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[This corrects the article DOI: 10.3389/fphar.2024.1345897.].
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Here, we report a silver carbene-enabled single-carbon insertion reaction of indoles via a one-pot, two-step sequence to deliver a dearomative quaternary center quinoline scaffold in a modular fashion. Specifically, we used N-triftosylhydrazones as masked donor-donor carbene precursors that facilitate the insertion of carbon atoms bearing various functional groups to the library of functionalized quinoline. Experimental and DFT evidence support the transient presence of a cyclopropane species and removal of protecting groups.
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Background: Alzheimer's disease (AD) is the most common sort of neurodegenerative dementia, characterized by its challenging, diverse, and progressive nature. Despite significant progress in neuroscience, the current treatment strategies remain suboptimal. Objective: Identifying a more accurate molecular target for the involvement of microglia in the pathogenic process of AD and exploring potential mechanisms via which it could influence disease. Methods: We utilized single-cell RNA sequencing (scRNA-seq) analysis in conjunction with APP/PS1 mouse models to find out the molecular mechanism of AD. With the goal of investigating the cellular heterogeneity of AD, we downloaded the scRNA-seq data from the Gene Expression Omnibus (GEO) database and identified differentially expressed genes (DEGs). Additionally, we evaluated learning and memory capacity using the behavioral experiment. We also examined the expression of proteins associated with memory using western blotting. Immunofluorescence was employed to investigate alterations in amyloid plaques and microglia. Results: Our findings revealed an upregulation of ITGAX expression in APP/PS1 transgenic mice, which coincided with a downregulation of synaptic plasticity-related proteins, an increase in amyloid-ß (Aß) plaques, and an elevation in the number of M1 microglia. Interestingly, deletion of ITGAX resulted in increased Aß plaque deposition, a rise in the M1 microglial phenotype, and decreased production of synaptic plasticity-related proteins, all of which contributed to a decline in learning and memory. Conclusions: This research suggested that ITGAX may have a beneficial impact on the APP/PS1 mice model, as its decreased expression could exacerbate the impairment of synaptic plasticity and worsen cognitive dysfunction.
Subject(s)
Alzheimer Disease , Down-Regulation , Mice, Transgenic , Microglia , Plaque, Amyloid , Animals , Male , Mice , Alzheimer Disease/metabolism , Alzheimer Disease/genetics , Alzheimer Disease/pathology , Amyloid beta-Peptides/metabolism , Amyloid beta-Protein Precursor/genetics , Amyloid beta-Protein Precursor/metabolism , Disease Models, Animal , Mice, Inbred C57BL , Microglia/metabolism , Microglia/pathology , Plaque, Amyloid/pathology , Plaque, Amyloid/metabolism , Presenilin-1/geneticsABSTRACT
Refraction is a basic beam bending effect at two media's interface. While traditional studies focus on stationary boundaries, moving boundaries or potentials could enable new laws of refractions. Meanwhile, media's discretization plays a pivotal role in refraction owing to Galilean invariance breaking principle in discrete-wave mechanics, making refraction highly moving-speed dependent. Here, by harnessing a synthetic temporal lattice in a fiber-loop circuit, we observe discrete time refraction by a moving gauge-potential barrier. We unveil the selection rules for the potential moving speed, which can only take an integer v = 1 or fractional v = 1/q (odd q) value to guarantee a well-defined refraction. We observe reflectionless/reflective refractions for v = 1 and v = 1/3 speeds, transparent potentials with vanishing refraction/reflection, refraction of dynamic moving potential and refraction for relativistic Zitterbewegung effect. Our findings may feature applications in versatile time control and measurement for optical communications and signal processing.
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Objectives: The purpose of the study was to comprehensively evaluate efficacy and safety of CDDP in patients with AMI undergoing PCI. Methods: A computerised search was conducted on the CNKI, WF, VIP, CBM, PubMed, Embase, Web of Science, and Cochrane Library databases for RCTs of CDDP adjuvant therapy for AMI up to May 2023. STATA 17.0 was used to perform meta-analyses, sensitivity analyses, subgroup analyses, meta-regression, and publication bias assessments. TSA 0.9.5.10 Beta was used for trial sequential analysis (TSA). Evidence confidence of meta results was evaluated by GRADE (Grading of Recommendations Assessment, Development and Evaluation) according to the instructions. Results: The results of the meta-analysis showed that CDDP combined with conventional western treatment (CWT) was superior to CWT in increasing LVEF and TCER and decreasing LVEDD, hs-CRP, IL-6 and TNF-α. The quality of evidence for TCER was moderate, LVEF, LVEDD, IL-6, and TNF-α were low. The TSA results showed that the total number of samples collected in this study met the requirements for meta-analysis and excluded the possibility of false positives, further confirming the efficacy of CDDP for the treatment of AMI undergoing PCI. Conclusion: Adjuvant treatment of AMI with CDDP has shown exciting and safe benefits in improving cardiac function and reducing inflammatory response in patients with AMI undergoing PCI, but the quality of some of the included studies was poor, and the results should be interpreted with caution until further confirmation by well-designed RCTs. Systematic Review Registration: [https://www.crd.york.ac.uk/PROSPERO/#recordDetails], identifier [CRD42023453293].
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As a frequently detected per- and polyfluoroalkyl substance in the environment, 6:6 perfluoroalkylhypophosphinic acid (6:6 PFPiA) is vulnerable to transformation in the liver of organisms, but the transformation in gut is still unclear. This study investigates the molecular mechanisms of 6:6 PFPiA transformation in the gut of Xenopus laevis upon a 28-day exposure in water. Before Day 16, a notable correlation (p = 0.03) was observed between the transformation product (PFHxPA) and cytochrome P450 (CYP450) enzyme concentration in gut. This suggests that CYP450 enzymes played an important role in the transformation of 6:6 PFPiA in the gut, which was verified by an in vitro incubation with gut tissues, and supported by the molecular docking results of 6:6 PFPiA binding with CYP450 enzymes. From the day 16, the CYP450 concentration in gut decreased by 31.3 % due to the damage caused by 6:6 PFPiA, leading to a decrease in the transformation capacity in gut, but the transformation rate was stronger than in liver. This was in contrast with the in vitro experiment, where transformation was stronger in liver. In the mean time, the abundance of Bacteroidota in gut increased, which released hydrolytic enzyme and then could participate in the transformation as well. This study reveals the potential of the gut in metabolizing environmental pollutants, and provides profound insights into the potential health risks caused by 6:6 PFPiA in organisms.
Subject(s)
Cytochrome P-450 Enzyme System , Gastrointestinal Microbiome , Xenopus laevis , Animals , Cytochrome P-450 Enzyme System/metabolism , Water Pollutants, Chemical/toxicity , Water Pollutants, Chemical/metabolism , Molecular Docking Simulation , Liver/enzymology , Liver/metabolism , Biotransformation , Organophosphorus Compounds/toxicity , Organophosphorus Compounds/metabolismABSTRACT
Expanding the network of connected and resilient protected areas (PAs) for climate change adaptation can help species track suitable climate conditions and safeguard biodiversity. This is often overlooked when expanding PAs and quantifying their benefits, resulting in an underestimate of the benefits of expanding PAs. We expanded PAs through terrestrial mammalian species distribution hotspots, Key Biodiversity Areas (KBAs), and wilderness areas. Then, we constructed climate connectivity networks using a resistance-based approach and further quantified the network resilience to propose resilient climate response strategies in China. The results showed that existing PAs suffered from location biases with important biodiversity areas. The existing PAs represented about half of the KBAs and wilderness areas, yet only 12.08% of terrestrial mammalian species distribution hotspots were located within existing PAs. Compared with the existing PA network, the network efficiency and resilience of the expanded PAs' climate connectivity increased to 1.80 times and 1.78 times, respectively. With 56% of the nodes remaining, the network efficiency of the expanded PAs was equivalent to that of the existing PAs with all nodes. The network resilience of preferentially protecting and restoring low human footprint patches was approximately 1.5-2 times that of the random scenario. These findings highlighted that confronted with the unoptimistic situation of global warming, nature conservation based on existing PAs was no longer optimal. It was critical to construct a connected and resilient conservation network relying on both important biodiversity areas and low human footprint patches.
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Biodiversity , Climate Change , Conservation of Natural Resources , China , Animals , Humans , Ecosystem , MammalsABSTRACT
Purpose: Patients undergoing arthroscopic hip surgery (AHS) require good analgesia and early rehabilitation after surgery, and there is no consensus on the optimal nerve block. We aimed to compare the efficacy of the pericapsular nerve group (PENG) block with lateral femoral cutaneous nerve (LFCN) block compared to fascia iliaca compartment block (FICB) in patients with AHS. Patients and Methods: A total of 80 patients receiving AHS under general anesthesia were randomized to receive either FICB (group F) or PENG block in combination with LFCN block (group P). The primary outcomes were the rate of quadriceps weakness after block on the afflicted side, as well as muscle strength grading and pain score after block, and the quality of recovery on the second postoperative day. Results: Compared with group F, group P had a lower incidence of quadriceps weakness 48 h after block (76.9% vs 28.2%, P < 0.001), and had less impact on muscle strength grade and lower static pain score at 6, 12, 18, 24, 36, and 48 h after block (P < 0.001), and a lower dynamic pain score at 6 and 12 h after block in group P (p < 0.05). The quality of recovery on the second postoperative day improved (p < 0.05). Conclusion: In comparison to FICB, PENG block in combination with LFCN block can affect less quadriceps muscle strength and reduce the use of postoperative analgesics, which is beneficial for the postoperative recovery of AHS patients.
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River CO2 emissions, which contribute 53 % of the basin's overall carbon emissions, are essential parts of the global and regional carbon cycles. Previous CO2 flux calculates are mostly based on single samples collected during ice-free periods; however, little is known about the effects of freeze-thaw cycles on the river CO2 flux (FCO2) of inland rivers in alpine regions. Based on one year-round monthly continuous field sampling, we quantified the FCO2 and determined their driving factors in typical rivers during different freeze-thaw periods in the Qinghai Lake Basin (QLB) using the thin boundary layer model (TBL) and the path analysis method. The findings indicated that (1) the average FCO2 in the typical rivers was 184.98 ± 329.12 mmol/m2/d, acting as a carbon source during different freeze-thaw periods, and showed a decreasing trend with completely thawed periods (CTP, 303.15 ± 376.56 mmol/m2/d) > unstable freezing periods (UFP, 189.44 ± 344.08 mmol/m2/d) > unstable thawing periods (UTP, 62.35 ± 266.71 mmol/m2/d); (2) pH, surface water temperature (Tw) and total alkalinity (TA) were the dominant controlling factors during different freeze-thaw periods. Interestingly, they significantly affected FCO2 more before completely frozen than after frozen, with Tw and TA changing from having promoting effects to having limiting effects; (3) in addition, dissolved carbon components indirectly affected FCO2, primarily through the indirect effects of pH and Tw in the UTP; wind speed (U) directly promoted FCO2 in the CTP; and Ca2+ and dissolved inorganic carbon (DIC) were susceptible to indirect effects, which promoted/limited the release of FCO2 in the UFP, respectively. Our results reveal the changes of FCO2 and the factors influencing it in inland rivers within alpine regions during different freeze-thaw periods, thereby offering valuable support for carbon emission-related studies in alpine regions.
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Alzheimer's disease (AD) is a severe neurological illness that causes memory loss and is a global problem. The calcium hypothesis recently steadily evolved in AD. The prospective targets for calcium homeostasis therapy, however, are limited, and gene expression-level research connected to calcium homeostasis in AD remains hazy. In this study, we analyzed the microarray dataset (GSE132903) taken from the Gene Expression Omnibus (GEO) database to investigate calcium homeostasis-related genes for AD. Using immunoblot analysis, we examined the association of ITPKB with inflammation in AD. Additionally, the immunofluorescence technique was employed to assess the impact of pharmacological inhibition of ITPKB on the amyloid-ß (Aß) plaque deposition in APP/PS1 mice. This article's further exploration of calcium homeostasis-related genes has propelled the validation of the calcium homeostasis theory in AD.
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Alzheimer Disease , Plaque, Amyloid , Animals , Mice , Plaque, Amyloid/genetics , Transcriptome , Calcium , Alzheimer Disease/genetics , Models, Animal , HomeostasisABSTRACT
Lactobacillus fermentum (L. fermentum) was first evaluated as a potential advanced glycation end-product (AGE) formation inhibitor by establishing a bovine serum albumin (BSA) + glucose (glu) glycation model in the present study. The results showed that the highest inhibition rates of pentosidine and total fluorescent AGEs by L. fermentum were approximately 51.67% and 77.22%, respectively, which were higher than that of aminoguanidine (AG). Mechanistic analysis showed that L. fermentum could capture methylglyoxal and glyoxal, inhibit carbonyl and sulfhydryl oxidation, reduce the binding of glucose and amino groups, increase total phenolic content and antioxidant activity, and release intracellular substances to scavenge free radicals; these abilities were the basis of the antiglycation mechanism of L. fermentum. In addition, L. fermentum significantly prevented conformational changes in proteins during glycation, reduced protein cross-linking by 35.67%, and protected the intrinsic fluorophore. Therefore, the inhibition of L. fermentum on glycation mainly occurs through antioxidation, the capture of dicarbonyl compounds, and the protection of the BSA structure. These findings collectively suggest that Lactobacillus is an inhibitor of protein glycation and AGE formation and has the potential for nutraceutical applications.
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Thermal stratification and mixing play important roles in the physicochemical composition of lakes and affect the geochemical cycle. However, the regulation of lake carbon exchange at the water-air interface by seasonal thermal structures remains unclear, especially for alpine saline lake on the Qinghai-Tibet Plateau (QTP). Based on continuous field sampling, carbon dioxide flux (FCO2) at the water-air interface in Qinghai Lake during the ice-free period was quantitatively analyzed by thin boundary layer model, as well as the driving factors of the change in FCO2 at the water-air interface. The findings revealed that the FCO2 was -22.16 ± 11.73 mmol m-2d-1 during the stratification period, and - 45.32 ± 29.67 mmol m-2d-1 during the mixing period. We found that thermal stratification limits the matter-energy exchange between the upper and bottom water columns, and carbonate precipitation results in a higher FCO2 than during mixing stage. However, the mixing process reduces the limiting effect of thermal stratification. During the carbonate process, water with higher salinity and pH at the bottom of the water column enters the upper part of the water column, reducing the partial pressure of carbon dioxide (pCO2) in the water column and causing the absorption of CO2 by the lake. Thermal stratification affects the vertical material-energy exchange and atmospheric CO2 uptake of lake. The present study further explains the possible underlying regulation of CO2 uptake in saline lake on the QTP involving the varied thermal structure.
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Epoxides, as a prominent small ring O-heterocyclic and the privileged pharmacophores for medicinal chemistry, have recently represented an ideal substrate for the development of single-atom replacements. The previous O-to-C replacement strategy for epoxides to date typically requires high temperatures to achieve low yields and lacks substrate range and functional group tolerance, so achieving this oxygen-carbon exchange remains a formidable challenge. Here, we report a silver-catalyzed direct conversion of epoxides into trifluoromethylcyclopropanes in a single step using trifluoromethyl N-triftosylhydrazones as carbene precursors, thereby achieving oxygen-carbon exchange via a tandem deoxygenation/[2 + 1] cycloaddition. The reaction shows broad tolerance of functional groups, allowing routine cheletropic olefin synthesis in a strategy for the net oxygen-carbon exchange reaction. The utility of this method is further showcased with the late-stage diversification of epoxides derived from bioactive natural products and drugs. Mechanistic experiments and DFT calculations elucidate the reaction mechanism and the origin of the chemo- and stereoselectivity.
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Background: Sepsis-induced acute lung injury (ALI) poses a significant threat to human health. Endothelial cells, especially pulmonary capillaries, are the primary barriers against sepsis in the lungs. Therefore, investigating endothelial cell function is essential to understand the pathophysiological processes of sepsis-induced ALI. Methods: We downloaded single-cell RNA-seq expression data from GEO with accession number GSE207651. The mice underwent cecal ligation and puncture (CLP) surgery, and lung tissue samples were collected at 0, 24, and 48 h. The cells were annotated using the CellMarker database and FindAllMarkers functions. GO enrichment analyses were performed using the Metascape software. Gene set enrichment Analysis (GSEA) and variation Analysis (GSVA) were performed to identify differential signaling pathways. Differential expression genes were collected with the "FindMarkers" function. The R package AUCell was used to score individual cells for pathway activities. The Cellchat package was used to explore intracellular communication. Results: Granulocytes increased significantly as the duration of endotoxemia increased. However, the number of T cells, NK cells, and B cells declined. Pulmonary capillary cells were grouped into three sub-clusters. Capillary-3 cells were enriched in the sham group, but declined sharply in the CLP.24 group. Capillary-1 cells peaked in the CLP.24 group, while Capillary-2 cells were enriched in the CLP.48 group. Furthermore, we found that Cd74+ Capillary-3 cells mainly participated in immune interactions. Plat+ Capillary-1 and Clec1a+ Capillary-2 are involved in various physiological processes. Regarding cell-cell interactions, Plat+ Capillary-1 plays the most critical role in granulocyte adherence to capillaries during ALI. Cd74+ Capillary cells expressing high levels of major histocompatibility complex (MHC) and mainly interacted with Cd8a+ T cells in the sham group. Conclusion: Plat+ capillaries are involved in the innate immune response through their interaction with neutrophils via ICAM-1 adhesion during endotoxemia, while Cd74+ capillaries epxressed high level of MHC proteins play a role in adaptive immune response through their interaction with T cells. However, it remains unclear whether the function of Cd74+ capillaries leans towards immunity or tolerance, and further studies are needed to confirm this.
Subject(s)
Acute Lung Injury , Endotoxemia , Sepsis , Mice , Animals , Humans , RNA/metabolism , Capillaries/metabolism , Endothelial Cells/metabolism , Endotoxemia/metabolism , Lung/metabolism , Acute Lung Injury/genetics , Acute Lung Injury/metabolism , Sepsis/complications , Sepsis/geneticsABSTRACT
Given the prevalence of heterocyclic scaffolds in drug-related molecules, converting these highly modular heterocyclic scaffolds into structural diversified and dearomatized analogs is an ideal strategy for improving their physicochemical and pharmacokinetic properties. Here, we described an efficient method for silver carbene-mediated dearomative N-N bond cleavage leading to skeletal hopping between indazole and 1,2-dihydroquinazoline via a highly selective single-carbon insertion procedure. Using this methodology, a series of dihydroquinazoline analogues with diarylmethylene-substituted quaternary carbon centers were constructed with excellent yields and good functional group compatibility, which was further illustrated by the late-stage diversification of important pharmaceutically active ingredients. DFT calculations indicated that the silver catalyst not only induces the formation of the silver carbene, but also activates the diazahexatriene intermediate, which plays a crucial role in the formation of the C-N bond.
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BACKGROUND: Guipi decoction (GPD) not only improves gastrointestinal (GI) function, but also depressive mood. The bioinformatics study aimed to reveal potential crosstalk genes and related pathways between depression and GI disorders. A network pharmacology approach was used to explore the molecular mechanisms and potential targets of GPD for the simultaneous treatment of depression comorbid GI disorders. METHODS: Differentially expressed genes (DEGs) of major depressive disorder (MDD) were identified based on GSE98793 and GSE19738, and GI disorders-related genes were screened from the GeneCards database. Overlapping genes between MDD and GI disorders were obtained to identify potential crosstalk genes. Protein-protein interaction (PPI) network was constructed to screen for hub genes, signature genes were identified by LASSO regression analysis, and single sample gene set enrichment analysis (ssGSEA) was performed to analyze immune cell infiltration. In addition, based on the Traditional Chinese Medicine Systems Pharmacology (TCMSP) database, we screened the active ingredients and targets of GPD and identified the intersection targets of GPD with MDD and GI disorder-related genes, respectively. A "component-target" network was constructed using Cytoscape, the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed. RESULTS: The MDD-corrected dataset contained 2619 DEGs, and a total of 109 crosstalk genes were obtained. 14 hub genes were screened, namely SOX2, CRP, ACE, LEP, SHH, CDH2, CD34, TNF, EGF, BDNF, FN1, IL10, PPARG, and KIT. These genes were identified by LASSO regression analysis for 3 signature genes, including TNF, EGF, and IL10. Gamma.delta.T.cell was significantly positively correlated with all three signature genes, while Central.memory.CD4.T.cell and Central.memory.CD8.T.cell were significantly negatively correlated with EGF and TNF. GPD contained 134 active ingredients and 248 targets, with 41 and 87 relevant targets for the treatment of depression and GI disorders, respectively. EGF, PPARG, IL10 and CRP overlap with the hub genes of the disease. CONCLUSION: We found that GPD may regulate inflammatory and oxidative stress responses through EGF, PPARG, IL10 and CRP targets, and then be involved in the treatment of both depression and GI disorders.
Subject(s)
Depressive Disorder, Major , Drugs, Chinese Herbal , Gastrointestinal Diseases , Humans , Network Pharmacology , Depression/drug therapy , Depression/genetics , Epidermal Growth Factor , Interleukin-10 , PPAR gamma , Comorbidity , Computational BiologyABSTRACT
Ischemic stroke (IS) remains one of the leading causes of death and disability in humans. Unfortunately, none of the treatments effectively provide functional benefits to patients with IS, although many do so by targeting different aspects of the ischemic cascade response. The advantages of traditional Chinese medicine (TCM) in preventing and treating IS are obvious in terms of early treatment and global coordination. The efficacy of TCM and its bioactive constituents has been scientifically proven over the past decades. Based on clinical trials, this article provides a review of commonly used TCM patent medicines and herbal decoctions indicated for IS. In addition, this paper also reviews the mechanisms of bioactive constituents in TCM for the treatment of IS in recent years, both domestically and internationally. A comprehensive review of preclinical and clinical studies will hopefully provide new ideas to address the threat of IS.
Subject(s)
Drugs, Chinese Herbal , Ischemic Stroke , Humans , Medicine, Chinese Traditional , Drugs, Chinese Herbal/pharmacology , Drugs, Chinese Herbal/therapeutic use , Ischemic Stroke/drug therapyABSTRACT
Chlorinated polyfluorooctane ether sulfonate (6:2 Cl-PFESA), hydrogenated polyfluorooctane ether sulfonate (6:2 H-PFESA), and chlorinated polyfluorooctanesulfonate (Cl-PFOS) share structural similarities with the regulated perfluorooctanesulfonate (PFOS), but their toxic potential is rarely known. Here, the thyroid disrupting potential of these four compounds in zebrafish larvae has been comparably investigated. PFOS, Cl-PFOS, and 6:2 Cl-PFESA were accumulated in the larvae at similar levels, approximately 1.3-1.6 times higher than 6:2 H-PFESA. Additionally, PFOS, Cl-PFOS, and 6:2 Cl-PFESA exhibited stronger disruption than 6:2 H-PFESA on genetic regulation, particularly concerning thyroid hormone (TH) activation and action and on TH homeostasis in both free and total forms of thyroxine (T4) and 3,5,3'-triiodothyronine (T3). These results indicate that chlorination or oxygen insertion does not substantially alter the thyrotoxicity of PFOS, but hydrogenation mitigates it. Molecular docking analysis and the luciferase reporter gene assay provided mechanistic perspectives that the PFOS-like substances could competitively replace THs to bind with TH plasma and membrane transporters, thereby disrupting TH transport and action, respectively. Moreover, they are also potent to disrupt TH synthesis and activation through Na+/K+-dependent transport of I- or competitive binding to the sites of deiodinases.
Subject(s)
Alkanesulfonic Acids , Fluorocarbons , Animals , Zebrafish , Thyroid Gland , Larva , Molecular Docking Simulation , Alkanesulfonic Acids/toxicity , Alkanesulfonic Acids/chemistry , Ethers , Fluorocarbons/toxicityABSTRACT
BACKGROUND AND AIM: Healthcare-associated infections (HAIs) after pancreaticoduodenectomy (PD) are one of the common postoperative complications. This study aims to investigate the epidemiology of postoperative HAIs in patients with open pancreaticoduodenectomy (OPD) and robotic pancreaticoduodenectomy (RPD). METHODS: This retrospective cohort study described the trend of HAIs in patients undergoing PD from January 2013 to December 2022 at a tertiary hospital. Patients were divided into OPD and RPD, and the HAIs and outcomes were compared. RESULTS: Among 2632 patients who underwent PD, 230 (8.7%, 95% confidence interval [CI] 7.7-9.9%) were diagnosed with HAIs, with a decreasing trend from 2013 to 2022 (P < 0.001 for trend). The incidence of postoperative HAIs was significantly higher in patients with OPD than RPD (9.6% vs 5.8%; P = 0.003). The incidence of HAIs for patients with OPD showed a decreasing trend (P = 0.001 for trend), and the trend for RPD was not significant (P = 0.554 for trend). Logistic regression showed that RPD was significantly associated with postoperative HAIs after adjusting for covariates (adjusted odds ratio = 0.654; 95% CI 0.443-0.965; P = 0.032), especially in the subgroup of patients without preoperative biliary drainage (adjusted odds ratio = 0.486; 95% CI 0.292-0.809; P = 0.006). Regarding clinical outcomes, RPD has a shorter length of stay and a more expensive charge than OPD (all P < 0.05). CONCLUSION: Postoperative HAIs in patients with PD showed a decreasing trend in recent years, especially in OPD. RPD was significantly associated with reduced postoperative HAIs and length of stay, although the charge is more expensive. Attention should be paid to postoperative HAIs in OPD, and it is imperative to continue reducing the costs of RPD.
Subject(s)
Laparoscopy , Pancreatic Neoplasms , Robotic Surgical Procedures , Humans , Retrospective Studies , Pancreaticoduodenectomy/adverse effects , Robotic Surgical Procedures/adverse effects , Pancreatic Neoplasms/surgery , Length of Stay , Postoperative Complications/etiology , Delivery of Health CareABSTRACT
The hepatotoxicities of perfluoroalkyl and polyfluoroalkyl substances (PFASs) have been extensively investigated, while little is known about the sex-specific differences. In this study, common carp were exposed to the emerging perfluoroalkyl phosphinic acids (6:6 and 8:8 PFPiAs) for 14 days to disclose sex-specific hepatotoxicity. Apparent hepatotoxicity, including cell necrosis, apoptosis, and steatosis, was observed in both male and female carp liver. The observed hepatocyte steatosis was predominantly attributed to the dysregulation of hepatic lipid metabolism but was based on sex-specific mechanisms. It was manifested as inhibited oxidative decomposition of fatty acids (FAs) in the female liver, whereas it enhanced the uptake of FAs into the male liver, both of which led to excessive lipid accumulation. Untargeted lipidomics validated that the metabolism pathways of FA, sphingolipid, glycerolipid, and glycerophospholipid were disrupted by both compounds, leading to the generation of reactive oxygen species and oxidative stress. The oxidative stress further evolved into inflammation, manifested as promoted expression of proinflammatory cytokines and repressed expression of anti-inflammatory cytokines. Consistently, all of the changes were more noticeable in male carp, suggesting that male fish were more susceptible to PFPiA disruption. 8:8 PFPiA was less accumulated but caused stronger hepatotoxicity than 6:6 PFPiA, possibly because of the stronger binding capacity of 8:8 PFPiA to nuclear transcription factors mediating lipid metabolism and inflammation. The findings of this study highlight the significance of sex- and chemical-dependent bioaccumulation and the toxicity of PFASs in organisms.