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Asian Pacific Journal of Cancer... Jun 2024
Topics: Humans; Cytochrome P-450 CYP3A; Rhabdomyosarcoma; Vincristine; Polymorphism, Genetic; Prognosis; Antineoplastic Agents, Phytogenic
PubMed: 38918644
DOI: 10.31557/APJCP.2024.25.6.1861 -
PloS One 2024Opioids administered in hospital during the immediate postoperative period are likely to influence post-surgical outcomes, but inpatient prescribing during the admission...
BACKGROUND
Opioids administered in hospital during the immediate postoperative period are likely to influence post-surgical outcomes, but inpatient prescribing during the admission is challenging to access. Modified-release(MR) preparations have been especially associated with harm, whilst certain populations such as the elderly or those with renal impairment may be vulnerable to complications. This study aimed to assess postoperative opioid utilisation patterns during hospital stay for people admitted for major/orthopaedic surgery.
METHODS
Patients admitted to a teaching hospital in the North-West of England between 2010-2021 for major/orthopaedic surgery with an admission for ≥1 day were included. We examined opioid administrations in the first seven days post-surgery in hospital, and "first 48 hours" were defined as the initial period. Proportions of MR opioids, initial immediate-release(IR) oxycodone and initial morphine milligram equivalents (MME)/day were calculated and summarised by calendar year. We also assessed the proportion of patients prescribed an opioid at discharge.
RESULTS
Among patients admitted for major/orthopaedic surgery, 71.1% of patients administered opioids during their hospitalisation. In total 50,496 patients with 60,167 hospital admissions were evaluated. Between 2010-2017 MR opioids increased from 8.7% to 16.1% and dropped to 11.6% in 2021. Initial use of oxycodone IR among younger patients (≤70 years) rose from 8.3% to 25.5% (2010-2017) and dropped to 17.2% in 2021. The proportion of patients on ≥50MME/day ranged from 13% (2021) to 22.9% (2010). Of the patients administered an opioid in hospital, 26,920 (53.3%) patients were discharged on an opioid.
CONCLUSIONS
In patients hospitalised with major/orthopaedic surgery, 4 in 6 patients were administered an opioid. We observed a high frequency of administered MR opioids in adult patients and initial oxycodone IR in the ≤70 age group. Patients prescribed with ≥50MME/day ranged between 13-22.9%. This is the first published study evaluating UK inpatient opioid use, which highlights opportunities for improving safer prescribing in line with latest recommendations.
Topics: Humans; Analgesics, Opioid; Male; Female; Middle Aged; Aged; Retrospective Studies; Pain, Postoperative; Orthopedic Procedures; Adult; Electronic Prescribing; Inpatients; England; Hospitalization; Aged, 80 and over; Oxycodone; Adolescent
PubMed: 38917135
DOI: 10.1371/journal.pone.0305531 -
JAMA Network Open Jun 2024Fentanyl has exacerbated the opioid use disorder (OUD) and opioid overdose epidemic. Data on the effectiveness of medications for OUD among patients using fentanyl are... (Randomized Controlled Trial)
Randomized Controlled Trial
IMPORTANCE
Fentanyl has exacerbated the opioid use disorder (OUD) and opioid overdose epidemic. Data on the effectiveness of medications for OUD among patients using fentanyl are limited.
OBJECTIVE
To assess the effectiveness of sublingual or extended-release injection formulations of buprenorphine for the treatment of OUD among patients with and without fentanyl use.
DESIGN, SETTING, AND PARTICIPANTS
Post hoc analysis of a 24-week, randomized, double-blind clinical trial conducted at 35 outpatient sites in the US from December 2015 to November 2016 of sublingual buprenorphine-naloxone vs extended-release subcutaneous injection buprenorphine (CAM2038) for patients with OUD subgrouped by presence vs absence of fentanyl or norfentanyl in urine at baseline. Study visits with urine testing occurred weekly for 12 weeks, then 6 times between weeks 13 and 24. Data were analyzed on an intention-to-treat basis from March 2022 to August 2023.
INTERVENTION
Weekly and monthly subcutaneous buprenorphine vs daily sublingual buprenorphine-naloxone.
MAIN OUTCOMES AND MEASURES
Retention in treatment, percentage of urine samples negative for any opioids (missing values imputed as positive), percentage of urine samples negative for fentanyl or norfentanyl (missing values not imputed), and scores on opiate withdrawal scales and visual analog craving scales.
RESULTS
Of 428 participants, 123 (subcutaneous buprenorphine, n = 64; sublingual buprenorphine-naloxone, n = 59; mean [SD] age, 39.1 [10.8] years; 75 men [61.0%]) had evidence of baseline fentanyl use and 305 (subcutaneous buprenorphine, n = 149; buprenorphine-naloxone, n = 156; mean [SD] age, 38.1 [11.1] years; 188 men [61.6%]) did not have evidence of baseline fentanyl use. Study completion was similar between the fentanyl-positive (60.2% [74 of 123]) and fentanyl-negative (56.7% [173 of 305]) subgroups. The mean percentage of urine samples negative for any opioid were 28.5% among those receiving subcutaneous buprenorphine and 18.8% among those receiving buprenorphine-naloxone in the fentanyl-positive subgroup (difference, 9.6%; 95% CI, -3.0% to 22.3%) and 36.7% among those receiving subcutaneous buprenorphine and 30.6% among those receiving buprenorphine-naloxone in the fentanyl-negative subgroup (difference, 6.1%; 95% CI, -1.9% to 14.1%), with significant main associations of baseline fentanyl status and treatment group. In the fentanyl-positive subgroup, the mean percentage of urine samples negative for fentanyl during the study was 74.6% among those receiving subcutaneous buprenorphine vs 61.9% among those receiving sublingual buprenorphine-naloxone (difference, 12.7%; 95% CI, 9.6%-15.9%). Opioid withdrawal and craving scores decreased rapidly after treatment initiation across all groups.
CONCLUSIONS AND RELEVANCE
In this post hoc analysis of a randomized clinical trial of sublingual vs extended-release injection buprenorphine for OUD, buprenorphine appeared to be effective among patients with baseline fentanyl use. Patients with fentanyl use had fewer opioid-negative urine samples during the trial compared with the fentanyl-negative subgroup. These findings suggest that the subcutaneous buprenorphine formulation may be more effective at reducing fentanyl use.
TRIAL REGISTRATION
ClinicalTrials.gov Identifier: NCT02651584.
Topics: Humans; Opioid-Related Disorders; Fentanyl; Male; Female; Administration, Sublingual; Adult; Double-Blind Method; Buprenorphine; Middle Aged; Delayed-Action Preparations; Injections, Subcutaneous; Narcotic Antagonists; Analgesics, Opioid; Opiate Substitution Treatment; Buprenorphine, Naloxone Drug Combination; Treatment Outcome
PubMed: 38916892
DOI: 10.1001/jamanetworkopen.2024.17377 -
Reumatismo Jun 2024Nicotine has major side effects on human health through numerous mechanisms, one of which is the alteration of the immune system and its genetic components. Such... (Review)
Review
OBJECTIVE
Nicotine has major side effects on human health through numerous mechanisms, one of which is the alteration of the immune system and its genetic components. Such alteration can be a predisposing factor for autoimmune diseases such as spondyloarthritis (SpA) and rheumatoid arthritis (RA). This review aims to shed light on the effects of nicotine smoking on the pathophysiology, clinical presentation, and management of SpA and RA.
METHODS
This review looked into the studies, excluding case reports and series, which were cited by PubMed/MEDLINE.
RESULTS
Patients with established autoimmune conditions may have a different underlying pathophysiology and disease course when exposed to nicotine through cigarette smoking. Through the involvement of several cytokines, endothelial dysfunction, and epigenetic mechanisms, the severity of SpA is more prominent in smokers. The global health status, pain, and fatigue are worse in SpA patients. The evidence on the effect of nicotine smoking on the treatment of SpA is still limited. Nicotine can contribute to RA via the disruption of cellular regulatory activity, inflammatory responses, morphological, physiological, biochemical, and enzymatic responses. As such, smokers with RA have higher disease activity and are more likely to be seropositive through the citrullination of peptides. In addition, these patients are at risk of achieving a suboptimal response to tumor necrosis factor inhibitors.
CONCLUSIONS
Cigarette smoking can substantially affect the pathophysiology and clinical presentation of patients with SpA and RA. The impact of nicotine on the management of these diseases still needs to be further studied.
Topics: Humans; Arthritis, Rheumatoid; Nicotine; Spondylarthritis; Smoking
PubMed: 38916171
DOI: 10.4081/reumatismo.2024.1572 -
Drug Design, Development and Therapy 2024SN-38 (7-ethyl-10-hydroxycamptothecin), the active metabolite of irinotecan, has been extensively studied in drug delivery systems. However, its impact on neural...
PURPOSE
SN-38 (7-ethyl-10-hydroxycamptothecin), the active metabolite of irinotecan, has been extensively studied in drug delivery systems. However, its impact on neural metabolism remains unclear. This study aims to investigate the toxic effects of SN-38 on mouse brain metabolism.
METHODS
Male mice were divided into an SN-38 group and a control group. The SN-38 group received SN-38 (20 mg/kg/day) via intraperitoneal injection, while the control group was given an equal volume of a blank solvent mixture (DMSO and saline, ratio 1:9). Gas chromatography-mass spectrometry (GC-MS) was employed to analyze differential metabolites in the cortical and hippocampal regions of the SN-38-treated mice.
RESULTS
SN-38 induced metabolic disturbances in the central nervous system. Eighteen differential metabolites were identified in the hippocampus and twenty-four in the cortex, with six common to both regions. KEGG pathway enrichment analysis revealed statistically significant alterations in six metabolic pathways in the hippocampus and ten in the cortex (P<0.05).
CONCLUSION
This study is the first to demonstrate the neurotoxicity of SN-38 in male mice through metabolomics. Differential metabolites in the hippocampal and cortical regions were closely linked to purine metabolism, pyrimidine metabolism, amino acid metabolism, and glyceride metabolism, indicating disruptions in the blood-brain barrier, energy metabolism, and central signaling pathways.
Topics: Animals; Male; Irinotecan; Mice; Metabolomics; Brain; Gas Chromatography-Mass Spectrometry; Injections, Intraperitoneal
PubMed: 38915864
DOI: 10.2147/DDDT.S457698 -
Frontiers in Pharmacology 2024Cervical cancer (CC) ranks as the fourth most prevalent malignant tumor among women worldwide, and is the fourth leading cause of cancer-related mortality. GuiErBai...
Cervical cancer (CC) ranks as the fourth most prevalent malignant tumor among women worldwide, and is the fourth leading cause of cancer-related mortality. GuiErBai (GEB), a compound preparation developed by our research team, is derived from the ancient Chinese medicine of the Miao nationality and is comprised of podophyllotoxin (PTOX), imperatorin, isoimperatorin, and alkaloids. These individual components have demonstrated notable efficacy in tumor treatment. However, the specific anti-tumor effect of the compound Chinese medicine GEB in the context of CC has yet to be validated. HeLa and SiHa cell lines were utilized for experiments and treated with 5 mg/mL and 10 mg/mL GEB concentrations, respectively. The cell cycle changes after GEB treatment were assessed using flow cytometry. Transmission electron microscopy was employed to observe autophagic bodies and apoptotic bodies, while MDC staining evaluated the occurrence of autophagy. CCK-8 was used to observe the effect of GEB on cell proliferation, and Transwell assays assessed cell migration and invasion. Western blotting detected cell cycle and apoptosis-related protein expression, along with the expression level of autophagy-related protein LC3I/II. Changes in ROS and mitochondrial membrane potential in cervical cancer cells following GEB treatment were determined using ROS detection and mitochondrial membrane potential detection kits. For the experiment, a nude mouse model of cervical cancer transplantation based on HeLa cells was established. Experimental animals were divided into negative control, positive control, high-dose GEB (10 mg/mL), and low-dose GEB (5 mg/mL) groups. In HeLa and SiHa cell lines, the G0/G1 phase of tumor cells significantly decreased ( < 0.001), while the G2/M phase increased notably ( < 0.001) following various GEB treatments. Electron microscopy showed GEB promoted apoptotic body and autophagosome formation in both cell lines. Compared to untreated HeLa and SiHa cells, GEB-treated cells exhibited significantly reduced caspase3 protein expression, and substantially increased autophagy-related protein LC3I/II expression. GEB treatment significantly reduced migration and invasion capabilities in both cell lines ( < 0.001), while ROS content and mitochondrial membrane potential were significantly elevated ( < 0.001). GEB effectively inhibited cervical cancer cell proliferation, with the optimal concentration being 10 mg/mL. A successful nude mouse model of cervical cancer transplantation was established using HeLa cells. Post-GEB treatment, the tumor volume and weight in nude mice significantly decreased ( < 0.001), with diminished expression of CD34, VEGF, and caspase3 proteins in tumor tissues. GEB exhibits a robust antitumor effect against cervical cancer, both and , in a concentration-dependent manner, by regulating autophagy and apoptosis of tumor cells.
PubMed: 38915466
DOI: 10.3389/fphar.2024.1296588 -
Lipids in Health and Disease Jun 2024Uric acid (UA), a liver-derived metabolite, is intimately tied to metabolic disorders. Although ample research underscores its connection with hypertriglyceridemia...
BACKGROUND
Uric acid (UA), a liver-derived metabolite, is intimately tied to metabolic disorders. Although ample research underscores its connection with hypertriglyceridemia (HTG), studies focusing on adolescents remain limited. To fill the gaps in epidemiology,this study focused on analyzing the relationship between the levels of uric acid and HTG in a demographic sample comprising adolescents from the United States.
METHODS
In this study, a total of 4,435 participants through the National Health and Nutrition Examination Survey (NHANES) from 2011 to 2020. The exposure variable was serum uric acid (SUA), the effect variable was HTG, and the covariates included demographic, questionnaire, physical examination and laboratory indicators. We utilized weighted logistic regression and meticulous subgroup evaluations to discern the intrinsic link between SUA and HTG. Stratified analyses augmented the validation of this association, while smooth curve fitting probed for potential nonlinear correlations.
RESULTS
The study included 4,435 participants. Male adolescents exhibit elevated SUA levels. After adjusting for all variables, the weighted multiple logistic regression model revealed that SUA was positively correlated with HTG risk (OR = 1.006, 95% CI: 1.005-1.007). This relationship was consistent across the three tertiles group of SUA (T1: OR = 1.006 [95% CI: 1.005-1.007]; T2: OR = 1.006 [95% CI: 1.005-1.007]; T3: OR = 1.004 [95% CI: 1.003-1.006]; P for trend < 0.001). Stratified analyses confirmed that the positive correlation between SUA and HTG risk was significant, irrespective of sex, age or race.
CONCLUSIONS
In American children and adolescents aged 12 to 18 years, there was a pronounced association between SUA and HTG. SUA could serve as a risk indicator for HTG. It is recommended that children diagnosed with HTG should be regularly tested for SUA levels. In addition, it is recommended that SUA be included in the comprehensive care of children diagnosed with HTG.
Topics: Humans; Uric Acid; Adolescent; Hypertriglyceridemia; Male; Female; Child; Cross-Sectional Studies; Nutrition Surveys; Logistic Models; Risk Factors; United States; Triglycerides
PubMed: 38915087
DOI: 10.1186/s12944-024-02182-1 -
Scientific Reports Jun 2024Cryptosporidiosis is a worldwide zoonotic disease. Oxymatrine, an alkaloid extracted and isolated from the plant bitter ginseng, has been reported to have therapeutic...
Cryptosporidiosis is a worldwide zoonotic disease. Oxymatrine, an alkaloid extracted and isolated from the plant bitter ginseng, has been reported to have therapeutic effects on cryptosporidiosis. However, the underlying mechanism of its action remains unclear. In this study, we utilized network pharmacology and experimental validation to investigate the mechanism of oxymatrine in the treatment of cryptosporidiosis. First, the potential targets of drugs and diseases were predicted by TCMSP, Gene Cards, and other databases. Following the intersection of drug-disease targets, the DAVID database was used to implement the enrichment analysis of GO functions and KEGG pathways, and then the network diagram of "intersected target-KEGG" relationship was constructed. Autodock 4.2.6 software was used to carry out the molecular docking of core targets to drug components. Based on the establishment of a mouse model of cryptosporidiosis, the validity of the targets in the TNF/NF-κB signaling pathway was confirmed using Western blot analysis and Quantitative Rea-ltime-PCR. A total of 41 intersectional targets of oxymatrine and Cryptosporidium were generated from the results, and five core targets were screened out by network analysis, including RELA, AKT1, ESR1, TNF, and CASP3. The enrichment analysis showed that oxymatrine could regulate multiple gene targets, mediate TNF, Apoptpsis, IL-17, NF-κB and other signaling pathways. Molecular docking experiments revealed that oxymatrine was tightly bound to core targets with stable conformation. Furthermore, we found through animal experiments that oxymatrine could regulate the mRNA and protein expression of IL-6, NF-κB, and TNF-α in the intestinal tissues of post-infected mice through the TNF/NF-κB signaling pathway. Therefore, it can be concluded that oxymatrine can regulate the inflammatory factors TNF-α, NF-κB, and IL-6 through the TNF/NF-κB signaling pathway for the treatment of cryptosporidiosis. This prediction has also been validated by network pharmacology and animal experiments.
Topics: Quinolizines; Cryptosporidiosis; Animals; Signal Transduction; Alkaloids; Mice; NF-kappa B; Network Pharmacology; Molecular Docking Simulation; Tumor Necrosis Factor-alpha; Disease Models, Animal; Humans; Matrines
PubMed: 38914662
DOI: 10.1038/s41598-024-65362-0 -
Sheng Wu Gong Cheng Xue Bao = Chinese... Jun 2024Plant synthetic biology has significant theoretical advantages in exploration and production of plant natural products. However, its contribution to the field of...
Plant synthetic biology has significant theoretical advantages in exploration and production of plant natural products. However, its contribution to the field of biosynthesis is currently limited due to the lack of efficient chassis systems and related enabling technologies. Synthetic biologists often avoid tobacco as a chassis system because of its long operation cycle, difficulties in genetic and metabolic modification, complex metabolism and purification background, nicotine toxicity, and challenges in accurately controlling for agricultural production. Nevertheless, the tobacco suspension cell chassis system offers a viable solution to these challenges. The objective of this research was to develop a tobacco suspension cell chassis with high scientific and industrial potential. This chassis should exhibit rapid growth, high biomass, excellent dispersion, high transformation efficiency, and minimal nicotine content. , which has high applicability in molecular technology, was used to induce suspension cells. The induced suspension cells, named NBS-1, exhibited rapid growth, excellent dispersion, and high biomass, reaching a maximum biomass of 476.39 g/L (fresh weight), which was significantly higher than that of BY-2. The transformation efficiency of the widely utilized pEAQ-HT transient expression system in NBS-1 reached 81%, which was substantially elevated compared to BY-2. The metabolic characteristics and bias of BY-2 and NBS-1 were analyzed using transcriptome data. It was found that the gene expression of pathways related to biosynthesis of flavonoids and their derivatives in NBS-1 was significantly higher, while the pathways related to alkaloid biosynthesis were significantly lower compared to BY-2. These findings were further validated by the total content of flavonoid and alkaloid. In summary, our research demonstrates NBS-1 possesses minimal nicotine content and provides valuable guidance for selecting appropriate chassis for specific products. In conclusion, this study developed NBS-1, a tobacco suspension cell chassis with excellent growth and transformation, high flavonoid content and minimal nicotine content, which has important guiding significance for the development of tobacco suspension cell chassis.
Topics: Nicotiana; Synthetic Biology; Plants, Genetically Modified; Metabolic Engineering; Cell Culture Techniques; Nicotine; Biomass
PubMed: 38914502
DOI: 10.13345/j.cjb.230735 -
PloS One 2024Non-alcoholic fatty liver disease (NAFLD) is independently associated with atrial fibrillation (AF) risk. The uric acid (UA) to high-density lipoprotein cholesterol...
BACKGROUND
Non-alcoholic fatty liver disease (NAFLD) is independently associated with atrial fibrillation (AF) risk. The uric acid (UA) to high-density lipoprotein cholesterol (HDL-C) ratio (UHR) has been shown to be closely associated with cardiovascular disease (CVD) and NAFLD. The aim of this study is to clarify whether elevated UHR is associated with the occurrence of AF in patients with NAFLD and to determine whether UHR predicted AF.
METHODS
Patients diagnosed with NAFLD in the Department of Cardiovascular Medicine of the Second Hospital of Shanxi Medical University from January 1, 2020, to December 31, 2021, were retrospectively enrolled in this study. The study subjects were categorized into AF group and non-AF group based on the presence or absence of combined AF. Logistic regression was performed to evaluate the correlation between UHR and AF. Sensitivity analysis and subgroup interaction analysis were performed to verify the robustness of the study results. Receiver operating characteristic (ROC) curve analysis was used to determine the optimal cutoff value for UHR to predict the development of AF in patients with NAFLD.
RESULTS
A total of 421 patients with NAFLD were included, including 171 in the AF group and 250 in the non-AF group. In the univariate regression analysis, NAFLD patients with higher UHR were more likely to experience AF, and the risk of AF persisted after confounding factors were adjusted for (OR: 1.010, 95%CI: 1.007-1.013, P<0.001). AF risk increased with increasing UHR quartile (P for trend < 0.001). Despite normal serum UA and HDL-C, UHR was still connected with AF in patients with NAFLD. All subgroup variables did not interact significantly with UHR in the subgroup analysis. The ROC curve analysis showed that the areas under the curve for UA, HDL-C, and UHR were 0.702, 0.606, and 0.720, respectively, suggesting that UHR has a higher predictive value for AF occurrence in NAFLD patients compared to HDL-C or UA alone.
CONCLUSION
Increased UHR level was independently correlated with a high risk of AF in NAFLD patients.
Topics: Humans; Uric Acid; Atrial Fibrillation; Non-alcoholic Fatty Liver Disease; Male; Female; Cholesterol, HDL; Middle Aged; Retrospective Studies; ROC Curve; Risk Factors; Aged; Adult
PubMed: 38913677
DOI: 10.1371/journal.pone.0305952