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BACKGROUND: In the beef industry, bull calves are usually castrated to improve flavor and meat quality; however, this can reduce their growth and slaughter performance. The gut microbiota is known to exert a significant influence on growth and slaughter performance. However, there is a paucity of research investigating the impact of castration on gut microbiota composition and its subsequent effects on slaughter performance and meat flavor. RESULT: The objective of this study was to examine the processes via which castration hinders slaughter productivity and enhances meat quality. Bull and castrated calves were maintained under the same management conditions, and at slaughter, meat quality was assessed, and ileum and epithelial tissue samples were obtained. The research employed metagenomic sequencing and non-targeted metabolomics techniques to investigate the makeup of the microbiota and identify differential metabolites. The findings of this study revealed the Carcass weight and eye muscle area /carcass weight in the bull group were significantly higher than those in the steer group. There were no significant differences in the length, width, and crypt depth of the ileum villi between the two groups. A total of 53 flavor compounds were identified in the two groups of beef, of which 16 were significantly higher in the steer group than in the bull group, and 5 were significantly higher in the bull group than in the steer group. In addition, bacteria, Eukaryota, and virus species were significantly separated between the two groups. The lipid metabolism pathways of α-linolenic acid, linoleic acid, and unsaturated fatty acids were significantly enriched in the Steers group. Compared with the steer group, the organic system pathway is significantly enriched in the bull group. The study also found that five metabolites (LPC (0:0/20:3), LPC (20:3/0:0), LPE (0:0/22:5), LPE (22:5/0:0), D-Mannosamine), and three species (s_Cloning_vector_Hsp70_LexA-HP1, s_Bacteroides_Coprophilus_CAG: 333, and s_Clostridium_nexile-CAG: 348) interfere with each other and collectively have a positive impact on the flavor compounds of beef. CONCLUSIONS: These findings provide a basic understanding that under the same management conditions, castration does indeed reduce the slaughter performance of bulls and improve the flavor of beef. Microorganisms and metabolites contribute to these changes through interactions.
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Microbioma Gastrointestinal , Íleon , Carne Roja , Animales , Bovinos , Masculino , Carne Roja/microbiología , Íleon/microbiología , Íleon/metabolismo , MetabolómicaRESUMEN
Sorafenib is one a first-line therapeutic drugs for advanced hepatocellular carcinoma (HCC). However, only 30% of patients benefit from sorafenib due to drug resistance. We and other groups have revealed that nuclear factor I B (NFIB) regulates liver regeneration and carcinogenesis, but its role in drug resistance is poorly known. We found that NFIB was more upregulated in sorafenib-resistant SMMC-7721 cells compared to parental cells. NFIB knockdown not only sensitized drug-resistant cells to sorafenib but also inhibited the proliferation and invasion of these cells. Meanwhile, NFIB promoted the proliferation and invasion of HCC cells in vitro and facilitated tumor growth and metastasis in vivo. Knocking down NFIB synergetically inhibited tumor growth with sorafenib. Mechanically, gene expression profiling and subsequent verification experiments proved that NFIB could bind with the promoter region of a complex I inhibitor NDUFA4L2 and promote its transcription. Transcriptional upregulation of NDUFA4L2 by NFIB could thus inhibit the sorafenib-induced reactive oxygen species accumulation. Finally, we found that NFIB was highly expressed in HCC tissues, and high NFIB expression level was associated with macrovascular invasion, advanced tumor stage, and poor prognosis of HCC patients (n = 156). In summary, we demonstrated that NFIB could transcriptionally upregulate NDUFA4L2 to enhance both intrinsic and acquired sorafenib resistance of HCC cells by reducing reactive oxygen species induction.
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Antineoplásicos , Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Antineoplásicos/farmacología , Carcinoma Hepatocelular/patología , Línea Celular Tumoral , Proliferación Celular , Resistencia a Antineoplásicos/genética , Regulación Neoplásica de la Expresión Génica , Neoplasias Hepáticas/patología , Factores de Transcripción NFI/genética , Especies Reactivas de Oxígeno/metabolismo , Sorafenib/farmacologíaRESUMEN
BACKGROUND: There is limited real-world evidence that describes patients with newly diagnosed multiple myeloma (NDMM) treated with the bortezomib, lenalidomide, and dexamethasone (VRd) triplet regimen. We evaluated patient characteristics and treatment outcomes among nontransplanted NDMM patients who received VRd as their first line of therapy (LOT) in US oncology practice settings. METHODS: This retrospective observational cohort study evaluated patients from the Flatiron MM Core Registry who received VRd as first LOT between November 1, 2015, and February 28, 2021. Progression-free survival (PFS) was analyzed using the Kaplan-Meier method. Associations between patient demographic and clinical characteristics and PFS were evaluated using a multivariable Cox proportional hazards model. RESULTS: A total of 2342 eligible patients with VRd as first LOT were identified (mean age, 67.0 years). Among all identified patients, 64.3% were ≥ 65 years of age, 25.5% were elderly (≥75 years), and 47.9% were frail. Among patients with available data, 21.2% had high-risk cytogenetics, and the majority had International Staging System (ISS) stage I/II disease (71.8%), and Eastern Cooperative Oncology Group performance status (ECOG PS) score 0/1 (81.2%). Median duration of therapy was 5.5 months. With median follow-up of 21.0 months, median PFS and time-to-next-treatment were 26.5 and 16.1 months, respectively. Higher risk of disease progression or death was seen in patients categorized as elderly (hazard ratio [HR] = 1.37; 95% confidence interval [CI]: 1.13-1.66 vs patients < 65 years), having high-risk cytogenetics (HR = 1.44; 95% CI: 1.19-1.75 vs standard risk), having ISS disease stages II and III (HR = 1.31; 95% CI: 1.06-1.63 and HR = 1.37; 95% CI: 1.10-1.70 versus stage I, respectively), and having worse ECOG PS score (≥2) (HR = 1.49; 95% CI: 1.22-1.81 versus functionally active patients). CONCLUSIONS: The majority of patients treated with VRd in this study were ≥ 65 years of age, were ISS stage I/II, had an ECOG PS score of 0/1, and had standard cytogenetic risk. Median PFS observed in real-world practice was notably shorter than that observed in the SWOG S0777 clinical trial. In nontransplanted patients treated with VRd as first LOT, a higher risk of disease progression or death was associated with older age, having high-risk cytogenetics, worse disease stage, and worse ECOG PS score.
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Mieloma Múltiple , Adulto , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Bortezomib , Dexametasona , Progresión de la Enfermedad , Humanos , Lenalidomida/uso terapéutico , Mieloma Múltiple/terapia , Estudios Retrospectivos , Resultado del Tratamiento , Estados UnidosRESUMEN
This study was designed to investigate the effects of dietary starch structure on muscle protein synthesis and gastrointestinal amino acid (AA) transport and metabolism of goats. Twenty-seven Xiangdong black female goats (average body weight = 9·00 ± 1·12 kg) were randomly assigned to three treatments, i.e., fed a T1 (normal maize 100 %, high amylose maize 0 %), T2 (normal maize 50 %, high amylose maize 50 %) and T3 (normal maize 0 %, high amylose maize 100 %) diet for 35 d. All AA in the ileal mucosa were decreased linearly as amylose:amylopectin increased in diets (P < 0·05). The plasma valine (linear, P = 0·03), leucine (linear, P = 0·04) and total AA content (linear, P = 0·03) increased linearly with the increase in the ratio of amylose in the diet. The relative mRNA levels of solute carrier family 38 member 1 (linear, P = 0·01), solute carrier family 3 member 2 (linear, P = 0·02) and solute carrier family 38 member 9 (linear, P = 0·02) in the ileum increased linearly with the increase in the ratio of amylose in the diet. With the increase in the ratio of amylose:amylopectin in the diet, the mRNA levels of acetyl-CoA dehydrogenase B (linear, P = 0·04), branched-chain amino acid transferase 1 (linear, P = 0·02) and branched-chain α-keto acid dehydrogenase complex B (linear, P = 0·01) in the ileum decreased linearly. Our results revealed that the protein abundances of phosphorylated mammalian target of rapamycin (p-mTOR) (P < 0·001), phosphorylated 4E-binding protein 1 (P < 0·001) and phosphorylated ribosomal protein S6 kinases 1 (P < 0·001) of T2 and T3 were significantly higher than that of T1. In general, a diet with a high amylose ratio could reduce the consumption of AA in the intestine, allowing more AA to enter the blood to maintain higher muscle protein synthesis through the mTOR pathway.
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Amilopectina , Amilosa , Sistemas de Transporte de Aminoácidos/genética , Aminoácidos de Cadena Ramificada/metabolismo , Amilopectina/farmacología , Amilosa/farmacología , Alimentación Animal/análisis , Animales , Dieta/veterinaria , Femenino , Cabras/metabolismo , Íleon/metabolismoRESUMEN
Aim: To evaluate among multiple myeloma (MM) patients, the proportions with first-line bortezomib/lenalidomide/dexamethasone (VRd) dose modifications and the associated baseline patient characteristics. Patients & methods: Adult MM patients treated with first-line VRd were selected from the Optum claims database. VRd dose modifications were defined based on lenalidomide dose. Results: Among 1497 MM patients, 33% received VRd lite and 22% VRd reduced. Compared with VRd regular, VRd lite usage was more likely to be associated with patients aged ≥75 years and female sex; VRd reduced usage was more likely to be associated with female sex and frailty. Conclusion: A large proportion of MM patients received VRd dose modifications in the real-world, which could potentially result in reduced effectiveness of VRd.
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Mieloma Múltiple , Adulto , Humanos , Femenino , Mieloma Múltiple/diagnóstico , Mieloma Múltiple/tratamiento farmacológico , Lenalidomida/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Bortezomib/efectos adversos , Dexametasona/uso terapéuticoRESUMEN
BACKGROUND AND AIMS: Screening for colorectal cancer (CRC) can effectively reduce CRC incidence and mortality. Besides colonoscopy, tests for the detection of biomarkers in stool, blood, or serum, including the fecal immunochemical test (FIT), ColoGuard, Epi proColon, and PolypDx, have recently been advanced. We aimed to identify the characteristics of theoretic, highly efficient screening tests and calculated the effectiveness and cost effectiveness of available screening tests. METHODS: Using the microsimulation-based colon modeling open-source tool (CMOST), we simulated 142,501 theoretic screening tests with variable assumptions for adenoma and carcinoma sensitivity, specificity, test frequency, and adherence, and we identified highly efficient tests outperforming colonoscopy. For available screening tests, we simulated 10 replicates of a virtual population of 2 million individuals, using epidemiologic characteristics and costs assumptions of the United States. RESULTS: Highly efficient theoretic screening tests were characterized by high sensitivity for advanced adenoma and carcinoma and high patient adherence. All simulated available screening tests were effective at 100% adherence to screening and at expected real-world adherence rates. All tests were cost effective below the threshold of 100,000 U.S. dollars per life year gained. With perfect adherence, FIT was the most effective and cost-efficient intervention, whereas Epi proColon was the most effective at expected real-world adherence rates. In our sensitivity analysis, assumptions for patient adherence had the strongest impact on effectiveness of screening. CONCLUSIONS: Our microsimulation study identified characteristics of highly efficient theoretic screening tests and confirmed the effectiveness and cost-effectiveness of colonoscopy and available urine-, blood-, and stool-based tests. Better patient adherence results in superior effectiveness for CRC prevention in the whole population.
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Neoplasias Colorrectales , Detección Precoz del Cáncer , Colonoscopía , Neoplasias Colorrectales/diagnóstico , Neoplasias Colorrectales/epidemiología , Análisis Costo-Beneficio , Humanos , Tamizaje Masivo , Sangre Oculta , Estados Unidos/epidemiologíaRESUMEN
Chimeric antigen receptor (CAR) T-cell therapy is a promising immunotherapy with high acquisition costs, and it has raised concerns about affordability and sustainability in many countries. Furthermore, the current centralized production paradigm for the T cells is less than satisfactory. Therefore, several countries are exploring alternative T-cell production modes. Our study is based on the T-cell production experience in a nonprofit setting in Germany. We first identified the work steps and main activities in the production process. Then we determined the fixed costs and variable costs. Main cost components included personnel and technician salaries, expenditure on equipment, a clean room, as well as production materials. All costs were calculated in 2018 euros and converted into U.S. dollars. For a clean room with one machine for closed and automated manufacturing installed, annual fixed costs summed up to approximately 438 098 ($584 131). The variable cost per production was roughly 34 798 ($46 397). At the maximum capacity of one machine, total cost per product would be close to 60 000 ($78 849). As shown in the scenario analysis, if three machines were to be installed in the clean room, per production cost could be as low as 45 000 (roughly $59905). If a cheaper alternative to lentivirus was used, per production total cost could be further reduced to approximately 33 000 (roughly $44309). Decentralized T-cell production might be a less costly and more efficient alternative to the current centralized production mode that requires a high acquisition cost.
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Técnicas de Cultivo de Célula/instrumentación , Laboratorios/economía , Receptores Quiméricos de Antígenos/metabolismo , Linfocitos T/citología , Centros Médicos Académicos , Técnicas de Cultivo de Célula/economía , Alemania , Humanos , Organizaciones sin Fines de Lucro , Linfocitos T/inmunologíaRESUMEN
Catalysis oxidization has been known to be an effective technique in environmental remediation. However, low efficiency for oxygen activation and difficult recovery of the catalysts in powdery form significantly limit the practical application. In this work, a new-type monolithic α-Ni(OH)2/Ni-foam was fabricated by the hydrothermal process. We found that H atoms of α-Ni(OH)2 can significantly promote oxygen activation, which endows it with favorable NO and NO2 oxidization confirmed by theoretical calculation and in situ DRIFTS. Furthermore, the introduction of Ni foam accelerated the pollutant gas transfer and charge carriers' separation because of its abundant porous structure and high conductivity and its monolithic property simplified the recycling operation. Consequently, the obtained α-Ni(OH)2/Ni-foam achieved an excellent NO oxidation (69.0%) and no toxic NO2 was detected under visible light illumination (λ > 420 nm), indicating its highly promising potential in environmental remediation. Our work provides a conceptually different fresh perception to promote oxygen activation for highly efficient gas purification.
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Hidrógeno , Oxígeno , Catálisis , Oxidación-Reducción , Luz SolarRESUMEN
BACKGROUND & AIMS: Widespread screening for colorectal cancer (CRC) has reduced its incidence and mortality. Previous studies investigated the economic effects of CRC screening. We performed a systematic review to provide up-to-date evidence of the cost effectiveness of CRC screening strategies by answering 3 research questions. METHODS: We searched PubMed, National Institute for Health Research Economic Evaluation Database, Social Sciences Citation Index (via the Web of Science), EconLit (American Economic Association) and 3 supplemental databases for original articles published in English from January 2010 through December 2017. All monetary values were converted to US dollars (year 2016). For all research questions, we extracted, or calculated (if necessary), per-person costs and life years (LYs) and/or quality-adjusted LYs, as well as the incremental costs per LY gained or quality-adjusted LY gained compared with the baseline strategy. A cost-saving strategy was defined as one that was less costly and equally or more effective than the baseline strategy. The net monetary benefit approach was used to answer research question 2. RESULTS: Our review comprised 33 studies (17 from Europe, 11 from North America, 4 from Asia, and 1 from Australia). Annual and biennial guaiac-based fecal occult blood tests, annual and biennial fecal immunochemical tests, colonoscopy every 10 years, and flexible sigmoidoscopy every 5 years were cost effective (even cost saving in most US models) compared to no screening. In addition, colonoscopy every 10 years was less costly and/or more effective than other common strategies in the United States. Newer strategies such as computed tomographic colonography, every 5 or 10 years, was cost effective compared with no screening. CONCLUSIONS: In an updated review, we found that common CRC screening strategies and computed tomographic colonography continued to be cost effective compared to no screening. There were discrepancies among studies from different regions, which could be associated with the model types or model assumptions.
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Neoplasias Colorrectales/diagnóstico , Detección Precoz del Cáncer/métodos , Neoplasias Colorrectales/economía , Análisis Costo-Beneficio , Detección Precoz del Cáncer/economía , Detección Precoz del Cáncer/tendencias , HumanosRESUMEN
BACKGROUND: Unintentional non-fire-related (UNFR) carbon monoxide (CO) poisoning has been among the leading causes of poisoning in the United States. Current estimation of its economic burden is important for an optimal allocation of resources for UNFR CO poisoning prevention. OBJECTIVE: This study was to estimate the morbidity costs of UNFR CO poisoning. We also compared the costs and benefits of installing CO detectors in residences. METHODS: We used 2010-2014 charges and cost data from Healthcare Cost and Utilization Project (HCUP), and Truven© Health MarketScan Commercial Claims and Encounters and Medicare Supplemental data. We directly measured the morbidity cost as the summation of costs for different healthcare services. Benefit of installing CO detector was estimated by summing up the avoidable morbidity cost and mortality cost (value of life). Cost of CO detectors was calculated using the average market price of CO detectors. We also calculated the benefit-to-cost ratio by dividing the benefit by its cost. All expenditures were converted into 2013 U.S. dollars. RESULTS: For UNFR CO poisoning, total annual medical cost ranged from $33.6 to $37.7 million. Annual non-health-sector costs varied from $3.7 to almost $4.4 million. The benefit-to-cost ratio can be as high as 7.2 to 1. CONCLUSION: UNFR CO poisoning causes substantial economic burden in the U.S. The benefit of using CO detectors in homes to prevent UNFR CO poisoning can considerably exceed the cost of installation. Public health programs could use these findings to promote broad installation of CO detectors in homes.
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Intoxicación por Monóxido de Carbono/economía , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Intoxicación por Monóxido de Carbono/epidemiología , Intoxicación por Monóxido de Carbono/mortalidad , Intoxicación por Monóxido de Carbono/prevención & control , Niño , Preescolar , Análisis Costo-Beneficio , Servicio de Urgencia en Hospital/economía , Servicio de Urgencia en Hospital/estadística & datos numéricos , Femenino , Costos de la Atención en Salud/estadística & datos numéricos , Costos de Hospital/estadística & datos numéricos , Hospitalización/economía , Hospitalización/estadística & datos numéricos , Humanos , Masculino , Persona de Mediana Edad , Estados Unidos/epidemiología , Adulto JovenRESUMEN
Only a small proportion of German health expenditure is spent on prevention and early detection (screening). The rationale for screening is to identify persons with disease precursors or at the early stage of diseases when they are still asymptomatic, in order to decrease disease-specific morbidity and mortality. In Germany, the economic evidence is one of the evaluation criteria for screening measures, which, among other things, takes into account the additional cost per additional case detected or per case-related event avoided, as well as a cost-benefit balance.For this purpose, cost-effectiveness analyses, which report marginal or incremental cost effectiveness ratios, comparing a measure with its appropriate alternatives, may be a useful tool. Their application requires a defensible benchmark (threshold) for cost effectiveness and a supplementary analysis of the necessary infrastructure and the budgetary impact associated with program implementation. Also (albeit not only) because of the usually long time required to observe the clinical outcomes of a screening measure, the economic evaluation of such programs regularly involves the application of decision analytic simulation models. With regard to cancer screening programs, the available models indicate an excellent cost-benefit ratio for the fecal occult blood test and colonoscopy for colorectal cancer screening and, similarly, for the use of mammography for breast cancer screening. On the other hand, the economic evidence in favor of low-dose computed tomography for lung cancer screening does not yet appear sufficiently strong, and the currently available health economic evidence does not support the use of PSA testing for prostate screening.
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Detección Precoz del Cáncer , Neoplasias , Análisis Costo-Beneficio , Detección Precoz del Cáncer/economía , Alemania , Humanos , Tamizaje Masivo , Neoplasias/diagnóstico , Neoplasias/economía , Sangre OcultaRESUMEN
Coal gangue is a byproduct of coal mining and processing, and according to incomplete statistics, China has amassed a substantial coal gangue stockpile exceeding 2600 large mountains, which poses a serious threat to the ecological environment. Utilizing gangue as a coarse aggregate to produce gangue concrete (GC) presents a promising avenue for addressing the disposal of coal gangue; however, gangue concrete presents several challenges that need to be tackled, such as low strength and poor resistance to repeated loads. In this study, polypropylene fibers (PPFs) were incorporated into gangue concrete to enhance its utilization rate. Uniaxial compressive and repeated loading experiments were then conducted to investigate the uniaxial strength and fatigue properties of polypropylene fiber-reinforced gangue concrete (PGC) with varying gangue substitution rates (20%, 40%, and 60%) and different polypropylene fiber admixtures (0, 0.1%, 0.2%, and 0.3%). The findings indicate that incorporating gangue at a substitution rate of 40% could notably enhance the uniaxial compressive strength of PGC, resulting in a maximum increase of 19.4%. In the repeated loading experiments, the ductility of PGC was enhanced with the incorporation of PPFs, resulting in a reduction of 33.76% in the damage factor and 19.42% in residual strain for PGC-40-0.2 compared to PGC-40-0. A PPF content of 0.2% was found to be optimal for enhancing the fatigue performance of PGC. Scanning electron microscope (SEM) testing proved the improvement effect of polypropylene fiber on gangue concrete from a microscopic perspective. This study provides crucial experimental data and a theoretical foundation for the utilization of gangue concrete in complex stress environments.
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The use of hemp as a forage source in livestock diets has been less studied because bioactive residues in animal tissues may pose a risk to consumers. This study investigated the effects of partial substitution of alfalfa hay (AH) with hemp forage (HF) in growing goat diets on growth performance, carcass traits, ruminal fermentation characteristics, rumen microbial communities, blood biochemistry, and antioxidant indices. Forty Xiangdong black goats with body weight (BW) 7.82 ± 0.57 kg (mean ± SD) were grouped by BW and randomly assigned into one of the four treatment diets (n = 10/treatment) in a completely randomized design. The goats were fed ad libitum total mixed rations containing 60% forage and 40% concentrate (DM basis). The diets included control (CON; 60% AH and 40% concentrate), 55% AH and 5% HF (HF5), 50% AH and 10% HF (HF10), and 40% AH and 20% HF (HF20). Increasing the substitution of HF for AH linearly decreased (P < 0.01) DM intake and improved feed conversion efficiency. However, final BW, average daily gain, carcass traits, meat quality, and most blood biochemistry indices did not differ among treatments. The ruminal NH3-N concentration and blood urine nitrogen linearly increased (P < 0.01) with increasing substitution rate of HF, whereas the total volatile fatty acids concentration quadratically changed (P < 0.01). Substitution of AH with HF had no effect on the diversity and richness of ruminal microbes, though it linearly decreased (P = 0.040) Prevotella_1 and linearly increased (P = 0.017) Rikenellaceae_RC9_gut_group. The cannabinoids and/or their metabolites were detected in both ruminal filtrates (8) and plasma (4), however, no detectable cannabinoid-related residues were observed in meat. These results indicate that the HF could be used to partially substitute AH in goat diets, whereas the effects vary between substitution rates of HF for AH. Although no cannabinoid-related residues were detected in meat, the presence of cannabinoids residues in blood warrants further study of HF feeding to confirm the cannabinoids residues are not present in the animal products.
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The overuse and misuse of antibiotics in the livestock and poultry industry has led to the development of multi-drug resistance in animal pathogens, and antibiotic resistance genes (ARGs) in bacteria transfer from animals to humans through the consumption of animal products, posing a serious threat to human health. Therefore, the use of antibiotics in livestock production has been strictly controlled. As a result, bacteriophages have attracted increasing research interest as antibiotic alternatives, since they are natural invaders of bacteria. Numerous studies have shown that dietary bacteriophage supplementation could regulate intestinal microbial composition, enhance mucosal immunity and the physical barrier function of the intestinal tract, and play an important role in maintaining intestinal microecological stability and normal body development of animals. The effect of bacteriophages used in animals is influenced by factors such as species, dose, and duration. However, as a category of mobile genetic elements, the high frequency of gene exchange of bacteriophages also poses risks of transmitting ARGs among bacteria. Hence, we summarized the mechanism and efficacy of bacteriophage therapy, and highlighted the feasibility and challenges of bacteriophage utilization in farm animal production, aiming to provide a reference for the safe and effective application of bacteriophages as an antibiotic alternative in livestock and poultry.
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INTRODUCTION: As of 2020, breast cancer has emerged as the predominant cause of cancer incidence globally. Anthracycline-based chemotherapy serves as a crucial element in the treatment regimen for breast cancer. However, these anthracycline-based drugs are associated with cardiac toxicity. This study represents the first clinical quantitative analysis aimed at accurately determining the incidences of arrhythmia and abnormal electrocardiogram (ECG) changes, thereby providing valuable data to bolster clinical drug usage and monitoring. METHODS: A systematic search was conducted across multiple databases including CNKI, VIP, Wanfang, PubMed, Embase, Web of Science, and the Cochrane Library. The incidence of combined arrhythmias in breast cancer patients and the associated heterogeneity were calculated using either a random effect model or a fixed effect model. Statistical analysis was performed using STATA16. RESULTS: The study encompassed a total of 37 articles, which included 5705 breast cancer patients undergoing anthracycline treatment. Among these patients, 2257 developed arrhythmias. The meta-analysis revealed that the incidence of anthracycline-associated arrhythmias and abnormal ECG changes in breast cancer patients was 0.41 (0.37, 0.44). Subgroup analysis indicated that the incidence of ST-T segment change was 0.19 (0.15, 0.23), the incidence of conduction block was 0.04 (0.02, 0.05), the incidence of premature beats was 0.09 (0.07, 0.11), and the incidence of atrial fibrillation was 0.04 (0.00, 0.12). Additional results are presented in Table 3. CONCLUSION: This pioneering study accurately assesses the incidence of arrhythmias in breast cancer patients treated with anthracyclines. The findings provide clinicians with valuable insights into understanding and managing the cardiac toxicity associated with such treatment. Moreover, this study lays the foundation for future research exploring the mechanisms underlying these arrhythmias and potential preventative strategies.
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Antraciclinas , Arritmias Cardíacas , Neoplasias de la Mama , Humanos , Neoplasias de la Mama/tratamiento farmacológico , Antraciclinas/efectos adversos , Arritmias Cardíacas/inducido químicamente , Arritmias Cardíacas/epidemiología , Femenino , Electrocardiografía , IncidenciaRESUMEN
Exploring the molecular mechanisms of PD-1/PDL-1 blockade for non-small cell lung cancer (NSCLC) would facilitate understanding for tumor microenvironment (TME) and development of individualized medicine. To date, biomarkers of response to PD-1 blockade therapy were still limited. In this study, we hypothesize that cell type in the tumor microenvironment can influence the effect of PD-1 blockade immunotherapy through specific genes. Therefore, we re-analyze the single-cell RNA sequencing data and validation in tissue from lung adenocarcinoma patients. Dynamic changes of cellular subpopulation were observed after anti-PD-1 immunotherapy among TMEs between primary/metastasis or good/poor response patients. Non-exhausted CD8 T cells and dysregulated genes were observed in responsing patients from PD-1 blockade therapy. Among all changed genes, JUN, involved in PD-1 blockade immunotherapy pathway, and could be considered as a PD-1 responsing biomarker.
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Neoplasias Pulmonares , Receptor de Muerte Celular Programada 1 , Microambiente Tumoral , Femenino , Humanos , Masculino , Adenocarcinoma del Pulmón/genética , Adenocarcinoma del Pulmón/tratamiento farmacológico , Adenocarcinoma del Pulmón/inmunología , Adenocarcinoma del Pulmón/patología , Biomarcadores de Tumor/genética , Carcinoma de Pulmón de Células no Pequeñas/genética , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/inmunología , Carcinoma de Pulmón de Células no Pequeñas/patología , Regulación Neoplásica de la Expresión Génica , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Inhibidores de Puntos de Control Inmunológico/farmacología , Inmunoterapia/métodos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/inmunología , Receptor de Muerte Celular Programada 1/antagonistas & inhibidores , Receptor de Muerte Celular Programada 1/genética , Proteínas Proto-Oncogénicas c-jun/genética , Proteínas Proto-Oncogénicas c-jun/metabolismo , Análisis de Secuencia de ARN , Análisis de la Célula Individual , Microambiente Tumoral/genética , Microambiente Tumoral/inmunologíaRESUMEN
Activation of hepatic stellate cells (HSCs) is critical in the progression of liver fibrosis and is a promising target for anti-hepatic fibrosis drug development. Moreover, effective pharmacological interventions targeting this pathomechanism are scarce. Our study confirms the therapeutic value of ß-sitosterol, a major constituent of Ranunculus ternatus Thunb, in hepatic fibrosis and identifies its underlying mechanisms. After treatment with ß-sitosterol, CCL4-induced hepatic fibrosis was reversed in mice, while inflammatory and hepatic fibrosis indices were improved. Meanwhile, we explored the molecular mechanism of ß-sitosterol treatment for hepatic fibrosis and, based on RNA-seq results, found that the ameliorative effect of ß-sitosterol on hepatic fibrosis was associated with the MK3 and NF-κB signalling pathways. MK3, an important kinase in the MAPK pathway, plays a role in transmitting upstream and downstream signals, whereas the NF-κB signalling pathway has been shown to be associated with HSC activation. We verified the interaction between MK3 and IκB in HSC cells using endogenous Co-IP, whereas ß-sitosterol reduced the binding of MK3 to IκB and the activation of the NF-κB signalling pathway. Our findings reveal the mechanism of ß-sitosterol in the treatment of liver fibrosis, suggesting that ß-sitosterol may be a promising drug for the treatment of liver fibrosis and deserves further investigation.
Asunto(s)
FN-kappa B , Ranunculus , Ratones , Animales , FN-kappa B/metabolismo , Ranunculus/metabolismo , Farmacología en Red , Cirrosis Hepática/metabolismo , Perfilación de la Expresión Génica , Hígado/metabolismoRESUMEN
Purpose: We aimed to evaluate the effect of intravenous esketamine combined with dexmedetomidine as supplemental analgesia in reducing intraoperative visceral pain during elective cesarean section under combined spinal-epidural anesthesia (CSEA). Patients and Methods: A total of 269 parturients scheduled for elective cesarean section under CSEA between May 2023 and August 2023 were assessed. The parturients were randomly allocated to receiving either intravenous infusion of 0.3-mg/kg esketamine combined with 0.5-µg/kg dexmedetomidine (group ED, n=76), 0.5-µg/kg dexmedetomidine (group D, n=76), or normal saline (group C, n=76) after umbilical cord clamping. The primary outcome was intraoperative visceral pain. Secondary outcomes included the visual analog scale (VAS) score for pain evaluation and other intraoperative complications. Results: The incidence of visceral pain was lower in group ED [9 (12.7%)] than in group D [32 (43.8%)] and group C [36 (48.6%), P <0.0001]. The VAS score was also lower in group ED when exploring abdominal cavity [0 (0), P <0.0001] and suturing the muscle layer [0 (0), P =0.036]. The mean arterial pressure was higher in group D [83 (9) mmHg] and group ED [81 (11) mmHg] than in group C [75 (10) mmHg, P <0.0001] after solution infusion. The heart rate after infusion of the solution was lower in group D [80 (12) bpm] than in group C [86 (14) bpm] and group ED [85 (12) bpm, P = 0.016]. The incidence of transient neurologic or mental symptoms was higher in group ED compared to group C and group D (76.1% vs 18.9% vs 23.3%, P<0.0001). Conclusion: During cesarean section, 0.3-mg/kg esketamine combined with 0.5-µg/kg dexmedetomidine can alleviate visceral traction pain and provide stable hemodynamics. Parturients receiving this regimen may experience transient neurologic or mental symptoms that can spontaneously resolve at the end of the surgery.
Some parturients endure experience indescribable pain and discomfort during fetal delivery. Esketamine combined with dexmedetomidine can alleviate this pain during cesarean section under combined spinal-epidural anesthesia. However, after intravenous injection of esketamine and dexmedetomidine, the parturients may experience nightmares, dizziness, hallucinations, and drowsiness, etc.
Asunto(s)
Anestesia Epidural , Anestesia Raquidea , Cesárea , Dexmedetomidina , Ketamina , Dolor Visceral , Humanos , Dexmedetomidina/administración & dosificación , Ketamina/administración & dosificación , Método Doble Ciego , Femenino , Adulto , Dolor Visceral/prevención & control , Dolor Visceral/tratamiento farmacológico , Embarazo , Quimioterapia Combinada , Procedimientos Quirúrgicos ElectivosRESUMEN
Bacteriophages (phages for short) are the most abundant biological entities on Earth and are natural enemies of bacteria. Genomics and molecular biology have identified subtle and complex relationships among phages, bacteria and their animal hosts. This review covers composition, diversity and factors affecting gut phage, their lifecycle in the body, and interactions with bacteria and hosts. In addition, research regarding phage in poultry, aquaculture and livestock are summarized, and application of phages in antibiotic substitution, phage therapy and food safety are reviewed.