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Background: Lung adenocarcinoma (LUAD), a predominant subtype of non-small cell lung cancers, continues to challenge treatment outcomes due to its heterogeneity and complex tumor microenvironment (TME). Dysregulation in nucleotide metabolism has been identified as a significant factor in tumorigenesis, suggesting its potential as a therapeutic target. Methods: This study analyzed LUAD samples from The Cancer Genome Atlas (TCGA) using Non-negative Matrix Factorization (NMF) clustering, Weighted Correlation Network Analysis (WGCNA), and various machine learning techniques. We investigated the role of nucleotide metabolism in relation to clinical features and immune microenvironment through large-scale data analysis and single-cell sequencing. Using in vivo and in vitro experiments such as RT-qPCR, Western Blot, immunohistochemistry, and subcutaneous tumor formation in mice, we further validated the functions of key nucleotide metabolism genes in cell lines and animals. Results: Nucleotide metabolism genes classified LUAD patients into two distinct subtypes with significant prognostic differences. The 'C1' subtype associated with active nucleotide metabolism pathways showed poorer prognosis and a more aggressive tumor phenotype. Furthermore, a nucleotide metabolism-related score (NMRS) calculated from the expression of 28 key genes effectively differentiated between patient outcomes and predicted associations with oncogenic pathways and immune responses. By integrating various immune infiltration algorithms, we delineated the associations between nucleotide metabolism signature genes and the tumor microenvironment, and characterized their distribution differences at the cellular level by analyzing single-cell sequencing dataset related to immunochemotherapy. Finally, we demonstrated the differential expression of the key nucleotide metabolism gene AUNIP acts as an oncogene to promote LUAD cell proliferation and is associated with tumor immune infiltration. Conclusion: The study underscores the pivotal role of nucleotide metabolism in LUAD progression and prognosis, highlighting the NMRS as a valuable biomarker for clinical outcomes and therapeutic responses. Specifically, AUNIP functions as a critical oncogene, offering a promising target for novel treatment strategies in LUAD.
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Adenocarcinoma del Pulmón , Biomarcadores de Tumor , Biología Computacional , Neoplasias Pulmonares , Nucleótidos , Microambiente Tumoral , Humanos , Adenocarcinoma del Pulmón/genética , Adenocarcinoma del Pulmón/metabolismo , Adenocarcinoma del Pulmón/inmunología , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/inmunología , Neoplasias Pulmonares/patología , Animales , Nucleótidos/metabolismo , Nucleótidos/genética , Microambiente Tumoral/genética , Microambiente Tumoral/inmunología , Biología Computacional/métodos , Ratones , Regulación Neoplásica de la Expresión Génica , Pronóstico , Línea Celular Tumoral , Perfilación de la Expresión GénicaRESUMEN
The present study aimed to assess the roles of peripheral circulating tumor cell (CTC) count, CTC subtypes and programmed death ligand 1 (PD-L1) expression in the clinical staging and prognosis of patients with non-small cell lung cancer (NSCLC). A total of 100 patients with NSCLC with available tumor tissues were enrolled in the present study, and 7.5 ml peripheral blood was collected. Patients were divided into PD-L1-positive and PD-L1-negative groups according to PD-L1 immunohistochemical staining. Peripheral blood samples from both groups were analyzed to determine the CTC count, epithelial-type CTCs (E-CTCs), mesenchymal-type CTCs (M-CTCs) and PD-L1 expression. Clinical data were collected, and patients were followed up for a maximum of 36 months, with patient death as the endpoint event. Patients with PD-L1-positive tumors had a worse prognosis compared with those with PD-L1-negative tumors (P=0.045). The PD-L1-positive group exhibited significantly higher numbers of CTCs and M-CTCs compared with the PD-L1-negative group (P≤0.05). However, the number of E-CTCs did not differ significantly between the two groups (P>0.05). PD-L1-positive patients with higher CTC and M-CTC counts had relatively poorer prognoses (P≤0.05), while the number of E-CTCs had no significant effect on prognosis (P>0.05). Compared with the early-stage NSCLC group, the late-stage NSCLC group exhibited a significant increase in the CTC count (P≤0.05), while E-CTC and M-CTC counts did not significantly differ between the two groups (P>0.05). The PD-L1-positive group exhibited a significant increase in the number of PD-L1+ CTCs and PD-L1+ M-CTCs compared with the PD-L1-negative group (P≤0.05), while PD-L1+ E-CTC counts did not differ significantly between the two groups (P>0.05). The PD-L1-positive patients with a higher number of PD-L1+ CTCs and PD-L1+ M-CTCs had relatively poorer prognoses (P≤0.05), while the PD-L1+ E-CTC count had no significant effect on prognosis (P>0.05). Compared with the early-stage NSCLC group, the late-stage NSCLC group exhibited a significant increase in the number of PD-L1+ CTCs and PD-L1+ M-CTCs (P≤0.05), while PD-L1+ E-CTC counts did not significantly differ between the two groups (P>0.05). Based on univariate and multivariate analyses, the number of PD-L1+ M-CTCs was identified as an independent prognostic factor for NSCLC. In conclusion, the presence of CTCs in peripheral blood, particularly PD-L1+ M-CTC subtype, indicated poorer clinical staging and prognosis in patients with NSCLC. These findings suggested that CTCs, specifically the PD-L1+ M-CTC subtype, could serve as a monitoring indicator for the clinical staging and prognosis of patients with NSCLC.
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Currently, cancer is the second leading cause of death worldwide, and potential targeted drugs and molecular pathways for cancer development and progression have been a hot research topic worldwide. In recent years, the importance of the kinase superfamily in diseases has been well demonstrated by studies on various molecular mechanisms of kinases and the successful application of their inhibitors in diseases. Pseudokinases are members of the kinase superfamily, which have been increasingly documented to play a crucial role in cancers year after year. As a member of pseudokinases, tribbles homolog 3 (TRIB3) also exerts diverse functions in different cancers through different interacting proteins and molecular pathways, especially in tumor immunity, stemness, drug resistance, metabolism, and autophagy. In addition, peptide drugs targeting TRIB3 have high specificity in preclinical studies, which shows great promise for TRIB3 application in diseases including cancers. In this review, we dissect diverse functions played by TRIB3 in different cancers, describing the underlying mechanisms in detail. Notably, inhibitors and agonists currently available for TRIB3 are discussed, indicating the potential for TRIB3 as a therapeutic target.
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Proteínas de Ciclo Celular , Neoplasias , Proteínas Serina-Treonina Quinasas , Humanos , Neoplasias/tratamiento farmacológico , Neoplasias/patología , Proteínas Serina-Treonina Quinasas/antagonistas & inhibidores , Proteínas Serina-Treonina Quinasas/metabolismo , Proteínas de Ciclo Celular/antagonistas & inhibidores , Proteínas de Ciclo Celular/metabolismo , Animales , Proteínas Represoras/antagonistas & inhibidores , Proteínas Represoras/metabolismo , Proteínas Represoras/genética , Terapia Molecular Dirigida/métodos , Autofagia , Antineoplásicos/uso terapéutico , Antineoplásicos/farmacología , Resistencia a AntineoplásicosRESUMEN
Objective: To retrospectively study the effects of budesonide inhalation combined with conventional symptomatic treatment on serum inflammatory factor expression levels and pulmonary function in patients with cough variant asthma (CVA) and to evaluate treatment efficacy. Methods: This retrospective cohort study included 200 patients diagnosed with CVA at the Second Hospital of Jiaxing between January 2022 and June 2023 and given conventional symptomatic treatment plus budesonide inhalation were included in this study. Patients were divided into a no remission group, a partial remission group and a complete remission group based on treatment effect. The expression levels of serum inflammatory factors, cough symptom scores, and small airway function indicators in the three groups of patients at different time points were compared. Results: In the three groups of CVA patients, after receiving budesonide inhalation combined with conventional symptomatic treatment, the expression levels of serum IL-5, IL-6, IL-8, TNF-α, TGF-ß1, and IgE and number of eosinophils significantly decreased (P <0.05). There were statistically significant differences in the IL-6 and TGF-ß1 levels among the three groups of CVA patients at T1, T2 and T3. There were statistically significant differences in IgE levels, number of eosinophils, cough symptom scores, and small airway function indicators between T2 and T3 (P<0.05). The receiver operating characteristic (ROC) curve prediction analysis revealed significant differences in the expression of IL-6 and TGF-ß1 at T1, T2, and T3. Conclusion: Budesonide inhalation combined with conventional symptomatic treatment can significantly reduce the levels of serum inflammatory factors in patients with CVA to reduce inflammation and the allergic response, thereby reducing the cough symptom score, improving pulmonary function, and improving therapeutic efficacy. In addition, IL-6 and TGF-ß1 can be used as early predictors of budesonide inhalation efficacy.
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The case of a patient with type B3 thymomacomorbid with Chlamydia psittaci (C. psittaci) pneumonia exhibiting rare features is presented in the current report. The patient was admitted at the Second Affiliated Hospital of Jiaxing University (Jiaxing, China) with a history of direct contact with poultry. Clinical manifestations included fever, shivers, cough, fatigue and poor appetite. Chest computed tomography (CT) indicated right lung pneumonia, while metagenomics next-generation sequencing using bronchoalveolar lavage fluid confirmed infection with C. psittaci. Additionally, positron emission tomography-CT suggested the presence of thymoma. After surgery and treatment with doxycycline and imipenem cilastatin, the patient was discharged showing signs of improvement.
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Bariatric metabolic surgery's global research interest is growing, particularly in Asia due to its high obesity rates. This study focuses on Asia, especially China, analyzing 3904 publications (1221 from China) from 1980 to 2022. Research output accelerated until the COVID-19 pandemic, driven by economic growth and rising obesity rates. China led contributions from 2010, but Western Asia led when adjusted for population. An intra-regional research collaboration network emerged, driven by geographic proximity and similar economic environments. Keyword analysis highlighted emerging topics like "laparoscopic sleeve gastrectomy" and "non-alcoholic fatty liver disease," indicating a shift in focus. The study recommends disseminating research in top-tier journals to enhance visibility and impact.
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Cirugía Bariátrica , Bibliometría , Humanos , Asia/epidemiología , Cirugía Bariátrica/estadística & datos numéricos , Investigación Biomédica , China/epidemiología , COVID-19/epidemiología , Obesidad/cirugía , Obesidad/epidemiología , Obesidad Mórbida/cirugía , Obesidad Mórbida/epidemiología , SARS-CoV-2RESUMEN
Rapid restoration of perfusion in ischemic myocardium is the most direct and effective treatment for coronary heart disease but may cause myocardial ischemia/reperfusion injury (MIRI). Cinnamaldehyde (CA, C9H8O), a key component in the well-known Chinese medicine cinnamomum cassia, has cardioprotective effects against MIRI. This study aimed to observe the therapeutic effect of CA on MIRI and to elucidate its potential mechanism. H9C2 rat cardiomyocytes were pretreated with CA solution at 0, 10, and 100 µM, respectively and subjected to oxygen-glucose deprivation/reoxygenation (OGD/R). Then the cell viability, the NF-κB and caspase3 gene levels, the reduced glutathione (GSH)/oxidized glutathione (GSSG) ratio, superoxide dismutase (SOD) level, reactive oxygen species (ROS) generation, 4-hydroxynonenal (4-HNE), and malondialdehyde (MDA) were detected. The severity of DNA damage was assessed by tail moment (TM) values using alkaline comet assay. Besides, the DNA damage-related proteins and the key proteins of the Nrf2 pathway were detected by western blot. CA treatment increased the cell viability, GHS/GSSG ratio, SOD level, PARP1, Nrf2, PPAR-γ, and HO-1 protein levels of H9C2 cardiomyocytes, while reducing NF-κB, caspase3, ROS level, 4-HNE and MDA content, γ-H2AX protein level, and TM values. Inhibition of the Nrf2 pathway reversed the effect of CA on cell viability and apoptosis of OGD/R induced H9C2 cardiomyocytes. Besides, 100 µM CA was more effective than 10 µM CA. In the OGD/R-induced H9C2 cardiomyocyte model, CA can protect cardiomyocytes from MIRI by attenuating lipid peroxidation and repairing DNA damage. The mechanism may be related to the activation of the Nrf2 pathway.
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Acroleína , Miocitos Cardíacos , Factor 2 Relacionado con NF-E2 , Oxígeno , Animales , Ratas , Acroleína/análogos & derivados , Acroleína/farmacología , Apoptosis , Daño del ADN , Glucosa/farmacología , Disulfuro de Glutatión/genética , Disulfuro de Glutatión/metabolismo , Disulfuro de Glutatión/farmacología , Peroxidación de Lípido , Miocitos Cardíacos/efectos de los fármacos , Miocitos Cardíacos/metabolismo , Factor 2 Relacionado con NF-E2/efectos de los fármacos , Factor 2 Relacionado con NF-E2/metabolismo , FN-kappa B/metabolismo , Estrés Oxidativo , Oxígeno/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Superóxido Dismutasa/metabolismoRESUMEN
BACKGROUND: Chemotherapeutic agents such as cisplatin are commonly used in patients with clinically unresectable or recurrent esophageal cancer (ESCA). However, patients often develop resistance to cisplatin, which in turn leads to a poor prognosis. Studies have shown that FAM111B may be involved in the development of tumors as an oncogene or tumor suppressor gene. However, the pathological role and corresponding mechanism of FAM111B in ESCA are still unclear. METHODS: The GEPIA web tool, ENCORI Pan-Cancer Analysis Platform and UALCAN-TCGA database were used to study the expression of FAM111B in ESCA. CCK-8, angiogenesis, Transwell and xenograft assays were applied to explore the biological function of FAM111B in ESCA. Western blot, RT-qPCR, and RNA-seq analyses were applied to study the FAM111B/GSDMA axis in the progression of ESCA cells. CCK-8 and xenograft assays were used to study the role of the FAM111B/GSDMA axis in determining the sensitivity of ESCA to cisplatin. RESULTS: Our results demonstrated that FAM111B is highly expressed in ESCA tissues compared to normal tissues. We showed that FAM111B promotes the progression of ESCC cells by binding to GSDMA and that the trypsin protease domain is essential for the activity of FAM111B. Furthermore, we showed that the FAM111B/GSDMA axis regulates cisplatin sensitivity in ESCA. CONCLUSIONS: Overall, we identified a novel FAM111B/GSDMA axis regulating ESCA tumorigenesis and chemosensitivity, at least in ESCC cells.
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Proteínas de Ciclo Celular , Cisplatino , Neoplasias Esofágicas , Gasderminas , Humanos , Carcinogénesis , Proteínas de Ciclo Celular/metabolismo , Transformación Celular Neoplásica , Cisplatino/farmacología , Neoplasias Esofágicas/metabolismo , Neoplasias Esofágicas/patología , Gasderminas/metabolismo , Sincalida , Resistencia a AntineoplásicosRESUMEN
OBJECTIVE: Nowadays, many studies focus on the relationship between microRNAs (miRs) and the development of oral squamous cell carcinoma (OSCC). Here, we broaden the understanding of miR-30a-5p in OSCC. METHODS: In silico analysis was implemented to screen differentially expressed genes in OSCC and the related upstream regulatory miR. OSCC SCC9 cells were manipulated with lentivirus-mediated miR-30a-5p mimic, oe-ITGA6 or sh-ITGA6 and LY294002 (the PI3K/AKT pathway inhibitor) for studying their roles in cell biological processes. Tumors were xenografted in nude mouse for in vivo mechanism verification. RESULTS: In silico analysis results depicted that ITGA6 was highly expressed in OSCC, and that miR-30a-5p was the upstream regulatory miR of ITGA6. miR-30a-5p was downregulated and ITGA6 was highly expressed in OSCC tissues and cells. miR-30a-5p targeted and downregulated ITGA6. ITGA6 promoted epithelial-mesenchymal transition, migration and invasion in OSCC cells by activating PI3K/AKT pathway. miR-30a-5p could suppress the in vivo growth and metastasis of OSCC by inhibiting the ITGA6/PI3K/AKT axis. CONCLUSION: Taken together, miR-30a-5p prevents OSCC progression by inhibiting PI3K/AKT pathway through inhibition of ITGA6 expression.
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Carcinoma de Células Escamosas , Neoplasias de Cabeza y Cuello , MicroARNs , Neoplasias de la Boca , Animales , Ratones , Carcinoma de Células Escamosas/patología , Carcinoma de Células Escamosas de Cabeza y Cuello/genética , Neoplasias de la Boca/patología , Proteínas Proto-Oncogénicas c-akt/metabolismo , Fosfatidilinositol 3-Quinasas/metabolismo , Línea Celular Tumoral , Proliferación Celular/genética , MicroARNs/genética , MicroARNs/metabolismo , Neoplasias de Cabeza y Cuello/genética , Movimiento Celular/genética , Regulación Neoplásica de la Expresión Génica/genéticaRESUMEN
OBJECTIVE: To investigate the clinical phenotype and genetic characteristics of a patient with a heterozygous 6p25.3 deletion and partial trisomy 15q. METHODS: A patient who had presented at the Genetics and Prenatal Diagnosis Center of the First Affiliated Hospital of Zhengzhou University on May 14, 2021 was selected as the study subject. Clinical data of the patient was collected, and G-banded chromosomal karyotyping and copy number variation sequencing (CNV-seq) were carried out. RESULTS: The patient's main clinical features have included complete uterine septum, vaginal septum, atrophy of left eyeball, abnormal fingers and toes, and mental retardation. The karyotype of the patient was 46,XX,der(6)t(6;15)(p25.3;q26.1). CNV-seq result has indicated a 1.20 Mb heterozygous deletion in the 6p25.3 region and a 10.20 Mb duplication in the 15q26.1q26.3 region. The deletion segment has included the FOXQ1 gene, which may be related with the abnormal development of the left eye. The duplication segment has a 96.16% overlap with the region associated with 15q26 overgrowth syndrome (including the IGF1R gene), which may be related to the patient' s abnormal development of the Müllerian duct, abnormal fingers and toes, and mental developmental delay. CONCLUSION: The heterozygous deletion of the 6p25.3 region and duplication of the 15q26.1q26.3 region probably underlay the abnormal clinical phenotype in this patient.
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Variaciones en el Número de Copia de ADN , Trisomía , Humanos , Embarazo , Femenino , Trisomía/genética , Fenotipo , Diagnóstico Prenatal , Deleción Cromosómica , Factores de Transcripción ForkheadRESUMEN
To compare the pancreatic proteomics and autophagy between Rehmanniae Radix-and Rehmanniae Radix Praeparata-treated mice with type 2 diabetes mellitus(T2DM). The T2DM mouse model was established by high-fat diet coupled with streptozotocin(STZ, intraperitoneal injection, 100 mg·kg~(-1), once a day for three consecutive days). The mice were then randomly assigned into a control group, low-(5 g·kg~(-1)) and high-dose(15 g·kg~(-1)) Rehmanniae Radix groups, low-(150 mg·kg~(-1)) and high-dose(300 mg·kg~(-1)) catalpol groups, low-(5 g·kg~(-1)) and high-dose(15 g·kg~(-1)) Rehmanniae Radix Praeparata groups, low-(150 mg·kg~(-1)) and high-dose(300 mg·kg~(-1)) 5-hydroxymethyl furfuraldehyde(5-HMF) groups, and a metformin(250 mg·kg~(-1)) group. In addition, a normal group was also set and each group included 8 mice. The pancreas was collected after four weeks of administration and proteomics tools were employed to study the effects of Rehmanniae Radix and Rehmanniae Radix Praeparata on protein expression in the pancreas of T2DM mice. The expression levels of proteins involved in autophagy, inflammation, and oxidative stress response in the pancreatic tissues of T2DM mice were determined by western blotting, immunohistochemical assay, and transmission electron microscopy. The results showed that the differential proteins between the model group and Rehmanniae Radix/Rehmanniae Radix Prae-parata group were enriched in 7 KEGG pathways, such as autophagy-animal, which indicated that the 7 pathways may be associated with T2DM. Compared with the control group, drug administration significantly up-regulated the expression levels of beclin1 and phosphorylated mammalian target of rapamycin(p-mTOR)/mTOR and down-regulated those of the inflammation indicators, Toll-like receptor-4(TLR4) and Nod-like receptor protein 3(NLRP3), in the pancreas of T2DM mice, and Rehmanniae Radix showed better performance. In addition, the expression levels of inducible nitric oxide synthase(iNOS), nuclear factor erythroid 2-related factor 2(Nrf2), and heine oxygenase-1(HO-1) in the pancreas of T2DM mice were down-regulated after drug administration, and Rehmanniae Radix Praeparata demonstrated better performance. The results indicate that both Rehmanniae Radix and Rehmanniae Radix Praeparata can alleviate the inflammatory symptoms, reduce oxidative stress response, and increase the autophagy level in the pancreas of T2DM mice, while they exert the effect on different autophagy pathways.
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Diabetes Mellitus Tipo 2 , Ratones , Animales , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Diabetes Mellitus Tipo 2/genética , Estreptozocina/farmacología , Dieta Alta en Grasa/efectos adversos , Proteómica , Inflamación , Serina-Treonina Quinasas TOR , Autofagia , MamíferosRESUMEN
We report a systematic study of the dynamics of self-propelled particles (SPPs) over a one-dimensional periodic potential landscape U_{0}(x), which is fabricated on a microgroove-patterned polydimethylsiloxane (PDMS) substrate. From the measured nonequilibrium probability density function P(x;F_{0}) of the SPPs, we find that the escape dynamics of the slow rotating SPPs across the potential landscape can be described by an effective potential U_{eff}(x;F_{0}), once the self-propulsion force F_{0} is included into the potential under the fixed angle approximation. This work demonstrates that the parallel microgrooves provide a versatile platform for a quantitative understanding of the interplay among the self-propulsion force F_{0}, spatial confinement by U_{0}(x), and thermal noise, as well as its effects on activity-assisted escape dynamics and transport of the SPPs.
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Conventional chemotherapy for multiple myeloma (MM) faces the challenges of a low complete remission rate and transformation to recurrence/refractory. The current MM first-line clinical drug Bortezomib (BTZ) faces the problem of enhanced tolerance and nonnegligible side effects. B cell maturation antigen (BCMA), for its important engagement in tumor signaling pathways and novel therapy technologies such as Chimeric antigen receptor T-Cell immunotherapy (CAR-T) and Antibody Drug Conjugate (ADC), has been identified as an ideal target and attracted attention in anti-MM therapy. Emerging nanotechnology provided feasible methods for drug delivery and new therapeutic strategies such as photothermal therapy (PTT). Herein, we developed a BCMA-Targeting biomimetic photothermal nanomissile BTZ@BPQDs@EM @anti-BCMA (BBE@anti-BCMA) by integration of BTZ, black phosphorus quantum dots (BPQDs), Erythrocyte membrane (EM) and BCMA antibody (anti-BCMA). We hypothesized that this engineered nanomissile could attack tumor cells in triple ways and achieve effective treatment of MM. Consequently, the intrinsic biomimetic nature of EM and the active targeting property of anti-BCMA enhanced the accumulation of therapeutic agents in the tumor site. Besides, owing to the decrease in BCMA abundance, the potential apoptosis-inducing ability was revealed. With the support of BPQDs' photothermal effect, Cleaved-Caspase-3 and Bax signal increased significantly, and the expression of Bcl-2 was inhibited. Furthermore, the synergistic photothermal/chemo therapy can effectively inhibit tumor growth and reverse the disorder of NF-κB in vivo. Importantly, this biomimetic nanodrug delivery system and antibody induced synergistic therapeutic strategy efficiently killed MM cells with ignorable systemic toxicity, which is a promising method for the future anticancer treatment of hematological malignancies in clinics.
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Mieloma Múltiple , Receptores Quiméricos de Antígenos , Humanos , Receptores Quiméricos de Antígenos/metabolismo , Receptores Quiméricos de Antígenos/uso terapéutico , Inmunoterapia Adoptiva/métodos , Mieloma Múltiple/terapia , Mieloma Múltiple/patología , FN-kappa B/metabolismo , Linfocitos T , BiomiméticaRESUMEN
Multiple myeloma (MM) is an incurable hematological malignant disorder of bone marrow. Patients with MM receive multiple lines of chemotherapeutic treatments which often develop bortezomib (BTZ) resistance and relapse. Therefore, it is crucial to identify an anti-MM agent to overcome the BTZ resistance of MM. In this study, we screened a library of 2370 compounds against MM wild-type (ARP1) and BTZ-resistant type (ARP1-BR) cell lines and found that periplocin (PP) was the most significant anti-MM natural compound. We further investigated the anti-MM effect of PP by using annexin V assay, clonogenic assays, aldefluor assay, and transwell assay. Furthermore, RNA sequencing (RNA-seq) was performed to predict the molecular effects of PP in MM followed by verification through qRT-PCR and Western blot analysis. Moreover, ARP1 and ARP1-BR xenograft mice models of MM were established to confirm the anti-MM effects of PP invivo. The results showed that PP significantly induced apoptosis, inhibited proliferation, suppressed stemness, and reduced the cell migration of MM. The expression of cell adhesion molecules (CAMs) was suppressed upon PP treatment in vitro and in vivo. Overall, our data recommend PP as an anti-MM natural compound with the potential to overcome BTZ resistance and downregulate CAMs in MM.
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BACKGROUND: The aim of this study was to build and validate a risk prediction model for diarrhea in patients in the intensive care unit (ICU) receiving enteral nutrition (EN) by identifying risk factors for diarrhea in these patients. METHODS: The risk factors for diarrhea were analyzed to build a prediction model for EN diarrhea in patients in the ICU based on the data collected from 302 patients receiving EN in the ICU. Subsequently, the model was validated by the area under the curve. RESULTS: In this study, the collected data were divided into two groups: a derivation cohort and a validation cohort. The results showed that 54.03% (114) of patients had diarrhea in the derivation cohort and 56.04% (51) of patients had diarrhea in the validation cohort. Moreover, days of EN, high urea nitrogen levels, probiotics, respiratory system disease, and daily doses of nutrient solution were included as predictive factors for diarrhea in patients receiving EN in the ICU. The predictive power of the model was 0.81 (95% CI, 0.752~0.868) in the derivation cohort and 0.736 (95% CI, 0.634~0.837) in the validation cohort. CONCLUSION: In accordance with the predictive factors, the model, characterized by excellent discrimination and high accuracy, can be used to clinically identify patients in the ICU with a high risk of EN diarrhea.
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Nutrición Enteral , Probióticos , Humanos , Nutrición Enteral/efectos adversos , Nutrición Enteral/métodos , Cuidados Críticos , Unidades de Cuidados Intensivos , Diarrea/etiología , Enfermedad CríticaRESUMEN
Objective: To investigate the clinical features, diagnosis, and treatment of Chlamydia psittaci (C. psittaci) pneumonia. Methods: We retrospectively analyzed the clinical data of six patients with C. psittaci pneumonia who were admitted to the Division of Pulmonary and Critical Care Medicine of the Second Hospital of Jiaxing from December 2021 to September 2022. Results: All patients reported a fever and other accompanying symptoms, including cough (5/6), chest tightness (1/6), fatigue (2/6), and headache (1/6). Laboratory results showed that all patients had high levels of C-reactive protein (CRP≥70 mg/L), procalcitonin (PCT; 2 patients with PCT levels ≥0.5 ng/L), and erythrocyte sedimentation rate (ESR). Lactate dehydrogenase (LDH) and aspartate aminotransferase (AST) levels were elevated in 3/6 and of 2/6 patients, respectively. Chest computed tomography (CT) of most patients showed patchy, high-density shadows with partial consolidation, accompanied by air bronchogram signs and pleural effusion. Six patients were diagnosed with C. psittaci pneumonia using metagenomic next-generation sequencing (mNGS). They showed favorable outcomes following immediate adjustment of the regimen to doxycycline-based therapy and hydration, nutrition, and other follow-up treatments. In the imaging findings obtained at one-two month, the lesions were completely cleared, suggesting a favorable prognosis. Conclusion: Patients with C. psittaci pneumonia commonly present sepsis and rapidly progressing disease. Early diagnosis is critical for C. psittaci pneumonia using mNGS, which can lead to favorable prognoses via immediate adjustment therapies.
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Chlamydophila psittaci , Neumonía , Psitacosis , Humanos , Estudios Retrospectivos , PulmónRESUMEN
Propylparaben (PrP) is a widely used preservative that is constantly detected in aquatic environments and poses a potential threat to aquatic ecosystems. In the present work, adult male mosquitofish were acutely (4d) and chronically (32d) exposed to environmentally and humanly realistic concentrations of PrP (0, 0.15, 6.00 and 240 µg/L), aimed to investigate the toxic effects, endocrine disruption and possible mechanisms of PrP. Histological analysis showed time- and dose-dependent manners in the morphological injuries of brain, liver and testes. Histopathological alterations in the liver were found in 4d and severe damage was identified in 32d, including hepatic sinus dilatation, cytoplasmic vacuolation, cytolysis and nuclear aggregation. Tissue impairments in the brain and testes were detected in 32d; cell cavitation, cytomorphosis and blurred cell boundaries appeared in the brain, while the testes lesions contained spermatogenic cell lesion, decreased mature seminal vesicle, sperm cells gathering, seminiferous tubules disorder and dilated intercellular space. Furthermore, delayed spermatogenesis had occurred. The transcriptional changes of 19 genes along the hypothalamus-pituitary-gonadal-liver (HPGL) axis were investigated across the three organs. The disrupted expression of genes such as Ers, Ars, Vtgs, cyp19a, star, hsd3b, hsd17b3 and shh indicated the possible abnormal steroidogenesis, estrogenic or antiandrogen effects of PrP. Overall, the present results provided evidences for the toxigenicity and endocrine disruptive effects on the male mosquitofish of chronic PrP exposure, which highlights the need for more investigations of its potential health risks.
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Ciprinodontiformes , Contaminantes Químicos del Agua , Masculino , Animales , Ecosistema , Semen , Hígado/metabolismo , Expresión Génica , Ciprinodontiformes/genética , Ciprinodontiformes/metabolismo , Contaminantes Químicos del Agua/toxicidadRESUMEN
Multiple myeloma (MM) is an incurable condition and the second most common hematological malignancy. Over the past few years, there has been progress in the treatment of MM, but most patients still relapse. Multiple myeloma stem-like cells (MMSCs) are believed to be the main reason for drug resistance and eventual relapse. Currently, there are not enough therapeutic agents that have been identified for eradication of MMSCs, and thus, identification of the same may alleviate the issue of relapse in patients. In the present study, we showed that luteolin (LUT), a natural compound obtained from different plants, such as vegetables, medicinal herbs, and fruits, effectively inhibits the proliferation of MM cells and overcomes bortezomib (BTZ) resistance in them in vitro and in vivo, mainly by decreasing the proportion of ALDH1+ cells. Furthermore, RNA sequencing after LUT treatment of MM cell lines and an MM xenograft mouse model revealed that the effects of the compound are mediated through inhibition of transforming growth factor-ß signaling. Similarly, we found that LUT also significantly reduced the proportion of ALDH1+ cells in primary CD138+ plasma cells. In addition, LUT could overcome the BTZ treatment-induced increase in the proportion of ALDH1+ cells, and the combination of LUT and BTZ had a synergistic effect against myeloma cells. Collectively, our findings suggested that LUT is a promising agent that manifests MMSCs to overcome BTZ resistance, alone or in combination with BTZ, and thus, is a potential therapeutic drug for the treatment of MM.
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Antineoplásicos , Mieloma Múltiple , Humanos , Animales , Ratones , Bortezomib/farmacología , Mieloma Múltiple/patología , Luteolina/farmacología , Resistencia a Antineoplásicos , Apoptosis , Línea Celular Tumoral , Recurrencia Local de Neoplasia/tratamiento farmacológico , Transducción de Señal , Factor de Crecimiento Transformador beta/farmacología , Antineoplásicos/farmacologíaRESUMEN
OBJECTIVES: To evaluate the benefit distribution of social health insurance among domestic migrants in China. DESIGN: A national cross-sectional survey. SETTING: 348 cities from 32 provincial units in China. PARTICIPANTS: 1165 domestic migrants who used inpatient care services in the city of a new residence and had social health insurance. PRIMARY AND SECONDARY OUTCOME MEASURES: The probability of receiving reimbursements from social health insurance, the amounts and ratio of reimbursement received. RESULTS: Among migrants who used inpatient care in 2013, only 67% received reimbursements from social health insurance, and the reimbursement amount only accounted for 47% of the inpatient care expenditure. The broader the geographical scope of migration, the lower the probability of receiving reimbursement and the reimbursement ratio, but the higher the reimbursement amount. Specifically, the probability of receiving reimbursements for those who migrated across cities or provinces was significantly lower by 14.7% or 26.0%, respectively, than those who migrated within a city. However, they received significantly higher reimbursement amounts by 33.4% or 27.2%, respectively, than those who migrated within a city. And those who migrated across provinces had the lowest reimbursement ratio, although not reaching significance level. CONCLUSIONS: The unequal benefit distribution among domestic migrants may be attributed to the fragmented health insurance design that relies on localised administration, and later reimbursement approach that migrating patients pay for health services up-front and get reimbursement later from health insurance. To improve the equity in social health insurance benefits, China has been promoting the portability of social health insurance, immediate reimbursement for inpatient care used across regions, and a more integrated health insurance system. Efforts should also be made to control inflation of healthcare expenditures and prevent inverse government subsidies from out-migration regions to in-migration regions. This study has policy implications for China and other low/middle-income countries that experience rapid urbanisation and domestic migration.
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Beneficios del Seguro , Seguro de Salud , China , Estudios Transversales , Humanos , Seguridad SocialRESUMEN
Variational methods have been widely used in soft matter physics for both static and dynamic problems. These methods are mostly based on two variational principles: the variational principle of minimum free energy (MFEVP) and Onsager's variational principle (OVP). Our interests lie in the applications of these variational methods to active matter physics. In our former work [H. Wang, T. Qian and X. Xu, Soft Matter, 2021, 17, 3634-3653], we have explored the applications of OVP-based variational methods for the modeling of active matter dynamics. In the present work, we explore variational (or energy) methods that are based on MFEVP for static problems in active elastic solids. We show that MFEVP can be used not only to derive equilibrium equations, but also to develop approximate solution methods, such as the Ritz method, for active solid statics. Moreover, the power of the Ritz-type method can be further enhanced using deep learning methods if we use deep neural networks to construct the trial functions of the variational problems. We then apply these variational methods and the deep Ritz method to study the spontaneous bending and contraction of a thin active circular plate that is induced by internal asymmetric active contraction. The circular plate is found to be bent towards its contracting side. The study of such a simple toy system gives implications for understanding the morphogenesis of solid-like confluent cell monolayers. In addition, we introduce a so-called activogravity length to characterize the importance of gravitational forces relative to internal active contraction in driving the bending of the active plate. When the lateral plate dimension is larger than the activogravity length (about 100 micron), gravitational forces become important. Such gravitaxis behaviors at multicellular scales may play significant roles in the morphogenesis and in the up-down symmetry broken during tissue development.