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INTRODUCTION: Diarrhea is the primary dose-limiting side effect of capecitabine(Cap) hindering its clinical application, but the mechanism is unclear. Clarifying this mechanism may enhance the patient compliance and improve the treatment outcome. OBJECTIVES: To assess if the endogenous metabolic profile could prodict the diarrhea induced by Cap and explore and validate underlying mechanisms. METHODS: Untargeted and targeted bile acids(BAs) metabolomics were performed to analyzed the metabolic profile of baseline samples from colorectal cancer(CRC) patients and the association with the diarrhea induced by Cap was assessed. The toxicity of BAs and Cap and its metabolites alone or their combinations to the human normal intestinal epithelial cell(HIEC) was assessed, and the key genes that mediated the BAs-enhanced toxicity of Cap were discovered by RNA-seq and then validated. A mouse model with high exposure levels of BAs was constructed and then treated with Cap to verify the Cap-induced diarrhea enhanced by BAs. RESULTS: The baseline endogenous metabolic profile showed obviously difference between diarrhea and non-diarrhea CRC patients, and the differential metabolites mainly enriched in BAs metabolism; the deoxycholic acid(DCA) and lithocholic acid(LCA) were selected to be the key BAs that enhanced the toxicity of Cap metabolite 5-FU to the HIEC cell; the DCA and LCA could inhibit the Wnt/ß-catenin signaling pathway, which then suppressed the P-glycoprotein and increased the exposure level of 5-FU in the HIEC cell. The results of animal experiment verified that the excessive DCA and LCA could aggravate the Cap-induced diarrhea through inhibiting Wnt/ß-catenin-P-glycoprotein pathway. CONCLUSIONS: The disordered BAs metabolic profile showed close relationship with diarrhea induced by Cap, and excessive DCA and LCA were proved to be the key BAs, which could aggravate the Cap-induced diarrhea through inhibiting Wnt/ß-catenin-P-glycoprotein pathway.
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PURPOSE: There is currently a lack of understanding of children's experience in the pediatric intensive care unit (PICU) environment. Additionally, pediatric patients may experience post-PICU syndrome following discharge. Thus, we aimed to adapt and evaluate the psychometric properties of a tool specifically for use with children in the PICU. DESIGN AND METHODS: According to Brislin's Model, the Intensive Care Unit Environment Stress Scale (ICUESS) was translated both forward and backward and adapted cross-culturally. A total of 210 PICU patients were selected from four hospitals in XXX to analyze the final translated version of the questionnaire, the Pediatric Intensive Care Unit Environmental Stress Scale (PICUESS). Content validity, exploratory factor analysis (EFA) and Confirmatory Factor Analysis (CFA) were used to assess the validity, while reliability was assessed using Cronbach's alpha and split-half reliability analysis. RESULTS: For PICUESS, seven of 42 items were modified. Content validity was high (overall = 0.96, item validity = 0.8 to 1.0). Exploratory factor analysis revealed eight common factors (Kaiser-Meyer-Olkin = 0.857, significant Bartlett's test). The results of the CFA indicate that the scale model fits well across the 8 factors. The entire scale demonstrated excellent internal consistency (Cronbach's alpha = 0.934). The overall split-half reliability was 0.935. CONCLUSIONS: The Chinese version of PICUESS demonstrates good reliability and validity, making it suitable for assessing pediatric patients' perceptions of the PICU environment. PRACTICE IMPLICATIONS: The PICUESS can assist healthcare professionals in providing personalized environment care for PICU patients. It has the potential to serve as a tool for further testing and international comparisons of pediatric patients' perceptions of the PICU environment.
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Unidades de Cuidado Intensivo Pediátrico , Psicometría , Estrés Psicológico , Traducciones , Humanos , Masculino , Femenino , Reproducibilidad de los Resultados , Niño , Encuestas y Cuestionarios/normas , China , Preescolar , Comparación Transcultural , Análisis FactorialRESUMEN
Using coconut shell and boric acid as raw materialsï¼ a new boron-doped coconut shell mesoporous carbon material ï¼B-CSCï¼ was prepared using a simple one-step pyrolysis method for efficient adsorption and removal of tetracycline pollutants in water. The effects of pyrolysis temperature and boron-carbon mass ratio on the adsorption performance under key preparation conditions were systematically studiedï¼ and their microstructure and physicochemical properties were characterized using a specific surface area and pore size analyzer ï¼BETï¼ï¼ field emission scanning electron microscopy ï¼SEMï¼ï¼ X-ray photon spectroscopy ï¼XPSï¼ï¼ Raman spectrometer ï¼Ramanï¼ï¼ and Zeta potentiometer ï¼Zetaï¼. The effects of initial pHï¼ different metal cationsï¼ and different background water quality conditions on the adsorption effect were systematically investigated. Combined with material characterization and correlation analysisï¼ the enhanced adsorption mechanism was discussed and analyzed in depth. The results showed that one-step pyrolysis could incorporate boron into the surface and crystal lattice of coconut shell charcoalï¼ resulting in a larger specific surface area and pore volumeï¼ and the main forms of boron introduced were H3BO3ï¼ B2O3ï¼ Bï¼ and B4C. The adsorption capacity of B-CSC to tetracycline reached 297.65 mg·g-1ï¼ which was 8.9 times that of the original coconut shell mesoporous carbon ï¼CSCï¼. At the same timeï¼ the adsorption capacity of B-CSC for rhodamine B ï¼RhBï¼ï¼ bisphenol Aï¼BPAï¼ï¼ and methylene blue ï¼MBï¼ï¼ common pollutants in aquatic environmentsï¼ was as high as 372.65ï¼ 255.24ï¼ and 147.82 mg·g-1ï¼ respectively. The adsorption process of B-CSC to tetracycline was dominated by physicochemical interactionï¼ mainly involving liquid film diffusionï¼ surface adsorptionï¼ mesoporous and microporous diffusionï¼ and active site adsorptionï¼ and H3BO3 was the main adsorption site. The adsorption strengthening mechanism mainly reduced the chemical inertness of the carbon network and enhanced its π-π interaction and hydrogen bonding with tetracycline molecules.
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Manipulation of the lactate metabolism is an efficient way for cancer treatment given its involvement in cancer development, metastasis, and immune escape. However, most of the inhibitors of lactate transport carriers suffer from poor specificity. Herein, we use the CRISPR/Cas9 system to precisely downregulate the monocarboxylate carrier 1 (MCT1) expression. To avoid the self-repairing during the gene editing process, a dual-Cas9 ribonucleoproteins (duRNPs) system is generated using the biological fermentation method and delivered into cells by the zeolitic imidazolate framework-8 (ZIF-8) nanoparticles, enabling precise removal of a specific DNA fragment from the genome. For efficient cancer therapy, a specific glucose transporter 1 inhibitor (BAY-876) is co-delivered with the duRNPs, forming BAY/duRNPs@ZIF-8 nanoparticle. ZIF-8 nanoparticles can deliver the duRNPs into cells within 1 h, which efficiently downregulates the MCT1 expression, and prohibits lactate influx. Through simultaneous inhibition of the lactate and glucose influx, BAY/duRNPs@ZIF-8 prohibits ATP generation, arrests cell cycle, inhibits cell proliferation, and finally induces cellular apoptosis both in vitro and in vivo. Consequently, we demonstrate that the biologically produced duRNPs delivered into cells by the nonviral ZIF-8 carrier have expanded the CRISPR/Cas gene editing toolbox and elevated the gene editing efficiency, which will promote biological studies and clinical applications. STATEMENT OF SIGNIFICANCE: The CRISPR/Cas9 system, widely used as an efficient gene editing tool, faces a challenge due to cells' ability to self-repair. To address this issue, a strategy involving dual-cutting of the genome DNA has been designed and implemented. This strategy utilizes biologically produced dual-ribonucleoproteins delivered by a metal-organic framework. The effectiveness of this dual-cut CRISPR-Cas9 system has been demonstrated through a therapeutic approach targeting the simultaneous inhibition of lactate and glucose influx in cancer cells. The utilization of the dual-cut gene editing strategy has provided valuable insights into gene editing and expanded the toolbox of the CRISPR/Cas-based gene editing system. It has the potential to enable more efficient and precise manipulation of specific protein expression in the future.
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Estructuras Metalorgánicas , Neoplasias , Edición Génica/métodos , Sistemas CRISPR-Cas/genética , ADN , Ribonucleoproteínas/genética , Lactatos , Glucosa , Neoplasias/genética , Neoplasias/terapiaRESUMEN
BACKGROUND: Increasing evidence suggests that long noncoding RNAs play significant roles in vascular biology and disease development. One such long noncoding RNA, PSMB8-AS1, has been implicated in the development of tumors. Nevertheless, the precise role of PSMB8-AS1 in cardiovascular diseases, particularly atherosclerosis, has not been thoroughly elucidated. Thus, the primary aim of this investigation is to assess the influence of PSMB8-AS1 on vascular inflammation and the initiation of atherosclerosis. METHODS: We generated PSMB8-AS1 knockin and Apoe (Apolipoprotein E) knockout mice (Apoe-/-PSMB8-AS1KI) and global Apoe and proteasome subunit-ß type-9 (Psmb9) double knockout mice (Apoe-/-Psmb9-/-). To explore the roles of PSMB8-AS1 and Psmb9 in atherosclerosis, we fed the mice with a Western diet for 12 weeks. RESULTS: Long noncoding RNA PSMB8-AS1 is significantly elevated in human atherosclerotic plaques. Strikingly, Apoe-/-PSMB8-AS1KI mice exhibited increased atherosclerosis development, plaque vulnerability, and vascular inflammation compared with Apoe-/- mice. Moreover, the levels of VCAM1 (vascular adhesion molecule 1) and ICAM1 (intracellular adhesion molecule 1) were significantly upregulated in atherosclerotic lesions and serum of Apoe-/-PSMB8-AS1KI mice. Consistently, in vitro gain- and loss-of-function studies demonstrated that PSMB8-AS1 induced monocyte/macrophage adhesion to endothelial cells and increased VCAM1 and ICAM1 levels in a PSMB9-dependent manner. Mechanistic studies revealed that PSMB8-AS1 induced PSMB9 transcription by recruiting the transcription factor NONO (non-POU domain-containing octamer-binding protein) and binding to the PSMB9 promoter. PSMB9 (proteasome subunit-ß type-9) elevated VCAM1 and ICAM1 expression via the upregulation of ZEB1 (zinc finger E-box-binding homeobox 1). Psmb9 deficiency decreased atherosclerotic lesion size, plaque vulnerability, and vascular inflammation in Apoe-/- mice in vivo. Importantly, endothelial overexpression of PSMB8-AS1-increased atherosclerosis and vascular inflammation were attenuated by Psmb9 knockout. CONCLUSIONS: PSMB8-AS1 promotes vascular inflammation and atherosclerosis via the NONO/PSMB9/ZEB1 axis. Our findings support the development of new long noncoding RNA-based strategies to counteract atherosclerotic cardiovascular disease.
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Aterosclerosis , Placa Aterosclerótica , ARN Largo no Codificante , Animales , Humanos , Ratones , Apolipoproteínas E/genética , Aterosclerosis/metabolismo , Células Endoteliales/metabolismo , Inflamación/genética , Ratones Endogámicos C57BL , Ratones Noqueados , Placa Aterosclerótica/patología , Complejo de la Endopetidasa Proteasomal/genética , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismoRESUMEN
Objective: This study sought to analyze the 18F-FDG PET/CT and contrast-enhanced computed tomography (CT) images of synchronous colorectal cancer (CRC) and renal clear cell carcinoma (ccRCC) and identify the shared genes between these two types of cancer through bioinformatic analysis. Methods: A retrospective analysis was conducted on a patient with synchronous CRC and ccRCC who underwent 18F-FDG PET/CT and contrast-enhanced CT before treatment. Databases were analyzed to identify differentially expressed genes between CRC and ccRCC, and co-expression genes were extracted for RCC and CRC. Results: 18F-FDG PET/CT revealed intense metabolic activity in the primary colorectal lesion (SUVmax 13.2), while a left renal mass (diameter = 35 mm) was observed with no significant uptake. Contrast-enhanced CT during the arterial phase showed heterogeneous intense enhancement of the renal lesion, and the lesion washed out earlier than in the renal cortex in the nephrographic and excretory phases, indicating ccRCC. The histopathological results confirmed synchronous double primary malignant tumors. Our bioinformatic analysis results showed that synchronous occurrence of CRC and ccRCC may correlate with simultaneous expression of Carbonic Anhydrase 9 (CA9), integrin-binding sialoprotein (IBSP), and Fibrinogen γ chain (FGG). Conclusion: 18F-FDG PET/CT combined with contrast-enhanced CT is an effective diagnostic tool in evaluating synchronous CRC and RCC. By analyzing this clinical case and conducting bioinformatic analysis, we improved our current understanding of the mechanisms underlying synchronous tumors.
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Carcinoma de Células Renales , Neoplasias Renales , Humanos , Carcinoma de Células Renales/diagnóstico por imagen , Carcinoma de Células Renales/genética , Carcinoma de Células Renales/patología , Fluorodesoxiglucosa F18 , Tomografía Computarizada por Tomografía de Emisión de Positrones/métodos , Radiofármacos , Estudios Retrospectivos , Neoplasias Renales/diagnóstico por imagen , Neoplasias Renales/genética , Neoplasias Renales/patologíaRESUMEN
Abnormal alternative splicing (AS) caused by alterations in spliceosomal factors is implicated in cancers. Standard models posit that splice site selection is mainly determined by early spliceosomal U1 and U2 snRNPs. Whether and how other mid/late-acting spliceosome components such as USP39 modulate tumorigenic splice site choice remains largely elusive. We observed that hepatocyte-specific overexpression of USP39 promoted hepatocarcinogenesis and potently regulated splice site selection in transgenic mice. In human liver cancer cells, USP39 promoted tumor proliferation in a spliceosome-dependent manner. USP39 depletion deregulated hundreds of AS events, including the oncogenic splice-switching of KANK2. Mechanistically, we developed a novel RBP-motif enrichment analysis and found that USP39 modulated exon inclusion/exclusion by interacting with SRSF6/HNRNPC in both humans and mice. Our data represented a paradigm for the control of splice site selection by mid/late-acting spliceosome proteins and their interacting RBPs. USP39 and possibly other mid/late-acting spliceosome proteins may represent potential prognostic biomarkers and targets for cancer therapy.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Ratones , Animales , Empalme Alternativo/genética , Carcinoma Hepatocelular/genética , Neoplasias Hepáticas/genética , Empalme del ARN , Carcinogénesis/genética , Factores de Empalme Serina-Arginina/metabolismo , Fosfoproteínas/metabolismo , Ribonucleoproteína Heterogénea-Nuclear Grupo C/metabolismo , Proteasas Ubiquitina-Específicas/metabolismoRESUMEN
Chinese medicinal resources are the material basis for the survival and development of traditional Chinese medicine(TCM)and the sustainable development of Chinese medicinal resources is also an important project for the modernization of TCM in China. With the increasing demand for Chinese medicinal resources in China, over-exploitation has destroyed Chinese medicinal resources, resulting in a shortage of many natural medicinal resources in China and making the sustainable development of TCM in trouble. The introduced new foreign medicinal resources have become effective supplement and replacement for Chinese medicinal resources to some extent. However, the development and utilization of new foreign medicinal resources in China are different. To fully understand the development of new foreign medicinal resources in China, this paper, taking 43 new foreign medicinal resources such as Acacia nilotica as objects, sorted out the introduction forms and policies of new foreign medicinal resources, overviewed its current development status in China, summarized the application experience of new foreign medicinal resources in the place of origin, as well as the research progress and problems of new foreign medicinal resources in China and abroad, and analyzed the research situation, which can enrich Chinese medicinal resources and other uses, promote the sustainable development of Chinese medicinal resources, and provide ideas for further development and research of new foreign medicinal resources.
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Medicamentos Herbarios Chinos , Medicamentos Herbarios Chinos/uso terapéutico , Medicina Tradicional China , Conservación de los Recursos Naturales , Desarrollo Sostenible , Internacionalidad , ChinaRESUMEN
Cancer stem cells (CSCs) contribute to tumor initiation, progression, and recurrence in many types of cancer, including hepatocellular carcinoma (HCC). Epigenetic reprogramming of CSCs has emerged as a promising strategy for inducing the transition from malignancy to benignity. Ubiquitin-like with PHD and ring finger domains 1 (UHRF1) is required for DNA methylation inheritance. Here, we investigated the role and mechanism of UHRF1 in regulating CSC properties and evaluated the impact of UHRF1 targeting on HCC. Hepatocyte-specific Uhrf1 knockout (Uhrf1HKO) strongly suppressed tumor initiation and CSC self-renewal in both diethylnitrosamine (DEN)/CCl4-induced and Myc-transgenic HCC mouse models. Ablation of UHRF1 in human HCC cell lines yielded consistent phenotypes. Integrated RNA-seq and whole genome bisulfite sequencing revealed widespread hypomethylation induced by UHRF1 silencing epigenetically reprogrammed cancer cells toward differentiation and tumor suppression. Mechanistically, UHRF1 deficiency upregulated CEBPA and subsequently inhibited GLI1 and Hedgehog signaling. Administration of hinokitiol, a potential UHRF1 inhibitor, significantly reduced tumor growth and CSC phenotypes in mice with Myc-driven HCC. Of pathophysiological significance, the expression levels of UHRF1, GLI1, and key axis proteins consistently increased in the livers of mice and patients with HCC. These findings highlight the regulatory mechanism of UHRF1 in liver CSCs and have important implications for the development of therapeutic strategies for HCC.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Proteínas Hedgehog , Carcinoma Hepatocelular/genética , Proteína con Dedos de Zinc GLI1 , Neoplasias Hepáticas/genética , Carcinogénesis/genética , Transformación Celular Neoplásica , Células Madre Neoplásicas , Proteínas Potenciadoras de Unión a CCAAT/genética , Ubiquitina-Proteína Ligasas/genéticaRESUMEN
Yippee-like 2 (YPEL2) is expressed in tissues and organs enriched in vascular networks, such as heart, kidney, and lung. However, the roles of YPEL2 in endothelial cell senescence and the expression of YPEL2 in atherosclerotic plaques have not yet been investigated. Here, we report the essential role of YPEL2 in promoting senescence in human umbilical vein endothelial cells (HUVECs) and the upregulation of YPEL2 in human atherosclerotic plaques. YPEL2 was significantly upregulated in both H2O2-induced senescent HUVECs and the arteries of aged mice. Endothelial YPEL2 deficiency significantly decreased H2O2-increased senescence-associated beta-galactosidase (SA-ß-gal) activity and reversed H2O2-inhibited cell viability. Additionally, endothelial YPEL2 knockdown reduced H2O2-promoted THP-1 cell adhesion to HUVECs and downregulated ICAM1 and VCAM1 expression. Mechanistic studies divulged that the p53/p21 pathway was involved in YPEL2-induced cellular senescence. We conclude that YPEL2 promotes cellular senescence via the p53/p21 pathway and that YPEL2 expression is elevated in atherosclerosis. These findings reveal YPEL2 as a potential therapeutic target in aging-associated diseases.
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Senescencia Celular , Células Endoteliales , Placa Aterosclerótica , Animales , Humanos , Ratones , Células Endoteliales de la Vena Umbilical Humana/metabolismo , Peróxido de Hidrógeno , Placa Aterosclerótica/metabolismo , Proteína p53 Supresora de Tumor/metabolismo , Proteínas de Ciclo Celular/metabolismo , Células Endoteliales/metabolismoRESUMEN
Soft materials have attracted widespread attention and brought a wave of novel potential applications. Accurate mechanical characterization is crucial for improving the ration design of the desired soft elements and understanding the influence of deformation properties on themselves. However, the intrinsic complexity of mixed elasticity and viscosity in terms of their material property, posing new challenges for constitutive modeling. In this work, a fractional visco-hyperelastic constitutive model is developed by introducing the fractional viscoelasticity into finite strain: two branches are incorporated where a hyperelastic spring is used to describe the equilibrium response, and a non-linear fractional dashpot is introduced to characterize the time-dependent material response by employing the 3D fractional viscoelasticity. It provides a method from the perspective of fractional mechanics to avoid the increased number of governing equations and the associated complex calibration process caused by introducing the internal variables. The results show that the proposed model can successfully describe the rate dependent mechanical behavior of soft materials as well as predict the material behavior in different deformation modes with reasonable accuracy.
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Modelos Biológicos , Estrés Mecánico , Elasticidad , ViscosidadRESUMEN
Atherosclerosis is a chronic inflammatory disease of arterial wall, and circulating monocyte adhesion to endothelial cells is a crucial step in the pathogenesis of atherosclerosis. Epithelial-stromal interaction 1 (EPSTI1) is a novel gene, which is dramatically induced by epithelial-stromal interaction in human breast cancer. EPSTI1 expression is not only restricted to the breast but also in other normal tissues. In this study we investigated the role of EPSTI1 in monocyte-endothelial cell adhesion and its expression pattern in atherosclerotic plaques. We showed that EPSTI1 was dramatically upregulated in human and mouse atherosclerotic plaques when compared with normal arteries. In addition, the expression of EPSTI1 in endothelial cells of human and mouse atherosclerotic plaques is significantly higher than that of the normal arteries. Furthermore, we demonstrated that EPSTI1 promoted human monocytic THP-1 cell adhesion to human umbilical vein endothelial cells (HUVECs) via upregulating VCAM-1 and ICAM-1 expression in HUVECs. Treatment with LPS (100, 500, 1000 ng/mL) induced EPSTI1 expression in HUVECs at both mRNA and protein levels in a dose- and time-dependent manner. Knockdown of EPSTI1 significantly inhibited LPS-induced monocyte-endothelial cell adhesion via downregulation of VCAM-1 and ICAM-1. Moreover, we revealed that LPS induced EPSTI1 expression through p65 nuclear translocation. Thus, we conclude that EPSTI1 promotes THP-1 cell adhesion to endothelial cells by upregulating VCAM-1 and ICAM-1 expression, implying its potential role in the development of atherosclerosis.
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Aterosclerosis , Placa Aterosclerótica , Animales , Humanos , Ratones , Aterosclerosis/metabolismo , Adhesión Celular , Células Cultivadas , Células Endoteliales de la Vena Umbilical Humana/metabolismo , Molécula 1 de Adhesión Intercelular/genética , Molécula 1 de Adhesión Intercelular/metabolismo , Lipopolisacáridos , Monocitos/metabolismo , Proteínas de Neoplasias/metabolismo , Placa Aterosclerótica/metabolismo , Molécula 1 de Adhesión Celular Vascular/genética , Molécula 1 de Adhesión Celular Vascular/metabolismoRESUMEN
Ovarian cancer is one of the three major cancers in gynecology. Ovarian cancer has insidious symptoms in its early stages and mostly has progressed to advanced stages when detected. Surgical treatment combined with chemotherapy is currently the main treatment, but the 5-year survival rate is still less than 45%. Angiogenesis is a key step in the growth and metastasis of ovarian cancer. The inhibition of ovarian cancer angiogenesis has become a new hotspot in anti-tumor targeted therapy, which has many advantages such as less drug resistance, high specificity, few side effects, and broad anti-tumor spectrum. Modern research has confirmed that traditional Chinese medicine(TCM) can inhibit tumor angiogenesis by inhibiting the expression of pro-angiogenic factors, up-regulating the expression of anti-angiogenic factors, inhibiting the proliferation of vascular endothelial cells, reducing the density of tumor microvessels, and regulating related signaling pathways, with unique advantages in the treatment of ovarian cancer. This paper presented a review of the role of TCM in inhibiting ovarian cancer angiogenesis in order to provide references for the optimization of clinical ovarian cancer treatment strategies.
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Medicina Tradicional China , Neoplasias Ováricas , Humanos , Femenino , Factor A de Crecimiento Endotelial Vascular/metabolismo , Células Endoteliales/metabolismo , Angiogénesis , Inhibidores de la Angiogénesis/farmacología , Inhibidores de la Angiogénesis/uso terapéutico , Neoplasias Ováricas/tratamiento farmacológico , Neoplasias Ováricas/genética , Neovascularización Patológica/tratamiento farmacológico , Neovascularización Patológica/genéticaRESUMEN
OBJECTIVES: To study the value of metagenomic next-generation sequencing (mNGS) in detecting intracranial Epstein-Barr virus (EBV) infection in children with hemophagocytic syndrome (HPS) with central nervous system involvement. METHODS: A retrospective analysis was performed for the cerebrospinal fluid mNGS results of 30 HPS children with central nervous system involvement, which were compared with the results of cerebrospinal fluid EBV-DNA detection and serum EBV antibody profile. The change in serum EBV-DNA copy number after treatment was used to evaluate the efficacy of targeted therapy. RESULTS: The positive rate of EBV in cerebrospinal fluid determined by mNGS was significantly higher than that of EBV-DNA in cerebrospinal fluid (100% vs 10%, P<0.001) and had no significant difference from the positive rate of serum EBV antibody profile (100% vs 93%, P>0.05). The median number of sequences determined by mNGS was 2 400, and serum EBV-DNA copy number before treatment was moderately positively correlated with the number of EBV sequences (rs=0.693, P<0.001). The multiple linear regression analysis showed that the number of sequences determined by mNGS in cerebrospinal fluid increased with the increase in serum EBV-DNA copy number before treatment (P<0.05). CONCLUSIONS: EBV-associated HPS often results in EBV-infected viral encephalitis, and mNGS can significantly increase the detection rate of EBV in cerebrospinal fluid, which may help with clinical diagnosis.
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Infecciones por Virus de Epstein-Barr , Linfohistiocitosis Hemofagocítica , Niño , Humanos , Linfohistiocitosis Hemofagocítica/diagnóstico , Linfohistiocitosis Hemofagocítica/genética , Infecciones por Virus de Epstein-Barr/complicaciones , Herpesvirus Humano 4/genética , Estudios Retrospectivos , Secuenciación de Nucleótidos de Alto Rendimiento , Sistema Nervioso CentralRESUMEN
The goblet cell-associated antigen passages (GAPs), formed in the intestine and conjunctiva, contribute to immune responses by delivering antigens to immune cells. It has been proved that dysfunctions of GAPs may contribute to intestinal inflammation and dry eye disease. GAPs were first discovered in the intestine with the help of intravital two-photon microscopy. The imaging of GAPs was subsequently captured in a frozen section and whole-mount immunofluorescent staining. Both protocols have their features. This study provides a new protocol for visualizing GAPs with better mucus preservation by combining 4% PFA and methanol-Carnoy's solution (PFA-MC). In addition, embedding samples in paraffin provides an opportunity for antigen retrieval for immunohistochemistry analysis. Using this protocol, we have successfully visualized GAPs in the intestine, intestinal organoids, conjunctiva, and trachea. It is worth mentioning that the visualization of GAPs in intestinal organoids and airways has rarely been discussed before, which may assist researchers in their studies. Moreover, we also discovered the active uptake of dextran of club cells in terminal bronchioles, which may provide a new direction for studying the function of club cells. Overall, we developed a new method to visualize GAP formation and identify GCs simultaneously in the intestine, organoid, conjunctiva, and airway.
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Conjuntiva , Células Caliciformes , Antígenos , Intestinos , MocoRESUMEN
BACKGROUND: Situs inversus totalis (SIT) is a rare group of congenital developmental malformations in the clinical setting, with all organs in the chest and abdomen existing in a mirror image reversal of their normal positions. Few reports have described laparoscopic surgery for colorectal cancer in patients with SIT, and it is considered difficult even for an experienced surgeon because of the mirror positioning. We present a case report of laparoscopic radical resection of a colonic splenic flexure carcinoma in a patient with SIT. CASE SUMMARY: A 72-year-old male was referred to our hospital with colonic splenic flexure carcinoma, and computed tomography showed that all the organs in the chest and abdomen were inverted. Laparoscopic hemicolectomy with complete mesocolic excision was safely performed. The operating surgeon stood on the patient's left side, which is opposite of the normal location. CONCLUSION: Abdominal computed tomography is an effective method for diagnosing SIT preoperatively in patients with colonic splenic flexure carcinomas. Laparoscopic radical resection is difficult, but it is well established and safe. The surgeon should stand in the opposite position and perform backhand operations.
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BACKGROUND: Stress fractures of the femoral neck are not common in clinical practice, and simultaneous stress fractures of the femoral neck and proximal femur of the unilateral femur are even more rare. We introduce a case of this type of fracture that was treated in our department, analyze the causes, and review similar stress fractures reported in the literature to provide references for the diagnosis and treatment of such conditions. CASE SUMMARY: A 62-year-old female, with a free medical history, was admitted to the hospital mainly due to pain in the right hip and worsening pain in the right thigh. The patient had no obvious history of trauma. X-ray and computed tomography showed fracture of the femoral neck and proximal femur. The patient had undergone surgery 1 year prior to address a fracture of the left proximal femur that had occurred in a traffic accident. Our first consideration was stress fracture of the femoral neck; however, simultaneous stress fractures of the femoral neck and proximal femur of the unilateral femur were seen. The femoral neck stress fracture was a tension fracture, with obvious displacement and varus deformity of the hip. Considering that the patient was an elderly female, we performed total hip arthroplasty. Follow-up X-rays showed that the stress fracture of the proximal femur had mostly healed after 3 mo. CONCLUSION: Muscle fatigue and hip varus deformity provide an anatomical basis for the occurrence of femoral neck stress fractures.
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With zinc acetate and butyl titanate as raw materials, pure ZnO and ZnTiO3/ZnO composite photocatalysts were synthesized by a sol-gel method and calcined at 550 °C. The crystal structure, morphology, surface area, optical property, and element valence states of samples were characterized and the photocatalytic activity of the prepared photocatalysts were assessed by the degradation of rhodamine B. Results show that the crystal structure of ZnO is a hexagonal wurtzite phase with a band gap of 3.20 eV. When the Zn/Ti molar ratio reaches 0.2, ZnTiO3 phase appears and ZnTiO3/ZnO composite forms, which advances the transfer of photogenerated charges. ZnTiO3/ZnO (Ti/Zn = 0.2) exhibits the highest photocatalytic activity, and the degradation degree of RhB reaches 99% after 60 min, which is higher than that of pure ZnO (90%). An exorbitant Ti/Zn molar ratio will reduce the crystallinity and form more amorphous components, which is not conducive to photocatalytic performance. Therefore, when the Ti/Zn molar ratio exceeds 0.2, the photocatalytic activities of ZnTiO3/ZnO composites decrease.
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Cerium carbonate crystal morphology is predicted using density functional theory (DFT) simulations in this paper. In the nucleation phase, the ketone group in polyvinylpyrrolidone (PVP) will preferentially bind to Ce3+ to form complexes and provide heterogeneous nucleation sites for the system, prompting the nucleation of cerium carbonate crystals. In the growth stage, due to the adsorption of PVP, the probability of (120) crystal plane appearing in the equilibrium state is the greatest, resulting in the formation of hexagonal flake cerium carbonate crystals with (120) crystal plane as the oblique edge. Experimentally, hexagonal sheet cerium carbonate crystals were successfully prepared using PVP as a template agent. Therefore, DFT can be used to predict the morphology of cerium carbonate crystals, which not only elucidates the growth mechanism of cerium carbonate crystals, but also greatly reduces the experimental cost.
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The anatase/rutile mixed crystal TiO2 was prepared and modified with Ag decoration and SnO2 coupling to construct a Ag@SnO2/anatase/rutile composite photocatalytic material. The crystal structure, morphology, element valence, optical properties and surface area were characterized, and the effects of Ag decoration and SnO2 coupling on the structure and photocatalytic properties of TiO2 were studied. Ag decoration and SnO2 coupling are beneficial to reduce the recombination of photogenerated electrons and holes. When the two modification are combined, a synergistic effect is produced in suppressing the photogenerated charge recombination, making Ag@SnO2/TiO2 exhibits the highest quantum utilization. After 30 min of illumination, the degradation degree of tetracycline hydrochloride (TC) by pure TiO2 increased from 63.3% to 83.1% with Ag@SnO2/TiO2.