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2.
Chem Biol Drug Des ; 104(2): e14598, 2024 Aug.
Article in English | MEDLINE | ID: mdl-39090783

ABSTRACT

Acne caused by inflammation of hair follicles and sebaceous glands is a common chronic skin disease. Arctigenin (ATG) is an extract of Arctium lappa L., which has significant anti-inflammatory effects. However, the effect and mechanism of ATG in cutaneous inflammation mediated by Cutibacterium acnes (C. acnes) has not been fully evaluated. The purpose of this study was to explore the effect and potential mechanism of ATG in the treatment of acne through network pharmacology and experimental confirmation. An acne model was established by injected live C. acnes into living mice and treated with ATG. Our data showed that ATG effectively improved acne induced by live C. acnes, which was confirmed by determining ear swelling rate, estradiol concentration and hematoxylin and eosin (H&E) staining. In addition, ATG inhibited the NLRP3 inflammasome signaling pathway in mice ear tissues and reduced the secretion of pro-inflammatory cytokines IL-1ß to relieve inflammation. The results of network pharmacology and molecular docking confirmed that ATG can regulate 17ß-Estradiol (E2) levels through targeted to CYP19A1, and finally inhibited skin inflammation. Taken together, our results confirmed that ATG regulated E2 secretion by targeting CYP19A1, thereby inhibiting the NLRP3 inflammasome signaling pathway and improving inflammation levels in acne mice. This study provides a basis for the feasibility of ATG in treating acne in clinical practice.


Subject(s)
Acne Vulgaris , Aromatase , Furans , Lignans , Molecular Docking Simulation , Network Pharmacology , Animals , Furans/chemistry , Furans/pharmacology , Mice , Lignans/pharmacology , Lignans/chemistry , Lignans/therapeutic use , Acne Vulgaris/drug therapy , Acne Vulgaris/microbiology , Aromatase/metabolism , Aromatase/chemistry , Signal Transduction/drug effects , Skin/pathology , Skin/drug effects , Skin/metabolism , Inflammation/drug therapy , Inflammation/metabolism , NLR Family, Pyrin Domain-Containing 3 Protein/metabolism , NLR Family, Pyrin Domain-Containing 3 Protein/antagonists & inhibitors , Inflammasomes/metabolism , Humans , Anti-Inflammatory Agents/pharmacology , Anti-Inflammatory Agents/chemistry , Anti-Inflammatory Agents/therapeutic use , Propionibacterium acnes/drug effects , Interleukin-1beta/metabolism , Disease Models, Animal
3.
World J Gastroenterol ; 30(28): 3386-3392, 2024 Jul 28.
Article in English | MEDLINE | ID: mdl-39091716

ABSTRACT

Acute appendicitis is a common surgical emergency. It is commonly caused by obstruction of the appendiceal lumen due to fecaliths, tumors, or lymphoid hyperplasia. For over a century, appendectomy has been the primary treatment for acute appendicitis. Abraham Groves performed the first open appendectomy in 1883. In 1983, Kurt Semm completed the first laparoscopic appendectomy, heralding a new era in appendectomy. However, appendectomy is associated with certain complications and a rate of negative appendectomies. Studies have suggested controversy over the impact of appendectomy on the development of inflammatory bowel disease and Parkinson's disease, but an increasing number of studies indicate a possible positive correlation between appendectomy and colorectal cancer, gallstones, and cardiovascular disease. With the recognition that the appendix is not a vestigial organ and the advancement of endoscopic te-chnology, Liu proposed the endoscopic retrograde appendicitis therapy. It is an effective minimally invasive alternative for treating uncomplicated acute appendicitis. Our team has developed an appendoscope with a disposable digital imaging system operated through the biopsy channel of a colonoscope and successfully applied it in the treatment of appendicitis. This article provides an overview of the progress in endoscopic treatment for acute appendicitis and offers a new perspective on the future direction of appendiceal disease treatment.


Subject(s)
Appendectomy , Appendicitis , Humans , Appendicitis/surgery , Appendectomy/adverse effects , Appendectomy/methods , Appendectomy/history , Treatment Outcome , Appendix/surgery , Appendix/pathology , Appendix/diagnostic imaging , Colonoscopes , Acute Disease , Equipment Design
4.
Medicine (Baltimore) ; 103(31): e39128, 2024 Aug 02.
Article in English | MEDLINE | ID: mdl-39093759

ABSTRACT

RATIONALE: Turner syndrome is characterized by complete or partial loss of the second sex chromosome. In patients with Turner syndrome, hypertension is well described. However, the literature regarding malignant hypertension is scarce. Therefore, an accurate and timely diagnosis and treatment are important. PATIENT CONCERNS: A 13-year-old female with Turner syndrome presented to the emergency department with malignant hypertension, headache, spraying vomiting, convulsion, and loss of consciousness. Considering her medical history, symptoms, and auxiliary examination, secondary hypertension (primary reninism) was suspected, but without any occupying or hyperplasia in renal and adrenal. DIAGNOSIS: A type of secondary hypertension, primary reninism. INTERVENTIONS: The patient was immediately transferred to the pediatric intensive care unit. Subsequently, she was given nifedipine 0.35 mg/kg and captopril 0.35mg/kg to reduce blood pressure (BP), mannitol and furosemide to reduce cranial pressure, and phenobarbital and midazolam to terminate restlessness successively. Three hours later, the BP was consistently higher than 170/120 mm Hg, sodium nitroprusside was pumped intravenously, then, giving oral drug transition. Finally, she was given Valsartan-Amlodipine Tablets (I) (80 mg valsartan and 5 mg amlodipine per day) and bisoprolol (2.5 mg per day). OUTCOMES: For 2.5 years of follow-up, the BP reduced to 110-130/60-85 mm Hg, heart rate ranged between 65 and 80 bpm, and she could go to school without any headache, convulsion, and syncope. LESSONS: The clinical phenotype of Turner syndrome is complex and varied, affecting multiple systems and organs. Turner syndrome with malignant hypertension is rare, so we should systematically evaluate secondary hypertension, target-organ damage, and accompanied by standard management when Turner syndrome presents with hypertension.


Subject(s)
Hypertension, Malignant , Turner Syndrome , Humans , Female , Turner Syndrome/complications , Adolescent , Hypertension, Malignant/drug therapy , Hypertension, Malignant/complications , Antihypertensive Agents/therapeutic use , Antihypertensive Agents/administration & dosage
5.
Indian Heart J ; 2024 Aug 02.
Article in English | MEDLINE | ID: mdl-39096964

ABSTRACT

OBJECTIVE: The CABANA study shows that atrial fibrillation (AF) paitents younger than 65 years benefit more from the AF radiofrequency catheter ablation (RFCA) procedure. The aim of this study is to investigate the impact of inherent patent foramen ovale (PFO) with a Left-to-Right Shunt on the RFCA procedure in young AF patients. METHODS: Based on the presence or absence of inherent PFO, the AF patients were divided into the PFO groups and the non-PFO group. Clinical follow-up was also investigated. RESULTS: A total of 285 AF patients were enrolled. PFO was detected by TEE in 42 patients. The age of patients at initial AF onset was younger in the PFO group than in the non-PFO group (58.3 ± 8.9 vs. 62.3 ± 9.6 years, P = 0.012). There were more AF patients aged <55 years in the PFO group than in the non-PFO group. For the 9 AF patients with PFO who experienced AF recurrence and the left-to-right shunts decreased in size in 5 of the patients aged <65 years. The LAD decreased in those patients. In the PeAF patients, 53/64 patients aged <65 years and 23/40 patients aged older than 65 years were free of AF (82.8 % vs. 57.5 %, respectively; P = 0.005). CONCLUSION: Success is not affected when AF is combined PFO compared with AF without PFO. Young patients have better PeAF RFCA outcomes. AF in young patients with left atria enlargement and a serious AF burden, may lead to reduced EF and render PFO easy to detect.

6.
Am J Otolaryngol ; 45(6): 104471, 2024 Aug 14.
Article in English | MEDLINE | ID: mdl-39151379

ABSTRACT

OBJECTIVE: To compare the graft success rates and hearing outcomes of underlay myringoplasty with or without perichondrium tucking of the attached perichondrium, graft perforation margins when repairing chronic large central dry perforations. STUDY DESIGN: Randomized controlled trial. MATERIAL AND METHODS: Chronic large central dry perforations were prospectively randomized to tucking perichondrium graft underlay (TPGU) and no-tucking perichondrium graft underlay (NTPG) groups. The graft outcomes and complications were compared between the two groups at 12 months postoperatively. RESULTS: In total, 61 patients with large central dry perforations were included. All patients completed 12-month follow-ups. Residual perforations occurred in 0.0 % of the TPGU group and in 12.9 % of the NTPG group (P = 0.129), and re-perforations occurred within 6 months in 0.0 % and 3.2 % of the two groups, respectively (P = 0.987). The graft success rates were 100.0 % (30/30) and 83.9 % (26/31) (P = 0.067). No significant between-group differences were observed in terms of preoperative (P = 0.547) or postoperative (P = 0.612) air bone gaps (ABGs) or mean ABG gains (P = 0.597). No graft-related complications were observed in either group during follow-up. No patients exhibited significant graft blunting or medialization; graft lateralization was noted in one patient of the NTPG group. CONCLUSIONS: Endoscopic cartilage with tucking of the attached perichondrium perforation margins during underlay myringoplasty may improve the graft success rate compared to that of the cartilage push-through technique when repairing large central dry perforations; however, the hearing improvements were comparable in the two groups.

7.
ACS Nano ; 18(33): 21779-21803, 2024 Aug 20.
Article in English | MEDLINE | ID: mdl-39132720

ABSTRACT

Aqueous zinc-ion batteries (AZIBs) are widely regarded as desirable energy storage devices due to their inherent safety and low cost. Hydrogel polymer electrolytes (HPEs) are cross-linked polymers filled with water and zinc salts. They are not only widely used in flexible batteries but also represent an ideal electrolyte candidate for addressing the issues associated with the Zn anode, including dendrite formation and side reactions. In HPEs, an abundance of hydrophilic groups can form strong hydrogen bonds with water molecules, reducing water activity and inhibiting water decomposition. At the same time, special Zn2+ transport channels can be constructed in HPEs to homogenize the Zn2+ flux and promote uniform Zn deposition. However, HPEs still face issues in practical applications, including poor ionic conductivity, low mechanical strength, poor interface stability, and narrow electrochemical stability windows. This Review discusses the issues associated with HPEs for advanced AZIBs, and the recent progresses are summarized. Finally, the Review outlines the opportunities and challenges for achieving high performance HPEs, facilitating the utilization of HPEs in AZIBs.

8.
Adv Sci (Weinh) ; : e2400176, 2024 Aug 20.
Article in English | MEDLINE | ID: mdl-39162029

ABSTRACT

Tuberculosis (TB), the leading cause of death from bacterial infections worldwide, results from infection with Mycobacterium tuberculosis (Mtb). The antitubercular agents delamanid (DLM) and pretomanid (PMD) are nitroimidazole prodrugs that require activation by an enzyme intrinsic to Mtb; however, the mechanism(s) of action and the associated metabolic pathways are largely unclear. Profiling of the chemical-genetic interactions of PMD and DLM in Mtb using combined CRISPR screening reveals that the mutation of rv2073c increases susceptibility of Mtb to these nitroimidazole drugs both in vitro and in infected mice, whereas mutation of rv0078 increases drug resistance. Further assays show that Rv2073c might confer intrinsic resistance to DLM/PMD by interfering with inhibition of the drug target, decaprenylphophoryl-2-keto-b-D-erythro-pentose reductase (DprE2), by active nicotinamide adenine dinucleotide (NAD) adducts. Characterization of the metabolic pathways of DLM/PMD in Mtb using a combination of chemical genetics and comparative liquid chromatography-mass spectrometry (LC-MS) analysis of DLM/PMD metabolites reveals that Rv0077c, which is negatively regulated by Rv0078, mediates drug resistance by metabolizing activated DLM/PMD. These results might guide development of new nitroimidazole prodrugs and new regimens for TB treatment.

9.
Infect Dis Poverty ; 13(1): 59, 2024 Aug 16.
Article in English | MEDLINE | ID: mdl-39152514

ABSTRACT

BACKGROUND: The co-infection of human immunodeficiency virus (HIV)/acquired immune deficiency syndrome (AIDS) and tuberculosis (TB) poses a significant clinical challenge and is a major global public health issue. This study aims to elucidate the disease burden of HIV-TB co-infection in global, regions and countries, providing critical information for policy decisions to curb the HIV-TB epidemic. METHODS: The ecological time-series study used data from the Global Burden of Disease (GBD) Study 2021. The data encompass the numbers of incidence, prevalence, mortality, and disability-adjusted life year (DALY), as well as age-standardized incidence rate (ASIR), prevalence rate (ASPR), mortality rate (ASMR), and DALY rate for HIV-infected drug-susceptible tuberculosis (HIV-DS-TB), HIV-infected multidrug-resistant tuberculosis (HIV-MDR-TB), and HIV-infected extensively drug-resistant tuberculosis (HIV-XDR-TB) from 1990 to 2021. from 1990 to 2021. The estimated annual percentage change (EAPC) of rates, with 95% confidence intervals (CIs), was calculated. RESULTS: In 2021, the global ASIR for HIV-DS-TB was 11.59 per 100,000 population (95% UI: 0.37-13.05 per 100,000 population), 0.55 per 100,000 population (95% UI: 0.38-0.81 per 100,000 population), for HIV-MDR-TB, and 0.02 per 100,000 population (95% UI: 0.01-0.03 per 100,000 population) for HIV-XDR-TB. The EAPC for the ASIR of HIV-MDR-TB and HIV-XDR-TB from 1990 to 2021 were 4.71 (95% CI: 1.92-7.59) and 13.63 (95% CI: 9.44-18.01), respectively. The global ASMR for HIV-DS-TB was 2.22 per 100,000 population (95% UI: 1.73-2.74 per 100,000 population), 0.21 per 100,000 population (95% UI: 0.09-0.39 per 100,000 population) for HIV-MDR-TB, and 0.01 per 100,000 population (95% UI: 0.00-0.03 per 100,000 population) for HIV-XDR-TB in 2021. The EAPC for the ASMR of HIV-MDR-TB and HIV-XDR-TB from 1990 to 2021 were 4.78 (95% CI: 1.32-8.32) and 10.00 (95% CI: 6.09-14.05), respectively. CONCLUSIONS: The findings indicate that enhancing diagnostic and treatment strategies, strengthening healthcare infrastructure, increasing access to quality medical care, and improving public health education are essential to combat HIV-TB co-infection.


Subject(s)
Coinfection , Global Burden of Disease , HIV Infections , Tuberculosis , Humans , Coinfection/epidemiology , HIV Infections/epidemiology , HIV Infections/complications , Tuberculosis/epidemiology , Global Burden of Disease/trends , Incidence , Prevalence , Global Health/statistics & numerical data , Female , Male , Adult , Tuberculosis, Multidrug-Resistant/epidemiology
10.
Cell Rep ; 43(8): 114633, 2024 Aug 17.
Article in English | MEDLINE | ID: mdl-39154343

ABSTRACT

Pancreatic ductal adenocarcinoma (PDAC) features substantial matrix stiffening and reprogrammed glucose metabolism, particularly the Warburg effect. However, the complex interplay between these traits and their impact on tumor advancement remains inadequately explored. Here, we integrated clinical, cellular, and bioinformatics approaches to explore the connection between matrix stiffness and the Warburg effect in PDAC, identifying CLIC1 as a key mediator. Elevated CLIC1 expression, induced by matrix stiffness through Wnt/ß-catenin/TCF4 signaling, signifies poorer prognostic outcomes in PDAC. Functionally, CLIC1 serves as a catalyst for glycolytic metabolism, propelling tumor proliferation. Mechanistically, CLIC1 fortifies HIF1α stability by curbing hydroxylation via reactive oxygen species (ROS). Collectively, PDAC cells elevate CLIC1 levels in a matrix-stiffness-responsive manner, bolstering the Warburg effect to drive tumor growth via ROS/HIF1α signaling. Our insights highlight opportunities for targeted therapies that concurrently address matrix properties and metabolic rewiring, with CLIC1 emerging as a promising intervention point.

11.
BMC Med Inform Decis Mak ; 24(1): 225, 2024 Aug 08.
Article in English | MEDLINE | ID: mdl-39118118

ABSTRACT

BACKGROUND: Despite improvement in treatment strategies for atrial fibrillation (AF), a significant proportion of patients still experience recurrence after ablation. This study aims to propose a novel algorithm based on Transformer using surface electrocardiogram (ECG) signals and clinical features can predict AF recurrence. METHODS: Between October 2018 to December 2021, patients who underwent index radiofrequency ablation for AF with at least one standard 10-second surface ECG during sinus rhythm were enrolled. An end-to-end deep learning framework based on Transformer and a fusion module was used to predict AF recurrence using ECG and clinical features. Model performance was evaluated using areas under the receiver operating characteristic curve (AUROC), sensitivity, specificity, accuracy and F1-score. RESULTS: A total of 920 patients (median age 61 [IQR 14] years, 66.3% male) were included. After a median follow-up of 24 months, 253 patients (27.5%) experienced AF recurrence. A single deep learning enabled ECG signals identified AF recurrence with an AUROC of 0.769, sensitivity of 75.5%, specificity of 61.1%, F1 score of 55.6% and overall accuracy of 65.2%. Combining ECG signals and clinical features increased the AUROC to 0.899, sensitivity to 81.1%, specificity to 81.7%, F1 score to 71.7%, and overall accuracy to 81.5%. CONCLUSIONS: The Transformer algorithm demonstrated excellent performance in predicting AF recurrence. Integrating ECG and clinical features enhanced the models' performance and may help identify patients at low risk for AF recurrence after index ablation.


Subject(s)
Atrial Fibrillation , Catheter Ablation , Deep Learning , Electrocardiography , Recurrence , Humans , Atrial Fibrillation/surgery , Male , Female , Middle Aged , Aged
12.
Ann Surg Oncol ; 2024 Aug 08.
Article in English | MEDLINE | ID: mdl-39117927

ABSTRACT

BACKGROUND: Intrahepatic cholangiocarcinoma (ICCA) with hepatic hilus involvement is a more aggressive type of cholangiocarcinoma with worse outcomes.1,2 Surgical resection with negative margins is the only effective treatment for ICCA.3,4 Neoadjuvant therapy is considered to improve the possibility of surgery for patients;5,6 however, laparoscopic radical resection after neoadjuvant therapy for ICCA with hepatic hilus involvement remains at the exploratory stage due to technical challenges.7 METHODS: A 19-year-old man presented with an ICCA on the left side of the liver invading the blood vessels and bile ducts in the hepatic hilum. Five courses of neoadjuvant therapy were administered after a multidisciplinary team determined that the tumor was extremely difficult and risky to operate on. A laparoscopic left hepatectomy plus caudal lobectomy was performed to complete the resection of the negative margins. Three-dimensional visualization enabled precise preoperative planning and intraoperative guidance, including visualization of the tumor location, simulation of bile duct and vessel dissection steps, as well as determining the extent of liver resection. Vascular skeletonization, lymphadenectomy and biliary reconstruction were performed during operation. RESULTS: The operation time was 415 min with a blood loss of 100 mL. Postoperative pathohistology confirmed cholangiocarcinoma with low to intermediate differentiation. The resection margin was negative (R0) and lymph node pathology was tumor-negative (0/10). The patient was discharged on postoperative day 10 without complications. CONCLUSION: Laparoscopic radical resection after neoadjuvant therapy for ICCA with hepatic hilus involvement is safe and feasible in a large-throughput hepatic surgery center.

13.
Adv Sci (Weinh) ; : e2400354, 2024 Aug 09.
Article in English | MEDLINE | ID: mdl-39120568

ABSTRACT

The mechanisms of anxiety disorders, the most common mental illness, remain incompletely characterized. The ventral hippocampus (vHPC) is critical for the expression of anxiety. However, current studies primarily focus on vHPC neurons, leaving the role for vHPC astrocytes in anxiety largely unexplored. Here, genetically encoded Ca2+ indicator GCaMP6m and in vivo fiber photometry calcium imaging are used to label vHPC astrocytes and monitor their activity, respectively, genetic and chemogenetic approaches to inhibit and activate vHPC astrocytes, respectively, patch-clamp recordings to measure glutamate currents, and behavioral assays to assess anxiety-like behaviors. It is found that vHPC astrocytic activity is increased in anxiogenic environments and by 3-d subacute restraint stress (SRS), a well-validated mouse model of anxiety disorders. Genetic inhibition of vHPC astrocytes exerts anxiolytic effects on both innate and SRS-induced anxiety-related behaviors, whereas hM3Dq-mediated chemogenetic or SRS-induced activation of vHPC astrocytes enhances anxiety-like behaviors, which are reversed by intra-vHPC application of the ionotropic glutamate N-methyl-d-aspartate receptor antagonists. Furthermore, intra-vHPC or systemic application of the N-methyl-d-aspartate receptor antagonist memantine, a U.S. FDA-approved drug for Alzheimer's disease, fully rescues SRS-induced anxiety-like behaviors. The findings highlight vHPC astrocytes as critical regulators of stress and anxiety and as potential therapeutic targets for anxiety and anxiety-related disorders.

14.
Sci Data ; 11(1): 883, 2024 Aug 14.
Article in English | MEDLINE | ID: mdl-39143120

ABSTRACT

Remote sensing technology has the potential to enhance the lake's large-scale and long-term dynamic monitoring capabilities significantly. High-quality in-situ datasets are essential for improving the accuracy and reliability of remote sensing retrieval of lake ecosystems. This dataset provides satellite-ground synchronized in-situ data on water multi-parameters for typical lakes in China spanning the period between 2020 and 2023. It includes quality-checked water optical parameters (remote sensing reflectance (Rrs), chlorophyll-a (Chl-a), total suspended matter (TSM) and Secchi disk depth (SDD)), and water surface temperature (WST) data. It encompasses 586 sampling points across 18 lakes. The dataset exhibits two significant highlights: Firstly, synchronous observations from multiple satellites are coordinated during the data collection effectively supporting the retrieval and validation of water remote sensing products. Secondly, it encompasses diverse data types, collecting synchronous measurements of Rrs and various parameters. This dataset will continuously update, substantially enhancing regional and global lake monitoring capabilities through satellite remote sensing data.

15.
CNS Neurosci Ther ; 30(8): e14924, 2024 Aug.
Article in English | MEDLINE | ID: mdl-39143678

ABSTRACT

AIMS: Postoperative cognitive dysfunction (POCD) is prevalent among the elderly, characterized primarily by cognitive decline after surgery. This study aims to explore how extracellular vesicles (EVs) derived from BV2 microglial cells, with and without the C-C chemokine receptor type 5 (CCR5), affect neuroinflammation, neuronal integrity, and cognitive function in a POCD mouse model. METHODS: We collected EVs from LPS-stimulated BV2 cells expressing CCR5 (EVsM1) and from BV2 cells with CCR5 knockdown (EVsM1-CCR5). These were administered to POCD-induced mice. Protein interactions between CCR5, G-protein-coupled receptors (GPCRs), and Ras were analyzed using structure-based docking and co-immunoprecipitation (Co-IP). We assessed the phosphorylation of p38 and Erk, the expression of synaptic proteins PSD95 and MAP2, and conducted Morris Water Maze tests to evaluate cognitive function. RESULTS: Structure-based docking and Co-IP confirmed interactions between CCR5, GPR, and Ras, suggesting a CCR5-GPCRs-Ras-MAPK pathway involvement in neuroinflammation. EVsM1 heightened neuroinflammation, reduced synaptic integrity, and impaired cognitive function in POCD mice. In contrast, EVsM1-CCR5 reduced neuroinflammatory markers, preserved synaptic proteins, enhanced dendritic spine structure, and improved cognitive outcomes. CONCLUSION: EVsM1 induced neuroinflammation via the CCR5-GPCRs-Ras-MAPK pathway, with EVsM1-CCR5 showing protective effects on POCD progression, suggesting a new therapeutic strategy for POCD management via targeted modification of microglial EVs.


Subject(s)
Mice, Inbred C57BL , Microglia , Neuroinflammatory Diseases , Postoperative Cognitive Complications , Receptors, CCR5 , Animals , Microglia/metabolism , Mice , Receptors, CCR5/metabolism , Neuroinflammatory Diseases/metabolism , Postoperative Cognitive Complications/metabolism , Male , Extracellular Vesicles/metabolism , Receptors, G-Protein-Coupled/metabolism , ras Proteins/metabolism , Cognition/physiology , Cognition/drug effects , MAP Kinase Signaling System/physiology , MAP Kinase Signaling System/drug effects , Cognitive Dysfunction/metabolism
16.
Int J Biol Macromol ; : 134830, 2024 Aug 16.
Article in English | MEDLINE | ID: mdl-39154694

ABSTRACT

Diabetic infected bone defects (DIBD) with abnormal immune metabolism are cline to the hard-to-treat bacterial infections and delayed bone regeneration, which present significant challenges in clinic. Control of immune metabolism is believed to be important in regulating fundamental immunological processes. Here, we developed a macrophage metabolic reprogramming hydrogel composed of modified silk fibroin (Silk-6) and poly-l-lysine (ε-PL) and further integrated with M2 Macrophage-derived Exo (M2-Exo), named as Silk-6/ε-PL@Exo. This degradable hydrogel showed a broad-spectrum antibacterial performance towards both Gram-positive and -negative bacteria. More importantly, the release of M2-Exo from Silk-6/ε-PL@Exo could target M1 macrophages, modulating the activity of the key enzyme hexokinase II (HK2) to control the inflammation-related NF-κB pathway, alleviate lactate accumulation, and inhibit glycolysis to normalize the cycle, thereby promoting M1-to-M2 balance. Using a rat model of DIBD, Silk-6/ε-PL@Exo hydrogel promoted infection control, balanced immune responses and accelerated the bone defect healing. Overall, this study demonstrates that this Silk-6/ε-PL @Exo is a promising filler biomaterials with multi-function to treat DIBD and emphasizes the importance of metabolic reprogramming in bone regeneration.

17.
Eur J Med Res ; 29(1): 407, 2024 Aug 05.
Article in English | MEDLINE | ID: mdl-39103966

ABSTRACT

BACKGROUND: Impaired hospitalizations for heart failure (HHF) and mortality are associated with tricuspid regurgitation (TR). OBJECTIVES: The objective of this study was to investigate the benefit of transcatheter tricuspid valve replacement (TTVR) over guideline-directed medical therapy (GDMT) in patients with symptomatic severe TR. METHODS: Between May 2020 and April 2023, 88 patients with symptomatic severe TR were treated in our center. Of these, 57 patients received GDMT alone, and 31 patients underwent combined TTVR and GDMT. We collected and analyzed baseline data, and follow-up information for both groups. The primary endpoints were all-cause mortality and the combined endpoint (including all-cause mortality and HHF). RESULTS: At a median follow-up of 20 (IQR 10-29) months, significant improvements were shown in TR severity, right ventricular function, and dimensions in TTVR group (all P < 0.001). It also resulted in superior survival rates (75.8% vs. 48.4%, P = 0.019), improved freedom from combined endpoint (61.5% vs. 45.9%, P = 0.007) and fewer major adverse events. After stratification by TRI-SCORE, the subgroup with < 6 points in the TTVR group exhibited a significant difference in the combined endpoint compared to the other subgroups (all P < 0.05), while no significant differences were observed in the GDMT subgroups (P = 0.680). CONCLUSIONS: The utilization of LuX-Valve in TTVR effectively improves TR and is associated with lower rates of major adverse events, HHF and all-cause mortality. The TRI-SCORE may help identify higher-benefit patients with TR from TTVR. Clinical trial registration ClinicalTrials.gov Protocol Registration System (NCT02917980).


Subject(s)
Heart Valve Prosthesis Implantation , Tricuspid Valve Insufficiency , Humans , Tricuspid Valve Insufficiency/surgery , Male , Female , Retrospective Studies , Aged , Heart Valve Prosthesis Implantation/methods , Tricuspid Valve/surgery , Middle Aged , Treatment Outcome , Severity of Illness Index , Cardiac Catheterization/methods
19.
J Am Chem Soc ; 146(32): 22145-22150, 2024 Aug 14.
Article in English | MEDLINE | ID: mdl-39101883

ABSTRACT

A heat-driven catch-and-release strategy for CoCl2 capture is described. It is based on the use of an immobilized neutral dicyclohexylacetamide-based receptor L supported on polystyrene (PS-L). An X-ray diffraction analysis of a single crystal of L·CoCl2 revealed an ion-pair complex comprising a hexacoordinated cobalt cation [L·Co]2+ and a tetrachlorocobaltate anion [CoCl4]2-. Temperature dependent binding was seen, as inferred from UV-vis spectroscopic studies. Fits to the van't Hoff equation yielded values of ΔH° = 12.4 kJ/mol and ΔS° = 56.0 J/K·mol for L + CoCl2, and ΔH° = 16.5 kJ/mol and ΔS° = 85.0 J/K·mol for PS-L + CoCl2 in 95% ethanol. Consequently, cobalt capture and release are mediated by heating and cooling, respectively. The material PS-L exhibits a preference for binding cobalt over manganese and nickel as inferred from Langmuir-Freundlich isotherm analyses that revealed binding constants of KLF = 88.5 M-1 for CoCl2, 52.7 M-1 for MnCl2, and 49.7 M-1 for NiCl2. In a simulated ion mixture containing equimolar CoCl2, MnCl2, and NiCl2, ICP-MS analyses served to confirm that cobalt was selectively enriched to 52 mol % (from an initial level of ca. 32 mol %) after one catch-and-release cycle and 76.6% after three cycles. Our experimental results were validated by density functional theory calculations, which also show stronger binding of Co over Mn and Ni to L.

20.
Ann Surg Oncol ; 2024 Aug 13.
Article in English | MEDLINE | ID: mdl-39138774

ABSTRACT

BACKGROUND: The regions of the liver with cholestasis caused by biliary tumors or thrombosis can be distinctly identified using indocyanine green (ICG) fluorescence imaging.1 The authors' team reported the application of bile-duct obstructed area imaging (BOAI) to assist open hepatectomy for intrahepatic cholangiocarcinoma (ICC) combined with intrahepatic bile duct obstruction previously.2 This video is the first report of real-time BOAI-guided three-dimensional (3D) laparoscopic hepatectomy using a 3D-4K fluorescence imaging system. METHODS: A 65-year-old man was admitted to the authors' institution with clonorchiasis. Preoperative computed tomography (CT) and magnetic resonance cholangiopancreatography (MRCP) showed an obstruction and diffuse dilation of the right hepatic duct. A 15-min retention of ICG (ICG R15) was performed 5 days before the operation, with a 3.3% result. Preoperative planning involved performing laparoscopic right hemi-hepatectomy with regional lymph node dissection assisted by visualization technology.3 During the procedure, significant fluorescence accumulation in the right liver was shown by fluorescence imaging. With the guidance of real-time BOAI (Fig. 1), the regions of biliary obstruction were precisely resected, and the middle hepatic vein (MHV) was passively and adequately exposed on the cutting plane. Fig. 1 Administration steps for real-time bile duct-obstructed area imaging. A ICG is injected intravenously 3-5 days before operation at a dose of 0.5 mg/kg. B ICG is accumulated in the whole liver within a few minutes after injection. C ICG is selectively absorbed by the liver and excreted into the intestines, whereby it is retained in areas of biliary obstruction RESULTS: The histopathologic diagnosis indicated high-grade intraepithelial neoplasia of the right bile duct tumor without lymph node metastases and clonorchiasis. The duration of the operation was 300 min, with an intraoperative blood loss of 50 ml. No postoperative complications occurred, and the patient was discharged after 7 days. CONCLUSION: Laparoscopic right hemi-hepatectomy for the bile-duct obstructed area with the guidance of real-time BOAI is feasible and effective.

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