RESUMEN
BACKGROUND: The association between tumor-infiltrating lymphocyte (TIL) levels and the response to neoadjuvant therapy (NAT) in patients with triple-negative breast cancer (TNBC) remains unclear. AIM: To investigate the predictive potential of TIL levels for the response to NAT in TNBC patients. METHODS: A systematic search of the National Center for Biotechnology Information PubMed database was performed to collect relevant published literature prior to August 31, 2023. The correlation between TIL levels and the NAT pathologic complete response (pCR) in TNBC patients was assessed using a systematic review and meta-analysis. Subgroup analysis, sensitivity analysis, and publication bias analysis were also conducted. RESULTS: A total of 32 studies were included in this meta-analysis. The overall meta-analysis results indicated that the pCR rate after NAT treatment in TNBC patients in the high TIL subgroup was significantly greater than that in patients in the low TIL subgroup (48.0% vs 27.7%) (risk ratio 2.01; 95% confidence interval 1.77-2.29; P < 0.001, I 2 = 56%). Subgroup analysis revealed that the between-study heterogeneity originated from differences in study design, TIL level cutoffs, and study populations. Publication bias could have existed in the included studies. The meta-analysis based on different NAT protocols revealed that all TNBC patients with high levels of TILs had a greater rate of pCR after NAT treatment in all protocols (all P ≤ 0.01), and there was no significant between-protocol difference in the statistics among the different NAT protocols (P = 0.29). Additionally, sensitivity analysis demonstrated that the overall results of the meta-analysis remained consistent when the included studies were individually excluded. CONCLUSION: TILs can serve as a predictor of the response to NAT treatment in TNBC patients. TNBC patients with high levels of TILs exhibit a greater NAT pCR rate than those with low levels of TILs, and this predictive capability is consistent across different NAT regimens.
RESUMEN
PCR-RFLP was used to analyze the polymorphisms of MC4R, LEP, H-FABP genes in a swine breed composite (DIV2) and 4 swine breeds (Yorkshire, Landrace, Meishan, Bamei). The association study of these polymorphisms with several economic traits was carried out on a DIV2 population. The results obtained showed that MC4R/TaqI genotype had an effect for average backfat thickness (P < 0.05) and lean meat percentage (P < 0.05). At locus LEP/HinfI animals of AA genotype had lower test daily gain than that of BB (P < 0.01) or AB genotype (P < 0.05). At the H-FABP/HaeIII locus lean meat percentage of the individuals with genotype DD were higher than that with genotype dd (P < 0.05). Linkage disequilibrium analysis among MC4R, LEP and H-FABP revealed that these genes were independent. This represented two or more genes that could be combined together within one genotype in order to facilitate breeding for objective traits. In addition, a method allowing simultaneous detection of fragments of MC4R and LEP gene was developed.
Asunto(s)
Proteínas de Unión a Ácidos Grasos/genética , Leptina/genética , Desequilibrio de Ligamiento/genética , Carne/economía , Polimorfismo Genético , Receptor de Melanocortina Tipo 4/genética , Sus scrofa/genética , Animales , Cruzamiento , Frecuencia de los Genes/genética , Estudios de Asociación Genética , Sitios Genéticos/genética , Genotipo , Reacción en Cadena de la Polimerasa , Polimorfismo de Longitud del Fragmento de Restricción/genética , Carácter Cuantitativo HeredableRESUMEN
The aim of the present study was to investigate the effects of high fructose and high fat feeding on muscle lipid metabolism and to illustrate the mechanisms by which the two different dietary factors induce muscle lipid accumulation. C57BL/J6 mice were fed either a standard, high-fructose (HFru) or high-fat diet. After 16 weeks feeding, mice were killed and plasma triglyceride (TG) and free fatty acid (FFA) levels were detected. In addition, muscle TG and long chain acyl CoA (LCACoA) content was determined, glucose tolerance was evaluated and the protein content of fatty acid translocase CD36 (FATCD36) in muscle was measured. Mitochondrial oxidative function in the muscle was evaluated by estimating the activity of oxidative enzymes, namely cytochrome oxidase (COx), citrate synthase (CS) and ß-hydroxyacyl CoA dehydrogenase (ß-HAD), and the muscle protein content of carnitine palmitoyltransferase-1 (CPT-1), cyclo-oxygenase (COX)-1 and proliferator-activated receptor coactivator (PGC)-1α was determined. Finally, sterol regulatory element-binding protein-1c (SREBP-1c) gene expression and fatty acid synthase (FAS) protein content were determined in muscle tissues. After 16 weeks, plasma TG and FFA levels were significantly increased in both the HFru and HF groups. In addition, mice in both groups exhibited significant increases in muscle TG and LCACoA content. Compared with mice fed the standard diet (control group), those in the HFru and HF groups developed glucose intolerance and exhibited increased FATCD36 protein levels, enzyme activity related to fatty acid utilization in the mitochondria and protein expressions of CPT-1, COX-1 and PGC-1α in muscle tissue. Finally, mice in both the HFru and HF groups exhibited increase SREBP-1c expression and FAS protein content. In conclusion, high fructose and high fat feeding lead to similar changes in muscle lipid metabolism in C57BL/J6 mice. Lipid accumulation in the muscle may be associated with increased expression of proteins related to lipid transportation and synthesis.
Asunto(s)
Dieta Alta en Grasa/efectos adversos , Grasas de la Dieta/efectos adversos , Fructosa/efectos adversos , Metabolismo de los Lípidos/efectos de los fármacos , Músculo Esquelético/metabolismo , Acilcoenzima A/sangre , Animales , Glucemia/metabolismo , Western Blotting , Antígenos CD36/metabolismo , Grasas de la Dieta/administración & dosificación , Activación Enzimática , Fructosa/administración & dosificación , Intolerancia a la Glucosa/sangre , Insulina/sangre , Masculino , Ratones , Ratones Endogámicos C57BL , Mitocondrias Musculares/efectos de los fármacos , Mitocondrias Musculares/metabolismo , Músculo Esquelético/efectos de los fármacos , Músculo Esquelético/enzimología , Reacción en Cadena en Tiempo Real de la Polimerasa , Triglicéridos/sangre , Triglicéridos/metabolismoRESUMEN
BACKGROUND: The association between atrial fibrillation (AF) and the prognosis of intravenous thrombolysis (IVT) in patients with Acute Ischemic Stroke (AIS) is debated. Hypokalemia is highly prevalent in patients with AF. We aimed to investigate the effect of hypokalemia and AF on the prognosis of AIS patients following IVT. METHODS: AIS patients undergoing IVT were enrolled and divided into four groups: normokalemia and non-AF, normokalemia and AF, hypokalemia and non-AF, hypokalemia and AF. Logistic regression was applied to analyze the impact of hypokalemia, AF, and their combination on the prognosis of patients. RESULTS: The analysis included 567 patients, 184 with 3-month poor prognosis (modified Rankin Scale score of 3-6). Following adjustment of risk factors, hypokalemia and AF increased the risks for 3-month poor prognosis (adjusted Odds Ratios (aOR) = 4.97; 95% confidence interval (CI), 1.99-12.44, P =.001), early neurological deterioration (END) (aOR=7.98; 95% CI, 3.55-17.95, P <.001), 1-year poor prognosis (aOR=5.05; 95% CI, 1.99-12.81, P =.001), 1-year all-cause death (aOR =6.95; 95% CI, 2.35-20.56, P <.001). Patients with normokalemia and AF merely increased the risk of 1-year all-cause death (aOR=2.69; 95% CI, 1.10-6.61, P=.013). Patients with hypokalemia and non-AF were not associated with any poor prognosis. There were combined and interactive effects of hypokalemia with AF on the 3-month poor prognosis (P for interaction =.039) and END (P for interaction=.005). CONCLUSION: Hypokalemia and AF synergistically increased the risk of near-term poor prognosis, END, long-term poor prognosis, and all-cause death of AIS patients following IVT.
Asunto(s)
Fibrilación Atrial , Isquemia Encefálica , Hipopotasemia , Accidente Cerebrovascular Isquémico , Accidente Cerebrovascular , Fibrilación Atrial/complicaciones , Fibrilación Atrial/tratamiento farmacológico , Isquemia Encefálica/complicaciones , Humanos , Hipopotasemia/complicaciones , Pronóstico , Accidente Cerebrovascular/complicaciones , Accidente Cerebrovascular/tratamiento farmacológico , Terapia Trombolítica/efectos adversos , Resultado del TratamientoRESUMEN
BACKGROUND: Triple negative breast cancer (TNBC) is usually aggressive and accompanied by a poor prognosis. The molecular biological mechanism of TNBC pathogenesis is still unclear, and requires more detailed research. The aim of this study was to screen and verify potential biomarkers of TNBC, and provide new clues for the treatment and diagnosis of TNBC. METHODS: In this work, GSE76250 was downloaded from the Gene Expression Omnibus (GEO) database and included 165 TNBC samples and 33 paired normal breast tissues. The R software and its related software package were used for data processing and analysis. Compared with normal tissues, genes with a false discovery rate (FDR) <0.01 and log fold change (logFC) ≥1 or ≤-1 were identified as differentially expressed genes (DEGs) by limma package. Survival prognoses were analyzed by Kaplan-Meier plotter database. RESULTS: In total, 160 up-regulated and 180 down-regulated genes were identified. The biological mechanism of enrichment analysis presented that DEGs were significantly enriched in chromosome segregation, extracellular matrix, and extracellular matrix structural constituent, among others. A total of 8 hub genes (CCNB1, CDK1, TOP2A, MKI67, TTK, CCNA2, BUB1, and PLK1) were identified by the protein-protein interaction network (PPIN) and Cytoscape software. Survival prognosis of these hub genes showed that they were negatively correlated with overall survival. CONCLUSIONS: The 8 hub genes and pathways that were identified might be involved in tumorigenesis and become new candidate biomarkers for TNBC treatment.
RESUMEN
Obese individuals are more susceptible to comorbidities than individuals of healthy weight, including cardiovascular disease and metabolic disorders. MicroRNAs are a class of small and noncoding RNAs that are implicated in the regulation of chronic human diseases. We previously reported that miR-125b plays a critical role in adipogenesis in vitro. However, the involvement of miR-125b-2 in fat metabolism in vivo remains unknown. In the present study, miR-125b-2 knockout mice were generated using CRISPR/CAS9 technology, resulting in mice with a 7 bp deletion in the seed sequence of miR-125b-2. MiR-125b-2 knockout increased the weight of liver tissue, epididymal white fat and inguinal white fat. MiR-125b-2 knockout also increased adipocyte volume in HFD-induced obese mice, while there were no significant differences in body weight and feed intake versus mice fed a normal diet. Additionally, qRT-PCR and western blot analysis revealed that the expression of the miR-125b-2 target gene SCD-1 and fat synthesis-associated genes, such as PPARγ and C/EBPα, were significantly up-regulated in miR-125b-2KO mice (P < 0.05). Moreover, miR-125b-2KO altered HFD-induced changes in glucose tolerance and insulin resistance. In conclusion, we show that miR-125b-2 is a novel potential target for regulating fat accumulation, and also a candidate target to develop novel treatment strategies for obesity and diabetes.
Asunto(s)
Dieta Alta en Grasa , Resistencia a la Insulina , MicroARNs/genética , Animales , Humanos , Ratones , Ratones Noqueados , Reproducibilidad de los ResultadosRESUMEN
Enterocytozoon bieneusi is an intestinal pathogen that infects a wide range of species, including humans. Cattle constitute an important host for E. bieneusi; however, there is a scarcity of information on the prevalence and genotyping of E. bieneusi in cattle in the Hainan Province of China. In this study, PCR analysis of 314 fecal samples from cattle in six cities of Hainan was performed for genotype identification. The average prevalence of E. bieneusi in these animals was 9.9% (31/314), and ranged from 0.0% (0/12) to 20.5% (8/39). Five known genotypes - EbpC (n = 14), BEB4 (n = 12), J (n = 2), I (n = 1), and CHG5 (n = 1) - and a novel genotype: HNC-I (n = 1) - were identified. Genotypes EbpC and HNC-I were placed in zoonotic Group 1, and the remaining four genotypes (BEB4, J, I, and CHG5) were placed in Group 2. Since 93.5% of the genotypes found in the cattle (29/31) (EbpC, BEB4, J, and I) have previously been found in humans, these genotypes are probably involved in the transmission of microsporidiosis to humans.
TITLE: Génotypage et potentiel zoonotique d'Enterocytozoon bieneusi chez les bovins élevés dans la province de Hainan, la région la plus au sud de la Chine. ABSTRACT: Enterocytozoon bieneusi est un pathogène intestinal qui infecte un large éventail d'espèces, y compris les humains. Le bétail constitue un hôte important pour E. bieneusi, mais les informations sur la prévalence et le génotypage d'E. bieneusi chez les bovins de la province de Hainan en Chine sont rares. Dans cette étude, une analyse PCR de 314 échantillons fécaux provenant de bovins dans six villes de Hainan a été réalisée pour l'identification du génotype. La prévalence moyenne d'E. bieneusi chez ces animaux était de 9,9 % (31/314), et variait de 0,0 % (0/12) à 20,5 % (8/39). Cinq génotypes connus, EbpC (n = 14), BEB4 (n = 12), J (n = 2), I (n = 1) et CHG5 (n = 1), et un nouveau génotype, HNC-I (n = 1), ont été identifiés. Les génotypes EbpC et HNC-I sont placés dans le groupe zoonotique 1, et les quatre génotypes restants (BEB4, J, I et CHG5) sont placés dans le groupe 2. Puisque 93,5 % (29/31) (EbpC, BEB4, J et I) des génotypes trouvés chez les bovins ont déjà été trouvés chez l'homme, ces génotypes sont probablement impliqués dans la transmission de la microsporidiose à l'homme.
Asunto(s)
Enterocytozoon , Microsporidiosis , Animales , Bovinos , China/epidemiología , Enterocytozoon/genética , Heces/parasitología , Genotipo , Especificidad del Huésped , Humanos , Microsporidiosis/epidemiología , Microsporidiosis/transmisión , Filogenia , Prevalencia , Zoonosis/epidemiología , Zoonosis/parasitologíaRESUMEN
OBJECTIVE: To explore the feasibility of combining human patient simulator (HPS) drivers with micro-division teaching during primary resident training by George Miller' medical education step-wised principle of goal and competence. METHOD: The 20 residents from department of anesthesia who are less than 3 years in clinical training were randomized into two Groups. The all residents in Group T received HPS training, and no HPS training in Group N. In simulation system, we designed 8 programmed critical and emergency events. We disassembled and quantified the programmed design and training process with Micro-division teaching principle. The training mode was run by test-feedback-self-analysis-instructor guide-summarize-re-practice-retest. The feedback assessment from all residents were collected after finishing HPS training. RESULTS: The training score in Group T was much higher than Group N (P < 0.05). CONCLUSIONS: The training mode with HPS is an accessory teaching means because it can improve clinical thinking and skill training of primary resident.
Asunto(s)
Simulación por Computador , Educación Médica Continua , Medicina de Emergencia/educación , Capacitación en Servicio , Médicos , Humanos , Programas InformáticosRESUMEN
Enterocytozoon bieneusi is an important pathogen commonly found in humans and animals. Farmed animals with close contact to humans are important hosts of E. bieneusi. The role of goats in the transmission of E. bieneusi, however, remains unclear. In this study, 341 fresh fecal samples of black goats were collected from five locations in Hainan Province, China. Enterocytozoon bieneusi was identified and genotyped by sequences of the internal transcribed spacer (ITS) region. Phylogenetic analysis was performed by constructing a neighbor-joining tree of the ITS gene sequences. The average prevalence of E. bieneusi in black goats was 24.0% (82/341) with rates ranging from 6.3% (4/63) to 37.2% (32/86) across the locations (χ2 = 17.252, p < 0.01). Eight genotypes of E. bieneusi were identified, including six known genotypes: CHG5 (n = 47); CHG3 (n = 23); CHG2 (n = 4); CM21 (n = 3); D (n = 2); and AHG1 (n = 1), and two novel genotypes termed HNG-I (n = 1) and HNG-II (n = 1). In the phylogenetic tree, genotype D was clustered into Group 1 and the other identified genotypes were included in Group 2. This represents the first report identifying E. bieneusi in black goats from Hainan Province, with a high prevalence and wide occurrence demonstrated. The two new genotypes identified provide additional insights into the genotypic variations in E. bieneusi. Due to the small percentage of zoonotic genotypes in these animals, there is minimal risk of zoonotic transmission of E. bieneusi.
TITLE: Identification du génotype et analyse phylogénétique d'Enterocytozoon bieneusi chez des chèvres noires (Capra hircus) de la province de Hainan, en Chine. ABSTRACT: Enterocytozoon bieneusi est un agent pathogène important que l'on trouve couramment chez l'homme et les animaux. Les animaux d'élevage, en contact étroit avec l'homme, sont des hôtes importants d'E. bieneusi. Le rôle des chèvres dans la transmission d'E. bieneusi reste toutefois incertain. Dans cette étude, 341 échantillons de fèces fraîches de chèvres noires ont été prélevés dans cinq sites de la province de Hainan, en Chine. Enterocytozoon bieneusi a été identifié et génotypé par des séquences de la région de l'espaceur interne transcrit (ITS). L'analyse phylogénétique a été réalisée en construisant un arbre de jonction voisine des séquences du gène ITS. La prévalence moyenne d'E. bieneusi chez les chèvres noires était de 24,0 % (82/341), avec des taux allant de 6,3 % (4/63) à 37,2 % (32/86) dans tous les sites (χ2 = 17,252, p < 0,01). Huit génotypes d'E. bieneusi ont été identifiés, dont six génotypes connus: CHG5 (n = 47) ; CHG3 (n = 23) ; CHG2 (n = 4) ; CM21 (n = 3) ; D (n = 2) ; AHG1 (n = 1) et deux nouveaux génotypes appelés HNG-I (n = 1) et HNG-II (n = 1). Dans l'arbre phylogénétique, le génotype D appartenait au groupe 1 et les autres génotypes identifiés étaient inclus dans le groupe 2. Il s'agit du premier rapport identifiant E. bieneusi chez des chèvres noires de la province de Hainan, avec une prévalence élevée et une occurrence étendue. Les deux nouveaux génotypes identifiés fournissent des informations supplémentaires sur les variations génotypiques chez E. bieneusi. En raison du faible pourcentage de génotypes zoonotiques chez ces animaux, le risque de transmission zoonotique d'E. bieneusi est minime.
Asunto(s)
Enterocytozoon/clasificación , Enterocytozoon/genética , Enfermedades de las Cabras/epidemiología , Cabras/microbiología , Microsporidiosis/veterinaria , Filogenia , Animales , China/epidemiología , ADN de Hongos/genética , ADN Espaciador Ribosómico/genética , Granjas , Heces/microbiología , Variación Genética , Genotipo , Enfermedades de las Cabras/transmisión , Microsporidiosis/epidemiología , PrevalenciaRESUMEN
Ammonia detoxification, which takes place via the hepatic urea cycle, is essential for nitrogen homeostasis and physiological well-being. It has been reported that a reduction in dietary protein reduces urea nitrogen. MicroRNAs (miRNAs) are major regulatory non-coding RNAs that have significant effects on several metabolic pathways; however, little is known on whether miRNAs regulate hepatic urea synthesis. The objective of this study was to assess the miRNA expression profile in a low protein diet and identify miRNAs involved in the regulation of the hepatic urea cycle using a porcine model. Weaned 28-days old piglets were fed a corn-soybean normal protein diet (NP) or a corn-soybean low protein diet (LP) for 30 d. Hepatic and blood samples were collected, and the miRNA expression profile was assessed by sequencing and qRT-PCR. Furthermore, we evaluated the possible role of miR-19b in urea synthesis regulation. There were 25 differentially expressed miRNAs between the NP and LP groups. Six of these miRNAs were predicted to be involved in urea cycle metabolism. MiR-19b negatively regulated urea synthesis by targeting SIRT5, which is a positive regulator of CPS1, the rate limiting enzyme in the urea cycle. Our study presented a novel explanation of ureagenesis regulation by miRNAs.
RESUMEN
Milk-derived exosomes were identified as a novel mechanism of mother-to-child transmission of regulatory molecules, but their functions in intestinal tissues of neonates are not well-studied. Here, we characterized potential roles of porcine milk-derived exosomes in the intestinal tract. In vitro, treatment with milk-derived exosomes (27 ± 3 ng and 55 ± 5 ng total RNA) significantly promoted IPEC-J2 cell proliferation by MTT, CCK8, EdU fluorescence and EdU flow cytometry assays. The qRT-PCR and Western blot analyses indicated milk-derived exosomes (0.27 ± 0.03 µg total RNA) significantly promoted expression of CDX2, IGF-1R and PCNA, and inhibited p53 gene expression involved in intestinal proliferation. Additionally, six detected miRNAs were significantly increased in IPEC-J2 cell, while FAS and SERPINE were significantly down-regulated relative to that in control. In vivo, treated groups (0.125 µg and 0.25 µg total RNA) significantly raised mice' villus height, crypt depth and ratio of villus length to crypt depth of intestinal tissues, significantly increased CDX2, PCNA and IGF-1R' expression and significantly inhibited p53' expression. Our study demonstrated that milk-derived exosomes can facilitate intestinal cell proliferation and intestinal tract development, thus giving a new insight for milk nutrition and newborn development and health.