismo de Nucleotídeo Único/genética , Esquizofrenia/genética , Adulto , Povo Asiático/genética , Estudos de Casos e Controles , China , Feminino , Frequência do Gene , Técnicas de Genotipagem , Humanos , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Escalas de Graduação Psiquiátrica , Valores de Referência , Fatores de Risco , Índice de Gravidade de Doença , Adulto JovemRESUMO
Background: To identify the critical amino acid residues that contribute to the high enzyme activity and good thermostability of Yersinia enterocolitica subsp. palearctica (Y. NSN), 15 mutants of Y. NSN were obtained by site-directed mutagenesis in this study. And their enzyme activity and thermostability were assayed. Effect of several factors on the enzyme activity and thermostability of Y. NSN, was also investigated. Results: The results showed that the I203F and D264E mutants retained approximately 75% and 70% enzyme activity, respectively, compared to the wild-type enzyme. In addition to the I203F and D264E mutants, the mutant E202A had an obvious influence on the thermostability of Y. NSN. According to the analysis of enzyme activity and thermostability of Y. NSN, we found that Glu202, Ile203 and Asp264 might be the key residues for its high enzyme activity and good thermostability. Conclusions: Among all factors affecting enzyme activity and thermostability of Y. NSN, they failed to explain the experimental results well. One reason might be that the enzyme activity and thermostability of Y. NSN were affected not only by a single factor but also by the entire environment.
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Desoxirribonucleases/química , Desoxirribonucleases/genética , Yersinia enterocolitica/enzimologia , Endonucleases/química , Endonucleases/genética , Ensaios Enzimáticos , Estabilidade Enzimática , Temperatura Alta , Mutagênese Sítio-DirigidaRESUMO
OBJECTIVE: Patients with nasopharyngeal carcinoma experience highly variable outcomes despite receiving similar therapeutic regimens. Identifying biomarkers that predict survival and guide individualized therapy is urgently needed. Cystatin C has been explored as a valuable prognostic marker in several malignancies. We retrospectively assessed the relationship between serum cystatin C levels and nasopharyngeal carcinoma prognosis in a large cohort of nasopharyngeal carcinoma patients receiving long-term follow-up. METHODS: A total of 1063 consecutive patients diagnosed with nasopharyngeal carcinoma from June 2006 to December 2010 were retrospectively analyzed. The serum levels of cystatin C at the time of diagnosis were collected. Receiver operating characteristic curve analysis, the Kaplan-Meier method and multivariate analyses using a Cox regression model were performed to assess the correlation of cystatin C levels with overall survival, progression-free survival, distant metastasis-free survival and loco-regional recurrence-free survival. RESULTS: The median follow-up duration was 68.3 months. The optimal cut-off value of cystatin C levels for predicting death was 0.945 mg/L. Compared with the low cystatin C group, the high cystatin C group experienced significantly shorter overall survival (hazard ratio=1.47, p=0.050), progression-free survival (hazard ratio=1.65, p=0.004), distant metastasis-free survival (hazard ratio=2.37, p<0.001) and loco-regional recurrence-free survival (hazard ratio=2.40, p=0.002). Based on multivariate analysis, a high cystatin C level was identified as a significant and independent negative predictor of overall survival (hazard ratio=1.47, p=0.050), progression-free survival (hazard ratio=1.65, p=0.004), distant metastasis-free survival (hazard ratio=2.37, p<0.001), and loco-regional recurrence-free survival (hazard ratio=2.40, p=0.002). CONCLUSION: Cystatin C levels are associated with the prognosis of nasopharyngeal carcinoma patients. A high cystatin C level is an independent indicator of poor prognosis for nasopharyngeal carcinoma patients.
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Biomarcadores Tumorais/sangue , Carcinoma/sangue , Cistatina C/sangue , Neoplasias Nasofaríngeas/sangue , Intervalo Livre de Doença , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Carcinoma Nasofaríngeo , Prognóstico , Estudos Retrospectivos , Análise de Sobrevida , Fatores de TempoRESUMO
OBJECTIVE: To develop and validate a novel decision tree-based clinical algorithm to differentiate Kawasaki disease (KD) from other pediatric febrile illnesses that share common clinical characteristics. STUDY DESIGN: Using clinical and laboratory data from 801 subjects with acute KD (533 for development, and 268 for validation) and 479 febrile control subjects (318 for development, and 161 for validation), we developed a stepwise KD diagnostic algorithm combining our previously developed linear discriminant analysis (LDA)-based model with a newly developed tree-based algorithm. RESULTS: The primary model (LDA) stratified the 1280 subjects into febrile controls (n = 276), indeterminate (n = 247), and KD (n = 757) subgroups. The subsequent model (decision trees) further classified the indeterminate group into febrile controls (n = 103) and KD (n = 58) subgroups, leaving only 29 of 801 KD (3.6%) and 57 of 479 febrile control (11.9%) subjects indeterminate. The 2-step algorithm had a sensitivity of 96.0% and a specificity of 78.5%, and correctly classified all subjects with KD who later developed coronary artery aneurysms. CONCLUSION: The addition of a decision tree step increased sensitivity and specificity in the classification of subject with KD and febrile controls over our previously described LDA model. A multicenter trial is needed to prospectively determine its utility as a point of care diagnostic test for KD.
Assuntos
Algoritmos , Febre/classificação , Febre/diagnóstico , Síndrome de Linfonodos Mucocutâneos/classificação , Síndrome de Linfonodos Mucocutâneos/diagnóstico , Pré-Escolar , Árvores de Decisões , Diagnóstico Diferencial , Feminino , Humanos , Masculino , Reprodutibilidade dos TestesRESUMO
OBJECTIVE: Patients with nasopharyngeal carcinoma experience highly variable outcomes despite receiving similar therapeutic regimens. Identifying biomarkers that predict survival and guide individualized therapy is urgently needed. Cystatin C has been explored as a valuable prognostic marker in several malignancies. We retrospectively assessed the relationship between serum cystatin C levels and nasopharyngeal carcinoma prognosis in a large cohort of nasopharyngeal carcinoma patients receiving long-term follow-up. METHODS: A total of 1063 consecutive patients diagnosed with nasopharyngeal carcinoma from June 2006 to December 2010 were retrospectively analyzed. The serum levels of cystatin C at the time of diagnosis were collected. Receiver operating characteristic curve analysis, the Kaplan-Meier method and multivariate analyses using a Cox regression model were performed to assess the correlation of cystatin C levels with overall survival, progression-free survival, distant metastasis-free survival and loco-regional recurrence-free survival. RESULTS: The median follow-up duration was 68.3 months. The optimal cut-off value of cystatin C levels for predicting death was 0.945 mg/L. Compared with the low cystatin C group, the high cystatin C group experienced significantly shorter overall survival (hazard ratio=1.47, p=0.050), progression-free survival (hazard ratio=1.65, p=0.004), distant metastasis-free survival (hazard ratio=2.37, p<0.001) and loco-regional recurrence-free survival (hazard ratio=2.40, p=0.002). Based on multivariate analysis, a high cystatin C level was identified as a significant and independent negative predictor of overall survival (hazard ratio=1.47, p=0.050), progression-free survival (hazard ratio=1.65, p=0.004), distant metastasis-free survival (hazard ratio=2.37, p<0.001), and loco-regional recurrence-free survival (hazard ratio=2.40, p=0.002). CONCLUSION: Cystatin C levels are associated with the prognosis of nasopharyngeal carcinoma patients. A high cystatin C level is an independent indicator of poor prognosis for nasopharyngeal carcinoma patients.
Assuntos
Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Biomarcadores Tumorais/sangue , Carcinoma/sangue , Cistatina C/sangue , Neoplasias Nasofaríngeas/sangue , Intervalo Livre de Doença , Seguimentos , Análise Multivariada , Prognóstico , Estudos Retrospectivos , Análise de Sobrevida , Fatores de TempoRESUMO
OBJECTIVE: To determine whether the gross tumor volume of resectable gastric adenocarcinoma on multidetector computed tomography could predict the presence of regional lymph node metastasis and could determine N categories. MATERIALS AND METHODS: A total of 202 consecutive patients with gastric adenocarcinoma who had undergone gastrectomy 1 week after contrast-enhanced multidetector computed tomography were retrospectively identified. The gross tumor volume was evaluated on multidetector computed tomography images. Univariate and multivariate analyses were performed to determine whether the gross tumor volume could predict regional lymph node metastasis, and the Mann-Whitney U test was performed to compare the gross tumor volume among N categories. Additionally, a receiver operating characteristic analysis was performed to identify the accuracy of the gross tumor volume in differentiating N categories. RESULTS: The gross tumor volume could predict regional lymph node metastasis (p<0.0001) in the univariate analysis, and the multivariate analyses indicated that the gross tumor volume was an independent risk factor for regional lymph node metastasis (p=0.005, odds ratio=1.364). The Mann-Whitney U test showed that the gross tumor volume could distinguish N0 from the N1-N3 categories, N0-N1 from N2-N3, and N0-N2 from N3 (all p<0.0001). In the T1-T4a categories, the gross tumor volume could differentiate N0 from the N1-N3 categories (cutoff, 12.3 cm3), N0-N1 from N2-N3 (cutoff, 16.6 cm3), and N0-N2 from N3 (cutoff, 24.6 cm3). In the T4a category, the gross tumor volume could differentiate N0 from the N1-N3 categories (cutoff, 15.8 cm3), N0-N1 from N2-N3 (cutoff, 17.8 cm3), and N0-N2 from N3 (cutoff, 24 cm3). CONCLUSION: The gross tumor volume of resectable gastric adenocarcinoma on multidetector computed tomography could predict regional lymph node metastasis and N categories.
Assuntos
Adenocarcinoma/secundário , Linfonodos/diagnóstico por imagem , Tomografia Computadorizada Multidetectores/métodos , Neoplasias Gástricas/patologia , Carga Tumoral , Adenocarcinoma/diagnóstico por imagem , Adenocarcinoma/patologia , Adenocarcinoma/cirurgia , Adulto , Idoso , Feminino , Humanos , Linfonodos/patologia , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Estadiamento de Neoplasias , Variações Dependentes do Observador , Prognóstico , Curva ROC , Estudos Retrospectivos , Neoplasias Gástricas/diagnóstico por imagem , Neoplasias Gástricas/cirurgia , Adulto JovemRESUMO
OBJECTIVE: To determine whether the gross tumor volume of resectable gastric adenocarcinoma on multidetector computed tomography could predict the presence of regional lymph node metastasis and could determine N categories. MATERIALS AND METHODS: A total of 202 consecutive patients with gastric adenocarcinoma who had undergone gastrectomy 1 week after contrast-enhanced multidetector computed tomography were retrospectively identified. The gross tumor volume was evaluated on multidetector computed tomography images. Univariate and multivariate analyses were performed to determine whether the gross tumor volume could predict regional lymph node metastasis, and the Mann-Whitney U test was performed to compare the gross tumor volume among N categories. Additionally, a receiver operating characteristic analysis was performed to identify the accuracy of the gross tumor volume in differentiating N categories. RESULTS: The gross tumor volume could predict regional lymph node metastasis (p<0.0001) in the univariate analysis, and the multivariate analyses indicated that the gross tumor volume was an independent risk factor for regional lymph node metastasis (p=0.005, odds ratio=1.364). The Mann-Whitney U test showed that the gross tumor volume could distinguish N0 from the N1-N3 categories, N0-N1 from N2-N3, and N0-N2 from N3 (all p<0.0001). In the T1-T4a categories, the gross tumor volume could differentiate N0 from the N1-N3 categories (cutoff, 12.3 cm3), N0-N1 from N2-N3 (cutoff, 16.6 cm3), and N0-N2 from N3 (cutoff, 24.6 cm3). In the T4a category, the gross tumor volume could differentiate N0 from the N1-N3 categories (cutoff, 15.8 cm3), N0-N1 from N2-N3 (cutoff, 17.8 cm3), and N0-N2 from N3 (cutoff, 24 cm3). CONCLUSION: The gross tumor volume of resectable gastric adenocarcinoma on multidetector computed tomography could predict regional lymph node metastasis and N categories.