Comprehensive Analysis of CLCA1 Expression, Immune Infiltration and Immune Checkpoints in Colon Adenocarcinoma / Análisis Completo de la Expresión de CLCA1, Infiltración Inmune y Puntos de Control Inmunológico en Colonadenocarcinoma

SUMMARY: Colon adenocarcinoma (COAD) is a prevalent disease worldwide, known for its high mortality and morbidity rates. Despite this, the extent of investigation concerning the correlation between COAD's CLCA1 expression and immune cell infiltration remains insufficient. This study seeks to examine the expression and prognosis of CLCA1 in COAD, along with its relationship to the tumor immune microenvironment. These findings will offer valuable insights for clinical practitioners and contribute to the existing knowledge in the field. In order to evaluate the prognostic significance of CLCA1 in individuals diagnosed with colorectal cancers, we conducted a comprehensive analysis using univariate and multivariate Cox regression models along with receiver operating characteristic curve (ROC) analysis. This study was performed on the patient data of COAD obtained from The Cancer Genome Atlas (TCGA) database. Nomograms were developed to anticipate CLCA1 prognostic influence. Furthermore, the CLCA1 association with tumor immune infiltration, immune checkpoints, immune checkpoint blockade (ICB) response, interaction network, and functional analysis of CLCA1-related genes was analyzed. We found that Colon adenocarcinoma tissues significantly had decreased CLCA1 expression compared to healthy tissues. Furthermore, the study revealed that the group with high expression of CLCA1 demonstrated a significantly higher overall survival rate (OS) as compared to the group with low expression. Multivariate and Univariate Cox regression analysis revealed the potential of CLCA1 as a standalone risk factor for COAD. These results were confirmed using nomograms and ROC curves. In addition, protein-protein interaction (PPI) network analysis and functional gene enrichment showed that CLCA1 may be associated with functional activities such as pancreatic secretion, estrogen signaling and cAMP signaling, as well as with specific immune cell infiltration. Therefor, as a new independent predictor and potential biomarker of COAD, CLCA1 plays a crucial role in the advancement of colon cancer.

El adenocarcinoma de colon (COAD) es una enfermedad prevalente a nivel mundial, conocida por sus altas tasas de mortalidad y morbilidad. Sin embargo, el alcance de la investigación sobre la correlación entre la expresión de CLCA1 de COAD y la infiltración de células inmunes sigue siendo insuficiente. Este estudio busca examinar la expresión y el pronóstico de CLCA1 en COAD, junto con su relación con el microambiente inmunológico del tumor. Estos hallazgos ofrecerán conocimientos valiosos para los profesionales clínicos y contribuirán al conocimiento existente en el campo. Para evaluar la importancia de pronóstico de CLCA1 en personas diagnosticadas con cáncer colorrectal, realizamos un análisis exhaustivo utilizando modelos de regresión de Cox univariados y multivariados junto con un análisis de la curva característica operativa del receptor (ROC). Este estudio se realizó con los datos de pacientes de COAD obtenidos de la base de datos The Cancer Genome Atlas (TCGA). Se desarrollaron nomogramas para anticipar la influencia pronóstica de CLCA1. Además, se analizó la asociación de CLCA1 con la infiltración inmunitaria tumoral, los puntos de control inmunitarios, la respuesta de bloqueo de los puntos de control inmunitarios (ICB), la red de interacción y el análisis funcional de genes relacionados con CLCA1. Descubrimos que los tejidos de adenocarcinoma de colon tenían una expresión significativamente menor de CLCA1 en comparación con los tejidos sanos. Además, el estudio reveló que el grupo con alta expresión de CLCA1 demostró una tasa de supervivencia general (SG) significativamente mayor en comparación con el grupo con baja expresión. El análisis de regresión de Cox multivariado y univariado reveló el potencial de CLCA1 como factor de riesgo independiente de COAD. Estos resultados se confirmaron mediante nomogramas y curvas ROC. Además, el análisis de la red de interacción proteína- proteína (PPI) y el enriquecimiento de genes funcionales mostraron que CLCA1 puede estar asociado con actividades funcionales como la secreción pancreática, la señalización de estrógenos y la señalización de AMPc, así como con la infiltración de células inmunes específicas. Por lo tanto, como nuevo predictor independiente y biomarcador potencial de COAD, CLCA1 desempeña un papel crucial en el avance del cáncer de colon.

Differences According to the Type of Exogenous Hyaluronic Acid and its Frequency of Infiltration in the Treatment of Temporomandibular Osteoarthritis / Diferencias Según el Tipo de Ácido Hiaurónico Exógeno y su Frecuencia de Infiltración en el Tratamiento de la Osteoartritis Temporomandibular

SUMMARY: One of the most important minimally invasive treatments today in temporomandibular joint osteoarthritis (TMJ- OA) is the intra-articular exogenous hyaluronic acid (HA) injection, which has yielded good results in pain relief and improves mandibular function with few side effects. However, the effectiveness of HA continues to be controversial, partly due to the heterogeneity in the injection protocols in their molecular weight, viscosity and frequency of infiltration, among other properties. The aim of this review is to identify the differences in the histological and clinical effects of the different types of HA and the frequency of infiltration on TMJ-OA treatment. Materials and methods: A bibliographic search was performed in the PubMed, Web of Science and Scopus databases. The search was limited up to September 2022. Search terms included "osteoarthritis", "hyaluronic acid, "molecular weight", "concentration", "viscosity", "dose" and "temporomandibular", using AND/OR as Boolean terms. Results: Exogenous HA in its different molecular weights offers an improvement in histological and clinical characteristics. Apparently, low and medium molecular weight HA presents better results. No clinical studies related to the degree of HA viscosity were found. Respect to the frequency of infiltration, single injection, weekly injections for 3 weeks, weekly injections for 5 weeks and other protocols are used. However, their comparison is complex. There seems to be differences in the effects of the different HA preparations for the treatment of TMJ-OA, mainly in their molecular weight. However, the evidence remains scant.

Uno de los tratamientos mínimamente invasivos más importantes en la actualidad en la artrosis de la articulación temporomandibular (OATM) es la inyección intraarticular de ácido hialurónico (AH) exógeno, que ha dado buenos resultados en el alivio del dolor y mejora la función mandibular con pocos efectos secundarios. Sin embargo, la efectividad del AH continúa siendo controversial, en parte debido a la heterogeneidad en los protocolos de inyección en cuanto a su peso molecular, viscosidad y frecuencia de infiltración, entre otras propiedades. El objetivo de esta revisión fue identificar las diferencias en los efectos histológicos y clínicos de los diferentes tipos de HA y la frecuencia de infiltración en el tratamiento de TMJ-OA. Se realizó una búsqueda bibliográfica en las bases de datos PubMed, Web of Science y Scopus. La búsqueda se limitó hasta septiembre de 2022. Los términos de búsqueda incluyeron "osteoartritis", "ácido hialurónico", "peso molecular", "concentración", "viscosidad", "dosis" y "temporomandibular", utilizando AND/OR como términos booleanos. El HA exógeno en sus diferentes pesos moleculares ofrece una mejora en las características histológicas y clínicas. Aparentemente, el AH de bajo y medio peso molecular presenta mejores resultados. No se encontraron estudios clínicos relacionados con el grado de viscosidad del HA. Respecto a la frecuencia de infiltración, se utilizan inyecciones únicas, inyecciones semanales durante 3 semanas, inyecciones semanales durante 5 semanas y otros protocolos. Sin embargo, su comparación es compleja. Parece haber diferencias en los efectos de las diferentes preparaciones de HA para el tratamiento de la OA-TMJ, principalmente en su peso molecular. Sin embargo, la evidencia sigue siendo escasa.

Integrated processing methodology to identify the spatial variability of accumulated infiltration for agricultural soil

The infiltration of water in the soil, and its variation in space, is essential to establish the irrigation schedule for crops and to evaluate the possible degrading effects on the soil. The objective was to develop an integrated processing methodology in Rstudio to identify the spatial variability of the accumulated infiltration, in two phases related to pea crops. Field sampling was carried out on a rectangular mesh with 48 points per moment, using double infiltrometer rings. The data were evaluated by means of geostatistical tools adjusted with programming code in Rstudio, defining the relationships between the magnitudes of the accumulated infiltration, for different test instants, without the need to make statistical adjustments to the normality of variables, discriminated over a period between 1 and 80 minutes. The results suggest the existence of spatial variability of the accumulated infiltration in the two evaluated phases, considering that most of the analyzed data were adjusted to multiple variance models, maintaining a degree of spatial dependence, and validating the effectiveness of the adjusted methodology developed and implemented. The spatial relationships were corroborated by means of contour maps, where the spatial variation of the accumulated infiltration between the two identified cultivation moments was observed. The reliability of the interpolation by the Ordinary Kriging method was verified by generating variance maps, establishing the degree of homogeneity of the interpolation. The variability of infiltration confirms the validity of the adjusted methodology implemented.

La infiltración del agua en el suelo y su variación espacial es fundamental para establecer la programación de riego en los cultivos y evaluar los posibles efectos degradativos en el suelo. El objetivo fue desarrollar una metodología de procesamiento integrado en Rstudio, para identificar la variabilidad espacial de la infiltración acumulada, en dos fases para un cultivo de arveja. El muestreo de campo se adelantó sobre una malla rectangular georreferenciada con 48 puntos, por cada momento, utilizando anillos infiltrómetros dobles. Los datos fueron evaluados por medio de herramientas geoestadísticas, ajustadas con código de programación en Rstudio, definiendo las relaciones entre las magnitudes de la infiltración acumulada, para diferentes instantes de prueba, sin la necesidad de realizar ajustes estadísticos de normalidad de variables, discriminados en un periodo entre 1 y 80 minutos. Los resultados sugieren la existencia de variabilidad espacial de la infiltración acumulada en las dos fases evaluadas, considerando que, la mayoría de los datos analizados, se ajustaron a múltiples modelos de semivarianza, manteniendo grados de dependencia espacial, particularmente, respecto al máximo valor acumulado de infiltración, validando la eficacia de la metodología ajustada. Las relaciones espaciales fueron corroboradas con mapas de contorno, en donde se observó la variación espacial de la infiltración acumulada entre los momentos de cultivo identificados. La confiabilidad de la interpolación por el método Kriging ordinario, se verificó mediante la generación mapas de varianza, estableciendo el grado de homogeneidad de la interpolación. La variabilidad de la infiltración confirma la validez de la metodología ajustada implementada.

Infiltración del nervio óptico como forma inicial de recaída de la leucemia linfoblástica aguda / Optic nerve infiltration as an initial form of relapse of acute lymphoblastic leukemia

Introducción: La infiltración del nervio óptico como forma inicial de recaída de la leucemia linfoblástica aguda es rara, aunque altamente indicativa de que el sistema nervioso central está involucrado. Objetivo: Actualizar el conocimiento sobre infiltración del nervio óptico como forma inicial de recaída de la leucemia linfoblástica aguda. Métodos: Se realizó una revisión de las publicaciones más relevantes relacionadas con el tema durante los últimos años. La búsqueda y la localización de la información se apoyaron en la elección de palabras clave/descriptores que configuraron el perfil de búsqueda. Se utilizó el MeSH Database de PubMed. Se realizó una extensa revisión en Google Académico y otros megabuscadores de revisión sistemática mediante TripDatabase y Cochrane. Conclusiones: La infiltración directa de células tumorales y las alteraciones hematológicas propias de la enfermedad constituyen los mecanismos fundamentales de la fisiopatogenia. El edema del disco óptico es su signo oftalmoscópico más distintivo. La imagen por resonancia magnética de cráneo, el análisis citológico del fluido cerebroespinal y la biopsia de médula ósea negativas no deben excluir el diagnóstico. La terapia combinada que incluye la radiación localizada constituye una buena opción de tratamiento. Un número considerable de ojos recuperan su agudeza visual y muestran resolución del cuadro infiltrativo(AU)

Introduction: Optic nerve infiltration as an initial form of relapse of acute lymphoblastic leukemia is rare, although it is highly indicative of central nervous system involvement. Objective: To update the knowledge about optic nerve infiltration as an initial form of relapse of acute lymphoblastic leukemia. Methods: A review of the most relevant publications related to the subject during the last years was carried out. The search and localization of information was supported by the choice of keywords/descriptors that configured the search profile. The MeSH Database of PubMed was used. An extensive review was performed in Google Scholar and other systematic review mega search engines using TripDatabase and Cochrane. Conclusions: Direct tumor cell infiltration and disease-specific hematologic alterations are the fundamental mechanisms of pathophysiology. Optic disc edema is the most distinctive ophthalmoscopic sign. Negative cranial magnetic resonance imaging, cytologic analysis of cerebrospinal fluid and bone marrow biopsy should not exclude the diagnosis. Combination therapy including localized radiation is a good treatment option. A considerable number of eyes recover visual acuity and show resolution of the infiltrative picture(AU)

TTYH3 is a prognostic biomarker and associates with immune cell infiltrations of lung adenocarcinoma / TTYH3 es un biomarcador pronóstico y se asocia con infiltraciones de células inmunitarias del adenocarcinoma de pulmón

SUMMARY: We investigated Tweety Family Member 3 (TTYH3) level in lung adenocarcinoma (LUAD) and its relationship with immune infiltration in tumors by bioinformatics. Differential expressions of TTYH3 in lung cancer were analyzed with Oncomine, TIMER, GEO, UALCAN and HPA. Relationship of TTYH3 mRNA/protein levels with clinical parameters was analyzed by UALCAN. Co-expressed genes of TTYH3 in LUAD were analyzed using Cbioportal. Its relationship with LUAD prognosis was analyzed by Kaplan-Meier plotter. GO and KEGG analysis were performed. Correlation between TTYH3 and tumor immune infiltration were tested by TIMER, TISIDB and GEPIA. We found that TTYH3 was significantly increased in LUAD tissues. TTYH3 high expression was closely related to poor overall survival, post progression survival and first progression in LUAD patients. TTYH3 mRNA/protein levels were significantly associated with multiple pathways. Specifically, TTYH3 up-regulation was mostly related to biological regulation, metabolic process, protein blinding, extracellular matrix organization and pathways in cancer. Moreover, TTYH3 was positively associated with immune cell infiltration in LUAD. Finally, TTYH3 was highly expressed in LUAD as revealed by meta-analysis. TTYH3 is closely related to the prognosis of LUAD and immune cell infiltration, and it can be used as a prognostic biomarker for LUAD and immune infiltration.

Investigamos por bioinformática el nivel de Tweety Family Member 3 (TTYH3) con adenocarcinoma de pulmón (LUAD) y su relación con la infiltración inmune en tumores. Las expresiones diferenciales de TTYH3 en cáncer de pulmón se analizaron con Oncomine, TIMER, GEO, UALCAN y HPA. Con UALCAN se analizó la relación de los niveles de ARNm/proteína de TTYH3 con los parámetros clínicos. Los genes coexpresados de TTYH3 en LUAD se analizaron utilizando Cbioportal. Su relación con el pronóstico LUAD se analizó mediante plotter de Kaplan- Meier. Se realizaron análisis GO y KEGG. TIMER, TISIDB y GEPIA probaron la correlación entre TTYH3 y la infiltración inmune tumoral. Encontramos que TTYH3 aumentó significativamente en los tejidos LUAD. La alta expresión de TTYH3 estuvo estrechamente relacionada con una supervivencia general deficiente, supervivencia posterior a la progresión y primera progresión en pacientes con LUAD. Los niveles de ARNm/ proteína de TTYH3 se asociaron significativamente con múltiples vías. Específicamente, la regulación positiva de TTYH3 se relacionó principalmente con la regulación biológica, el proceso metabólico, el cegamiento de proteínas, la organización de la matriz extracelular y las vías en el cáncer. Además, TTYH3 se asoció positivamente con la infiltración de células inmunitarias en LUAD. Finalmente, TTYH3 se expresó altamente en LUAD como lo reveló el metanálisis. TTYH3 está estrechamente relacionado con el pronóstico de LUAD y la infiltración de células inmunitarias, y se puede utilizar como biomarcador pronóstico para LUAD y la infiltración de células inmunitarias.

Pioderma gangrenoso. Presentación de un caso

El pioderma gangrenoso es una enfermedad inflamatoria, poco común, de etilogía desconocida, caracterizada por la infiltración neutrófila estéril de la dermis, que puede o no estar asociada con enfermedades sistémicas. Su descripción clásica es la presencia de una o más lesiones ulceradas cutáneas, dolorosas, de aspecto infeccioso, bordes irregulares, socavados y con una desmesurada respuesta al trauma local denominado patergia. Se presenta el caso de una paciente de 58 años de edad, con lesiones en piel de dos meses de evolución y varios tratamientos previos sin mejorar. Al ser reevaluada, fue diagnosticado y tratado su caso como un pioderma gangrenoso con evolución satisfactoria.

Pyoderma gangrenosum is a rare inflammatory disease of unknown etiology characterized by sterile neutrophilic infiltration of the dermis, which may or may not be associated with systemic disease. Its classic description is the presence of one or more ulcerated skin lesions, painful, with an infectious appearance, irregular edges, undermined and with an excessive response to local trauma called pathergy. The case of a 58-years-old patient is presented, with skin lesions of two months' evolution and several previous treatments without improvement. Upon reassessment, her case was diagnosed and treated as pyoderma gangrenosum with satisfactory evolution.

Diagnostic study of actinic cheilitis by reflectance confocal microscopy / 口腔疾病防治

Objective @#To explore the clinical application value of reflectance confocal microscopy(RCM) in the diagnosis of actinic cheilitis(AC).@*Methods@#After approval by the hospital ethics committee and informed consent given by the patients, from October 2020 to July 2022, 17 patients who were diagnosed with actinic cheilitis in the Ninth People's Hospital affiliated with Shanghai Jiao Tong University School of Medicine were retrospectively analyzed. The white keratotic lesions of the lips were scanned with reflectance confocal microscopy, and the image characteristics were summarized and analyzed, including epithelial hyperplasia/atrophy, hyperkeratosis, inflammatory cell infiltration, blood vessel dilatation, solar elastosis, atypical keratinocytes, widening of intercellular spaces, degeneration of basal cell layer, and pigmentation. We used the sample compliance rate to measure the correlation between RCM parameters and histopathological diagnostic criteria for AC and kappa concordance analysis to calculate the concordance between RCM and pathological diagnosis. @* Results@# Under RCM, the sample correct rates for epithelial hyperplasia/atrophy, hyperkeratosis, inflammatory cell infiltration, vasodilation, and solar elastosis were 76.5%, 100%, 100%, 64.7%, and 70.6%, the sample accuracy compared with pathological diagnosis was 82.4%, 47.1%, 94.1%, 88.2% and 76.5%, respectively. We also observed that 100%, 88.2%, 76.5%, and 88.2% of AC patients showed RCM features of atypical keratinocytes, widening of intercellular spaces, degeneration of the basal cell layer, and pigmentation, respectively. The kappa value of hyperkeratosis and inflammatory cell infiltration was 1. The kappa value of blood vessel dilatation was 0.645. @* Conclusion @#Reflectance confocal microscopy is noninvasive and versatile and has clinical application value in the diagnosis of actinic cheilitis.

Ferroptosis-related Recurrence Risk Model Predicts Clinical Outcomes and Immune Infiltration in Glioblastoma / 肿瘤防治研究

Objective To construct a ferroptosis-related glioblastoma (GBM) recurrence risk model and evaluate the prognosis of patients. Methods Differentially expressed genes (DEGs) related to ferroptosis in recurrent GBM were screened by CGGA and FerrDb databases. Key genes were obtained by Lasso regression. Then, nomogram was constructed according to the key risk genes, and the prediction efficiency was verified using the TCGA database. GO, KEGG, and GSEA databases were used in exploring the mechanism of prognosis. ESTIMATE and TIMER were used in studying tumor immune infiltration and the expression of immune check points. Results WWTR1, PLIN2, and BID were important prognostic factors for GBM recurrence. The nomogram was constructed according to gender and age, and the observed values were in good agreement with the predicted values. The AUC values were 0.65 (1 year), 0.66 (3 years), and 0.63 (5 years) for CGGA and 0.68 (1 year), 0.76 (3 years), and 0.79 (5 years) for TCGA. Epithelial mesenchymal transition, KRAS pathway, and inflammatory response were significantly upregulated in the high-risk subtypes (P < 0.05). Immune cell infiltration was lower (P < 0.05). Risk score was positively correlated with the expression of immunosuppression check points. Conclusion Ferroptosis-related genes WWTR1, PLIN2, and BID can be used in constructing a nomogram with good predictive performance. These risk genes may affect prognosis through tumor-infiltrating immune cells and immune check points.

Construction of a prognostic model for hepatocellular carcinoma based on pyroptosis-related genes / 中华肝脏病杂志

Objective: To study the construction of a prognostic model for hepatocellular carcinoma (HCC) based on pyroptosis-related genes (PRGs). Methods: HCC patient datasets were obtained from the Cancer Genome Atlas (TCGA) database, and a prognostic model was constructed by applying univariate Cox and least absolute shrinkages and selection operator (LASSO) regression analysis. According to the median risk score, HCC patients in the TCGA dataset were divided into high-risk and low-risk groups. Kaplan-Meier survival analysis, receiver operating characteristic (ROC) curves, univariate and multivariate Cox analysis, and nomograms were used to evaluate the predictive ability of the prognostic models. Functional enrichment analysis and immune infiltration analysis were performed on differentially expressed genes between the two groups. Finally, two HCC datasets (GSE76427 and GSE54236) from the Gene Expression Omnibus database were used to externally validate the prognostic value of the model. Univariate and multivariate Cox regression analysis or Wilcoxon tests were performed on the data. Results: A total of 366 HCC patients were included after screening the HCC patient dataset obtained from the TCGA database. A prognostic model related to HCC was established using univariate Cox regression analysis, LASSO regression analysis, and seven genes (CASP8, GPX4, GSDME, NLRC4, NLRP6, NOD2, and SCAF11). 366 cases were evenly divided into high-risk and low-risk groups based on the median risk score. Kaplan-Meier survival analysis showed that there were statistically significant differences in the survival time between patients in the high-risk and low-risk groups in the TCGA, GSE76427, and GSE54236 datasets (median overall survival time was 1 149 d vs. 2 131 d, 4.8 years vs. 6.3 years, and 20 months vs. 28 months, with P = 0.000 8, 0.034 0, and 0.0018, respectively). ROC curves showed good survival predictive value in both the TCGA dataset and two externally validated datasets. The areas under the ROC curves of 1, 2, and 3 years were 0.719, 0.65, and 0.657, respectively. Multivariate Cox regression analysis showed that the risk score of the prognostic model was an independent predictor of overall survival time in HCC patients. The risk model score accurately predicted the survival probability of HCC patients according to the established nomogram. Functional enrichment analysis and immune infiltration analysis showed that the immune status of the high-risk group was significantly decreased. Conclusion: The prognostic model constructed in this study based on seven PRGs accurately predicts the prognosis of HCC patients.

Correlation of DNA Damage Repair Gene FANCI with Prognosis and Immune Infiltration of Hepatocellular Carcinoma / 中山大学学报(医学科学版)

ObjectiveTo evaluate the expression level of DNA damage repair gene FANCI in hepatocellular carcinoma （HCC） and its relationship with prognosis， clinical stage and immune infiltration. MethodsIn this study， TCGA， GTEx， TIMER2.0， HPA database and qRT-PCR， western blot and immunohistochemistry were used to analyze the expression of FANCI in HCC and its correlation with different clinical stages； Kaplan-Meier Plotter database was used to explore the relationship between FANCI and the prognosis of HCC； the TISIDB database was used to analyze the relationship between FANCI and immune cell infiltration and immune checkpoints in HCC； the STRING database was used to detect the protein binding with FANCI； the TCGA and GTEx databases were used for GO and KEGG enrichment analysis； Cell experiments were used to explore the role of FANCI in HCC. ResultsCompared with normal tissues， the mRNA and protein expression levels of FANCI in tumor tissues were up-regulated （P<0.001）； and HCC patients with high expression of FANCI had poor prognosis （P<0.001）； the expression of FANCI in tumor tissues was positively correlated with the number of activated CD4+ T cells， the number of Th2 cells and the expression of immune checkpoints， and B-cell and macrophage infiltration was significantly lower in the FANCI high expression group （P<0.01）； GO and KEGG enrichment analysis showed that FANCI-related genes were enriched in various biological processes such as amino acid transmembrane transporter activity； Cell experiments showed that knockdown of FANCI could inhibit the proliferation， invasion and migration of HCC （P<0.05）. ConclusionsFANCI is highly expressed in hepatocellular carcinoma tissues， which may play a role in suppressing anti-tumor immunity and acting on pathways such as amino acid transmembrane transport， and is associated with poor prognosis. The proliferation， invasion and migration ability of hepatocellular carcinoma are inhibited after knocking down FANCI.

The suppression of cervical cancer ferroptosis by macrophages: The attenuation of ALOX15 in cancer cells by macrophages-derived exosomes

Induction of cancer cell ferroptosis has been proposed as a potential treatment in several cancer types. Tumor-associated macrophages (TAMs) play a key role in promoting tumor malignant progression and therapy resistance. However, the roles and mechanisms of TAMs in regulating tumor ferroptosis is still unexplored and remains enigmatic. This study shows ferroptosis inducers has shown therapeutic outcomes in cervical cancer in vitro and in vivo. TAMs have been found to suppress cervical cancer cells ferroptosis. Mechanistically, macrophage-derived miRNA-660-5p packaged into exosomes are transported into cancer cells. In cancer cells, miRNA-660-5p attenuates ALOX15 expression to inhibit ferroptosis. Moreover, the upregulation of miRNA-660-5p in macrophages depends on autocrine IL4/IL13-activated STAT6 pathway. Importantly, in clinical cervical cancer cases, ALOX15 is negatively associated with macrophages infiltration, which also raises the possibility that macrophages reduce ALOX15 levels in cervical cancer. Moreover, both univariate and multivariate Cox analyses show ALOX15 expression is independent prognostic factor and positively associated with good prognosis in cervical cancer. Altogether, this study reveals the potential utility of targeting TAMs in ferroptosis-based treatment and ALOX15 as prognosis indicators for cervical cancer.

Diagnostic Study of Multi-spectral Intelligent Analyzer in Diagnosis of the Infiltration Degree of Lung Adenocarcinoma / 中国肺癌杂志

BACKGROUND@#Lung cancer is one of the most common malignant tumors in the world. The accuracy of intraoperative frozen section (FS) in the diagnosis of lung adenocarcinoma infiltration cannot fully meet the clinical needs. The aim of this study is to explore the possibility of improving the diagnostic efficiency of FS in lung adenocarcinoma by using the original multi-spectral intelligent analyzer.@*METHODS@#Patients with pulmonary nodules who underwent surgery in the Department of Thoracic Surgery, Beijing Friendship Hospital, Capital Medical University from January 2021 to December 2022 were included in the study. The multispectral information of pulmonary nodule tissues and surrounding normal tissues were collected. A neural network model was established and the accuracy of the neural network diagnostic model was verified clinically.@*RESULTS@#A total of 223 samples were collected in this study, 156 samples of primary lung adenocarcinoma were finally included, and a total of 1,560 sets of multispectral data were collected. The area under the curve (AUC) of spectral diagnosis in the test set (10% of the first 116 cases) of the neural network model was 0.955 (95%CI: 0.909-1.000, P<0.05), and the diagnostic accuracy was 95.69%. In the clinical validation group (the last 40 cases), the accuracy of spectral diagnosis and FS diagnosis were both 67.50% (27/40), and the AUC of the combination of the two was 0.949 (95%CI: 0.878-1.000, P<0.05), and the accuracy was 95.00% (38/40).@*CONCLUSIONS@#The accuracy of the original multi-spectral intelligent analyzer in the diagnosis of lung invasive adenocarcinoma and non-invasive adenocarcinoma is equivalent to that of FS. The application of the original multi-spectral intelligent analyzer in the diagnosis of FS can improve the diagnostic accuracy and reduce the complexity of intraoperative lung cancer surgery plan.
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Correlation Analysis between Cerebrospinal Fluid Status and Prognosis in Childhood with Acute Lymphoblastic Leukemia by Flow Cytometry / 中国实验血液学杂志

OBJECTIVE@#To study the cerebrospinal fluid (CSF) status and prognosis value in patients with newly diagnosed acute lymphoblastic leukemia (ALL) by flow cytometry (FCM).@*METHODS@#The clinical features of the 75 newly diagnosed ALL patients from September 2020 to December 2021 in our centre were retrospective analyzed, as well as the bone marrow (BM) and CSF minimal residual disease (MRD) data, and the CSF conventional cytology data. Central nervous system infiltration(CNSI) positive was as CSF MRD positive by FCM or leukemia cells detected by conventional cytology. The status of CSF were compared and analyzed by FCM and conventional cytology, the clinical features and the prognosis value of different CNSI status in these patients were analyzed.@*RESULTS@#Among 75 newly diagnosed ALL, 16 cases (21%) with CNSI positive (CNSI+) were detected by FCM, while only 2 positive cases (3%) were detected by conventional cytology. The CNSI+ rate detected by FCM was significantly higher than conventional cytology(P<0.05). Compared with CNSI- ALL patients, the median age of CNSI+ ALL patients was significantly younger, and the median platelet count was significantly lower, the difference was statistically significant (P<0.05). Up to follow-up time (August 31, 2022), four ALL patients were died, including 3 patients were CNSI- and 1 patient was CNSI+. Furthermore, three cases were primary disease relapse, including 1 case was CNSI+. There was no significant difference in overall survival (OS) rate and relapse-free survival (RFS) rate of the patients with different CNSI status.@*CONCLUSION@#Compared with conventional cytology, FCM is a more sensitive assay to evaluate the central nervous system status in ALL patients. After active treatment, there was no significant difference in OS and RFS between patients with different CNSI status at diagnosis.

Progress of injection sites of local infiltration analgesia in total knee arthroplasty / 中国修复重建外科杂志

OBJECTIVE@#To review the research progress of injection sites of local infiltration analgesia (LIA) in total knee arthroplasty (TKA).@*METHODS@#The relevant domestic and foreign literature in recent years was extensively reviewed. The neuroanatomy of the knee, and the research progress of the selection and the difference of effectiveness between different injection sites of LIA in clinical studies were summarized.@*RESULTS@#Large concentrations of nociceptors are present throughout the various tissues of the knee joint. Patellar tendon, subpatellar fat pad, lateral collateral ligament insertions, iliotibial band insertions, suprapatellar capsule, and posterior capsule were more sensitive to pain. Most current studies support injections into the lateral capsule, collateral ligament, retinaculum, quadriceps tendon, fat pad, and subcutaneous tissue. Whether to inject into the back of the knee and subperiosteum is controversial.@*CONCLUSION@#The relative difference of knee tissue sensitivity to pain has guiding significance for the selection of LIA injection site after TKA. Although researchers have conducted clinical trials on injection site and technique of LIA in TKA, there are certain limitations. The optimal scheme has not been determined yet, and further studies are needed.

Long-term effectiveness of arthroscopic partial repair for massive irreparable rotator cuff tears / 中国修复重建外科杂志

OBJECTIVE@#To explore the long-term effectiveness of arthroscopic partial repair in treatment of massive irreparable rotator cuff tears from both the radiological and clinical perspectives.@*METHODS@#A retrospective analysis was conducted on the clinical data of 24 patients (25 sides) with massive irreparable rotator cuff tears who met the inclusion criteria between May 2006 and September 2014. Among them, there were 17 males (18 sides) and 7 females (7 sides) with an age range of 43-67 years (mean, 55.0 years). There were 23 cases of unilateral injury and 1 case of bilateral injuries. All patients were treated with the arthroscopic partial repair. The active range of motion of forward elevation and abduction, external rotation, and internal rotation, as well as the muscle strength for forward flexion and external rotation, were recorded before operation, at the first postoperative follow-up, and at last follow-up. The American Association of Shoulder and Elbow Surgeons (ASES) score, the University of California at Los Angeles (UCLA) shoulder scoring, and Constant score were used to evaluate shoulder joint function. And the visual analogue scale (VAS) score was used to evaluate shoulder joint pain. MRI examination was performed. The signal-to-noise quotient (SNQ) was measured above the anchor point near the footprint area (m area) and above the glenoid (g area) in the oblique coronal T2 fat suppression sequence. The atrophy of the supraspinatus muscle was evaluated using the tangent sign. The global fatty degeneration index (GFDI) was measured to assess fat infiltration in the supraspinatus muscle, infraspinatus muscle, teres minor muscle, upper and lower parts of the subscapularis muscle. The mean GFDI (GFDI-5) of 5 muscles was calculated.@*RESULTS@#The incisions healed by first intention. All patients were followed up with the first follow-up time of 1.0-1.7 years (mean, 1.3 years) and the last follow-up time of 7-11 years (mean, 8.4 years). At last follow-up, the range of motion and muscle strength of forward elevation and abduction, ASES score, Constant score, UCLA score, and VAS score of the patients significantly improved when compared with those before operation ( P<0.05). Compared with the first follow-up, except for a significant increase in ASES score ( P<0.05), there was no significant difference in the other indicators ( P>0.05). Compared with those before operation, the degree of supraspinatus muscle infiltration worsened at last follow-up ( P<0.05), GFDI-5 increased significantly ( P<0.05), and there was significant difference in the tangent sign ( P<0.05); while there was no significant difference in the infiltration degree of infraspinatus muscle, teres minor muscle, and subscapularis muscle, upper and lower parts of the subscapularis muscle ( P>0.05). Compared with the first follow-up, the SNQm and SNQg decreased significantly at last follow-up ( P<0.05). At the first and last follow-up, there was no correlation between the SNQm and SNQg and the ASES score, Constant score, UCLA score, and VAS score of the shoulder ( P>0.05).@*CONCLUSION@#Arthroscopic partial repair is effective in treating massive irreparable rotator cuff tear and significantly improves long-term shoulder joint function. For patients with severe preoperative fat infiltration involving a large number of tendons and poor quality of repairable tendons, it is suggested to consider other treatment methods.

A novel defined risk signature of endoplasmic reticulum stress-related genes for predicting the prognosis and immune infiltration status of ovarian cancer / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

Endoplasmic reticulum (ER) stress, as an emerging hallmark feature of cancer, has a considerable impact on cell proliferation, metastasis, invasion, and chemotherapy resistance. Ovarian cancer (OvCa) is one of the leading causes of cancer-related mortality across the world due to the late stage of disease at diagnosis. Studies have explored the influence of ER stress on OvCa in recent years, while the predictive role of ER stress-related genes in OvCa prognosis remains unexplored. Here, we enrolled 552 cases of ER stress-related genes involved in OvCa from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) cohorts for the screening of prognosis-related genes. The least absolute shrinkage and selection operator (LASSO) regression was applied to establish an ER stress-related risk signature based on the TCGA cohort. A seven-gene signature revealed a favorable predictive efficacy for the TCGA, International Cancer Genome Consortium (ICGC), and another GEO cohort (P<0.001, P<0.001, and P=0.04, respectively). Moreover, functional annotation indicated that this signature was enriched in cellular response and senescence, cytokines interaction, as well as multiple immune-associated terms. The immune infiltration profiles further delineated an immunologic unresponsive status in the high-risk group. In conclusion, ER stress-related genes are vital factors predicting the prognosis of OvCa, and possess great application potential in the clinic.

Diagnosis Significance of the Levels of Cytokines IL-6, IL-10 and CXCL-13 in Cerebrospinal Fluid for Central Nervous System Infiltration of Lymphoma / 中国实验血液学杂志

OBJECTIVE@#To evaluate the diagnostic value of the expression levels of cytokines interleukin-6(IL-6), interleukin-10 (IL-10) and chemokine （C-X-C motif） ligand-13 (CXCL-13) in cerebrospinal fluid (CSF) for central nervous system infiltration of lymphoma.@*METHODS@#Forty patients diagnosed as lymphoma or acute lymphoblastic leukemia in General Hospital of Northern Theater Command from July 2020 to July 2021 were collected and recorded their CSF indexes, including pressure, protein, Pandy test, nucleated cell count, glucose and chlorine content in CSF. The levels of cytokines IL-6, IL-10 and CXCL-13 were detected by Enzyme-linked immunosorbent assay.@*RESULTS@#The patients were divided into CNSI (central nervous system infiltration) group and non-CNSI group, the average levels of IL-6, IL-10, CXCL-13 and IL-10/IL-6 ratio in CNSI group were higher than those in non-CNS group, but the difference of IL-10/IL-6 ratio between the two groups was statistically significant (P<0.05). Then the patients were divided into protein elevated(n=14) group and protein normal group(n=26), the levels of IL-6 ［ (5.78±2.69) pg/ ml］ and CXCL-13 ［(0.83±0.59) pg/ml］ in protein elevated group were significantly higher than those in the protein normal group ［IL-6: (2.41±1.16) pg/ml; CXCL-13: (0.38±0.18) pg/ml］ (P<0.05). Further analysis of the expression levels of the cytokines in non-CNSI group (n=32), IL-6, IL-10, CXCL-13 level and IL-10/IL-6 ratio in the protein elevated group (n=12) were higher than those in the protein normal group (n=20), but the difference was not statistically significant.@*CONCLUSION@#The levels of IL-6, IL-10 and CXCL-13 in CSF of lymphoma patients with CNS infiltration were higher than those in non-CNS infiltration group, and those in patients with protein elevated group are higher than those in the protein normal group.

Risk factors analysis and prediction model construction of submucosal deep infiltration of early colorectal tumor / 中华肿瘤杂志

Objective: To investigate the risk factors for the development of deep infiltration in early colorectal tumors (ECT) and to construct a prediction model to predict the development of deep infiltration in patients with ECT. Methods: The clinicopathological data of ECT patients who underwent endoscopic treatment or surgical treatment at the Cancer Hospital, Chinese Academy of Medical Sciences from August 2010 to December 2020 were retrospectively analyzed. The independent risk factors were analyzed by multifactorial regression analysis, and the prediction models were constructed and validated by nomogram. Results: Among the 717 ECT patients, 590 patients were divided in the within superficial infiltration 1 (SM1) group (infiltration depth within SM1) and 127 patients in the exceeding SM1 group (infiltration depth more than SM1). There were no statistically significant differences in gender, age, and lesion location between the two groups (P>0.05). The statistically significant differences were observed in tumor morphological staging, preoperative endoscopic assessment performance, vascular tumor emboli and nerve infiltration, and degree of tumor differentiation (P<0.05). Multivariate regression analysis showed that only erosion or rupture (OR=4.028, 95% CI: 1.468, 11.050, P=0.007), localized depression (OR=3.105, 95% CI: 1.584, 6.088, P=0.001), infiltrative JNET staging (OR=5.622, 95% CI: 3.029, 10.434, P<0.001), and infiltrative Pit pattern (OR=2.722, 95% CI: 1.347, 5.702, P=0.006) were independent risk factors for the development of deep submucosal infiltration in ECT. Nomogram was constructed with the included independent risk factors, and the nomogram was well distinguished and calibrated in predicting the occurrence of deep submucosal infiltration in ECT, with a C-index and area under the curve of 0.920 (95% CI: 0.811, 0.929). Conclusion: The nomogram prediction model constructed based on only erosion or rupture, local depression, infiltrative JNET typing, and infiltrative Pit pattern has a good predictive efficacy in the occurrence of deep submucosal infiltration in ECT.

A bioinformatic analysis of the role of TP53 status on the infiltration of CD8+ T cells into the tumor microenvironment

CD8+ T cells play basic roles in the immune system in a tumor microenvironment (TME) to fight cancer. Several reports have suggested signs of the involvement of tumor protein p53 (TP53) in a complex immune system network. Moreover, our previous research indicated that TP53 orchestrates the polarization and infiltration of macrophages into the TME. In the present study, the clinical function of TP53 status (wild/mutant) in CD8+ T cell infiltration was assessed using more than 10,000 The Cancer Genome Atlas (TCGA) samples from 30 cancer types through Tumor Immune Estimation (TIMER). Our investigation revealed that CD8+ T cell infiltration was higher in head and neck squamous cell carcinoma (HNSC) and uterine corpus endometrial carcinoma (UCEC) patients with wild-type TP53 than in those with mutant TP53. Wild-type TP53 conferred a good prognosis for HNSC and UCEC (P<0.05). In contrast, CD8+ T cell infiltration in lung adenocarcinoma (LUAD) patients with wild-type TP53 was much lower than in those with mutant TP53. Notably, clinical outcomes for LUAD with wild-type TP53 were poor (P<0.05). This study was the first to provide insights into the novel association of TP53 with CD8+ T cells infiltration in the TME in patients with HNSC, LUAD, and UCEC. Therefore, TP53 status acts as a prognostic marker, and this can be used as a basis to further study the effect of targeting TP53 in these patients. Furthermore, our study found that TP53 status was a reliable predictive factor and therapeutic target in patients with HNSC and UCEC.

Diagnostic Efficacy of 18F-FDG PET/CT in Detecting Bone Marrow Infiltration in Patients with Newly Diagnosed Diffuse Large B-Cell Lymphoma / 生物医学与环境科学（英文）

OBJECTIVE@#Diffuse large B-cell lymphoma (DLBCL) is often associated with bone marrow infiltration, and 2-deoxy-2-(18F) fluorodeoxyglucose positron emission tomography/computed tomography ( 18F-FDG PET/CT) has potential diagnostic significance for bone marrow infiltration in DLBCL.@*METHODS@#A total of 102 patients diagnosed with DLBCL between September 2019 and August 2022 were included. Bone marrow biopsy and 18F-FDG PET/CT examinations were performed at the time of initial diagnosis. Kappa tests were used to evaluate the agreement of 18F-FDG PET/CT with the gold standard, and the imaging features of DLBCL bone marrow infiltration on PET/CT were described.@*RESULTS@#The total detection rate of bone marrow infiltration was not significantly different between PET/CT and primary bone marrow biopsy ( P = 0.302) or between the two bone marrow biopsies ( P = 0.826). The sensitivity, specificity, and Youden index of PET/CT for the diagnosis of DLBCL bone marrow infiltration were 0.923 (95% CI, 0.759-0.979), 0.934 (95% CI, 0.855-0.972), and 0.857, respectively.@*CONCLUSION@#18F-FDG PET/CT has a comparable efficiency in the diagnosis of DLBCL bone marrow infiltration. PET/CT-guided bone marrow biopsy can reduce the misdiagnosis of DLBCL bone marrow infiltration.