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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.
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Anestesia Epidural , Raquianestesia , Cesárea , Dexmedetomidina , Ketamina , Dor Visceral , Humanos , Dexmedetomidina/administração & dosagem , Ketamina/administração & dosagem , Método Duplo-Cego , Feminino , Adulto , Dor Visceral/prevenção & controle , Dor Visceral/tratamento farmacológico , Gravidez , Quimioterapia Combinada , Procedimentos Cirúrgicos EletivosRESUMO
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 Morte Celular Programada 1 , Microambiente Tumoral , Feminino , Humanos , Masculino , Adenocarcinoma de Pulmão/genética , Adenocarcinoma de Pulmão/tratamento farmacológico , Adenocarcinoma de Pulmão/imunologia , Adenocarcinoma de Pulmão/patologia , Biomarcadores Tumorais/genética , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/imunologia , Carcinoma Pulmonar de Células não Pequenas/patologia , Regulação Neoplásica da Expressão Gênica , Inibidores de Checkpoint Imunológico/uso terapêutico , Inibidores de Checkpoint Imunológico/farmacologia , Imunoterapia/métodos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/imunologia , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Receptor de Morte Celular Programada 1/genética , Proteínas Proto-Oncogênicas c-jun/genética , Proteínas Proto-Oncogênicas c-jun/metabolismo , Análise de Sequência de RNA , Análise de Célula Única , Microambiente Tumoral/genética , Microambiente Tumoral/imunologiaRESUMO
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 da Mama , Humanos , Neoplasias da Mama/tratamento farmacológico , Antraciclinas/efeitos adversos , Arritmias Cardíacas/induzido quimicamente , Arritmias Cardíacas/epidemiologia , Feminino , Eletrocardiografia , IncidênciaRESUMO
The aim of this study was to investigate the effects of dietary Allium mongolicum Regel powder (AMRP) supplementation on the growth performance, meat quality, antioxidant capacity and muscle fibre characteristics of fattening Angus calves. Growth performance data and longissimus thoracis (LT) samples were collected from four groups of fattening Angus, which were fed either a basal diet (CON) or a basal diet supplemented with an AMRP dose of 10 (LAMR), 15 (MAMR), or 20 g/animal/day AMRP (HAMR) for 120 days before slaughter. AMRP addition to the feed improved growth performance and meat quality and altered muscle fibre type. Some responses to AMRP supplementation were dose dependent, whereas others were not. Together, the results of this study demonstrated that dietary supplementation with 10 g/animal/day AMRP was the optimal dose in terms of fattening calf growth performance, while 20 g/animal/day AMRP supplementation was the optimal dose in terms of meat quality.
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Ração Animal , Antioxidantes , Suplementos Nutricionais , Carne , Animais , Bovinos/metabolismo , Bovinos/crescimento & desenvolvimento , Antioxidantes/metabolismo , Suplementos Nutricionais/análise , Ração Animal/análise , Carne/análise , Fibras Musculares Esqueléticas/metabolismo , Fibras Musculares Esqueléticas/efeitos dos fármacos , Pós/química , Masculino , Resposta ao Choque Térmico/efeitos dos fármacos , Allium/química , Allium/crescimento & desenvolvimento , Allium/metabolismo , Temperatura AltaRESUMO
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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Rubber concrete (RC) is a new type of concrete that is currently receiving a lot of attention, solving serious pollution problems by grinding waste tires into granules and adding them to concrete. However, rubber concrete has deficiencies in mechanics and durability, and has been reinforced by adding fibers in many studies. In this study, the mechanical and durability properties of rubber concrete with added polypropylene and basalt fibers (PBRC) were investigated in a series of experiments including apparent morphology, mass, static compressive and tensile tests, ultrasonic non-destructive testing, and scanning electron microscope (SEM) tests under coupled environments of sulfate attack and freeze-thaw. The results showed that the mass loss rate of RC and PBRC gradually increased with the number of freeze-thaw cycles, with more pits and cement paste peeling from the specimen surface. Moreover, the compressive and splitting tensile strengths of RC and PBRC groups exhibited distinct trends, with the former group showing a lower residual strength relative to the latter. The residual compressive strength of the RC group was only 69.4% after 160 freeze-thaw cycles in 5% MgSO4 solution. However, it is worth noting that the addition of too many fibers also had a negative effect on the strength of the rubber concrete. Additionally, the scanning electron microscopy (SEM) results indicated that the fibers restricted the formation of microcracks in the microstructure and curtailed the brittleness of the concrete. This study can provide a valuable reference for the application of environmentally friendly material fibers in recycled aggregate concrete.
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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/farmacologia , Carcinoma Hepatocelular/patologia , Linhagem Celular Tumoral , Proliferação de Células , Resistencia a Medicamentos Antineoplásicos/genética , Regulação Neoplásica da Expressão Gênica , Neoplasias Hepáticas/patologia , Fatores de Transcrição NFI/genética , Espécies Reativas de Oxigênio/metabolismo , Sorafenibe/farmacologiaRESUMO
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 Múltiplo , Adulto , Humanos , Feminino , Mieloma Múltiplo/diagnóstico , Mieloma Múltiplo/tratamento farmacológico , Lenalidomida/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Bortezomib/efeitos adversos , Dexametasona/uso terapêuticoRESUMO
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 Múltiplo , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Bortezomib , Dexametasona , Progressão da Doença , Humanos , Lenalidomida/uso terapêutico , Mieloma Múltiplo/terapia , Estudos Retrospectivos , Resultado do Tratamento , Estados UnidosRESUMO
Background: Active surveillance (AS) has been considered the first-line management for patients with clinical low-risk papillary thyroid microcarcinoma (PTMC) who often have lymph node micrometastasis (m-LNM) when diagnosed. The "low-risk" and "high prevalence of m-LNM" paradox is a potential barrier to the acceptance of AS for thyroid cancer by both surgeons and patients. Methods: Patients diagnosed with PTMC who underwent thyroidectomy with at least one lymph node (LN) examined were identified from a tertiary center database (n = 5,399). A ß-binomial distribution was used to estimate the probability of missing nodal disease as a function of the number of LNs examined. Overall survival (OS) probabilities of groups with adequate and inadequate numbers of LNs examined were estimated using the Kaplan-Meier method in the Surveillance, Epidemiology, and End Results (SEER) database (n = 15,340). A multivariable model with restricted cubic splines was also used to verify the association of OS with the number of LNs examined. Results: The risk of residual m-LNM (missed nodal disease) ranged from 31.3% to 10.0% if the number of LNs examined ranged from 1 and 7 in patients with PTMC. With 7 LNs examined serving as the cutoff value, the intergroup comparison showed that residual positive LNs did not affect OS across all patients and patients aged ≥55 years (P = 0.72 and P = 0.112, respectively). After adjusting for patient and clinical characteristics, the multivariate model also showed a slight effect of the number of LNs examined on OS (P = 0.69). Conclusions: Even with the high prevalence, OS is not significantly compromised by persistent m-LNM in the body of patients with low-risk PTMC. These findings suggest that the concerns of LNM should not be viewed as an obstacle to developing AS for thyroid cancer. For patients with PTMC who undergo surgery, prophylactic central LN dissection does not provide a survival benefit.
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Sea urchin (Strongylocentrotus intermedius) is an economically important mariculture species in Asia, and its gonads are the only edible part. The efficiency of genetic breeding in sea urchins is hampered due to the inability to distinguish gender by appearance. In this study, we first identified a sex-associated single nucleotide polymorphism (SNP) by combining type IIB endonuclease restriction site-associated DNA sequencing (2b-RAD-seq) and genome survey. Importantly, this SNP is located within spata4, a gene specifically expressed in male. Knocking down of spata4 by RNA interference (RNAi) in male individuals led to the downregulation of other conserved testis differentiation-related genes and germ cell marker genes. We also revealed that sex ratio in this validated culture population of S. intermedius is not 1:1. Moreover, after a 58-day feeding experiment with estradiol, the expression levels of several conserved genes that are related to testis differentiation, ovary differentiation, and estrogen metabolism were dynamically changed. Taken together, our results will contribute toward improving breeding efficiency, developing sex-controlled breeding, and providing a solid base for understanding sex determination mechanisms in sea urchins.
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Análise para Determinação do Sexo/métodos , Strongylocentrotus/genética , Sequência de Aminoácidos , Animais , Sequência de Bases , Estradiol , Feminino , Masculino , Polimorfismo de Nucleotídeo Único , Strongylocentrotus/metabolismo , TranscriptomaRESUMO
Objectives: To investigate the impact of portal vein thrombosis (PVT) on cirrhosis decompensation and survival of cirrhosis. Methods: In this retrospective observational study between January 2012 and August 2020, 117 patients with cirrhotic PVT and 125 patients with cirrhosis were included. Propensity score matching (PSM) was applied to reduce the bias. The clinical characteristics of non-tumoral PVT in cirrhosis and its influence on cirrhosis decompensation and survival were analyzed. Results: The median follow-up for the PVT group was 15 (8.0-23.0) months and for the non-thrombosis group 14 (8.0-23.5) months. The presence of PVT was related with esophageal varices, higher Child-Pugh score and MELD score (P < 0.05). Most PVTs were partial (106/117). Non-occlusive PVT disappeared on later examinations in 32/106 patients (30.19%), of which six patients reappeared. All the 11 patients with occlusive PVT remained occlusive, among which five patients (45.45%) developed portal cavernoma. There was no significant correlation between PVT and decompensation or survival before or after PSM. Multivariate analysis identified only Child-Pugh score (HR = 2.210, 95% CI: 1.332-3.667) and serum sodium level (HR = 0.818, 95% CI: 0.717-0.933) as independent factors for death. Conclusion: Though PVT is associated with greater Child-Pugh score and MELD score, it has no significant impact on the progression of cirrhosis.
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BACKGROUND AND OBJECTIVE: Gastric cancer (GC) is a common tumor malignancy with high incidence and poor prognosis. Laminin is an indispensable component of basement membrane and extracellular matrix, which is responsible for bridging the internal and external environment of cells and transmitting signals. This study mainly explored the association of the LAMB1 expression with clinicopathological characteristics and prognosis in gastric cancer. METHODS: The expression data and clinical information of gastric cancer patients were downloaded from The Cancer Genome Atlas (TCGA) and Asian Cancer Research Group (ACRG). And we analyzed the relationship between LAMB1 expression and clinical characteristics through R. CIBERSORTx was used to calculate the absolute score of immune cells in gastric tumor tissues. Then COX proportional hazard models and Kaplan-Meier curves were performed to evaluate the role of LAMB1 and its influence on prognosis in gastric cancer patients. Finally, GO and KEGG analysis were applied for LAMB1-related genes in gastric cancer, and PPI network was constructed in Cytoscape software. RESULTS: In the TCGA cohort, patients with gastric cancer frequently generated LAMB1 gene copy number variation, but had little effect on mRNA expression. Both in the TCGA and ACRG cohorts, the mRNA expression of LAMB1 in gastric cancer tissues was higher than it in normal tissues. All patients were divided into high expression group and low expression group according to the median expression level of LAMB1. The elevated expression group obviously had more advanced cases and higher infiltration levels of M2 macrophages. COX proportional hazard models and Kaplan-Meier curves revealed that patients with enhanced expression of LAMB1 have a worse prognosis. GO/KEGG analysis showed that LAMB1-related genes were enriched in PI3K-Akt signaling pathway, focal adhesion, ECM-receptor interaction, etc. CONCLUSIONS: The high expression of LAMB1 in gastric cancer is related to the poor prognosis of patients, and it may be related to microenvironmental changes in tumors.
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Laminina/genética , Neoplasias Gástricas/genética , Neoplasias Gástricas/patologia , Idoso , Biologia Computacional , Bases de Dados Genéticas , Feminino , Ontologia Genética , Humanos , Metástase Linfática , Linfócitos do Interstício Tumoral , Macrófagos , Masculino , Pessoa de Meia-Idade , Mutação , Estadiamento de Neoplasias , Prognóstico , Modelos de Riscos Proporcionais , Mapas de Interação de Proteínas , Estudos Retrospectivos , Neoplasias Gástricas/imunologia , Taxa de Sobrevida , TranscriptomaRESUMO
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 Colorretais , Detecção Precoce de Câncer , Colonoscopia , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/epidemiologia , Análise Custo-Benefício , Humanos , Programas de Rastreamento , Sangue Oculto , Estados Unidos/epidemiologiaRESUMO
BACKGROUND: Brewers' spent grain (BSG) typically contains 20% - 29% crude protein (CP) with high concentrations of glutamine, proline and hydrophobic and non-polar amino acid, making it an ideal material for producing value-added products like bioactive peptides which have antioxidant properties. For this study, protein was extracted from BSG, hydrolyzed with 1% alcalase and flavourzyme, with the generated protein hydrolysates (AlcH and FlaH) showing antioxidant activities. This study evaluated the effects of AlcH and FlaH on gas production, ruminal fermentation characteristics, nutrient disappearance, microbial protein synthesis and microbial community using an artificial rumen system (RUSITEC) fed a high-grain diet. RESULTS: As compared to the control of grain only, supplementation of FlaH decreased (P < 0.01) disappearances of dry matter (DM), organic matter (OM), CP and starch, without affecting fibre disappearances; while AlcH had no effect on nutrient disappearance. Neither AlcH nor FlaH affected gas production or VFA profiles, however they increased (P < 0.01) NH3-N and decreased (P < 0.01) H2 production. Supplementation of FlaH decreased (P < 0.01) the percentage of CH4 in total gas and dissolved-CH4 (dCH4) in dissolved gas. Addition of monensin reduced (P < 0.01) disappearance of nutrients, improved fermentation efficiency and reduced CH4 and H2 emissions. Total microbial nitrogen production was decreased (P < 0.05) but the proportion of feed particle associated (FPA) bacteria was increased with FlaH and monensin supplementation. Numbers of OTUs and Shannon diversity indices of FPA microbial community were unaffected by AlcH and FlaH; whereas both indices were reduced (P < 0.05) by monensin. Taxonomic analysis revealed no effect of AlcH and FlaH on the relative abundance (RA) of bacteria at phylum level, whereas monensin reduced (P < 0.05) the RA of Firmicutes and Bacteroidetes and enhanced Proteobacteria. Supplementation of FlaH enhanced (P < 0.05) the RA of genus Prevotella, reduced Selenomonas, Shuttleworthia, Bifidobacterium and Dialister as compared to control; monensin reduced (P < 0.05) RA of genus Prevotella but enhaced Succinivibrio. CONCLUSIONS: The supplementation of FlaH in high-grain diets may potentially protect CP and starch from ruminal degradation, without adversely affecting fibre degradation and VFA profiles. It also showed promising effects on reducing CH4 production by suppressing H2 production. Protein enzymatic hydrolysates from BSG using flavourzyme showed potential application to high value-added bio-products.
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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 Cultura de Células/instrumentação , Laboratórios/economia , Receptores de Antígenos Quiméricos/metabolismo , Linfócitos T/citologia , Centros Médicos Acadêmicos , Técnicas de Cultura de Células/economia , Alemanha , Humanos , Organizações sem Fins Lucrativos , Linfócitos T/imunologiaRESUMO
Hepatocellular carcinoma (HCC) is one of the most prevalent cancers and currently the second leading cause of cancer-related mortality worldwide. One recent study reported that lncRNA-LALR1 promotes liver regeneration, the role and underlying mechanisms of lncRNA-LALR1 in HCC remain largely unknown. In this study, we demonstrated that lncRNA-LALR1 was significantly upregulated in HCC tissues compared with adjacent tissues and high expression of lncRNA-LALR1 was associated with advanced TNM stage, poor differentiation, and distant metastasis. RNA Fluorescence in situ hybridization analysis showed lncRNA-LALR1 was expressed not only in cytoplasm but also in nucleolus. Knockdown of lncRNA-LALR1 obviously inhibited HCC cells growth and invasion in vivo and in vitro. Besides, transcriptomic analysis and subsequent confirmation revealed that lncRNA-LALR1 upregulated small nucleolar RNA SNORD72 via binding with SNORD72 and stabilized ID2 mRNA. SNORD72 was overexpressed in HCC tissues and enhanced HCC cells proliferation, colony formation and invasion. Overexpression of SNORD72 could also stabilize ID2 mRNA and rescue the inhibitory effect of silencing lncRNA-LALR1. In conclusion, lncRNA-LALR1 is highly expressed in HCC and promotes tumor growth and invasion by upregulating SNORD72 to stabilize ID2 mRNA, implying that lncRNA-LALR1 might be a novel target for intervention of HCC.
Assuntos
Carcinoma Hepatocelular/genética , Proliferação de Células/genética , Neoplasias Hepáticas/genética , Invasividade Neoplásica/genética , RNA Longo não Codificante , RNA Nucleolar Pequeno , Regulação para Cima , Carcinoma Hepatocelular/patologia , Progressão da Doença , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Hepáticas/patologia , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica/patologia , Estadiamento de NeoplasiasRESUMO
Nicotinamide adenine dinucleotide (NAD) is a profoundly important cofactor in redox reactions. Nicotinamide phosphoribosyltransferase (NAMPT) and nicotinate phosphoribosyltransferase (NAPRT) are key enzymes for NAD salvage biosynthesis pathway, which reciprocally synthesize NAD to supply the main source of NAD biosythesis. However, the prognostic value of NAMPT and NAPRT in colorectal cancer (CRC) remains largely unknown. Our present study detected NAMPT and NAPRT protein expression in cancer and adjacent tissues from 261 CRC using immunohistochemical staining. We found that high expression of NAMPT or NAPRT was associated with vascular invasion, invasion depth and advanced TNM stage in CRC. High expression of NAMPT or NAPRT predicts short overall survival and disease-free survival time in CRC patients, which were further confirmed by public datasets. Furthermore, positive correlation between expression of NAMPT and NAPRT was revealed in CRC tissues and cell lines. NAPRThigh/NAMPThigh patients tended to have the shortest survival time. Using the TCGA RNA-sequencing data, we showed that gene amplification, mutation, and methylation of NAPRT are more common than NAMPT. On the other hand, NAMPT gene might be targeted by more miRNAs. Finally, genes that are correlated with NAPRT or NAMPT are enriched in different pathways. In conclusion, we found that high expression of NAMPT or NAPRT predicts poor prognosis of CRC patients, but the regulatory mechanism might be distinct from each other.
RESUMO
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.