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Postpancreatectomy hemorrhage (PPH) is an important risk factor for postoperative complications after laparoscopic pancreaticoduodenectomy (LPD). Recent studies have reported that the use of ligamentum teres hepatis (LTH) in LPD may reduce the risk of PPH. Therefore, this study aims to investigate whether wrapping the hepatic hilar artery with the LTH can reduce PPH after LPD. We reviewed the data of 131 patients who underwent LPD in our team from April 2018 to December 2023. The patients were divided into Groups A (60 patients) and B (71 patients) according to whether the hepatic portal artery was wrapped or not. The perioperative data of the two groups were compared to evaluate the effect of LTH wrapping the hepatic hilar artery on LPD. The platelet count of Group A was (225.25 ± 87.61) × 10^9/L, and that of Group B was (289.38 ± 127.35) × 10^9/L, with a statistically significant difference (p < 0.001). The operation time of group A [300.00 (270.00, 364.00)] minutes was shorter than that of group B [330.00 (300.00, 360.00)] minutes, p = 0.037. In addition, A set of postoperative hospital stay [12.00 (10.00, 15.00)] days shorter than group B [15.00 (12.00, 19.50)] days, p < 0.001. No PPH occurred in Group A, while 8 patients in Group B had PPH (7 cases of gastroduodenal artery hemorrhage and 1 case of proper hepatic artery hemorrhage), p = 0.019. The new technique of wrapping the hepatic hilar artery through the LTH can effectively reduce the occurrence of PPH after LPD.
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Arteria Hepática , Laparoscopía , Pancreaticoduodenectomía , Hemorragia Posoperatoria , Humanos , Pancreaticoduodenectomía/efectos adversos , Pancreaticoduodenectomía/métodos , Masculino , Femenino , Persona de Mediana Edad , Laparoscopía/efectos adversos , Laparoscopía/métodos , Arteria Hepática/cirugía , Hemorragia Posoperatoria/etiología , Hemorragia Posoperatoria/prevención & control , Anciano , Ligamentos/cirugía , Estudios Retrospectivos , Tempo Operativo , Adulto , Complicaciones Posoperatorias/prevención & control , Complicaciones Posoperatorias/etiología , Tiempo de InternaciónRESUMEN
Glucuronidation, a crucial process in phase II metabolism, plays a vital role in the detoxification and elimination of endogenous substances and xenobiotics. A comprehensive and confident profiling of glucuronate-conjugated metabolites is imperative to understanding their roles in physiological and pathological processes. In this study, a chemical isotope labeling and dual-filtering strategy was developed for global profiling of glucuronide metabolites in biological samples. N,N-Dimethyl ethylenediamine (DMED-d0) and its deuterated counterpart DMED-d6 were used to label carboxylic acids through an amidation reaction. First, carboxyl-containing compounds were extracted based on a characteristic mass difference (Δm/z, 6.037 Da) observed in MS between light- and heavy-labeled metabolites (filter I). Subsequently, within the pool of carboxyl-containing compounds, glucuronides were identified using two pairs of diagnostic ions (m/z 247.1294/253.1665 and 229.1188/235.1559 for DMED-d0/DMED-d6-labeled glucuronides) originating from the fragmentation of the derivatized glucuronic acid group in MS/MS (filter II). Compared with non-derivatization, DEMD labeling significantly enhanced the detection sensitivity of glucuronides, as evidenced by a 3- to 55-fold decrease in limits of detection for representative standards. The strategy was applied to profiling glucuronide metabolites in urine samples from colorectal cancer (CRC) patients. A total of 685 features were screened as potential glucuronides, among which 181 were annotated, mainly including glucuronides derived from lipids, organic oxygen, and phenylpropanoids. Enzymatic biosynthesis was employed to accurately identify unknown glucuronides without standards, demonstrating the reliability of the dual-filtering strategy. Our strategy exhibits great potential for profiling the glucuronide metabolome with high coverage and confidence to reveal changes in CRC and other diseases.
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Glucurónidos , Marcaje Isotópico , Humanos , Glucurónidos/orina , Glucurónidos/metabolismo , Glucurónidos/química , Espectrometría de Masas en Tándem/métodos , Neoplasias Colorrectales/orina , Neoplasias Colorrectales/diagnóstico , Neoplasias Colorrectales/metabolismoRESUMEN
BACKGROUND: In recent years, pure laparoscopic radical surgery for Bismuth-Corlette type III and IV hilar cholangiocarcinoma (HCCA) has been preliminarily explored and applied, but the surgical strategy and safety are still worthy of further improvement and attention. AIM: To summarize and share the application experience of the emerging strategy of "hepatic hilum area dissection priority, liver posterior separation first" in pure laparoscopic radical resection for patients with HCCA of Bismuth-Corlette types III and IV. METHODS: The clinical data and surgical videos of 6 patients with HCCA of Bismuth-Corlette types III and IV who underwent pure laparoscopic radical resection in our department from December 2021 to December 2023 were retrospectively analyzed. RESULTS: Among the 6 patients, 4 were males and 2 were females. The average age was 62.2 ± 11.0 years, and the median body mass index was 20.7 (19.2-24.1) kg/m2. The preoperative median total bilirubin was 57.7 (16.0-155.7) µmol/L. One patient had Bismuth-Corlette type IIIa, 4 patients had Bismuth-Corlette type IIIb, and 1 patient had Bismuth-Corlette type IV. All patients successfully underwent pure laparoscopic radical resection following the strategy of "hepatic hilum area dissection priority, liver posterior separation first". The operation time was 358.3 ± 85.0 minutes, and the intraoperative blood loss volume was 195.0 ± 108.4 mL. None of the patients received blood transfusions during the perioperative period. The median length of stay was 8.3 (7.0-10.0) days. Mild bile leakage occurred in 2 patients, and all patients were discharged without serious surgery-related complications. CONCLUSION: The emerging strategy of "hepatic hilum area dissection priority, liver posterior separation first" is safe and feasible in pure laparoscopic radical surgery for patients with HCCA of Bismuth-Corlette types III and IV. This strategy is helpful for promoting the modularization and process of pure laparoscopic radical surgery for complicated HCCA, shortens the learning curve, and is worthy of further clinical application.
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Corticotropin-releasing hormone (CRH) has been well documented playing a role in the regulation of cellular processes, immune responses, and inflammatory processes that can influence the occurrence and development of tumors. Supervillin (SVIL) is a membrane-associated and actin-binding protein, which is actively involved in the proliferation, spread, and migration of cancer cells. This work investigated CRH's influence on bladder cancer cells' migration and relevant mechanisms. By using human bladder cancer cells T24 and RT4 in wound healing experiments and transwell assay, we found that the migration ability of the T24 cells was significantly increased after CRH treatment. In vivo experiments showed that CRH significantly promoted the metastases of T24 cells in cell line-derived xenograft (CDX) mouse model. Interestingly, downregulation of SVIL by SVIL-specifc small hairpin RNAs significantly reduced the promoting effect of CRH on bladder cancer cell migration. Furthermore, CRH significantly increased SVIL messenger RNA and protein expression in T24 cells, accompanied with AKT and ERK phosphorylation in T24 cells. Pretreatment with AKT inhibitor (MK2206) blocked the CRH-induced SVIL expression and ERK phosphorylation. Also, inhibition of ERK signaling pathway by U0126 significantly reduced the CRH-induced SVIL expression and AKT phosphorylation. It suggested that cross-talking between AKT and ERK pathways was involved in the effect of CRH on SVIL. Taken together, we demonstrated that CRH induced migration of bladder cancer cells, in which AKT and ERK pathways -SVIL played a key role.
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Spent graphite, as the main component of retired batteries, have attracted plenty of attentions. Although a series of recycling strategies are proposed, they still suffer from high cost of regeneration and large CO2 emission, mainly ascribed to the full-recovery of surface and internal phase at ultra-high temperature. However, the existing of suitable internal defects is conductive to their energy-storage abilities. Herein, with the introduction of Fe-based catalysts, spent graphite is successfully repaired at low temperature with the tailored surface traits, including conductivities, isotropy and so on. As Li-storage anodes, all of samples can display a capacity of 340 mAh g-1 above at 1.0 C after 200 cycles. At high rate 5.0 C, their capacity can be also kept ≈300 mAh g-1, and remained ≈233 mAh g-1 even after 1000 cycles. Assisted by electrochemical and kinetic behaviors, their cycling traits with dynamic surface transformations are detailed explored, including activated/fading mechanism, Li-depositions forming etc. Moreover, the calculated constant time of as-optimized regenerated sample is ≈3.0 × 10-4 s, further revealing the importance of surface designing. Therefore, the work is expected to shed light on their energy-storage behaviors, and offer low-temperature regenerated strategies of spent graphite with high value.
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OBJECTIVE: To demonstrate the value of using 50 keV virtual monochromatic images with deep learning image reconstruction (DLIR) in low-dose dual-energy CT enterography (CTE). METHODS: In this prospective study, 114 participants (62 % M; 41.9 ± 16 years) underwent dual-energy CTE. The early-enteric phase was performed using standard-dose (noise index (NI): 8) and images were reconstructed at 70 keV and 50 keV with 40 % strength ASIR-V (ASIR-V40%). The late-enteric phase used low-dose (NI: 12) and images were reconstructed at 50 keV with ASIR-V40%, and DLIR at medium (DLIR-M) and high strength (DLIR-H). Image standard deviation (SD), signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR), edge-rise-slope (ERS) were computed. The quantitative comb sign score was calculated for the 27 patients with Crohn's disease. The subjective noise, image contrast, display of rectus artery were scored using a 5-point scale by two radiologists blindly. RESULTS: Effective dose was reduced by 50 % (P < 0.001) in the late-enteric phase to 3.26 mSv. The lower-dose 50 keV-DLIR-H images (SD:17.7 ± 0.5HU) had similar image noise (P = 0.97) as the standard-dose 70 keV-ASIR-V40% images (SD:17.7 ± 0.73HU), but with higher (P < 0.001) SNR, CNR, ERS and quantitative comb sign score (5.7 ± 0.17, 1.8 ± 0.12, 156.04 ± 5.21 and 5.05 ± 0.73, respectively). Furthermore, the lower-dose 50 keV-DLIR-H images obtained the highest score in the rectus artery visibility (4.27 ± 0.6). CONCLUSIONS: The 50 keV images in dual-energy CTE with DLIR provides high-quality images, with a 50 % reduction in radiation dose. Images with high contrast and density resolutions significantly enhance the diagnostic confidence of Crohn's disease and are essential for the clinical development of individualized treatment plans.
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Aprendizaje Profundo , Dosis de Radiación , Interpretación de Imagen Radiográfica Asistida por Computador , Imagen Radiográfica por Emisión de Doble Fotón , Tomografía Computarizada por Rayos X , Humanos , Femenino , Masculino , Adulto , Estudios Prospectivos , Tomografía Computarizada por Rayos X/métodos , Imagen Radiográfica por Emisión de Doble Fotón/métodos , Interpretación de Imagen Radiográfica Asistida por Computador/métodos , Persona de Mediana Edad , Relación Señal-Ruido , Anciano , Enfermedad de Crohn/diagnóstico por imagenRESUMEN
OBJECTIVE: The primary objective of this study is to explore the significance of concurrent evaluation of HER2 gene amplification and p53 and Ki67 expression in gastric cancer tissues. METHODS: Fluorescence in situ hybridization (FISH) and immunohistochemistry (IHC) methodologies were used to detect HER2 gene amplification, as well as the expression levels of HER2, p53, and Ki67 proteins, across a group of 78 gastric cancer cases. RESULTS: The expression rate of the HER2 protein was determined to be 43.6% (34/78), with 17.9% (14/78) categorized as HER2 protein 3 + , 14.1% (11/78) as HER2 protein 2 + , and 11.5% (9/78) as HER2 protein 1 + . Using FISH technology, the HER2 gene amplification rate was identified as 19.2% (15/78), including 3 cases of HER2 gene cluster amplification, 5 cases of large granular amplification, 4 cases of punctate amplification, and 3 cases of high polysomy. The positive rate of p53 in gastric cancer cells was 52.6% (41/78), with 62.8% (49/78) of patients exhibiting a ki67 proliferation index ≤ 30, and 37.2% (29/78) accounting for a ki67 proliferation index > 30. The expression rates of the HER2 gene, p53, and ki67 in gastric cancer tissues were significantly associated with both gastric cancer staging and lymph node metastasis (P < 0.05). CONCLUSION: The HER2 gene amplification rate and gene copy number exhibit a positive correlation with the expression rates of p53 and ki67. Combining these assessments can provide crucial insights into the assessment of metastatic potential, disease progression, and prognosis of gastric tumor cells. This holds paramount importance in steering the formulation of individualized treatment strategies.
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PURPOSE: The copper metabolism MURR1 domain 10 (COMMD10) plays a role in a variety of tumors. Here, we investigated its role in gastric cancer (GC). METHODS: Online prediction tools, quantitative real-time PCR, western blotting and immunohistochemistry were used to evaluate the expression of COMMD10 in GC. The effect of COMMD10 knockdown was investigated in the GC cell lines and in in vivo xenograft tumor experiments. Western blotting and immunofluorescence were used to explore the relationships between COMMD10 and DNA damage. RESULTS: The expression of COMMD10 was upregulated in GC compared to that in para-cancerous tissue and correlated with a higher clinical TNM stage (P = 0.044) and tumor size (P = 0.0366). High COMMD10 expression predicted poor prognosis in GC. Knockdown of COMMD10 resulted in the suppression of cell proliferation, migration, and invasion, accompanied by cell cycle arrest and an elevation in apoptosis rate. Moreover, the protein expression of COMMD10 was decreased in cisplatin-induced DNA-damaged GC cells. Suppression of COMMD10 impeded DNA damage repair, intensified DNA damage, and activated ATM-p53 signaling pathway in GC. Conversely, restoration of COMMD10 levels suppressed DNA damage and activation of the ATM-p53 signaling cascade. Additionally, knockdown of COMMD10 significantly restrained the growth of GC xenograft tumors while inhibiting DNA repair, augmenting DNA damage, and activating the ATM-p53 signaling pathway in xenograft tumor tissue. CONCLUSION: COMMD10 is involved in DNA damage repair and maintains genomic stability in GC; knockdown of COMMD10 impedes the development of GC by exacerbating DNA damage, suggesting that COMMD10 may be new target for GC therapy.
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Proliferación Celular , Daño del ADN , Progresión de la Enfermedad , Neoplasias Gástricas , Neoplasias Gástricas/patología , Neoplasias Gástricas/genética , Neoplasias Gástricas/metabolismo , Humanos , Animales , Ratones , Femenino , Masculino , Ratones Desnudos , Línea Celular Tumoral , Apoptosis , Pronóstico , Persona de Mediana Edad , Ensayos Antitumor por Modelo de Xenoinjerto , Ratones Endogámicos BALB C , Movimiento Celular , Proteínas Adaptadoras Transductoras de Señales/genética , Proteínas Adaptadoras Transductoras de Señales/metabolismo , Regulación Neoplásica de la Expresión GénicaRESUMEN
In order to investigate the acoustic oscillation characteristics of gas-liquid pintle rocket engines and elucidate the path by which spray combustion process provides energy to the combustor pressure oscillation, a LOX/GCH4 pintle engine with rectangular combustor was designed. By adding transverse velocity disturbance for the first time, the acoustic response of spray combustion process was simulated, and the effect of excitation amplitude on acoustic response was researched. Numerical results show that the adopted transverse velocity disturbance can excite the first-order transverse acoustic oscillation with same excitation frequency in the engine combustor. The acoustic response maintenance mechanism under extrinsic excitation is summarized for pintle engines. Besides, the temperature distribution inside the engine combustor tends to be uniform, and the low-frequency oscillation caused by the flame transverse swing gradually disappears. The amplitude of combustor pressure oscillation is dominated by excitement amplitude and phase difference between the pressure and heat release in combustion reaction region. In addition, the time-averaged combustor pressure can be amplified mainly by transverse velocity disturbance. The research work can provide a reference for related fire tests on the acoustic response of a subscale gas-liquid pintle engine.
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Purpose: The aim of this study was to investigate the causal relationships between circulating cell traits and risk of renal disorders. Methods: We applied a comprehensive two-sample Mendelian randomization (MR) analysis. Single nucleotide polymorphisms (SNPs) from publicly available genome-wide association studies (GWAS) databases were utilized. Genetically predicted instrumental variables of human blood cell traits were extracted from Blood Cell Consortium (BCX) while data on renal diseases was obtained from Finngen consortium. The primary MR analysis was conducted using the inverse variance weighted (IVW) method, with the weighted median (WM) and MR-Egger models used as additional methods. Sensitivity analyses, including MR-PRESSO, radial regression and MR-Egger intercept were conducted to detect outliers and assess horizontal pleiotropy. We further utilized the leave-one-out analysis to assess the robustness of the results. Causal associations were considered significant based on false rate correction (FDR), specifically when the IVW method provided a pFDR < 0.05. Results: Our results demonstrated that both white blood cell (WBC) count (OR = 1.50, 95% CI = 1.10-2.06, pFDR = 0.033, pIVW = 0.011) and lymphocyte count (OR = 1.50, 95% CI = 1.13-1.98, pFDR = 0.027, pIVW = 0.005) were causally associated with a higher risk of IgA nephropathy. Furthermore, WBC count was identified as a significant genetic risk factor for renal malignant neoplasms (OR = 1.23, 95% CI = 1.06-1.43, pFDR = 0.041, pIVW = 0.007). Additionally, an increased level of genetically predicted eosinophils was found to be causally associated with a higher risk of diabetic nephropathy (OR = 1.21, 95% CI = 1.08-1.36, pFDR = 0.007, pIVW = 0.001). No evidence of pleiotropy was determined. Conclusion: Our findings provide evidence of causal associations of circulating WBC count, lymphocyte count and IgA nephropathy, WBC count and renal malignant neoplasms, and eosinophil count and diabetic nephropathy. These results have the potential to contribute to the development of novel diagnostic options and therapeutic strategies for renal disorders.
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BACKGROUND: As a member of the Cullin family, Cullin2 (CUL2) is involved in the development and spread of different types of cancers. However, the precise role of CUL2 in human cancer remains largely elusive. METHODS: In this study, various databases were applied to observe the CUL2 expression. Kaplan-Meier and Spearman correlation analyses were employed to investigate the potential links between CUL2 level, patient prognosis, and the infiltration of immune cells. In addition, the association between CUL2 and the efficacy of immunotherapy in an immunotherapy cohort was investigated. Moreover, the expression and distribution of CUL2 in cells were observed using the Human Protein Atlas (THPA) database. Finally, clinical tissue specimens and in vitro function assays were conducted to validate the expressions and effects of CUL2 on the biological functions in hepatocellular carcinoma (HCC) cells. RESULTS: While there are variations in CUL2 expression across different organs and cell types, it is notably upregulated in a majority of tumor tissues. In addition, CUL2 gene mutations are common in multiple cancers with low mutation rates and CUL2 is closely related to the prognosis of some cancer's patients, some immune regulatory factors, TMB, MSI, MMR genes, and DNA methylation. Further, our results found that downregulating CUL2 inhibits the proliferation, and migration abilities. CONCLUSIONS: The expression of CUL2 has an impact on the prognosis of various tumors, and this correlation is particularly noteworthy due to its significant association with the infiltration of immune cells within tumors. CUL2 was an oncogene contributing to the progression of HCC.
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Carcinoma Hepatocelular , Proteínas Cullin , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/inmunología , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patología , Proteínas Cullin/genética , Proteínas Cullin/metabolismo , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/inmunología , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patología , Pronóstico , Regulación Neoplásica de la Expresión Génica , Línea Celular Tumoral , Biomarcadores de Tumor/metabolismo , Biomarcadores de Tumor/genética , Proliferación Celular/genética , Mutación , Movimiento Celular/genéticaRESUMEN
OBJECTIVE: The high mortality rate of gastric cancer, traditionally managed through surgery, underscores the urgent need for advanced therapeutic strategies. Despite advancements in treatment modalities, outcomes remain suboptimal, necessitating the identification of novel biomarkers to predict sensitivity to immunotherapy. This study focuses on utilizing single-cell sequencing for gene identification and developing a random forest model to predict immunotherapy sensitivity in gastric cancer patients. METHODS: Differentially expressed genes were identified using single-cell RNA sequencing (scRNA-seq) and gene set enrichment analysis (GESA). A random forest model was constructed based on these genes, and its effectiveness was validated through prognostic analysis. Further, analyses of immune cell infiltration, immune checkpoints, and the random forest model provided deeper insights. RESULTS: High METTL1 expression was found to correlate with improved survival rates in gastric cancer patients (P = 0.042), and the random forest model, based on METTL1 and associated prognostic genes, achieved a significant predictive performance (AUC = 0.863). It showed associations with various immune cell types and negative correlations with CTLA4 and PDCD1 immune checkpoints. Experiments in vitro and in vivo demonstrated that METTL1 enhances gastric cancer cell activity by suppressing T cell proliferation and upregulating CTLA4 and PDCD1. CONCLUSION: The random forest model, based on scRNA-seq, shows high predictive value for survival and immunotherapy sensitivity in gastric cancer patients. This study underscores the potential of METTL1 as a biomarker in enhancing the efficacy of gastric cancer immunotherapy.
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Inmunoterapia , Análisis de la Célula Individual , Neoplasias Gástricas , Neoplasias Gástricas/genética , Neoplasias Gástricas/terapia , Neoplasias Gástricas/inmunología , Neoplasias Gástricas/mortalidad , Humanos , Análisis de la Célula Individual/métodos , Inmunoterapia/métodos , Animales , Ratones , Pronóstico , Biomarcadores de Tumor/genética , Análisis de Secuencia de ARN/métodos , Femenino , Masculino , Regulación Neoplásica de la Expresión Génica , Ensayos Antitumor por Modelo de Xenoinjerto , Línea Celular Tumoral , Bosques AleatoriosRESUMEN
The regulatory potential of long noncoding RNA (lncRNA) FBXL19-AS1 has been highlighted in various cancers, but its effect on triple-negative breast cancer (TNBC) remains unclear. Here, we aimed to elucidate the role of FBXL19-AS1 in TNBC and its underlying mechanism. RT-qPCR was employed to detect the expressions of FBXL19-AS1 and miR-378a-3p in tissues and cells. Immunohistochemical staining and western blot were utilized to detect the expression levels of proteins. Cell activities were detected using flow cytometry, CCK-8, and transwell assay. Dual-luciferase reporter and RNA immunoprecipitation (RIP) assays were deployed to investigate interactions of different molecules. Protein-protein interaction (PPI) network, gene ontology (GO), and Kyoto encyclopedia of genes and genomes (KEGG) pathways were used to analyze the downstream pathway. In vivo xenograft model was conducted to detect the effect of FBXL19-AS1 on tumor growth. FBXL19-AS1 was overexpressed in TNBC tissues and cell lines compared with counterparts. FBXL19-AS1 knockdown suppressed TNBC cell activities, whereas its overexpression exhibited the opposite effect. Mechanistically, FBXL19-AS1 was found to interact with miR-378a-3p. Further analysis revealed that miR-378a-3p exerted tumor-suppressive effects in TNBC cells. Additionally, miR-378a-3p targeted and downregulated the expression of ubiquitin aldehyde binding 2 (OTUB2), a deubiquitinase associated with TNBC progression. In vivo experiments substantiated the inhibitory effects of FBXL19-AS1 knockdown on TNBC tumorigenesis, and a miR-378a-3p inhibitor partially rescued these effects. The downstream pathway of the miR-378a-3p/OTUB2 axis was explored, revealing connections with proteins involved in modifying other proteins, removing ubiquitin molecules, and influencing signaling pathways, including the Hippo signaling pathway. Western blot analysis confirmed changes in YAP and TAZ expression levels, indicating a potential regulatory network. In summary, FBXL19-AS1 promotes exacerbation in TNBC by suppressing miR-378a-3p, leading to increased OTUB2 expression. The downstream mechanism may be related to the Hippo signaling pathway. These findings propose potential therapeutic targets for TNBC treatment.
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MicroARNs , ARN Largo no Codificante , Neoplasias de la Mama Triple Negativas , Animales , Femenino , Humanos , Ratones , Línea Celular Tumoral , Proliferación Celular , Enzimas Desubicuitinizantes/metabolismo , Proteínas F-Box/metabolismo , Proteínas F-Box/genética , Regulación Neoplásica de la Expresión Génica , Ratones Endogámicos BALB C , Ratones Desnudos , MicroARNs/metabolismo , MicroARNs/genética , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismo , Neoplasias de la Mama Triple Negativas/metabolismo , Neoplasias de la Mama Triple Negativas/patología , Neoplasias de la Mama Triple Negativas/genéticaRESUMEN
OBJECTIVE: Focal cervical kyphotic deformity (FCK) without neurologic compression is not uncommon in patients with cervical spondylotic myelopathy (CSM) who underwent anterior cervical decompression and fusion (ACDF) surgery. It remains unclear whether FCK at non-responsible levels needs to be treated simultaneously. This study aims to investigate whether FCK at non-responsible levels is the prognostic factor for CSM and elucidate the surgical indication for FCK. METHODS: Patients with CSM who underwent ACDF between January 2016 and April 2021 were included. Patients were divided into two groups according to the presence of FCK and two classifications according to global cervical sagittal alignment. Clinical outcomes were compared using Japanese Orthopaedic Association (JOA) scores and recovery rate (RR) of neurologic function. Univariate and multivariate analysis based on RR assessed the relationship between various possible prognostic factors and clinical outcomes. The receiver operating characteristic curve (ROC) was used to determine the optimal cutoff value of the focal Cobb angle to predict poor clinical outcomes. RESULTS: A total of 94 patients were included, 41 with FCK and 53 without. Overall, the RR of neurologic function was significantly lower in the FCK than in the non-FCK group. Further analysis showed that the RR difference between the two groups was only observed in hypo-lordosis classification (kyphotic and sigmoid alignment), but not in the lordosis classification. Multivariate analysis showed that the preoperative focal Cobb angle in the FCK level (OR = 0.42; 95% CI = 0.18-0.97) was independently associated with clinical outcomes in the hypo-lordosis classification. The optimal cutoff point of the preoperative focal kyphotic Cobb angle was calculated at 4.05°. CONCLUSION: For CSM with hypo-lordosis, FCK was a risk factor for poor postoperative outcomes. Surgeons may consider treating the FCK simultaneously if the focal kyphotic Cobb angle of FCK is greater than 4.05° and is accompanied by cervical global kyphotic or sigmoid deformity.
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Vértebras Cervicales , Descompresión Quirúrgica , Cifosis , Fusión Vertebral , Humanos , Fusión Vertebral/métodos , Femenino , Masculino , Descompresión Quirúrgica/métodos , Persona de Mediana Edad , Cifosis/cirugía , Vértebras Cervicales/cirugía , Anciano , Estudios Retrospectivos , Espondilosis/cirugía , PronósticoRESUMEN
OBJECTIVE: The objective of this study is to assess the clinical pathological attributes of Hepatoid Adenocarcinoma of the Stomach (HAS) and to delineate the differential diagnostic considerations about it. METHOD: The investigation involved analyzing 31 HAS cases using histomorphological assessment, immunohistochemical profiling, and relevant gene detection methodologies. RESULTS: Among the 31 HAS cases, 9 (29.0%) were of trabecular hepatoid adenocarcinoma of the stomach, 7 (22.6%) were of glandular hepatoid adenocarcinoma of the stomach, 4 (12.9%) were of nesting hepatoid adenocarcinoma of the stomach, 3 (9.7%) were of clear cell hepatoid adenocarcinoma of the stomach, and 8 (25.8%) were of diverse hepatoid adenocarcinoma of the stomach. Of these 31 cases, 24 were male, accounting for 77.4% of the cases. Serum alpha-fetoprotein (AFP) levels were notably elevated, with radioimmunoassay results reaching 1240 ng/ml; 28 out of 31 cases had AFP levels below 25 µg/l, accounting for 90.3%. Related genes: HER2 protein indicated positive expression on the cell membrane in 35.5% (11/31) of the cases; HER2 gene amplification detected by the FISH technique was 12.9% (4/31). Tumoral stromal lymphocytes exhibited a PD-1 positive expression rate of 58.1% (18/31). In gastric cancer tissues, the PD-L1 positive rate was 45.1% (14/31). CONCLUSION: HAS represents a distinctive subtype of gastric cancer with a propensity for mimicking other forms of tumors, underscoring the significance of discerning its unique histopathological attributes for accurate differential diagnosis and tailored therapeutic interventions.
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Fish typically adapt to their environment through evolutionary traits, and this adaptive strategy plays a critical role in promoting species diversity. Onychostoma macrolepis is a rare and endangered wild species that exhibits a life history of overwintering in caves and breeding in mountain streams. We analyzed the morphological characteristics, histological structure, and expression of circadian clock genes in O. macrolepis to elucidate its adaptive strategies to environmental changes in this study. The results showed that the relative values of O. macrolepis eye diameter, body height, and caudal peduncle height enlarged significantly during the breeding period. The outer layer of the heart was dense; the ventricular myocardial wall was thickened; the fat was accumulated in the liver cells; the red and white pulp structures of the spleen, renal tubules, and glomeruli were increased; and the goblet cells of the intestine were decreased in the breeding period. In addition, the spermatogenic cyst contained mature sperm, and the ovaries were filled with eggs at various stages of development. Throughout the overwintering period, the melano-macrophage center is located between the spleen and kidney, and the melano-macrophage center in the cytoplasm has the ability to synthesize melanin, and is arranged in clusters to form cell clusters or white pulp scattered in it. Circadian clock genes were identified in all organs, exhibiting significant differences between the before/after overwintering period and the breeding period. These findings indicate that the environment plays an important role in shaping the behavior of O. macrolepis, helping the animals to build self-defense mechanisms during cyclical habitat changes. Studying the morphological, histological structure and circadian clock gene expression of O. macrolepis during the overwintering and breeding periods is beneficial for understanding its unique hibernation behavior in caves. Additionally, it provides an excellent biological sample for investigating the environmental adaptability of atypical cavefish species.
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Adaptación Fisiológica , Relojes Circadianos , Cyprinidae , Relojes Circadianos/genética , Cyprinidae/anatomía & histología , Cyprinidae/genética , Cyprinidae/fisiología , Cruzamiento , Conducta Sexual Animal/fisiología , Adaptación Fisiológica/fisiología , Animales , Masculino , Femenino , Estaciones del Año , Hígado/metabolismo , Bazo , Riñón , Proteínas de Peces/genética , Expresión Génica/fisiologíaRESUMEN
Due to their assembly properties and variable molecular weights, the potential biological toxicity effects of macromolecular organic ligand heavy metal complexes are more difficult to predict and their mechanisms are more complex. This study unraveled the toxicity response and metabolic compensation mechanism of tannic acid-Cr(III) (TA-Cr(III)) complex on alga Raphidocelis subcapitata using multi-omics approaches. Results showed TA-Cr(III) complex caused oxidative damage and photosystem disruption, destroying the cell morphology and inhibiting algal growth by >80 % at high exposure levels. TA-Cr(III) complex stress down-regulated proteins linked to proliferation, photosynthesis and antioxidation while upregulating carbon fixation, TCA cycle and amino acid metabolism. The increase of fumarate, citrate, isocitrate and semialdehyde succinate was validated by metabolomics analysis, which improved the TCA cycle, amino acid metabolism and carbon fixation. Activation of the above cellular processes somewhat compensated for the inhibition of algal photosynthesis by TA-Cr(III) complex exposure. In conclusion, physiological toxicity coupled with downstream metabolic compensation in response to Cr(III) complex of macromolecular was characterized in Raphidocelis subcapitata, unveiling the adaptive mechanism of algae under the stress of heavy metal complexes with macromolecular organic ligands.
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Taninos , Cromo/toxicidad , Fotosíntesis/efectos de los fármacos , Contaminantes Químicos del Agua/toxicidad , PolifenolesRESUMEN
Objective: To study the histopathological staging of atrophic lesions of the gastric mucosa. Methods: Histology and immunohistochemistry were used to closely examine 2144 specimens of atrophic gastric mucosa that were taken from endoscopic biopsies. Results: When the gastric mucosa epithelium is affected by infection, chemical stimulation, immune factors, genetic factors, and other factors, it may cause an atrophy of gastric mucosa epithelium and a decrease in the number of glands, intestinal metaplasia, hyperplasia of smooth muscle fibers, and atrophy of stem cells in the proliferative zone. In this study, we characterized the above lesions as atrophic lesions of the gastric mucosa. Based on the morphological and histological characteristics of the lesion, as well as the law of cell proliferation and transformation during its occurrence and development, we propose five stages. We also noted the onset age, gender correlation, and histopathological characteristics of each stage of gastric mucosal atrophies. Conclusion: Understanding the pathological staging of gastric mucosal atrophy is essential for treating patients correctly and keeping track of changes in malignant cells. It is also very important in preventing the initiation of gastric cancer or from getting worse.
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BACKGROUND: Malignant esophageal fistula (MEF), which occurs in 5% to 15% of esophageal cancer (EC) patients, has a poor prognosis. Accurate identification of esophageal cancer patients at high risk of MEF is challenging. The goal of this study was to build and validate a model to predict the occurrence of esophageal fistula in EC patients. METHODS: This study retrospectively enrolled 122 esophageal cancer patients treated by chemotherapy or chemoradiotherapy (53 with fistula, 69 without), and all patients were randomly assigned to a training (n = 86) and a validation (n = 36) cohort. Radiomic features were extracted from pre-treatment CTs, clinically predictors were identified by logistic regression analysis. Lasso regression model was used for feature selection, and radiomics signature building. Multivariable logistic regression analysis was used to develop the clinical nomogram, radiomics-clinical nomogram and radiomics prediction model. The models were validated and compared by discrimination, calibration, reclassification, and clinical benefit. RESULTS: The radiomic signature consisting of ten selected features, was significantly associated with esophageal fistula (P = 0.001). Radiomics-clinical nomogram was created by two predictors including radiomics signature and stenosis, which was identified by logistic regression analysis. The model showed good discrimination with an AUC = 0.782 (95% CI 0.684-0.8796) in the training set and 0.867 (95% CI 0.7461-0.987) in the validation set, with an AIC = 101.1, and good calibration. When compared to the clinical prediction model, the radiomics-clinical nomogram improved NRI by 0.236 (95% CI 0.153, 0.614) and IDI by 0.125 (95% CI 0.040, 0.210), P = 0.004. CONCLUSION: We developed and validated the first radiomics-clinical nomogram for malignant esophageal fistula, which could assist clinicians in identifying patients at high risk of MEF.
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Fístula Esofágica , Neoplasias Esofágicas , Humanos , Fístula Esofágica/diagnóstico por imagen , Fístula Esofágica/etiología , Neoplasias Esofágicas/complicaciones , Neoplasias Esofágicas/diagnóstico por imagen , Modelos Estadísticos , Nomogramas , Pronóstico , Radiómica , Estudios RetrospectivosRESUMEN
Corticotropin-releasing factor family peptides (CRF peptides) comprise corticotropin releasing hormone (CRH), urocortin (UCN1), UCN2 and UCN3. CRH is first isolated in the brain and later with UCNs found in many peripheral cells/tissues including the colon. CRH and UCNs function via the two types of receptors, CRF1 and CRF2, with CRH mainly acting on CRF1, UCN1 on both CRF1 &CRF2 and UCN2-3 on CRF2. Compiling evidence shows that CRH participates in inflammation and cancers via both indirect central effects related to stress response and direct peripheral influence. CRH, as a stress-response mediator, plays a significant central role in promoting the development of colitis involving colon motility, immunity and gut flora, while a few anti-colitis results of central CRH are also reported. Moreover, CRH is found to directly influence the motility and immune/inflammatory cells in the colon. Likewise, CRH is believed to be greatly related to tumorigenesis of many kinds of cancers including colon cancer via the central action during chronic stress while the peripheral effects on colitis-associated-colon cancer (CAC) are also proved. We and others observe that CRH/CRF1 plays a significant peripheral role in the development of colitis and CAC in that CRF1 deficiency dramatically suppresses the colon inflammation and CAC. However, up to date, there still exist not many relevant experimental data on this topic, and there seems to be no absolute clearcut between the central and direct peripheral effects of CRH in colitis and colon cancer. Taken together, CRH, as a critical factor in stress and immunity, may participate in colitis and CAC as a centrally active molecule; meanwhile, CRH has direct peripheral effects regulating the development of colitis and CAC, both of which will be summarized in this review.