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1.
World J Surg Oncol ; 22(1): 189, 2024 Jul 24.
Article in English | MEDLINE | ID: mdl-39049011

ABSTRACT

BACKGROUND: The aim of this study was to elucidate the histogenesis and genetic underpinnings of fibromatosis-like undifferentiated gastric carcinoma (FLUGC), a rare pathological entity. METHOD: Through a detailed analysis of seven cases, including histopathological evaluation, CTNNB1 gene mutation screening, human epidermal growth factor receptor 2 (HER2) protein level quantification, and HER2 gene amplification assessment to identify the pathological and molecular characteristics of FLUGC. RESULTS: Of the seven patients in this study, five were male and two were female (age: 39-73 years). Four patients presented with lesions in the gastric antrum and three had lesions in the lateral curvature of the stomach. Histopathologically, over 90% of the tumor consisted of aggressive fibromatosis-like tissue, including proliferating spindle fibroblasts and myofibroblasts and varying amounts of collagenous fibrous tissues. Undifferentiated cancer cells, accounting for less than 10%, were dispersed among the aggressive fibromatosis-like tissues. These cells were characterized by their small size and were relatively sparse without glandular ducts or nested mass-like structures. Immunophenotyping results showed positive expression of CKpan, CDX2, villin, and p53 in undifferentiated cancer cells; positive expression of vimentin in aggressive fibromatosis-like tissue; positive cytoplasmic expression of ß-catenin; and focal cytoplasmic positive expression of smooth muscle actin (SMA). Genetic analysis did not reveal any mutations in the CTNNB1 gene test, nor was there amplification in the HER2 gene fluorescence in situ hybridization (FISH) test. Additionally, the Epstein-Barr encoding region (EBER) of in situ hybridization was negative; and the mismatch repair (MMR) protein was positive. Programmed cell death-1 (PD-1) was < 1-5%; programmed cell death ligand 1 (PD-L1): TPS = 1-4%, CPS = 3-8. CONCLUSION: The study highlights the significance of CTNNB1, HER2, EBER, and MMR as pivotal genetic markers in FLUGC, underscoring their relevance for diagnosis and clinical management. The rarity and distinct pathological features of FLUGC emphasize the importance of accurate diagnosis to prevent underdiagnosis or misdiagnosis and to raise awareness within the medical community.


Subject(s)
Biomarkers, Tumor , Receptor, ErbB-2 , Stomach Neoplasms , beta Catenin , Humans , Stomach Neoplasms/genetics , Stomach Neoplasms/pathology , Female , Middle Aged , Male , Aged , Adult , beta Catenin/genetics , beta Catenin/metabolism , Biomarkers, Tumor/genetics , Biomarkers, Tumor/metabolism , Receptor, ErbB-2/genetics , Receptor, ErbB-2/metabolism , Prognosis , Mutation , Follow-Up Studies , Fibroma/genetics , Fibroma/pathology , Fibroma/diagnosis
2.
Adv Healthc Mater ; : e2400766, 2024 Jul 15.
Article in English | MEDLINE | ID: mdl-39007249

ABSTRACT

Mild photothermal therapy (PTT) has attracted attention for effectively avoiding the severe side effects associated with high-temperature tumor ablation. However, its progress is hindered by the limited availability of high-performance photothermal agents (PTAs) and the thermoresistance of cancer cells induced by heat shock reactions. Herein, this work proposes a new strategy to expand the library of high-performance organic small-molecule PTAs and utilize it to construct a multifunctional nano-theranostic platform. By incorporating additional acceptors and appropriate π-bridges, a diketopyrrolopyrrole-based dye BDB is developed, which exhibits strong absorption and bright fluorescence emission in the near-infrared (NIR) region. Subsequently, BDB is co-coated with the heat shock protein (HSP) inhibitor tanespimycin (17-AAG) using the functional amphiphilic polymers DSPE-Hyd-PEG2000-cRGD to form an all-in-one nanoplatform BAG NPs. As a result, BAG NPs can precisely target tumor tissue, guide the treatment process in real-time through NIR-II fluorescence/photoacoustic/photothermal imaging, and release 17-AAG on demand to enhance mild PTT. Additionally, the mild PTT has been demonstrated to induce immunogenic cell death (ICD) and activate a systemic anti-tumor immune response, thereby suppressing both primary and distant tumors. Overall, this study presents a multifunctional nanoplatform designed for precise mild PTT combined with immunotherapy for effective tumor treatment.

3.
BMC Genomics ; 25(1): 675, 2024 Jul 08.
Article in English | MEDLINE | ID: mdl-38977976

ABSTRACT

BACKGROUND: The number of spikelets per spike is a key trait that affects the yield of bread wheat (Triticum aestivum L.). Identification of the QTL for spikelets per spike and its genetic effects that could be used in molecular assistant breeding in the future. RESULTS: In this study, four recombinant inbred line (RIL) populations were generated and used, having YuPi branching wheat (YP), with Supernumerary Spikelets (SS) phenotype, as a common parent. QTL (QSS.sicau-2 A and QSS.sicau-2D) related to SS trait were mapped on chromosomes 2 A and 2D through bulked segregant exome sequencing (BSE-Seq). Fourteen molecular markers were further developed within the localization interval, and QSS.sicau-2 A was narrowed to 3.0 cM covering 7.6 Mb physical region of the reference genome, explaining 13.7 - 15.9% the phenotypic variance. Similarly, the QSS.sicau-2D was narrowed to 1.8 cM covering 2.4 Mb physical region of the reference genome, and it explained 27.4 - 32.9% the phenotypic variance. These two QTL were validated in three different genetic backgrounds using the linked markers. QSS.sicau-2 A was identified as WFZP-A, and QSS.sicau-2D was identified a novel locus, different to the previously identified WFZP-D. Based on the gene expression patterns, gene annotation and sequence analysis, TraesCS2D03G0260700 was predicted to be a potential candidate gene for QSS.sicau-2D. CONCLUSION: Two significant QTL for SS, namely QSS.sicau-2 A and QSS.sicau-2D were identified in multiple environments were identified and their effect in diverse genetic populations was assessed. QSS.sicau-2D is a novel QTL associated with the SS trait, with TraesCS2D03G0260700 predicted as its candidate gene.


Subject(s)
Chromosome Mapping , Phenotype , Quantitative Trait Loci , Triticum , Triticum/genetics , Chromosomes, Plant/genetics , Genetic Association Studies , Genes, Plant
4.
Phytomedicine ; 132: 155846, 2024 Jun 27.
Article in English | MEDLINE | ID: mdl-38964155

ABSTRACT

BACKGROUND: The lack of effective treatments for methicillin-resistant Staphylococcus aureus (MRSA) infection, which often leads to severe acute lung injury (ALI), poses a grave threat to human life. Sophoricoside (SOP), an isoflavone glycoside abundant in the fruit of traditional Chinese herbal Sophora japonica l., showed anti-inflammatory effects against atopic dermatitis, allergic inflammation, and lipopolysaccharide-induced ALI. However, its effect and underlying mechanism on MRSA-induced ALI remain unclear. PURPOSE: The aim of this study is to assess the protective effect of SOP in MRSA-induced ALI and elucidate its underlying molecular mechanisms. METHODS: In vivo experiments were conducted using wild-type mice to establish MRSA-induced ALI mouse model, and the effects of SOP on ALI were evaluated by hematoxylin-eosin staining, flow cytometry, quantitative real-time polymerase chain reaction, and several biochemical indicators. Adoptive transfer experiments and BTB and CNC homology 1 knockout (Bach1-/-) mice were also utilized in this study. In vitro studies employed murine macrophages RAW264.7 cells, primary bone marrow-derived macrophages (BMDMs), and primary lung macrophages to explore the underlying molecular mechanisms. RESULTS: The administration of SOP ameliorated MRSA-induced ALI by improving pulmonary histological damages, reducing neutrophil infiltration, suppressing oxidative stress levels, and decreasing the expression of inflammatory cytokines. In isolation experiments with ALI mouse lung macrophages and macrophage adoptive transfer experiments, SOP prevented macrophage activation, thereby reducing the production of proinflammatory cytokines. In vitro experiments demonstrated that SOP decreased the expression of inflammatory mediators in lipoteichoic acid (LTA)-stimulated RAW264.7 cells, BMDMs, and primary lung macrophages. Additionally, SOP inhibited protein kinase B (Akt) phosphorylation and treatment with MK2206-a specific inhibitor of Akt-eliminated SOP's ability to suppress LTA-stimulated macrophage inflammation. Furthermore, stimulation with LTA or MRSA up-regulated Bach1 expression; however, deletion of Bach1 abolished the inhibitory effect of SOP on p-Akt activation as well as inflammation and ALI development. CONCLUSION: This study provides the first evidence that SOP effectively mitigates MRSA-induced ALI via suppressing macrophage activation through the inhibition of Bach1/Akt pathway. These findings highlight the potential of SOP as a novel therapeutic agent for treating MRSA-induced ALI.

5.
Front Neurol ; 15: 1420942, 2024.
Article in English | MEDLINE | ID: mdl-38966083

ABSTRACT

Introduction: Intervertebral disc degeneration (IVDD) is a complex disease caused by genetic and environmental factors, but its pathogenesis is still unclear. Although studies of inflammatory cytokines have been used in recent years to unravel the biological mechanisms of a variety of diseases, such analyses have not yet been applied to IVDD. Therefore, we used a Mendelian Randomization approach to explore the potential mechanisms underlying the pathogenesis of IVDD. Methods: We obtained GWAS data from publicly available databases for inflammatory cytokines and IVDD, respectively, and explored the causal relationship between individual inflammatory cytokines and IVDD using instrumental variable (IV) analysis. We primarily used IVW methods to assess causality, while sensitivity, heterogeneity and multidirectionality analyses were performed for positive results (p < 0.05). All analyses were performed using R software. Results: In our study, we performed a two-sample MR analysis of 41 inflammatory cytokines to identify metabolites causally associated with IVDD. Ultimately, 2 serum metabolites associated with IVDD were identified (pval<0.05), IFN-γ and IL-18. sensitivity, heterogeneity, and Pleiotropy test analyses were performed for all results. Conclusion: Our study identified a causal relationship between IFN-γ and IL-18 and IVDD. It is valuable for the monitoring and prevention of IVDD and the exploration of targeted drugs. However, more evidence is needed to validate our study.

6.
Front Nutr ; 11: 1404123, 2024.
Article in English | MEDLINE | ID: mdl-38966421

ABSTRACT

Background: Renshen Yangrong decoction (RSYRD) has been shown therapeutic effects on secondary malaise and fatigue (SMF). However, to date, its bioactive ingredients and potential targets remain unclear. Purpose: The purpose of this study is to assess the potential ingredients and targets of RSYRD on SMF through a comprehensive strategy integrating network pharmacology, Mendelian randomization as well as molecular docking verification. Methods: Search for potential active ingredients and corresponding protein targets of RSYRD on TCMSP and BATMAN-TCM for network pharmacology analysis. Mendelian randomization (MR) was performed to find therapeutic targets for SMF. The eQTLGen Consortium (sample sizes: 31,684) provided data on cis-expression quantitative trait loci (cis-eQTL, exposure). The summary data on SMF (outcome) from genome-wide association studies (GWAS) were gathered from the MRC-IEU Consortium (sample sizes: 463,010). We built a target interaction network between the probable active ingredient targets of RSYRD and the therapeutic targets of SMF. We next used drug prediction and molecular docking to confirm the therapeutic value of the therapeutic targets. Results: In RSYRD, network pharmacology investigations revealed 193 possible active compounds and 234 associated protein targets. The genetically predicted amounts of 176 proteins were related to SMF risk in the MR analysis. Thirty-seven overlapping targets for RSYRD in treating SMF, among which six (NOS3, GAA, IMPA1, P4HTM, RB1, and SLC16A1) were prioritized with the most convincing evidence. Finally, the 14 active ingredients of RSYRD were identified as potential drug molecules. The strong affinity between active components and putative protein targets was established by molecular docking. Conclusion: This study revealed several active components and possible RSYRD protein targets for the therapy of SMF and provided novel insights into the feasibility of using Mendelian randomization for causal inference between Chinese medical formula and disease.

8.
ACS Cent Sci ; 10(6): 1201-1210, 2024 Jun 26.
Article in English | MEDLINE | ID: mdl-38947212

ABSTRACT

Coacervates formed by liquid-liquid phase separation emerge as important biomimetic models for studying the dynamic behaviors of membraneless organelles and synchronously motivating the creation of smart architectures with the regulation of cell fate. Despite continuous progress, it remains challenging to balance the trade-offs among structural stability, versatility, and molecular communication for regulation of cell fate and systemic investigation in a complex physiological system. Herein, we present a self-stabilizing and fastener-bound gain-of-function methodology to create a new type of synthetic DNA membraneless organelle (MO) with high stability and controlled bioactivity on the basis of DNA coacervates. Specifically, long single-strand DNA generated by rolling circle amplification (RCA) is selected as the scaffold that assembles into membraneless coacervates via phase separation. Intriguingly, the as-formed DNA MO can recruit RCA byproducts and other components to achieve self-stabilization, nanoscale condensation, and function encoding. As a proof of concept, photoactivatable DNA MO is constructed and successfully employed for time-dependent accumulation and spatiotemporal management of cancer in a mouse model. This study offers new, important insights into synthetic membraneless organelles for the basic understanding and manipulation of important life processes.

9.
ACS Appl Mater Interfaces ; 16(30): 39215-39224, 2024 Jul 31.
Article in English | MEDLINE | ID: mdl-39038493

ABSTRACT

Li dendrite and the shuttle effect are the two primary hindrances to the commercial application of lithium-sulfur batteries (LSBs). Here, a multifunctional separator has been fabricated via successively coating carbon nanotubes (CNTs) and lithium phytate (LP) onto a commercial polypropylene (PP) separator to improve the performance of LSBs. The LP coating layer with abundant electronegative phosphate group as permselective ion sieve not only reduces the polysulfide shuttle but also facilitates uniform Li+ flux through the PP separator. And the highly conductive CNTs on the second layer act as a second collector to accelerate the reversible conversion of sulfide species. The synergistic effect of LP and CNTs further increases the electrolyte wettability and reaction kinetics of cells with a modified separator and suppresses the shuttle effect and growth of Li dendrite. Consequently, the LSBs present much enhanced rate performance and cyclic performance. It is expected that this study may generate an executable tactic for interface engineering of separator to accelerate the industrial application process of LSBs.

10.
J Mater Chem B ; 12(30): 7429-7439, 2024 Jul 31.
Article in English | MEDLINE | ID: mdl-38967310

ABSTRACT

The development of nanoformulations with simple compositions that can exert targeted combination therapy still remains a great challenge in the area of precision cancer nanomedicine. Herein, we report the design of a multifunctional nanoplatform based on methotrexate (MTX)-loaded layered double hydroxide (LDH) coated with chlorin e6 (Ce6)-modified MCF-7 cell membranes (CMM) for combined chemo/sonodynamic therapy of breast cancer. LDH nanoparticles were in situ loaded with MTX via coprecipitation, and coated with CMM that were finally functionalized with phospholipid-modified Ce6. The created nanoformulation of LDH-MTX@CMM-Ce6 displays good colloidal stability under physiological conditions and can release MTX in a pH-dependent manner. We show that the formulation can homologously target breast cancer cells, and induce their significant apoptosis through arresting the cell cycle via cooperative MTX-based chemotherapy and ultrasound (US)-activated sonodynamic therapy. The assistance of US can not only trigger sonosensitizer Ce6 to produce reactive oxygen species, but also enhance the cellular uptake of LDH-MTX@CMM-Ce6 via an acoustic cavitation effect. Upon intravenous injection and US irradiation, LDH-MTX@CMM-Ce6 displays an admirable antitumor performance towards a xenografted breast tumor mouse model. Furthermore, the modification of Ce6 on the CMM endows the LDH-based nanoplatform with fluorescence imaging capability. The developed LDH-based nanoformulation here provides a general intelligent cancer nanomedicine platform with simple composition and homologous targeting specificity for combined chemo/sonodynamic therapy and fluorescence imaging of tumors.


Subject(s)
Chlorophyllides , Hydroxides , Methotrexate , Nanoparticles , Porphyrins , Ultrasonic Therapy , Humans , Animals , Methotrexate/chemistry , Methotrexate/pharmacology , Hydroxides/chemistry , Hydroxides/pharmacology , Mice , Female , Porphyrins/chemistry , Porphyrins/pharmacology , Nanoparticles/chemistry , MCF-7 Cells , Antineoplastic Agents/chemistry , Antineoplastic Agents/pharmacology , Apoptosis/drug effects , Cell Membrane/chemistry , Cell Membrane/metabolism , Mice, Inbred BALB C , Biomimetic Materials/chemistry , Biomimetic Materials/pharmacology , Mice, Nude , Cell Proliferation/drug effects , Breast Neoplasms/drug therapy , Breast Neoplasms/pathology , Particle Size , Drug Screening Assays, Antitumor , Surface Properties
11.
J Med Chem ; 67(14): 11789-11813, 2024 Jul 25.
Article in English | MEDLINE | ID: mdl-38990190

ABSTRACT

The exploration of novel anticancer compounds based on natural cyclopeptides has emerged as a pivotal paradigm in the contemporary advancement of macrocyclic pharmaceuticals. Phakellistatin 13 is a cycloheptapeptide derived from the brown snubby sponge and exhibits remarkable antitumor activity. In this study, we have designed and synthesized a series of chiral cyclopeptides incorporating the rigid isoindolinone moiety at various sites within the natural cycloheptapeptide Phakellistatin 13, with the aim of investigating conformationally constrained cyclopeptides as potential antitumor agents. Cyclopeptide 3, comprising alternating l-/d-amino acid residues, exhibited promising antihepatocellular carcinoma effects. Detailed biological experiments have revealed that Phakellistatin 13 analogs effectively inhibit the proliferation of tumor cells and induce apoptosis and autophagy, while also causing cell cycle arrest through the modulation of the p53 and mitogen-activated protein kinase (MAPK) signaling pathway. This study not only provides valuable insights into chemical structural modifications but also contributes to a deeper understanding of the biological mechanisms underlying the development of natural cyclopeptide-based drugs.


Subject(s)
Antineoplastic Agents , Apoptosis , Cell Proliferation , Peptides, Cyclic , Peptides, Cyclic/chemistry , Peptides, Cyclic/pharmacology , Peptides, Cyclic/chemical synthesis , Antineoplastic Agents/pharmacology , Antineoplastic Agents/chemistry , Antineoplastic Agents/chemical synthesis , Humans , Apoptosis/drug effects , Cell Proliferation/drug effects , Cell Line, Tumor , Structure-Activity Relationship , Drug Screening Assays, Antitumor , Autophagy/drug effects , Cell Cycle Checkpoints/drug effects , Tumor Suppressor Protein p53/metabolism , Animals
12.
J Pineal Res ; 76(5): e12989, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38978438

ABSTRACT

Colistin is renowned as a last-resort antibiotic due to the emergence of multidrug-resistant pathogens. However, its potential toxicity significantly hampers its clinical utilization. Melatonin, chemically known as N-acetyl-5-hydroxytryptamine, is an endogenous hormone produced by the pineal gland and possesses diverse biological functions. However, the protective role of melatonin in alleviating antibiotic-induced intestinal inflammation remains unknown. Herein, we reveal that colistin stimulation markedly elevates intestinal inflammatory levels and compromises the gut barrier. In contrast, pretreatment with melatonin safeguards mice against intestinal inflammation and mucosal damage. Microbial diversity analysis indicates that melatonin supplementation prevents a reduction in the abundance of Erysipelotrichales and Bifidobacteriales, as well as an increase in Desulfovibrionales abundance, following colistin exposure. Remarkably, short-chain fatty acids (SCFAs) analysis shows that propanoic acid contributes to the protective effect of melatonin on colistin-induced intestinal inflammation. Furthermore, the protection effects of melatonin and propanoic acid on LPS-induced cellular inflammation in RAW 264.7 cells are confirmed. Mechanistic investigations suggest that intervention with melatonin and propanoic acid can repress the activation of the TLR4 signal and its downstream NF-κB and MAPK signaling pathways, thereby mitigating the toxic effects of colistin. Our work highlights the unappreciated role of melatonin in preventing the potential detrimental effects of colistin on intestinal health and suggests a combined therapeutic strategy to effectively manage intestinal infectious diseases.


Subject(s)
Colistin , Dysbiosis , Gastrointestinal Microbiome , Melatonin , Melatonin/pharmacology , Animals , Mice , Colistin/adverse effects , Dysbiosis/chemically induced , Dysbiosis/metabolism , Dysbiosis/microbiology , Gastrointestinal Microbiome/drug effects , RAW 264.7 Cells , Inflammation/metabolism , Inflammation/drug therapy , Inflammation/chemically induced , Male , Anti-Bacterial Agents/pharmacology , Mice, Inbred C57BL
13.
ACS Appl Mater Interfaces ; 16(29): 37927-37937, 2024 Jul 24.
Article in English | MEDLINE | ID: mdl-38980948

ABSTRACT

Fine tuning of the metal site coordination environment of a single-atom catalyst (SAC) to boost its catalytic activity for oxygen reduction reaction (ORR) is of significance but challenging. Herein, we report a new SAC bearing Fe-N3C-N sites with asymmetric in-plane coordinated Fe-N3C and axial coordinated N atom for ORR, which was obtained by pyrolysis of an iron isoporphyrin on polyvinylimidazole (PVI) coated carbon black. The C@PVI-(NCTPP)Fe-800 catalyst exhibited significantly improved ORR activity (E1/2 = 0.89 V vs RHE) than the counterpart SAC with Fe-N4-N sites in 0.1 M KOH. Significantly, the Zn-air batteries equipped with the C@PVI-(NCTPP)Fe-800 catalyst demonstrated an open-circuit voltage (OCV) of 1.45 V and a peak power density (Pmax) of 130 mW/cm2, outperforming the commercial Pt/C catalyst (OCV = 1.42 V; Pmax = 119 mW/cm2). The density functional theory (DFT) calculations revealed that the d-band center of the asymmetric Fe-N3C-N structure shifted upward, which enhances its electron-donating ability, favors O2 adsorption, and supports O-O bond activation, thus leading to significantly promoted catalytic activity. This research presents an intriguing strategy for the designing of the active site architecture in metal SACs with a structure-function controlled approach, significantly enhancing their catalytic efficiency for the ORR and offering promising prospects in energy-conversion technologies.

14.
Diagn Microbiol Infect Dis ; 110(1): 116415, 2024 Sep.
Article in English | MEDLINE | ID: mdl-38970947

ABSTRACT

Carbapenem-resistant organism (CRO) are defined as gram-negative bacteria. The lack of safe and effective antibiotics has led to an increase in incidence rate. The purpose of this study is to establish and determine a risk nomogram to predict CRO infection in hospitalized patients. Hospitalized patients' information were collected from the electronic medical record system of hospital between January 2019 and December 2022. Based on the inclusion and exclusion criteria, we identified 131390 inpatients who met the criteria for this study. For the training cohort, the area under the curves (AUC) for predicting the CRO infection was 0.935. For the validation cohort, the AUC for predicting the CRO infection was 0.937. We have developed the first novel nomogram to predict CRO infection in hospitalized patients, which is reliable and high-performance. The nomogram performs well among hospitalized patients and has good predictive ability.


Subject(s)
Anti-Bacterial Agents , Carbapenems , Gram-Negative Bacterial Infections , Nomograms , Humans , Carbapenems/pharmacology , Male , Female , Middle Aged , Gram-Negative Bacterial Infections/microbiology , Gram-Negative Bacterial Infections/drug therapy , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/therapeutic use , Aged , Hospitalization , Gram-Negative Bacteria/drug effects , Gram-Negative Bacteria/isolation & purification , Adult , Retrospective Studies , Aged, 80 and over , Electronic Health Records
15.
Aging Clin Exp Res ; 36(1): 155, 2024 Aug 01.
Article in English | MEDLINE | ID: mdl-39085739

ABSTRACT

BACKGROUND AND OBJECTIVE: Malnutrition is prevalent among elderly patients with COPD, who also experience a high rate of readmission. Therefore, it is imperative to investigate the nutrition status of these patients, identify risk factors for readmission, and offer insights for clinical management. To achieve this, a cross-sectional study was conducted to investigate factors influencing nutrition status using GLIM criteria and explore the 180-day readmission factors among hospitalized elderly COPD patients. METHORDS AND RESULTS: The data were collected from a hospital in Southwest China, encompassing a cohort of 319 eligible patients. Among elderly hospitalized COPD patients, the prevalence of malnutrition was 49.53% (158/319). Multivariate logistic regression revealed malnutrition (OR = 3.184), very severe airway obstruction (OR = 3.735), and Number of comorbidities ≥ 3 (OR = 5.754) as significant risk factors for 180-day readmission. CONCLUSIONS: These findings suggest that malnutrition is a prevalent issue among elderly hospitalized patients with COPD and constitutes one of the risk factors contributing to the 180-day readmission rate. Therefore, timely identification and treatment for malnourished patients are crucial.


Subject(s)
Malnutrition , Nutritional Status , Patient Readmission , Pulmonary Disease, Chronic Obstructive , Humans , Pulmonary Disease, Chronic Obstructive/epidemiology , Aged , Male , Female , Patient Readmission/statistics & numerical data , Malnutrition/epidemiology , Cross-Sectional Studies , Risk Factors , Aged, 80 and over , Hospitalization/statistics & numerical data , Prevalence , China/epidemiology , Comorbidity
16.
Med ; 2024 Jun 06.
Article in English | MEDLINE | ID: mdl-38870932

ABSTRACT

BACKGROUND: The interim analysis of the randomized phase 3 ESCORT-1st study demonstrated significantly longer overall survival (OS) and progression-free survival (PFS) for camrelizumab-chemotherapy than placebo-chemotherapy in untreated advanced/metastatic esophageal squamous cell carcinoma (ESCC). Here, we present the final analysis of this study and investigate potential indicators associated with OS. METHODS: Patients were randomized 1:1 to receive camrelizumab (200 mg) or placebo, both in combination with up to six cycles of paclitaxel (175 mg/m2) and cisplatin (75 mg/m2). All treatments were administered intravenously every 3 weeks. The co-primary endpoints were OS and PFS assessed by the independent review committee. FINDINGS: As of April 30, 2022, the median OS was significantly longer in the camrelizumab-chemotherapy group compared to the placebo-chemotherapy group (15.6 [95% confidence interval (CI): 14.0-18.4] vs. 12.6 months [95% CI 11.2-13.8]; hazard ratio [HR]: 0.70 [95% CI 0.58-0.84]; one-sided p < 0.0001), with 3-year OS rates of 25.6% and 12.8% in the two groups, respectively. The 2-year PFS rates were 20.4% in the camrelizumab-chemotherapy group and 3.4% in the placebo-chemotherapy group. Adverse events were consistent with those reported in the interim analysis. Higher PD-L1 expression correlated with extended OS, and multivariate analysis identified sex and prior history of radiotherapy as independent indicators of OS. CONCLUSIONS: The sustained and significant improvement in efficacy with camrelizumab-chemotherapy compared to placebo-chemotherapy, along with the absence of accumulating or delayed toxicities, supports the long-term use of camrelizumab-chemotherapy as a standard therapy in untreated advanced/metastatic ESCC. FUNDING: This study was funded by Jiangsu Hengrui Pharmaceuticals Co., Ltd.

17.
Int J Nanomedicine ; 19: 5605-5618, 2024.
Article in English | MEDLINE | ID: mdl-38882547

ABSTRACT

Patients diagnosed with glioma typically face a limited life expectancy (around 15 months on average), a bleak prognosis, and a high likelihood of recurrence. As such, glioma is recognized as a significant form of malignancy. Presently, the treatment options for glioma include traditional approaches such as surgery, chemotherapy, and radiotherapy. Regrettably, the efficacy of these treatments has been less than optimal. Nevertheless, a promising development in glioma treatment lies in the use of hydrogel nano-systems as sophisticated delivery systems. These nano-systems have demonstrated exceptional therapeutic effects in the treatment of glioma by various responsive ways, including temperature-response, pH-response, liposome-response, ROS-response, light-response, and enzyme-response. This study seeks to provide a comprehensive summary of both the therapeutic application of hydrogel nano-systems in managing glioma and the underlying immune action mechanisms.


Subject(s)
Brain Neoplasms , Glioma , Hydrogels , Glioma/therapy , Humans , Hydrogels/chemistry , Brain Neoplasms/therapy , Brain Neoplasms/drug therapy , Animals , Liposomes/chemistry , Drug Delivery Systems/methods , Nanomedicine , Nanoparticles/chemistry
18.
PLoS Negl Trop Dis ; 18(6): e0012151, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38843297

ABSTRACT

BACKGROUND: Hemorrhagic Fever with Renal Syndrome (HFRS) continues to pose a significant public health threat to the well-being of the population. Given that the spread of HFRS is susceptible to meteorological factors, we aim to probe into the meteorological drivers of HFRS. Thus, novel techniques that can discern time-delayed non-linear relationships from nonlinear dynamical systems are compulsory. METHODS: We analyze the epidemiological features of HFRS in Weifang City, 2011-2020, via the employment of the Empirical Dynamic Modeling (EDM) method. Our analysis delves into the intricate web of time-delayed non-linear associations between meteorological factors and HFRS. Additionally, we investigate the repercussions of minor perturbations in meteorological variables on future HFRS incidence. RESULTS: A total of 2515 HFRS cases were reported in Weifang from 2011 to 2020. The number of cases per week was 4.81, and the average weekly incidence was 0.52 per 1,000,000. The propagation of HFRS is significantly impacted by the mean weekly temperature, relative humidity, cumulative rainfall, and wind speed, and the ρCCM converges to 0.55,0.48,0.38 and 0.39, respectively. The graphical representation of the relationship between temperature (lagged by 2 weeks) and the incidence of HFRS exhibits an inverted U-shaped curve, whereby the incidence of HFRS culminates as the temperature reaches 10 °C. Moreover, temperature, relative humidity, cumulative rainfall, and wind speed exhibit a positive correlation with HFRS incidence, with a time lag of 4-6 months. CONCLUSIONS: Our discoveries suggest that meteorological factors can drive the transmission of HFRS both at a macroscopic and microscopic scale. Prospective alterations in meteorological conditions, for instance, elevations in temperature, relative humidity, and precipitation will instigate an upsurge in the incidence of HFRS after 4-6 months, and thus, timely public health measures should be taken to mitigate these changes.


Subject(s)
Hemorrhagic Fever with Renal Syndrome , Meteorological Concepts , Hemorrhagic Fever with Renal Syndrome/epidemiology , Humans , China/epidemiology , Incidence , Temperature , Male , Female , Adult , Middle Aged , Humidity , Young Adult , Adolescent
19.
Conserv Biol ; : e14310, 2024 Jun 06.
Article in English | MEDLINE | ID: mdl-38842221

ABSTRACT

Climate change may diminish biodiversity; thus, it is urgent to predict how species' ranges may shift in the future by integrating multiple factors involving more taxa. Bats are particularly sensitive to climate change due to their high surface-to-volume ratio. However, few studies have considered geographic variables associated with roost availability and even fewer have linked the distributions of bats to their thermoregulation and energy regulation traits. We used species distribution models to predict the potential distributions of 12 bat species in China under current and future greenhouse gas emission scenarios (SSP1-2.6 and SSP5-8.5) and examined factors that could affect species' range shifts, including climatic, geographic, habitat, and human activity variables and wing surface-to-mass ratio (S-MR). The results suggest that Ia io, Rhinolophus ferrumequinum, and Rhinolophus rex should be given the highest priority for conservation in future climate conservation strategies. Most species were predicted to move northward, except for I. io and R. rex, which moved southward. Temperature seasonality, distance to forest, and distance to karst or cave were the main environmental factors affecting the potential distributions of bats. We found significant relationships between S-MR and geographic distribution, current potential distribution, and future potential distribution in the 2050s. Our work highlights the importance of analyzing range shifts of species with multifactorial approaches, especially for species traits related to thermoregulation and energy regulation, to provide targeted conservation strategies.


Patrones y correlaciones de los cambios potenciales en la distribución de las especies de murciélago de China en el contexto del cambio climático Resumen El cambio climático puede disminuir la biodiversidad, por lo que es urgente pronosticar cómo puede cambiar en el futuro la distribución de las especies mediante la integración de múltiples factores que involucren a más taxones. Los murciélagos son particularmente sensibles al cambio climático debido a que tienen una gran proporción superficie­volumen. Sin embargo, hay pocos estudios que han considerado las variables asociadas con la disponibilidad de nidos y son todavía menos los que han conectado la distribución de los murciélagos con sus rasgos de termorregulación y regulación de energía. Usamos modelos de distribución de especies para pronosticar la distribución potencial de doce especies de murciélago en China bajo escenarios actuales y futuros de emisión de gases de efecto invernadero (SSP1­2.6 y SSP5­8.5) y analizamos los factores que podrían afectar el cambio en la distribución de las especies, incluyendo las variables climáticas, geográficas, de hábitat y de actividad humana y la proporción entre la superficie del ala y la masa (P S­M). Los resultados sugieren que Ia io, Rhinolophus ferrumequinum y R. rex deberían ser la mayor prioridad de conservación para las estrategias de conservación climáticas en el futuro. Pronosticamos que la mayoría de las especies se desplazarían al norte, a excepción de I. io y R. rex, que se desplazarían hacia el sur. Los principales factores que afectaron la distribución potencial de los murciélagos fueron la estacionalidad de la temperatura, la distancia al bosque y la distancia a la cueva o al karst. Encontramos una relación significativa entre la P S­M y la distribución geográfica, la distribución potencial actual y la distribución potencial para la década de 2050. Nuestra investigación destaca la importancia del análisis de los cambios de distribución de las especies con enfoques multifactoriales, especialmente para los rasgos de especie relacionados con la termorregulación y la regulación de energía, para proporcionar estrategias de conservación focalizadas.

20.
Acta Neurochir (Wien) ; 166(1): 275, 2024 Jun 24.
Article in English | MEDLINE | ID: mdl-38910196

ABSTRACT

PURPOSE: The purpose of this study was to describe the effectiveness and evaluation of open surgical treatment of basilar artery aneurysms in the context of interventional therapy era, including surgical clipping and blood reconstruction, by retrospectively analyzing the clinical data of basilar artery aneurysms in our center. METHODS: Patients with basilar artery aneurysms who were treated at our center were retrospectively included according to the inclusion and exclusion criteria. The basic clinical data, surgical approach, clinical follow-up and prognosis of the enrolled patients were analyzed in detail. In this study, the mRS score was applied to assess the neurological prognosis of the patients, and the relevant data were statistically analyzed using SPSS. RESULTS: A total of 104 eligible patients treated at our center from January 2010 to August 2023 were included in this study, of which 67 were treated by open surgery and 37 by bypass. For the 67 patients with open surgical clipping, the mean age was 60.0 (52.0, 65.0) years. The maximum diameter of the aneurysms ranged from 2.0 mm to 54.0 mm, with a mean of 13.9 (10.0, 19.0) mm. The mean follow-up time was 38 (20, 58) months. At the last follow-up, 61 (91.0%) completely obliterated aneurysms and 6 (9.0%) incompletely obliterated aneurysms were found. The prognosis was good in 59 (88.1%) patients and poor in 8 (11.9%). After surgical clipping, the difference between complete and incomplete postoperative aneurysm elimination was statistically significant between the favorable and poor prognosis groups (P < 0.001). For the 37 bypass group patients, the mean age was 52.0 (45.5, 59.0) years. The maximum diameter of the aneurysm ranged from 10.5 mm to 55.0 mm, with a mean of 28.55 ± 12.08 mm. Bypass combined with proximal occlusion was performed in 18 (48.6%) patients, and bypass only was performed in 19 (51.4%) patients. Clinical follow-up was 19.0 (10.5, 43.0) months. There were 19 (51.4%) patients with complete elimination of the aneurysm, 13 (35.1%) with incomplete elimination of the aneurysm, and 5 (13.5%) with aneurysm stabilization. The prognosis was good in 32 (86.5%) patients and poor in 5 (13.5%) patients. CONCLUSION: Treatment of basilar artery aneurysms is challenging. In the context of the rapidly evolving interventional therapy era, open surgery including surgical clipping and bypass is an ideal option for complex basilar artery aneurysms not amenable to intervention.


Subject(s)
Intracranial Aneurysm , Humans , Intracranial Aneurysm/surgery , Male , Female , Middle Aged , Aged , Retrospective Studies , Treatment Outcome , Neurosurgical Procedures/methods , Follow-Up Studies , Basilar Artery/surgery , Adult
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