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1.
Nutr Hosp ; 2024 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-38666338

RESUMO

INTRODUCTION: to explore the effect of individualized nutritional intervention on the nutritional status of patients with liver cancer after transcatheter arterial chemoembolization (TACE). METHODS: 56 patients who underwent TACE in our hospital from March 2022 to March 2023 were selected as the study subjects. The patients were randomly divided into a control group (28 cases) and an intervention group (28 cases). The control group received routine dietary intervention, while the intervention group received individualized nutritional intervention. We analyzed the body mass index (BMI), nutritional risk screening 2002 (NRS 2002), nutritional status, liver function status, and incidence of complications in two groups of patients before TACE, 3 days after TACE, and 1 month after TACE. RESULTS: on the third day after TACE, the nutritional related indicators of both groups of patients showed a significantly decrease compared to those before TACE (p < 0.05), while the majority of liver function indicators significantly increased (p < 0.05). Compared with those at 3 days after TACE, the nutritional status of the intervention group patients significantly improved (p < 0.05) and liver function indicators significantly decreased (p < 0.05) 1 month after TACE. 1 month after TACE, all nutritional indicators in the intervention group were significantly higher than those in the control group (p < 0.05), and AST was significantly lower than that in the control group (p < 0.05). The incidence of gastrointestinal complications and electrolyte disorders in the intervention group were significantly lower than that in the control group (p < 0.05). Conclusion Individualized nutritional intervention can effectively improve nutritional status, improve liver function, and reduce the incidence of postoperative complications in liver cancer patients after TACE. It was worth promoting.

2.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 32(2): 505-511, 2024 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-38660859

RESUMO

OBJECTIVE: To analyze the effect of recombinant human thrombopoietin (rhTPO) on platelet (PLT) reconstitution after autologous peripheral blood stem cell transplantation (APBSCT) in patients with multiple myeloma (MM). METHODS: The clinical data of 147 MM patients who were diagnosed in the First Affiliated Hospital of Soochow University and received APBSCT as the first-line therapy were retrospectively analyzed. According to whether rhTPO was used during APBSCT, the patients were divided into rhTPO group (80 cases) and control group (67 cases). The time of PLT engraftment, blood product infusion requirements, the proportion of patients with PLT recovery to≥50×109/L and≥100×109/L at +14 days and +100 days after transplantation, and adverse reactions including the incidence of bleeding were compared between the two groups. RESULTS: There were no significant differences between the two groups in sex, age, M protein type, PLT count at the initial diagnosis, median duration of induction therapy before APBSCT, and number of CD34+ cells reinfused (all P >0.05). The median time of PLT engraftment in the rhTPO group was 10 (6-14) days, which was shorter than 11 (8-23) days in the control group (P < 0.001). The median PLT transfusion requirement in the rhTPO group during APBSCT was 15(0-50)U, which was less than 20 (0-80)U in the control group (P =0.001). At +14 days after transplantation, the proportions of patients with PLT≥50×109/L in the rhTPO group and the control group were 66.3% and 52.2%, while the proportions of patients with PLT≥100×109/L were 23.8% and 11.9%, respectively, with no significant differences (all P >0.05). At +100 days after transplantation, the proportion of patients with PLT≥50×109/L in rhTPO group and control group was 96.3% and 89.6%, respectively (P >0.05), but the proportion of patients with PLT≥100×109/L in rhTPO group was higher than that in control group (75.0% vs 55.2%, P =0.012). There was no difference in the overall incidence of bleeding events in different locations during period of low PLT level of patients between the two groups. In rhTPO group, the rhTPO administration was well tolerated, and the incidences of abnormal liver and kidney function and infection were similar to those in the control group. CONCLUSION: When MM patients undergo first-line APBSCT, subcutaneous injection of rhTPO can shorten the time of platelet engraftment, reduce the transfusion volume of blood products, and be well tolerated, moreover, more patients have achieve a high level of PLT recovery after transplantation, which is very important for ensuring the safety of APBSCT and maintenance therapy.


Assuntos
Mieloma Múltiplo , Transplante de Células-Tronco de Sangue Periférico , Proteínas Recombinantes , Trombopoetina , Transplante Autólogo , Humanos , Mieloma Múltiplo/terapia , Proteínas Recombinantes/administração & dosagem , Plaquetas , Contagem de Plaquetas , Masculino , Feminino
3.
Ecotoxicol Environ Saf ; 277: 116399, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38677070

RESUMO

Perfluoroalkyl and polyfluoroalkyl substances (PFASs), as pollutants, can cause palpable environmental and health impacts around the world, as endocrine disruptors, can disrupt endocrine homeostasis and increase the risk of diseases. Chlorinated polyfluoroalkyl ether sulfonate (F-53B), as a substitute for PFAS, was determined to have potential toxicity. Puberty is the stage when sexual organs develop and hormones change dramatically, and abnormal uterine development can increase the risk of uterine lesions and lead to infertility. This study was designed to explore the impact of F-53B on uterine development during puberty. Four-week-old female SD rats were exposed to 0.125 and 6.25 mg/L F-53B during puberty. The results showed that F-53B interfered with growth and sex hormone levels and bound to oestrogen-related receptors, which affected their function, contributed to the accumulation of reactive oxygen species, promoted cell apoptosis and inhibited cell proliferation, ultimately causing uterine dysplasia.


Assuntos
Apoptose , Disruptores Endócrinos , Ratos Sprague-Dawley , Espécies Reativas de Oxigênio , Maturidade Sexual , Útero , Animais , Feminino , Útero/efeitos dos fármacos , Apoptose/efeitos dos fármacos , Ratos , Espécies Reativas de Oxigênio/metabolismo , Disruptores Endócrinos/toxicidade , Maturidade Sexual/efeitos dos fármacos , Fluorocarbonos/toxicidade , Proliferação de Células/efeitos dos fármacos , Poluentes Ambientais/toxicidade , Receptores de Estrogênio/metabolismo
4.
Artigo em Inglês | MEDLINE | ID: mdl-38551603

RESUMO

BACKGROUND: Jianxin (JX) granules is a traditional Chinese medicine widely used in the treatment of heart failure (HF), but the mechanism is unclear. This study aimed to investigate the mechanism of JX granules in the treatment of HF based on network pharmacology analysis and in-vivo experiments. METHODS: A series of network pharmacology methods was employed to ascertain potential targets and critical pathways implicated in the therapeutic action of JX granules against HF. Subsequently, molecular docking was utilized to investigate the binding affinity of key active constituents within JX granules to these targets. In-vivo experiments, echocardiography, hematoxylin and eosin, Masson's trichrome assay, and western blot analysis were conducted to validate the efficacy and mechanism of JX granules in treating rats with HF. RESULTS: A total of 122 active components, 896 drug targets, 1216 HF-related targets, and 136 targets pertinent to drug-disease interactions were identified. 151 key targets and 725 core clusters were detected through protein-protein interaction network analysis. Among these, interleukin 6 (IL-6), vascular endothelial growth factor a (VEGFA), and serine/threonine kinase 1 (AKT1) were core hub genes. Kyoto encyclopedia of genes and genomes (KEGG) enrichment analysis revealed the critical pathways, including epidermal growth factor receptor (EGFR), advanced glycation end products (AGEs) and their receptors (RAGE) pathway, along with hypoxia-inducible factor 1 (HIF-1) signaling pathway. Molecular docking studies demonstrated high binding affinities between key targets and the pivotal active ingredients of Danshenol A, salvianolic acid B, and arachidonic acid. Furthermore, animal studies corroborated that JX granules improve cardiac function and reduce myocardial fibrosis, potentially by modulating the expression of IL-6, VEGFA, and p-AKT1. CONCLUSIONS: The bioactive components within JX granules, such as Danshenol A, salvianolic acid B, and arachidonic acid may exert therapeutic effects on HF through modulation of IL-6, VEGFA, and AKT1 gene expression. This study provides a scientific basis for subsequent clinical application of JX granules and an in-depth investigation of their mechanisms of action.

5.
Am J Clin Oncol ; 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38488761

RESUMO

PURPOSE: To analyze the risk factors for grade ≥2 ARE in patients with cervical cancer receiving concurrent chemoradiotherapy. METHODS: A total of 273 patients with cervical cancer receiving concurrent chemoradiotherapy at our hospital were retrospectively enrolled. The patients were divided into training and validation groups. Clinical parameters were analyzed using univariate analysis and multivariate logistic regression analysis. A nomogram model was established based on the independent risk factors selected using multivariate logistic regression. The areas under the receiver operating characteristic (ROC) curve, calibration curve, and decision curve analysis (DCA) were used to evaluate the nomogram. The patients were divided into low-score and high-score groups based on the scores calculated using the nomogram model and compared. RESULTS: Malnutrition, monocyte-lymphocyte ratio ≥0.82 after radiotherapy, platelet-lymphocyte ratio <307.50 after radiotherapy, and bowelbag volume receiving at least 5 and 40 Gy were independent risk factors for grade ≥2 ARE and were incorporated into the nomogram ( P <0.05). The ROC curve, calibration curve, and DCA suggested that the nomogram had good discrimination, concordance, and net benefit in the clinical. A medium nomogram score of 146.50 points was used as the cutoff point, and the incidence of grade ≥2 ARE in the high-score group was higher than that in the low-score group ( P <0.05). CONCLUSION: The nomogram model for grade ≥2 ARE has good predictive ability and clinical utility, and is convenient for clinicians to identify high-risk groups and develop early prevention and treatment strategies.

6.
Int J Pharm ; 654: 123968, 2024 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-38460771

RESUMO

Wound healing constitutes a formidable challenge within the healthcare system, attributable to infection risks and protracted recovery periods. The pressing need for innovative wound healing methods has spurred the urgency to develop novel approaches. This study sought to advance wound healing by introducing a novel approach employing a composite sponge dressing. The composite sponge dressing, derived from LFL-ZnO (synthesized through the green methodology utilizing Lactobacillus plantarum ZDY2013 fermentation liquid), polyvinyl alcohol (PVA), and sodium alginate (SA) via a freeze-thaw cycle and freeze-drying molding process, demonstrated notable properties. The findings elucidate the commendable swelling, moisturizing, and mechanical attributes of the SA/LFL-ZnO/PVA composite sponge dressing, characterized by a porous structure. Remarkably, the dressing incorporating LFL-ZnO exhibited substantial inhibition against both methicillin-resistant Staphylococcus aureus (MRSA) and Staphylococcus aureus (S. aureus). Hemolysis and cytotoxicity tests corroborated the excellent biocompatibility of the sponge dressing. In vivo evaluation of the therapeutic efficacy of the 1 mg/mL LFL-ZnO composite dressing on scald wounds and S. aureus-infected wounds revealed its capacity to accelerate wound healing and exert pronounced antibacterial effects. Consequently, the composite sponge dressings synthesized in this study hold significant potential for application in wound treatment.


Assuntos
Staphylococcus aureus Resistente à Meticilina , Óxido de Zinco , Álcool de Polivinil/química , Óxido de Zinco/química , Staphylococcus aureus , Alginatos/química , Bandagens/microbiologia , Antibacterianos/farmacologia , Antibacterianos/química , Hidrogéis/química , Cicatrização
7.
Adv Sci (Weinh) ; 11(18): e2309984, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38430531

RESUMO

The induction of cuproptosis, a recently identified form of copper-dependent immunogenic cell death, is a promising approach for antitumor therapy. However, sufficient accumulation of intracellular copper ions (Cu2+) in tumor cells is essential for inducing cuproptosis. Herein, an intelligent cuproptosis-inducing nanosystem is constructed by encapsulating copper oxide (CuO) nanoparticles with the copper ionophore elesclomol (ES). After uptake by tumor cells, ES@CuO is degraded to release Cu2+ and ES to synergistically trigger cuproptosis, thereby significantly inhibiting the tumor growth of murine B16 melanoma cells. Moreover, ES@CuO further promoted cuproptosis-mediated immune responses and reprogrammed the immunosuppressive tumor microenvironment by increasing the number of tumor-infiltrating lymphocytes and secreted inflammatory cytokines. Additionally, combining ES@CuO with programmed cell death-1 (PD-1) immunotherapy substantially increased the antitumor efficacy in murine melanoma. Overall, the findings of this study can lead to the use of a novel strategy for cuproptosis-mediated antitumor therapy, which may enhance the efficacy of immune checkpoint inhibitor therapy.


Assuntos
Cobre , Imunoterapia , Melanoma Experimental , Animais , Camundongos , Imunoterapia/métodos , Cobre/química , Melanoma Experimental/tratamento farmacológico , Melanoma Experimental/imunologia , Modelos Animais de Doenças , Microambiente Tumoral/efeitos dos fármacos , Microambiente Tumoral/imunologia , Camundongos Endogâmicos C57BL , Linhagem Celular Tumoral , Clorofilídeos , Nanopartículas/química
8.
Int J Surg ; 110(2): 1068-1078, 2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-37924501

RESUMO

AIM: This paper aimed to explore the application of three-dimensional (3D) printing in cardiovascular diseases, to reach an insight in this field and prospect the future trend. METHODS: The articles were selected from the Web of Science Core Collection database. Excel 2019, VOSviewer 1.6.16, and CiteSpace 6.1.R6 were used to analyze the information. RESULTS: A total of 467 papers of 3D printing in cardiovascular diseases were identified, and the first included literature appeared in 2000. A total of 692 institutions from 52 countries participated in the relevant research, while the United States of America contributed to 160 articles and were in a leading position. The most productive institution was Curtin University , and Zhonghua Sun who has posted the most articles ( n =8) was also from there. The Frontiers in Cardiovascular Medicine published most papers ( n =25). The Journal of Thoracic and Cardiovascular Surgery coveted the most citations ( n =520). Related topics of frontiers will still focus on congenital heart disease, valvular heart disease, and left atrial appendage closure. CONCLUSIONS: The authors summarized the publication information of the application of 3D printing in cardiovascular diseases related literature from 2000 to 2023, including country and institution of origin, authors, and publication journal. This study can reflect the current hotspots and novel directions for the application of 3D printing in cardiovascular diseases.


Assuntos
Doenças Cardiovasculares , Humanos , Doenças Cardiovasculares/cirurgia , Bibliometria , Impressão Tridimensional , Bases de Dados Factuais , Instalações de Saúde
9.
Cytokine ; 173: 156415, 2024 01.
Artigo em Inglês | MEDLINE | ID: mdl-37952311

RESUMO

BACKGROUND: Endothelial nitric oxide (NO) produced by endothelial Nitric Oxide Synthase (eNOS) can promote the expression of pro-angiogenic cytokines and is favorable for angiogenesis. However, the relationship between NOS3 gene polymorphisms and genetic susceptibility to congenital heart disease (CHD) was still unclear. METHODS: We searched five databases including Pubmed, Cochrane Library, Embase, Web of Science, CNKI, and Wan Fang, to find all studies on NOS3 gene polymorphisms and CHD. Rstudio was used to merge the data included in the study to obtain OR, 95%CI, and forest plots. RESULTS: Five relevant literatures were included, including three sites of NOS3 gene, rs1799983 (G894T), rs2070744 (T-786C), and rs7830 (G10T). Several models including the homozygous model of rs1799983 (G894T) gene polymorphism (TT VS GG: OR = 1.602, 95%CI: 1.098 âˆ¼ 2.337, P = 0.027), rs7830 (G10T) gene polymorphism allele model (A VS C: OR = 1.171, 95%CI: 1.029 âˆ¼ 1.333, P = 0.017), homozygous model (AA VS CC: OR = 1.474, 95%CI: 1.122 âˆ¼ 1.936, P = 0.005) and implicit model (AA VS CC + AC: OR = 1.451, 95%CI: 1.133 âˆ¼ 1.859, P = 0.003) indicated that there was a correlation. The results of the combined analysis of each gene model of rs2070744 (T-786C) gene polymorphism sites were not statistically significant, and their P values were all>0.05. CONCLUSION: rs1799983 (G894T) and rs7830 (G10T) polymorphic sites might play a role in the susceptibility of sporadic congenital heart disease and increase the risk of CHD. Yet, it is still necessary to expand the sample size and conduct more prospective/retrospective studies to confirm whether the rs2070744 (T-786C) polymorphism tended to increase the incidence of CHD.


Assuntos
Cardiopatias Congênitas , Óxido Nítrico Sintase Tipo III , Humanos , Óxido Nítrico Sintase Tipo III/genética , Estudos Retrospectivos , Estudos Prospectivos , Polimorfismo Genético , Predisposição Genética para Doença , Estudos de Casos e Controles , Cardiopatias Congênitas/genética , Polimorfismo de Nucleotídeo Único/genética , Genótipo
11.
Int J Mol Sci ; 24(17)2023 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-37686229

RESUMO

Cyclophosphamide causes side effects in cancer patients, including hepatotoxicity. Probiotics have recently emerged as potential approaches for the administration of many diseases. This study aimed to evaluate the protective effects of Lactiplantibacillus plantarum P101 against cyclophosphamide-induced liver injury and elucidate the underlying mechanism. In this study, Lactiplantibacillus plantarum P101 or Lactobacillus rhamnosus GG were pre-administered to mice with varying duration (1 week, 2 weeks, and 3 weeks) before being intraperitoneally injected with cyclophosphamide at a dose of 30 mg/kg/day for 7 days to induce liver injury. Results demonstrated that cyclophosphamide-induced liver injury was characterized by histopathological disorders, including irregular central venous shape and hepatic vascular rupture, as well as a severe inflammation response and oxidative stress. The administration of probiotics for 3 weeks exerted the most significant improvements in alleviating liver injury, oxidative stress, and inflammation when compared to the shorter intervention duration. Notably, Lactiplantibacillus plantarum P101 exhibited more pronounced effects than Lactobacillus rhamnosus GG. Furthermore, Lactiplantibacillus plantarum P101 enhanced the antioxidant defense system by activating the Nrf2/ARE signaling pathway, ultimately alleviating hepatotoxicity and hepatocyte apoptosis. In conclusion, this study highlighted the potential of Lactiplantibacillus plantarum P101 to alleviate cyclophosphamide-induced hepatotoxicity.


Assuntos
Doença Hepática Crônica Induzida por Substâncias e Drogas , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Lacticaseibacillus rhamnosus , Animais , Camundongos , Ciclofosfamida/toxicidade , Inflamação , Fator 2 Relacionado a NF-E2 , Transdução de Sinais
12.
Front Oncol ; 13: 1216446, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37583930

RESUMO

Background: Breast cancer (BC) is the most common cancer in women and is highly heterogeneous. BC can be classified into four molecular subtypes based on the status of estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2) and proliferation marker protein Ki-67. However, they can only be obtained by biopsy or surgery, which is invasive. Radiomics can noninvasively predict molecular expression via extracting the image features. Nevertheless, there is a scarcity of data available regarding the prediction of molecular biomarker expression using ultrasound (US) images in BC. Objectives: To investigate the prediction performance of US radiomics for the assessment of molecular profiling in BC. Methods: A total of 342 patients with BC who underwent preoperative US examination between January 2013 and December 2021 were retrospectively included. They were confirmed by pathology and molecular subtype analysis of ER, PR, HER2 and Ki-67. The radiomics features were extracted and four molecular models were constructed through support vector machine (SVM). Pearson correlation coefficient heatmaps are employed to analyze the relationship between selected features and their predictive power on molecular expression. The receiver operating characteristic curve was used for the prediction performance of US radiomics in the assessment of molecular profiling. Results: 359 lesions with 129 ER- and 230 ER+, 163 PR- and 196 PR+, 265 HER2- and 94 HER2+, 114 Ki-67- and 245 Ki-67+ expression were included. 1314 features were extracted from each ultrasound image. And there was a significant difference of some specific radiomics features between the molecule positive and negative groups. Multiple features demonstrated significant association with molecular biomarkers. The area under curves (AUCs) were 0.917, 0.835, 0.771, and 0.896 in the training set, while 0.868, 0.811, 0.722, and 0.706 in the validation set to predict ER, PR, HER2, and Ki-67 expression respectively. Conclusion: Ultrasound-based radiomics provides a promising method for predicting molecular biomarker expression of ER, PR, HER2, and Ki-67 in BC.

13.
Sensors (Basel) ; 23(12)2023 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-37420582

RESUMO

The von Neumann architecture with separate memory and processing presents a serious challenge in terms of device integration, power consumption, and real-time information processing. Inspired by the human brain that has highly parallel computing and adaptive learning capabilities, memtransistors are proposed to be developed in order to meet the requirement of artificial intelligence, which can continuously sense the objects, store and process the complex signal, and demonstrate an "all-in-one" low power array. The channel materials of memtransistors include a range of materials, such as two-dimensional (2D) materials, graphene, black phosphorus (BP), carbon nanotubes (CNT), and indium gallium zinc oxide (IGZO). Ferroelectric materials such as P(VDF-TrFE), chalcogenide (PZT), HfxZr1-xO2(HZO), In2Se3, and the electrolyte ion are used as the gate dielectric to mediate artificial synapses. In this review, emergent technology using memtransistors with different materials, diverse device fabrications to improve the integrated storage, and the calculation performance are demonstrated. The different neuromorphic behaviors and the corresponding mechanisms in various materials including organic materials and semiconductor materials are analyzed. Finally, the current challenges and future perspectives for the development of memtransistors in neuromorphic system applications are presented.


Assuntos
Inteligência Artificial , Nanotubos de Carbono , Humanos , Encéfalo
14.
Biomol Biomed ; 23(6): 1118-1124, 2023 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-37485959

RESUMO

Elevated lactate levels are common in sepsis patients. This study aimed to assess the effect of dynamic changes in lactate levels within the first 24 hours following admission on patient prognosis. We extracted data from the Medical Information Mart for Intensive Care (MIMIC)-IV database and classified patients using latent class growth analysis (LCGA). This analysis classified sepsis patients into different groups based on dynamic changes in lactate levels during the initial 24 hours post-admission, dividing this time frame into four periods (0-3 h, 3-6 h, 6-12 h, and 12-24 h). The highest lactate level recorded in each period was then used for patient classification. We subsequently compared the baseline characteristics and outcomes between these different groups. Our study encompassed 7,830 patients, whom LCGA successfully divided into two classes: class 1 (steady lactate class) and class 2 (increasing lactate class). Class 2 demonstrated a worse clinical status at baseline, as indicated by vital signs, disease severity scores, and laboratory results. Importantly, class 2 also had a significantly higher 28-day mortality rate than class 1 (55.6% vs 13.5%, P < 0.001). In conclusion, LCGA effectively categorized sepsis patients into two distinct groups based on their dynamic changes in lactate levels during the first 24 hours post-admission. This methodology has potential utility in clinical practice for managing sepsis patients.


Assuntos
Sepse , Humanos , Prognóstico , Estudos Retrospectivos , Ácido Láctico , Cuidados Críticos
15.
Front Oncol ; 13: 1036458, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37434983

RESUMO

Background: Metabolic syndrome (MetS) is associated with poor prognosis in many cancers. However, the relationship between metabolic syndrome and overall survival (OS) in patients with colorectal cancer (CRC) remains unclear. We aimed to comprehensively analyze whether MetS could affect postoperative complications and long-term survival in patients with CRC. Methods: We included patients who underwent CRC resection at our center between January 2016 and December 2018. Bias was reduced through propensity score matching analysis. Patients with CRC were divided into the MetS and non-MetS groups based on whether they had MetS. Univariate and multivariate analyses were used to identify risk factors affecting OS. Results: We included 268 patients; among them, 120 were included for further analysis after propensity score matching. There were no significant between-group differences in the clinicopathological features after matching. Compared with the non-MetS group, the MetS group had a shorter OS (P = 0.027); however, there was no significant between-group difference in postoperative complications. Multivariate analysis revealed that MetS (hazard ratio [HR] = 1.997, P = 0.042), tumor-node-metastasis stage (HR = 2.422, P = 0.003), and intestinal obstruction (HR = 2.761, P = 0.010) were independent risk factors for OS. Conclusions: MetS affects the long-term survival of patients with CRC without affecting postoperative complications.

16.
ACS Nano ; 17(14): 13917-13937, 2023 07 25.
Artigo em Inglês | MEDLINE | ID: mdl-37429012

RESUMO

Inflammatory infiltration and bone destruction are important pathological features of rheumatoid arthritis (RA), which originate from the disturbed niche of macrophages. Here, we identified a niche-disrupting process in RA: due to overactivation of complement, the barrier function of VSIg4+ lining macrophages is disrupted and mediates inflammatory infiltration within the joint, thereby activating excessive osteoclastogenesis and bone resorption. However, complement antagonists have poor biological applications due to superphysiologic dose requirements and inadequate effects on bone resorption. Therefore, we developed a dual-targeted therapeutic nanoplatform based on the MOF framework to achieve bone-targeted delivery of the complement inhibitor CRIg-CD59 and pH-responsive sustained release. The surface-mineralized zoledronic acid (ZA) of ZIF8@CRIg-CD59@HA@ZA targets the skeletal acidic microenvironment in RA, and the sustained release of CRIg-CD59 can recognize and prevent the complement membrane attack complex (MAC) from forming on the surface of healthy cells. Importantly, ZA can inhibit osteoclast-mediated bone resorption, and CRIg-CD59 can promote the repair of the VSIg4+ lining macrophage barrier to achieve sequential niche remodeling. This combination therapy is expected to treat RA by reversing the core pathological process, circumventing the pitfalls of traditional therapy.


Assuntos
Artrite Reumatoide , Reabsorção Óssea , Estruturas Metalorgânicas , Humanos , Estruturas Metalorgânicas/farmacologia , Preparações de Ação Retardada/farmacologia , Macrófagos/patologia , Osteoclastos/patologia , Ácido Zoledrônico/farmacologia
17.
Cardiovasc Res ; 119(9): 1811-1824, 2023 08 07.
Artigo em Inglês | MEDLINE | ID: mdl-37279540

RESUMO

AIMS: Chemoattractants and their cognate receptors are essential for leucocyte recruitment during atherogenesis, and atherosclerotic plaques preferentially occur at predilection sites of the arterial wall with disturbed flow (d-flow). In profiling the endothelial expression of atypical chemoattractant receptors (ACKRs), we found that Ackr5 (CCRL2) was up-regulated in an endothelial subpopulation by atherosclerotic stimulation. We therefore investigated the role of CCRL2 and its ligand chemerin in atherosclerosis and the underlying mechanism. METHODS AND RESULTS: By analysing scRNA-seq data of the left carotid artery under d-flow and scRNA-seq datasets GSE131776 of ApoE-/- mice from the Gene Expression Omnibus database, we found that CCRL2 was up-regulated in one subpopulation of endothelial cells in response to d-flow stimulation and atherosclerosis. Using CCRL2-/-ApoE-/- mice, we showed that CCRL2 deficiency protected against plaque formation primarily in the d-flow areas of the aortic arch in ApoE-/- mice fed high-fat diet. Disturbed flow induced the expression of vascular endothelial CCRL2, recruiting chemerin, which caused leucocyte adhesion to the endothelium. Surprisingly, instead of binding to monocytic CMKLR1, chemerin was found to activate ß2 integrin, enhancing ERK1/2 phosphorylation and monocyte adhesion. Moreover, chemerin was found to have protein disulfide isomerase-like enzymatic activity, which was responsible for the interaction of chemerin with ß2 integrin, as identified by a Di-E-GSSG assay and a proximity ligation assay. For clinical relevance, relatively high serum levels of chemerin were found in patients with acute atherothrombotic stroke compared to healthy individuals. CONCLUSIONS: Our findings indicate that d-flow-induced CCRL2 promotes atherosclerotic plaque formation via a novel CCRL2-chemerin-ß2 integrin axis, providing potential targets for the prevention or therapeutic intervention of atherosclerosis.


Assuntos
Aterosclerose , Antígenos CD18 , Placa Aterosclerótica , Animais , Camundongos , Aterosclerose/genética , Aterosclerose/metabolismo , Antígenos CD18/metabolismo , Quimiocinas/metabolismo , Células Endoteliais/metabolismo , Endotélio Vascular/metabolismo , Peptídeos e Proteínas de Sinalização Intercelular/genética , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Camundongos Knockout para ApoE , Monócitos/metabolismo , Placa Aterosclerótica/metabolismo
18.
Int J Surg ; 109(7): 2082-2095, 2023 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-37300887

RESUMO

BACKGROUND: Uncertainties persist about whether to aggressively and effectively treat tricuspid regurgitation (TR) during mitral valve (MV) surgery. REVIEW METHODS: Systematic literature searches were performed in five databases to collect all relevant studies published before May 2022 on whether the tricuspid valve was treated during MV surgery. Separate meta-analyses were performed on data from unmatched studies and randomized controlled trials (RCT)/adjusted studies. MAIN RESULTS: A total of 44 publications were included, of which eight were RCT studies and the rest were retrospective studies. There was no difference in 30-day mortality [odds ratio (OR): 1.00, 95% CI: 0.71-1.42, OR: 0.66, 95% CI: 0.30-1.41)] or overall survival [hazard ratio (HR): 1.01, 95% CI: 0.85-1.19, HR: 0.77, 95% CI: 0.52-1.14] in unmatched studies and RCT/adjusted studies. Late mortality (OR: 0.37, 95% CI: 0.21-0.64) and cardiac-related mortality (OR: 0.36, 95% CI: 0.21-0.62) were lower in the tricuspid valve repair (TVR) group in the RCT/adjusted studies. In the unmatched studies, overall cardiac mortality (OR: 0.48, 95% CI: 0.26-0.88) was lower in the TVR group. In the late TR progression analysis, the late TR progression was lower among patients in the concomitantly intervened tricuspid group, and patients in the untreated tricuspid group were prone to TR progression in both studies (HR: 0.30, 95% CI: 0.22-0.41, HR: 0.37, 95% CI: 0.23-0.58). CONCLUSIONS: TVR concomitant with MV surgery is most effective in patients with significant TR and dilated tricuspid annulus, especially those with a significantly reduced risk of distant TR progression.


Assuntos
Implante de Prótese de Valva Cardíaca , Insuficiência da Valva Mitral , Insuficiência da Valva Tricúspide , Humanos , Valva Tricúspide/cirurgia , Valva Mitral/cirurgia , Insuficiência da Valva Mitral/complicações , Insuficiência da Valva Mitral/cirurgia , Resultado do Tratamento , Implante de Prótese de Valva Cardíaca/efeitos adversos , Insuficiência da Valva Tricúspide/cirurgia , Insuficiência da Valva Tricúspide/complicações , Estudos Retrospectivos
19.
Cancer Sci ; 114(8): 3396-3410, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37290894

RESUMO

Gastric cancer (GC) has high rates of morbidity and mortality, and this phenomenon is particularly evident in coastal regions where local dietary habits favor the consumption of pickled foods such as salted fish and vegetables. In addition, the diagnosis rate of GC remains low due to the lack of diagnostic serum biomarkers. Therefore, in this study, we aimed to identify potential serum GC biomarkers for use in clinical practice. To identify candidate biomarkers of GC, 88 serum samples were first screened using a high-throughput protein microarray to measure the levels of 640 proteins. Then, 333 samples were used to validate the potential biomarkers using a custom antibody chip. ELISA, western blot, and immunohistochemistry were then used to verify the expression of the target proteins. Finally, logistic regression was performed to select serum proteins for the diagnostic model. As a result, five specific differentially expressed proteins, TGFß RIII, LAG-3, carboxypeptidase A2, Decorin and ANGPTL3, were found to have the ability to distinguish GC. Logistic regression analysis showed that the combination of carboxypeptidase A2 and TGFß RIII had superior potential for diagnosing GC (area under the ROC curve [AUC] = 0.801). The results suggested that these five proteins alone and the combination of carboxypeptidase A2 and TGFß RIII may be used as serum markers for the diagnosis of GC.


Assuntos
Biomarcadores Tumorais , Neoplasias Gástricas , Humanos , Análise Serial de Proteínas , Neoplasias Gástricas/diagnóstico , Carboxipeptidases A , Detecção Precoce de Câncer , Curva ROC , Proteína 3 Semelhante a Angiopoietina
20.
Heliyon ; 9(6): e16708, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37303539

RESUMO

Background: Ventricular septal defects (VSDs) are one of the mechanical complications of acute myocardial infarction (AMI). Because of the high risks of mortality and postoperative complications, a new alternative method is needed. With the development of interventional medicine, transcatheter closure has been increasingly performed for postmyocardial infarction ventricular septal defects (PMIVSDs). The aim of this study is to explore the feasibility and safety of transcatheter closure of PMIVSDs by meta-analysis. Methods: The included studies were mainly single-arm studies of transcatheter closure of PMIVSDs. We compared VSD size, device size, preoperative risk factors and interventions among PMIVSD patients. We analysed the transcatheter closure success rate, the 30-day mortality rate, and the incidence of residual shunts. Results: A total of 12 single-arm articles (284 patients) were included. The combined incidences of preoperative hypertension, hyperlipidaemia, and diabetes were 66% [95% CI 0.56-0.75], 54% [95% CI 0.40-0.68], and 33% [95% CI] 0.21-0.46], respectively. Multiple studies reported the combined incidences of preoperative PCI, IABP, and CABG, which were 46% [95% CI 0.15-0.80], 60% [95% CI 0.44-0.75], and 8% [95% CI 0.02-0.18]. Eleven studies reported the number of successful closures and the 30-day mortality rate; the success rate was 90% [95% CI 0.86-0.94], and the 30-day mortality rate reached 27% [95% CI 0.86-0.94]. Conclusion: For patients with PMIVSD, transcatheter closure in the acute phase can be used as a rescue measure, while in the chronic phase, it is more effective and has a lower mortality rate, but the effect of selection bias should be considered. Residual shunts are a long-term complication that have a high incidence and long-lasting effects on patients. More large, multicentre, randomized controlled trials are needed in the future to confirm the safety and reliability of transcatheter closure of PMIVSDs.

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