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1.
Oncol Res ; 32(4): 659-678, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38560572

RESUMO

Background: IQGAP3 plays a crucial role in regulating cell proliferation, division, and cytoskeletal organization. Abnormal expression of IQGAP3 has been linked to various tumors, but its function in glioma is not well understood. Methods: Various methods, including genetic differential analysis, single-cell analysis, ROC curve analysis, Cox regression, Kaplan-Meier analysis, and enrichment analysis, were employed to analyze the expression patterns, diagnostic potential, prognostic implications, and biological processes involving IQGAP3 in normal and tumor tissues. The impact of IQGAP3 on immune infiltration and the immune microenvironment in gliomas was evaluated using immunofluorescence. Additionally, the cBioPortal database was used to analyze copy number variations and mutation sites of IQGAP3. Experimental validation was also performed to assess the effects of IQGAP3 on glioma cells and explore underlying mechanisms. Results: High IQGAP3 expression in gliomas is associated with an unfavorable prognosis, particularly in wild-type IDH and 1p/19q non-codeleted gliomas. Enrichment analysis revealed that IQGAP3 is involved in regulating the cell cycle, PI3K/AKT signaling, p53 signaling, and PLK1-related pathways. Furthermore, IQGAP3 expression may be closely related to the immunosuppressive microenvironment of glioblastoma. BRD-K88742110 and LY-303511 are potential drugs for targeting IQGAP3 in anti-glioma therapy. In vitro experiments showed that downregulation of IQGAP3 inhibits the proliferation and migration of glioma cells, with the PLK1/PI3K/AKT pathway potentially playing a crucial role in IQGAP3-mediated glioma progression. Conclusion: IQGAP3 shows promise as a valuable biomarker for diagnosis, prognosis, and immunotherapeutic strategies in gliomas.


Assuntos
Neoplasias Encefálicas , Glioma , Humanos , Prognóstico , Neoplasias Encefálicas/patologia , Variações do Número de Cópias de DNA , Fosfatidilinositol 3-Quinases/genética , Proteínas Proto-Oncogênicas c-akt/genética , Glioma/patologia , Microambiente Tumoral/genética , Proteínas Ativadoras de GTPase
2.
Environ Toxicol Chem ; 2024 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-38563658

RESUMO

The microplastics (MPs) formed by broken plastic film may migrate in the soil under drip irrigation. To investigate the migration distribution of MPs in desert farmland soil under drip irrigation conditions, our study was conducted on farmland in Xinjiang (China). A MP drip irrigation penetration migration testing device was set up in combination with Xinjiang farmland irrigation methods to conduct a migration simulation experiment. The results showed that the migration amount of MPs in soil was significantly positively correlated with the amount of drip irrigation, and significantly negatively correlated with the soil depth; in addition, the relationship between the migration amount of MPs in different types of soil was: clay < sandy loam < sandy soil. Under drip irrigation conditions, the migration rates of MPs were 30.51%, 19.41%, and 10.29% in sandy soil, sandy loam soil, and clay, respectively. The migration ability of these three particle sizes of polyethylene MPs in soil was ranked as follows: 25 to 147 µm > 0 to 25 µm > 147 to 250 µm. When the drip irrigation volume was 2.6 to 3.2 L, horizontal migration distances of MPs exceeded 5 cm, and vertical migration distances reached more than 30 cm. Our findings provide reference data for the study of soil MP migration. Environ Toxicol Chem 2024;00:1-10. © 2024 SETAC.

3.
Heliyon ; 10(7): e28889, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38596088

RESUMO

Background: Mild depression is not just a mental disease, but also a serious and long-term public health issue. It affects the quality of life of patients and can quickly develop into major depression. There are currently no effective drug treatments with high efficacy and few adverse reactions. Acupuncture may be an alternative treatment option. Preliminary experiments and practices have demonstrated that "Tiaoshen" acupuncture improves symptoms in patients who have depression, however the underlying data and method remain unclear at present. Methods: This is a prospective, single-center, single-blind, randomized controlled trial. We plan to recruit 70 participants and randomly assign them to receive "Tiaoshen" acupuncture or traditional acupuncture at a ratio of 1:1. Then, all the participants will receive the appropriate acupuncture treatment for four weeks. The results of the Hamilton Depression Rating Scale (HDSR-24) will serve as the primary outcome, while the results of the Patient Health Questionnaire-9 (PHQ-9) and the World Health Organization Quality of Life Brief Version (WHOQOL-BREF) will serve as secondary outcomes. Evaluations will be conducted at baseline, 1, 2, and 4 weeks after treatment initiation, and 1 and 3 months after treatment completion. The safety of the intervention will be evaluated every week using the Columbia-Suicide Severity Rating Scale (C-SSRS) and the Treatment Emergent Symptoms Scale (TESS). Serum levels of oxidative stress markers 8-iso-prostaglandin F2α (8-iso-PGF2α), superoxide dismutase (SOD), uric acid (UA), and total bilirubin (TBIL) will be measured at baseline and the end of the treatment. We will conduct a statistical analysis of intention to treat (ITT) and conformance to protocol set (PPS) data. Discussion: This research aims to provide high-quality evidence for the efficacy and safety of "Tiaoshen" acupuncture as a treatment for mild depression. In addition, the mechanism through which acupuncture heals mild depression will be investigated.

4.
Toxicol Mech Methods ; : 1-9, 2024 Apr 04.
Artigo em Inglês | MEDLINE | ID: mdl-38572673

RESUMO

The protective effect of isoflurane on cardiomyocyte ischemia/reperfusion injury (I/RI) was explored in hypoxia and reoxygenation (H/R) induced cardiomyocyte injury model. In terms of mechanism, the participation of long non-coding RNA CASC15/microR-542-3p axis was further discussed. H9c2 cells received H/R treatment to mimic myocardial I/RI. RT-qPCR was performed to quantify mRNA levels. Cell viability and apoptosis were evaluated after isoflurane pretreatment and cell transfection. ELISA was performed to measure the concentrations of inflammatory/oxidative stress-related cytokines (TNF-α, IL-6, MDA, SOD). The target relationship between CASC12 and miR-542-3p was determined via dual-luciferase reporter assay. Isoflurane pretreatment alleviated H/R-induced cell viability suppression and cell apoptosis promotion, which was accompanied by CASC15 downregulation. CASC15 overexpression abolished the influence of isoflurane on cardiomyocytes' viability and apoptosis. H/R-induced excessive release of TNF-α and IL-6 was hold down by isoflurane, which was re-activated after CASC15 overexpression. The concentration changes of both MDA and SOD by isoflurane were reversed by CASC15 overexpression. CASC15 functioned as miR-542-3p sponger, and miR-542-3p overexpression attenuated the effect of isoflurane and CASC15 on H/R-induced cardiac I/RI. Isoflurane pretreatment was beneficial for the alleviation of cardiac I/RI by inhibiting oxidative stress and myocardial inflammatory response. CASC15/miR-542-3p axis was required for isoflurane to exhibit its protective activity against cardiac I/RI.

5.
Front Oncol ; 14: 1345288, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38577330

RESUMO

Background: In patients with pulmonary nodules undergoing computed tomography (CT)-guided localization procedures, a range of liquid-based materials have been employed to date in an effort to guide video-assisted thoracoscopic surgery (VATS) procedures to resect target nodules. However, the relative performance of these different liquid-based localization strategies has yet to be systematically evaluated. Accordingly, this study was developed with the aim of examining the relative safety and efficacy of CT-guided indocyanine green (IG) and blue-stained glue (BSG) PN localization. Methods: Consecutive patients with PNs undergoing CT-guided localization prior to VATS from November 2021 - April 2022 were enrolled in this study. Safety and efficacy outcomes were compared between patients in which different localization materials were used. Results: In total, localization procedures were performed with IG for 121 patients (140 PNs), while BSG was used for localization procedures for 113 patients (153 PNs). Both of these materials achieved 100% technical success rates for localization, with no significant differences between groups with respect to the duration of localization (P = 0.074) or visual analog scale scores (P = 0.787). Pneumothorax affected 8 (6.6%) and 8 (7.1%) patients in the respective IG and BSG groups (P = 0.887), while 12 (9.9%) and 10 (8.8%) patients of these patients experienced pulmonary hemorrhage. IG was less expensive than BSG ($17.2 vs. $165). VATS sublobar resection procedure technical success rates were also 100% in both groups, with no instances of conversion to thoracotomy. Conclusions: IG and BSG both offer similarly high levels of clinical safety and efficacy when applied for preoperative CT-guided PN localization, with IG being less expensive than BSG.

6.
BMC Microbiol ; 24(1): 113, 2024 Apr 04.
Artigo em Inglês | MEDLINE | ID: mdl-38575881

RESUMO

BACKGROUND: Cryptosporidium is a highly pathogenic parasite responsible for diarrhea in children worldwide. Here, the epidemiological status and genetic characteristics of Cryptosporidium in children with or without diarrhea were investigated with tracking of potential sources in Wenzhou City, China. METHODS: A total of 1032 children were recruited, 684 of whom had diarrhea and 348 without, from Yuying Children's Hospital in Wenzhou, China. Samples of stool were collected from each participant, followed by extraction of DNA, genotyping, and molecular identification of Cryptosporidium species and subtypes. RESULTS: Twenty-two of the 1032 (2.1%) children were infected with Cryptosporidium spp. with 2.5% (17/684) and 1.4% (5/348) in diarrhoeic and asymptomatic children, respectively. Four Cryptosporidium species were identified, including C. parvum (68.2%; 15/22), C. felis (13.6%; 3/22), C. viatorum (9.1%; 2/22), and C. baileyi (9.1%; 2/22). Two C. parvum subtypes named IIdA19G1 (n = 14) and IInA10 (n = 1), and one each of C. felis (XIXa) and C. viatorum (XVaA3g) subtype was found as well. CONCLUSIONS: This is the first research that identified Cryptosporidium in children of Wenzhou, China, using PCR. Identification of zoonotic C. parvum, C. felis, C. viatorum, and their subtypes indicate potential cross-species transmission of Cryptosporidium between children and animals. Additionally, the presence of C. baileyi in children suggests that this species has a wider host range than previously believed and that it possesses the capacity to infect humans.


Assuntos
Criptosporidiose , Cryptosporidium , Criança , Animais , Humanos , Cryptosporidium/genética , Criptosporidiose/epidemiologia , Criptosporidiose/parasitologia , Diarreia/epidemiologia , China/epidemiologia , Fezes/parasitologia , Genótipo , Probabilidade
7.
J Nanobiotechnology ; 22(1): 152, 2024 Apr 04.
Artigo em Inglês | MEDLINE | ID: mdl-38575979

RESUMO

Infected wound healing remains a challenging task in clinical practice due to several factors: (I) drug-resistant infections caused by various pathogens, (II) persistent inflammation that hinders tissue regeneration and (III) the ability of pathogens to persist intracellularly and evade antibiotic treatment. Microneedle patches (MNs), recognized for their effecacious and painless subcutaneous drug delivery, could greatly enhance wound healing if integrated with antibacterial functionality and tissue regenerative potential. A multifunctional agent with subcellular targeting capability and contained novel antibacterial components, upon loading onto MNs, could yield excellent therapeutic effects on wound infections. In this study, we sythesised a zeolitic imidazolate framework-8 nanoparticles (ZIF-8 NPs) loaded with low molecular weight fucoidan (Fu) and further coating by hyaluronic acid (HA), obtained a multifunctional HAZ@Fu NPs, which could hinders Methicillin-resistant Staphylococcus aureus (MRSA) growth and promotes M2 polarization in macrophages. We mixed HAZ@Fu NPs with photocrosslinked gelatin methacryloyl (GelMA) and loaded it into the tips of the MNs (HAZ@Fu MNs), administered to mice model with MRSA-infected full-thickness cutaneous wounds. MNs are able to penetrate the skin barrier, delivering HAZ@Fu NPs into the dermal layer. Since cells within infected tissues extensively express the HA receptor CD44, we also confirmed the HA endows the nanoparticles with the ability to target MRSA in subcellular level. In vitro and in vivo murine studies have demonstrated that MNs are capable of delivering HAZ@Fu NPs deep into the dermal layers. And facilitated by the HA coating, HAZ@Fu NPs could target MRSA surviving at the subcellular level. The effective components, such as zinc ions, Fu, and hyaluronic acid could sustainably released, which contributes to antibacterial activity, mitigates inflammation, promotes epithelial regeneration and fosters neovascularization. Through the RNA sequencing of macrophages post co-culture with HAZ@Fu, the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis reveals that the biological functionalities associated with wound healing could potentially be facilitated through the PI3K-Akt pathway. The results indicate that the synergistic application of HAZ@Fu NPs with biodegradable MNs may serve as a significant adjunct in the treatment of infected wounds. The intricate mechanisms driving its biological effects merit further investigation.


Assuntos
Anti-Infecciosos , Staphylococcus aureus Resistente à Meticilina , Polissacarídeos , Infecção dos Ferimentos , Camundongos , Animais , Ácido Hialurônico/farmacologia , Fosfatidilinositol 3-Quinases , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Cicatrização , Anti-Infecciosos/farmacologia , Infecção dos Ferimentos/tratamento farmacológico , Inflamação
8.
J Hazard Mater ; 470: 134245, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38603910

RESUMO

This study delved into the physiological and molecular mechanisms underlying the mitigation of cadmium (Cd) stress in the model medicinal plant Salvia miltiorrhiza through the application of ZnO quantum dots (ZnO QDs, 3.84 nm). A pot experiment was conducted, wherein S. miltiorrhiza was subjected to Cd stress for six weeks with foliar application of 100 mg/L ZnO QDs. Physiological analyses demonstrated that compared to Cd stress alone, ZnO QDs improved biomass, reduced Cd accumulation, increased the content of photosynthetic pigments (chlorophyll and carotenoids), and enhanced the levels of essential nutrient elements (Ca, Mn, and Cu) under Cd stress. Furthermore, ZnO QDs significantly lowered Cd-induced reactive oxygen species (ROS) content, including H2O2, O2-, and MDA, while enhancing the activity of antioxidant enzymes (SOD, POD, APX, and GSH-PX). Additionally, ZnO QDs promoted the biosynthesis of primary and secondary metabolites, such as total protein, soluble sugars, terpenoids, and phenols, thereby mitigating Cd stress in S. miltiorrhiza. At the molecular level, ZnO QDs were found to activate the expression of stress signal transduction-related genes, subsequently regulating the expression of downstream target genes associated with metal transport, cell wall synthesis, and secondary metabolite synthesis via transcription factors. This activation mechanism contributed to enhancing Cd tolerance in S. miltiorrhiza. In summary, these findings shed light on the mechanisms underlying the mitigation of Cd stress by ZnO QDs, offering a potential nanomaterial-based strategy for enhancing Cd tolerance in medicinal plants.


Assuntos
Cádmio , Pontos Quânticos , Espécies Reativas de Oxigênio , Salvia miltiorrhiza , Óxido de Zinco , Pontos Quânticos/química , Óxido de Zinco/química , Óxido de Zinco/toxicidade , Salvia miltiorrhiza/efeitos dos fármacos , Salvia miltiorrhiza/metabolismo , Cádmio/toxicidade , Espécies Reativas de Oxigênio/metabolismo , Estresse Fisiológico/efeitos dos fármacos , Antioxidantes/metabolismo , Regulação da Expressão Gênica de Plantas/efeitos dos fármacos
9.
Org Lett ; 26(15): 3026-3031, 2024 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-38602395

RESUMO

A series of nitrogen-bridged BODIPY oligomers were synthesized via nucleophilic aromatic substitution (SNAr) as a convenient approach. Further transformations achieved novel α,α-aryl BODIPY dimers as well as a BODIPY hexamer efficiently. These BODIPY oligomers showed good photophysical properties, such as apparent absorption and emission both in visible and near-infrared regions. Interestingly, the high air and photothermal stability, strong NIR absorption, and high photothermal conversion rates of hexamer B6 suggest potential applications in photothermal therapy.

10.
Nat Comput Sci ; 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38622347

RESUMO

Cooperation is key to prosperity in human societies. Population structure is well understood as a catalyst for cooperation, where research has focused on pairwise interactions. But cooperative behaviors are not simply dyadic, and they often involve coordinated behavior in larger groups. Here we develop a framework to study the evolution of behavioral strategies in higher-order population structures, which include pairwise and multi-way interactions. We provide an analytical treatment of when cooperation will be favored by higher-order interactions, accounting for arbitrary spatial heterogeneity and nonlinear rewards for cooperation in larger groups. Our results indicate that higher-order interactions can act to promote the evolution of cooperation across a broad range of networks, in public goods games. Higher-order interactions consistently provide an advantage for cooperation when interaction hyper-networks feature multiple conjoined communities. Our analysis provides a systematic account of how higher-order interactions modulate the evolution of prosocial traits.

11.
Sci Total Environ ; 928: 172499, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38631645

RESUMO

In this work, a novel 3D-DNA walker signal amplification strategy was designed to construct a fluorescent aptasensor for the detection of kanamycin (KAN). The aptasensor utilizes split aptamers for the synergistic recognition of KAN. The presence of KAN induces the split aptamers recombination to form the Mg2+-DNAzyme structure, which is activated by Mg2+ to drive the 3D-DNA walker process for cascading signal amplification. Employing gold nanoflowers (AuNFs) as walking substrate material increases the local DNA concentration to enhance the walker efficiency. The prepared fluorescent aptasensor achieved efficient and sensitive detection of KAN with satisfactory results in the concentration range of 1 × 10-8 - 1 × 10-3 µg/kg and the detection limit of 5.63 fg/kg. Meanwhile, the designed fluorescent aptasensor exhibited favorable specificity, anti-interference, storage stability and reproducibility, and verified the feasibility of its application in milk samples. The present work provides an effective tool for the regulation of KAN contamination in animal-derived foods with promising prospects.

12.
Int J Surg ; 2024 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-38640513

RESUMO

BACKGROUND: Decompressive craniectomy, a surgery to remove part of the skull and open the dura mater, maybe an effective treatment for controlling intracranial hypertension. It remains great interest to elucidate whether decompressive craniectomy is beneficial to intracerebral hemorrhage patients who warrant clot removal to prevent intracranial hypertension. METHODS: The trial was a prospective, pragmatic, controlled trial involving adult patients with intracerebral hemorrhage who were undergoing removal of hematoma. Intracerebral hemorrhage patients were randomly assigned at a 1:1 ratioto undergo clot removal with or without decompressive craniectomy under the monitoring of intracranial pressure. The primary outcome was the proportion of unfavorable functional outcome (modified Rankin Scale 3-6) at 3 months. Secondary outcomes included the mortality at 3 months and the occurrence of re-operation. RESULTS: A total of 102 patients were assigned to the clot removal with decompressive craniectomy group and 102 to the clot removal group. Median hematoma volume was 54.0 mL (range 30-80 mL) and median preoperative Glasgow Coma Scale was 10 (range 5-15). At 3 months, 94 patients (92.2%) in clot removal with decompressive craniectomy group and 83 patients (81.4%) in the clot removal group had unfavorable functional outcome (P=0.023). Fourteen patients (13.7%) in the clot removal with decompressive craniectomy group died versus five patients (4.9%) in the clot removal group (P=0.030). The number of patients with re-operation was similar between the clot removal with decompressive craniectomy group and clot removal group (5.9% vs. 3.9%; P=0.517). Postoperative intracranial pressure values were not significantly different between two groups and the mean values were less than 20 mmHg. CONCLUSIONS: Clot removal without decompressive craniectomy decreased the rate of modified Rankin Scale score of 3-6 and mortality in patients with intracerebral hemorrhage, compared with clot removal with decompressive craniectomy.

13.
Chemosphere ; : 142070, 2024 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-38641297

RESUMO

Calcium (Ca2+) and phosphorous (PO43-) significantly influence the form and effectiveness of nitrogen (N), however, the precise mechanisms governing the adsorption of ammonium nitrogen (NH4+-N) and nitrate nitrogen (NO3--N) are still lacking. This study employed batch adsorption experiments, charge distribution and multi-site complexation (CD-MUSIC) models and density functional theory (DFT) calculations to elucidate the mechanism by which Ca2+ and PO43- affect the adsorption of NH4+-N and NO3--N on the goethite (GT) surface. The results showed that the adsorption of NH4+-N on the GT exhibited an initial increase followed by a decrease as pH increased, peaking at a pH of 8.5. Conversely, the adsorption of NO3--N decreased with rising pH. According to the CD-MUSIC model, Ca2+ minimally affected the NH4+-N adsorption on the GT but enhanced NO3--N adsorption via electrostatic interaction, promoting the adsorption of ≡FeOH-NO3- and ≡Fe3O-NO3- species. Similarly, PO43- inhibited the adsorption of ≡FeOH-NO3- and ≡Fe3O-NO3- species. However, PO43- boosted NH4+-N adsorption by facilitating the formation of ≡Fe3O-NH4+ via electrostatic interaction and site competition. DFT calculations indicates that although bidentate phosphate (BP) was beneficial to stabilize NH4+-N than monodentate phosphate (SP), SP-NH4+ was the main adsorption configuration at pH 5.5-9.5 owing the prevalence of SP on the GT surface under site competition of NH4+-N. The results of CD-MUSIC model and DFT calculation were verified mutually, and provide novel insights into the mechanisms underlying N fixation and migration in soil.

14.
Gut Microbes ; 16(1): 2340487, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38626129

RESUMO

Obesity is becoming a major global health problem in children that can cause diseases such as type 2 diabetes and metabolic disorders, which are closely related to the gut microbiota. However, the underlying mechanism remains unclear. In this study, a significant positive correlation was observed between Prevotella copri (P. copri) and obesity in children (p = 0.003). Next, the effect of P. copri on obesity was explored by using fecal microbiota transplantation (FMT) experiment. Transplantation of P. copri. increased serum levels of fasting blood glucose (p < 0.01), insulin (p < 0.01) and interleukin-1ß (IL-1ß) (p < 0.05) in high-fat diet (HFD)-induced obese mice, but not in normal mice. Characterization of the gut microbiota indicated that P. copri reduced the relative abundance of the Akkermansia genus in mice (p < 0.01). Further analysis on bile acids (BAs) revealed that P. copri increased the primary BAs and ursodeoxycholic acid (UDCA) in HFD-induced mice (p < 0.05). This study demonstrated for the first time that P. copri has a significant positive correlation with obesity in children, and can increase fasting blood glucose and insulin levels in HFD-fed obese mice, which are related to the abundance of Akkermansia genus and bile acids.


Assuntos
Diabetes Mellitus Tipo 2 , Microbioma Gastrointestinal , Obesidade Pediátrica , Prevotella , Humanos , Criança , Animais , Camundongos , Insulina , Ácidos e Sais Biliares/farmacologia , Glicemia , Camundongos Obesos , Dieta Hiperlipídica/efeitos adversos , Camundongos Endogâmicos C57BL
15.
Artigo em Inglês | MEDLINE | ID: mdl-38606576

RESUMO

OBJECTIVE: Paragangliomas of the urinary bladder (UBPGLs) are rare neuroendocrine tumours and pose a diagnostic and surgical challenge. It remains unclear what factors contribute to a timely presurgical diagnosis. The purpose of this study is to identify factors contributing to missing the diagnosis of UBPGLs before surgery. DESIGN, PATIENTS AND MEASUREMENTS: A total of 73 patients from 11 centres in China, and 51 patients from 6 centres in Europe and 1 center in the United States were included. Clinical, surgical and genetic data were collected and compared in patients diagnosed before versus after surgery. Logistic regression analysis was used to identify clinical factors associated with initiation of presurgical biochemical testing. RESULTS: Among all patients, only 47.6% were diagnosed before surgery. These patients were younger (34.0 vs. 54.0 years, p < .001), had larger tumours (2.9 vs. 1.8 cm, p < .001), and more had a SDHB pathogenic variant (54.7% vs. 11.9%, p < .001) than those diagnosed after surgery. Patients with presurgical diagnosis presented with more micturition spells (39.7% vs. 15.9%, p = .003), hypertension (50.0% vs. 31.7%, p = .041) and catecholamine-related symptoms (37.9% vs. 17.5%, p = .012). Multivariable logistic analysis revealed that presence of younger age (<35 years, odds ratio [OR] = 6.47, p = .013), micturition spells (OR = 6.79, p = .007), hypertension (OR = 3.98, p = .011), and sweating (OR = 41.72, p = .013) increased the probability of initiating presurgical biochemical testing. CONCLUSIONS: Most patients with UBPGL are diagnosed after surgery. Young age, hypertension, micturition spells and sweating are clues in assisting to initiate early biochemical testing and thus may establish a timely presurgical diagnosis.

17.
Int J Biol Sci ; 20(6): 2236-2260, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38617546

RESUMO

Thrombocytopenia, a prevalent hematologic challenge, correlates directly with the mortality of numerous ailments. Current therapeutic avenues for thrombocytopenia are not without limitations. Here, we identify genistin, an estrogen analogue, as a promising candidate for thrombocytopenia intervention, discovered through AI-driven compound library screening. While estrogen's involvement in diverse biological processes is recognized, its role in thrombopoiesis remains underexplored. Our findings elucidate genistin's ability to enhance megakaryocyte differentiation, thereby augmenting platelet formation and production. In vivo assessments further underscore genistin's remedial potential against radiation-induced thrombocytopenia. Mechanistically, genistin's efficacy is attributed to its direct interaction with estrogen receptor ß (ERß), with subsequent activation of both ERK1/2 and the Akt signaling pathways membrane ERß. Collectively, our study positions genistin as a prospective therapeutic strategy for thrombocytopenia, shedding light on novel interplays between platelet production and ERß.


Assuntos
Isoflavonas , Trombocitopenia , Humanos , Receptor beta de Estrogênio/genética , Trombocitopenia/tratamento farmacológico , Bibliotecas de Moléculas Pequenas
18.
Front Surg ; 11: 1329771, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38655210

RESUMO

Objectives: The diameter, area, and volume of the true lumen and false lumen (FL) have been measured in previous studies to evaluate the extent of DeBakey type I aortic dissection. However, these indicators have limitations because of the irregular shapes of the true and false lumens and the constant oscillation of intimal flap during systole and diastole. The ratio of arch lengths seems to be a more reliable indicator. FL% was defined as the ratio of the arch length of FL to the circumference of the aorta at the different levels of the aorta. The purpose of this article was to investigate whether FL% is a predictor of the severity of acute DeBakey type I aortic dissection in patients undergoing frozen elephant trunk (FET) and total arch replacement. Methods: In this retrospective observational study, we analyzed a total of 344 patients with acute DeBakey type I aortic dissection that underwent FET and total arch replacement at our center from October 2015 to October 2019. The patients were divided into two groups by cluster analysis according to the perioperative course. Binary logistic regression analyses were performed to determine whether FL% could predict the severity of acute DeBakey type I aortic dissection. The area under the receiver operating characteristic curve (AUROC) was used to assess the power of the multivariate logistic regression model for the severity of acute DeBakey type I aortic dissection. Results: The patients in the ultra-high-risk group (109 patients) had significantly more severe clinical comorbidities and complications than the patients in the high-risk group (235 patients). The ascending aortic FL% [odds ratio (OR), 11.929 (95% CI: 1.421-100.11); P = 0.022], location of initial tear [OR, 0.68 (95% CI: 0.47-0.98); P = 0.041], the degree of left iliac artery involvement [OR, 1.95 (95% CI: 1.15-3.30); P = 0.013], and the degree of right coronary artery involvement [OR, 1.46 (95% CI: 1.01-2.12); P = 0.045] on preoperative computed tomography angiography were associated with the severity of acute DeBakey type I aortic dissection. The AUROC value of this multivariate logistic regression analysis was 0.940 (95% CI: 0.914-0.967; P < 0.001). The AUROC value of ascending aortic FL% was 0.841 (95% CI: 0.798-0.884; P < 0.001) for the severity of acute DeBakey type I aortic dissection in patients undergoing FET and total arch replacement. Conclusions: Ascending aortic FL% was validated as an essential radiologic index for assessing the severity of acute DeBakey type I aortic dissection in patients undergoing FET and total arch replacement. Higher values of ascending aortic FL% were more severe.

19.
Drug Des Devel Ther ; 18: 1189-1198, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38645990

RESUMO

Purpose: Postoperative nausea and vomiting (PONV) frequently occur in patients after surgery. In this study, the authors investigated whether perioperative S-ketamine infusion could decrease the incidence of PONV in patients undergoing video-assisted thoracoscopic surgery (VATS) lobectomy. Patients and Methods: This prospective, randomized, double-blinded, controlled study was conducted a total of 420 patients from September 2021 to May 2023 at Xuzhou Central Hospital in China, who underwent elective VATS lobectomy under general anesthesia with tracheal intubation. The patients were randomly assigned to either the S-ketamine group or the control group. The S-ketamine group received a bolus injection of 0.5 mg/kg S-ketamine and an intraoperative continuous infusion of S-ketamine at a rate of 0.25 mg/kg/h. The control group received an equivalent volume of saline. All patients were equipped with patient-controlled intravenous analgesia (PCIA), with a continuous infusion rate of 0.03 mg/kg/h S-ketamine in the S-ketamine group or 0.03 µg/kg/h sufentanil in the control group. The primary outcome was the incidence of PONV. Secondary outcomes included perioperative opioid consumption, hemodynamics, postoperative pain, and adverse events. Results: The incidence of PONV in the S-ketamine group (9.7%) was significantly lower than in the control group (30.5%). Analysis of perioperative opioid usage revealed that remifentanil usage was 40.0% lower in the S-ketamine group compared to the control group (1414.8 µg vs 2358.2 µg), while sufentanil consumption was 75.2% lower (33.1 µg vs 133.6 µg). The S-ketamine group demonstrated better maintenance of hemodynamic stability. Additionally, the visual analogue scale (VAS) scores on postoperative day 1 (POD-1) and postoperative day 3 (POD-3) were significantly lower in the S-ketamine group. Finally, no statistically significant difference in other postoperative adverse reactions was observed between the two groups. Conclusion: The results of this trial indicate that perioperative S-ketamine infusion can effectively reduce the incidence of PONV in patients undergoing VATS lobectomy.


Assuntos
Ketamina , Náusea e Vômito Pós-Operatórios , Cirurgia Torácica Vídeoassistida , Humanos , Ketamina/administração & dosagem , Náusea e Vômito Pós-Operatórios/prevenção & controle , Cirurgia Torácica Vídeoassistida/efeitos adversos , Masculino , Método Duplo-Cego , Feminino , Pessoa de Meia-Idade , Estudos Prospectivos , Adulto , Idoso
20.
Mol Pharm ; 2024 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-38647653

RESUMO

Doxorubicin (DOX) is one of the most commonly used anticancer drugs; however, its clinical application is greatly limited due to its toxicity and chemotherapy resistance. The delivery of DOX by liposomes (Lipos) can improve the blood circulation time in vivo and reduce toxic side effects, but the drug's accumulation in the tumor is often insufficient for effective treatment. In this study, we present a calcium cross-linked liposome gel for the encapsulation of DOX, demonstrating its superior long-term release capabilities compared to conventional Lipos. By leveraging this enhanced long-term release, we can enhance drug accumulation within tumors, ultimately leading to improved antitumor efficacy. Lipos were prepared using the thin-film dispersion method in this study. We utilized the ion-responsiveness of glutathione-gelatin (GSH-GG) to form the gel outside the Lipos and named the nanoparticles coated with GSH-GG on the outside of Lipos as Lipos@GSH-GG. The average size of Lipos@GSH-GG was around 342.9 nm, with a negative charge of -25.6 mV. The in vitro experiments revealed that Lipos@GSH-GG exhibited excellent biocompatibility and slower drug release compared to conventional Lipos. Further analysis of cellular uptake and cytotoxicity demonstrated that Lipos@GSH-GG loading DOX (DOX&Lipos@GSH-GG) exhibited superior long-term release effects and lower toxic side effects compared to Lipos loading DOX (DOX&Lipos). Additionally, the findings regarding the long-term release effect in vivo and the tumor accumulation within tumor-bearing mice of Lipos@GSH-GG suggested that, compared to Lipos, it demonstrated superior long-term release capabilities and achieved greater drug accumulation within tumors. In vivo antitumor efficacy experiments showed that DOX&Lipos@GSH-GG demonstrated superior antitumor efficacy to DOX&Lipos. Our study highlights Lipos@GSH-GG as a promising nanocarrier with the potential to enhance efficacy and safety by means of long-term release effects and may offer an alternative approach for effective antitumor therapy in the future.

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