Infiltração resinosa em lesões brancas cariosas e não cariosas: relato de casos / Infiltración resinosa em lesiones blancas cariosas y no cariosas: Reporte de Casos / Resinous infiltration in carious and non-carious white lesions: Case Reports

Introdução: O processo de desmineralização proveniente da cárie leva à formação de manchas brancas que são a primeira manifestação visível da doença. Os infiltrantes resinosos surgem como uma alternativa para o tratamento dessas lesões não cavitadas, pois sãoresinas de baixa viscosidade e faz parte dos procedimentos que visam uma odontologia menos invasiva. Objetivo: Este estudo objetiva relatar a experiência clínica no uso de infiltrante resinoso, Icon, em lesões de mancha branca de etiologias cariosa e não cariosa em dois pacientes distintos, insatisfeitos com a estética do seu sorriso. Descrição do caso: Ao exame clínico foi observado nos pacientes com lesões brancas. No primeiro paciente, de 14 anos, verificou-se a presença da atividade de cárie e micro cavitações. Dessa forma, o plano de tratamento perpassou orientação de higiene oral supervisionada, aplicação de verniz fluoretado, Enamelast, semanal, adequação do meio com restaurações em resina, e só então o uso do infiltrante. A segunda paciente, de 11 anos, já possuía saúde bucal adequada e tinha queixa estética devido à lesão branca não cariosa, hipoplasia, cujo plano de tratamento foi à utilização do Icon apenas. Conclusões: Nos dois casos obteve-se melhoria estética considerável com este procedimento microinvasivo. Melhoria na saúde bucal, aliado à devolução da estética, pode ser observada com o uso de infiltrantes resinosos (AU).

Introduction: The process of demineralization resulting from caries leads to the formation of white spots that are the first visible manifestation of the disease. Resin infiltrants appear as an alternative for the treatment of these non-cavitated lesions, since they are low viscosity resins and are part of the procedures that aim at a less invasive dentistry.Objective:This study aims to report the clinical experience in the use of a resin infiltrant, Icon,in white spot lesions of carious and non-carious etiologies in two different patients who were dissatisfied with the esthetics of their smiles.Methodology: On clinical examination, white lesions were observed in both patients. In the first patient,14 years old,the presence of caries activity and micro cavitations was verified. Thus, the treatment plan included supervised oral hygiene guidance, weekly application of fluoride varnish,Enamelast, adaptation of the environment with resin restorations, and, onlythen, the use of the infiltrant, Icon. The second patient, 11 years old,already had adequate oral health and had an esthetic complaint due to a non-carious white lesion, hypoplasia, whose treatment plan consisted of the use of Icon only.Conclusions:In both cases considerable esthetic improvement was obtained with this microinvasive procedure. Improvement in oral health, combined with the return of esthetics, can be observed with the use of resin infiltrants (AU).

Introducción: El proceso de desmineralización resultante de la caries conduce a la formación de manchas blancas, que son la primera manifestación visible de la enfermedad. Losinfiltrantes de resina aparecen como una alternativa para el tratamiento de estas lesiones no cavitadas, pues se tratan de resinas de baja viscosidad y forman parte de los procedimientos que buscan una odontología menos invasiva. Objetivo:Este estudio tiene como objetivo relatar la experiencia clínica en el uso del infiltrante de resina,Iconen lesiones de mancha blanca de etiologías cariosas y no cariosas en dos pacientes diferentes, insatisfechos con la estética de sus sonrisas.Metodología: En el examen clínico se observaron lesiones blancas en ambos pacientes. En el primer paciente, 14 añosse verificó la presencia de actividad de caries y micro cavitaciones. De ese modo, el plan de tratamiento incluyó la orientación supervisada de la higiene bucal,la aplicación semanal de barniz de flúor (Enamelast), la adaptación del entorno con restauraciones de resina y, sólo después, el uso del infiltrante,Icon. La segunda paciente, 11 años,ya tenía una salud bucal adecuada y presentaba una queja estética debido a una lesión blanca no cariosa, hipoplasia, cuyo plan de tratamiento fue el uso exclusivo de Icon. Conclusiones: En ambos casos, se consiguió una mejora estética considerable con este procedimiento microinvasivo. La mejora de la salud bucal, unida a la recuperación de la estética, puede observarse con el uso de infiltrantes de resina (AU).

Classification of bladder cancer based on immune cell infiltration and construction of a risk prediction model for prognosis / 浙江大学学报·医学版

OBJECTIVES@#To classify bladder cancer based on immune cell infiltration score and to construct a risk assessment model for prognosis of patients.@*METHODS@#The transcriptome data and data of breast cancer patients were obtained from the TCGA database. The single sample gene set enrichment analysis was used to calculate the infiltration scores of 16 immune cells. The classification of breast cancer patients was realized by unsupervised clustering, and the sensitivity of patients with different types to immunotherapy and chemotherapy was analyzed. The key modules significantly related to the infiltration of key immune cells were identified by weighted correlation network analysis (WGCNA), and the key genes in the modules were extracted. A risk scoring model and a nomogram for risk assessment of prognosis for bladder cancer patients were constructed and verified.@*RESULTS@#The immune cell infiltration scores of normal tissues and tumor tissues were calculated, and B cells, mast cells, neutrophils, T helper cells and tumor infiltrating lymphocytes were determined to be the key immune cells of bladder cancer. Breast cancer patients were clustered into two groups (Cluster 1 and Custer 2) based on immune cell infiltration scores. Compared with patients with Cluster 1, patients with Cluster 2 were more likely to benefit from immunotherapy (P<0.05), and patients with Cluster 2 were more sensitive to Enbeaten, Docetaxel, Cyclopamine, and Akadixin (P<0.05). WGCNA screened out 35 genes related to key immune cells, and 4 genes (GPR171, HOXB3, HOXB5 and HOXB6) related to the prognosis of bladder cancer were further screened by LASSO Cox regression. The areas under the ROC curve (AUC) of the bladder cancer prognosis risk scoring model based on these 4 genes to predict the 1-, 3- and 5-year survival of patients were 0.735, 0.765 and 0.799, respectively. The nomogram constructed by combining risk score and clinical parameters has high accuracy in predicting the 1-, 3-, and 5-year overall survival of bladder cancer patients.@*CONCLUSIONS@#According to the immune cell infiltration score, bladder cancer patients can be classified. And the bladder cancer prognosis risk scoring model and nomogram based on key immune cell-related genes have high accuracy in predicting the prognosis of bladder cancer patients.

Evaluation of early effectiveness of local infiltration anesthesia with compound betamethasone in total knee arthroplasty / 中国修复重建外科杂志

OBJECTIVE@#To evaluate the early effectiveness of local infiltration anesthesia (LIA) with compound betamethasone in total knee arthroplasty (TKA).@*METHODS@#The clinical data of 102 patients with knee osteoarthritis who were treated by TKA and met the selection criteria between May 2022 and March 2023 were retrospectively analyzed. They were divided into control group and study group according to whether LIA preparation was added with compound betamethasone, with 51 cases in each group. There was no significant difference of baseline data, such as age, gender, body mass index, operative side, preoperative range of motion (ROM), Knee Society Score (KSS), white blood cell (WBC), and hematocrit between the two groups ( P>0.05). The intraoperative total blood loss and hidden blood loss were recorded, and WBC was recorded on the 1st, 2nd, and 3rd days after operation. Pain was assessed by visual analogue scale (VAS) score on the 1st, 2nd, and 3rd days after operation and morphine intake milligrames equivalent within 48 hours after operation. Passive ROM, maximum extension and flexion angles of knee joint were measured on the 3rd day after operation; the early postoperative complications were recorded.@*RESULTS@#There was no significant difference in total blood loss and hidden blood loss between the two groups ( P>0.05). The postoperative pain levels in both groups were relatively mild, and there was no significant difference in VAS scores in the first 3 days after operation and in morphine intake milligrams equivalent within 48 hours after operation between the two groups ( P>0.05). The WBC in the first 3 days after operation was significantly improved in both groups ( P<0.05). The WBC in the study group was significantly higher than that in the control group on the 1st and 2nd days after operation ( P<0.05), but there was no significant difference between the two groups on the 3rd day after operation ( P>0.05). On the 3rd day after operation, the maximum extension angle of knee joint in the study group was smaller than that in the control group, while the maximum flexion angle and passive ROM of knee joint in the study group were larger than those in the control group, and the differences were significant ( P<0.05). There were 6 cases of fever and 17 cases of deep venous thrombosis in the control group, and 1 case and 14 cases in the study group, respectively. There was no poor wound healing and periprosthetic joint infection in the two groups, and there was no significant difference in the incidence of complications between the two groups ( P>0.05).@*CONCLUSION@#The application of compound betamethasone in LIA during TKA is a safe and optimal strategy to promote the early postoperative rehabilitation of patients.

Identification and Analysis of SND1 as an Oncogene and Prognostic Biomarker for Lung Adenocarcinoma / 中国肺癌杂志

BACKGROUND@#Transcription factor (TF) can bind specific sequences that either promotes or represses the transcription of target genes, and exerts important effects on tumorigenesis, migration, invasion. Staphylococcal nuclease-containing structural domain 1 (SND1), which is a transcriptional co-activator, is considered as a promising target for tumor therapy. However, its role in lung adenocarcinoma (LUAD) remains unclear. This study aims to explore the role of SND1 in LUAD.@*METHODS@#Data from The Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO), Clinical Proteomic Tumor Analysis Consortium (CPTAC), and Human Protein Atlas (HPA) database was obtained to explore the association between SND1 and the prognosis, as well as the immune cell infiltration, and subcellular localization in LUAD tissues. Furthermore, the functional role of SND1 in LUAD was verified in vitro. EdU assay, CCK-8 assay, flow cytometry, scratch assay, Transwell assay and Western blot were performed.@*RESULTS@#SND1 was found to be upregulated and high expression of SND1 is correlated with poor prognosis of LUAD patients. In addition, SND1 was predominantly present in the cytoplasm of LUAD cells. Enrichment analysis showed that SND1 was closely associated with the cell cycle, as well as DNA replication, and chromosome segregation. Immune infiltration analysis showed that SND1 was closely associated with various immune cell populations, including T cells, B cells, cytotoxic cells and dendritic cells. In vitro studies demonstrated that silencing of SND1 inhibited cell proliferation, invasion and migration of LUAD cells. Besides, cell cycle was blocked at G1 phase by down-regulating SND1.@*CONCLUSIONS@#SND1 might be an important prognostic biomarker of LUAD and may promote LUAD cells proliferation and migration.

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.

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.

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.

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)

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.

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.

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 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.

Prognostic value of CC motif chemokine receptor 2 in the microenvironment of glioblastoma and its relationship with the immune cell infiltration / 肿瘤研究与临床

Objective:To explore the prognostic biomarkers of glioblastoma (GBM) in the tumor microenvironment (TME) and its function.Methods:A total of 169 GBM samples of 161 GBM patients were collected from the Cancer Genome Atlas (TCGA) database. ESTIMATE algorithm in R4.1.0 software was used to calculate the proportion of immune components and stromal components in TME, which were expressed as immune score and stromal score, respectively. According to the median value of the two scores, 169 GBM samples were divided into the high score group and the low score group, respectively, 84 each in each group (those whose scores were equal to the median were not involved in the grouping). The differentially expressed genes (DEG) [false discovery rate (FDR) < 0.05] between the high score group and the low score group of the two scores were obtained by using limma package, and the co-up-regulated and co-down-regulated DEG of the two scores were obtained by using Venn program. Based on the STRING database, the protein interaction (PPI) network of co-up-regulated and down-regulated DEG of immune score and stromal score was constructed, and the top 30 genes with connectivity were selected. Univariate Cox proportional hazard model analysis of overall survival (OS) of 161 GBM patients in the TCGA database was performed on co-up-regulated and down-regulated DEG between immune score and stromal score by using R4.1.0 software to obtain the DEG affecting OS. The intersection of the DEG obtained from PPI analysis and Cox analysis was taken as the prognostic core genes. According to the median expression value of prognostic core genes in GBM samples from the TCGA database, 161 patients were divided into prognostic core genes high expression group and low expression group (patients whose scores were equal to the median were not involved in the grouping), with 80 cases in each group. Kaplan-Meier survival analysis of OS was performed by using R4.1.0 software. GSEA 4.2.1 software was used to perform gene set enrichment analysis (GSEA) on all genes with transcriptome data of GBM patients in the two groups of the TCGA databases, and the main enriched functions of the two groups of genes were obtained. The CIBERSORT algorithm was used to test the accuracy of the proportion of tumor infiltrating immune cell (TIC) subsets in 169 GBM samples from the TCGA database, and 57 GBM samples were finally obtained. Immune cells with differential expression levels and immune cells related to the expression of prognostic core genes among the samples with different expression levels of prognostic core genes were analyzed; Venn program was used to obtain the intersection of immune cells with differential levels and related immune cells, and differentially expressed TIC related to expressions of prognostic core genes in GBM were obtained.Results:Based on the immune score and stromal score of GBM samples in the TCGA database, a total of 693 co-up-regulated and co-down-regulated DEG of both scores were screened out. After the intersection of 78 DEG related to OS obtained by univariate Cox regression analysis and 30 DEG obtained by PPI network results, CC motif chemokine receptor 2 (CCR2) was identified as the prognostic core gene ( HR = 1.294, 95% CI 1.060-1.579, P = 0.011). GBM patients with CCR2 high expression had worse OS compared with those with CCR2 low expression ( P = 0.009). GSEA analysis showed that genes in the CCR2 high expression group were mainly enriched in immune-related pathways, while genes in the CCR2 low expression group were mainly enriched in metabolism-related pathways. Among 57 screened GBM samples, there were differences in the levels of 3 immune cells between the CCR2 high expression group and the CCR2 low expression group ( P < 0.05). CCR2 expression was correlated with the levels of 9 immune cells (all P < 0.05). Venn program analysis showed that differentially expressed 3 TIC in GBM related to CCR2 gene expression were obtained; among them, M2 macrophages were positively correlated with CCR2 expression, while T follicular helper cell and activated NK cells were negatively correlated with CCR2 expression. Conclusions:CCR2 may be the core gene related to the prognosis in the TME of GBM. As reference, the level of CCR2 can help to predict the status of TME and prognosis in GBM patients, which is expected to provide a new direction for the treatment of GBM.

The efficacy and safety of transurethral partial cystectomy combined with intravesical suturation in the treatment of bladder cancer / 中华泌尿外科杂志

Objective:To summarize the efficacy and safety of transurethral partial cystectomy combined with intravesical suturation in the treatment of bladder cancer.Methods:The clinical data of 28 patients with bladder cancer who were admitted in Zhengzhou People's Hospital from July 2020 to October 2021 were analyzed retrospectively. There were 22 males and 6 females, with the average age of (68.8±8.9) years old. Twenty cases were with single bladder tumor, and 8 cases were with multiple bladder tumors. The diameter of single bladder tumor measured by CT was less than 4 cm, with a median tumor diameter of 2.3(0.9, 2.8)cm. All 28 patients underwent transurethral partial cystectomy combined with intravesical suturation for the first time. Intraoperative intravesical instillation was conducted with 1 g gemcitabine. Bladder hot reperfusion treatment was performed with gemcitabine 2 g at 45℃ immediately after operation. The patients underwent reexamination with cystoscopy every 3 months after operation.Results:All the 28 patients successfully completed the operation. The average operation time was (128.3±16.3)min. No obturator nerve reflection was induced during operation. Muscularis tissue was found in all tumor pathological specimens after operation, among which 4 cases showed muscularis infiltration. Pathology of tumor basal and peripheral tissues showed tumor cell infiltration in 3 cases (1 case full-thickness infiltration, namely the incision margin was positive). The median continuous irrigation time of bladder after operation was 24.0(20.9, 25.0)h. The median time of indwelling catheter after operation was 6.5(6.0, 7.0)days, and one case developed severe bladder spasm. All patients were followed up, with a median follow-up of 7.5(4.0, 10.8) months.Postoperative recurrence occurred in 3 cases, all of which were ectopic recurrence in bladder.The 1-year recurrence rate was 10.7% (3/28).Conclusions:In the first surgical treatment of bladder cancer, transurethral partial cystectomy combined with intravesical suturation can provide accurate pathological staging, and low positive surgical margin rate. Immediate suturation of bladder wound during operation and immediate bladder perfusion chemotherapy can provide short bladder irrigation time, with few adverse reactions and low incidence of complications.

Analysis of diagnosis and treatment of invasive renal parenchymal urothelial carcinoma / 中华泌尿外科杂志

Objective:To investigate the clinical features of diagnosis and treatment of renal parenchymal invasive urothelial carcinoma.Methods:The clinical data of 23 patients with renal parenchymal invasive urothelial carcinoma admitted to Beijing Chaoyang Hospital Affiliated to Capital Medical University from January 2014 to December 2020 were retrospectively analyzed. There were 12 males and 11 females. The mean age was (67.3±10.1) years old. Among them, 7 cases complained of painless hematuria and 9 cases were asymptomatic. Three cases underwent preoperative MRI examination, 19 patients underwent preoperative enhanced CT examination, and 1 patient underwent both MRI and enhanced CT examination. MRI examination showed renal lobulated and other T1 mixed with T2 signals, the boundary was not clear, and DWI showed obvious restricted diffusion. The tumor was located on the left side in 15 cases and on the right side in 8 cases. Preoperative diagnosis was made by fine needle aspiration biopsy in 1 patient, and specimens were obtained by flexible ureteroscope in 2 patients. No tumor was reported. The preoperative diagnosis of 22 patients was unclear and the nature of the tumor could not be determined. One patient was considered to have urothelial carcinoma by fine needle aspiration. All patients were treated by surgery, including 20 cases of laparoscopic radical nephrectomy and 3 cases of nephroureterectomy with bladder sleeve resection.Results:Postoperative pathological specimens showed yellow-white mass, high-grade invasive urothelial carcinoma invading renal parenchyma. Nine cases were T 3a stage, 14 cases were T 3b stage, and 5 cases were lymph node metastasis. The average postoperative follow-up time was (18.6±6.72)months, 2 patients were lost to follow-up, 8 patients died, and the overall mortality rate was 38.1%. Seven patients died of recurrence or metastasis. There were 3 cases of bladder recurrence and 5 cases of metastasis after operation. Conclusions:Renal parenchymal infiltrating urothelial carcinoma is difficult to diagnose in the early stage, with poor clinical biological behavior and poor overall prognosis. For patients diagnosed with renal parenchymal invasive urothelial carcinoma preoperatively, laparoscopic nephroureterectomy + bladder sleeve resection is recommended.

Nanoparticles (NPs)-mediated Siglec15 silencing and macrophage repolarization for enhanced cancer immunotherapy

T cell infiltration and proliferation in tumor tissues are the main factors that significantly affect the therapeutic outcomes of cancer immunotherapy. Emerging evidence has shown that interferon-gamma (IFNγ) could enhance CXCL9 secretion from macrophages to recruit T cells, but Siglec15 expressed on TAMs can attenuate T cell proliferation. Therefore, targeted regulation of macrophage function could be a promising strategy to enhance cancer immunotherapy via concurrently promoting the infiltration and proliferation of T cells in tumor tissues. We herein developed reduction-responsive nanoparticles (NPs) made with poly (disulfide amide) (PDSA) and lipid-poly (ethylene glycol) (lipid-PEG) for systemic delivery of Siglec15 siRNA (siSiglec15) and IFNγ for enhanced cancer immunotherapy. After intravenous administration, these cargo-loaded could highly accumulate in the tumor tissues and be efficiently internalized by tumor-associated macrophages (TAMs). With the highly concentrated glutathione (GSH) in the cytoplasm to destroy the nanostructure, the loaded IFNγ and siSiglec15 could be rapidly released, which could respectively repolarize macrophage phenotype to enhance CXCL9 secretion for T cell infiltration and silence Siglec15 expression to promote T cell proliferation, leading to significant inhibition of hepatocellular carcinoma (HCC) growth when combining with the immune checkpoint inhibitor. The strategy developed herein could be used as an effective tool to enhance cancer immunotherapy.

Antitumor synergism between PAK4 silencing and immunogenic phototherapy of engineered extracellular vesicles

Immunotherapy has revolutionized the landscape of cancer treatment. However, single immunotherapy only works well in a small subset of patients. Combined immunotherapy with antitumor synergism holds considerable potential to boost the therapeutic outcome. Nevertheless, the synergistic, additive or antagonistic antitumor effects of combined immunotherapies have been rarely explored. Herein, we established a novel combined cancer treatment modality by synergizing p21-activated kinase 4 (PAK4) silencing with immunogenic phototherapy in engineered extracellular vesicles (EVs) that were fabricated by coating M1 macrophage-derived EVs on the surface of the nano-complex cores assembled with siRNA against PAK4 and a photoactivatable polyethyleneimine. The engineered EVs induced potent PAK4 silencing and robust immunogenic phototherapy, thus contributing to effective antitumor effects in vitro and in vivo. Moreover, the antitumor synergism of the combined treatment was quantitatively determined by the CompuSyn method. The combination index (CI) and isobologram results confirmed that there was an antitumor synergism for the combined treatment. Furthermore, the dose reduction index (DRI) showed favorable dose reduction, revealing lower toxicity and higher biocompatibility of the engineered EVs. Collectively, the study presents a synergistically potentiated cancer treatment modality by combining PAK4 silencing with immunogenic phototherapy in engineered EVs, which is promising for boosting the therapeutic outcome of cancer immunotherapy.

Aconite aqueous extract inhibits the growth of hepatocellular carcinoma through CCL2-dependent enhancement of natural killer cell infiltration / 中西医结合学报

OBJECTIVE@#Aconite is a traditional Chinese herbal medicine that has been found to inhibit the development of liver cancer; however, its exact molecular mechanisms in this process remain unclear. This study explores how aconite aqueous extract (AAE) inhibits hepatocellular carcinoma (HCC).@*METHODS@#An in vivo mouse model of subcutaneous liver cancer was established. After AAE treatment, immunohistochemistry (IHC) was used to determine the effect of AAE on natural killer (NK) cells. Subsequently, C57BL/6 mice were used to establish the subcutaneous tumor model, and a group of these mice were treated with anti-PK163 antibody to remove NK cells, which was verified by flow cytometry and IHC. The effect of AAE on the proliferation of HCC cells in vitro was determined using cell counting kit-8. The effect of AAE on chemokine production in HCC cells was measured using real-time quantitative polymerase chain reaction and an enzyme-linked immunosorbent assay. The effect of AAE on the migration of NK cells was determined using a transwell assay. Finally, the molecular mechanism was investigated using the Western blotting method.@*RESULTS@#We demonstrated that the ability of AAE to induce overexpression of the cytokine C-C motif chemokine ligand 2 (CCL2) in HCC cells is fundamental to the infiltration of NK cells into the tumor bed. Mechanistically, we found that the upregulation of CCL2 was achieved by the activation of c-Jun N-terminal kinase but not extracellular regulated protein kinase or p38.@*CONCLUSION@#Our findings suggest that AAE can be used as an effective immune adjuvant to enhance antitumor immunity by increasing NK cell infiltration into tumors, which could help to improve the efficacy of HCC treatments. Please cite this article as: Yang KD, Zhang X, Shao MC, Wang LN. Aconite aqueous extract inhibits the growth of hepatocellular carcinoma through CCL2-dependent enhancement of natural killer cell infiltration. J Integr Med. 2023; 21(6): 575-583.

Effects of immune infiltration-related gene CSAG1 on the progression of renal clear cell carcinoma / 现代泌尿外科杂志

【Objective】 To explore the correlation between CSAG1 expression and the prognosis and tumor-infiltrating lymphocytes in renal clear cell carcinoma (RCCC), and to predict the survival and tumor progression. 【Methods】 The gene expression profiles and clinical information of CSAG1 were downloaded from the Cancer Genome Atlas (TCGA). Based on the differential mRNA expression, GO annotation and KEGG pathway analysis were performed. The relationship between CSAG1 and tumor immune infiltration was assessed with Tumor Immunoassay Resource (Timer 2.0) database. The mRNA expression of CSAG1 in human RCCC specimens was validated with qRT-PCR. 【Results】 CSAG1 expression was significantly higher in RCCC tissues than in normal tissues (P<0.05). The qRT-PCR results revealed that the mRNA level of CSAG1 was consistent with that predicted by bioinformatic analysis. The KEGG analysis and GO annotation indicated high GSAG1 expression in RCCC was related to transmembrane transport, tricarboxylic acid cycle and lysosome. CSAG1 expression was positively related to the infiltration of pDC, aDC, CD8+ T cells, cytotoxic cells, TFH, TH1 cells, Tem, NK CD56dm cells, Treg and T cells, but negatively correlated with macrophage infiltration. 【Conclusion】 CSAG1 may be associated with poor prognosis of RCCC and become a potential immunotherapy target.

Bioinformatic analysis of the expression of KIF14 and its clinical significance and biological functions in clear cell renal cell carcinoma / 现代泌尿外科杂志

【Objective】 To investigate the expression of Kinesin family member 14 (KIF14), and its correlation with clinical prognosis and immune cell infiltration of clear cell renal cell carcinoma (ccRCC). 【Methods】 The correlation between KIF14 expression in ccRCC and different clinicopathological features were analyzed with TCGA, GEO and Ualcan databases. The correlation between KIF14 expression and prognosis was analzyed with Kaplan-Meier method. The correlation between KIF14 expression and immune cell infiltration was analzyed with TIMER. The protein-protein interaction network of KIF14 was conducted with Genemania. The co-expression genes of KIF14 in TCGA-KIRC were picked out in Linkedomics database and were used to perform GO annotations and KEGG pathway enrichment analysis with R software. The biological functions of KIF14 were verified with in vitro functional assay. 【Results】 KIF14 was highly expressed in ccRCC tissue and was positively correlated with clinical stage, pathological grade, and lymphatic metastasis, but negatively correlated with clinical prognosis. KIF14 expression was an independent risk factor for overall survival of ccRCC patients. GO annotations showed that KIF14 was involved in DNA replication, nuclear division, organelle fission, and cell adhesion. KEGG pathway enrichment analysis showed that KIF14 participated in cell cycle and p53 signaling pathway. Genemania analysis indicated KIF14 interacted with CENPE, CIT, KIF23, and other proteins. Timer showed that KIF14 was positively correlated with immune cell infiltration. Knockdown of KIF14 expression suppressed cell proliferation, migration, and invasion of ccRCC. 【Conclusions】 KIF14 may serve as a novel prognostic marker and a potential therapeutic target of clear cell renal cell carcinoma.