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1.
J Inflamm Res ; 17: 461-468, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38288422

RESUMEN

Objective: To investigate the association of S100A12 protein and C-reactive protein (CRP) with the onset of malignant ventricular arrhythmias (MVA) after acute myocardial infarction (AMI) in the elderly. Methods: A total of 159 elderly AMI patients admitted to Chongming Hospital affiliated to Shanghai University of Medicine & Health Sciences from January 2018 to January 2023 were enrolled in the study. CRP levels were determined using an automatic biochemical analyzer, and S100A12 levels were measured using enzyme-linked immunosorbent assay (ELISA). Patients were categorized based on the Lown classification into groups without MVA and with MVA. Univariate analysis was initially performed to identify independent variables, followed by multivariate logistic regression to determine the risk factors for malignant ventricular arrhythmias post-AMI. The predictive value of S100A12 protein and CRP for malignant ventricular arrhythmias after acute myocardial infarction in the elderly was analyzed using the receiver operating characteristic (ROC) curve. Results: Among the 159 patients with AMI, 27 (17%) had MVA. Multivariate logistic regression analysis indicated that both S100A12 protein and CRP could be independent risk factors for malignant ventricular arrhythmias following acute myocardial infarction in the elderly (p < 0.05). The area under the ROC curve showed the area under the curve (AUC) for S100A12 protein to be 0.7147, for CRP 0.7356, and for the combined diagnosis 0.8350 (p < 0.05). Conclusion: S100A12 protein and CRP are independent risk factors for MVA after MI in the elderly. The combined application of S100A12 protein and CRP has higher diagnostic sensitivity and specificity.

2.
J Biopharm Stat ; : 1-18, 2023 Nov 13.
Artículo en Inglés | MEDLINE | ID: mdl-37955423

RESUMEN

It is widely recognized that treatment effects could differ across subgroups of patients. Subgroup analysis, which assesses such heterogeneity, provides valuable information in developing personalized therapies. There has been extensive research developing novel statistical methods for subgroup identification. The recent contribution is a value-guided subgroup identification method that directly maximizes treatment benefit at the subgroup level for survival outcome, rather than relying on individual treatment effect estimation. In this paper, we first completed this framework by illustrating its application to continuous and binary outcomes. More importantly, we extended the original framework to account for the prognostic effects and named this new method Covariate-Adjusted Value-guided subgroup identification via boosting (CAVboost). The original method directly used the outcome to formulate the value function for subgroup identification. Since the outcome can further be decomposed as prognostic effects and treatment effects, specifying the prognostic effects as the covariates of a model for the outcome can single out the treatment effects and improve the power to detect them across subgroups. Our proposed CAVboost was based on this key idea. It used a covariate-adjusted treatment effect estimator, instead of the outcome itself, to formulate the value function for subgroup identification. CAVboost estimates the treatment effect by using covariates to account for the prognostic effects, which mimics the idea of using covariates in an ANCOVA estimator. We showed that CAVboost could effectively improve the subgroup identification capability for both continuous and binary outcomes.

3.
J Clin Oncol ; 41(22): 3839-3850, 2023 08 01.
Artículo en Inglés | MEDLINE | ID: mdl-37290035

RESUMEN

PURPOSE: There is an unmet need for therapeutic options that prolong survival for patients with heavily pretreated, metastatic castration-resistant prostate cancer (mCRPC). The phase III, open-label KEYLYNK-010 study evaluated pembrolizumab plus olaparib versus a next-generation hormonal agent (NHA) for biomarker-unselected, previously treated mCRPC. METHODS: Eligible participants had mCRPC that progressed on or after abiraterone or enzalutamide (but not both) and docetaxel. Participants were randomly assigned (2:1) to pembrolizumab plus olaparib or NHA (abiraterone or enzalutamide). The dual primary end points were radiographic progression-free survival (rPFS) by blinded independent central review per Prostate Cancer Working Group-modified RECIST 1.1 and overall survival (OS). Time to first subsequent therapy (TFST) was a key secondary end point. Safety and objective response rate (ORR) were secondary end points. RESULTS: Between May 30, 2019, and July 16, 2021, 529 participants were randomly assigned to pembrolizumab plus olaparib and 264 to NHA. At final rPFS analysis, median rPFS was 4.4 months (95% CI, 4.2 to 6.0) with pembrolizumab plus olaparib and 4.2 months (95% CI, 4.0 to 6.1) with NHA (hazard ratio [HR], 1.02 [95% CI, 0.82 to 1.25]; P = .55). At final OS analysis, median OS was 15.8 months (95% CI, 14.6 to 17.0) and 14.6 months (95% CI, 12.6 to 17.3), respectively (HR, 0.94 [95% CI, 0.77 to 1.14]; P = .26). At final TFST analysis, median TFST was 7.2 months (95% CI, 6.7 to 8.1) versus 5.7 months (95% CI, 5.0 to 7.1), respectively (HR, 0.86 [95% CI, 0.71 to 1.03]). ORR was higher with pembrolizumab plus olaparib versus NHA (16.8% v 5.9%). Grade ≥3 treatment-related adverse events occurred in 34.6% and 9.0% of participants, respectively. CONCLUSION: Pembrolizumab plus olaparib did not significantly improve rPFS or OS versus NHA in participants with biomarker-unselected, heavily pretreated mCRPC. The study was stopped for futility. No new safety signals occurred.


Asunto(s)
Neoplasias de la Próstata Resistentes a la Castración , Masculino , Humanos , Neoplasias de la Próstata Resistentes a la Castración/patología , Resultado del Tratamiento , Prednisona , Supervivencia sin Enfermedad , Biomarcadores , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos
4.
Invest. clín ; 63(2): 156-162, jun. 2022. tab
Artículo en Inglés | LILACS-Express | LILACS | ID: biblio-1534652

RESUMEN

Abstract Acute coronary syndrome (ACS), including acute myocardial infarction (AMI) and unstable angina (UA), is the most threatening and lethal form of coronary heart disease. ACS has an abrupt onset and rapid development, which may lead to fatal conditions at any time. Thus, it is never too early to detect and diagnose patients with ACS. The objective of this work was to explore the significance of the combined detection of plasma thrombus precursor protein (TpP) and serum P-selectin (Ps), in the detection and diagnosis of patients with early ACS. A total of 126 subjects were included in the study, 64 ACS patients, 30 individuals with stable angina (SA) and 32 healthy persons who were selected as the control groups. There were no differences in gender, age, ethnicity, or blood glucolipid levels among the groups. Enzyme linked immunosorbent assay (Elisa) was used to quantitatively determine the plasma levels of TpP and Ps. The levels of the two biomarkers in the case group were significantly higher than those in the control groups. Among the ACS patients, the levels of TpP and Ps were higher in AMI patients than in the UA patients. In addition, there was no significant differences in the levels of Ps between SA patients and healthy persons. In conclusion, plasma TpP and serum Ps are remarkably increased in patients with ACS. Therefore, TpP and Ps may serve as ACS indicators, and their measurement may provide a support for an early clinical identification of ACS.


Resumen El síndrome coronario agudo (SCA), que incluye el infarto agudo de miocardio (IAM) y la angina inestable (AI), es la forma más amenazante y letal de enfermedad coronaria. El SCA tiene un inicio abrupto y un desarrollo rápido, lo que puede conducir a condiciones fatales en cualquier momento. Por lo tanto, nunca es demasiado pronto para detectar y diagnosticar pacientes con SCA. El objetivo de este trabajo fue explorar la importancia de la detección combinada de la proteína precursora de trombos plasmáticos (TpP) y la selectina P sérica (Ps), en la detección y diagnóstico de pacientes con SCA precoz. Se incluyeron en el estudio un total de 126 sujetos, 64 pacientes con SCA, 30 individuos con angina estable (AE) y 32 personas sanas que fueron seleccionadas como grupos de control. No hubo diferencias en el género, la edad, el origen étnico o los niveles de glucolípidos en sangre entre los grupos. Se usó el ensayo inmunoabsorbente ligado a enzimas (Elisa) para determinar cuantitativamente los niveles plasmáticos de TpP y Ps. Los niveles de los dos biomarcadores en el grupo de casos (SCA) fueron significativamente más altos que los de los grupos de control. Entre los pacientes con SCA, los niveles de TpP y Ps fueron más altos en los pacientes con IAM que en los pacientes con AI. Además, no hubo diferencias significativas en los niveles de Ps entre pacientes con SA y personas sanas. En conclusión, la TpP plasmática y la Ps sérica están notablemente aumentadas en pacientes con SCA. Por lo tanto, TpP y Ps pueden servir como indicadores de SCA y su medición puede proporcionar un apoyo para una identificación clínica temprana de SCA.

6.
Artículo en Inglés | MEDLINE | ID: mdl-35280513

RESUMEN

Objective: To assess the efficacy of Bushen Yiqi Huayu Decoction on ovarian reserve and inflammatory factors in patients after hysterectomy plus salpingectomy. Methods: Between January 2020 and December 2020, sixty patients with benign uterine lesions scheduled for a hysterectomy plus salpingectomy in the obstetrics and gynecology department of our hospital were recruited and assigned at a ratio of 1 : 1 via the random number table method to receive conventional therapy (control group) or conventional therapy plus Bushen Yiqi Huayu Decoction (study group) for 2 months. The traditional Chinese medicine (TCM) symptom scores, TCM efficacy, various postoperative recovery time indexes, inflammatory factor levels, and hormone levels were compared between the two groups of patients. Results: The study group had lower TCM symptom scores and milder inflammatory responses compared to the control group after treatment (P < 0.05). The Bushen Yiqi Huayu Decoction plus conventional therapy achieved an efficacy of 96.67% versus the efficacy of 76.67% by conventional therapy alone (P < 0.05). In contrast to the control group, a shorter postoperative recovery duration of patients was recorded in the study group (P < 0.05). The study group showed significantly better improvement in hormone levels than the control group after treatment (P < 0.05). Conclusion: Bushen Yiqi Huayu Decoction can significantly mitigate the inflammatory response of patients after hysterectomy plus salpingectomy, improve the hormone level and the ovarian reserve of patients, and promote rapid recovery, so it is worthy of clinical promotion.

7.
Nat Commun ; 13(1): 463, 2022 01 24.
Artículo en Inglés | MEDLINE | ID: mdl-35075135

RESUMEN

Germ cells are essential to pass DNA from one generation to the next. In human reproduction, germ cell development begins with the specification of primordial germ cells (PGCs) and a failure to specify PGCs leads to human infertility. Recent studies have revealed that the transcription factor network required for PGC specification has diverged in mammals, and this has a significant impact on our understanding of human reproduction. Here, we reveal that the Hominidae-specific Transposable Elements (TEs) LTR5Hs, may serve as TEENhancers (TE Embedded eNhancers) to facilitate PGC specification. LTR5Hs TEENhancers become transcriptionally active during PGC specification both in vivo and in vitro with epigenetic reprogramming leading to increased chromatin accessibility, localized DNA demethylation, enrichment of H3K27ac, and occupation of key hPGC transcription factors. Inactivation of LTR5Hs TEENhancers with KRAB mediated CRISPRi has a significant impact on germ cell specification. In summary, our data reveals the essential role of Hominidae-specific LTR5Hs TEENhancers in human germ cell development.


Asunto(s)
Retrovirus Endógenos/fisiología , Hominidae/virología , Reproducción , Retroelementos , Infecciones por Retroviridae/virología , Animales , Retrovirus Endógenos/genética , Elementos de Facilitación Genéticos , Regulación del Desarrollo de la Expresión Génica , Células Germinativas/fisiología , Células Germinativas/virología , Hominidae/genética , Hominidae/fisiología , Humanos , Infecciones por Retroviridae/fisiopatología , Factores de Transcripción/genética , Factores de Transcripción/metabolismo
8.
JAMA Netw Open ; 5(1): e2147375, 2022 01 04.
Artículo en Inglés | MEDLINE | ID: mdl-35076698

RESUMEN

Importance: Identifying which patients with COVID-19 are likely to benefit from COVID-19 convalescent plasma (CCP) treatment may have a large public health impact. Objective: To develop an index for predicting the expected relative treatment benefit from CCP compared with treatment without CCP for patients hospitalized for COVID-19 using patients' baseline characteristics. Design, Setting, and Participants: This prognostic study used data from the COMPILE study, ie, a meta-analysis of pooled individual patient data from 8 randomized clinical trials (RCTs) evaluating CCP vs control in adults hospitalized for COVID-19 who were not receiving mechanical ventilation at randomization. A combination of baseline characteristics, termed the treatment benefit index (TBI), was developed based on 2287 patients in COMPILE using a proportional odds model, with baseline characteristics selected via cross-validation. The TBI was externally validated on 4 external data sets: the Expanded Access Program (1896 participants), a study conducted under Emergency Use Authorization (210 participants), and 2 RCTs (with 80 and 309 participants). Exposure: Receipt of CCP. Main Outcomes and Measures: World Health Organization (WHO) 11-point ordinal COVID-19 clinical status scale and 2 derivatives of it (ie, WHO score of 7-10, indicating mechanical ventilation to death, and WHO score of 10, indicating death) at day 14 and day 28 after randomization. Day 14 WHO 11-point ordinal scale was used as the primary outcome to develop the TBI. Results: A total of 2287 patients were included in the derivation cohort, with a mean (SD) age of 60.3 (15.2) years and 815 (35.6%) women. The TBI provided a continuous gradation of benefit, and, for clinical utility, it was operationalized into groups of expected large clinical benefit (B1; 629 participants in the derivation cohort [27.5%]), moderate benefit (B2; 953 [41.7%]), and potential harm or no benefit (B3; 705 [30.8%]). Patients with preexisting conditions (diabetes, cardiovascular and pulmonary diseases), with blood type A or AB, and at an early COVID-19 stage (low baseline WHO scores) were expected to benefit most, while those without preexisting conditions and at more advanced stages of COVID-19 could potentially be harmed. In the derivation cohort, odds ratios for worse outcome, where smaller odds ratios indicate larger benefit from CCP, were 0.69 (95% credible interval [CrI], 0.48-1.06) for B1, 0.82 (95% CrI, 0.61-1.11) for B2, and 1.58 (95% CrI, 1.14-2.17) for B3. Testing on 4 external datasets supported the validation of the derived TBIs. Conclusions and Relevance: The findings of this study suggest that the CCP TBI is a simple tool that can quantify the relative benefit from CCP treatment for an individual patient hospitalized with COVID-19 that can be used to guide treatment recommendations. The TBI precision medicine approach could be especially helpful in a pandemic.


Asunto(s)
COVID-19/terapia , Hospitalización , Selección de Paciente , Plasma , Índice Terapéutico , Anciano , Tipificación y Pruebas Cruzadas Sanguíneas , Comorbilidad , Femenino , Humanos , Inmunización Pasiva , Masculino , Persona de Mediana Edad , Oportunidad Relativa , Pandemias , Respiración Artificial , SARS-CoV-2 , Índice de Severidad de la Enfermedad , Resultado del Tratamiento , Organización Mundial de la Salud , Sueroterapia para COVID-19
9.
Nucleic Acids Res ; 50(D1): D1244-D1254, 2022 01 07.
Artículo en Inglés | MEDLINE | ID: mdl-34606616

RESUMEN

T-cell receptors (TCRs) and B-cell receptors (BCRs) are critical in recognizing antigens and activating the adaptive immune response. Stochastic V(D)J recombination generates massive TCR/BCR repertoire diversity. Single-cell immune profiling with transcriptome analysis allows the high-throughput study of individual TCR/BCR clonotypes and functions under both normal and pathological settings. However, a comprehensive database linking these data is not yet readily available. Here, we present the human Antigen Receptor database (huARdb), a large-scale human single-cell immune profiling database that contains 444 794 high confidence T or B cells (hcT/B cells) with full-length TCR/BCR sequence and transcriptomes from 215 datasets. All datasets were processed in a uniform workflow, including sequence alignment, cell subtype prediction, unsupervised cell clustering, and clonotype definition. We also developed a multi-functional and user-friendly web interface that provides interactive visualization modules for biologists to analyze the transcriptome and TCR/BCR features at the single-cell level. HuARdb is freely available at https://huarc.net/database with functions for data querying, browsing, downloading, and depositing. In conclusion, huARdb is a comprehensive and multi-perspective atlas for human antigen receptors.


Asunto(s)
Bases de Datos Genéticas , Receptores de Antígenos de Linfocitos B/clasificación , Receptores de Antígenos de Linfocitos T/clasificación , Programas Informáticos , Linfocitos B , Humanos , Receptores de Antígenos de Linfocitos B/inmunología , Receptores de Antígenos de Linfocitos T/inmunología , Análisis de la Célula Individual , Transcriptoma/genética , Recombinación V(D)J/genética
10.
Biochem Biophys Res Commun ; 578: 21-27, 2021 11 12.
Artículo en Inglés | MEDLINE | ID: mdl-34534741

RESUMEN

Serine and arginine-rich splicing factor 3 (SRSF3), the smallest member of the Ser/Arg-rich (SR) RNA-binding protein family, regulates multiple aspects of post-transcriptional gene expression program. Although SRSF3 is essential for early embryo development, reprogramming, and pluripotency maintenance, the RNA targets and specificity of RNA recognition of SRSF3 are not well understood in human pluripotent stem cells. In this study, we used inducible TRIBE (targets of RNA binding sites by editing) to identify RNA targets and binding motifs of SRSF3 in human embryonic stem cells (hESCs). We identified 3888 confident binding sites of SRSF3, corresponding to 1222 gene targets. Our results showed that nearly half of the binding sites were distributed in exons, reflecting the alternative splicing function of SRSF3. Motif analysis demonstrated that two of the SRSF3 recognition sequences were the same as the motifs identified in mouse embryonic stem cells, suggesting the recognition sequences of SRSF3 may be conserved in mammals. Overall, our analyses revealed the RNA targets of SRSF3 and uncovered its RNA recognition specificity, providing a valuable resource for understanding the function of SRSF3 in human embryonic stem cells.


Asunto(s)
Células Madre Embrionarias Humanas/metabolismo , Edición de ARN , ARN Mensajero/antagonistas & inhibidores , Factores de Empalme Serina-Arginina/metabolismo , Animales , Línea Celular , Bases de Datos Genéticas , Células Madre Embrionarias Humanas/citología , Humanos , Ratones , ARN Mensajero/genética , Factores de Empalme Serina-Arginina/genética
12.
J Cardiothorac Surg ; 16(1): 178, 2021 Jun 21.
Artículo en Inglés | MEDLINE | ID: mdl-34154628

RESUMEN

BACKGROUND: Drug-coated balloon (DCB) is a new technology that has emerged in recent years and has been proven to be effective and safe in the treatment of in-stent restenosis. The purpose of this article is to observe the safety and effectiveness of drug-coated balloons in patients with acute myocardial infarction. METHOD: We selected 80 patients admitted to the hospital for STEMI from January 2018 to December 2019. The subjects were randomly divided into a Yinyi (Liaoning) Biotech Bingo Drug Coated Balloon treatment group (balloon group, n = 38) and a drug-eluting stent (DES) treatment group (stent group, n = 42). Patients were followed up to understand the incidence of major adverse cardiovascular events (MACE) at 1 month, 6 months and 1 year after surgery. Coronary angiography was rechecked 1 year after surgery to understand the late lumen loss (LLL) in the two groups. RESULT: During the one-year follow-up, the LLL of the target lesion in the balloon group was -0.12±0.46 mm, while the target lesion in the stent group was 0.14±0.37 mm ( P <0.05). Within 1 year, the incidence of MACE in the balloon group was 11%, while the incidence of MACE in the stent group was 12%. There was no significant difference between the two groups. IN CONCLUSION: When PCI is used for STEMI, only DCB therapy is safe and effective, and has shown good clinical effects during a one-year follow-up period.


Asunto(s)
Angioplastia Coronaria con Balón , Materiales Biocompatibles Revestidos , Stents Liberadores de Fármacos , Intervención Coronaria Percutánea/métodos , Infarto del Miocardio con Elevación del ST/terapia , Angioplastia Coronaria con Balón/efectos adversos , Enfermedades Cardiovasculares/etiología , Angiografía Coronaria , Reestenosis Coronaria , Stents Liberadores de Fármacos/efectos adversos , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Intervención Coronaria Percutánea/efectos adversos , Infarto del Miocardio con Elevación del ST/diagnóstico por imagen , Resultado del Tratamiento
13.
J Vasc Interv Radiol ; 32(6): 907-915.e3, 2021 06.
Artículo en Inglés | MEDLINE | ID: mdl-33794372

RESUMEN

PURPOSE: To calculate the volume of greenhouse gases (GHGs) generated by a hospital-based interventional radiology (IR) department. MATERIALS AND METHODS: Life cycle assessment (LCA) was used to calculate GHGs emitted by an IR department at a tertiary care academic medical center. The volume of waste generated, amount of disposable supplies and linens used, and the operating times of electrical equipment were recorded for procedures performed between 7:00 AM and 7:00 PM on 5 consecutive weekdays. LCA was then performed using purchasing data, plug loads for electrical hardware, data from temperature control units, and estimates of emissions related to travel in the area surrounding the medical center. RESULTS: Ninety-eight procedures were performed on 97 patients. The most commonly performed procedures were drainages (30), placement and removal of venous access (21), and computed tomography-guided biopsies (13). Approximately 23,500 kg CO2e were emitted during the study. Sources of CO2 emissions in descending order were related to indoor climate control (11,600 kg CO2e), production and transportation of disposable surgical items (9,640 kg CO2e), electricity plug load for equipment and lighting (1,060 kg CO2e), staff transportation (524 kg CO2e), waste disposal (426 kg CO2e), production, laundering, and disposal of linens (279 kg CO2e), and gas anesthetics (19.3 kg CO2e). CONCLUSIONS: The practice of IR generates substantial GHG volumes, a majority of which come from energy used to maintain climate control, followed by emissions related to single-use surgical supplies. Efforts to reduce the environmental impact of IR may be focused accordingly.


Asunto(s)
Contaminantes Atmosféricos/análisis , Dióxido de Carbono/análisis , Monitoreo del Ambiente , Gases de Efecto Invernadero/análisis , Radiografía Intervencional , Centros Médicos Académicos , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Aire Acondicionado , Contaminantes Atmosféricos/efectos adversos , Anestesia por Inhalación , Dióxido de Carbono/efectos adversos , Niño , Equipos Desechables , Electricidad , Femenino , Gases de Efecto Invernadero/efectos adversos , Humanos , Servicio de Lavandería en Hospital , Masculino , Eliminación de Residuos Sanitarios , Persona de Mediana Edad , Radiografía Intervencional/efectos adversos , Factores de Riesgo , Factores de Tiempo , Emisiones de Vehículos/análisis , Adulto Joven
14.
ACS Omega ; 5(29): 18490-18498, 2020 Jul 28.
Artículo en Inglés | MEDLINE | ID: mdl-32743227

RESUMEN

This paper is focused on the effects of some controllable operating parameters on the robustness of the coke/coal entrained flow cogasification process considering some uncertainties in it. In the present work, the operating variables were categorized into controllable parameters (CPs) (oxygen and steam concentrations, OC and SC) and hard-to-control parameters (temperature and coal/coke blending ratio) according to the actual modes during the cogasification process. Then, some robust response surface methodology (RSM) models, that is, mean RSM model and variance RSM model, for some important performance indexes [H2, CO, and (H2 + CO) production] with the CPs as independent variables, were found using combined array methodology. Then, the effects of OC and SC not only on the mean but also on the variance of each performance index were systematically investigated. Finally, the cogasification process was robustly optimized using the mean square criterion and desirability function. The result shows that the average production of H2 and that of (H2+ CO) increases with increasing OC but decreases with increasing SC. Additionally, higher OC suppresses the fluctuations in H2 and (H2 + CO) production, while higher SC enlarges the fluctuations in H2 production. Assuming that the variance of temperature in a gasifier is 20 °C and the variance of the coal/coke blending ratio is 5%, the multiobjective robust optimization solutions of OC and SC are 1.56 and 50%, respectively, and a satisfactory performance for high syngas production with low fluctuation can be gained.

15.
BMC Med Genomics ; 10(1): 23, 2017 04 20.
Artículo en Inglés | MEDLINE | ID: mdl-28427387

RESUMEN

BACKGROUND: Colon cancer, one of the most common causes of cancer-related deaths, arises from adenomatous polyps. In these years, circulating microRNAs (miRNAs) have attracted increasing attention as novel biomarkers for colon cancers. The dysregulated circulating miRNAs in patients with colon adenomas has not been well-understood. METHODS: Here, we aimed to identify miRNA profile in the serum of patients with colon adenomas or colon cancer by using microarray. Then we validated eight differentially expressed miRNAs (DEMs) by qRT-PCR and predicted their targets. RESULTS: We identified 26 DEMs from Adenomas versus Normal comparison (11 up-regulations and 15 down-regulations), 72 DEMs from Cancer versus Normal comparison (19 up-regulations and 53 down-regulations) and 17 DEMs from Cancer versus Adenomas comparison (4 up-regulations and 13 down-regulations). Moreover, three DEMs identified from Cancer versus Normal comparison were included in the list of DEMs identified from Cancer versus Adenomas comparison, and may be specific diagnostic biomarkers for colon cancer. Five down-regulated miRNAs identified from Cancer versus Normal comparison were included in the list of DEMs identified from Adenomas versus Normal comparison, and may be important for the development of colon polyps and cancer. CONCLUSIONS: We discovered 8 circulating miRNAs associated with colon adenomas and colon cancer, and these miRNAs may potentially serve as noninvasive screening biomarkers for colon cancer. Our study is useful for expanding our understanding in the development of colon adenomas and colon cancer, and thus provide novel insights into colon cancer pathogenesis and prevention.


Asunto(s)
Adenoma/sangre , Neoplasias del Colon/sangre , MicroARNs/sangre , Adenoma/metabolismo , Anciano , Biomarcadores de Tumor/sangre , Biomarcadores de Tumor/genética , Neoplasias del Colon/metabolismo , Femenino , Regulación Neoplásica de la Expresión Génica , Humanos , Masculino , MicroARNs/genética , Persona de Mediana Edad
16.
Sci Rep ; 6: 19229, 2016 Jan 13.
Artículo en Inglés | MEDLINE | ID: mdl-26759270

RESUMEN

FAS rs2234767 (-1377 G>A), rs1800682 (-670 A>G) and FASLG rs763110 (-844 C>T) promoter polymorphisms can influence transcriptional activities of the genes and thus multiple tumors susceptibility. To investigate their association with risk of colorectal cancer (CRC), the three SNPs were genotyped in 878 cases and 884 controls and the results showed that the FAS rs2234767 and rs1800682 were in a high linkage disequilibrium (LD) with each other (D' = 0.994) and jointly contributed to an increased risk of CRC (without vs. with rs2234767 GG/rs1800682 AA genotypes, adjusted OR = 1.30, 95% CI = 1.05 - 1.61). In vivo ChIP assays evaluated the effect of rs2234767 and rs1800682 on recruitment of SP1 and STAT1, respectively, to chromatin. The results showed SP1 interacting specifically with STAT1 recruited to their respective motifs for transcriptional activation. The mutant alleles rs2234767 A and rs1800682 G jointly affected coupled SP1 and STAT1 recruitment to chromatin. The interplay between SP1 and STAT1 was critical for the functional outcome of rs2234767 and rs1800682 in view of their high LD. In conclusion, the FAS rs2234767 and rs1800682 polymorphisms were in high LD with each other, and they jointly contributed to an increased risk of CRC by altering recruitment of SP1/STAT1 complex to the FAS promoter for transcriptional activation.


Asunto(s)
Alelos , Cromatina/metabolismo , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/metabolismo , Polimorfismo de Nucleótido Simple , Factor de Transcripción STAT1/metabolismo , Factor de Transcripción Sp1/metabolismo , Receptor fas/genética , Estudios de Casos y Controles , Neoplasias Colorrectales/patología , Progresión de la Enfermedad , Proteína Ligando Fas/genética , Estudios de Asociación Genética , Predisposición Genética a la Enfermedad , Genotipo , Humanos , Regiones Promotoras Genéticas , Unión Proteica , Riesgo
17.
World J Gastroenterol ; 21(43): 12370-80, 2015 Nov 21.
Artículo en Inglés | MEDLINE | ID: mdl-26604644

RESUMEN

AIM: To investigate the protective effect of magnesium isoglycyrrhizinate (MgIG) on excessive hepatectomy animal model and its possible mechanism. METHODS: We used the standard 90% hepatectomy model in Sprague-Dawley rats developed using the modified Emond's method, in which the left, middle, right upper, and right lower lobes of the liver were removed. Rats with 90% liver resection were divided into three groups, and were injected intraperitoneally with 3 mL saline (control group), 30 mg/kg (low-dose group) and 60 mg/kg (high-dose group) of MgIG, respectively. Animals were sacrificed at various time points and blood was drawn from the vena cava. Biochemical tests were performed with an automatic biochemical analyzer for the following items: serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), glutamyl endopeptidase, total bilirubin (TBil), direct bilirubin (DBil), total protein, albumin, blood glucose (Glu), hyper-sensitivity C-reactive protein, prothrombin time (PT), and thrombin time (TT). Postoperative survival time was observed hourly until death. Hepatocyte regeneration was analyzed by immunohistochemistry. Serum inflammatory cytokines (IL-1, IL-6, IL-10, and iNOS) was analyzed by ELISA. STAT3 protein and mRNA were analyzed by Western blot and quantitative reverse-transcription PCR, respectively. RESULTS: The high-dose group demonstrated a significantly prolonged survival time, compared with both the control and the low-dose groups (22.0 ± 4.7 h vs 8.9 ± 2.0 vs 10.3 ± 3.3 h, P = 0.018). There were significant differences among the groups in ALT, Glu and PT levels starting from 6 h after surgery. The ALT levels were significantly lower in the MgIG treated groups than in the control group. Both Glu and PT levels were significantly higher in the MgIG treated groups than in the control group. At 12 h, ALT, AST, TBil, DBil and TT levels showed significant differences between the MgIG treated groups and the control group. No significant differences in hepatocyte regeneration were found. Compared to the control group, the high-dose group showed a significantly increase in serum inflammatory cytokines IL-1 and IL-10, and a decrease in IL-6. Both STAT3 protein and mRNA levels were significantly lower in the MgIG treated groups than in the control group at 6 h, 12 h, and 18 h after surgery. CONCLUSION: High-dose MgIG can extend survival time in rats after excessive hepatectomy. This hepatoprotective effect is mediated by inhibiting the inflammatory response through inhibition of the STAT3 pathway.


Asunto(s)
Antiinflamatorios/farmacología , Hepatectomía/efectos adversos , Inflamación/prevención & control , Hígado/efectos de los fármacos , Factor de Transcripción STAT3/metabolismo , Saponinas/farmacología , Transducción de Señal/efectos de los fármacos , Triterpenos/farmacología , Animales , Biomarcadores/sangre , Coagulación Sanguínea/efectos de los fármacos , Citocinas/sangre , Citoprotección , Relación Dosis-Respuesta a Droga , Inflamación/sangre , Inflamación/genética , Mediadores de Inflamación/sangre , Hígado/metabolismo , Hígado/patología , Hígado/cirugía , Regeneración Hepática/efectos de los fármacos , Masculino , Modelos Animales , Ratas Sprague-Dawley , Factor de Transcripción STAT3/genética , Factores de Tiempo
18.
Int J Clin Exp Med ; 8(7): 11803-10, 2015.
Artículo en Inglés | MEDLINE | ID: mdl-26380021

RESUMEN

OBJECTIVE: To characterized the gene polymorphisms of connexin 40 (cx40) and angiotensin II receptor type 1 (AT1R) in Chongming adults with atrial fibrillation (AF) and to explore their relationships with AF. METHODS: 82 patients with AF, and 82 subjects without AF were enrolled. Polymorphisms of cx40 G-44A and AT1 A1166C were detected. Moreover, several samples were randomly selected to validate the gene polymorphisms of cx40 and AT1. RESULTS: Genotypes AA, AG and GG of cx40 G-44A were found in both AF patients and controls. The frequencies of genotypes AA, AG and GG were 39%, 29% and 32%, respectively, in AF patients and 31%, 35% and 34%, respectively in controls. The frequencies of alleles A and G were 54% and 46%, respectively in AF patients and 48% and 52%, respectively, in controls (P < 0.05). The risk for AF in patients with allele A increased 1.31 times (OR = 1.31, P < 0.05). The frequencies of genotypes AA, AC and CC were 88%, 8% and 4%, respectively in AF patients and 93%, 6% and 1%, respectively in controls. The frequencies of alleles A and C were 92% and 8%, respectively in AF patients and 96% and 4%, respectively in controls (P < 0.05). More AF patients had allele C as compared to controls. The risk for AF increased by 1.43 times in patients with allele C (OR = 1.43, P < 0.05). CONCLUSION: There were relationships between gene polymorphisms of cx40 and AT1 and AF in Chongming adults. Allele A of cx40 G-44A and allele C of AT1 A1166C significantly increase the risk for AF.

19.
Int J Clin Exp Med ; 8(1): 845-53, 2015.
Artículo en Inglés | MEDLINE | ID: mdl-25785065

RESUMEN

OBJECTIVE: To investigate the changes in expression profile of circulating microRNAs (miRNAs) and the regulatory effect of atrial fibrilation (AF)-related miRNAs on ion channels. METHODS: 112 patients with AF were assigned into observation group, and another 112 non-AF people were assigned into control group. Total plasma RNAs were extracted from patients' blood samples. Differentially expressed miRNA-1s were transfected into primary-cultured neonatal rat cardiac myocytes. RESULTS: Compared with control group, significant differences were observed in 15 kinds of miRNAs in observation group. Down-regulation of the expression of miRNAs included hsa-miR-328, hsa-miR-145, hsa-miR-222, hsa-miR-1, hsa-miR-162, hsa-miR-432, and hsa-miR-493b; Up-regulation of the expression included hsa-miR634, hsa-miR-664, hsa-miR-9, hsa-miR-152, hsa-miR-19, hsa-miR-454, hsa-miR-146, and hsa-miR-374a. The expression level of CACNB2 protein in miRNA-1 group was significantly lower than that in blank control group, negative control group, MTmiRNA-1 group, AMO-1 group and miRNA-1+AMO-1 cotransfection group (P < 0.05), while in AMO-1 group, the expression level of CACNB2 protein was significantly higher than that in other groups (P < 0.05). These results indicated that transfected miRNA-1 could significantly inhibit the expression of CACNB2 protein. CONCLUSIONS: Circulating miRNAs can be used in studies concerning on the regulation mechanism of the occurrence and development of AF. MiRNA-1 can decrease the intracellular Ca(2+) concentration and prevent the AF.

20.
Opt Express ; 22(23): 27921-31, 2014 Nov 17.
Artículo en Inglés | MEDLINE | ID: mdl-25402033

RESUMEN

A new accurate method for long focal-length measurement based on Talbot interferometry is proposed. A divergent beam and two Ronchi gratings of different periods are employed, as the alternative of the collimated beam and two identical gratings, to achieve higher measurement accuracy. Moreover, with divergent beam, lenses of large aperture can be easily measured without scanning, which is required when it comes to traditional collimated beam. Numerical analysis and experiments were carried out. The results demonstrate the proposed method features remarkably high accuracy and repeatability.


Asunto(s)
Algoritmos , Interferometría/instrumentación , Lentes , Diseño de Equipo
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