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1.
J Nutr ; 154(6): 1853-1860, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38614238

RESUMEN

BACKGROUND: Obesity paradox has been reported in patients with cardiovascular disease, showing an inverse association between obesity as defined by BMI (in kg/m2) and prognosis. Nutritional status is associated with systemic inflammatory response and affects cardiovascular disease outcomes. OBJECTIVES: This study sought to examine the influence of obesity and malnutrition on the prognosis of patients with acute coronary syndrome (ACS). METHODS: This study included consecutive patients diagnosed with ACS and underwent coronary angiogram between January 2009 and February 2023. At baseline, patients were categorized according to their BMI as follows: underweight (<18), normal weight (18-24.9), overweight (25.0-29.9), and obese (>30.0). We assessed the nutritional status by Prognostic Nutritional Index (PNI). Malnutrition was defined as a PNI value of <38. RESULTS: Of the 21,651 patients with ACS, 582 (2.7%) deaths from any cause were observed over 28.7 months. Compared with the patient's state of normal weight, overweight, and obesity were associated with decreased risk of all-cause mortality. Malnutrition was independently associated with poor survival (hazards ratio: 2.64; 95% CI: 2.24, 3.12; P < 0.001). In malnourished patients, overweight and obesity showed a 39% and 72% reduction in the incidence of all-cause mortality, respectively. However, in nourished patients, no significant reduction in the incidence of all-cause mortality was observed (all P > 0.05). CONCLUSIONS: Obesity paradox appears to occur in patients with ACS. Malnutrition may be a significant independent risk factor for prognosis in patients with ACS. The obesity paradox is influenced by the status of malnutrition.


Asunto(s)
Síndrome Coronario Agudo , Desnutrición , Obesidad , Humanos , Síndrome Coronario Agudo/complicaciones , Síndrome Coronario Agudo/mortalidad , Masculino , Femenino , Desnutrición/complicaciones , Obesidad/complicaciones , Persona de Mediana Edad , Anciano , Índice de Masa Corporal , Estado Nutricional , Pronóstico , Factores de Riesgo , Evaluación Nutricional , Paradoja de la Obesidad
3.
J Transl Int Med ; 11(4): 423-432, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-38130645

RESUMEN

Objective: QL0911, a recombinant human thrombopoietin mimetic peptide-Fc fusion protein, is a romiplostim (Nplate®) biosimilar used to treat primary immune thrombocytopenia (ITP). This phase III study aimed to assess the efficacy and safety of QL0911 in adult patients with chronic primary ITP over a 24-week treatment period. Methods: We conducted a double-blind, placebo-controlled, phase III study in patients diagnosed with primary ITP for at least 12 months who had received at least one first-line ITP treatment with no response or recurrence after treatment, or who relapsed after splenectomy at 44 sites in China. Patients were randomly allocated (2:1 ratio) to QL0911 or placebo injection subcutaneously once weekly at an initial dose of 1 µg/kg for 24 weeks. The doses were adjusted to maintain the target platelet counts from 50 × 109/L to 200 × 109/L. Patients and investigators were blinded to the assignment. The primary endpoints were the proportion of patients who achieved a durable platelet response at week 24 (platelet count, ≥ 50 × 109/L during 6 of the last 8 weeks of treatment) and safety. The study was registered at ClinicalTrials.gov (NCT05621330). Results: Between October 2019 and December 2021, 216 patients were randomly assigned (QL0911,144; placebo,72). A durable platelet response was achieved by significantly more patients in the QL0911 group (61.8%, 95% CI: 53.3-69.8; P < 0.0001) than in the placebo group (0%). The mean duration of platelet responses was 15.9 (SE: 0.43) weeks with QL0911, and 1.9 (SE:0.26) week with placebo. Consistent results were achieved in subgroup analyses categorized by baseline splenectomy status (yes/no), concomitant ITP treatment (yes/no), and baseline platelet count (≤ 10 × 109/L, > 10 × 109/L, ≤ 20 × 109/L, > 20 × 109/L, and < 30 × 109/L). The incidence of TEAEs was comparable between the QL0911 and the placebo groups (91.7% and 88.9%, respectively). The most common adverse events overall were ecchymosis (28.5% for QL0911 vs. 37.5% for placebo), upper respiratory tract infections respiratory tract infections (31.9% for QL0911 vs. 27.8% for placebo), and gingival bleeding (17.4% for QL0911 vs. 26.4% for placebo). Conclusion: QL0911 was well-tolerated and increased and maintained platelet counts in adults with ITP. QL0911, a biosimilar to romiplostim (Nplate®), may be a novel treatment option for patients with ITP who have failed or relapsed from first-line treatment in China. Ongoing studies will provide further data on long-term efficacy and safety in such patient populations.

4.
Sci Bull (Beijing) ; 68(18): 2106-2114, 2023 09 30.
Artículo en Inglés | MEDLINE | ID: mdl-37599175

RESUMEN

Rare but critical bleeding events in primary immune thrombocytopenia (ITP) present life-threatening complications in patients with ITP, which severely affect their prognosis, quality of life, and treatment decisions. Although several studies have investigated the risk factors related to critical bleeding in ITP, large sample size data, consistent definitions, large-scale multicenter findings, and prediction models for critical bleeding events in patients with ITP are unavailable. For the first time, in this study, we applied the newly proposed critical ITP bleeding criteria by the International Society on Thrombosis and Hemostasis for large sample size data and developed the first machine learning (ML)-based online application for predict critical ITP bleeding. In this research, we developed and externally tested an ML-based model for determining the risk of critical bleeding events in patients with ITP using large multicenter data across China. Retrospective data from 8 medical centers across the country were obtained for model development and prospectively tested in 39 medical centers across the country over a year. This system exhibited good predictive capabilities for training, validation, and test datasets. This convenient web-based tool based on a novel algorithm can rapidly identify the bleeding risk profile of patients with ITP and facilitate clinical decision-making and reduce the occurrence of adversities.


Asunto(s)
Púrpura Trombocitopénica Idiopática , Trombocitopenia , Humanos , Púrpura Trombocitopénica Idiopática/complicaciones , Calidad de Vida , Estudios Retrospectivos , Estudios Prospectivos , Hemorragia/diagnóstico , Trombocitopenia/complicaciones
6.
BMC Anesthesiol ; 23(1): 113, 2023 04 04.
Artículo en Inglés | MEDLINE | ID: mdl-37016294

RESUMEN

BACKGROUND: Red blood cell distribution width (RDW) to platelet ratio (RPR) is a novel inflammatory indicator. It integrates the risk prediction of RDW and platelet, which is associated with adverse outcomes. However, the predictive power of RPR in mortality for patients with acute myocardial infarction (AMI) remains uncertain. Thus, we aimed to explore the association between RPR and 180-day in-hospital mortality in patients with AMI. METHODS: Data on patients with AMI were extracted from the Medical Information Mart for Intensive Care IV (MIMIC-IV) database. Patients were divided into two groups according to the optimal RPR cut-off value. The survival curve between high and low RPR groups was plotted via the Kaplan-Meier (KM) method. Univariate and multivariate Cox regression analyses were performed to determine the association between RPR on admission and 180-day in-hospital mortality. RESULTS: A total of 1266 patients were enrolled, of which 83 (6.8%) died within 180 days during the hospitalization. Compared with the survivor group, the non-survivor group had higher RPR on admission (0.11 ± 0.07 vs. 0.08 ± 0.06, P < 0.001). The KM curve indicated that the survival probability of low RPR group was higher than that of high RPR group. Multivariate Cox regression analysis demonstrated that higher RPR on admission was an independent and effective predictor of 180-day mortality in patients with AMI (hazard ratio [HR]: 2.677, 95% confidence interval [CI]: 1.159-6.188, P = 0.021). CONCLUSION: Higher RPR was associated with higher in-hospital 180-day mortality in patients with AMI.


Asunto(s)
Infarto del Miocardio , Humanos , Estudios Retrospectivos , Mortalidad Hospitalaria , Pronóstico , Eritrocitos , Cuidados Críticos
7.
Blood Rev ; 60: 101074, 2023 07.
Artículo en Inglés | MEDLINE | ID: mdl-36963988

RESUMEN

Because of successful thalassaemia prevention programmes in resource-rich countries and it's huge population China now has the greatest number of new cases of thalassaemia globally as well as more people with thalassaemia than any other country. 30 million Chinese have thalassaemia-associated mutations and about 300,000 have thalassaemia major or intermedia requiring medical intervention. Over the past 2 decades there has been tremendous economic growth in China including per capita spending on health care. There is now nation-wide availability and partial or full insurance for prenatal genetic testing, RBC-transfusions, iron-chelating drugs and haematopoietic cell transplants. Prenatal screening and educational programmes have reduced the incidence of new cases. However, substantial challenges remain. For example, regional differences in access to medical care and unequal economic development require innovations to reduce the medical, financial and psychological burdens of Chinese with thalassaemia and their families. In this review we discuss success in preventing and treating thalassaemia in China highlighting remaining challenges. Our discussion has important implications for resource-poor geospaces challenged with preventing and treating thalassaemia.


Asunto(s)
Talasemia , Talasemia beta , Embarazo , Femenino , Humanos , Talasemia/diagnóstico , Talasemia/epidemiología , Talasemia/terapia , Quelantes del Hierro/uso terapéutico , Talasemia beta/diagnóstico , Talasemia beta/epidemiología , Talasemia beta/genética , Pruebas Genéticas , Transfusión Sanguínea
8.
J Interv Card Electrophysiol ; 66(4): 1005-1013, 2023 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-35804257

RESUMEN

BACKGROUND: Upgrading to His-Purkinje conduction system pacing (HPCSP) has been proven to reverse ventricular remodeling and improve cardiac function in patients with pacing-induced cardiomyopathy (PICM). This meta-analysis aimed to assess the efficacy and clinical benefit of upgrading to HPCSP in patients with PICM after chronic right ventricular pacing (RVP). METHODS: We systematically searched PubMed, Cochrane Library, and Embase for relevant articles from databases' establishment to April 22, 2022. Clinical outcomes and pacing parameters included left ventricular ejection fraction (LVEF) pre-RVP, pre-HPCSP, and during follow-up, New York Heart Association (NYHA) functional class at baseline and follow-up, lead-related complications, heart failure hospitalization (HFH), all-cause mortality, pacing thresholds at implant and during follow-up, and QRS duration (QRSd) pre-RVP, pre-HPCSP, and during follow-up. RESULTS: A total of 6 articles including 144 patients were enrolled in this meta-analysis. QRSd increased from 127 ± 29 ms at baseline to 175 ± 19 ms (P < 0.001) during RVP and then significantly narrowed to 116 ± 18 ms (P < 0.001) after upgrading to HPCSP. During a mean follow-up of 17.9 ± 10.5 months, LVEF improved from 35 ± 8% pre-HPSCP to 48 ± 12% after upgrading to HPCSP (P < 0.001). The capture thresholds were 1.2 ± 0.9 V at baseline and increased slightly during follow-up. NYHA functional class improved significantly from 2.7 ± 0.8 to 1.9 ± 0.8 during follow-up (P < 0.001). CONCLUSION: Our meta-analysis indicates that upgrading to HPCSP in patients with PICM is feasible and efficient, as it significantly improves electrical synchrony and cardiac function.


Asunto(s)
Cardiomiopatías , Insuficiencia Cardíaca , Humanos , Volumen Sistólico , Función Ventricular Izquierda , Estimulación Cardíaca Artificial/efectos adversos , Cardiomiopatías/terapia , Fascículo Atrioventricular , Resultado del Tratamiento , Electrocardiografía
9.
Blood Adv ; 6(14): 4320-4329, 2022 07 26.
Artículo en Inglés | MEDLINE | ID: mdl-35679462

RESUMEN

Intracranial hemorrhage (ICH) is a rare and life-threatening hemorrhagic event in patients with immune thrombocytopenia (ITP). However, its mortality and related risk factors remain unclear. Herein, we conducted a nationwide multicenter real-world study of ICH in adult ITP patients. According to data from 27 centers in China from 2005 to 2020, the mortality rate from ICH was 33.80% (48/142) in ITP adults. We identified risk factors by logistic univariate and multivariate logistic regression for 30-day mortality in a training cohort of 107 patients as follows: intraparenchymal hemorrhage (IPH), platelet count ≤10 × 109/L at ICH, a combination of serious infections, grade of preceding bleeding events, and Glasgow coma scale (GCS) level on admission. Accordingly, a prognostic model of 30-day mortality was developed based on the regression equation. Then, we evaluated the performance of the prognostic model through a bootstrap procedure for internal validation. Furthermore, an external validation with data from a test cohort with 35 patients from 11 other centers was conducted. The areas under the receiver operating characteristic (ROC) curves for the internal and external validation were 0.954 (95% confidence interval [CI], 0.910-0.998) and 0.942 (95% CI, 0.871-1.014), respectively. Both calibration plots illustrated a high degree of consistency in the estimated and observed risk. In addition, the decision curve analysis showed a considerable net benefit for patients. Thus, an application (47.94.162.105:8080/ich/) was established for users to predict 30-day mortality when ICH occurred in adult patients with ITP.


Asunto(s)
Púrpura Trombocitopénica Idiopática , Adulto , Hemorragia Cerebral/complicaciones , Escala de Coma de Glasgow , Humanos , Hemorragias Intracraneales/etiología , Púrpura Trombocitopénica Idiopática/complicaciones , Púrpura Trombocitopénica Idiopática/epidemiología , Curva ROC
10.
Ther Adv Hematol ; 13: 20406207221095226, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35510211

RESUMEN

Background: The responses of intravenous immunoglobulin (IVIg) or corticosteroids as the initial treatment on pregnancy with ITP were unsatisfactory. This study aimed to assess the safety and effectiveness of prednisone plus IVIg versus prednisone or IVIg in pregnant patients with immune thrombocytopenia (ITP). Methods: Between 1 January 2010 and 31 December 2020, 970 pregnancies diagnosed with ITP at 19 collaborative centers in China were reviewed in this observational study. A total of 513 pregnancies (52.89%) received no intervention. Concerning the remaining pregnancies, 151 (33.04%) pregnancies received an initial treatment of prednisone plus IVIg, 105 (22.98%) pregnancies received IVIg alone, and 172 (37.64%) pregnancies only received prednisone. Results: Regarding the maternal response to the initial treatment, no differences were found among the three treatment groups (41.1% for prednisone plus IVIg, 33.1% for prednisone, and 38.1% for IVIg). However, a significant difference was observed in the time to response between the prednisone plus IVIg group (4.39 ± 2.54 days) and prednisone group (7.29 ± 5.01 days; p < 0.001), and between the IVIg group (6.71 ± 4.85 days) and prednisone group (p < 0.001). The median prednisone duration in the monotherapy group was 27 days (range, 8-195 days), whereas that in the combination group was 14 days (range, 6-85 days). No significant differences were found among these three treatment groups in neonatal outcomes, particularly concerning the neonatal platelet counts. The time to response in the combination treatment group was shorter than prednisone monotherapy. The duration of prednisone application in combination group was shorter than prednisone monotherapy. The combined therapy showed a lower predelivery platelet transfusion rate than IVIg alone. Conclusion: These findings suggest that prednisone plus IVIg may represent a potential combination therapy for pregnant patients with ITP.

11.
Adv Ther ; 38(4): 1889-1903, 2021 04.
Artículo en Inglés | MEDLINE | ID: mdl-33751401

RESUMEN

INTRODUCTION: Patients with diffuse large B-cell lymphoma (DLBCL) have limited access to rituximab. IBI301 is a recombinant chimeric murine/human anti-CD20 monoclonal antibody and is a candidate biosimilar to rituximab. This study aimed to assess the therapeutic equivalence of IBI301 and rituximab in previously untreated patients with diffuse large B-cell lymphoma (DLBCL). METHODS: This multicenter, randomized, double-blind, parallel-group, phase 3 trial compared IBI301 and rituximab, both plus the chemotherapy of doxorubicin, cyclophosphamide, vindesine, and prednisone (CHOP), was conducted in 68 centers across China. Eligible patients with untreated CD20 positive (CD20+) DLBCL randomly received IBI301 (375 mg/m2) plus the standard CHOP or rituximab (375 mg/m2) plus the standard CHOP for six cycles of a 21-day cycle. The primary end point was the overall remission rate (ORR). Efficacy equivalence was defined if 95% CIs for the ORR difference between the two groups were within a ± 12.0% margin. RESULTS: Between August 22, 2016, and September 5, 2018, 419 patients were randomly allocated into the IBI301 group (N = 209) and rituximab group (N = 210). In the full analysis set, the ORR was 89.9% and 93.8% in the IBI301 and rituximab groups, respectively, and the ORR difference was -3.9% (95% CI - 9.1%-1.3%), falling within a ± 12.0% margin. The occurrences of treatment-emergent adverse events (TEAEs) (100% vs. 99.0%) and AEs of grade ≥ 3 (87.1% vs. 83.3%) were similar in the two groups (P > 0.05). CONCLUSIONS: IBI301 had a non-inferiority efficacy and a comparable safety compared with rituximab. IBI301 plus CHOP could be suggested as a candidate treatment regimen for untreated patients with CD20+ DLBCL. TRIAL REGISTRATION: This trial is registered on ClinicalTrials.gov (NCT02867566).


Asunto(s)
Biosimilares Farmacéuticos , Linfoma de Células B Grandes Difuso , Animales , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Biosimilares Farmacéuticos/uso terapéutico , China , Humanos , Linfoma de Células B Grandes Difuso/tratamiento farmacológico , Ratones , Estándares de Referencia , Rituximab/uso terapéutico , Resultado del Tratamiento , Vincristina/uso terapéutico
12.
Cancer Med ; 10(8): 2611-2617, 2021 04.
Artículo en Inglés | MEDLINE | ID: mdl-33733588

RESUMEN

OBJECTIVE: This study is to determine whether the addition of cisplatin-based chemotherapy after radical hysterectomy will improve the survival of low-risk squamous cervical carcinoma with poor differentiation. METHODS: Patients with low-risk squamous cervical cancer (FIGO IA2-IIA, absent high- and intermediate-risk factors after pathological evaluation) were eligible for this study. As first, the prognostic relevance of G3 versus G1/G2 among patients with low-risk squamous cervical cancer was analyzed, then, the oncological results of postoperative chemotherapy among low-risk squamous cervical cancer with poor differentiation was explored. RESULTS: Totally, there were 367 low-risk squamous cervical cancer patients, of whom 161 were poor-differentiated (47 in the chemotherapy group and 114 in the nonchemotherapy group), with a median follow-up time of 56 months. Patients with G3 displayed a significantly worse overall survival (p = 0.035), and a higher recurrence rate (p = 0.014) than patients with G1/G2. Compared with the nonchemotherapy group, the hazard ratios (95%CI) for recurrence-free survival in the chemotherapy group was 0.24 (0.06-0.93), (p = 0.038). No difference in overall survival was observed between the chemotherapy group and the nonchemotherapy group. CONCLUSIONS: The addition of cisplatin-based chemotherapy following surgery significantly improved recurrence-free survival for low-risk, poor differentiation, and early stage squamous cervical cancer patients.


Asunto(s)
Carcinoma de Células Escamosas/tratamiento farmacológico , Carcinoma de Células Escamosas/patología , Neoplasias del Cuello Uterino/tratamiento farmacológico , Neoplasias del Cuello Uterino/patología , Adulto , Carcinoma de Células Escamosas/mortalidad , Carcinoma de Células Escamosas/cirugía , Quimioterapia Adyuvante , Femenino , Humanos , Histerectomía , Persona de Mediana Edad , Recurrencia Local de Neoplasia , Pronóstico , Estudios Retrospectivos , Análisis de Supervivencia , Neoplasias del Cuello Uterino/mortalidad , Neoplasias del Cuello Uterino/cirugía
13.
Am J Hematol ; 96(5): 561-570, 2021 05 01.
Artículo en Inglés | MEDLINE | ID: mdl-33606900

RESUMEN

Globally, postpartum hemorrhage (PPH) is the leading cause of maternal death. Women with immune thrombocytopenia (ITP) are at increased risk of developing PPH. Early identification of PPH helps to prevent adverse outcomes, but is underused because clinicians do not have a tool to predict PPH for women with ITP. We therefore conducted a nationwide multicenter retrospective study to develop and validate a prediction model of PPH in patients with ITP. We included 432 pregnant women (677 pregnancies) with primary ITP from 18 academic tertiary centers in China from January 2008 to August 2018. A total of 157 (23.2%) pregnancies experienced PPH. The derivation cohort included 450 pregnancies. For the validation cohort, we included 117 pregnancies in the temporal validation cohort and 110 pregnancies in the geographical validation cohort. We assessed 25 clinical parameters as candidate predictors and used multivariable logistic regression to develop our prediction model. The final model included seven variables and was named MONITOR (maternal complication, WHO bleeding score, antepartum platelet transfusion, placental abnormalities, platelet count, previous uterine surgery, and primiparity). We established an easy-to-use risk heatmap and risk score of PPH based on the seven risk factors. We externally validated this model using both a temporal validation cohort and a geographical validation cohort. The MONITOR model had an AUC of 0.868 (95% CI 0.828-0.909) in internal validation, 0.869 (95% CI 0.802-0.937) in the temporal validation, and 0.811 (95% CI 0.713-0.908) in the geographical validation. Calibration plots demonstrated good agreement between MONITOR-predicted probability and actual observation in both internal validation and external validation. Therefore, we developed and validated a very accurate prediction model for PPH. We hope that the model will contribute to more precise clinical care, decreased adverse outcomes, and better health care resource allocation.


Asunto(s)
Hemorragia Posparto/etiología , Complicaciones Hematológicas del Embarazo , Púrpura Trombocitopénica Idiopática/complicaciones , Adulto , Área Bajo la Curva , China/epidemiología , Estudios de Cohortes , Susceptibilidad a Enfermedades , Registros Electrónicos de Salud , Femenino , Estudios de Seguimiento , Predicción , Geografía Médica , Humanos , Inmunoglobulinas Intravenosas/uso terapéutico , Inmunosupresores/uso terapéutico , Recién Nacido , Modelos Logísticos , Modelos Teóricos , Hemorragia Posparto/epidemiología , Hemorragia Posparto/prevención & control , Prednisona/uso terapéutico , Embarazo , Resultado del Embarazo , Pronóstico , Púrpura Trombocitopénica Idiopática/tratamiento farmacológico , Púrpura Trombocitopénica Idiopática/terapia , Estudios Retrospectivos , Factores de Riesgo , Centros de Atención Terciaria/estadística & datos numéricos
14.
Minerva Med ; 112(2): 310-312, 2021 04.
Artículo en Inglés | MEDLINE | ID: mdl-31317691
15.
Platelets ; 32(5): 633-641, 2021 Jul 04.
Artículo en Inglés | MEDLINE | ID: mdl-32614630

RESUMEN

Intracranial hemorrhage (ICH) is a devastating complication of immune thrombocytopenia (ITP). However, information on ICH in ITP patients under the age of 60 years is limited, and no predictive tools are available in clinical practice. A total of 93 adult patients with ITP who developed ICH before 60 years of age were retrospectively identified from 2005 to 2019 by 27 centers in China. For each case, 2 controls matched by the time of ITP diagnosis and the duration of ITP were provided by the same center. Multivariate analysis identified head trauma (OR = 3.216, 95%CI 1.296-7.979, P =.012), a platelet count ≤ 15,000/µL at the time of ITP diagnosis (OR = 1.679, 95%CI 1.044-2.698, P =.032) and severe/life-threatening bleeding (severe bleeding vs. mild bleeding, OR = 1.910, 95%CI 1.088-3.353, P =.024; life-threatening bleeding vs. mild bleeding, OR = 2.620, 95%CI 1.360-5.051, P =.004) as independent risk factors for ICH. Intraparenchymal hemorrhage (OR = 5.191, 95%CI 1.717-15.692, P =.004) and a history of severe bleeding (OR = 4.322, 95%CI 1.532-12.198, P =.006) were associated with the 30-day outcome of ICH. These findings may facilitate ICH risk stratification and outcome prediction in patients with ITP.


Asunto(s)
Hemorragias Intracraneales/etiología , Púrpura Trombocitopénica Idiopática/complicaciones , Femenino , Humanos , Hemorragias Intracraneales/patología , Masculino , Persona de Mediana Edad , Pronóstico , Factores de Riesgo , Resultado del Tratamiento
16.
Mol Genet Genomic Med ; 8(9): e1369, 2020 09.
Artículo en Inglés | MEDLINE | ID: mdl-32638549

RESUMEN

BACKGROUND: Despite targeted sequencing have identified several mutations for leukemia, there is still a limit of mutation screening for Chinese leukemia. Here, we used targeted next-generation sequencing for testing the mutation patterns of Chinese leukemia patients. METHODS: We performed targeted sequencing of 504 tumor-related genes in 109 leukemia samples to identify single-nucleotide variants (SNVs) and insertions and deletions (INDELs). Pathogenic variants were assessed based on the American College of Medical Genetics and Genomics (ACMG) guidelines. The functional impact of pathogenic genes was explored through gene ontology (GO), pathway analysis, and protein-protein interaction network in silico. RESULTS: We identified a total of 4,655 SNVs and 614 INDELs in 419 genes, in which PDE4DIP, NOTCH2, FANCA, BCR, and ROS1 emerged as the highly mutated genes. Of note, we were the first to demonstrate an association of PDE4DIP mutation and leukemia. Based on ACMG guidelines, 39 pathogenic and likely pathogenic mutations in 27 genes were found. GO annotation showed that the biological process including gland development, leukocyte differentiation, respiratory system development, myeloid leukocyte differentiation, mesenchymal to epithelial transition, and so on were involved. CONCLUSION: Our study provided a map of gene mutations in Chinese patients with leukemia and gave insights into the molecular pathogenesis of leukemia.


Asunto(s)
Sitios Genéticos , Mutación INDEL , Leucemia/genética , Polimorfismo de Nucleótido Simple , Proteínas Adaptadoras Transductoras de Señales/genética , Adulto , Anciano , Proteínas del Citoesqueleto/genética , Proteína del Grupo de Complementación A de la Anemia de Fanconi/genética , Femenino , Secuenciación de Nucleótidos de Alto Rendimiento , Humanos , Masculino , Persona de Mediana Edad , Proteínas Tirosina Quinasas/genética , Proteínas Proto-Oncogénicas/genética , Proteínas Proto-Oncogénicas c-bcr/genética , Receptor Notch2/genética , Análisis de Secuencia de ADN
17.
Respir Res ; 21(1): 86, 2020 Apr 15.
Artículo en Inglés | MEDLINE | ID: mdl-32295578

RESUMEN

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a complex pulmonary disease. Cytochrome P450 family 4 subfamily F member 2 (CYP4F2) belongs to cytochrome P450 superfamily of enzymes responsible for metabolism, its single nucleotide polymorphisms (SNPs) were reported to be involved in metabolism in the development of many diseases. The study aimed to assess the relation between CYP4F2 SNPs and COPD risk in the Hainan Han population. METHOD: We genotyped five SNPs in CYP4F2 in 313 cases and 508 controls by Agena MassARRAY assay. The association between CYP4F2 SNPs and COPD risk were assessed by χ2 test and genetic models. Besides, logistic regression analysis was introduced into the calculation for odds ratio (OR) and 95% confidence intervals (CIs). RESULTS: Allele model analysis indicated that rs3093203 A was significantly correlated with an increased risk of COPD. Also, rs3093193 G and rs3093110 G were associated with a reduced COPD risk. In the genetic models, we found that rs3093203 was related to an increased COPD risk, while rs3093193 and rs3093110 were related to a reduced risk of COPD. After gender stratification, rs3093203, rs3093193 and rs3093110 showed the association with COPD risk in males. With smoking stratification, rs3093144 was significantly associated with an increased risk of COPD in smokers. CYP4F2 SNPs were significantly associated with COPD risk. CONCLUSIONS: Our findings illustrated potential associations between CYP4F2 polymorphisms and COPD risk. However, large-scale and well-designed studies are needed to determine conclusively the association between the CYP4F2 SNPs and COPD risk.


Asunto(s)
Pueblo Asiatico/genética , Familia 4 del Citocromo P450/genética , Predisposición Genética a la Enfermedad/genética , Variación Genética/genética , Vigilancia de la Población , Enfermedad Pulmonar Obstructiva Crónica/genética , Anciano , Anciano de 80 o más Años , China/epidemiología , Femenino , Predisposición Genética a la Enfermedad/epidemiología , Humanos , Masculino , Persona de Mediana Edad , Polimorfismo de Nucleótido Simple/genética , Enfermedad Pulmonar Obstructiva Crónica/epidemiología , Distribución Aleatoria
18.
Arch Bronconeumol (Engl Ed) ; 56(11): 697-703, 2020 Nov.
Artículo en Inglés, Español | MEDLINE | ID: mdl-32224017

RESUMEN

INTRODUCTION: Cytochrome P450 (CYP) 2J2 is a major enzyme that controls epoxyeicosatrienoic acids biosynthesis, which may play a role in chronic obstructive pulmonary disease (COPD) development. In this study, we aimed to assess the influence of CYP2J2 polymorphisms with COPD susceptibility. MATERIAL AND METHODS: A case-control study enrolled 313 COPD cases and 508 controls was to investigate the association between CYP2J2 polymorphisms and COPD risk. Agena MassARRAY platform was used to genotype CYP2J2 polymorphisms. Odds ratios (OR) and 95% confidence intervals (CI) were calculated to evaluate the association between CYP2J2 polymorphisms and COPD risk. RESULTS: We observed rs11207535 (homozygote: OR=0.08, 95%CI=0.01-0.96, p=0.047; recessive: OR=0.08, 95%CI=0.01-0.94, p=0.044), rs10889159 (homozygote: OR=0.08, 95%CI=0.01-0.92, p=0.043; recessive: OR=0.08, 95%CI=0.01-0.90, p=0.040) and rs1155002 (heterozygote: OR=1.63, 95%CI=1.13-2.36, p=0.009; dominant: OR=1.64, 95%CI=1.15-2.35, p=0.006; additive: OR=1.45, 95%CI=1.09-1.92, p=0.011) were significantly associated with COPD risk. Allelic tests showed T allele of rs2280274 was related to a decreased risk of COPD and T allele of rs1155002 was associated with an increased COPD risk. Stratified analyses indicated the effects of CYP2J2 polymorphisms and COPD risk were dependent on gender and smoking status (p<0.05). Additionally, two haplotypes (Ars11207535Crs10889159Trs1155002 and Ars11207535Crs10889159Crs1155002) significantly decreased COPD risk. CONCLUSION: It suggested CYP2J2 polymorphisms were associated with COPD susceptibility in the Chinese Han population.


Asunto(s)
Predisposición Genética a la Enfermedad , Enfermedad Pulmonar Obstructiva Crónica , Estudios de Casos y Controles , China , Citocromo P-450 CYP2J2 , Sistema Enzimático del Citocromo P-450/genética , Humanos , Polimorfismo de Nucleótido Simple , Enfermedad Pulmonar Obstructiva Crónica/genética
19.
Photodiagnosis Photodyn Ther ; 30: 101731, 2020 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-32171880

RESUMEN

OBJECTIVE: To evaluate the clinical efficacy and safety of 5-aminolevulinic acid photodynamic therapy (ALA-PDT) combined with a carbon dioxide laser (CO2 laser + PDT) versus CO2 laser for the treatment of low-grade vaginal intraepithelial neoplasms (vaginal LSIL). METHODS: We recruited 40 patients with vaginal LSIL and persistent HR-HPV infection and divided these individuals into two groups. The CO2 laser + PDT group (20 patients) received one CO2 laser treatment and three treatments of ALA-PDT over a one-week interval. The CO2 laser group (20 patients) received up to three CO2 laser treatments. All patients were followed up at 1 month, 3 month, 6 month and 1 year. Hybrid capture HPV DNA assay and colposcopic biopsy were performed for both groups before treatment and during each of the follow-ups. Adverse effects were also assessed. RESULTS: The complete remission (CR) rates were 65 % (13/20) in the CO2 laser group and 85 % (17/20) in the CO2 laser + PDT group (p > 0.05). HR-HPV remission rates were 25 % (5/20) in the CO2 laser group and 95 % (19/20) in the CO2 laser + PDT group (p < 0.05) at one year after treatment. In the CO2 laser group, one patient experienced severe bleeding during treatment. Twelve patients had varying degrees of adhesions and vaginal scar stenosis. One patient underwent vaginal "dead angle" after repeated CO2 laser treatment. No severe adverse events or systemic side effects were observed in the CO2 + PDT group. CONCLUSION: Topical ALA-PDT combined with CO2 laser is an effective, safe, and well-tolerated treatment for vaginal LSIL and HR-HPV infections.


Asunto(s)
Carcinoma in Situ , Terapia por Láser , Láseres de Gas , Fotoquimioterapia , Ácido Aminolevulínico/uso terapéutico , Carcinoma in Situ/tratamiento farmacológico , Femenino , Humanos , Láseres de Gas/uso terapéutico , Fotoquimioterapia/métodos , Fármacos Fotosensibilizantes/uso terapéutico , Estudios Retrospectivos
20.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 28(1): 130-135, 2020 Feb.
Artículo en Chino | MEDLINE | ID: mdl-32027265

RESUMEN

OBJECTIVE: To study the expression level of TGFß1 and VEGF gene in patients with acute myeloid leukemia (AML) and its clinical prognostic value. METHODS: Seventy-eight AML patients treated in our hospital from July 2016 to September 2018 were selected. After isolation of bone marrow mononuclear cells from the patients, the levels of TGFß1 and VEGF genes were detected by RT-PCR, and the correlation of TGFß1 with VEGF genes and clinical characteristics of AML patients was analyzed. OS and EFS of the patients were evaluated by Kaplan-Meier, and Cox risk ratio model was used to analyze the prognostic risk factors of AML patients. RESULTS: The relative expression level of TGFß1 gene in AML patients was 0.32±0.04, which was significantly lower than that in control group (P<005). The relative expression level of vascular endothelial growth factor(VEGF) gene in the patients was 2.65±0.15, which was significantly higher than that in the control group (P<0.05). The levels of TGFß1 and VEGF genes significantly correlated with leukocyte count, hemoglobin, platelet and peripheral blast levels in AML patients (P<0.05). The level of TGFß1 in AML patients with complete remission was higher than that in patients with partial remission or non-remission (P<0.05). The level of TGFß1 in AML patients with partial remission was significantly higher than that in patients with non-remission (P<0.05). The level of VEGF in AML patients with complete remission was lower than at in patients with partial remission or non-remission (P<0.05). The level of VEGF in AML patients with partial remission was significantly lower than that in patients with non-remission (P<0.05). Kaplan-Meier survival analysis showed that OS and DFS in AML patients with high expression of TGFß1 were better than those in patients with low expression of TGFß1 (P<0.05), OS and DFS in AML patients with low expression of VEGF were better than those in patients with high expression of VEGF (P<0.05). Multivariate Cox regression analysis showed that platelet, TGFß1 and VEGF gene were independent influencing factors of OS (P<0.05). Leukocyte, TGFß1 and VEGF gene were independent influencing factors of DFS (P<0.05). CONCLUSION: Decreased expression of TGFß1 and increased expression of VEGF gene in AML patients closely relate to the poor prognosis of AML patients, which can provide reference for improving clinical efficacy of AML patients.


Asunto(s)
Leucemia Mieloide Aguda , Factor de Crecimiento Transformador beta1/genética , Factor A de Crecimiento Endotelial Vascular/genética , Humanos , Estimación de Kaplan-Meier , Leucemia Mieloide Aguda/genética , Pronóstico , Inducción de Remisión
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