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1.
Zhonghua Er Ke Za Zhi ; 62(5): 451-456, 2024 May 02.
Artigo em Chinês | MEDLINE | ID: mdl-38623013

RESUMO

Objective: To investigate the clinical characteristics of 130 children with severe SARS-CoV-2 infection in Yunnan province after the relaxation of non-pharmaceutical interventions, and analyze the risk factors for mortality. Methods: This study is a retrospective case summary that analyzed the demographic data, underlying diseases, clinical diagnoses, disease outcomes, and laboratory results of 130 children with severe COVID-19 infections admitted to nine top-tier hospitals in Yunnan Province from December 2022 to March 2023. According to the prognosis, the patients were divided into survival group and death group. The clinical and laboratory data between the two groups were compared, and the risk factors of death were evaluated. The χ2 test and Mann-Whitney U test were employed to compare between groups, while Spearman correlation test and multiple Logistic regression were used to analyze the risk factors for death. The predictive value of independent risk factors was evaluated by receiver operating characteristic curve. Results: The 130 severe patients included 80 males and 50 females with an onset age of 28.0 (4.5, 79.5) months. There were 97 cases in the survival group and 33 cases in the death group with no significant differences in gender and age between the two groups (P>0.05). Twenty-five cases (19.2%) out of the 130 patients had underlying diseases, and the number with underlying diseases was significantly higher in death group than in survival group (36.4% (12/33) vs. 13.4%(13/97), χ2=8.36, P=0.004). The vaccination rate in the survival group was significantly higher than that in the death group (86.1% (31/36) vs. 7/17, χ2=9.38, P=0.002). A total of 42 cases (32.3%) of the 130 patients were detected to be infected with other pathogens, but there was no significant difference in the incidence of co-infection between the death group and the survival group (39.3%(13/33) vs. 29.9% (29/97), χ2=1.02, P>0.05). Among the 130 cases, severe respiratory cases were the most common 66 cases (50.8%), followed by neurological severe illnesses 34 cases (26.2%) and circulatory severe 13 cases (10%). Compared to the survival group, patients in the death group had a significantly higher levels of neutrophil, ferritin, procalcitonin, alanine aminotransferase, lactate dehydrogenase, creatine kinase isoenzyme, B-type natriuretic peptide, interleukin-6 and 10 (6.7 (4.0, 14.0) vs. 3.0 (1.6, 7.0)×109/L, 479 (298, 594) vs. 268 (124, 424) µg/L, 4.8 (1.7, 10.6) vs. 2.0 (1.1, 3.1) µg/L, 66 (20, 258) vs. 23 (15, 49) U/L, 464 (311, 815) vs. 304 (252, 388) g/L, 71(52, 110) vs. 24(15, 48) U/L, 484 (160, 804) vs. 154 (26, 440) ng/L, 43 (23, 102) vs. 19 (13, 27) ng/L, 216 (114, 318) vs. 86 (45, 128) ng/L, Z=-4.21, -3.67, -3.76, -3.31, -3.75, -5.74, -3.55, -4.65, -5.86, all P<0.05). The correlated indexes were performed by multivariate Logistic regression and the results showed that vaccination was a protective factor from death in severe cases (OR=0.01, 95%CI 0-0.97, P=0.049) while pediatric sequential organ failure assessment (PSOFA) (OR=3.31, 95%CI 1.47-7.47, P=0.004), neutrophil-to-lymphocyte ratio (NLR) (OR=1.56, 95%CI 1.05-2.32, P=0.029) and D dimer (OR=1.49, 95%CI 1.00-1.02, P=0.033) were independent risk factors for death (all P<0.05). The area under the curve of the three independent risk factors for predicting death were 0.86 (95%CI 0.79-0.94), 0.89 (95%CI 0.84-0.95) and 0.87 (95%CI 0.80-0.94), all P<0.001, and the cut-off values were 4.50, 3.66 and 4.69 mg/L, respectively. Conclusions: Severe SARS-CoV-2 infection can occur in children of all ages, primarily affecting the respiratory system, but can also infect the nervous system, circulatory system or other systems. Children who died had more severe inflammation, tissue damage and coagulation disorders. The elevations of PSOFA, NLR and D dimer were independent risk factors for death in severe children.


Assuntos
COVID-19 , SARS-CoV-2 , Humanos , COVID-19/mortalidade , COVID-19/epidemiologia , COVID-19/diagnóstico , Masculino , Feminino , Estudos Retrospectivos , Criança , China/epidemiologia , Pré-Escolar , SARS-CoV-2/isolamento & purificação , Fatores de Risco , Lactente , Prognóstico , Índice de Gravidade de Doença , Estado Terminal
2.
Mol Ther ; 32(6): 1835-1848, 2024 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-38659225

RESUMO

While conventional chimeric antigen-receptor (CAR)-T therapies have shown remarkable clinical activity in some settings, they can induce severe toxicities and are rarely curative. To address these challenges, we developed a controllable cell therapy where synthetic D-domain-containing proteins (soluble protein antigen-receptor X-linker [SparX]) bind one or more tumor antigens and mark those cells for elimination by genetically modified T cells (antigen-receptor complex [ARC]-T). The chimeric antigen receptor was engineered with a D-domain that specifically binds to the SparX protein via a unique TAG, derived from human alpha-fetoprotein. The interaction is mediated through an epitope on the TAG that is occluded in the native alpha-fetoprotein molecule. In vitro and in vivo data demonstrate that the activation and cytolytic activity of ARC-T cells is dependent on the dose of SparX protein and only occurs when ARC-T cells are engaged with SparX proteins bound to antigen-positive cells. ARC-T cell specificity was also redirected in vivo by changing SparX proteins that recognized different tumor antigens to combat inherent or acquired tumor heterogeneity. The ARC-SparX platform is designed to expand patient and physician access to cell therapy by controlling potential toxicities through SparX dosing regimens and enhancing tumor elimination through sequential or simultaneous administration of SparX proteins engineered to bind different tumor antigens.


Assuntos
Imunoterapia Adotiva , Receptores de Antígenos Quiméricos , Linfócitos T , Humanos , Receptores de Antígenos Quiméricos/metabolismo , Receptores de Antígenos Quiméricos/imunologia , Receptores de Antígenos Quiméricos/genética , Animais , Camundongos , Linfócitos T/imunologia , Linfócitos T/metabolismo , Imunoterapia Adotiva/métodos , Antígenos de Neoplasias/imunologia , Antígenos de Neoplasias/metabolismo , Linhagem Celular Tumoral , Ensaios Antitumorais Modelo de Xenoenxerto , Receptores de Antígenos de Linfócitos T/metabolismo , Receptores de Antígenos de Linfócitos T/imunologia , Neoplasias/terapia , Neoplasias/imunologia , Neoplasias/metabolismo , Ligação Proteica
4.
Plant Biol (Stuttg) ; 23(5): 760-769, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-33915008

RESUMO

Rainfall use efficiency (RUE) is crucial for understanding the changes in grassland productivity due to variations in future rainfall patterns. Recently, numerous studies have been conducted on the relationship between RUE and the amount of rainfall, but there has been little research on the influence of rainfall distribution and the interactive effect of rainfall amounts and distribution on RUE. Here, a simulated rainfall experiment was conducted to evaluate the impacts of rainfall amount (average rainfall amount (R0), 334 mm; decreased (R-) and increased (R+) rainfall amounts, 233 mm and 434 mm, respectively) and dry intervals (comprising 6-day, 9-day, 12-day, 15-day, 18-day and 21-day intervals between rainfall) on productivity and RUE in Leymus chinensis (Trin.) Tzvel., a dominant grass of the Eastern Eurasian Steppe. Our results showed that (1) for biomass production and RUE, moderate extension of dry intervals was conducive to enhancing total biomass production and RUE. The peak values of total biomass and RUE appeared during the 15-day interval for R-, and the 18-day interval for R0 and R+. (2) For biomass allocation, extension of dry intervals decreased the stem to leaf ratio (S/L) and the root to shoot ratio (R/S). (3) Further, the S/L ratio was significantly negatively correlated with RUE. These results suggest that variations in rainfall patterns can alter the RUE by changing the S/L ratio, and finally influence biomass production in L. chinensis. These findings have important implications for understanding and predicting the effect of future climate change on productivity in semi-arid grassland.


Assuntos
Pradaria , Poaceae , Biomassa , China , Mudança Climática , Folhas de Planta
5.
Zhonghua Xin Xue Guan Bing Za Zhi ; 49(2): 128-135, 2021 Feb 24.
Artigo em Chinês | MEDLINE | ID: mdl-33611898

RESUMO

Objective: To evaluate the 4-year clinical outcomes of patients following Firesorb bioresorbable scaffold (BRS) implantation. Methods: The study reported the 4-year follow-up results of the FUTURE I study. FUTURE I was a prospective, single-center, open-label, first-in-man study which evaluated the feasibility, preliminary safety, and efficacy of Firesorb stent in the treatment of coronary artery stenosis. A total of 45 patients with single de novo lesions in native coronary arteries ,who hospitalized in Fuwai Hospital from January to March 2016 were enrolled. After successfully stent implantation these patients were randomized in a 2∶1 ratio into cohort 1 (n=30) or cohort 2 (n=15). The patients in cohort 1 underwent angiographic, IVUS or OCT examination at 6 months and 2 years; and cohort 2 underwent angiographic, IVUS or OCT at 1 and 3 years. All patients underwent clinical follow-up at 1, 6 months and 1 year and annually thereafter up to 5 years. The primary endpoint was target lesion failure (TLF, including cardiac death, target vessel myocardial infarction, and ischemia-driven target lesion revascularization). Secondary endpoints included patient-oriented composite endpoint (PoCE, defined as composite of all death, all miocardial infarction, or any revascularization). Results: A total of 45 patients were enrolled and implanted with Firesorb BRS, including 35 males (77.8%), and the age was (54.4±9.3) years. At 4 years, 10 patients in cohort 1 were reexamined by coronary angiography and OCT examination. Among them, 2 patients' stents were completely degraded and absorbed. Compared with the OCT images of the other 8 patients in cohort 2 at 3 years, the degree of stent degradation was increased, and no stent adherence was found. The 4-year clinical follow-up rate was 100%. In 4-year clinical following up, 2 patients suffered PoCE (4.4%): 1 patient underwent non-target vessel revascularization the day after index procedure and target vessel revascularization (Non-target lesion revascularization) at 2-year imaging follow-up; the other patient underwent target lesion revascularization during imaging follow-up at 4 years but not due to ischemic driven. There was no scaffold thrombosis or TLF events through 4 years. Conclusions: Four years after the implantation, complete degradation and absorption of the Firsorb stent are evidenced in some patients. Firesorb stent is feasible and effective in the treatment of patients with non-complex coronary lesions.


Assuntos
Fármacos Cardiovasculares , Doença da Artéria Coronariana , Stents Farmacológicos , Intervenção Coronária Percutânea , Implantes Absorvíveis , Doença da Artéria Coronariana/diagnóstico por imagem , Doença da Artéria Coronariana/cirurgia , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Sirolimo , Resultado do Tratamento
6.
Animal ; 15(3): 100172, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33589350

RESUMO

Some grain processing by-products rich in digestible fiber are good feed resources for ruminants. This experiment was conducted to investigate the effects of replacing a portion of corn and corn stover with the combinations of corn bran and soybean hulls in the diet of fattening lambs on nutrient digestion, rumen microbial protein synthesis, and growth performance. A total of 36 Dorper × Small Thin-Tailed crossbred ram lambs (BW = 22.2 ±â€¯0.92 kg; mean ±â€¯SD) were randomly divided into three groups, and each group was fed 1 of 3 treatment diets: 1) 0% corn bran and soybean hulls (control); 2) 9% corn bran and 9% soybean hulls (18MIX); and 3) 17% corn bran and 17% soybean hulls (34MIX). The feeding experiment was conducted for 70 days, with the first 10 days for adaption. The DM intake was higher for 34MIX (1635.3 g/d) than for control diet (1434.7 g/d; P = 0.001). Lambs fed 18MIX and 34MIX diets (230.2 and 263.6 g/d, respectively) had higher average daily gain and feed efficiency than those fed control diet (194.8 g/d; P < 0.01). Dry matter and NDF digestibility for 34MIX group (60.9 and 49.5%) were higher than for control (55.2 and 41.3%; P < 0.01). No difference was observed in nitrogen digestibility among treatment diets (P = 0.778). The lambs fed 34MIX diet excreted more urinary purine derivatives, indicating that more microbial protein was yielded than those fed control diet (P < 0.01), while 18MIX was not different from the other two diets (P > 0.05). The metabolizable protein supplies were improved with increasing co-products inclusion rate. The results indicated that corn bran and soybean hulls in combination can effectively replace a portion of corn and corn stover in the ration of finishing lambs with positive effect on nutrient digestion and growth performance.


Assuntos
Glycine max , Rúmen , Ração Animal/análise , Fenômenos Fisiológicos da Nutrição Animal , Animais , Dieta/veterinária , Digestão , Masculino , Nutrientes , Ovinos , Zea mays
7.
Zhonghua Yi Xue Za Zhi ; 101(4): 271-275, 2021 Jan 26.
Artigo em Chinês | MEDLINE | ID: mdl-33486936

RESUMO

Objectives: To analyze the reasons of residual partial anomalous pulmonary venous connection (PAPVC) after previous cardiac surgery, and summarize the strategies and experience for diagnosis and treatment of secondary correction operation. Methods: The clinical data of 18 patients who were admitted to Fuwai Hospital of Chinese Academy of Medical Sciences and Fuwai Yunnan Cardiovascular Hospital from June 2009 to May 2019 were retrospectively analyzed. All the patients underwent secondary cardiac surgery to treat PAPVC. The preoperative and intraoperative characteristics and postoperative complications of the patients were summarized and analyzed. Results: Totally, there were 7 male and 11 female cases, aged 1-49 years (median age: 4.5 years). In the first cardiac surgery, 3 patients were diagnosed with PAPVC, which existed after surgery. One patient was diagnosed with total anomalous pulmonary venous connection (TAPVC), but left PAPVC after surgery. The remaining 14 patients were all missed preoperative and intraoperative diagnosis. After the initial surgery, most patients had no significant symptoms (11/18), but PAPVC was found in 11 cases due to postoperative cardiac murmur or transthoracic echocardiography (TTE). In the secondary surgery, there were 4 cases of type A, 10 cases of type B, 2 cases of type C, no type D, and 2 cases of mixed type, respectively, according to Bordy classification. The diagnostic accuracy of TTE and CT angiography (CTA) was 50.0% and 92.9%, respectively. There was no death after the second surgery, but pulmonary vein occlusion, pericardial effusion, anastomotic stenosis and other complications occurred in 4 patients. Conclusions: The main causes of missed diagnosis of PAPVC are the undefined cardiac structural deformities before operation and the lack of careful exploration during the operation. TTE is simple and feasible to diagnose PAPVC, and it can improve the diagnostic accuracy when combined with CTA.


Assuntos
Procedimentos Cirúrgicos Cardíacos , Veias Pulmonares , Síndrome de Cimitarra , Adolescente , Adulto , Criança , Pré-Escolar , China , Feminino , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Veias Pulmonares/cirurgia , Estudos Retrospectivos , Síndrome de Cimitarra/cirurgia , Adulto Jovem
9.
Animal ; 14(10): 2042-2053, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32436487

RESUMO

Antibiotics are designed to affect gut microbiota and subsequently gut homeostasis. However, limited information exists about short- and long-term effects of early antibiotic intervention (EAI) on gut homeostasis (especially for the small intestine) of pigs following antibiotic withdrawal. We investigated the impact of EAI on specific bacterial communities, microbial metabolites and mucosal immune parameters in the small intestine of later-growth-stage pigs fed with diets differing in CP levels. Eighteen litters of piglets were fed creep feed with or without antibiotics from day 7 to day 42. At day 42, pigs within each group were offered a normal- or low-CP diet. Five pigs per group were slaughtered at days 77 and 120. At day 77, EAI increased Enterobacteriaceae counts in the jejunum and ileum and decreased Bifidobacterium counts in the jejunum and ileum (P < 0.05). Moreover, tryptamine, putrescine, secretory immunoglobulin (Ig) A and IgG concentrations in the ileum and interleukin-10 (IL-10) mRNA and protein levels in the jejunum and ileum were decreased in pigs with EAI (P < 0.05). At day 120, EAI only suppressed Clostridium cluster XIVa counts in the jejunum and ileum (P < 0.05). These results suggest that EAI has a short-term effect on specific bacterial communities, amino acid decarboxylation and mucosal immune parameters in the small intestine (particularly in the ileum). At days 77 and 120, feeding a low-CP diet affected Bifidobacterium, Clostridium cluster IV, Clostridium cluster XIVa and Enterobacteriaceae counts in the jejunum or ileum (P < 0.05). Moreover, feeding a low-CP diet increased the concentrations of Igs in the jejunum and decreased pro-inflammatory cytokines levels in the jejunum and ileum (P < 0.05). At day 120, feeding a low-CP diet increased short-chain fatty acid concentrations, reduced ammonia and spermidine concentrations and up-regulated genes related to barrier function in the jejunum and ileum (P < 0.05). These results suggest that feeding a low-CP diet changes specific bacterial communities and intestinal metabolite concentrations and modifies mucosal immune parameters. These findings contribute to our understanding on the duration of the impact of EAI on gut homeostasis and may provide basis data for nutritional modification in young pigs after antibiotic treatment.


Assuntos
Ração Animal , Antibacterianos , Suínos , Ração Animal/análise , Animais , Dieta/veterinária , Proteínas Alimentares , Íleo , Intestino Delgado , Suínos/microbiologia
10.
Animal ; 14(9): 1841-1848, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32172723

RESUMO

Flax seed meal (FSM) is rich in various nutrients, especially CP and energy, and can be used as animal protein feed. In animal husbandry production, it is a long-term goal to replace soybean meal (SBM) in animal feed with other plant protein feed. However, studies on the effects of replacing SBM with FSM in fattening sheep are limited. The aim of this experiment was to study the effects of replacing a portion of SBM with FSM on nutrient digestibility, rumen microbial protein synthesis and growth performance in sheep. Thirty-six Dorper × Small Thin-Tailed crossbred rams (BW = 40.4 ± 1.73 kg, mean ± SD) were randomly assigned into four groups. The dietary treatments (forage/concentrate, 45 : 55) were isocaloric according to the nutrient requirements of rams. Soybean meal was replaced with FSM at different levels (DM basis): (1) 18% SBM (18SBM), (2) 12% SBM and 6% FSM (6FSM), (3) 6% SBM and 12% FSM (12FSM) and (4) 18% FSM (18FSM). The rams were fed in individual pens for 60 days, with the first 10 days for adaptation to diets, and then the digestibility of nutrients was determined. There was no significant difference in DM intake, but quadratic (P < 0.001) effects on the average daily gain and feed efficiency were detected, with the highest values in the 6FSM and 12FSM groups. For DM and NDF digestibility, quadratic effects were observed with the higher values in the 6FSM and 12FSM groups, but the digestibility of CP linearly decreased with the increase in FSM in the diet (P = 0.043). There was a quadratic (P < 0.001) effect of FSM inclusion rate on the estimated microbial CP yield. However, the values of intestinally absorbable dietary protein decreased linearly (P < 0.001). For the supply of metabolisable protein, both the linear (P = 0.001) and quadratic (P = 0.044) effects were observed with the lowest value in the 18FSM group. Overall, the results indicated that SBM can be effectively replaced by FSM in the diets of fattening sheep and the optimal proportion was 12.0% under the conditions of this experiment.


Assuntos
Ração Animal , Linho , Glycine max , Rúmen , Ração Animal/análise , Fenômenos Fisiológicos da Nutrição Animal , Animais , Dieta/veterinária , Digestão , Masculino , Nutrientes , Rúmen/metabolismo , Sementes , Ovinos/crescimento & desenvolvimento
11.
Eur Rev Med Pharmacol Sci ; 24(2): 604-610, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-32016961

RESUMO

OBJECTIVE: This study aims to investigate the clinical value of combined detection of serum soluble epidermal growth factor receptor (sEGFR), cancer antigen 125 (CA125), and human epididymis protein 4 (HE4) in the diagnosis of epithelial ovarian cancer (EOC). PATIENTS AND METHODS: From December 2017 to October 2018, the serum samples were obtained from the Affiliated Hospital of Xuzhou Medical University, with 30 patients as EOC group, 30 patients with benign ovarian neoplasms as benign group, and 17 healthy subjects as healthy group. Besides, among 30 EOC patients, 9 serum samples were obtained from pre-operative and post-operative EOC patients. The levels of serum sEGFR were detected by enzyme-linked immunosorbent assay (ELISA), while CA125 and HE4 were detected by enhanced chemiluminescence immunoassay (ECLIA). The diagnostic value was evaluated by receiver operating characteristic (ROC) curve analysis. RESULTS: The levels of serum sEGFR, CA125, and HE4 in EOC group were significantly higher than those in benign group (p<0.05) and healthy group (p<0.05). When using a single tumor marker, the CA125 shows the highest sensitivity (93.30%) and HE4 shows the highest specificity (97.87%). The specificity of combined detection of serum sEGFR, CA125, and HE4 was 100%, which was significantly higher than that using a single tumor marker. The area under the ROC curve (AUC) of combined detection of serum sEGFR, CA125, and HE4 (0.965) was much higher than that of the single detection and higher than that of combined detection of CA125 and HE4 (0.940). Moreover, the level of serum sEGFR in post-operative EOC group was significantly lower than that in the corresponding pre-operative EOC group (p<0.05). CONCLUSIONS: Our study shows that combined detection of serum sEGFR, CA125, and HE4 increases the specificity and efficiency in EOC diagnosis, indicating that sEGFR could be a potential biomarker for the diagnosis and prognosis of EOC.


Assuntos
Biomarcadores Tumorais/sangue , Antígeno Ca-125/sangue , Carcinoma Epitelial do Ovário/sangue , Carcinoma Epitelial do Ovário/diagnóstico , Proteínas de Membrana/sangue , Proteína 2 do Domínio Central WAP de Quatro Dissulfetos/metabolismo , Adulto , Receptores ErbB/sangue , Feminino , Humanos , Pessoa de Meia-Idade
12.
Zhonghua Kou Qiang Yi Xue Za Zhi ; 54(7): 492-497, 2019 Jul 09.
Artigo em Chinês | MEDLINE | ID: mdl-31288331

RESUMO

The development of computer hardware allows rapid accumulation of medical imaging data. Deep learning has shown great potential in medical imaging data analysis and establish a new area of machine learning. The commonly used deep learning models were firstly introduced in the paper, and then, summarized with the application of deep learning in the detection, classification, diagnosis, segmentation, identification of medical imaging. The application of deep learning in oral and maxillofacial radiology and other discipline of stomatology was proposed. At the end, the paper discussed the problems of deep learning in medical imaging research.


Assuntos
Aprendizado Profundo , Diagnóstico por Imagem , Redes Neurais de Computação , Pesquisa , Diagnóstico por Imagem/tendências , Aprendizado de Máquina , Pesquisa/tendências
13.
Mol Ther ; 27(7): 1262-1274, 2019 07 03.
Artigo em Inglês | MEDLINE | ID: mdl-31043341

RESUMO

Chimeric antigen receptor (CAR) T cell therapies have demonstrated impressive initial response rates in hematologic malignancies. However, relapse rates are significant, and robust efficacies in other indications, such as solid tumors, will likely require novel therapeutic strategies and CAR designs. To that end, we sought to develop simple, highly selective targeting domains (D domains) that could be incorporated into complex, multifunctional therapeutics. Herein, we describe the identification and characterization of D domains specific for CD123, a therapeutic target for hematologic malignancies, including acute myelogenous leukemia (AML). CARs comprised of these D domains mediate potent T cell activation and cytolysis of CD123-expressing target cells and induce complete durable remission in two AML xenograft models. We describe a strategy of engineering less immunogenic D domains through the identification and removal of putative T cell epitopes and investigate the binding kinetics and affinity requirements of the resultant D domain CARs. Finally, we extended the utility of D domains by generating functional, bi-specific CARs comprised of a CD123-specific D domain and a CD19-specific scFv. The properties of D domains suggest that this class of targeting domain may facilitate the development of multi-functional CARs where conventional, scFv-based designs may be suboptimal.


Assuntos
Antineoplásicos/uso terapêutico , Imunoterapia Adotiva/métodos , Subunidade alfa de Receptor de Interleucina-3/imunologia , Domínios Proteicos/imunologia , Proteínas/uso terapêutico , Receptores de Antígenos Quiméricos/uso terapêutico , Linfócitos T/imunologia , Animais , Antígenos CD19/imunologia , Antineoplásicos/imunologia , Epitopos de Linfócito T/imunologia , Células HEK293 , Humanos , Células K562 , Leucemia Mieloide Aguda/terapia , Ativação Linfocitária/imunologia , Camundongos , Camundongos Endogâmicos NOD , Camundongos SCID , Ligação Proteica/imunologia , Proteínas/imunologia , Receptores de Antígenos Quiméricos/imunologia , Anticorpos de Cadeia Única/imunologia , Transfecção , Ensaios Antitumorais Modelo de Xenoenxerto
14.
Animal ; 13(2): 262-272, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29954466

RESUMO

Gut microbes, especially those in the large intestine, are actively involved in nutrient metabolism; however, their impact on host nitrogen (N) metabolism remains largely unknown. This study was designed to investigate the effects of feeding a cocktail of antibiotics (AGM) (ampicillin, gentamycin and metronidazole) on intestinal microbiota, N utilization efficiency, and amino acid (AA) digestibility in cannulated pigs, with the aim of exploring the impact of gut microbiota on host N metabolism. In total, 16 piglets were surgically fitted with a simple distal ileal T-cannula and a jugular venous catheter. The pigs were fed a basal diet without antibiotics (control; CON) or with antibiotics (antibiotic; ANTI), for 2 weeks. The results showed that feeding AGM did not affect weight gain or digestive enzyme activity. The antibiotics increased the concentration of urea N (P<0.05). However, they reduced N utilization, and the total tract apparent digestibility of isoleucine, methionine, valine, tyrosine and total AA (P<0.05). Furthermore, the antibiotics increased the terminal ileum apparent digestibility of CP, phenylalanine, valine, alanine, tyrosine and total AA (P<0.05). AGM markedly altered the composition of the microbiota in the ileum and feces, with a reduction in populations of Bifidobacterium, Lactobacillus and Ruminococcus, and an increase in the abundance of Escherichia coli (P<0.05). The antibiotics also significantly increased the concentration of cadaverine and ammonia, both in ileal digesta and feces (P<0.05), suggesting a marked impact on N metabolism in the intestine. The analyses indicated that the alteration of gut microbiota was correlated with the apparent digestibility of CP and AA in the intestine. These findings suggest that the AGM-induced alteration of gut microbiota may contribute to the change in intestinal N metabolism, and consequently, N excretion from the body. These results also suggest that antibiotics could have a significant effect on host N metabolism. The present study contributes to our understanding of the effects of antibiotics and provides a rational scientific basis for diet formulation during AGM use.


Assuntos
Antibacterianos/farmacologia , Microbioma Gastrointestinal/efeitos dos fármacos , Nitrogênio/metabolismo , Suínos/metabolismo , Animais , Dieta/veterinária , Fermentação/efeitos dos fármacos , Masculino , Suínos/microbiologia
15.
Zhonghua Liu Xing Bing Xue Za Zhi ; 39(2): 184-187, 2018 Feb 10.
Artigo em Chinês | MEDLINE | ID: mdl-29495202

RESUMO

Objective: To understand the rate on tobacco use and associated factors in junior middle school students in Shaanxi province. Methods: We used a multi-stage stratified random sampling method to select students from 30 junior middle schools in 10 areas of Shaanxi province in 2013. All the participants completed a self-administered questionnaire. Results: A total of 4 633 questionnaires were dispatched and 4 298 were qualified for further analysis. The current smoking rate of junior middle school students in Shaanxi was 6.5%, with rate in male (11.1%) higher than that of female students (1.7%). The current smoking rate of students in grade three (9.3%) was higher than those of students in grade one (3.5%) or in grade two (7.0%). The smoking rate of students with pocket money more than 31 Yuan per week was (10.0%) higher than those of students with pocket money less than 10 Yuan (4.6%) or 10-30 Yuan (6.3%) per week. Results from the logistic regression analysis showed that factors as: male, school located in the city, older age, with more pocket money, having smokers in the family and exposure to second hand smoking were high risk factors for current smoking. Conclusion: Rate on current smoking was high in junior middle schools students in Shaanxi, suggesting that comprehensive intervention programs be developed to reduce the rate of tobacco use in junior middle school students.


Assuntos
Cidades , Fumar/epidemiologia , Estudantes/estatística & dados numéricos , Uso de Tabaco/epidemiologia , China/epidemiologia , Estudos Transversais , Feminino , Humanos , Masculino , Prevalência , Instituições Acadêmicas , Inquéritos e Questionários , Poluição por Fumaça de Tabaco/efeitos adversos
16.
Oncogene ; 36(35): 5023-5034, 2017 08 31.
Artigo em Inglês | MEDLINE | ID: mdl-28459460

RESUMO

Melanoma-associated antigen A1 (MAGEA1) is member of the MAGE gene family that is expressed in male germ line cells and placenta under normal physiological conditions. Although MAGEA1's expression levels have been evaluated as one of the cancer testis (CT) antigens for immunotherapy in melanoma and several other cancers, its functional role and signaling mechanisms are largely unknown. In this study, we examined the functional involvement and signaling mechanisms of MAGEA1 in breast and ovarian cancer cells. Inhibitory effects of MAGEA1 on cell proliferation and migration were observed using both gain-of- (MAGEA1 overexpression) and loss-of- (siRNA interference) function approaches in breast (MCF-7 and MDA-MB-231) and ovarian (SKOV3 and SKOV3ip) cancer cell lines. We revealed a novel interaction between MAGEA1 and the intracellular segment of NOTCH1 receptor (NICD1). MAGEA1 reduced NICD1's stability by promoting the ubiquitin modification of NICD1. MAGEA1 also interacted with FBXW7, subunit of E3 ubiquitin protein ligase complex SCF, and the latter was functionally involved in NICD1 ubiquitination and degradation. In addition, siRNA interference of FBXW7 reversed the inhibitory effect of MAGEA1 on migration and proliferation of MCF-7 and MDA-MB-231 cells. These newly discovered MAGEA1-NICD1 and MAGEA1-FBXW7 interactions have potential clinical implications in breast and ovarian cancer treatment.


Assuntos
Neoplasias da Mama/metabolismo , Proteínas de Ciclo Celular/metabolismo , Proteínas F-Box/metabolismo , Antígenos Específicos de Melanoma/metabolismo , Neoplasias Ovarianas/metabolismo , Receptor Notch1/metabolismo , Ubiquitina-Proteína Ligases/metabolismo , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Proteínas de Ciclo Celular/genética , Linhagem Celular Tumoral , Proliferação de Células/fisiologia , Proteínas F-Box/genética , Proteína 7 com Repetições F-Box-WD , Feminino , Humanos , Células MCF-7 , Antígenos Específicos de Melanoma/genética , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/patologia , Receptor Notch1/genética , Transdução de Sinais , Transfecção , Ubiquitina-Proteína Ligases/genética , Ubiquitinação
18.
Genet Mol Res ; 15(1)2016 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-26909991

RESUMO

The whole-genome sequencing of coxsackievirus (CV)-A10 does not follow a conventional experimental protocol. To fully understand the genetic variation and evolution of CV-A10, complete genome amplification is necessary. Most previous studies have concentrated on partial sequences of the CV-A10 genome, such as the VP1 gene. The few studies that have investigated CV-A10 at the genomic level have reported only two complete genome sequences to GenBank. The basic fault may be attributed to the regional nature of the genetics and evolution of CV-A10 and to the lack of laboratory procedures for obtaining the genomes. In this study, we present a robust "three-step" protocol performed with A105UF/A820, EVP4/A6141, and A4879/A1005R for the full-length genome amplification of CV-A10. The results revealed that the method is able to accurately and reproducibly amplify three fragments with overlaps of the full-length genome of eight CV-A10 strains. Compared with other methods, this assay is both quick and specific. In addition, the three-step protocol could be capable of amplifying the full-length genomes of CV-A10 strains isolated from different countries and regions. The specific three-step protocol may be particularly useful for investigating samples co-infected with CV-A10 and other viruses.


Assuntos
Enterovirus Humano A/genética , Genoma Viral , RNA Viral/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa/métodos , Mapeamento Cromossômico , Primers do DNA/síntese química , Primers do DNA/genética , Genótipo
20.
West Indian Med J ; 65(2): 267-270, 2015 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-26716799

RESUMO

BACKGROUND: The prevalence of end-stage renal disease in Taiwan is the highest in the world; haemodialysis accounts for about 7% of the expenditure of the National Health Insurance. Nursing home residents with chronic kidney disease (CKD) have not been identified yet in Taiwan, along with associated risk factors. The objective of this study is to investigate the risk factors of CKD in long-term care facilities in Taiwan and those significantly associated with the presence of CKD. METHODS: The nursing home residents who received health examination between January and June 2012, age ≥ 55 years, were enrolled in this study. They were categorized into two subgroups according to estimated glomerular filtration rate (eGFR): < 60 and ≥ 60 mL/min. Risk factors were evaluated per recommendations from the National Kidney Foundation: body mass index (BMI), waist circumference, blood pressure, fasting glucose and lipid profile. Metabolic syndrome among the residents was also identified. RESULTS: Fifty-three nursing home residents were enrolled in the final study; 16 (30%) had eGFR below 60 mL/min, and nine (56%) of them had BMI higher than 25 kg/m2. The residents with advanced CKD had significantly higher BMI, triglyceride and lower high-density lipoprotein (HDL). Twelve (75%) had metabolic syndrome. Central obesity was observed in 10 (63%) with advanced CKD. CONCLUSION: Most of the nursing home elderly with advanced CKD have poor control of associated risk factors, including obesity, hypertension, dyslipidaemia and hyperglycaemia. For them, metabolic syndrome may be a major contributant to the aetiology. Monitoring their BMI and waist circumference is a simple but effective way to suspect the presence of CKD.

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