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AIM: Patients with permanent colostomy need continuous nursing management measures. Therefore, this study aimed to investigate the impact of discharge planning combined with "Internet home ostomy care platform'' on post-discharge complications, self-management abilities, quality of life, and satisfaction of patients with permanent colostomy after rectal cancer surgery. METHODS: This retrospective analysis included 72 rectal cancer patients who underwent permanent colostomy in Zhejiang Provincial People's Hospital between January 2021 and December 2021. Patients receiving routine nursing management were included in the control group (n = 36), and those receiving discharge planning combined with "Internet home ostomy care platform'' were included in the study group (n = 36). We collected baseline data, complication rate, self-management behavior questionnaire for Chinese enterostomy patients (SBQ-CEP), and Chinese version of the City of Hope Quality of Life-Ostomy Questionnaire (COH-QOL-OQ) and Medical Experience Scale for Outpatient Care of Enterostomy (MES-OCE) score. The complication rate, self-management ability, quality of life, and satisfaction of the two groups were statistically compared and analyzed. RESULTS: The study group demonstrated significantly higher medical compliance behavior, dietary behavior, symptom management behavior, psychosocial behavior, information management behavior scores, and SBQ-CEP total scores compared to the control group six months after discharge (p < 0.05). However, the study group showed a significantly lower incidence of complications than the control group at 1 week, 2 weeks, 1 month, 3 months, and 6 months after discharge (p < 0.05). Furthermore, the study group demonstrated significantly lower psychological well-being, physical well-being, spiritual well-being, social well-being scores, and COH-QOL-OQ total scores compared to the control group 6 months after discharge (p < 0.05). Additionally, the study group indicated significantly higher environment and process, service attitude, health guidance, diagnosis and treatment effect, overall evaluation of treatment experience scores, and MES-OCE total scores compared to the control group 6 months after discharge (p < 0.05). CONCLUSIONS: Discharge planning combined with "Internet home ostomy care platform'' can effectively reduce the risk of complications in patients with permanent colostomy after rectal cancer surgery. It improves patients' self-management abilities, quality of life, and satisfaction. This finding provides an ongoing guarantee for the quality of rehabilitation at home for patients with permanent colostomy.
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Colostomía , Alta del Paciente , Calidad de Vida , Neoplasias del Recto , Humanos , Femenino , Masculino , Estudios Retrospectivos , Persona de Mediana Edad , Neoplasias del Recto/cirugía , Anciano , Satisfacción del Paciente , Complicaciones Posoperatorias/prevención & control , Complicaciones Posoperatorias/epidemiología , Encuestas y Cuestionarios , Servicios de Atención de Salud a DomicilioRESUMEN
OBJECTIVES: Using a sporadic case of listeriosis suspected to have been caused by consuming a pre-packaged cold-chain ready-to-eat (RTE) food in Beijing, China in 2021 as an exemplar, this study demonstrated the importance of thoroughly investigating the source of listeriosis up to the production point for mitigating infection risk during routine monitoring of Listeria in food facilities and national surveillance program using whole-genome sequencing (WGS). METHODS: Epidemiological, laboratory, traceback, and plant investigations were used to identify the source of infection. RESULTS: WGS showed the isolate from the patient was genetically indistinguishable from that of the implicated food. During a plant investigation, L. monocytogenes was detected in 26% (9/35) of the environmental samples and one of two raw material samples, confirming the source. CONCLUSION: To our knowledge, this is the first investigation in China linking a case of L. monocytogenes infection to a suspected food and its production environment. This report highlights the risk of L. monocytogenes contamination of RTE food and demonstrates the role of food safety risk monitoring in identifying potential sources of infection. Reinforcing control programs in RTE processing plants, intensified surveillance of microorganisms in food products and targeted health education is required to mitigate the infection risk.
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Age-related intervertebral disk degeneration (IVDD) involves increased oxidative damage, cellular senescence, and matrix degradation. Pyrroloquinoline quinone (PQQ) is a water-soluble vitamin-like compound with strong anti-oxidant capacity. The goal of this study was to determine whether PQQ can prevent aging-related IVDD, and the underlying mechanism. Here, we found that dietary PQQ supplementation for 12 months alleviated IVDD phenotypes in aged mice, including increased disk height index and reduced histological scores and cell loss, without toxicity. Mechanistically, PQQ inhibited oxidative stress, cellular senescence, and senescence-associated secretory phenotype (SASP) in the nucleus pulposus and annulus fibrosus of aged mice. Similarly, PQQ protected against interleukin-1ß-induced matrix degradation, reactive oxygen species accumulation, and senescence in human nucleus pulposus cells (NPCs) in vitro. Molecular docking predicted and biochemical assays validated that PQQ interacts with specific residues to dissociate the Keap1-Nrf2 complex, thereby increasing nuclear Nrf2 translocation and activation of Nrf2-ARE signaling. RNA sequencing and luciferase assays revealed Nrf2 can transcriptionally upregulate Wnt5a by binding to its promoter, while Wnt5a knockdown prevented PQQ inhibition of matrix metalloproteinase-13 in NPCs. Notably, PQQ supplementation failed to alleviate aging-associated IVDD phenotypes and oxidative stress in aged Nrf2 knockout mice, indicating Nrf2 is indispensable for PQQ bioactivities. Collectively, this study demonstrates Nrf2 activation by PQQ inhibits aging-induced IVDD by attenuating cellular senescence and matrix degradation. This study clarifies Keap1-Nrf2-Wnt5a axis as the novel signaling underlying the protective effects of PQQ against aging-related IVDD, and provides evidence for PQQ as a potential agent for clinical prevention and treatment of natural aging-induced IVDD.
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Envejecimiento , Degeneración del Disco Intervertebral , Factor 2 Relacionado con NF-E2 , Cofactor PQQ , Animales , Degeneración del Disco Intervertebral/metabolismo , Degeneración del Disco Intervertebral/tratamiento farmacológico , Degeneración del Disco Intervertebral/patología , Factor 2 Relacionado con NF-E2/metabolismo , Ratones , Envejecimiento/efectos de los fármacos , Envejecimiento/metabolismo , Cofactor PQQ/farmacología , Humanos , Masculino , Ratones Endogámicos C57BL , Senescencia Celular/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacosRESUMEN
OBJECTIVE: The aim of this study is to observe the anesthetic effect and safety of intravenous anesthesia without muscle relaxant with propofol-remifentanil combined with regional block under laryngeal mask airway in pediatric ophthalmologic surgery. METHODS: A total of 90 undergoing ophthalmic surgery were anesthetized with general anesthesia using the laryngeal mask airway without muscle relaxant. They were randomly divided into two groups: 45 children who received propofol-remifentanil intravenous anesthesia combined with regional block (LG group), and 45 children who received total intravenous anesthesia (G group). The peri-operative circulatory indicators, awakening time after general anesthesia, postoperative analgesic effect and the incidence of anesthesia-related adverse events were respectively compared between the two groups. RESULTS: All the children successfully underwent the surgical procedure. The awakening time after general anesthesia and removal time of laryngeal mask were significantly shorter in the LG group than in the G group (P < 0.05). There was no statistically significant difference in the heart rates in the perioperative period between the two groups (P > 0.05). There was no statistically significant difference in the incidence of intraoperative physical response, respiratory depression, postoperative nausea and vomiting (PONV) and emergence agitation (EA) between the two groups (P > 0.05). The pain score at the postoperative hour 2 was lower in the LG group than in the G group (P < 0.05). CONCLUSION: Propofol-remifentanil intravenous anesthesia combined with long-acting local anesthetic regional block anesthesia, combined with laryngeal mask ventilation technology without muscle relaxants, can be safely used in pediatric eye surgery to achieve rapid and smooth recovery from general anesthesia and better postoperative analgesia. This anesthesia scheme can improve the comfort and safety of children in perioperative period, and has a certain clinical popularization value.
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Propofol , Niño , Humanos , Anestesia General , Anestesia Intravenosa/métodos , Anestésicos Intravenosos , Propofol/uso terapéutico , RemifentaniloRESUMEN
BACKGROUND: In recent years, the rectus sheath block (RSB) has become increasingly prevalent in laparoscopic surgery. However, there is currently no definitive research on its use in the open repair of umbilical hernias with cirrhotic ascites. OBJECTIVE: In this study, we assessed the safety and clinical efficacy of ultrasound-guided (US-guided) bilateral RSBs in open umbilical hernia repair for patients diagnosed with cirrhotic ascites. STUDY DESIGN: Seventy-two patients diagnosed with umbilical hernias that presented with cirrhotic ascites and who were admitted to our hospital were randomly divided into 2 groups. These categories were labeled the RSB group (Group R) and the local infiltration group (Group L); we used US-guided RSBs in Group R and local infiltration in Group L. SETTING: The clinical outcomes of the patients in each group were compared to one another. Heart rate (HR), systolic blood pressure (SBP), and diastolic blood pressure (DBP) were recorded at various time points in both groups. METHODS: Measurements of the patients' outcomes were taken before anesthesia (T0), at the beginning of surgery (T1), at the time of the separation of the hernia sac (T2), at the end of surgery (T3), 6 hours postoperatively (T4), and 24 hours postoperatively (T5). On the Visual Analog Scale (VAS), pain scores at rest (T1-T3) and during activity (T4-T5) were recorded, as were the incidence of perioperative remedial analgesia and adverse effects. RESULTS: Compared to T0, both groups' HR was significantly higher at T1-T3 (P < 0.05). The SBP and DBP were also significantly higher (P < 0.05). At T1-T3, the HR of Group R was significantly slower than that of Group L (P < 0.05), and at T4-T5, the VAS score for activity in Group R was significantly lower than that of Group L (P < 0.05). Group R had a significantly lower incidence of intraoperative remedial analgesia and postoperative nausea and vomiting than did Group L (P < 0.05). Neither group required postoperative remedial analgesia, and no patient experienced adverse reactions during the perioperative period. LIMITATIONS: This study has limitations in its sample size, lack of blood ammonia levels, and absence of data on patient satisfaction, necessitating future studies to address these issues. CONCLUSION: US-guided RSBs are an efficient method of anesthesia for open umbilical hernia repair in patients diagnosed with cirrhosis. This technique not only provides precise anesthesia and appropriate analgesia but also results in a low incidence of postoperative nausea and vomiting.
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Hernia Umbilical , Bloqueo Nervioso , Humanos , Hernia Umbilical/cirugía , Hernia Umbilical/complicaciones , Dolor Postoperatorio/etiología , Náusea y Vómito Posoperatorios , Ascitis/complicaciones , Ascitis/cirugía , Ultrasonografía Intervencional/métodos , Bloqueo Nervioso/métodos , Cirrosis Hepática/complicaciones , Cirrosis Hepática/cirugíaRESUMEN
Engrailed 2 (EN2) is a homeodomain-containing protein that is dysregulated in many types of cancer. However, the role of EN2 in non-small cell lung cancer (NSCLC) and the mechanism underlying its biological function are largely unclear. Here, we showed that EN2 played an oncogenic function in NSCLC and greatly enhanced the malignant phenotype of NSCLC cells. Meanwhile, EN2 was able to boost the expression of a well-studied oncogenic Tenascin-C (TNC) gene, which in turn activated the AKT signaling pathway. Interestingly, we found that EN2 directly bound to the super-enhancer (SE) region in the TNC locus. The histone marker H3K27ac was also enriched in the region, indicating the activation of the SE. Treatment of the cells with JQ1, an inhibitor of SE activity, abrogated the effect of EN2 on the expression of TNC and phosphorylation of AKT-Ser473. Collectively, our work unveils a novel mode of EN2 function, in which EN2 governs the SE in the TNC locus, consequently activating the oncogenic TNC-AKT axis in NSCLC.
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Carcinoma de Pulmón de Células no Pequeñas , Proteínas de Homeodominio , Neoplasias Pulmonares , Tenascina , Humanos , Carcinoma de Pulmón de Células no Pequeñas/metabolismo , Proteínas de Homeodominio/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Transducción de Señal , Tenascina/genéticaRESUMEN
The stem cell theory of aging dictates that a decline in the number and/or function of stem cells causes tissue degeneration and aging; however, it still lacks unequivocal experimental support. Here, using lineage tracing and single-cell transcriptomics, we identify a population of CD133+ bone marrow-derived endothelial-like cells (ELCs) as potential endothelial progenitor cells, which contribute to tubular structures in vitro and neovascularization in vivo. We demonstrate that supplementation with wild-type and young ELCs respectively restores neovascularization and extends lifespan in progeric and naturally aged mice. Mechanistically, we identify an upregulation of farnesyl diphosphate synthase (FDPS) in aged CD133+ ELCs-a key enzyme in isoprenoid biosynthesis. Overexpression of FDPS compromises the neovascularization capacity of CD133+ ELCs, whereas FDPS inhibition by pamidronate enhances neovascularization, improves health measures and extends lifespan in aged mice. These findings highlight stem cell-based strategies for the treatment of progeria and age-related pathologies.
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Células Progenitoras Endoteliales , Ratones , Animales , Células Progenitoras Endoteliales/patología , Longevidad , Neovascularización Patológica/patología , Células Madre/patologíaRESUMEN
CCAAT/enhancer binding protein α (C/EBPα) regulates myeloid differentiation, and its dysregulation contributes to acute myeloid leukaemia (AML) progress. Clarifying its functional implementation mechanism is of great significance for its further clinical application. Here, we show that C/EBPα regulates AML cell differentiation through liquid-liquid phase separation (LLPS), which can be disrupted by C/EBPα-p30. Considering that C/EBPα-p30 inhibits the functions of C/EBPα through the LZ region, a small peptide TAT-LZ that could instantaneously interfere with the homodimerization of C/EBPα-p42 was constructed, and dynamic inhibition of C/EBPα phase separation was observed, demonstrating the importance of C/EBPα-p42 homodimers for its LLPS. Mechanistically, homodimerization of C/EBPα-p42 mediated its phosphorylation at the novel phosphorylation site S16, which promoted LLPS and subsequent AML cell differentiation. Finally, decreasing the endogenous C/EBPα-p30/C/EBPα-p42 ratio rescued the phase separation of C/EBPα in AML cells, which provided a new insight for the treatment of the AML.
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Proteína alfa Potenciadora de Unión a CCAAT , Leucemia Mieloide Aguda , Humanos , Proteína alfa Potenciadora de Unión a CCAAT/genética , Proteína alfa Potenciadora de Unión a CCAAT/metabolismo , Diferenciación Celular , Hematopoyesis , Leucemia Mieloide Aguda/metabolismo , FosforilaciónRESUMEN
Recently, noninvasive preimplantation genetic testing (ni-PGT) using degenerate oligonucleotide primer PCR (DOP-PCR) and multiple annealing and looping-based amplification cycle (MALBAC)-based whole-genome amplification (WGA) methods has demonstrated predictable results in embryo testing. However, a considerable heterogeneity of results has been reported in numerous studies on these two WGA methods. Our aim was to evaluate the current WGA method for ni-PGT while further clarifying the applicable scenarios of ni-PGT in the fresh cycle. A total of 173 embryos were tested with trophectoderm biopsy and ni-PGT. In the whole preimplantation genetic testing, the clinical concordance rates of the detection results of DOP-PCR and MALBAC with the corresponding trophectoderm biopsy results were 64.12% (84/131) and 68.99% (89/129), respectively (P = 0.405). However, in the detection of abnormal embryos, the detection efficiency of ni-PGT is significantly improved [MALBAC: 96.55% versus 68.99% (P < 0.001); and DOP-PCR: 89.09% versus 64.12% (P < 0.001)]. In addition, the diagnostic efficiency of ni-PGT in low-quality blastocysts was significantly higher than that in high-quality blastocysts [MALBAC: 95.24% versus 51.85% (P = 0.001); and DOP-PCR: 91.30% versus 48.15% (P = 0.001)]. These results contribute to further understanding ni-PGT and to clarifying its application scenario in the fresh cycle.
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Diagnóstico Preimplantación , Embarazo , Femenino , Humanos , Diagnóstico Preimplantación/métodos , Pruebas Genéticas/métodos , Blastocisto , Técnicas de Amplificación de Ácido Nucleico/métodos , Reacción en Cadena de la Polimerasa , AneuploidiaRESUMEN
Homeodomain (HD)-containing proteins are typically recognized as transcription factors. Engrailed 2 (EN2) is an HD-containing protein that is highly expressed in various types of cancers, however, the mechanism underlying the biological function of EN2 is not fully understood. Here, we report a transcription-independent function of EN2 in addition to its role as a transcription factor. EN2 expression leads to the activation of multiple signaling pathways mediated by phosphorylation cascades. A phosphoproteomic analysis revealed that the phosphorylation status of numerous protein sites was altered after EN2 is expressed. Notably, EN2 was shown to interact with a myriad of proteins implicated in phosphorylation signaling cascades, as determined by immunoprecipitation-mass spectrometry (IP-MS). We validated the interaction between EN2 and B55α, the regulatory subunit of the PP2A-B55α complex, and confirmed that the phosphatase activity of the complex was suppressed by EN2 binding. To target EN2-induced malignancy, two kinds of small molecules were utilized to inhibit the EN2-activated NF-κB and AKT signaling pathways. A clear synergistic effect was observed when the activation of the two pathways was simultaneously blocked. Collectively, the data show that EN2 functions in a transcription-independent manner in addition to its role as a transcription factor. This finding may have therapeutic implications in treating esophageal squamous cell carcinoma (ESCC).
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Neoplasias Esofágicas , Carcinoma de Células Escamosas de Esófago , Humanos , Fosforilación , Proteínas del Tejido Nervioso/metabolismo , Transducción de Señal , Proteínas de Homeodominio/metabolismo , Factores de Transcripción/metabolismoRESUMEN
BACKGROUND: Chemotherapy is still the standard regimen for treating acute myeloid leukemia (AML) and its disappointing efficacy requires the urgent need for new therapeutic targets. It is well known that immune response plays an increasingly significant role in the pathogenesis of AML. METHODS: We detected nine single nucleotide polymorphisms (SNPs) in immune checkpoint-related genes, including PD1, LAG3, TIM3, and TIGIT in 285 AML inpatients and 324 healthy controls. SNP genotyping was performed on the MassARRAY platform. Furthermore, we analyzed the relationship between the susceptibility and prognosis of AML and the selected SNPs. RESULTS: Our results showed that rs2227982 and rs10204525 in PD1 were significantly associated with susceptibility to AML after false discovery rate correction. PD1 rs10204525 also showed a significant correlation with the response to chemotherapy and risk stratification of AML. Importantly, the AA genotype of PD1 (rs2227982) under the recessive model showed a negative impact on AML prognosis independently. CONCLUSIONS: Our results indicate that PD1 SNPs are important for susceptibility and prognosis in AML, which may provide a new therapeutic target for AML patients.
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Leucemia Mieloide Aguda , Humanos , Leucemia Mieloide Aguda/tratamiento farmacológico , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/patología , Polimorfismo de Nucleótido Simple , Pronóstico , Predisposición Genética a la Enfermedad , GenotipoRESUMEN
Introduction: Acute myeloid leukemia (AML) is a heterogeneous myeloid malignancy with abnormal molecular diversity. Tissue kallikrein 2 (KLK2) is a kind of serine protease, and has a close relationship with the occurrence and development of malignant tumors. Single nucleotide polymorphism (SNP) of various genes are associated with susceptibility, treatment and survival of AML. Methods: We investigated the association of KLK2 SNPs rs198977 and rs2664155 with AML. We recruited 284 AML patients and 280 healthy controls from the Han population and genotyping KLK2 SNPs rs198977 and rs2664155 by MassARRAY system. Results: Using clinical data from AML patients and controls, including AML susceptibility, blood count, risk stratification, response to induced chemotherapy and survival, our results showed an increased risk of AML susceptibility with KLK2 rs198977 TT genotype in the recessive model. Regarding white blood cell counts in AML patients, the results showed an increased risk of hyperleukocytosis with the TT genotype of KLK2 rs198977 in a codominant model. Moreover, in the recessive model, AML with KLK2 SNPs rs198977 TT genotype had an increased risk of hyperleukocytosis. No significant correlation was found between KLK2 rs2664155 and AML. Discussion: This study suggests that KLK2 rs198977 may be an important genetic factor in the occurrence of AML and hyperleukocytosis in AML, providing a new perspective for disease progression and new therapeutic targets.
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Background: Although anthracyclines are the first-line chemotherapy drugs for treating non-M3 acute myeloid leukaemia (AML), their efficacy remains limited. It is important to identify factors that influence the efficacy of anthracyclines against AML. Mitochondrial apoptosis-related genes play significant roles in the pathogenesis, treatment, and prognosis of AML. Methods: We utilized the CRISPR/Cas9 screening system to find AML anthracyclines resistance related genes and several mitochondrial apoptosis-related genes, such as BCL2L11, CASP8, TP63, TP53BP2, PLAUR, SOD2, BNIP3L, and MMP9, were screened out. Then, DNA from 279 patients with AML and 321 healthy individuals were extracted and the contributions of single nucleotide polymorphisms (SNPs) within these genes to the patient's chemotherapy response, susceptibility to AML, and overall survival were investigated. Results: Our findings indicated that SNP rs4251864 in the PLAUR gene was associated with an increase in complete remission after anthracycline-based induction chemotherapy. rs4880 in SOD2 was associated with the response to the second course of chemotherapy, whereas rs3789068 in BCL2L11 was associated with susceptibility to AML. Conclusions: Our results about the association of SNPs in mitochondrial apoptosis-related genes with the response to anthracycline-based chemotherapy in AML provide an important reference for predicting the treatment outcomes in patients with this disease.
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BACKGROUND: Breast cancer with low human epidermal growth factor receptor (HER2) expression is increasingly considered as a distinct subtype which consists of types of HER2 immunohistochemistry (IHC) 1+ and HER2 IHC 2+/in-situ hybridization (ISH)-negative. We aim to assess the survival difference between HER2 IHC 1+ and HER2 IHC 2+/ISH-negative breast cancer patients with metastasis at presentation and construct a prognostic nomogram for HER2-low patients. METHOD: Patients diagnosed with de novo metastatic HER2-low breast cancer from 2010 to 2015 were included and analyzed using the National Cancer Database (NCDB). Cox proportional hazards regression model and Kaplan-Meier (KM) method were used for survival analysis. Nomograms were built to predict survival. RESULT: A total of 7897 patients were included in the final analysis, among which 5458 (69.1%) patients were HER2 IHC 1+ and 2439 (30.9%) were HER2 IHC 2+/ISH-negative. Although the Kaplan-Meier survival analysis showed difference in survival, this survival difference was lost in the multivariate Cox analysis (multivariate: HR (hazard ratio) = 0.97; 95% CI (confidence interval) [0.92-1.03]). A prognostic nomogram was successfully constructed for individually predicting the long-term survival rate of HER2-low patients, which exhibited an acceptable predictive capability in training (C index: 0.719) and validation cohort (C index: 0.706). This nomogram could easily divide patients into high and low-risk subgroups with distinct prognoses. CONCLUSIONS: Our data suggest no statistical survival differences between HER2 1+ and HER2 2+ breast cancer. Additionally, a nomogram was constructed with an acceptable capacity to individually predict the long-term outcome of HER2-low metastatic breast cancer patients.
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Neoplasias de la Mama , Humanos , Femenino , Neoplasias de la Mama/metabolismo , Receptor ErbB-2/genética , Receptor ErbB-2/metabolismo , Pronóstico , InmunohistoquímicaRESUMEN
Diffuse large B-cell lymphoma (DLBCL) is malignant hyperplasia of B lymphocytes and standard care cannot satisfactorily meet clinical needs. Potential diagnostic and prognostic DLBCL biomarkers are needed. NCBP1 could bind to the 5'-end cap of pre-mRNAs to participate in RNA processing, transcript nuclear export and translation. Aberrant NCBP1 expression is involved in the pathogenesis of cancers, but little is known about NCBP1 in DLBCL. We proved that NCBP1 is significantly elevated in DLBCL patients and is associated with their poor prognosis. Then, we found that NCBP1 is important for the proliferation of DLBCL cells. Moreover, we verified that NCBP1 enhances the proliferation of DLBCL cells in a METTL3-dependent manner and found that NCBP1 enhances the m6A catalytic function of METTL3 by maintaining METTL3 mRNA stabilization. Mechanistically, the expression of c-MYC is regulated by NCBP1-enhanced METTL3, and the NCBP1/METTL3/m6A/c-MYC axis is important for DLBCL progression. We identified a new pathway for DLBCL progression and suggest innovative ideas for molecular targeted therapy of DLBCL.
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Linfoma de Células B Grandes Difuso , Metiltransferasas , Humanos , Metiltransferasas/genética , Metiltransferasas/metabolismo , Línea Celular Tumoral , Proliferación Celular/genética , Linfoma de Células B Grandes Difuso/genéticaRESUMEN
Aiming at the difficulties of lumbar vertebrae segmentation in computed tomography (CT) images, we propose an automatic lumbar vertebrae segmentation method based on deep learning. The method mainly includes two parts: lumbar vertebra positioning and lumbar vertebrae segmentation. First of all, we propose a lumbar spine localization network of Unet network, which can directly locate the lumbar spine part in the image. Then, we propose a three-dimensional XUnet lumbar vertebrae segmentation method to achieve automatic lumbar vertebrae segmentation. The method proposed in this paper was validated on the lumbar spine CT images on the public dataset VerSe 2020 and our hospital dataset. Through qualitative comparison and quantitative analysis, the experimental results show that the method proposed in this paper can obtain good lumbar vertebrae segmentation performance, which can be further applied to detection of spinal anomalies and surgical treatment.
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Aprendizaje Profundo , Vértebras Lumbares , Humanos , Vértebras Lumbares/diagnóstico por imagen , Algoritmos , Columna Vertebral , Tomografía Computarizada por Rayos X/métodos , Hospitales , Procesamiento de Imagen Asistido por Computador/métodosRESUMEN
To determine the overall tumor microenvironment (TME), characteristics, and transition mechanisms in primary central nervous system lymphoma (PCNSL), we performed spatial transcriptomics and matched the corresponding single-cell sequencing data of PCNSL patients. We found that tumor cells may achieve a "TME remodeling pattern" through an "immune pressure-sensing model", in which they could choose to reshape the TME into a barrier environment or a cold environment according to the immune pressure. A key FKBP5+ tumor subgroup was found to be responsible for pushing tumors into the barrier environment, which provides a possible way to evaluate the stage of PCNSL. The specific mechanism of the TME remodeling pattern and the key molecules of the immune pressure-sensing model were identified through the spatial communication analysis. Finally, we discovered the spatial and temporal distributions and variation characteristics of immune checkpoint molecules and CAR-T target molecules in immunotherapy. These data clarified the TME remodeling pattern of PCNSL, provided a reference for its immunotherapy, and provided suggestions for the TME remodeling mechanism of other cancers.
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Linfoma , Neoplasias , Humanos , Microambiente Tumoral , Neoplasias/patología , Inmunoterapia , Linfoma/patología , Análisis de la Célula Individual , Sistema Nervioso Central/patologíaRESUMEN
Engineered cysteines are frequently used for site-specific conjugation in antibody-drug conjugate (ADC) development. When cysteine-engineered mAbs are produced in the cell culture process, the sulfhydryl groups on the engineered cysteines are mostly in an oxidized form. The oxidized cysteines require multiple steps (such as reduction, reoxidation, and buffer exchanges) to reactivate for bioconjugation, which complicates the ADC production process and reduces yields. In this study, we identified a Q166C mutation in the light chain that allows the presence of free sulfhydryl groups during cell culture and purification process. This mutation is in the constant region and away from sites involved in antigen binding or Fc-mediated functions. The free sulfhydryl reacts readily with maleimide in a mild solution at a high conjugation rate. This is only the second such site reported (the first one is Q124C in the light chain). Using the Q166C mutation, we conjugated an anti-angiopoietin-2 (Ang-2) peptide on bevacizumab, an anti-vascular endothelial growth factor (VEGF) antibody, to construct a peptide antibody conjugate, Ava-Plus, which could block two pro-angiogenic factors simultaneously. Ava-Plus showed high affinity for both VEGF and Ang-2 and demonstrated higher activity than bevacizumab in inâ vitro cell migration and inâ vivo mouse xenograft models.
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Anticuerpos Monoclonales , Inmunoconjugados , Ratones , Humanos , Animales , Anticuerpos Monoclonales/genética , Factor A de Crecimiento Endotelial Vascular/genética , Bevacizumab , Cisteína/genética , Compuestos de Sulfhidrilo , Inmunoconjugados/genéticaRESUMEN
Background: Non-obstructive azoospermia (NOA) is a common clinical cause of male infertility. Research suggests that macrophages are linked to testicular function; however, their involvement in NOA remains unknown. Methods: To evaluate the importance of macrophages infiltration in NOA and identify the macrophage-related biomarkers, the gene-expression microarray data GSE45885 and the single-cell transcriptomic data GSE149512 were utilized from the Gene Expression Omnibus (GEO). A single-sample gene set enrichment analysis (ssGSEA) was conducted to investigate immune cell proliferation. The Seurat package was used for the single-cell data analysis, and the limma package was used to identify the differentially expressed genes between the NOA and normal samples. Moreover, we conducted a weighted gene co-expression network analysis (WGCNA) to identify the macrophage-related key modules and genes, and conducted Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) analyses for the functional exploration. To identify the macrophage-related biomarkers, we conducted least absolute shrinkage and selection operator (LASSO) and support vector machine-recursive feature elimination (SVM-RFE) analyses. Real-time quantitative polymerase chain reaction (RT-qPCR) was used to verify the marker genes present in NOA. Results: We confirmed that open reading frame 72 gene on chromosome 9 (C9orf72) [area under the curve (AUC) =0.861] and cartilage-associated protein (CRTAP) (AUC =0.917) were the hub genes of NOA, and the RT-qPCR analysis revealed the critical expression of both genes in NOA. Conclusions: Through the combination of tissue transcriptomic and single-cell RNA-sequencing analyses, we concluded that macrophage infiltration is significant in different subtypes of NOA, and we hypothesized that C9orf72 and CRTAP play critical roles in NOA due to their high expression in macrophages.