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1.
World J Clin Cases ; 10(14): 4480-4493, 2022 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-35663077

RESUMO

BACKGROUND: Hepatitis C virus (HCV) causes a large number of infections worldwide. New infections seem to be increasing according to a report of the World Health Organization in 2015. Although direct-acting antivirals are quite effective for most genotypes of the HCV, some genotypes fail to respond. Therefore, the trend of genotype distribution is vital to better control the development of this infection. AIM: To analyze the distribution and trends of the HCV genotype before and after the emergence of direct-acting antivirals in China. METHODS: We searched all literature published in five electronic databases-China National Knowledge Infrastructure, Wan Fang Data, VIP Chinese Journal Database, Chinese Biomedical Literature Service System, and PubMed-from January 1, 2010 to December 31, 2020. The search strategy combined medical subject headings and free-text terms, including "hepatitis C virus" or "HCV" and "genotype" or "subtype" and "China" or "Chinese". Additional relevant articles were searched by manual selection. Data were extracted to build a database. All of the data were totaled according to regions, periods, routes of transmission, and sexes. The percentages in various stratifications were calculated. RESULTS: There were 76110 samples from 30 provinces included in the study. Genotype 1 (G1) accounted for 58.2% of cases nationwide, followed by G2, G6, G3b, G3a, unclassified and mixed infections (17.5%, 7.8%, 6.4%, 4.9%, 1.8%, and 1.2%, respectively). The constitution of genotype varied among different regions, with G6 and G3b being more common in the south and southwest, respectively (28.1%, 15.4%). The past ten years have witnessed a decrease in G1 and G2 and an increase in G3 and G6 in almost all regions. The drug-use population had the most abundant genotypes, with G6 ranking first (33.3%), followed by G1 and G3b (23.4%, 18.5%). CONCLUSION: G3 and G6 pose a new challenge for HCV infection. This study revealed the distribution of HCV genotypes in China over the past 10 years, providing information for HCV management strategies.

2.
Front Nutr ; 9: 899829, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35747264

RESUMO

Clinical cases and animal experiments show that high-fat (HF) diet is involved in inflammatory bowel disease (IBD), but the specific mechanism is not fully clear. A close association between long-term HF-induced obesity and IBD has been well-documented. However, there has been limited evaluation of the impact of short-term HF feeding on the risk of intestinal inflammation, particularly on the risk of disrupted metabolic homeostasis. In this study, we analyzed the metabolic profile and tested the vulnerability of 2,4,6-trinitrobenzenesulfonic acid (TNBS)-induced colitis after short-term HF feeding in mice. The results showed that compared with the control diet (CD), the fatty acid (FA), amino acid (AA), and bile acid (BA) metabolisms of mice in the HF group were significantly changed. HF-fed mice showed an increase in the content of saturated and unsaturated FAs and a decrease in the content of tryptophan (Trp). Furthermore, the disturbed spatial distribution of taurocholic acid (TCA) in the ileum and colon was identified in the HF group using matrix-assisted laser desorption/ionization-mass spectrometry imaging (MALDI-MSI). After HF priming, mice on TNBS induction were subjected to more severe colonic ulceration and histological damage compared with their CD counterparts. In addition, TNBS enema induced higher gene expressions of mucosal pro-inflammatory cytokines under HF priming conditions. Overall, our results show that HF may promote colitis by disturbing lipid, AA, and BA metabolic homeostasis and inflammatory gene expressions.

3.
Ther Adv Hematol ; 13: 20406207221095226, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35510211

RESUMO

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.

4.
Front Nutr ; 9: 858603, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35433798

RESUMO

Changes in overall bile acid (BA) levels and specific BA metabolites are involved in metabolic diseases, gastrointestinal, and liver cancer. BAs have become established as important signaling molecules that enable fine-tuned inter-tissue communication within the enterohepatic circulation. The liver, BAs site of production, displayed physiological and functional zonal differences in the periportal zone versus the centrilobular zone. In addition, BA metabolism shows regional differences in the intestinal tract. However, there is no available method to detect the spatial distribution and molecular profiling of BAs within the enterohepatic circulation. Herein, we demonstrated the application in mass spectrometry imaging (MSI) with a high spatial resolution (3 µm) plus mass accuracy matrix-assisted laser desorption ionization (MALDI) to imaging BAs and N-1-naphthylphthalamic acid (NPA). Our results could clearly determine the zonation patterns and regional difference characteristics of BAs on mouse liver, ileum, and colon tissue sections, and the relative content of BAs based on NPA could also be ascertained. In conclusion, our method promoted the accessibility of spatial localization and quantitative study of BAs on gastrointestinal tissue sections and demonstrated that MALDI-MSI was a valuable tool to investigate and locate several BA molecules in different tissue types leading to a better understanding of the role of BAs behind the gastrointestinal diseases.

5.
Biomed Environ Sci ; 34(5): 364-371, 2021 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-34059173

RESUMO

OBJECTIVE: To study the polymorphism in P66 and its human B-cell epitopes of Borrelia burgdorferi strains in China. METHODS: Polymerase chain reaction (PCR) and sequencing were used to obtain the P66 sequences of 59 Chinese B. burgdorferi. Then the sequences were analyzed by MEGA 5.10 software and compared with the human B-cell epitope sequences from the Immune Epitope Database (IEDB) based on the reference strain of each genotype. RESULTS: Results showed that genetic and amino acid diversity presented in the 66 kD protein of all 59 Chinese strains, especially in Borrelia garinii ( B.g) and Borrelia afzelii ( B.a) strains. B.g strains were divided into three subclusters and two scattered strains JC1-7 and JC2-2 according to the amino acid sequences of P66. The P66 sequences of 15 Xinjiang strains represented by XI91-12 in the B.g subcluster 1, changed from CAA to TAA codon at 508aa position, resulting in early termination. Bases A and C were inserted at sequence position 1 523 bp of strains FP1, LB20, LB21, and SZ21 in the B.a genotype, which resulted to early termination at position 511 aa. G base was inserted at 438 bp of LIP94-11 strain, which led to early termination at position 172 aa. CONCLUSION: In P66 of 59 Chinese strains, polymorphisms were widely distributed. More importantly, the P66 amino acid sequences of B.g strains had a certain regional character. One of the characteristics of Xinjiang B.g isolates might be the variation at the 508aa location in 15 Xinjiang B.g strains, which may be related to the strains' pathogenicity in this area.


Assuntos
Proteínas de Bactérias/genética , Borrelia burgdorferi/genética , Epitopos de Linfócito B/genética , Polimorfismo Genético , Porinas/genética , Borrelia burgdorferi/classificação , China , Análise por Conglomerados , Marcadores Genéticos , Genótipo , Humanos , Mutação , Reação em Cadeia da Polimerase
6.
Bone Marrow Transplant ; 56(9): 2097-2107, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-33846561

RESUMO

Diffuse alveolar haemorrhage (DAH) is a life-threatening pulmonary complication occurring after allogeneic haematopoietic stem cell transplantation (allo-HSCT) without an explicit aetiology or a standard treatment. This study aimed to explore the occurrence and prognosis of DAH after allo-HSCT, in addition to comparing discrepancies in the incidence, clinical characteristics and outcomes of DAH between patients undergoing haploidentical HSCT (HID-HSCT) and matched related donor HSCT (MRD-HSCT). We retrospectively evaluated 92 consecutive patients among 3987 patients with a confirmed diagnosis of DAH following allo-HSCT (HID: 71 patients, MRD: 21 patients). The incidence of DAH after allo-HSCT was 2.3%, 2.4% after HID-HSCT and 2.0% after MRD-HSCT (P = 0.501). The prognosis of patients with DAH after transplantation is extremely poor. The duration of DAH was 7.5 days (range, 1-48 days). The probabilities of overall survival (OS) were significantly different between patients with and without DAH within 2 years after transplantation (P < 0.001). According to the Cox regression analysis, a significant independent risk factor for the occurrence of DAH was delayed platelet engraftment (P < 0.001), and a high D-dimer level (>500 ng/ml) was a significant risk factor for the poor prognosis of DAH. HID-HSCT is similar to MRD-HSCT in terms of the outcomes of DAH.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Hemorragia/etiologia , Humanos , Estudos Retrospectivos , Fatores de Risco , Doadores de Tecidos
7.
Am J Hematol ; 96(5): 561-570, 2021 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-33606900

RESUMO

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.


Assuntos
Hemorragia Pós-Parto/etiologia , Complicações Hematológicas na Gravidez , Púrpura Trombocitopênica Idiopática/complicações , Adulto , Área Sob a Curva , China/epidemiologia , Estudos de Coortes , Suscetibilidade a Doenças , Registros Eletrônicos de Saúde , Feminino , Seguimentos , Previsões , Geografia Médica , Humanos , Imunoglobulinas Intravenosas/uso terapêutico , Imunossupressores/uso terapêutico , Recém-Nascido , Modelos Logísticos , Modelos Teóricos , Hemorragia Pós-Parto/epidemiologia , Hemorragia Pós-Parto/prevenção & controle , Prednisona/uso terapêutico , Gravidez , Resultado da Gravidez , Prognóstico , Púrpura Trombocitopênica Idiopática/tratamento farmacológico , Púrpura Trombocitopênica Idiopática/terapia , Estudos Retrospectivos , Fatores de Risco , Centros de Atenção Terciária/estatística & dados numéricos
8.
Chin Med J (Engl) ; 134(5): 532-538, 2021 Feb 08.
Artigo em Inglês | MEDLINE | ID: mdl-33560666

RESUMO

BACKGROUND: Models to predict mortality in trauma play an important role in outcome prediction and severity adjustment, which informs trauma quality assessment and research. Hospitals in China typically use the International Classification of Diseases, Tenth Revision, Clinical Modification (ICD-10-CM) to describe injury. However, there is no suitable prediction model for China. This study attempts to develop a new mortality prediction model based on the ICD-10-CM lexicon and a Chinese database. METHODS: This retrospective study extracted the data of all trauma patients admitted to the Beijing Red Cross Emergency Center, from January 2012 to July 2018 (n = 40,205). We used relevant predictive variables to establish a prediction model following logistic regression analysis. The performance of the model was assessed based on discrimination and calibration. The bootstrapping method was used for internal validation and adjustment of model performance. RESULTS: Sex, age, new region-severity codes, comorbidities, traumatic shock, and coma were finally included in the new model as key predictors of mortality. Among them, coma and traumatic shock had the highest scores in the model. The discrimination and calibration of this model were significant, and the internal validation performance was good. The values of the area under the curve and Brier score for the new model were 0.9640 and 0.0177, respectively; after adjustment of the bootstrapping method, they were 0.9630 and 0.0178, respectively. CONCLUSIONS: The new model (China Mortality Prediction Model in Trauma based on the ICD-10-CM lexicon) showed great discrimination and calibration, and performed well in internal validation; it should be further verified externally.


Assuntos
Classificação Internacional de Doenças , Ferimentos e Lesões , Pequim , China , Humanos , Valor Preditivo dos Testes , Estudos Retrospectivos
9.
Platelets ; 32(5): 633-641, 2021 Jul 04.
Artigo em Inglês | MEDLINE | ID: mdl-32614630

RESUMO

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.


Assuntos
Hemorragias Intracranianas/etiologia , Púrpura Trombocitopênica Idiopática/complicações , Feminino , Humanos , Hemorragias Intracranianas/patologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Fatores de Risco , Resultado do Tratamento
10.
Blood Adv ; 4(22): 5846-5857, 2020 11 24.
Artigo em Inglês | MEDLINE | ID: mdl-33232474

RESUMO

Infection is one of the primary causes of death from immune thrombocytopenia (ITP), and the lungs are the most common site of infection. We identified the factors associated with hospitalization for community-acquired pneumonia (CAP) in nonsplenectomized adults with ITP and established the [corrected] (ACPA) prediction model to predict the incidence of hospitalization for CAP. This was a retrospective study of nonsplenectomized adult patients with ITP from 10 large medical centers in China. The derivation cohort included 145 ITP inpatients with CAP and 1360 inpatients without CAP from 5 medical centers, and the validation cohort included the remaining 63 ITP inpatients with CAP and 526 inpatients without CAP from the other 5 centers. The 4-item ACPA model, which included age, Charlson Comorbidity Index score, initial platelet count, and initial absolute lymphocyte count, was established by multivariable analysis of the derivation cohort. Internal and external validation were conducted to assess the performance of the model. The ACPA model had an area under the curve of 0.853 (95% confidence interval [CI], 0.818-0.889) in the derivation cohort and 0.862 (95% CI, 0.807-0.916) in the validation cohort, which indicated the good discrimination power of the model. Calibration plots showed high agreement between the estimated and observed probabilities. Decision curve analysis indicated that ITP patients could benefit from the clinical application of the ACPA model. To summarize, the ACPA model was developed and validated to predict the occurrence of hospitalization for CAP, which might help identify ITP patients with a high risk of hospitalization for CAP.


Assuntos
Pneumonia , Púrpura Trombocitopênica Idiopática , Adulto , China , Hospitalização , Humanos , Pneumonia/epidemiologia , Púrpura Trombocitopênica Idiopática/epidemiologia , Estudos Retrospectivos , Fatores de Risco
11.
Chin Med J (Engl) ; 133(19): 2274-2280, 2020 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-32925291

RESUMO

BACKGROUND: After radical hysterectomy for cervical cancer, the most common complication is lower urinary tract symptoms. Post-operatively, bladder capacity can alter bladder function for a prolonged period. This study aimed to identify factors affecting bladder storage function. METHODS: A multicenter, retrospective cohort study was conducted. Information of patients with stages IA2 to IIB cervical cancer with urodynamic study results were retrospectively collected from nine hospitals between June 2013 and June 2018 according to the inclusion criteria. Demographic, surgical, and oncological data were collected. The univariate and multivariate logistic regression was used to identify clinical factors associated with bladder storage function. RESULTS: Two hundred and three patients with cervical cancer had urodynamic testing post-operatively. Ninety-five (46.8%) patients were diagnosed with stress urinary incontinence (SUI). The incidence of low bladder compliance (LBC) was 23.2%. Twenty-seven (13.3%) patients showed detrusor overactivity (DO). Fifty-seven patients (28.1%) presented with a decreased maximum cystometric capacity (DMCC). The probability of composite bladder storage dysfunction was 68.0%. Multivariate analysis confirmed that laparoscopy represents a protective factor for SUI with an odds ratio of 0.498 (P = 0.034). Patients who underwent a nerve-sparing procedure were less odds to experience SUI (P = 0.014). A significant positive correlation between LBC and DO was observed (P < 0.001). A greater length of the resected vagina and chemoradiotherapy were common risk factors for LBC and DO, while radiotherapy exerted a stronger effect than chemotherapy. Additionally, patients who received chemoradiotherapy frequently developed a DMCC. The follow-up time was not correlated with bladder storage function. CONCLUSION: A nerve-sparing procedure without longer resected vagina is recommended for protecting the bladder storage function.


Assuntos
Urodinâmica , Neoplasias do Colo do Útero , Feminino , Humanos , Histerectomia/efeitos adversos , Estudos Retrospectivos , Bexiga Urinária/cirurgia , Neoplasias do Colo do Útero/cirurgia
12.
Ann Hematol ; 99(11): 2659-2670, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32734550

RESUMO

Cytomegalovirus (CMV) can cause end-organ diseases including pneumonia, gastroenteritis, retinitis, and encephalitis in hematopoietic stem cell transplantation recipients. Potential differences among different CMV diseases remain uncertain. This study aimed to compare the clinical characteristics, risk factors, and mortality among different CMV diseases. A retrospective nested case-control study was performed based on a cohort of 3862 patients who underwent haploidentical hematopoietic stem cell transplantation at a single-center. CMV diseases occurred in 113 (2.92%) of 3862 haplo-HSCT recipients, including probable CMV pneumonia (CMVP, n = 34), proven CMV gastroenteritis (CMVG, n = 34), CMV retinitis (CMVR, n = 31), probable CMV encephalitis (CMVE, n = 7), and disseminated CMV disease (Di-CMVD, n = 7). Most (91.2%) cases of CMVG developed within 100 days, while most (90.3%) cases of CMVR were late onset. Refractory CMV infection and CMV viral load at different levels were associated with an increased risk of CMVP, CMVG, and CMVR. Compared with patients without CMV diseases, significantly higher non-relapse mortality at 1 year after transplantation was observed in patients with CMVP and CMVR, rather than CMVG. Patients with CMVP, Di-CMVD, and CMVE had higher overall mortality after diagnosis than that of patients with CMVG and CMVR (61.7%, 57.1%, 40.0% vs 27.7%, 18.6%, P = 0.001). In conclusion, the onset time, viral dynamics, and mortality differ among different CMV diseases. The mortality of CMV diseases remains high, especially for CMVP, Di-CMVD, and CMVE.


Assuntos
Infecções por Citomegalovirus , Citomegalovirus , Transplante de Células-Tronco Hematopoéticas , Adolescente , Adulto , Aloenxertos , Criança , Pré-Escolar , Infecções por Citomegalovirus/diagnóstico , Infecções por Citomegalovirus/etiologia , Infecções por Citomegalovirus/mortalidade , Infecções por Citomegalovirus/terapia , Intervalo Livre de Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Taxa de Sobrevida , Fatores de Tempo
13.
Br J Haematol ; 191(2): 269-281, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32452543

RESUMO

Immune-mediated thrombotic thrombocytopenic purpura (iTTP) is a rare and life-threatening haematological emergency. Although therapeutic plasma exchange together with corticosteroids achieve successful outcomes, a considerable number of patients remain refractory to this treatment and require early initiation of intensive therapy. However, a method for the early identification of refractory iTTP is not available. To develop and validate a model for predicting the probability of refractory iTTP, a cohort of 265 consecutive iTTP patients from 17 large medical centres was retrospectively identified. The derivation cohort included 94 patients from 11 medical centres. For the validation cohort, we included 40 patients from the other six medical centres using geographical validation. An easy-to-use risk score system was generated, and its performance was assessed using internal and external validation cohorts. In the multivariable logistic analysis of the derivation cohort, three candidate predictors were entered into the final prediction model: age, haemoglobin and creatinine. The prediction model had an area under the curve of 0.886 (95% CI: 0.679-0.974) in the internal validation cohort and 0.862 (95% CI: 0.625-0.999) in the external validation cohort. The calibration plots showed a high agreement between the predicted and observed outcomes. In conclusion, we developed and validated a highly accurate prediction model for the early identification of refractory iTTP. It has the potential to guide tailored therapy and is a step towards more personalized medicine.


Assuntos
Creatinina/sangue , Bases de Dados Factuais , Hemoglobinas/metabolismo , Modelos Biológicos , Púrpura Trombocitopênica Trombótica/sangue , Adulto , Fatores Etários , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Medição de Risco , Fatores de Risco
14.
JHEP Rep ; 2(2): 100093, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32195457

RESUMO

BACKGROUND & AIMS: Metabolism supports cell proliferation and growth. Surprisingly, the tumor suppressor miR-22 is induced by metabolic stimulators like bile acids. Thus, this study examines whether miR-22 could be a metabolic silencer. METHODS: The relationship between miR-22 and the expression of fibroblast growth factor 21 (FGF21) and its receptor FGFR1 was studied in cells and fatty livers obtained from patients and mouse models. We evaluated the effect of an miR-22 inhibitor alone and in combination with obeticholic acid (OCA) for the treatment of steatosis. RESULTS: The levels of miR-22 were inversely correlated with those of FGF21, FGFR1, and PGC1α in human and mouse fatty livers, suggesting that hepatic miR-22 acts as a metabolic silencer. Indeed, miR-22 reduced FGFR1 by direct targeting and decreased FGF21 by reducing the recruitment of PPARα and PGC1α to their binding motifs. In contrast, an miR-22 inhibitor increases hepatic FGF21 and FGFR1, leading to AMPK and ERK1/2 activation, which was effective in treating alcoholic steatosis in mouse models. The farnesoid x receptor-agonist OCA induced FGF21 and FGFR1, as well as their inhibitor miR-22. An miR-22 inhibitor and OCA were effective in treating diet-induced steatosis, both alone and in combination. The combined treatment was the most effective at improving insulin sensitivity, releasing glucagon-like peptide 1, and reducing hepatic triglyceride in obese mice. CONCLUSION: The simultaneous induction of miR-22, FGF21 and FGFR1 by metabolic stimulators may maintain FGF21 homeostasis and restrict ERK1/2 activation. Reducing miR-22 enhances hepatic FGF21 and activates AMPK, which could be a novel approach to treat steatosis and insulin resistance. LAY SUMMARY: This study examines the metabolic role of a tumor suppressor, miR-22, that can be induced by metabolic stimulators such as bile acids. Our novel data revealed that the metabolic silencing effect of miR-22 occurs as a result of reductions in metabolic stimulators, which likely contribute to the development of fatty liver. Consistent with this finding, an miR-22 inhibitor effectively reversed both alcohol- and diet-induced fatty liver; miR-22 inhibition is a promising therapeutic option which could be used in combination with obeticholic acid.

15.
Medicine (Baltimore) ; 99(13): e19654, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32221092

RESUMO

BACKGROUND: Endovascular coiling and surgical clipping are routinely used to treat unruptured cerebral aneurysms (UCAs). However, the evidence to support the efficacy of these approaches is limited. We aimed to analyze the efficacy of endovascular coiling compared with surgical clipping in patients with UCAs. METHOD: A systematic search of 4 databases was conducted to identify comparative articles involving endovascular coiling and surgical clipping in patients with UCAs. We conducted a meta-analysis using the random-effects model when I> 50%. Otherwise, a meta-analysis using the fixed-effects model was performed. RESULTS: Our results showed that endovascular coiling was associated with a shorter length of stay (WMD: -4.14, 95% CI: (-5.75, -2.531), P < .001) and a lower incidence of short-term complications compared with surgical clipping (OR: 0.518; 95% CI (0.433, 0.621); P < .001), which seems to be a result of ischemia complications (OR: 0.423; 95% CI (0.317, 0.564); P < .001). However, surgical clipping showed a higher rate of complete occlusion after surgery, in both short-term (OR: 0.179, 95% CI (0.064, 0.499), P = .001) and 1-year follow-ups (OR: 0.307, 95% CI (0.146, 0.646), P = .002), and a lower rate of short-term retreatment (OR: 0.307, 95% CI (0.146, 0.646), P = .002). Meanwhile, there was no significant difference in postoperative death, bleeding, and modified Rankin Scale (mRS) > 2 between the 2 groups. CONCLUSIONS: The latest evidence illustrates that surgical clipping resulted in lower retreatment rates and was associated with a higher incidence of complete occlusion, while endovascular coiling was associated with shorter LOS and a lower rate of complications, especially ischemia.


Assuntos
Procedimentos Endovasculares/métodos , Aneurisma Intracraniano/cirurgia , Procedimentos Neurocirúrgicos/métodos , Procedimentos Endovasculares/efeitos adversos , Mortalidade Hospitalar , Humanos , Aneurisma Intracraniano/mortalidade , Tempo de Internação , Procedimentos Neurocirúrgicos/efeitos adversos , Complicações Pós-Operatórias/epidemiologia , Reoperação/estatística & dados numéricos
16.
Soft Matter ; 16(4): 1029-1033, 2020 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-31854429

RESUMO

A novel approach for the detection and separation of toxic ions was successfully developed via the introduction of competitive reactions into a long-alkyl-chained acylhydrazone-based coumarin supramolecular polymer, chemosensor OGC (3%, n-BuOH/H2O), which showed sequential detection and separation of CN-, Fe3+ and S2-, Ag+ in the gel state with high selectivity and sensitivity. Moreover, the ion-responsive films were prepared for the convenient and continuous detection of CN-, Fe3+ and S2-, Ag+ in water solution.

17.
World Neurosurg ; 135: e598-e609, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31870823

RESUMO

BACKGROUND: Dual and single antiplatelet therapies are routinely used in carotid artery endarterectomy (CEA). However, the efficacy and safety of these therapies are controversial. The present study aimed to comprehensively compare the clinical outcomes between dual and single antiplatelet therapies in CEA. METHODS: This study retrieved available academic studies evaluating the complications related to antiplatelet therapy between dual and single antiplatelet therapies in CEA from the databases of ScienceDirect, the Cochrane Library, EMBASE, and PubMed. References to previous reviews and related clinical trials were manually checked to retrieve potential literature that was not included in our electronic search results. RESULTS: A total of 10 articles (1 randomized controlled trial, 9 non-randomized controlled trials) were included in the study. The overall number of patients in the dual antiplatelet group was 14,280, and the number of patients in the single antiplatelet group was 125,850. The results revealed that the single antiplatelet group had a lower incidence of 30-day death (rate difference [RD] 0.002; 95% confidence interval [CI] 0.000-0.003; P = 0.014), neck hematoma (odds ratio [OR] 2.120; 95% CI 1.431-3.142; P < 0.001), myocardial infarction (RD 0.004; 95% CI 0.001-0.007; P = 0.003), and major bleeding (RD 0.005; 95% CI 0.002-0.008; P < 0.001). Meanwhile, the single antiplatelet group was associated with a shorter operation time (weighted mean difference 4.000; 95% CI= 2.564-5.436; P < 0.001). However, there was no significant difference in the rate of postoperative transient ischemic attack (P = 0.215), stroke (P = 0.130), or length of stay (P = 0.563). CONCLUSIONS: Based on current evidence, using single antiplatelet therapy in CEA may reduce operation time and the incidences of 30-day death, neck hematoma, major bleeding, and myocardial infarction without increasing the risks of transient ischemic attack, stroke, or a longer operation time.


Assuntos
Endarterectomia das Carótidas/efeitos adversos , Ataque Isquêmico Transitório/cirurgia , Inibidores da Agregação Plaquetária/efeitos adversos , Acidente Vascular Cerebral/cirurgia , Idoso , Métodos Epidemiológicos , Feminino , Humanos , Tempo de Internação/estatística & dados numéricos , Masculino , Duração da Cirurgia , Resultado do Tratamento
18.
Blood Adv ; 3(21): 3406-3418, 2019 11 12.
Artigo em Inglês | MEDLINE | ID: mdl-31714962

RESUMO

Thrombocytopenia is associated with life-threatening bleeding and is common in myelodysplastic syndromes (MDS). Robust molecular prognostic biomarkers need to be developed to improve clinical decision making for patients with MDS with thrombocytopenia. Wilms tumor 1 (WT1) and preferentially expressed antigen in melanoma (PRAME) are promising immunogenic antigen candidates for immunotherapy, and their clinical effects on patients with MDS with thrombocytopenia are still not well understood. We performed a multicenter observational study of adult patients with MDS with thrombocytopenia from 7 different tertiary medical centers in China. We examined bone marrow samples collected at diagnosis for WT1 and PRAME transcript levels and then analyzed their prognostic effect for patients with MDS with thrombocytopenia. In total, we enrolled 1110 patients diagnosed with MDS with thrombocytopenia. Overexpression of WT1 and PRAME was associated with elevated blast percentage, worse cytogenetics, and higher Revised International Prognostic Scoring System (IPSS-R) risk. Further, both WT1 and PRAME overexpression were independent poor prognostic factors for acute myeloid leukemia evolution, overall survival, and progression-free survival. Together, the 2 genes overexpression identified a population of patients with MDS with substantially worse survival. On the basis of WT1 and PRAME transcript levels, patients with MDS with IPSS-R low risk were classified into 2 significantly divergent prognostic risk groups: a low-favorable group and a low-adverse group. The low-adverse group had survival similar to that of patients in the intermediate-risk group. Our study demonstrates that the evaluation of WT1/PRAME transcript analysis may improve the prognostication precision and better risk-stratify the patients.


Assuntos
Antígenos de Neoplasias/genética , Expressão Gênica , Síndromes Mielodisplásicas/diagnóstico , Síndromes Mielodisplásicas/genética , Trombocitopenia/diagnóstico , Proteínas WT1/genética , Adulto , Idoso , Algoritmos , Biomarcadores , Transformação Celular Neoplásica/genética , Terapia Combinada , Gerenciamento Clínico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Síndromes Mielodisplásicas/complicações , Síndromes Mielodisplásicas/terapia , Prognóstico , Estudos Retrospectivos , Análise de Sobrevida , Trombocitopenia/etiologia , Resultado do Tratamento
19.
FASEB J ; 33(2): 2314-2326, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30252536

RESUMO

This study investigates the mechanism and consequences of microRNA-22 ( miR-22) induction. Our data revealed for the first time that retinoic acid (RA) and histone deacetylase (HDAC) inhibitors, including short-chain fatty acids and suberanilohydroxamic acid (SAHA), could individually or in combination induce miR-22. This induction was mediated via RA receptor ß (RARß) binding to a direct repeat 5 (DR5) motif. In addition, we uncovered HDAC1 as a novel miR-22 target. In an miR-22-dependent manner, HDAC inhibitors and RA reduced HDAC1, HDAC4, and sirtuin 1 (SIRT1), which were involved in chromatin remodeling of the RARß and nerve growth factor IB ( NUR77). Thus, HDAC inhibitors and RA-induced miR-22 resulted in simultaneous induction of cytoplasmic RARß and NUR77, leading to apoptosis of colon cancer cells. In mice, miR-22 and its inducers inhibited the growth of xenograft colon cancer. Moreover, tumor size reduction was accompanied by elevated miR-22, NUR77, and RARß and by reduced HDACs. In human colon polyps and adenocarcinomas, miR-22 and RARß were consistently reduced, which was associated with elevated HDAC1, HDAC4, and SIRT1 in colon adenocarcinomas. Results from this study revealed a novel anticancer mechanism of RARß via miR-22 induction to epigenetically regulate itself and NUR77, providing a promising cancer treatment modality using miR-22 and its inducers.-Hu, Y., French, S. W., Chau, T., Liu, H.-X., Sheng, L., Wei, F., Stondell, J., Garcia, J. C., Du, Y., Bowlus, C. L., Wan, Y.-J. Y. RARß acts as both an upstream regulator and downstream effector of miR-22, which epigenetically regulates NUR77 to induce apoptosis of colon cancer cells.


Assuntos
Adenocarcinoma/patologia , Apoptose/genética , Neoplasias do Colo/patologia , Epigênese Genética/genética , MicroRNAs/genética , Membro 1 do Grupo A da Subfamília 4 de Receptores Nucleares/genética , Receptores do Ácido Retinoico/metabolismo , Animais , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Inativação Gênica , Xenoenxertos , Histona Desacetilase 1/genética , Inibidores de Histona Desacetilases/farmacologia , Humanos , Camundongos , Receptores do Ácido Retinoico/genética , Transdução de Sinais , Tretinoína/metabolismo
20.
BMJ Open ; 8(12): e023347, 2018 12 04.
Artigo em Inglês | MEDLINE | ID: mdl-30518584

RESUMO

INTRODUCTION: The implementation of first aid processes for patients with trauma in China faces significant challenges. These challenges include long response times of prehospital first aid services, lack of information exchange between prehospital first aid services and in-hospital emergency services, lack of a professional rescue team in the majority of hospitals, and lack of standardised training for prehospital and in-hospital emergency personnel. The purpose of the trial is to guide the establishment of an urban trauma treatment system in China, highlight the construction of a trauma treatment system tailored to the Chinese context and improve levels of medical treatment by selecting approximately 100 counties across China as pilots to establish a regional trauma treatment system. METHODS AND ANALYSIS: A cluster-randomised controlled trial will be performed in 98 county-level research institutes. Included research institutes will be randomised into an experimental group and a control group. Patients in both experimental and control groups will receive basic treatments. A trauma treatment team will be established in the experimental group. The primary outcome measure is in-hospital mortality rate of patients. The secondary outcome measures include mortality rate of patients within 30 days after trauma attack and within 30 days after discharge, the time between arrival in the institution and receiving consultation, and the time from admission to the start of surgery. The effects of establishment of trauma treatment teams on the treatment of severe trauma will be evaluated in all counties. ETHICS AND DISSEMINATION: The procedures have been approved by The Medical Ethics Committee of Peking University People's Hospital (No.2017PHB098-01) and conform to the Declaration of Helsinki. Data will be collected and analysed in accordance with participant privacy laws and regulations. Results will be disseminated through policy briefs, workshops, peer-reviewed publications and conferences. TRIAL REGISTRATION NUMBER: NCT03363880; Pre-results.


Assuntos
Primeiros Socorros , Equipe de Assistência ao Paciente/organização & administração , Regionalização da Saúde/organização & administração , Ferimentos e Lesões/cirurgia , China , Análise por Conglomerados , Acesso aos Serviços de Saúde/organização & administração , Mortalidade Hospitalar , Humanos , Taxa de Sobrevida , Estudos de Tempo e Movimento , Ferimentos e Lesões/mortalidade
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