RESUMO
Objective: Approximately 10%-70% of patients may develop diaphragmatic dysfunction after cardiac surgery, which may lead to delayed weaning from mechanical ventilation, increased ICU stays, postoperative hospitalization stays, and respiratory complications. However, its impact on prognosis and risk factors remain controversy. Therefore, we conducted a retrospective cohort study in which we evaluated diaphragmatic dysfunction in patients who underwent cardiac surgery via bedside diaphragm ultrasound to investigate its prognosis and possible risk factors. Methods: Data from the electronic medical records system included case records and ultrasound images of the diaphragm for 177 consecutive patients admitted to the ICU following cardiac thoracotomy surgeries performed between June and September 2020. Diaphragmatic dysfunction was defined as a diaphragmatic excursion of less than 9 mm in women and less than 10 mm in men at rest, with an average thickening fraction of less than 20%. SPSS 25.0 software was used to analyse the relationships between patients' general information, intraoperative and postoperative factors and diaphragmatic dysfunction, as well as the impact on patients' hospitalization days, mechanical ventilation time and respiratory system complications. Results: The incidence of early postoperative diaphragmatic dysfunction after cardiac surgery was 40.7%. Patients with diaphragmatic insufficiency were more likely to sequentially use noninvasive ventilation within 24â h after weaning off mechanical ventilation (3.8% vs. 12.5%, P = 0.029) and to require more oxygen support (23.8% vs. 40.3%, P = 0.019). Although there was no significant difference, the diaphragmatic dysfunction group tended to have longer ICU stays and postoperative hospital stays than did the normal diaphragmatic function group (P = 0.119, P = 0.073). Univariate and multivariate logistic regression analyses both revealed that chest tube drainage placed during surgery accompanied by bloody drainage fluid was an independent risk factor for diaphragmatic dysfunction (univariate analysis: 95% CI: 1.126-4.137, P = 0.021; multivariate analysis: 95% CI: 1.036-3.897, P = 0.039). Conclusion: Eearly diaphragmatic dysfunction after cardiac surgery increased the proportion of patients who underwent sequential noninvasive ventilation after weaning from mechanical ventilation and who required more oxygen. Chest tube drainage placed during surgery accompanied by bloody drainage fluid was an independent risk factor for diaphragmatic dysfunction, providing evidence-based guidance for respiratory rehabilitation after cardiac surgery.
RESUMO
Background: Annual Chinese National negotiations for including innovative drugs in the National Reimbursement Drug List (NRDL) reveal an increasing number of new drugs with overlapping action mechanisms of action and similar indications. Yet, it is unclear if competition affects reimbursement decisions. Thus, we explored the impact of competition on reimbursement decisions for cancer drugs in China. Methods: We identified the cancer drugs involved in NRDL negotiations from 2017 to 2022 and focused on the initial reimbursement decision for eligible newly negotiated drugs. Drugs were classified as within-class competitors based on their equivalent biological mechanisms of action and approved indications, including identified and potential competitors. Other variables included drug type, clinical benefit and safety, monthly drug cost, and disease incidence rate. We employed traditional univariate and multivariate Firth's penalized logistic regression to assess the association between reimbursement decisions and variables at the indication and drug levels. Findings: Between 2017 and 2022, 102 cancer drugs corresponding to 141 indications were studied, and 66 drugs (64.7%) covering 95 indications (67.4%) were added to the NRDL. The proportion of reimbursements for indications with identified competition was significantly higher than that for indications without identified competition (84.6% vs 52.6%, p < 0.0001). However, the difference in reimbursement proportions between groups with and without potential competition was not statistically significant (66.7% vs 68.3%, p = 0.84). Firth's penalized logistic regression showed that identified competition was positively correlated with successful NRDL inclusion, whereas potential competition had no significant effect on negotiation outcomes. Improved overall survival or progression-free survival were positively associated with NRDL inclusion, whereas disease incidence negatively impacted reimbursement decisions. Interpretation: Improved clinical benefit and identified competition were positively correlated with NRDL inclusion. In China's value-based negotiation model, clinical benefits served as a crucial foundation of price negotiation for cancer drugs, and market competition helped these drugs enter the NRDL at more reasonable prices. This has important implications for reimbursement decisions and accessibility and affordability improvement for innovative drugs worldwide. Funding: National Natural Science Foundation of China (No. 72104151).
RESUMO
Background: Several studies have systematically assessed the efficacy and safety of progressive or recurrent glioblastoma multiforme (GBM). However, the discernible limitations of efficacy and the elevated costs of interventions instigate an investigation into the cost-effectiveness of these treatments. Objectives: This study aimed to evaluate cost-effectivenesses of 11 pharmacotherapeutic interventions for recurrent GBM from the perspective of healthcare payers in the United States (US) and China. Design: A model-based pharmacoeconomic evaluation. Methods: A partitioned survival model was employed to evaluate the cost-effectiveness of 11 distinct drug-based treatments. The clinical efficacy and safety data were obtained from a network meta-analysis, while the medical expenditure and health utility were primarily derived from published literature. One-way sensitivity analyses, scenario analyses, and probabilistic sensitivity analyses (PSA) were performed to scrutinize the impact of potential uncertainties to ensure the robustness of the model. The primary endpoint was the incremental cost-effectiveness ratio. Results: Among the therapeutic interventions evaluated, lomustine emerged as the cheapest option, with costs amounting to $78,998 in the United States and $30,231 in China, respectively. Regorafenib displayed the highest quality-adjusted life years at 0.475 in the United States and 0.465 in China. The one-way sensitivity analyses underscored that drug price was a key factor influencing cost-effectiveness. Both scenario and PSA consistently demonstrated that, considering the willingness-to-pay thresholds, lomustine was a cost-effective treatment with probability of more than 94%. Conclusion: In comparison to the alternative antitumor agents, lomustine was likely to be a cost-effective option for relapsed GBM patients from the perspective of healthcare payers in both the United States and China.
RESUMO
AIMS: Specific identification of a hydatidiform mole (HM) and subclassification of a complete hydatidiform mole (CHM) or partial hydatidiform mole (PHM) are critical. This study aimed to reappraise the diagnostic performance of ultrasonography and histology with a refined diagnosis. METHODS: This was a retrospective, multicentre cohort study of 821 patients with histologically suspected HM specimens. Refined diagnostic algorithms with p57 immunohistochemistry and short tandem repeat (STR) genotyping were performed and used as the true standard for assessing the diagnostic performance of the original ultrasonography and morphology methods. The diagnostic performance was calculated using accuracy, agreement rate, sensitivity and the positive predictive value (PPV) compared with refined diagnostic results. RESULTS: Of the 821 histologically suspected HM cases included, 788 (95.98%) were successfully reclassified into 448 CHMs, 213 PHMs and 127 non-molar (NM) abortuses. Ultrasonography showed an overall accuracy of 44.38%, with a sensitivity of 44.33% for CHM and 37.5% for PHM. The overall classification accuracy of the original morphological diagnosis was 65.97%. After exclusion of the initially untyped HMs, the overall agreement rate was 59.11% (κ=0.364, p<0.0001) between the original and refined diagnoses, with a sensitivity of 40.09% and PPV of 96.05% for diagnosing CHMs and a sensitivity of 84.98% and a PPV of 45.59% for diagnosing PHMs. The interinstitutional variability of morphology in diagnosing HMs was significant among the 15 centres (range, 8.33%-100.00%, p<0.0001). CONCLUSION: The current diagnosis of HM based solely on ultrasound or morphology remains problematic, and ancillary techniques, particularly p57 immunohistochemistry and DNA genotyping, should be integrated into routine practice as much as possible.
RESUMO
Ginger polysaccharides (GP) promote growth and development in fish. However, the effects of GP on crucian carp remain unclear. The present study investigated the effects of GP on the growth performance, immunity, intestinal microbiota, and disease resistance in crucian carp. Four treatment groups were established with different concentrations of GP (0.1 %, 0.2 %, 0.4 %, and 0.8 %). GP was not added as the control group, and the feeding period lasted for 56 d, followed by a 96-h anti-infection treatment using Aeromonas hydrophila. The results showed that dietary GP significantly improved growth performance, especially in the 0.4 % GP group. Furthermore, GP administration notably increased serum lysozyme (LMZ) activity, digestive enzyme performance, and antioxidant capacity of crucian carp. Moreover, dietary inclusion of GP up-regulated the expression of tumour necrosis factor-α (TNF-α), interleukin-8 (IL-8), interferon-γ (IFN-γ), and nuclear factor kappa-B (NF-κB) genes while down-regulating IL-10 and transforming growth factor-ß (TGF-ß) gene expressions, thus promoting liver health in crucian carp. Additionally, incorporating GP into the diet regulated both the diversity and composition of the intestinal microbiota in crucian carp, explicitly enhancing the relative abundance of beneficial bacteria, such as Fusobacteriota and Firmicutes. Therefore, GP reduces the mortality of crucian carp infected with A. hydrophila. In conclusion, this study provides novel insights into the application of dietary GP in cultured fish and evaluates the value of traditional Chinese medicinal polysaccharides against pathogenic bacteria.
Assuntos
Aeromonas hydrophila , Antioxidantes , Carpas , Resistência à Doença , Doenças dos Peixes , Microbioma Gastrointestinal , Polissacarídeos , Zingiber officinale , Animais , Aeromonas hydrophila/efeitos dos fármacos , Microbioma Gastrointestinal/efeitos dos fármacos , Polissacarídeos/farmacologia , Polissacarídeos/química , Resistência à Doença/efeitos dos fármacos , Antioxidantes/farmacologia , Doenças dos Peixes/microbiologia , Doenças dos Peixes/imunologia , Zingiber officinale/química , Carpas/crescimento & desenvolvimento , Carpas/imunologia , Carpas/microbiologia , Infecções por Bactérias Gram-Negativas/veterinária , Infecções por Bactérias Gram-Negativas/imunologia , Infecções por Bactérias Gram-Negativas/tratamento farmacológico , Suplementos Nutricionais , Ração AnimalRESUMO
BACKGROUND: Although various aspects of cisplatin resistance have been studied, the impact of genetic variations still needs to be explored. AIM: This study aimed to investigate the impact of cisplatin on meningiomas using a two-sample Mendelian randomization (MR) approach, employing genetic variants associated with cisplatin use as instrumental variables. METHOD: We conducted a two-sample MR analysis using genome-wide association study (GWAS) data. Instrumental variables were derived from single-nucleotide polymorphisms (SNPs) associated with meningioma to estimate the causal relationship with cisplatin resistance. Sensitivity analyses were performed to confirm the findings. RESULTS: Genetic predisposition to meningioma significantly increased the risk of cisplatin resistance (odds ratio (OR): 1.63; 95% confidence interval (CI) 1.44-1.85, P < 0.05). Sensitivity analyses supported the causal link. CONCLUSION: This MR study suggests that genetic predisposition to meningioma increases susceptibility to cisplatin resistance. Further research is needed to uncover the mechanisms behind these causal effects.
Assuntos
Antineoplásicos , Cisplatino , Resistencia a Medicamentos Antineoplásicos , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Análise da Randomização Mendeliana , Neoplasias Meníngeas , Meningioma , Polimorfismo de Nucleotídeo Único , Humanos , Meningioma/genética , Cisplatino/farmacologia , Resistencia a Medicamentos Antineoplásicos/genética , Neoplasias Meníngeas/genética , Neoplasias Meníngeas/epidemiologia , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêuticoRESUMO
AIM: To investigate the relationship between thyroid function and weight regain in patients with obesity after metabolic surgery. METHODS: This retrospective study enrolled 162 patients who underwent metabolic surgery. Correlations between decreases in thyroid hormone levels and changes in weight, waist circumference (WC) and the Chinese visceral adiposity index (CVAI) were assessed. Binary logistic regression and receiver operating characteristic (ROC) curves were used to identify predictors and clinically useful cut-off values, respectively. RESULTS: The levels of thyroid-stimulating hormone (TSH) and free triiodothyronine (FT3) decreased markedly at 1 year after surgery, as did weight, body mass index (BMI), triglycerides, total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, WC and CVAI. Decreases in TSH and FT3 after metabolic surgery were associated with changes in weight, BMI and CVAI. Binary logistic regression and ROC curve analyses confirmed that decreases in TSH can predict good weight loss after metabolic surgery to some extent. Finally, binary logistic regression and ROC curve analyses confirmed that changes in TSH can predict weight regain after metabolic surgery. CONCLUSIONS: Changes in TSH and FT3 after metabolic surgery were correlated with changes in weight and CVAI. Changes in thyroid hormones can predict weight regain in patients with obesity who underwent metabolic surgery.
Assuntos
Tireotropina , Tri-Iodotironina , Aumento de Peso , Humanos , Masculino , Feminino , Aumento de Peso/fisiologia , Estudos Retrospectivos , Pessoa de Meia-Idade , Tireotropina/sangue , Tri-Iodotironina/sangue , Adulto , Índice de Massa Corporal , Obesidade/cirurgia , Obesidade/sangue , Obesidade/complicações , Cirurgia Bariátrica , Circunferência da Cintura , Hormônios Tireóideos/sangue , Redução de Peso/fisiologia , Valor Preditivo dos Testes , Curva ROCRESUMO
Acute myeloid leukemia (AML) with mixed-lineage leukemia (MLL) gene rearrangements (MLL-r) is an aggressive subtype of blood cancer with dismal prognosis, underscoring the urgent need for novel therapeutic strategies. E1A-binding protein (EP300) and CREB-binding protein (CREBBP) function as essential transcriptional coactivators and acetyltransferases, governing leukemogenesis through diverse mechanisms. Targeting EP300/CREBBP holds great promise for treating leukemia with some certain cytogenetic abnormalities. Here, we demonstrated that EP300 and CREBBP are core epigenetic regulators in the pathogenesis of MLL-r AML through assaying the transposase-accessible chromatin with high-throughput sequencing (ATAC-seq). Knocking-out EP300/CREBBP and inhibitor (A-485) treatment depressed the MLL-r cells proliferation, while the MLL wild-type cells remained uninfluenced. We found that the CDK4/RB/E2F axis was downregulated specifically in MLL-r AML cell after A-485 treatment by RNA-seq, western blot and cut-tag analyses. EP300/CREBBP inhibitor selectively exerted potent anti-leukemia activity through blocking the MLL-r-BET complex binding to H3K27Ac modification on critical genes loci, distinct from global histone acetylation. Collectively, our study identified EP300/CREBBP as a critical epigenetic driver of MLL-r leukemia and validated their therapeutic potential through targeting inhibition, offering a promising avenue for improving clinical outcomes in this aggressive leukemia.
RESUMO
In recent years, saline-alkaline aquaculture development has become an important measure for China to expand its fishery development space to ensure food safety. Previous studies have verified that salinity and alkalinity positively influence the quality of Chinese mitten crabs (Eriocheir sinensis). However, the regulatory mechanism of E. sinensis endures saline-alkaline stress which remains obscure. This study investigated the metabolic changes in puberty-molting E. sinensis gills exposed to freshwater (FW), sodium chloride salinity of 5 ppt (SW), and carbonate alkalinity 10.00 mmol/L (AW) for 50 days using untargeted liquid chromatography-mass spectrometry metabolomics (LC-MS). A total of 5802 (positive-ion mode) and 6520 (negative-ion mode) peaks were extracted by LC-MS, respectively. A total of 188 (50 upregulated and 138 downregulated), 141 (94 upregulated and 47 downregulated), and 130 (87 upregulated and 43 downregulated) significantly regulated metabolites (SRMs) were observed in the FW-SW, FW-AW, and SW-AW treatments, respectively, wherein 42 generic SRMs were also found by Venn diagram analysis. Seven of the top 10 SRMs with the highest (variable importance in projection) VIP values were similarly identified in FW-SW and SW-AW. Integrated analysis of key metabolic pathways revealed glycerophospholipid, choline in cancer, phenylalanine, and butanoate metabolism. Overall, significant differences were observed in the metabolites and key metabolic pathways of E. sinensis gill exposed to salinity and alkalinity stress. These results will be helpful in understanding the environmental adaptability of aquatic crustaceans to saline-alkaline water.
Assuntos
Braquiúros , Brânquias , Metabolômica , Salinidade , Animais , Braquiúros/metabolismo , Braquiúros/efeitos dos fármacos , Brânquias/metabolismo , Brânquias/efeitos dos fármacos , Espectrometria de Massa com Cromatografia Líquida , Espectrometria de Massas , Metaboloma , Estresse Salino , Estresse FisiológicoRESUMO
Background: Prostate cancer (PCa) is one of the most common malignancies in men with a poor prognosis. It is therefore of great clinical importance to find reliable prognostic indicators for PCa. Many studies have revealed the pivotal role of protein lactylation in tumor development and progression. This research aims to analyze the effect of lactylation-related genes on PCa prognosis. Methods: By downloading mRNA-Seq data of TCGA PCa, we obtained the differential genes related to lactylation in PCa. Five machine learning algorithms were used to screen for lactylation-related key genes for PCa, then the five overlapping key genes were used to construct a survival prognostic model by lasso cox regression analysis. Furthermore, the relationships between the model and related pathways, tumor mutation and immune cell subpopulations, and drug sensitivity were explored. Moreover, two risk groups were established according to the risk score calculated by the five lactylation-related genes (LRGs). Subsequently, a nomogram scoring system was established to predict disease-free survival (DFS) of patients by combining clinicopathological features and lactylation-related risk scores. In addition, the mRNA expression levels of five genes were verified in PCa cell lines by qPCR. Results: We identified 5 key LRGs (ALDOA, DDX39A, H2AX, KIF2C, RACGAP1) and constructed the LRGs prognostic model. The AUC values for 1 -, 3 -, and 5-year DFS in the TCGA dataset were 0.762, 0.745, and 0.709, respectively. The risk score was found a better predictor of DFS than traditional clinicopathological features in PCa. A nomogram that combined the risk score with clinical variables accurately predicted the outcome of the patients. The PCa patients in the high-risk group have a higher proportion of regulatory T cells and M2 macrophage, a higher tumor mutation burden, and a worse prognosis than those in the low-risk group. The high-risk group had a lower IC50 for certain chemotherapeutic drugs, such as Docetaxel, and Paclitaxel than the low-risk group. Furthermore, five key LRGs were found to be highly expressed in castration-resistant PCa cells. Conclusion: The lactylation-related genes prognostic model can effectively predict the DFS and therapeutic responses in patients with PCa.
RESUMO
Recently, horizontal well L47-1CH in the Longdong area of the southwestern Ordos Basin made a significant breakthrough in bauxite natural gas exploration, changing the traditional geological understanding that bauxite could not form effective reservoirs. To further explore the exploration and development potential of bauxite natural gas reservoirs in the northeast of the Ordos Basin, it is urgent to carry out basic geological studies. This paper discusses the sedimentary environment, reservoir characteristics, and formation patterns of the bauxite gas reservoirs in the LX Block using trace elements, thin sections, X-ray diffraction, scanning electron microscopy, conventional physical properties, constant pressure mercury, etc. Then, the distribution pattern of bauxite was studied according to the restoration of the karst paleogeomorphology, and the formation model of bauxite was ultimately established. The results show that bauxite developed a clear triple-segment structure vertically, characterized by rich iron at the bottom, high aluminum at the middle, and low iron at the top. The mineral composition of the bauxite section mainly includes diaspore, iron minerals, titanium minerals, and birnessite. The types of pores mainly include intra- and intergranular dissolved pores, matrix-dissolved pores, intercrystalline pores, and microfractures. The porosity ranges from 1.51 to 9.90%, with a relatively good sorting and connectivity of the pore and throat. The bauxite was formed in a hot and humid climate, deposited in a shallow-water tidal flat and lagoon sedimentary environment with oxygen depleted, and experienced oscillatory regression during the deposition process. The thickness of bauxite is significantly controlled by karst paleogeomorphology, and it is mainly distributed at the negative terrain positions of karat pits and karst terraces. The above results can provide a geological basis for the exploration and development of bauxite in the Ordos Basin and similar basins worldwide.
RESUMO
The objective is to compare the clinical efficacy and safety of the S8 navigation system and the Tinavi orthopaedic surgery robot in the treatment of upper cervical instability. The research methods adopted are as follows. The clinical data of patients with upper cervical instability who underwent surgery from May 2021 to December 2021 were analysed retrospectively. Patients were divided into a navigation group (assisted by the S8 navigation system) and a tinavi group (assisted by the Tinavi robot) according to the auxiliary system used. Computed tomography and digital radiography were performed after the operation. The accuracy of pedicle screw placement was evaluated using the criteria put forward by Rampersaud. Degree of facet joint violation, visual analogue scale score, neck disability index and Japanese orthopaedic association score were recorded and assessed during follow-up examinations in both groups. Record two groups of surgery-related indicators. Record the complications of the two groups. A total of 50 patients were included. 21 patients in the navigation group and 29 in the tinavi group. The results of the study are as follows. The average follow-up time was 12.1 months. There was no significant difference in nail placement accuracy between the navigation and tinavi groups (P > 0.05); however, the navigation group had a significantly higher rate of facet joint violation than that of tinavi group (P < 0.05), and the screws were placed closer to the anterior cortex (P < 0.05). Significantly more intraoperative fluoroscopies were performed in the tinavi group than in the navigation group, and the operation time was significantly longer in the tinavi group than in the navigation group (P < 0.05). The time of single nail implantation, intraoperative blood loss and incision length in navigation group were significantly longer than those in tinavi group. There were no statistically significant differences in other indicators between the two groups (P > 0.05). We come to the following conclusion. The Stealth Station S8 navigation system (Medtronic, USA), which also uses an optical tracking system, and the Tinavi Orthopedic robot have shown the same high accuracy and satisfactory clinical results in the treatment of upper cervical instability. Although the S8 navigation system still has many limitations, it still has good application prospects and is a new tool for spine surgery.
Assuntos
Ortopedia , Parafusos Pediculares , Robótica , Fusão Vertebral , Humanos , Estudos Retrospectivos , Resultado do TratamentoRESUMO
INTRODUCTION: High-dose methotrexate (HDMTX) therapy poses challenges in various neoplasms due to individualized pharmacokinetics and associated adverse effects. Our purpose is to identify early risk factors associated with HDMTX-induced toxicities, paving the way for personalized treatment. AREAS COVERED: A systematic review of PubMed and Cochrane databases was conducted for articles from inception to July 2023. Eligible studies included reviews, clinical trials, and real-world analyses. Irrelevant studies were excluded, and manual searches and citation reviews were performed. Factors such as MTX exposure, drug interactions, demographics, serum albumin, urine pH, serum calcium, and genetic polymorphisms affecting MTX transport (e.g. SLCO1B1), intracellular folate metabolism (MTHFR), cell development (ARID5B), metabolic pathways (UGT1A1, PNPLA3), as well as epigenetics were identified. EXPERT OPINION: This comprehensive review aids researchers and clinicians in early identification of HDMTX toxicity risk factors. By understanding the multifaceted risk factors associated with hematologic malignancies, personalized treatment approaches can be tailored to optimize therapeutic outcomes.
Assuntos
Antimetabólitos Antineoplásicos , Relação Dose-Resposta a Droga , Metotrexato , Humanos , Antimetabólitos Antineoplásicos/efeitos adversos , Antimetabólitos Antineoplásicos/administração & dosagem , Antimetabólitos Antineoplásicos/farmacocinética , Interações Medicamentosas , Neoplasias Hematológicas/tratamento farmacológico , Metotrexato/efeitos adversos , Metotrexato/administração & dosagem , Polimorfismo Genético , Medicina de Precisão/métodos , Fatores de RiscoRESUMO
Aims: To develop and validate a UHPLC-MS/MS method for lamotrigine (LTG) analysis in human plasma and evaluate its agreement with a homogenous enzyme immunoassay (HEIA). Materials & methods: The UHPLC-MS/MS method was developed and validated according to the USFDA/EMA guidelines. A Bland-Altman plot was used to evaluate the agreement between UHPLC-MS/MS and HEIA. Results: Samples were pretreated with one-step protein precipitation and separated in 2.6 min. The intra- and inter-day bias and imprecisions were -15.8 to 15.0% and less than 11.17%, respectively. The recovery and matrix factor were 98.30 to 111.97%. The mean overestimation of UHPLC-MS/MS compared with HEIA was 21.57%. Conclusion: A rapid, sensitive and robust UHPLC-MS/MS method for plasma LTG analysis was developed and validated and was a 21.57% overestimation compared with HEIA.
Assuntos
Anticonvulsivantes , Espectrometria de Massas em Tandem , Humanos , Lamotrigina , Espectrometria de Massas em Tandem/métodos , Cromatografia Líquida de Alta Pressão/métodos , Técnicas Imunoenzimáticas , Imunoensaio/métodos , Reprodutibilidade dos TestesRESUMO
Alkaline stress poses a significant challenge to the healthy growth of fish. Ginger polysaccharide (GP) is one of the main active substances in ginger and has pharmacological effects, such as anti-oxidation and immune regulation. However, the physiological regulatory mechanism of GP addition to diet on alkalinity stress in crucian carp remains unclear. This study aimed to investigate the potential protective effects of dietary GP on antioxidant capacity, gene expression levels, intestinal microbiome, and metabolomics of crucian carp exposed to carbonate (NaHCO3). The CK group (no GP supplementation) and COG group (NaHCO3 stress and no GP supplementation) were set up. The GPCS group (NaHCO3 stress and 0.4% GP supplementation) was stressed for seven days. Based on these data, GP significantly increased the activities of total antioxidant capacity (T-AOC), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-PX), acid phosphatase (ACP), and alkaline phosphatase (AKP) in carp under alkalinity stress (p < 0.05) and decreased the activity of malon dialdehyde (MDA) (p < 0.05). GP restored the activity of GSH-PX, ACP, and AKP to CK levels. The expression levels of tumor necrosis factor ß (TGF-ß), tumor necrosis factor-alpha (TNF-α), interferon-gamma (IFN-γ), and interleukin 8 (IL-8) genes were decreased, and the expression levels of determination factor kappa-B (NF-κB) and interleukin 10 (IL-10) genes were increased (p < 0.05). Based on 16â¯S rRNA high-throughput sequencing, GP improved the changes in the intestinal microbial diversity and structural composition of crucian carp caused by NaHCO3 exposure. In particular, GP increased the relative abundance of Proteobacteria and Bacteroidetes and decreased the relative abundance of Actinobacteria. The metabolic response of GP to NaHCO3 exposed crucian carp guts was studied using LC/MS. Compared to the COG group, the GPCS group had 64 different metabolites and enriched 10 metabolic pathways, including lipid metabolism, nucleotide metabolism, and carbohydrate metabolism. The addition of GP to feed can promote galactose metabolism and provide an energy supply to crucian carp, thus alleviating the damage induced by alkalinity stress. In conclusion, GP can mitigate the effects of NaHCO3 alkalinity stress by regulating immune function, intestinal flora, and intestinal metabolism in crucian carp. These findings provide a novel idea for studying the mechanism of salt-alkali tolerance in crucian carp by adding GP to feed.
Assuntos
Carpas , Microbioma Gastrointestinal , Zingiber officinale , Animais , Carpa Dourada/metabolismo , Carpas/metabolismo , Antioxidantes/metabolismo , Dieta , Carbonatos , Ração Animal/análiseRESUMO
PURPOSE: Prostate cancer (PCa) is often considered as a "cold" tumor with low responsiveness to immunotherapy. Recent evidence suggests the activation of specific immune cells, such as tumor-associated macrophages (TAMs), could potentially influence the efficacy of immunotherapy in PCa. However, the relationship between TAMs and PD-L1, a significant regulator in immunotherapy, within PCa remains unexplored. METHODS: In this study, we assessed TAM infiltration and PD-L1 expression levels in a local cohort of 95 PCa tissue samples and two publicly available PCa datasets. We employed a combination of bioinformatics and experimental techniques, including gene set enrichment analysis, CIBERSORTx, tissue microarray, immunohistochemistry staining, and analysis of single-cell sequencing datasets, to provide a comprehensive understanding of the association between PD-L1 and TAMs in the PCa microenvironment. RESULTS: The study showed that CD68+ TAMs and CD163+ TAMs (M2-TAMs) were more abundant in the tumor microenvironment than in non-cancerous surrounding tissues. The infiltration of CD163+ TAMs was significantly associated with the Gleason score and risk stratification of PCa. Importantly, elevated PD-L1 expression correlated significantly with high infiltration of CD163+ TAMs. Furthermore, patients displaying high levels of CD163+ TAMs and PD-L1 expression exhibited shorter times to biochemical recurrence-free survival. CONCLUSION: Our study suggests that CD163+ TAMs are closely associated with PD-L1 expression and can act as a valuable prognostic indicator for PCa. The high infiltration of M2-TAMs, coupled with the overexpression of PD-L1, may contribute to immune escape mechanisms in PCa, thereby influencing disease prognosis.
Assuntos
Neoplasias da Próstata , Macrófagos Associados a Tumor , Humanos , Masculino , Antígeno B7-H1/metabolismo , Imunoterapia , Macrófagos/metabolismo , Prognóstico , Neoplasias da Próstata/patologia , Microambiente Tumoral , Macrófagos Associados a Tumor/metabolismoRESUMO
A method using ultrahigh-performance liquid chromatography-tandem mass spectrometry was developed, validated, and applied to simultaneously determine plasma methotrexate (MTX) and 7-hydroxy-methotrexate (7-OH-MTX) in 117 patients with central nervous system (CNS) lymphoma. The ion transitions utilized were m/z 455.2 > 308.2 for MTX and m/z 471.2 > 324.1 for 7-OH-MTX. Samples were prepared through protein precipitation using methanol. Chromatographic separation was achieved within 3.0 min on a CMS9030 column (Ruixi, 2.1 × 50 mm, 3 µm) through a gradient elution of methanol and a 10% ammonium acetate solution at a flow rate of 0.4 mL/min. The method demonstrated linearity in the concentration range of 0.05-10 µM for MTX and 0.25-50 µM for 7-OH-MTX. The intra- and inter-day inaccuracy ranged from -7.38% to 7.83%, and the imprecision was less than 6.00% for both analytes. The recovery and matrix effect normalized by the internal standard (MTX-D3 ) remained consistent. Both analytes remained stable under nine different storage conditions. In patients with CNS lymphoma, MTX levels at 12 h and 7-OH-MTX levels at 12, 36, and 60 h after dosing in individuals with impaired renal function were significantly higher compared with those with normal renal function. 7-OH-MTX could potentially serve as a superior indicator for nephrotoxicity compared with MTX.
Assuntos
Linfoma , Metotrexato , Humanos , Metotrexato/uso terapêutico , Espectrometria de Massas em Tandem/métodos , Monitoramento de Medicamentos/métodos , Metanol , Cromatografia Líquida de Alta Pressão/métodos , Sistema Nervoso Central/química , Sistema Nervoso Central/metabolismo , Linfoma/tratamento farmacológicoRESUMO
OBJECTIVES: This study evaluated the benefits and risks of patients with refractory or relapsed acute lymphocytic leukemia (R/R ALL) treated with anti-CD19 chimeric antigen receptor (CAR) T-cell therapy and blinatumomab. METHODS: PubMed, Web of Science, Embase, and the Cochrane Library were searched for relevant studies. RESULTS: The pooled complete remission (CR) rate and minimal residual disease (MRD) negative rate were 48%, 31% for blinatumomab, and 86% and 80% for CAR T-cell therapy. CONCLUSIONS: The CAR T-cell therapy group exhibited a higher likelihood of CR rate than the blinatumomab group in every analysis regardless of adjustment subgroups. CAR T-cell therapy was associated with a significantly prolonged overall survival (OS) and relapse-free survival (RFS) compared with blinatumomab (2-year OS 55% vs 25%; 2-year RFS 40% vs 22%). CAR T-cell therapy was more effective for achieving CR and bridging to allogeneic hematopoietic stem cell transplantation (allo-SCT) than blinatumomab (2-year OS 75% vs. 57%). An emerging role for blinatumomab is as a bridging agent pre-SCT, and for patients who achieve an MRD-negative state pre-SCT, post-SCT outcomes are expected to be the same as CAR-T. For adverse effects (AEs), blinatumomab was associated with a lower rate of grade ≥3 hematological toxicity, CRS, and neurological events.
Assuntos
Anticorpos Biespecíficos , Transplante de Células-Tronco Hematopoéticas , Leucemia-Linfoma Linfoblástico de Células Precursoras , Humanos , Imunoterapia Adotiva/efeitos adversos , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Anticorpos Biespecíficos/efeitos adversos , Recidiva , Antígenos CD19RESUMO
The objective was to compare the clinical efficacy of percutaneous pedicle screw internal fixation with the aid of the TINAVI orthopaedic surgery robot with that of traditional open surgery for Levine-Edward type IIA (postreduction) hangman fractures and to evaluate the safety and efficacy of the TINAVI robot-assisted orthopaedic surgery procedure. The clinical data of 60 patients with Levine-Edward type IIA (postreduction) hangman fractures treated surgically from June 2015 to February 2022 were analysed retrospectively. Among these patients, 25 were treated with percutaneous pedicle screw fixation under TINAVI (the robot group), and 35 were treated with pedicle screw implantation assisted by a conventional C-arm X-ray machine (the traditional operation group). The pedicle screw placement grade was evaluated according to the Rampersaud scale. The correct rate of pedicle screw placement was calculated. The invasion of adjacent facet joints, VAS score (Visual Analogue Scale), NDI score (Neck Disability Index), SF-36 score (36-Item Short-Form Health Survey questionnaire), EQ-5D score (EuroQol-5 dimensions questionnaire) and operation-related data were recorded, and patients were followed up. All patients were followed up for an average of 15.0 ± 3.4 months. The accuracy of screw placement in the robot group was higher than that in the traditional operation group, while the rates of intraoperative blood loss and invasion of the facet joint were lower and the incision length and length of hospital stay were shorter. On the 3rd day after the operation, the VAS score in the robot group was significantly higher than that in the traditional operation group, but there was no significant difference in the NDI score. On the 3rd day after the operation, the SF-36 and EQ-5 questionnaire scores of the robot group were better than those of the traditional operation group. No complications occurred in any of the patients. Postoperative cervical X-ray showed that the cervical vertebra was stable, and there was no fracture, angle or displacement. Postoperative CT showed that all fractures healed, and the average healing time was 3.4 months. The treatment of Levine-Edward IIA (postrepositioning) hangman fractures with percutaneous pedicle fixation assisted by the TINAVI orthopaedic surgery robot can significantly improve screw placement accuracy with a low rate of invasion of the adjacent facet joint, a short operation time, a low bleeding rate, and high patient satisfaction. Although there are still many disadvantages, it still has good prospects for application.
Assuntos
Fraturas Ósseas , Ortopedia , Procedimentos Cirúrgicos Robóticos , Fraturas da Coluna Vertebral , Humanos , Procedimentos Cirúrgicos Robóticos/efeitos adversos , Estudos RetrospectivosRESUMO
Background: Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is a first-line approach for diagnosing hilar and mediastinal lymph node metastasis. Endobronchial ultrasound (EBUS) elastography is an imaging technique for describing the elasticity of intrathoracic lesions. However, the reported accuracy of EBUS elastography needs to be improved. In this study, we aimed to explore the diagnostic value of EBUS elastography for differentiating between benign and malignant hilar and mediastinal lymph nodes. Methods: We conducted a single-center, retrospective study enrolling consecutive patients who received EBUS elastography followed by EBUS-TBNA at the Chinese PLA General Hospital from October 2015 to October 2022. The pathological results of EBUS-TBNA confirmed by 6-month follow-up were used as the gold standard. The ultrasound elastography parameters of lymph nodes included strain rate, stiff area ratio, and elasticity score, along with the conventional ultrasound characteristics such as short axis diameter, shape, margin, echogenicity distribution and intensity, and blood flow. The diagnostic performance of these parameters was compared, and conjointly analyzed using multivariate logistic regression. Bootstrapping resampling was applied for internal validation of the regression model. Results: A total of 83 patients were enrolled with an average age of 57 years, and 66.3% of patients were male. In total, 131 lymph nodes were punctured, among which 79 (60.3%) were malignant. All the conventional ultrasound characteristics were significantly different between benign and malignant lymph nodes. All the ultrasound elastography parameters of malignant lymph nodes were markedly higher than those of benign lymph nodes. Multivariate logistic regression analysis showed that the margin, echogenicity intensity, blood flow, short axis diameter, and stiff area ratio were the main factors affecting the lymph node property. The diagnostic accuracy, sensitivity, and specificity were 91.8% [95% confidence interval (CI): 85.4-96.0%], 94.4% (95% CI: 86.4-98.5%), and 88.0% (95% CI: 75.7-95.5%), respectively. Bootstrap resampling validation showed a concordance index (C-index) of 0.949. The calibration plot indicated good agreement between the predicted and observed results. Conclusions: EBUS elastography is a promising approach for differentiating between benign and malignant lymph nodes. The combination of conventional EBUS and elastography can improve diagnostic efficacy, provide reliable complementary information, and guide the implementation of EBUS-TBNA more accurately.