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Objective: This study reviews the development of rhubarb processing and the current status of pharmacological research. We summarized the effects of different processing methods on the active compounds, pharmacological effects, and toxicity of rhubarb, as well as the clinical application of different concoctions, providing reference for further pharmacological research and clinical application of rhubarb. Methods: A comprehensive literature review was conducted using databases such as Pubmed, Embase, National Science and Technology Library, Web of science, CNKI, China Science and Technology Journal Database, SinoMed, and the Pharmacopoeia of the People's Republic of China. Search terms included "rhubarb", "raw rhubarb", "wine rhubarb", "cooked rhubarb", "rhubarb charcoal", "herbal processing", "compounds", "pharmacological effects", "inflammation", "gastrointestinal bleeding", and "tumor". Results: Historical records of rhubarb processing date back to the Han Dynasty, with continual innovations. Currently, the types of rhubarb used in traditional Chinese medicine have stabilized to three species: Rheum palmatum L., Rheum tanguticum Maxim.ex Balf. and Rheum officinale Baill. Common concoctions include raw rhubarb, wine rhubarb, cooked rhubarb and rhubarb charcoal. The active compounds of rhubarb are known to defecation, exhibit antibacterial and anti-inflammatory properties, regulate coagulation, protect the digestive system, and possess anti-tumor activities. Guided by Chinese medicine theory, the use of different rhubarb concoctions can enhance specific effects such as purgation to eliminate accumulation, clearing heat and toxins, cooling blood to stop hemorrhages, activating blood circulation to remove blood stasis, and inducing dampness to descend jaundice, thereby effectively treating various diseases. The therapeutic impact of these concoctions on diseases reflects not only in the changes to the active compounds of rhubarb but also in the formulations of traditional Chinese medicine. Processing has also shown advantages in reducing toxicity. Conclusion: Different processing methods alter the active compounds of rhubarb, thereby enhancing its various pharmacological effects and meeting the therapeutic needs of diverse diseases. Selecting an appropriate processing method based on the patient's specific conditions can maximize its pharmacological properties and improve clinical outcomes.
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Importance: The acute kidney injury (AKI) electronic alert (e-alert) system was hypothesized to improve the outcomes of AKI. However, its association with different patient outcomes and clinical practice patterns remains systematically unexplored. Objective: To assess the association of AKI e-alerts with patient outcomes (mortality, AKI progression, dialysis, and kidney recovery) and clinical practice patterns. Data Sources: A search of Embase and PubMed on March 18, 2024, and a search of the Cochrane Library on March 20, 2024, to identify all relevant studies. There were no limitations on language or article types. Study Selection: Studies evaluating the specified outcomes in adult patients with AKI comparing AKI e-alerts with standard care or no e-alerts were included. Studies were excluded if they were duplicate cohorts, had insufficient outcome data, or had no control group. Data Extraction and Synthesis: Two investigators independently extracted data and assessed bias. The systematic review and meta-analysis followed the PRISMA guidelines. Random-effects model meta-analysis, with predefined subgroup analysis and trial sequential analyses, were conducted. Main Outcomes and Measures: Primary outcomes included mortality, AKI progression, dialysis, and kidney recovery. Secondary outcomes were nephrologist consultations, post-AKI exposure to nonsteroidal anti-inflammatory drugs (NSAID), post-AKI angiotensin-converting enzyme inhibitor and/or angiotensin receptor blocker (ACEI/ARB) prescription, hospital length of stay, costs, and AKI documentation. Results: Thirteen unique studies with 41â¯837 unique patients were included (mean age range, 60.5-79.0 years]; 29.3%-48.5% female). The risk ratios (RRs) for the AKI e-alerts group compared with standard care were 0.96 for mortality (95% CI, 0.89-1.03), 0.91 for AKI stage progression (95% CI, 0.84-0.99), 1.16 for dialysis (95% CI, 1.05-1.28), and 1.13 for kidney recovery (95% CI, 0.86-1.49). The AKI e-alerts group had RRs of 1.45 (95% CI, 1.04-2.02) for nephrologist consultation, 0.75 (95% CI, 0.59-0.95) for post-AKI NSAID exposure. The pooled RR for post-AKI ACEI/ARB exposure in the AKI e-alerts group compared with the control group was 0.91 (95% CI, 0.78-1.06) and 1.28 (95% CI, 1.04-1.58) for AKI documentation. Use of AKI e-alerts was not associated with lower hospital length of stay (mean difference, -0.09 [95% CI, -0.47 to 0.30] days) or lower cost (mean difference, US $655.26 [95% CI, -$656.98 to $1967.5]) but was associated with greater AKI documentation (RR, 1.28 [95% CI, 1.04-1.58]). Trial sequential analysis confirmed true-positive results of AKI e-alerts on increased nephrologist consultations and reduced post-AKI NSAID exposure and its lack of association with mortality. Conclusions and Relevance: In this systematic review and meta-analysis, AKI e-alerts were not associated with a lower risk for mortality but were associated with changes in clinical practices. They were associated with lower risk for AKI progression. Further research is needed to confirm these results and integrate early AKI markers or prediction models to improve outcomes.
Subject(s)
Acute Kidney Injury , Acute Kidney Injury/mortality , Acute Kidney Injury/therapy , Humans , Male , Female , Middle Aged , Medical Order Entry Systems , Aged , Disease Progression , Renal Dialysis/methodsABSTRACT
Intermittent hypoxia (IH) is an independent risk factor for metabolic dysfunction-associated fatty liver disease (MAFLD). Copper deficiency can disrupt redox homeostasis, iron, and lipid metabolism. Here, we investigated whether hepatic copper deficiency plays a role in IH-associated MAFLD and explored the underlying mechanism(s). Male C57BL/6 mice were fed a western-type diet with adequate copper (CuA) or marginally deficient copper (CuD) and were exposed separately to room air (RA) or IH. Hepatic histology, plasma biomarkers, copper-iron status, and oxidative stress were assessed. An in vitro HepG2 cell lipotoxicity model and proteomic analysis were used to elucidate the specific targets involved. We observed that there were no differences in hepatic phenotypes between CuA-fed and CuD-fed mice under RA. However, in IH exposure, CuD-fed mice showed more pronounced hepatic steatosis, liver injury, and oxidative stress than CuA-fed mice. IH induced copper accumulation in the brain and heart and exacerbated hepatic copper deficiency and secondary iron deposition. In vitro, CuD-treated cells with IH exposure showed elevated levels of lipid accumulation, oxidative stress, and ferroptosis susceptibility. Proteomic analysis identified 360 upregulated and 359 downregulated differentially expressed proteins between CuA and CuD groups under IH; these proteins were mainly enriched in citrate cycle, oxidative phosphorylation, fatty acid metabolism, the peroxisome proliferator-activated receptor (PPAR)α pathway, and ferroptosis. In IH exposure, CuD significantly upregulated the ferroptosis-promoting factor arachidonyl-CoA synthetase long chain family member (ACSL)4. ACSL4 knockdown markedly eliminated CuD-induced ferroptosis and lipid accumulation in IH exposure. In conculsion, IH can lead to reduced hepatic copper reserves and secondary iron deposition, thereby inducing ferroptosis and subsequent MAFLD progression. Insufficient dietary copper may worsen IH-associated MAFLD.
Subject(s)
Copper , Ferroptosis , Hypoxia , Mice, Inbred C57BL , Animals , Copper/metabolism , Copper/deficiency , Male , Mice , Hypoxia/metabolism , Humans , Hep G2 Cells , Liver/metabolism , Liver/pathology , Oxidative Stress , Lipid Metabolism , Fatty Liver/metabolism , Fatty Liver/pathology , Fatty Liver/etiology , Iron/metabolism , Coenzyme A Ligases/metabolism , Coenzyme A Ligases/genetics , PPAR alpha/metabolism , PPAR alpha/geneticsABSTRACT
BACKGROUND AND AIM: Primary liver cancer, particularly hepatocellular carcinoma (HCC), represents a substantial global health challenge. Although immune checkpoint inhibitors are effective in HCC treatment, several patients still experience disease progression. Interleukin-1 (IL-1) regulates immunity and inflammation. We investigate the role of IL-1 in HCC development and progression and determine the potential therapeutic impact of gemcitabine in treating HCC. METHODS: Hydrodynamics-based transfection, employing the sleeping beauty transposase system, delivered surrogate tumor antigens, NRAS (NRAS proto-oncogene, GTPase), ShP53, and SB100 to C57BL/6 mice. A basic HCC mouse model was established. Pathogen-free animals were tested for serum and hepatotoxicity. The HCC prognosis was monitored using alanine aminotransferase and aspartate aminotransferase levels. Liver histology immunohistochemistry and mouse splenocyte/intra-hepatic immune cell flow cytometry were conducted. IL-1ß levels in human and mouse serum were assessed. RESULTS: Interleukin-1ß levels were elevated in patients with HCC compared with those in non-HCC controls. Hepatic IL-1ß levels were higher in HCC mouse models than those in non-HCC mice, suggesting localized hepatic inflammation. IL-1 receptor type 1 (IL-1R1) knockout (IL-1R1-/-) mice exhibited less severe HCC progression than that in wild-type mice, despite the high intra-hepatic IL-1ß concentration. IL-1R1-/- mice exhibited increased hepatic levels of myeloid-derived suppressor cells and regulatory T cells, which may exacerbate HCC. Gemcitabine significantly reduced the HCC tumor burden, improved liver conditions, and increased survival rates in HCC mouse models. Gemcitabine reduced the hepatic levels of myeloid-derived suppressor cells and regulatory T cells, potentially alleviating immune suppression in the liver. CONCLUSIONS: Targeting IL-1 or combining gemcitabine with immunotherapy is a promising approach for treating advanced-stage HCC.
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Purpose: This study aimed to investigate the relationship between temporomandibular joint (TMJ) effusion and TMJ pain, as well as jaw function limitation in patients via two-dimensional (2D) and three-dimensional (3D) magnetic resonance imaging (MRI) evaluation. Patients and Methods: 121 patients diagnosed with temporomandibular disorder (TMD) were included. TMJ effusion was assessed qualitatively using MRI and quantified with 3D Slicer software, then graded accordingly. In addition, a visual analogue scale (VAS) was employed for pain reporting and an 8-item Jaw Functional Limitations Scale (JFLS-8) was utilized to evaluate jaw function limitation. Statistical analyses were performed appropriately for group comparisons and association determination. A probability of p<0.05 was considered statistically significant. Results: 2D qualitative and 3D quantitative strategies were in high agreement for TMJ effusion grades (κ = 0.766). No significant associations were found between joint effusion and TMJ pain, nor with disc displacement and JLFS-8 scores. Moreover, the binary logistic regression analysis showed significant association between sex and the presence of TMJ effusion, exhibiting an Odds Ratio of 5.168 for females (p = 0.008). Conclusion: 2D qualitative evaluation was as effective as 3D quantitative assessment for TMJ effusion diagnosis. No significant associations were found between TMJ effusion and TMJ pain, disc displacement or jaw function limitation. However, it was suggested that female patients suffering from TMD may be at a risk for TMJ effusion. Further prospective research is needed for validation.
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OBJECTIVES: To evaluate magnetic susceptibility artefacts produced by orthodontic wires on MRI and the influence of wire properties and MRI image sequences on the magnitude of the artefact. METHODS: Arch form orthodontic wires [four stainless steels (SS), one cobalt chromium (CC) alloy, 13 titanium (Ti) alloys] were embedded in a polyester phantom, and scanned using a 1.5-T superconducting magnet scanner with an eight-channel phased-array coil. All wires were scanned with T1-weighted spin echo (SE) and gradient echo (GRE) sequences according to the American Society for Testing and Materials (ASTM) F2119-07 standard. The phantom also scanned other eight sequences. Artefacts were measured using the ASTM F2119-07 definition and OsiriX software. Artefact volume was analysed according to metal composition, wire length, number of wires, wire thickness, and imaging sequence as factors. RESULTS: With SE/GRE, black/white artefacts volumes from all SS wires were significantly larger than those produced by CC and Ti wires (P < .01). With the GRE, the black artefacts volume was the highest with the SS wires. With the SE, the black artefacts volume was small, whereas white artefacts were noticeable. The cranio-caudal extent of the artefacts was significantly longer with SS wires (P < .01). Although a direct relationship of wire length, number of wires, and wire thickness with artefact volume was noted, these factors did not influence artefact extension in the cranio-caudal direction. CONCLUSIONS: Ferromagnetic/paramagnetic orthodontic wires create artefacts due to local alteration of magnetic field homogeneity. The SS-type wires produced the largest artefacts followed by CC and Ti.
Subject(s)
Artifacts , Magnetic Resonance Imaging , Orthodontic Wires , Phantoms, Imaging , Magnetic Resonance Imaging/methods , Titanium , Stainless Steel , Humans , Chromium Alloys/chemistry , Dental AlloysABSTRACT
INTRODUCTION: Extracorporeal membrane oxygenation (ECMO) is widely used; however, studies on the long-term outcomes of ECMO are scarce. We investigated the long-term clinical outcomes of acute kidney disease (AKD) in patients receiving ECMO. METHODS: Electronic data (2009-2018) were retrospectively collected from a multicenter database. Patients were divided into two groups (AKD and non-AKD) according to their AKD status 8-90 days after the initiation of ECMO. Inverse probability of treatment weighting was used to balance baseline covariates between the two groups. The primary outcomes were major adverse kidney events (MAKEs) and major adverse cardiovascular events (MACEs), and the secondary outcomes were all-cause readmission, sepsis-related readmission, infection-related readmission, and dementia. RESULTS: Totally, 395 patients were eligible for analysis; of them, 160 patients (40.5%) developed AKD. The AKD group had a higher risk of MAKEs (hazard ratio [HR]: 2.06; 95% confidence interval [CI]: 1.68-2.53) than did the non-AKD group. Subgroup analysis revealed that the observed unfavorable effect of AKD on the risk of MAKEs was more pronounced in patients receiving venovenous ECMO than in those receiving venoarterial ECMO (HR: 5.69 vs. 1.85, respectively; p for interaction = 0.004). AKD group had a higher risk of MACE during the initial 3-year post-ECMO in comparison to those without (HR: 1.68; 95% CI: 1.22-2.30). Moreover, the risks of all-cause, sepsis-related, and infection-related readmissions were high in AKD survivors. CONCLUSIONS: AKD is associated with an increased risk of long-term MAKEs and initial 3-year MACE in ECMO recipients. In addition, AKD is associated with increased risks of all-cause, infection-related, and sepsis-related readmissions.
Subject(s)
Acute Kidney Injury , Extracorporeal Membrane Oxygenation , Humans , Extracorporeal Membrane Oxygenation/adverse effects , Extracorporeal Membrane Oxygenation/methods , Male , Female , Middle Aged , Acute Kidney Injury/therapy , Acute Kidney Injury/etiology , Retrospective Studies , Patient Readmission/statistics & numerical data , Aged , Adult , Sepsis/complications , Sepsis/etiology , Time Factors , Treatment OutcomeABSTRACT
Chronic pelvic pain caused by the sequelae of inflammatory pelvic disease is a common clinical condition of pelvic pain in women. At present, the main challenges in its treatment are the limited effectiveness of pain relief and the frequent recurrence of symptoms, which significantly impact patients' quality of life and impose a considerable psychological burden on them. It is a clinically challenging disease. After summarizing years of treatment experience, the author's team discovered that acupoint catgut embedding demonstrated notable clinical efficacy in managing chronic pelvic pain stemming from pelvic inflammatory disease sequelae. Compared to existing Western medicine treatment methods, acupoint catgut embedding offers advantages such as a good analgesic effect, lower recurrence rate, economic benefits, and a relatively straightforward procedure. This article provides a comprehensive guide on embedding absorbable catgut into patients' acupoints for the treatment of chronic pelvic pain in females resulting from the sequelae of pelvic inflammatory disease.
Subject(s)
Acupuncture Points , Catgut , Chronic Pain , Pelvic Inflammatory Disease , Pelvic Pain , Humans , Pelvic Pain/therapy , Pelvic Pain/etiology , Female , Chronic Pain/therapy , Chronic Pain/etiology , Pelvic Inflammatory Disease/complications , Pelvic Inflammatory Disease/therapy , Acupuncture Therapy/methodsABSTRACT
OBJECTIVES: To compare the efficacy of nadroparin and fondaparinux sodium for prevention of deep vein thromboembolism (DVT) in lower extremities after total hip arthroplasty (THA) and total knee arthroplasty (TKA). METHODS: A total of 592 patients were enrolled in the study. Clinical data of patients who underwent total hip arthroplasty (THA) and total knee arthroplasty (TKA) in our hospital from December 2021 to September 2022 were retrospectively collected, which mainly included patients' general information, surgery-related information, and DVT-related information. The patients were categorized into the nadroparin group(n = 278) and the fondaparinux sodium group(n = 314) according to the types of anticoagulants used. Anticoagulant therapy began 12-24 h after operation and continued until discharge. DVT prevalence between two groups was compared. The Statistical Package for Social Sciences (SPSS) software version 25 (SPSS, Armonk, NY, USA) was used for statistical analysis. RESULTS: The prevalence of DVT in the nadroparin group and the fondaparinux sodium group was 8.3% (23/278) and 15.0% (47/314), respectively(p = 0.012). Statistical analysis showed that nadroparin group showed a lower prevalence of thrombosis than fondaparinux group (OR = 1.952, P = 0.012). Subgroup analyses showed that nadroparin group had a lower prevalence of DVT than fondaparinux group in some special patients groups such as female patients (OR = 2.258, P = 0.007), patients who are 65-79 years old (OR = 2.796, P = 0.004), patients with hypertension (OR = 2.237, P = 0.042), patients who underwent TKA (OR = 2.091, P = 0.011), and patients who underwent combined spinal-epidural anesthesia (OR = 2.490, P = 0.003) (P < 0.05). CONCLUSION: Nadroparin may have an advantage over fondaparinux sodium in preventing DVT in lower extremities after THA and TKA.
Subject(s)
Anticoagulants , Arthroplasty, Replacement, Hip , Arthroplasty, Replacement, Knee , Fondaparinux , Nadroparin , Postoperative Complications , Venous Thromboembolism , Humans , Fondaparinux/therapeutic use , Female , Male , Retrospective Studies , Arthroplasty, Replacement, Hip/adverse effects , Arthroplasty, Replacement, Knee/adverse effects , Nadroparin/therapeutic use , Nadroparin/administration & dosage , Middle Aged , Venous Thromboembolism/prevention & control , Venous Thromboembolism/etiology , Venous Thromboembolism/epidemiology , Aged , Anticoagulants/therapeutic use , Anticoagulants/administration & dosage , Postoperative Complications/prevention & control , Postoperative Complications/epidemiology , Postoperative Complications/etiology , Lower Extremity/blood supply , Lower Extremity/surgery , Treatment OutcomeABSTRACT
Antibiotic pollution and biological invasion pose significant risks to freshwater biodiversity and ecosystem health. However, few studies have compared the ecological adaptability and ciprofloxacin (CIPR) degradation potential between alien and native macrophytes. We examined growth, physiological response, and CIPR accumulation, translocation and metabolic abilities of two alien plants (Eichhornia crassipes and Myriophyllum aquaticum) and one native submerged species (Vallisneria natans) exposed to CIPR at 0, 1 and 10 mg/L. We found that E. crassipes and M. aquaticum's growth were unaffected by CIPR while V. natans was significantly hindered under the 10 mg/L treatment. CIPR significantly decreased the maximal quantum yield of PSII, actual quantum yield of PSII and relative electron transfer rate in E. crassipes and V. natans but didn't impact these photosynthetic characteristics in M. aquaticum. All the plants can accumulate, translocate and metabolize CIPR. M. aquaticum and E. crassipes in the 10 mg/L treatment group showed greater CIPR accumulation potential than V. natans indicated by higher CIPR contents in their roots. The oxidative cleavage of the piperazine ring acts as a key pathway for these aquatic plants to metabolize CIPR and the metabolites mainly distributed in plant roots. M. aquaticum and E. crassipes showed a higher production of CIPR metabolites compared to V. natans, with M. aquaticum exhibiting the strongest CIPR metabolic ability, as indicated by the most extensive structural breakdown of CIPR and the largest number of potential metabolic pathways. Taken together, alien species outperformed the native species in ecological adaptability, CIPR accumulation and metabolic capacity. These findings may shed light on the successful invasion mechanisms of alien aquatic species under antibiotic pressure and highlight the potential ecological impacts of alien species, particularly M. aquaticum. Additionally, the interaction of antibiotic contamination and invasion might further challenge the native submerged macrophytes and pose greater risks to freshwater ecosystems.
Subject(s)
Ciprofloxacin , Water Pollutants, Chemical , Water Pollutants, Chemical/toxicity , Water Pollutants, Chemical/metabolism , Introduced Species , Eichhornia/metabolism , Eichhornia/physiology , Anti-Bacterial Agents/toxicity , Hydrocharitaceae/physiology , Hydrocharitaceae/metabolism , Biodegradation, EnvironmentalABSTRACT
The delineation of biomarkers and neuropsychiatric symptoms across normal cognition, mild cognitive impairment (MCI), and dementia stages holds significant promise for early diagnosis and intervention strategies. This research investigates the association of neuropsychiatric symptoms, evaluated via the Neuropsychiatric Inventory (NPI), with cerebrospinal fluid (CSF) biomarkers (Amyloid-ß42, P-tau, T-tau) across a spectrum of cognitive states to enhance diagnostic accuracy and treatment approaches. Drawing from the National Alzheimer's Coordinating Center's Uniform Data Set Version 3, comprising 977 individuals with normal cognition, 270 with MCI, and 649 with dementia. To assess neuropsychiatric symptoms, we employed the NPI to understand the behavioral and psychological symptoms associated with each cognitive category. For the analysis of CSF biomarkers, we measured levels of Amyloid-ß42, P-tau, and T-tau using the enzyme-linked immunosorbent assay (ELISA) and Luminex multiplex xMAP assay protocols. These biomarkers are critical in understanding the pathophysiological underpinnings of Alzheimer's disease and its progression, with specific patterns indicative of disease stage and severity. This study cohort consists of 1896 participants, which is composed of 977 individuals with normal cognition, 270 with MCI, and 649 with dementia. Dementia is characterized by significantly higher NPI scores, which are largely reflective of mood-related symptoms (p < 0.001). In terms of biomarkers, normal cognition shows median Amyloid-ß at 656.0 pg/mL, MCI at 300.6 pg/mL, and dementia at 298.8 pg/mL (p < 0.001). Median P-tau levels are 36.00 pg/mL in normal cognition, 49.12 pg/mL in MCI, and 58.29 pg/mL in dementia (p < 0.001). Median T-tau levels are 241.0 pg/mL in normal cognition, 140.6 pg/mL in MCI, and 298.3 pg/mL in dementia (p < 0.001). Furthermore, the T-tau/Aß-42 ratio increases progressively from 0.058 in the normal cognition group to 0.144 in the MCI group, and to 0.209 in the dementia group (p < 0.001). Similarly, the P-tau/Aß-42 ratio also escalates from 0.305 in individuals with normal cognition to 0.560 in MCI, and to 0.941 in dementia (p < 0.001). The notable disparities in NPI and CSF biomarkers among normal, MCI and Alzheimer's patients underscore their diagnostic potential. Their combined assessment could greatly improve early detection and precise diagnosis of MCI and dementia, facilitating more effective and timely treatment strategies.
Subject(s)
Alzheimer Disease , Cognitive Dysfunction , Humans , Alzheimer Disease/diagnosis , Cognitive Dysfunction/diagnosis , Affect , Amyloidogenic Proteins , Biomarkers , CognitionABSTRACT
Acute kidney injury is a common and complex complication that has high morality and the risk for chronic kidney disease among survivors. The accuracy of current AKI biomarkers can be affected by water retention and diuretics. Therefore, we aimed to identify a urinary non-recovery marker of acute kidney injury in patients with acute decompensated heart failure. We used the isobaric tag for relative and absolute quantification technology to find a relevant marker protein that could divide patients into control, acute kidney injury with recovery, and acute kidney injury without recovery groups. An enzyme-linked immunosorbent assay of the endothelial cell protein C receptor (EPCR) was used to verify the results. We found that the EPCR was a usable marker for non-recovery renal failure in our setting with the area under the receiver operating characteristics 0.776 ± 0.065; 95%CI: 0.648-0.905, (p < 0.001). Further validation is needed to explore this possibility in different situations.
Subject(s)
Acute Kidney Injury , Blood Coagulation Factors , Heart Failure , Receptors, Cell Surface , Humans , Endothelial Protein C Receptor , Proteomics , Prognosis , Kidney , Acute Kidney Injury/etiology , Heart Failure/complications , BiomarkersABSTRACT
Arsenite-induced stress granule (SG) formation can be cleared by the ubiquitin-proteasome system aided by the ATP-dependent unfoldase p97. ZFAND1 participates in this pathway by recruiting p97 to trigger SG clearance. ZFAND1 contains two An1-type zinc finger domains (ZF1 and ZF2), followed by a ubiquitin-like domain (UBL); but their structures are not experimentally determined. To shed light on the structural basis of the ZFAND1-p97 interaction, we determined the atomic structures of the individual domains of ZFAND1 by solution-state NMR spectroscopy and X-ray crystallography. We further characterized the interaction between ZFAND1 and p97 by methyl NMR spectroscopy and cryo-EM. 15N spin relaxation dynamics analysis indicated independent domain motions for ZF1, ZF2, and UBL. The crystal structure and NMR structure of UBL showed a conserved ß-grasp fold homologous to ubiquitin and other UBLs. Nevertheless, the UBL of ZFAND1 contains an additional N-terminal helix that adopts different conformations in the crystalline and solution states. ZFAND1 uses the C-terminal UBL to bind to p97, evidenced by the pronounced line-broadening of the UBL domain during the p97 titration monitored by methyl NMR spectroscopy. ZFAND1 binding induces pronounced conformational heterogeneity in the N-terminal domain of p97, leading to a partial loss of the cryo-EM density of the N-terminal domain of p97. In conclusion, this work paved the way for a better understanding of the interplay between p97 and ZFAND1 in the context of SG clearance.
Subject(s)
Intracellular Signaling Peptides and Proteins , Models, Molecular , Stress Granules , Valosin Containing Protein , Humans , Arsenites/metabolism , Arsenites/chemistry , Crystallography, X-Ray , Protein Binding , Protein Domains , Stress Granules/metabolism , Ubiquitin/metabolism , Valosin Containing Protein/metabolism , Valosin Containing Protein/chemistry , Valosin Containing Protein/genetics , Zinc Fingers , Protein Folding , Magnetic Resonance Imaging , Intracellular Signaling Peptides and Proteins/chemistry , Intracellular Signaling Peptides and Proteins/genetics , Intracellular Signaling Peptides and Proteins/metabolismABSTRACT
OBJECTIVE: The objective of the study was to investigate the relationship between types of disc displacement (DD) diagnosed by magnetic resonance imaging (MRI), and the risk (presence or absence) and severity of condylar erosion (CE) graded using cone-beam computed tomography (CBCT) in adult Temporomandibular disorders (TMD) patients. METHODS: A total of 353 TMD patients (283 females, 70 males) underwent MRI scans to categorise DD as normal (NA), anterior displacement with reduction (ADDR), or anterior displacement without reduction (ADDNR). CE severity was graded on a scale of 0-3 (absence, mild, moderate or severe) using CBCT. To establish the plausibility and cut-off points for CE diagnosis, the severity of CE was then further divided into three classifications: Grade 0 versus 1 + 2 + 3; Grades 0 + 1 versus 2 + 3; Grades 0 + 1 + 2 versus 3. Logistic regression analysis was performed, adjusting for age, gender and joint correlation. RESULTS: ADDNR significantly increased the risk of CE compared with NA (OR = 10.04, 95% CI: [6.41, 15.73]) and showed a significant increase in CE severity across all classifications (ORs = 10.04-18.95). The effects of ADDNR were significant in both genders (p < .001) and had a greater impact in females. ADDR was predominantly associated with mild CE. CONCLUSIONS: ADDNR significantly increased the risk and severity of CE independent of gender when compared to NA, whereas ADDR was mainly associated with mild CE. Slight cortical discontinuity may represent a subclinical diagnosis requiring further investigation.
Subject(s)
Cone-Beam Computed Tomography , Joint Dislocations , Magnetic Resonance Imaging , Mandibular Condyle , Temporomandibular Joint Disc , Temporomandibular Joint Disorders , Humans , Female , Male , Temporomandibular Joint Disorders/diagnostic imaging , Temporomandibular Joint Disorders/physiopathology , Temporomandibular Joint Disorders/pathology , Adult , Joint Dislocations/diagnostic imaging , Joint Dislocations/pathology , Temporomandibular Joint Disc/diagnostic imaging , Temporomandibular Joint Disc/pathology , Mandibular Condyle/diagnostic imaging , Mandibular Condyle/pathology , Middle Aged , Severity of Illness Index , Young Adult , Risk FactorsABSTRACT
BACKGROUND: At present, most articles mainly focused on the diagnosis of thyroid nodules by using artificial intelligence (AI), and there was little research on the detection performance of AI in thyroid nodules. OBJECTIVE: To explore the value of a real-time AI based on computer-aided diagnosis system in the detection of thyroid nodules and to analyze the factors influencing the detection accuracy. METHODS: From June 1, 2022 to December 31, 2023, 224 consecutive patients with 587 thyroid nodules were prospective collected. Based on the detection results determined by two experienced radiologists (both with more than 15 years experience in thyroid diagnosis), the detection ability of thyroid nodules of radiologists with different experience levels (junior radiologist with 1 year experience and senior radiologist with 5 years experience in thyroid diagnosis) and real-time AI were compared. According to the logistic regression analysis, the factors influencing the real-time AI detection of thyroid nodules were analyzed. RESULTS: The detection rate of thyroid nodules by real-time AI was significantly higher than that of junior radiologist (Pâ=â0.013), but lower than that of senior radiologist (Pâ=â0.001). Multivariate logistic regression analysis showed that nodules size, superior pole, outside (near carotid artery), close to vessel, echogenicity (isoechoic, hyperechoic, mixed-echoic), morphology (not very regular, irregular), margin (unclear), ACR TI-RADS category 4 and 5 were significant independent influencing factors (all Pâ<â0.05). With the combination of real-time AI and radiologists, junior and senior radiologist increased the detection rate to 97.4% (Pâ<â0.001) and 99.1% (Pâ=â0.015) respectively. CONCLUSONS: The real-time AI has good performance in thyroid nodule detection and can be a good auxiliary tool in the clinical work of radiologists.
Subject(s)
Artificial Intelligence , Thyroid Nodule , Humans , Thyroid Nodule/diagnostic imaging , Thyroid Nodule/diagnosis , Thyroid Nodule/pathology , Male , Female , Middle Aged , Adult , Prospective Studies , Aged , Diagnosis, Computer-Assisted/methodsABSTRACT
INTRODUCTION: Chronic kidney disease is related to neurodegeneration and structural changes in the brain which might lead to cognitive decline. The Fazekas scale used for assessing white matter hyperintensities (WMHs) was associated with poor cognitive performance. Therefore, this study investigated the associations between the mini-mental status examination (MMSE), Montreal cognitive assessment (MoCA), cognitive abilities screening instrument (CASI), and Fazekas scale in patients under hemodialysis (HD). METHODS: The periventricular (PV) WMHs and deep WMHs (DWMHs) in brain magnetic resonance images of 59 patients under dialysis were graded using the Fazekas scale. Three cognition function tests were also performed, then multivariable ordinal regression and logistic regression were used to identify the associations between cognitive performance and the Fazekas scale. RESULTS: There were inverse associations between the three cognitive function tests across the Fazekas scale of PVWMHs (p = .037, .006, and .008 for MMSE, MoCA, and CASI, respectively), but the associations were attenuated in the DWMHs group. In CASI, significant differences were identified in short-term memory, mental manipulation, abstract thinking, language, spatial construction, and name fluency in the PVWMHs group. However, DWMHs were only significantly correlated with abstract thinking and short-term memory. CONCLUSION: An inverse correlation existed between the Fazekas scale, predominantly in PVWMHs, and cognition in patients undergoing HD. The PVWMHs were associated with cognitive performance assessed by MMSE, MoCA, and CASI, as well as with subdomains of CASI such as memory, language and name fluency in patients undergoing HD.
An inverse correlation existed between the Fazekas scale and cognition in patients undergoing hemodialysis, predominantly in periventricular white matter hyperintensities.The periventricular white matter hyperintensities were associated with cognitive performance assessed by mini-mental status examination (MMSE), Montreal cognitive assessment (MoCA), cognitive abilities screening instrument (CASI), as well as with subdomains of CASI such as memory, language and name fluency in patients undergoing HD.
Subject(s)
Cognitive Dysfunction , White Matter , Humans , White Matter/diagnostic imaging , White Matter/pathology , Cognition , Brain/diagnostic imaging , Cognitive Dysfunction/etiology , Cognitive Dysfunction/diagnosis , Magnetic Resonance Imaging , Renal Dialysis/adverse effectsABSTRACT
Introduction: Hypertriglyceridemia is the most prevalent dyslipidemia in patients with chronic kidney disease (CKD). However, research about fibrate treatment in CKD patients is limited, and assessing its benefits becomes challenging due to the frequent concurrent use of statins. Thus, this study is aimed to investigate the role of fibrate in CKD stage 3 patients with hypertriglyceridemia who did not receive other lipid-lowering agents. Methods: This study enrolled patients newly diagnosed CKD3 with LDL-C<100mg/dL and had never received statin or other lipid-lowering agents from Chang Gung Research Database. The participants were categorized into 2 groups based on the use of fibrate: fibrate group and non-fibrate group (triglyceride >200mg/dL but not receiving fibrate treatment). The inverse probability of treatment weighting was performed to balance baseline characteristics. Results: Compared with the non-fibrate group (n=2020), the fibrate group (n=705) exhibited significantly lower risks of major adverse cardiac and cerebrovascular events (MACCEs) (10.4% vs. 12.8%, hazard ratios [HRs]: 0.69, 95% confidence interval [CI]: 0.50 to 0.95), AMI (2.3% vs. 3.9%, HR: 0.52, 95% CI: 0.37 to 0.73), and ischemic stroke (6.3% vs. 8.0%, HR: 0.67, 95% CI: 0.52 to 0.85). The risk of all-cause mortality (5.1% vs. 4.5%, HR: 1.09, 95% CI: 0.67 to 1.79) and death from CV (2.8% vs. 2.3%, HR: 1.07, 95% CI: 0.29 to 2.33) did not significantly differ between the 2 groups. Conclusion: This study suggests that, in moderate CKD patients with hypertriglyceridemia but LDL-C < 100mg/dL who did not take other lipid-lowering agents, fibrates may be beneficial in reducing cardiovascular events.
Subject(s)
Cardiovascular Diseases , Hydroxymethylglutaryl-CoA Reductase Inhibitors , Hyperlipidemias , Hypertriglyceridemia , Renal Insufficiency, Chronic , Humans , Cardiovascular Diseases/etiology , Cardiovascular Diseases/chemically induced , Fibric Acids/therapeutic use , Cholesterol, LDL , Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use , Hypolipidemic Agents/therapeutic use , Hypertriglyceridemia/complications , Hypertriglyceridemia/drug therapy , Renal Insufficiency, Chronic/complications , Renal Insufficiency, Chronic/drug therapy , Renal Insufficiency, Chronic/chemically inducedABSTRACT
Corticotrophin-releasing hormone (CRH) neurons in the hypothalamic paraventricular nucleus (PVN) play a critical role in the modulation of the hypothalamic-pituitary-adrenal (HPA) axis. Early-life exposure to di-(2-ethylhexyl) phthalate (DEHP) has been associated with an increased risk of developing psychiatric disorders in adulthood. The present work was designed to explore the impact of neonatal exposure to DEHP on adult PVN CRH neuronal activity. DEHP or vehicle was given to male rat pups from PND16 to PND22. Then, anxiety-like behaviors, serum corticosterone and testosterone, immunohistochemistry, western blotting, fluorescence in situ hybridization and acute ex vivo slice electrophysiological recordings were used to evaluate the influence of DEHP on adult PVN secretory CRH neurons. Neonatal DEHP-exposed rats exhibited enhanced anxiety-like behaviors in adults, with an increase in CORT. Secretory CRH neurons showed higher spontaneous firing activity but could be inhibited by GABAAR blockers. CRH neurons displayed fewer firing spikes, prolonged first-spike latency, depolarizing shifts in GABA reversal potential and strengthened GABAergic inputs, as indicated by increases in the frequency and amplitude of sIPSCs. Enhancement of GABAergic transmission was accompanied by upregulated expression of GAD67 and downregulated expression of GABABR1, KCC2 and GAT1. These findings suggest that neonatal exposure to DEHP permanently altered the characteristics of secretory CRH neurons in the PVN, which may contribute to the development of psychiatric disorders later in life.
Subject(s)
Corticotropin-Releasing Hormone , Diethylhexyl Phthalate , Humans , Rats , Male , Animals , Corticotropin-Releasing Hormone/metabolism , In Situ Hybridization, Fluorescence , Diethylhexyl Phthalate/toxicity , Diethylhexyl Phthalate/metabolism , Hypothalamus , Paraventricular Hypothalamic Nucleus , Neurons/metabolism , gamma-Aminobutyric Acid/metabolism , CorticosteroneABSTRACT
PURPOSE: This study evaluated the value of contrast-enhanced ultrasonography (CEUS) in the ultrasound-guided microwave ablation (MWA) treatment of symptomatic focal uterine adenomyosis. METHODS: This retrospective study was conducted between March 2020 and January 2023, enrolling 52 patients with symptomatic focal uterine adenomyosis who had undergone MWA. All patients were examined with CEUS before and after MWA. The non-perfused volume (NPV) was compared between CEUS and dynamic contrast-enhanced magnetic resonance imaging (DCEMRI) following ablation. Therapeutic efficacy and safety were evaluated at 3-, 6-, and 12-month follow-ups. Additionally, this study explored the correlations between pre-treatment CEUS features and a volume reduction ratio indicating sufficient ablation, defined as 50% or more at the 3-month follow-up. RESULTS: No significant differences in NPV were noted between CEUS and DCE-MRI immediately after MWA and during follow-up (all P>0.05). At the 3-month follow-up, the median VRRs for the uterus and adenomyosis were 33.2% and 63.9%, respectively. Sufficient ablation was achieved in 69.2% (36/52) of adenomyosis cases, while partial ablation was observed in the remaining 30.8% (16/52). The identification of non-enhancing areas on pre-treatment CEUS was associated with sufficient ablation (P=0.016). At the 12-month follow-up, significant decreases were observed in both the uterine and adenomyosis volumes (all P<0.001). Dysmenorrhea and menorrhagia were significantly alleviated at 12 months, and no major complications were encountered. CONCLUSION: CEUS can be used to evaluate the ablation zone of focal adenomyosis that has been treated with MWA, similarly to DCE-MRI. The identification of non-enhancing areas on pretreatment CEUS indicates satisfactory treatment outcomes.