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PURPOSE: To investigate the association between proton pump inhibitors (PPIs) administration during hospitalization and mortality and length of stay in critically ill pediatric patients. MATERIALS AND METHODS: This is a retrospective observational cohort study on pediatric ICU patients (0 to 18 years). Propensity score matching (PSM), Kaplan-Meier curves, Cox proportional hazards model and Linear regression model was applied for assessing the effects of PPIs on mortality and other outcomes during hospitalization. RESULTS: A total of 2269 pediatric ICU patients were included, involving 1378 omeprazole (OME) users and 891 non-OME users. The results showed significant association between OME exposure and decreased ICU stay (ß -0.042; 95% CI -0.073--0.011; P = 0.008) but prolonged non-ICU hospital stay (ß 0.121; 95% CI 0.097-0.155; P = 0.040). No statistical significance was observed between OME exposure and reduced mortality, but the OME group had a slightly decreased tendency in 28-day mortality (HR 0.701; 95% CI 0.418-1.176) and in-hospital mortality (HR 0.726; 95% CI 0.419-1.257). Furthermore, subgroup analyses revealed that the decreased tendency of mortality were more obvious in patients less than 1 year old compared with older pediatric patients, although not statistically significant. In addition, we also observed that OME exposure was significantly associated with reduced mortality of general ICU subgroup. CONCLUSIONS: This study provided a sign that PPIs used only in the ICU, rather than throughout hospital stay, might provide more benefit for critically ill pediatric patients. Additionally, younger pediatric patients might gain relatively more benefit than older children when receiving PPIs.
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Estado Terminal , Omeprazol , Humanos , Criança , Adolescente , Lactente , Tempo de Internação , Estudos de Coortes , Omeprazol/uso terapêutico , Estado Terminal/terapia , Mortalidade Hospitalar , Inibidores da Bomba de Prótons/uso terapêutico , Unidades de Terapia Intensiva , Estudos RetrospectivosRESUMO
BACKGROUND: Recently, increasing evidence has demonstrated that IL-10 single nucleotide polymorphisms (SNPs) are associated with the risk of acute leukemia (AL), but the findings of different articles remain controversial. Thus, we performed a meta-analysis to further investigate the exact roles of IL-10 SNPs in AL susceptibility. METHODS: Six common Chinese and English databases were utilized to retrieve eligible studies. The strength of the association was assessed by calculating odds ratios and 95 % confidence intervals. All analyses were carried out using Review Manager (version 5.3) and STATA (version 15.1). The registered number of this research is CRD42022373362. RESULTS: A total of 6391 participants were enrolled in this research. The results showed that the AG genotype of rs1800896 increased AL risk in the heterozygous codominant model (AG vs. AA, OR = 1.41, 95 % CI = 1.04-1.92, P = 0.03) and overdominant model (AG vs. AA + GG, OR = 1.32, 95 % CI = 1.04-1.70, P = 0.03). In the subgroup analysis, associations between the G allele, GG genotype, AG genotype, AG + GG genotype of rs1800896 and increased AL risk were also observed in the mixed population based on allelic, homozygote codominant, heterozygous codominant, dominant, and overdominant models. Furthermore, an association between the AC genotype of rs1800872 and increased AL risk was observed in the Caucasian population in the overdominant model. However, the rs1800871, rs3024489 and rs3024493 polymorphisms did not affect AL risk. CONCLUSION: IL-10 rs1800896 and rs1800872 affected the susceptibility of AL and therefore may be biomarkers for early screening and risk prediction of AL.
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Interleucina-10 , Leucemia Mieloide Aguda , Humanos , Estudos de Casos e Controles , Predisposição Genética para Doença/genética , Genótipo , Interleucina-10/genética , Leucemia Mieloide Aguda/genética , Polimorfismo de Nucleotídeo Único/genéticaRESUMO
Background: Antisense transcript of the B-cell translocation gene 3 (ASBEL) is a highly conserved antisense non-coding RNA (ncRNA) and participates in a variety of biological processes. However, the ASBEL expression status in pancreatic ductal adenocarcinoma (PDAC) and its correlation with BTG3 expression and tumor cell progression were not completely clear. Objective: We conducted cell experiments and animal experiments to confirm that ASBEL plays a crucial role in the tumorigenesis of PDAC by targeting BTG3. Methods: ASBEL regulation in PDAC tumorigenesis was evaluated using Western blotting, quantitative polymerase chain reaction, Cell Counting Kit-8 assay, flow cytometry, and cell transfection. We also evaluated the expression of ASBEL and BTG3 in tumor tissues and cells using Western blotting and quantitative real-time polymerase chain reaction. Finally, we explored the role of ASBEL in tumor development by silencing or overexpressing ASBEL gene in AsPC-1 or CFPAC-1 cells, respectively, and evaluated the antitumor activity in vivo using an ASBEL antagonist. Results: Our study revealed the expression of ASBEL in all pancreatic cell lines. The expression level of ASBEL in tumor tissues was found to be higher than that of paracarcinomatous tissues. ASBEL suppresses expression of BTG3, enhances proliferation and suppresses apoptosis, and promotes migration and invasion in pancreatic cancer cell. Antagonist regulates the expression of ASBEL in AsPC-1, and suppresses tumor growth in xenograft mouse model. Conclusions: Our results indicate that ASBEL may play a tumor-promoting factor in PDAC by targeting BTG3 and could be as an important biomarker for PDAC treatment. (Curr Ther Res Clin Exp. 2023; 84:XXX-XXX).
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IMPORTANCE: Asian-Americans are more likely than other ethnic groups to care for older family members and less likely to seek mental health services. The research on caregiver burden among Asian-American intergenerational caregivers is limited. OBJECTIVE: To investigate how spirituality and mental health help-seeking attitudes correlate with and predict perceived feelings of caregiver burden among Asian-American caregivers. Favorable mental health help-seeking attitudes were predicted to negatively correlate with caregiver burden, and spirituality was predicted to negatively correlate with and negatively predict caregiver burden. DESIGN: Quantitative survey research. SETTING: Community mental health. PARTICIPANTS: One hundred one participants were recruited using the following inclusion criteria: Asian-Americans who currently or previously provided care to an Asian family member at least one generation older than the caregiver for at least 1 mo and in the past 3 yr. Outcomes and Measures: Items from the Burden Scale for Family Caregivers, Spirituality Scale, Expressions of Spirituality Inventory-Revised, Mental Help Seeking Attitudes Scale, and Self-Stigma of Seeking Psychological Help measured caregiver burden, spirituality, and mental health help-seeking attitudes. RESULTS: A statistically significant negative correlation was found between caregiver burden and spirituality and between caregiver burden and mental health help-seeking attitudes. Spirituality and number of domains of care were statistically significant predictors of caregiver burden. CONCLUSIONS AND RELEVANCE: Spirituality was found to negatively predict caregiver burden among Asian-American intergenerational caregivers. Mental health help-seeking attitudes were negatively correlated with caregiver burden. Occupational therapy practitioners have the opportunity to integrate spirituality and culturally sensitive mental health promotion into their services to Asian-Americans. What This Article Adds: Evidence that spirituality is a negative predictor of caregiver burden for Asian-American intergenerational caregivers offers a unique opportunity for occupational therapy practitioners to offer alternative methods of mental health promotion with this population. Understanding that spirituality and mental health help-seeking attitudes are culturally mediated allows practitioners to be informed about a dynamic in Asian-American culture.
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Cuidadores , Espiritualidade , Atitude Frente a Saúde , Humanos , Saúde Mental , Projetos PilotoRESUMO
Histamine H2 receptor (HRH2) is closely associated with the development of cardiovascular and cerebrovascular diseases. However, systematic Hrh2 knockout mice did not exactly reflect the HRH2 function in specific cell or tissue types. To better understand the physiological and pathophysiological functions of endothelial HRH2, this study constructed a targeting vector that contained loxp sites flanking the ATG start codon located in Hrh2 exon 2 upstream and a neomycin (Neo) resistance gene flanked by self-deletion anchor sites within the mouse Hrh2 allele. The targeting vector was then electroporated into C57BL/6J embryonic stem (ES) cells, and positively targeted ES cell clones were micoinjected into C57BL/6J blastocysts, which were implanted into pseudopregnant females to obtain chimeric mice. The F1 generation of Hrh2flox/+ mice was generated via crossing chimeric mice with wild-type mice to excise Neo. We also successfully generated endothelial cell-specific knockout (ECKO) mice by crossing Hrh2flox/+ mice with Cdh5-Cre mice that specifically express Cre in endothelial cells and identified that Hrh2 deletion was only observed in endothelial cells. Hrh2flox/+ and Hrh2ECKO mice were normal, healthy and fertile and did not display any obvious abnormalities. These novel animal models will create new prospects for exploring roles of HRH2 during the development and treatment of related diseases.
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Blastocisto/metabolismo , Quimera/genética , Células-Tronco Embrionárias/metabolismo , Receptores Histamínicos H2/genética , Animais , Antígenos CD/genética , Caderinas/genética , Quimera/crescimento & desenvolvimento , Códon de Iniciação/genética , Células Endoteliais/metabolismo , Éxons/genética , Regulação da Expressão Gênica no Desenvolvimento/genética , Integrases/genética , Camundongos , Camundongos Knockout , Neomicina/metabolismoRESUMO
This article reviews the clinical applications of Superb Microvascular Imaging (SMI; Canon Medical Systems, Otawara, Japan) in the liver, breast, thyroid, skeletal muscle, and carotid plaques. Diseases that are closely associated with angiogenesis can be diagnosed by SMI in a relatively early phase, and using SMI can prevent adverse reactions associated with the contrast agents used in contrast-enhanced ultrasound. Super Microvascular Imaging also shows particular value in grading disease activities and monitoring therapeutic responses. Although SMI has some limitations, such as a lack of clinical standards, it can add information to conventional ultrasound examinations and may become a noninvasive alternative to invasive diagnostic procedures for many clinical conditions.
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Microvasos/diagnóstico por imagem , Placa Aterosclerótica/diagnóstico por imagem , Ultrassonografia/métodos , Mama/irrigação sanguínea , Mama/diagnóstico por imagem , Artérias Carótidas/diagnóstico por imagem , Humanos , Fígado/irrigação sanguínea , Fígado/diagnóstico por imagem , Músculo Esquelético/irrigação sanguínea , Músculo Esquelético/diagnóstico por imagem , Glândula Tireoide/irrigação sanguínea , Glândula Tireoide/diagnóstico por imagemRESUMO
KEY MESSAGE: Genetic improvement through overexpressing PuP5CS in switchgrass is feasible for enhancing plant salt stress tolerance. Switchgrass (Panicum virgatum L.) has developed into a dedicated bioenergy crop. To improve the biomass production of switchgrass grown on different types of soil, abiotic stress tolerance traits are considered for its genetic improvement. Proline accumulation is a widespread response when plants are subjected to abiotic stresses such as drought, cold and salinity. In plants, P5CS gene encodes the key regulatory enzyme that plays a crucial role in proline biosynthesis. Here, we introduced the PuP5CS gene (from Puccinellia chinampoensis) into switchgrass by Agrobacterium-mediated transformation. Transgenic lines overexpressing the PuP5CS gene showed phenotypic advantages, in leaf width, internode diameter, internode length, tiller numbers and precocious flowering under normal conditions, and the transgenic lines displayed better regenerative capacity in forming more tillers after harvest. Moreover, the PuP5CS gene enhanced the salt tolerance of transgenic switchgrass by altering a wide range of physiological responses. In accordance with the physiological results, histological analysis of cross sections through the leaf blade showed that the areas of bulliform cells and bundle sheath cells were significantly increased in PuP5CS-overexpressing leaves. The expression levels of ROS scavenging-associated genes in transgenic plants were higher than in control plants under salt stress. The results show that genetic improvement through overexpressing PuP5CS in switchgrass is feasible for enhancing plant stress tolerance.
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Panicum/efeitos dos fármacos , Panicum/metabolismo , Proteínas de Plantas/metabolismo , Plantas Geneticamente Modificadas/efeitos dos fármacos , Plantas Geneticamente Modificadas/metabolismo , Regulação da Expressão Gênica de Plantas/efeitos dos fármacos , Regulação da Expressão Gênica de Plantas/genética , Proteínas de Plantas/genética , Tolerância ao Sal/genéticaRESUMO
We investigated the effects of deficient and excess dietary selenium (Se) on growth, blood cells apoptosis and liver heat shock protein 70 (HSP70) expression in juvenile yellow catfish (Pelteobagrus fulvidraco). After 8 weeks, yellow catfish (initial weight: 2.12 ± 0.01 g) fed isonitrogenous and isolipid diets containing <0.05 (deficient dietary Se) or 6.5 (excess dietary Se) mg Se/kg displayed a significantly lower weight gain ratio (WGR) than those fed a diet containing 0.23 (normal dietary Se) mg Se/kg. As dietary Se levels increased, liver Se concentration, glutathione peroxidase activity and the hepatosomatic index increased significantly. Plasma glucose concentration was highest in the normal treatment compared with the excess dietary Se treatment. Both deficient and excess dietary Se lead to increased reactive oxygen species (ROS) production and apoptosis ratio in blood cells, whereas only excess dietary Se increased their cytoplasmic free-Ca(2+) (CF-Ca(2+)) concentration. Excess dietary Se also resulted in the highest level of HSP70 expression, thereby possibly providing a protective mechanism against oxidative stress. These results indicate that both deficient and excess dietary Se restrained the growth of juvenile yellow catfish and caused oxidative stress. The overproduction of ROS may act as a signal molecule mediate apoptosis when dietary Se deficiency. Both ROS and CF-Ca(2+) were recorded when dietary Se excess, suggesting that Ca(2+) may be activated by Se and play a major role during Se-induced oxidative stress and cell apoptosis.
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Peixes-Gato , Selênio/deficiência , Selênio/farmacologia , Animais , Apoptose/efeitos dos fármacos , Células Sanguíneas/efeitos dos fármacos , Glicemia/análise , Peixes-Gato/crescimento & desenvolvimento , Peixes-Gato/metabolismo , Dieta , Proteínas de Peixes/metabolismo , Glutationa Peroxidase/metabolismo , Proteínas de Choque Térmico HSP70/metabolismo , Fígado/efeitos dos fármacos , Fígado/metabolismo , Óxido Nítrico/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismoRESUMO
OBJECTIVE: The aim of this study was to compare the outcomes of robotic surgery, laparoscopy, and laparotomy for the surgical treatment of stage IA to IIB cervical cancer. METHODS: This retrospective study was carried out in a university-affiliated teaching hospital. A total of 100 women with an initial diagnosis of stage IA to IIB cervical cancer, without preoperative brachytherapy or chemotherapy, were included in this study. With selection of the cases, 44 patients received laparotomy surgery, 32 patients received laparoscopic surgery, and 24 patients received robotic surgery. The perioperative parameters measured included operation time, blood loss, transfusion rate, lymph node yield, adhesion score, laparotomy conversion rate, postoperative and 24-hour pain scores, time to full diet resumption, and hospital stay. The perioperative complication and disease-free survival were also evaluated. RESULTS: The robotic group showed a shorter operation time, less blood loss, lower transfusion rate, and lower laparotomy conversion rate than the laparoscopic or laparotomy group. As for the postoperative parameters, the robotic group showed reduced postoperative and 24-hour pain scores, shortened length of hospital stay, and decreased time to full diet resumption compared with the other 2 surgical groups. No significant differences were found between the groups in perioperative complication rate or disease-free survival. CONCLUSIONS: The data suggested that robotic surgery is a feasible and potentially optimal option for the treatment of stage IA to IIB cervical cancer with favorable short-term surgical outcomes.
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Adenocarcinoma/cirurgia , Carcinoma de Células Escamosas/cirurgia , Laparoscopia , Laparotomia , Complicações Pós-Operatórias , Robótica , Neoplasias do Colo do Útero/cirurgia , Adenocarcinoma/mortalidade , Adenocarcinoma/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Escamosas/mortalidade , Carcinoma de Células Escamosas/patologia , Feminino , Seguimentos , Humanos , Histerectomia , Tempo de Internação/estatística & dados numéricos , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida , Neoplasias do Colo do Útero/mortalidade , Neoplasias do Colo do Útero/patologiaRESUMO
Previous studies found that histamine H2 receptor antagonists (H2RAs) had blood pressure lowering and cardioprotective effects, but the impact of H2RAs on the survival outcomes of critically ill patients with essential hypertension is still unclear. The aim of this study was to investigate the association of H2RAs exposure with all-cause mortality in patients with essential hypertension based on Medical Information Mart for Intensive Care III database. A total of 17,739 patients were included, involving 8482 H2RAs users and 9257 non-H2RAs users. Propensity score matching (PSM) was performed to improve balance between 2 groups that were exposed to H2RAs or not. Kaplan-Meier survival curves were used to compare the cumulative survival rates and multivariable Cox regression models were performed to evaluate the association between H2RAs exposure and all-cause mortality. After 1:1 PSM, 4416 pairs of patients were enrolled. The results revealed potentially significant association between H2RAs exposure and decreased 30-day, 90-day, and 1-year mortalities in multivariate analyses (HR = 0.783, 95% CI: 0.696-0.882 for 30-day; HR = 0.860, 95% CI: 0.778-0.950 for 90-day; and HR = 0.883, 95% CI: 0.811-0.961 for 1-year mortality, respectively). Covariate effect analyses showed that the use of H2RAs was more beneficial in essential hypertension patients with age ≥ 60, BMI ≥ 25 kg/m2, coronary arteriosclerosis, stroke, and acute kidney failure, respectively. In conclusion, H2RAs exposure was related to lower mortalities in critically ill patients with essential hypertension, which provided novel potential strategy for the use of H2RAs in essential hypertension patients.
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Fibrogenesis and hepatocyte degeneration are the main pathological processes in chronic liver diseases. Transforming growth factor-ß1 (TGF-ß1) is the key profibrotic cytokine in hepatic fibrosis. Bone morphogenetic protein-7 (BMP-7) is a potent antagonist of TGF-ß1 and an antifibrotic factor. In this study, we generated a recombinant adeno-associated virus carrying BMP-7 (AAV-BMP-7) and tested its ability to suppress carbon tetrachloride (CCl(4))-induced hepatic fibrosis when orally administered to mice. Our results show that the ectopic expression of BMP-7 in gastrointestinal (GI) mucosa due to the AAV-BMP-7 administration led to the long-term elevation of serum BMP-7 concentrations and resulted in the drastic amelioration of CCl(4)-induced hepatic fibrosis in BALB/c mice. Immunostaining for α-smooth muscle actin (α-SMA) and desmin demonstrated that AAV-BMP-7 inhibited the activation of hepatic stellate cells (HSCs) in the fibrotic mouse liver. Moreover, the ectopic expression of BMP-7 promoted hepatocyte proliferation, as confirmed by an increase in the amount of proliferating cell nuclear antigen (PCNA)-positive hepatocytes in the mice that received AAV-BMP-7. Our results clearly indicate that BMP-7 is capable of inhibiting hepatic fibrosis and promoting hepatocyte regeneration. We suggest that oral AAV-BMP-7 could be developed into a safe, simple, and effective therapy for hepatic fibrosis.
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Proteína Morfogenética Óssea 7/genética , Dependovirus/genética , Cirrose Hepática/terapia , Actinas/metabolismo , Administração Oral , Animais , Proteína Morfogenética Óssea 7/biossíntese , Proteína Morfogenética Óssea 7/sangue , Proliferação de Células , Quimiocina CCL4 , Desmina/metabolismo , Trato Gastrointestinal/metabolismo , Expressão Gênica , Vetores Genéticos/administração & dosagem , Células Estreladas do Fígado/metabolismo , Células Estreladas do Fígado/fisiologia , Ácido Hialurônico/sangue , Hidroxiprolina/metabolismo , Fígado/metabolismo , Fígado/patologia , Cirrose Hepática/induzido quimicamente , Cirrose Hepática/patologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Proteínas Recombinantes/biossíntese , Proteínas Recombinantes/sangue , Proteínas Recombinantes/genéticaRESUMO
OBJECTIVE: To analyze clinical features of 4 families with hereditary hemorrhagic telangiectasia (HHT) and potential mutations of ENG, ACVRL1 and SMAD4 genes. METHODS: Four unrelated HHT patients and their affected family members were analyzed. All exons and flanking regions of ENG, ACVRL1 and SMAD4 genes were analyzed with PCR and direct sequencing and multiplex ligation-dependent probe amplification (MLPA) methods. RESULTS: Eleven patients from the 4 families were enrolled in this study. Two ENG and 1 ACVRL1 mutations were identified, among which an ENG mutation (c.207G>A; p.L69L) and an ACVRL1 mutation (c.817C>T; p.L273L) have been previously reported. In addition, a novel ENG mutation (c.1004A>T; p.Q335L) has been found in 3 different families. Similar mutations were not detected in 200 healthy individuals. No mutations of ENG, ACVRL1 and SMAD4 were found in the fourth family. CONCLUSION: A novel mutation c.1004A>T (p. Q335L) of ENG has been identified in patients with HHT. And there is significant phenotypic variability and genetic heterogeneity with the disease.
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Testes Genéticos , Mutação , Telangiectasia Hemorrágica Hereditária/genética , Receptores de Activinas Tipo II/genética , Adolescente , Adulto , Sequência de Aminoácidos , Antígenos CD/genética , Endoglina , Feminino , Humanos , Masculino , Dados de Sequência Molecular , Receptores de Superfície Celular/genética , Proteína Smad4/genética , Telangiectasia Hemorrágica Hereditária/diagnósticoRESUMO
Near infrared reflectance spectroscopy technology, as a new analytic method, can be used to determine the content of lignin, cellulose and hemi-cellulose which is faster, effective, easier to operate, and more accurate than the traditional wet chemical methods. Nowadays it has been widely used in measuring the composition of lignocelluloses in woody plant and herbaceous plant. The domestic and foreign research progress in determining the lignin, cellulose and hemi-cellulose content in woody plant ( wood and bamboo used as papermaking raw materials and wood served as potential biomass energy) and herbaceous plant (forage grass and energy grass) by near infrared reflectance spectroscopy technology is comprehensively summarized and the advances in method studies of measuring the composition of lignocelluloses by near infrared reflectance spectroscopy technology are summed up in three aspects, sample preparation, spectral data pretreatment and wavelength selection methods, and chemometric analysis respectively. Four outlooks are proposed combining the development statues of wood, forage grass and energy grass industry. First of all, the authors need to establish more feasible and applicable models for a variety of uses which can be used for more species from different areas, periods and anatomical parts. Secondly, comprehensive near infrared reflectance spectroscopy data base of grass products quality index needs to be improved to realize on-line quality and process control in grassproducts industry, which can guarantee the quality of the grass product. Thirdly, the near infrared reflectance spectroscopy quality index model of energy plant need to be built which can not only contribute to breed screening, but also improve the development of biomass industry. Besides, modeling approaches are required to be explored and perfected any further. Finally, the authors need to try our best to boost the advancement in the determination method of lignin, cellulose and hemi-cellulose by near infrared reflectance spectroscopy from the laboratory to the practical applications. Along with the method of determining the lignin, cellulose and hemi-cellulose by near infrared spectroscopy being unceasingly perfected and matured, this technique will actively have a positive effect on the development of papermaking, forage grass and energy grass industry.
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Celulose/análise , Lignina/análise , Polissacarídeos/análise , Espectroscopia de Luz Próxima ao Infravermelho , Madeira , Biomassa , PoaceaeRESUMO
Histamine H2 receptor antagonists (H2RAs) were widely used to inhibit gastric acid secretion, but its association with adverse events remains controversial and unclear. We conducted an umbrella review of meta-analyses to systematically assess the quality and credibility of the correlations between H2RA use with the risk of adverse outcomes through searching 4 major databases from inception to April 30, 2022. Forty-six individual meta-analyses were identified, including 29 meta-analyses of observation studies with 32 unique outcomes and 19 meta-analyses of randomized controlled trials with 3 unique outcomes for comparing the H2RA versus non-H2RA group. A Measurement Tool to Assess Systematic Reviews 2 rating for the included meta-analyses showed that 4 of 46 meta-analyses were assigned as high scores, 3 were assigned as "moderate," and 25 were assigned as low scores. Grading of Recommendations Assessment, Development and Evaluation assessment for combined results demonstrated that 6 outcomes were rated as "moderate," 9 outcomes were rated as "low," and 17 outcomes were rated as "very low." We confirmed significant associations of H2RA use with pneumonia, peritonitis, necrotizing enterocolitis, Clostridium difficile infection, liver cancer, gastric cancer, and hip fracture diseases. No associations for colorectal cancer, melanoma, kidney cancer, lung cancer, or common reproductive system cancer or renal, neurological, and cardiovascular system diseases were observed. We found a variety of evidence for the associations between H2RAs and adverse outcomes, which would give clinicians more positive guidance on prescription of H2RAs in clinical practice.
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Enterocolite Necrosante , Pneumonia , Humanos , Recém-Nascido , Antagonistas dos Receptores H2 da Histamina/efeitos adversos , Inibidores da Bomba de Prótons/efeitos adversosRESUMO
RATIONALE: Sepsis is a severe inflammatory response to infection that leads to long-lasting cognitive impairment and depression after resolution. The lipopolysaccharide (LPS)-induced endotoxaemia model is a well-established model of gram-negative bacterial infection and recapitulates the clinical characteristics of sepsis. However, whether LPS-induced endotoxaemia during adolescence can modulate depressive and anxiety-like behaviours in adulthood remains unclear. OBJECTIVES: To determine whether LPS-induced endotoxaemia in adolescence can modulate the stress vulnerability to depressive and anxiety-like behaviours in adulthood and explore the underlying molecular mechanisms. METHODS: Quantitative real-time PCR was used to measure inflammatory cytokine expression in the brain. A stress vulnerability model was established by exposure to subthreshold social defeat stress (SSDS), and depressive- and anxiety-like behaviours were evaluated by the social interaction test (SIT), sucrose preference test (SPT), tail suspension test (TST), force swimming test (FST), elevated plus-maze (EPM) test, and open field test (OFT). Western blotting was used to measure Nrf2 and BDNF expression levels in the brain. RESULTS: Our results showed that inflammation occurred in the brain 24 h after the induction of LPS-induced endotoxaemia at P21 but resolved in adulthood. Furthermore, LPS-induced endotoxaemia during adolescence promoted the inflammatory response and the stress vulnerability after SSDS during adulthood. Notably, the expression levels of nuclear factor erythroid 2-related factor 2 (Nrf2) and BDNF in the mPFC were decreased after SSDS exposure in mice treated with LPS during adolescence. Activation of the Nrf2-BDNF signalling pathway by sulforaphane (SFN), an Nrf2 activator, ameliorated the effect of LPS-induced endotoxaemia during adolescence on stress vulnerability after SSDS during adulthood. CONCLUSIONS: Our study identified adolescence as a critical period during which LPS-induced endotoxaemia can promote stress vulnerability during adulthood and showed that this effect is mediated by impairment of Nrf2-BDNF signalling in the mPFC.
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Endotoxemia , Fator 2 Relacionado a NF-E2 , Córtex Pré-Frontal , Animais , Camundongos , Comportamento Animal , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Depressão/metabolismo , Depressão/patologia , Endotoxemia/metabolismo , Hipocampo/metabolismo , Lipopolissacarídeos/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Córtex Pré-Frontal/metabolismo , Córtex Pré-Frontal/patologia , Adolescente , Humanos , Modelos Animais de Doenças , Transdução de SinaisRESUMO
Background: Our previous study reported that histamine H2 receptor antagonists (H2RAs) exposure was associated with decreased mortality in critically ill patients with heart failure (HF) through the same pharmacological mechanism as ß-blockers. However, population-based clinical study directly comparing the efficacy of H2RAs and ß-blockers on mortality of HF patients are still lacking. This study aims to compare the association difference of H2RAs and ß-blockers on mortality in critically ill patients with HF using the Medical Information Mart for Intensive Care III database (MIMIC-III). Methods: Study population was divided into 4 groups: ß-blockers + H2RAs group, ß-blockers group, H2RAs group, and Non-ß-blockers + Non-H2RAs group. Kaplan-Meier curves and multivariable Cox regression models were employed to evaluate the differences of all-cause mortalities among the 4 groups. Propensity score matching (PSM) was used to increase comparability of four groups. Results: A total of 5593 patients were included. After PSM, multivariate analyses showed that patients in H2RAs group had close all-cause mortality with patients in ß-blockers group. Furthermore, 30-day, 1-year, 5-year and 10-year all-mortality of patients in ß-blockers + H2RAs group were significantly lower than those of patients in ß-blockers group, respectively (HR: 0.64, 95%CI: 0.50-0.82 for 30-day; HR: 0.80, 95%CI: 0.69-0.93 for 1-year mortality; HR: 0.83, 95%CI: 0.74-0.93 for 5-year mortality; and HR: 0.85, 95%CI: 0.76-0.94 for 10-year mortality, respectively). Conclusion: H2RAs exposure exhibited comparable all-cause mortality-decreasing effect as ß-blockers; and, furthermore, H2RAs and ß-blockers had additive or synergistic interactions to improve survival in critically ill patients with HF.
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OBJECTIVE: To analyze the liver function in patients with diffuse large B-cell lymphoma(DLBCL), who are hepatitis B surface antigen negative/antibody to hepatitis B core antigen positive (HBsAg-/HBcAb+), treated with CHOP and R-CHOP regimens. METHODS: In this retrospective study, 86 DLBCL patients, who were HBsAg-/HBcAb+, were collected from Cancer Hospital of Chinese Academy of Medical Sciences between January 2005 and December 2008. The patients were given at least two cycles of chemotherapy using CHOP-like or R-CHOP-like regimen without anti-HBV treatment, and followed-up for at least 12 months after completion of therapy. RESULTS: Forty-seven patients received CHOP-like regimen while 39 patients received R-CHOP-like regimen. There were no significant differences in the degree of liver dysfunction between CHOP group and R-CHOP group after the 1st, 2nd, 3rd, 4th and 6th cycles (22.7% - 46.7% with CHOP and 17.6% - 34.2% with R-CHOP, respectively, (all P > 0.05), except for the 5th cycles (28.6% vs. 6.2%, P = 0.026). Liver function in most patients in CHOP group and R-CHOP group was normal after every cycle (53.3% - 77.3% and 65.8%-93.8%, respectively). Meanwhile, there were no significant differences in the degree of liver dysfunction between CHOP group and R-CHOP group in the 1st-3rd month, 4th-6th month, 7th-9th month and 10th-12th month after completion of therapy (7.7% - 40.0% with CHOP and 7.4% - 32.0% with R-CHOP, respectively, all P > 0.05). CONCLUSIONS: The present study reveals a low incidence of liver dysfunction in HBsAg-/HBcAb+ DLBCL patients, both in CHOP group and in R-CHOP group. It may indicate a potential low incidence of HBV reactivation in these groups, and Rituximab do not increase the rate of liver dysfunction. Therefore, these data may not support regularly prophylactic antiviral therapy during chemotherapy, but close monitoring of liver function, HBV serum markers and HBV DNA level are demanded.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Alanina Transaminase/sangue , Anticorpos Monoclonais Murinos/uso terapêutico , Aspartato Aminotransferases/sangue , Bilirrubina/sangue , Ciclofosfamida/uso terapêutico , Doxorrubicina/uso terapêutico , Feminino , Seguimentos , Anticorpos Anti-Hepatite B/metabolismo , Antígenos do Núcleo do Vírus da Hepatite B/imunologia , Antígenos de Superfície da Hepatite B/metabolismo , Humanos , Testes de Função Hepática , Linfoma Difuso de Grandes Células B/sangue , Linfoma Difuso de Grandes Células B/imunologia , Linfoma Difuso de Grandes Células B/virologia , Masculino , Prednisolona/uso terapêutico , Prednisona/uso terapêutico , Estudos Retrospectivos , Rituximab , Vincristina/uso terapêuticoRESUMO
BACKGROUND: Synchronous primary cancers (SPCs) have become increasingly frequent over the past decade. However, the coexistence of duodenal papillary and gallbladder cancers is rare, and such cases have not been previously reported in the English literature. Here, we describe an SPC case with duodenal papilla and gallbladder cancers and its diagnosis and successful management. CASE SUMMARY: A 68-year-old Chinese man was admitted to our hospital with the chief complaint of dyspepsia for the past month. Contrast-enhanced computed tomography of the abdomen performed at the local hospital revealed dilatation of the bile and pancreatic ducts and a space-occupying lesion in the duodenal papilla. Endoscopy revealed a tumor protruding from the duodenal papilla. Pathological findings for the biopsied tissue revealed tubular villous growth with moderate heterogeneous hyperplasia. Surgical treatment was selected. Macroscopic examination of this surgical specimen revealed a 2-cm papillary tumor and another tumor protruding by 0.5 cm in the gallbladder neck duct. Intraoperative rapid pathology identified adenocarcinoma in the gallbladder neck duct and tubular villous adenoma with high-grade intraepithelial neoplasia and local canceration in the duodenal papilla. After an uneventful postoperative recovery, the patient was discharged without complications. CONCLUSION: It is essential for clinicians and pathologists to maintain a high degree of suspicion while evaluating such synchronous cancers.
RESUMO
OBJECTIVE: FOXP3 single nucleotide polymorphisms (SNPs) were recently elucidated to influence the development of preeclampsia (PE), but the results on this issue still remained controversial. Thus, a meta-analysis was implemented to systematically investigate the roles of FOXP3 SNPs in PE. METHODS: Eligible publications were identified by retrieving relevant electronic databases. Meanwhile, the association intensity was estimated by calculating odds ratios (ORs) and 95% confidence intervals (CIs) in various genetic models. RESULTS: Totally eight investigations involving 3446 subjects were enrolled in the final meta-analysis. The AC and AC + CC genotypes of FOXP3 rs3761548 were related to the susceptibility of PE in over-dominant (OR = 1.19, 95%CI = 1.02-1.38, P = 0.03) and recessive (OR = 0.59, 95% CI: 0.36-0.97, P = 0.04) models. Furthermore, correlation between rs2232365 and PE was observed in recessive model (GG vs. GA + AA) (OR = 0.79, 95%CI: 0.65-0.97, P = 0.03). Moreover, rs2232365 GA and GG + GA genotypes were associated with the severity of PE. However, rs4824747, rs3761547 and rs2280883 polymorphisms had no significant impact on PE susceptibility. CONCLUSIONS: FOXP3 rs3761548 and rs2232365 SNPs influenced the PE susceptibility and therefore may be potential biomarkers for prediction of PE risk.
Assuntos
Fatores de Transcrição Forkhead , Pré-Eclâmpsia , Feminino , Fatores de Transcrição Forkhead/genética , Predisposição Genética para Doença , Genótipo , Humanos , Razão de Chances , Polimorfismo de Nucleotídeo Único , Pré-Eclâmpsia/genética , GravidezRESUMO
OBJECTIVES: Increasing evidence suggested that proton pump inhibitors (PPIs) use might affect the development of cancers, but previous conclusions remain controversial. Therefore, an umbrella review was performed to clarify the associations between PPIs and various types of cancer by summarizing the existing meta-analyses and systematic reviews. METHODS: We searched PubMed, Cochrane Library, Embase, CNKI, Wanfang, and VIP database up to June 2022 for eligible meta-analyses or systematic reviews. The summary effect size, 95% CI, heterogeneity, small study effect, and 95% prediction interval were considered in the present study. A Measurement Tool to Assess Systematic Review 2 and grading of recommendation, assessment, development, and evaluation were used to assess methodological quality and evidence. RESULTS: The umbrella review included 21 meta-analyses containing 65 studies and 10 cancer types with 6.8 million subjects. The results showed that PPI use was significantly associated with increased risks of certain types of cancer, including gastric cancer (odds ratio [OR]: 2.07; 95% CI, 1.30 to 3.29), pancreatic cancer (OR: 1.73; 95% CI, 1.23 to 2.44), colorectal cancer (OR: 1.84; 95% CI, 1.26 to 2.67), and liver cancer (OR: 1.80; 95% CI, 1.27 to 2.54), but was not associated with esophageal cancer. In addition, PPI use was associated with decreased risk of breast cancer (OR: 0.69; 95% CI, 0.50 to 0.96). CONCLUSIONS: These findings suggested that clinicians should pay more attention to the occurrence of gastric cancer, pancreatic cancer, colorectal cancer, and liver cancer in patients who used PPIs, and PPI prescription should be written only when an accurate specific diagnosis has been made. Furthermore, additional PPIs to the treatment regimen may be benefit for women with a higher-than-average risk of breast cancer.