Effect of electrochemically dealloying Ti6Al4V abutments on human gingival fibroblasts / 口腔疾病防治

Objective@#To investigate the effects of electrochemically dealloying of Ti6Al4V abutments on human gingival fibroblasts (HGFs) and to provide experimental evidence for surface modification of implant abutments.@*Methods@#The samples were divided into an NC group (negative control, no other treatment on a smooth surface), an NM-1 group (nanomesh-1, electrochemical dealloying treatment in 1 mol/L NaOH 1 h on 2 V voltage), and an NM-2 group (nanomesh-2, electrochemical dealloying treatment in 5 mol/L NaOH 1 h on 2 V voltage). The surface morphologies of the samples and the adhesion of HGFs on the sample surfaces were observed with scanning electron microscopy (SEM). The surface hydrophilicities of the samples were measured with a contact angle measuring instrument. The proliferation of HGFs on the different samples were evaluated with CCK-8, and the expression of adhesion-related genes, including collagen Ⅰ (COL1A1), collagen Ⅲ (COL3A1), fibronectin 1 (FN1), focal adhesion kinase (FAK), vinculin (VCL), integrin α2 (ITGA2), and integrin β1 (ITGB1), on the different samples was measured with qRT-PCR. The expression of vinculin on the surfaces of HGFs was observed via confocal laser scanning microscopy (CLSM) after immunofluorescent staining. Collagen fiber secretion and syntheses of HGFs from different samples were evaluated via Sirius red staining.@*Results@#SEM revealed the formation of ordered and uniform three-dimensional mesh structures on the surfaces of the NM-1 and NM-2 groups, with grid diameters of approximately 30 nm for the NM-1 group and approximately 150 nm for the NM-2 group. Compared with that of the NC group, the water contact angles of the NM-1 group and NM-2 groups were significantly lower (P<0.000 1). Cell proliferation in the NM-1 group was significantly greater than that in the NC group (P<0.01). Moreover, there was no significant difference in the water contact angles or cell proliferation between the NM-1 group and the NM-2 group. SEM revealed that HGFs were adhered well to the surfaces of all samples, while the HGFs in the NM-1 and NM-2 groups showed more extended areas, longer morphologies, and more developed pseudopodia than did those in the NC group after 24 h. qRT-PCR revealed that the expression levels of the adhesion-related genes COL1A1, COL3A1, FN1, FAK and VCL in the NM-1 group were significantly greater than those in the NC and NM-2 groups (P<0.01). The expression of vinculin protein in the NM-1 group was the highest, and the number of focal adhesions was greatest in the NM-1 group (P<0.01). The results of Sirius red staining showed that the NM-1 group had the highest secretion and syntheses of collagen fibers (P<0.000 1).@*Conclusion@#The three-dimensional nanomechanical structure of Ti6Al4V modified by electrochemical dealloying promoted the adhesion, proliferation, collagen fiber secretion and syntheses of HGFs, and electrochemical dealloying of Ti6Al4V with a grid diameter of approximately 30 nm obviously promoted HGF formation.

Research progress of long-term efficacy after implantation of implantable collamer lens V4c / 国际眼科杂志(Guoji Yanke Zazhi)

With the rapid development of science and technology and the wide application of electronic products, the number of patients with high myopia is gradually increasing. Meanwhile, owing to the continuous optimization of surgical skils and the continuous advancement in materials of posterior chamber intraocular lens and manufacturing processes, implantable collamer lens(ICL)V4c implantation has gradually become one of the main surgeries for the treatment of high myopia. In the rapid era of social information, people pay more attention to the long-term efficacy after ICL V4c implantation, they not only want clear vision, but also the pursuit of visual comfort and durability. Therefore, this paper will specifically discuss the research progress of the post-implantation efficacy of ICL V4c with at least 2 a of follow-up observation within 3 a, aiming to review the latest research progress on the long-term efficacy of ICL V4c implantation from the three dimensions of visual quality, safety, efficacy and stability and possible surgical complications after ICL V4c implantation.

Evaluation of early binocular visual function after implantable collamer lens V4c implantation in patients with high myopia / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To evaluate the binocular visual function in high myopia patients after the implantation of implantable collamer lens(ICL)V4c.METHODS: A total of 35 cases(70 eyes)that received binocular ICL implantation at our hospital from May 2019 to May 2021 were enrolled in this prospective study. Binocular full-range visual acuity, contrast sensitivity, stereopsis, mesopic vision and glare sensitivity, and monocular wavefront and the quality of vision questionnaire were assessed before the surgery and at 1 mo postoperatively.RESULTS: At 1 mo postoperatively, 35 cases(100%)had binocular uncorrected distance visual acuity(UDVA)≤0.00(LogMAR), 16 cases(46%)had binocular UDVA≥preoperative corrected distance visual acuity(CDVA). Binocular UDVA and uncorrected intermediate visual acuity(UIVA,80 cm)were improved compared to preoperative CDVA and distance-corrected intermediate visual acuity(DCIVA,80 cm)(all P&#x003C;0.05).While there were no differences in the binocular postoperative UIVA(60 cm)and preoperative DCIVA(60 cm),and uncorrected near visual acuity(UNVA,40 cm)and preoperative distance-corrected near visual acuity(DCNVA,40 cm)(all P&#x003E;0.05). The binocular contrast sensitivity was significantly improved postoperatively(P=0.001), and the postoperative binocular mesopic vision, glare sensitivity(no glare/glare)and binocular stereopsis(5 m/40 cm)had no differences(all P&#x003E;0.05). The postoperative total higher-order aberration, trefoil aberration, coma and spherical aberration were increased, besides the median of total coma in the right eye with a pupil diameter of 3.0 mm was decreased after surgery. The mean total score of quality of vision questionnaire was significantly increased from 54.87 preoperatively to 80.92 after implantation(P&#x003C;0.05), with high satisfaction and no obvious visual disturbance in patients.CONCLUSION: Although the monocular high-order aberrations increased in the early stage after ICL V4c binocular implantation in patients with high myopia, the binocular visual function was improved.

Early outcomes of anterior segment parameters in patients with high myopia after implantable collamer lens V4c implantation / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To study the early outcomes of anterior segment parameters after implantation of an implantable collamer lens with a central hole(ICL V4c)in patients with high myopia.METHODS:A total of 82 cases(160 eyes)with high myopia, including 42 males(82 eyes)and 40 females(78 eyes), aged 26.0±4.6(21 to 37)years, who underwent ICL V4c implantation at our institution from February 2019 to September 2022 and were followed up for 1 a, were included. The general characteristics of the anterior segment of the eye were measured preoperatively: spherical equivalent, mean horizontal corneal curvature, white-to-white(WTW), and axial length(AL); intraocular pressure(IOP), endothelial cell density(ECD), central anterior chamber depth(CACD), anterior chamber volume(ACV)and anterior chamber angle(ACA)were measured preoperatively and at 1 d, 1 wk, 1, 3 and 6 mo postoperatively. Furthermore, the distance from the centre of the posterior surface of the ICL V4c optical zone to the anterior surface of the lens(vault)was measured at 1 d, 1 wk, 1, 6 mo, and 1 a after surgery.RESULTS: The mean preoperative spherical equivalent of the patients was -7.56±2.55 D, mean horizontal corneal curvature was 42.89±1.47 D, WTW was 11.64±0.37 mm, and AL was 26.64±0.93 mm. The baseline IOP was 15.97±2.13 mmHg, and the differences in IOP at each time point after ICL V4c implantation compared to preoperative were not statistically significant(F=0.875, P=0.504); ECD was 2 989.30±140.78 cells/mm2 at baseline, and ECD at 6 mo after ICL V4c implantation was not statistically significant compared with preoperative ECD(t=1.475, P=0.142); CACD was 3.19±0.21 mm at baseline, and ACV was 210.30±27.7 mm3, and CACD and ACV were significantly lower than preoperative at all postoperative time points(F=111.10, 288.38, all P&#x003C;0.001). The baseline ACA was 35.44°±11.27°, and the ACA at each time point after ICL V4c implantation was significantly lower than preoperatively(F=21.23, P&#x003C;0.001). The vault was 665.32±184.03 μm at 1 d postoperatively, and continued to be significantly reduced at 1 wk, 1, 6 mo, and 1 a postoperatively compared with 1 d(F=52.10, P&#x003C;0.001). However, it remained stable at 6 mo and 1 a postoperatively, and the difference was not statistically significant compared with vault at 1 mo postoperatively(P&#x003E;0.05).CONCLUSION: ICL V4c has certain safety and efficiency in 1 a postoperative follow-up, and the parameters of the anterior segment of the eye stabilized in the early period.

Consensus Auditory Perceptual Evaluation of Voice (CAPE-V): revisión sistemática de los métodos utilizados para su adaptación y validación

Introducción: CAPE-V es ampliamente utilizado para evaluación perceptual vocal y ha sido adaptado y validado en múltiples idiomas. A través de un análisis exhaustivo, este estudio buscó avanzar en establecer un estándar en el método utilizado para su adaptación y validación. Objetivo: Revisar los artículos publicados entre 2002 y 2022 que han adaptado y validado CAPE-V a distintos idiomas, para evaluar exhaustivamente la adaptación, metodología y estadísticas utilizadas. Métodos: Se realizó una revisión sistemática utilizando Scopus, Google Scholar y PubMed para identificar artículos que adaptaran y/o validaran CAPE-V entre 2002 y 2022. Se analizó el título y resumen para preseleccionar la muestra. Para evaluar el riesgo de sesgo de los estudios incluidos se analizó de forma crítica el texto completo. Resultados: La búsqueda inicial identificó 568 artículos. Al eliminar duplicados se revisaron 559 y 23 fueron preseleccionados. 12 se incluyeron finalmente y fueron analizados, considerando adaptación, metodología y análisis estadístico. Los resultados revelan que la adaptación y validación de CAPE-V a diversos idiomas es fundamental para garantizar mediciones precisas y confiables en diferentes poblaciones. Análisis y discusión: Existe heterogeneidad en la forma de realizar la adaptación y validación de CAPE-V. No obstante, todos los estudios tuvieron éxito en producir resultados válidos, subrayando la importancia de estos procesos para la práctica clínica. Conclusiones: Las adaptaciones y validaciones de CAPE-V se realizaron heterogéneamente por ausencia de un protocolo estándar. Es necesario generar orientaciones para realizar estos procesos por el aporte de esta escala a la clínica, asegurando calidad y confiabilidad de los resultados.

Introduction: CAPE-V is widely used for vocal perceptual evaluation and has been adapted and validated in multiple languages. Through an exhaustive analysis, this study sought to advance in establishing a standard in the method used in its adaptation and validation. Objective: To review articles published between 2002 and 2022 that have adapted and validated CAPE-V in different languages, to thoroughly evaluate the adaptation, methodology, and statistics used. Methods: A systematic review was conducted using Scopus, Google Scholar and PubMed to identify articles that adapted and/or validated CAPE-V between 2002 and 2022. The title and summary were analyzed to pre-select the sample. To evaluate the risk of bias of the included studies, the full text was critically analyzed. Results: The initial search identified 568 items. When duplicates were removed, 559 were reviewed and 23 were pre-selected. 12 were finally included and analyzed considering adaptation, methodology, and statistical analysis. The results show that the adaptation and validation of CAPE-V to different languages is essential to ensure accurate and reliable measurements in different populations. Analysis and discussion: There is heterogeneity in how CAPE-V is adapted and validated. However, all studies were successful in producing valid results, underlining the importance of these processes for clinical practice. Conclusions: Adaptations and validations of CAPE-V were performed heterogeneously due to the absence of a standard protocol. It is necessary to generate guidelines to perform these processes by providing this scale to the clinic, ensuring quality and reliability of results.

Detection and evaluation of the presence of the BRAF V600E mutation in ameloblastomas in an Indian population

Introduction: Ameloblastoma is a benign epithelial odontogenic neoplasm that constitutes approximately 1% of all oral tumors and about 9 to 11% of all odontogenic tumors. They are slow-growing, locally invasive, and demonstrate a potential for metastasis and malignant transformation. The molecular pathogenesis of ameloblastoma is attributed to aberrant activity of the signal transduction pathways relating to developmental stages of odontogenesis including the mitogen-activated protein kinase (MAPK) pathway. The BRAF V600E mutation was identified as the most frequently mutated gene in this neoplasm. Studies have shown that use of BRAF inhibitors in patients diagnosed with ameloblastomas led to a significant reduction in tumor volume. Aims: To detect the expression of BRAF V600E mutation in ameloblastomas in an Indian population using immunohistochemistry. To compare the difference in the occurrence of the BRAF V600E mutation between mandibular and maxillary cases. Materials and Methods: Thirty-three formalin-fixed paraffin-embedded tissues of histopathologically proven cases of ameloblastoma were assessed for the BRAF V600E mutation by immunohistochemistry using the BRAF V600E monoclonal antibody. Patient data such as age, sex, anatomical site, recurrence were documented. Statistical Analysis: The statistical analysis was performed using the Pearson Chi-square test and Student's t-test. Results: The present study revealed a high expression of the BRAFV600E mutation in mandibular cases of ameloblastoma among Indians irrespective of the age, sex, site, recurrence or histological pattern. Conclusions: The identification of this driver mutation opens the possibility of an adjuvant therapeutic modality to reduce the significant facial disfigurement and morbidity following surgical management.

Faceta Direta de Resina Composta utilizando Pigmentos Opacificadores para Reabilitação Estética Anterior de Dente Escurecido: Relato de Caso / Direct Composite Resin Veneer using Opacifying Pigments for Anterior Aesthetic Rehabilitation of Discolored Teeth: Case Report

O tratamento estético de dentes com alteração de cor é um grande desafio na Odontologia Restauradora. Nesse sentido, a utilização de técnicas de estratificação com resina composta associada ao uso de pigmentos opacificadores permite que seja possível restaurar por meio de uma técnica direta, que resulta em um menor desgaste da estrutura dental durante o preparo. Dessa forma, o presente trabalho apresenta um caso clínico de faceta direta de resina composta utilizando associação de três pigmentos opacificadores. Paciente do sexo masculino, 54 anos, procurou atendimento apresentando alteração de cor severa do dente 21, relato de trauma dental, tratamento endodôntico e contraindicação de novo protocolo de clareamento interno, sendo sugerido, como plano de tratamento, a restauração direta com resina composta. Para a confecção da faceta direta de resina, foi utilizada uma mistura de três opacificadores na consistência fluida. Para verificar o valor da camada aplicada da mistura, foram feitas fotografias em preto e branco. A estratificação prosseguiu com camadas de resina translúcida para a base palatina, resina opaca de dentina e resina acromática translúcida para o esmalte. Como resultado, constatou-se a função e eficácia do uso da associação de pigmentos opacificadores na resolução do caso, em seguida, foi realizada uma reavaliação após 30 dias e 7 meses do procedimento restaurador, quando verificou-se a estabilidade de cor da restauração. Concluiu-se, portanto, que a utilização da técnica de estratificação de resinas compostas associada a utilização de pigmentos opacificadores traz resultados estéticos satisfatórios e favoráveis por meio de uma técnica direta, realizada em sessão clínica única e com alta previsibilidade.

The esthetic treatment of teeth with discoloration is a major challenge in restorative dentistry. In this sense, the use of composite resin veneering techniques associated with the use of opacifying stains allows restorations to be made using a direct technique, which results in less wear to the tooth structure during preparation. Thus, the present study presents a clinical case of a direct composite resin veneer using an association of three opacifying pigments. A 54-year-old male patient presented with severe color change on the central upper left incisor, a report of dental trauma, endodontic treatment, and contraindication for a new internal bleaching protocol. In order to make the direct resin veneer, a mixture of three opacifiers in a fluid consistency was used. To check the value of the applied layer of the mixture, black and white photographs were taken. Layering proceeded with translucent resin layers for the palatal base, opaque dentin resin and translucent achromatic resin for the enamel. As a result, the function and efficacy of the use of the association of opacifying pigments was verified in the resolution of the case. A reevaluation was performed 30 days and 7 months after the restorative procedure, when the color stability of the restoration was verified. This case allows to conclude that using composite resin layering technique associated with the use of opacifying pigments brings satisfactory and favorable aesthetic results through a direct technique, performed in a single clinical session and with high predictability.

Microarray analysis reveals distinct immune signatures in BCR?ABL positive and negative myeloproliferative neoplasms

Background: BCR?ABL mutation on the Philadelphia chromosome is the key driver of chronic myeloid leukemia (CML) pathogenesis. However, there are certain cases of myeloproliferative neoplasms (MPN) wherein no inherent driver mutation is detected resulting in clinical phenotype. It is important to identify key genes and pathways in driving the disease. The aim of the study was to use a gene-based omics approach to molecularly characterize these mutation-positive and negative cases to further strengthen diagnostics and precision medicine. Methods: A microarray profiling was done on CD34 positive cells isolated from two BCR?ABL positive and five BCR?ABL negative samples. JAK2V617F mutation testing was also done to rule out the presence of any other mutation in the latter group. The fold change cut-off was taken as �5 with p?0.5 for significant genes. The gene network and pathway analysis were done using DAVID and STRING software. Results: The genes upregulated in BCR?ABL negative samples were shown to be involved in immune regulation, signal transduction and T- and B-cell signalling. The protein-protein interaction network of upregulated genes in these samples were enriched for various immunomodulatory genes such as HLADP, HLADQ , IL7R, CCR7, CD3 subtypes. These genes further formed a network with signal transduction genes such as LCK, FYN, RAG1, DOCK1, AKT3, SMAD3, LEF1. Conclusion: The results suggested a modulation of immune response genes and its subsequent effect on oncogenic signalling in BCR?ABL negative samples as compared to BCR?ABL positive samples. The protein network analysis was enriched for genes involved in Src, TGF-beta and PI3K-AKT pathway contributing to the proliferation of neoplastic clone.

Epidemiological profile of Adolescents living with HIV/AIDS in Espirito Santo, Brazil: A cross-sectional study / Perfil epidemiológico de adolescentes vivendo com HIV/AIDS no Espírito Santo, Brasil: um estudo transversal

Introduction: The AIDS epidemic has undergone several transformations, and, in recent years, there has been an increase in cases of HIV/AIDS among adolescents and young people. Thus, it is essential to know this population to base health actions scientifically.Objective: This study aims to analyze the epidemiological profile of adolescents living with HIV/AIDS in Espírito Santo, Brazil.Methods: A descriptive, sectional study in which notifications of HIV/AIDS among adolescents aged 13 to 19 between 2010 and 2020 were analyzed.Results: 523 adolescents with HIV/AIDS were found in the analyzed period (an average of 47 cases/year). There was a predominance of male adolescents (68.8%), older than 16 years (mean=18.0 years), of mixed race/colour (54.6%), living in the metropolitan region near the capital. It was observed that the schooling of females is lower, with 47.2% of them in elementary school, while 45.0% of the boys are in high school. In most cases, the infection occurred via sexual intercourse, among men, through homosexual relations (55.0%), and among women, through heterosexual relations (82.2%). The HIV viral load was detectable in almost all (84.8%) cases, and 11 (6.8%) of these adolescents died.Conclusion: The epidemiological profile of HIV and AIDS cases among adolescents in Espírito Santo shows a higher frequency of cases in males aged 16 to 19 years, with incomplete high school education, who acquired HIV through unprotected sex in homosexual relationships. We highlight the high percentage of young people with detectable viral loads and deaths due to complications of AIDS

Introdução: A epidemia da AIDS passou por diversas transformações e, nos últimos anos, observa-se aumento de casos de HIV/AIDS entre adolescentes e jovens. Assim, é fundamental conhecer essa população para embasar cientificamente as ações em saúde. Objetivo: analisar o perfil epidemiológico de adolescentes que vivem com HIV/AIDS no Estado do Espírito Santo, Brasil. Método: estudo descritivo, seccional, no qual foram analisadas notificações de HIV/AIDS entre adolescentes de 13 a 19 anos, entre 2010 e 2020.Resultados: foram encontrados 523 adolescentes vivendo com HIV/AIDS no período analisado (média de 47 casos/ano). Prevaleceu os adolescentes do sexo masculino (68,8%), com mais de 16 anos (média=18,0 anos), de raça/cor parda (54,6%), residentes na região metropolitana, próxima a capital. Foi observado que a escolaridade do sexo feminino é menor, estando 47,2% delas no ensino fundamental, enquanto 45,0% dos rapazes já estão no ensino médio. Em grande parte dos casos a infecção ocorreu via sexual, sendo, entre os homens, através de relações homossexuais (55,0%) e entre as mulheres por meio de relações heterossexuais (82,2%). A carga viral de HIV foi detectável em quase totalidade (84,8%) dos casos e 11 (6,8%) destes adolescentes evoluíram para óbito. Conclusão: O perfil epidemiológico dos casos de HIV e AIDS, entre os adolescentes, no Estado do Espírito Santo, demonstra maior frequência de casos no sexo masculino, na faixa etária de 16 a 19 anos, com ensino médio incompleto, que adquiriram HIV por via sexual desprotegida, em relações homossexuais. Destaca-se a alta porcentagem de jovens com carga viral detectável e os óbitos em decorrência de complicações da AIDS.

Leptospirosis con enfermedad de Weil que debuta como abdomen agudo. Reporte de caso / Leptospirosis with Weil Syndrome debuting with acute abdomen, Case Report

La leptospirosis es una enfermedad de distribución mundial que se ubica dentro de las zoonosis, siendo un punto de partida importante el ambiente donde se desarrolla el paciente, pasa de ser una infección leve, hasta su presentación más complicada que es el síndrome de Weil (presentación diseminada), que al no detectarse a tiempo se relaciona con altas tasas de mortalidad. Su diagnóstico de probabilidad se establece por medio del criterio clínico (signos y síntomas de sospecha), más el nexo epidemiológico, el cual podrá corroborarse con los resultados de los estudios complementarios (marcadores inmunológicos), siendo indispensable para el tratamiento un soporte oportuno y la selección adecuada del esquema antibiótico. A continuación, se expone un caso de una mujer de 25 años con antecedente personal de infección por SARS-CoV-2 (RT-PCR positivo) cuatro meses antes de su ingreso, que presento leptospirosis que debutó con dolor abdominal simulando un abdomen agudo que motivó realización de laparoscopia exploratoria. La serología para leptospira fue positiva y el paciente recibió tratamiento antibiótico específico con evolución favorable.

Leptospirosis is a disease of worldwide that is considered within zoonoses. It is important to know the environment where the patient performs its activities. The clinical presentation goes from a mild infection to its more complicated presentation, the Weil´s Syndrome (disseminated affectation), which is related to high mortality rates if not detected in time. Its probability diagnosis is established based on clinical criteria (signs and symptoms of suspicion), plus the epidemiological link, which can be corroborated with the results of complementary studies (immunological markers). This is essential for the adequate treatment and selection of the antibiotic scheme. The following is a case of a 25-years-old woman with a personal history of SARS-Co V-2 infection (RT-PCR positive) four months before admission, who presented Leptospirosis that debuted with abdominal pain simulating an acute abdomen that required exploratory laparoscopy. Serology for Leptospira was positive and the patient received specific antibiotic treatment with favorable evolution

Investigation of associations between apolipoprotein A5 and C3 gene polymorphisms with plasma triglyceride and lipid levels

SUMMARY OBJECTIVE: The aim of this study was to determine frequency and associations between APOA5 c.56C>G, −1131T>C, c.553G>T, and APOC3 −482C>T and SstI gene polymorphisms with hypertriglyceridemia. METHODS: Under a case-control study model, 135 hypertriglyceridemic and 178 normotriglyceridemic control participants were recruited. Polymerase chain reaction and restriction fragment length polymorphism methods were utilized for genotyping. Statistical calculations were performed by comparing allele and genotype frequencies between groups. Clinical characteristics were compared between groups and intra-group genotypes. RESULTS: APOC3 gene −482C>T and SstI polymorphic genotypes and allele frequencies were significantly higher in hypertriglyceridemic group (genotype frequencies, p=0.035, p=0.028, respectively). Regression analysis under unadjusted model confirmed that APOC3 −482C>T and SstI polymorphisms were significantly contributing to have hypertriglyceridemia (p=0.02, odds ratio [OR]=1.831 (95% confidence interval [CI] 1.095-3.060); p=0.04, OR=1.812 (1.031-3.183), respectively). APOA5 c.56C>G was in complete linkage disequilibrium with APOA5 c.553G>T polymorphism (D'=1). CONCLUSION: For the first time in a population sample from Turkey, among the five polymorphisms of APOA5 and APOC3 genes investigated, APOC3 −482C>T and SstI polymorphisms were associated with elevated serum TG levels, while APOA5 c.56C>G, −1131T>C, and c.553G>T polymorphisms were not.

Design and synthesis of peptide-drug conjugates and fluorescent probe based on α-conotoxin ArIBV11L,V16D / 药学学报

italic>α-Conotoxin ArIB[V11L,V16D] is currently the most optimal selective inhibitor of α7 nicotinic acetylcholine receptor (nAChR) known. In order to explore chemical modification methods and enrich its application in targeting nAChR, this study utilized the linker to covalently connect camptothecin and 7-amino-4-methylcoumarin to the [2,4] disulfide bond of ArIB[V11L,V16D]. Therefore, two peptide-drug conjugates (PDCs), ArIB[V11L,V16D]-5 and ArIB[V11L,V16D]-6, and one fluorescent-labeled peptide, ArIB[V11L,V16D]-7 were constructed. Cytotoxicity evaluation showed that the IC50 values against non-small cell lung cancer cell line A549 of the two PDCs were respectively 1.3 and 4.1 times of camptothecin, indicating slight reduction in activity at the cellular level which was related to the linker structure. Fluorescence spectrum scanning revealed that the excitation and emission wavelength of the fluorescent-labeled peptide were 340 nm and 403 nm respectively, and the fluorescence features of 7-amino-4-methylcoumarin as a marker were retained without fluorescence quenching. This modification strategy laid a solid foundation for the further application of α-conotoxin ArIB[V11L,V16D] in PDCs and fluorescent probes.

Guanxin V Relieves Ventricular Remodeling by Inhibiting Inflammation: Implication from Virtual Screening, Systematic Pharmacology, Molecular Docking, and Experimental Validation / 中国结合医学杂志

OBJECTIVE@#To reveal the anti-inflammatory mechanism of Guanxin V, which is prescribed for ventricular remodeling in clinical practice.@*METHODS@#Guanxin V-, ventricular remodeling-, and inflammation-related targets were obtained through an integrated strategy of virtual screening and systematic pharmacology, and then the shared targets were visualised with a Venn diagram. Guanxin V network and the protein-protein interaction network were drawn, and enrichment analysis was conducted. Finally, the main results obtained from the integrated strategy were validated by molecular docking and in vivo experiments.@*RESULTS@#A total of 251, 11,425, and 15,246 Guanxin V-, ventricular remodeling-, and inflammation-related targets were acquired, respectively. Then, 211 shared targets were considered to contribute to the mechanism of ventricular remodeling treated by Guanxin V. Guanxin network and the protein-protein interaction network were drawn, and enrichment analysis showed some cardiovascular-related biological processes and signaling pathways. Molecular docking revealed that the Guanxin V-derived compounds could align with key targets. Final in vivo experiments proved that Guanxin V reverses ventricular remodeling by inhibiting inflammation.@*CONCLUSION@#Guanxin V relieves ventricular remodeling by regulating inflammation, which provides new ideas for the anti-ventricular remodeling mechanism of Guanxin V.

A Rare Case of Lung Adenocarcinoma with EGFR L833V/H835L Co-mutation and Literature Review / 中国肺癌杂志

Epidermal growth factor receptor (EGFR) mutations are the most common driver genes in the development of non-small cell lung cancer (NSCLC), of which mutations in exons 18-21 are frequent, especially the loss of exon 19 and exon 21 L858R mutation are the most frequent. Other rare gene mutations are rare. Simultaneous occurrence of two or more rare EGFR mutations are extremely rare in lung cancer, and the incidence of EGFR L833V/H835L rare gene compound mutations is very low, and there is little clinical data and evidence of relevant treatment methods. Some EGFR-tyrosine kinase inhibitors (EGFR-TKIs) are effective in treating lung cancer patients with rare gene mutations. In this article, we reported a case of NSCLC patient with a rare gene compound mutation EGFR L833V/H835L, who responded to Afatinib in combination with Anilotinib treatment well after 5 months of treatment, and computed tomography (CT) showed shrinkage of lung lesions. Meanwhile, we also compiled previously reported NSCLC patients with EGFR L833V/H835L rare gene compound mutation and summarized the characteristics of this group of patients and the effect of applying different kinds of EGFR-TKIs treatment.
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Research Progress of BRAF Fusion in Non-small Cell Lung Cancer / 中国肺癌杂志

In advanced non-small cell lung cancer (NSCLC), V-Raf murine sarcoma viral oncogene homolog B1 (BRAF) mutation is highly malignant and has poor prognosis, and currently Dabrafenib in combination with Trametinib is approved for first-line treatment of patients with BRAF V600 mutation. In addition to mutations, BRAF fusion can also occur. With the development of gene detection, the detection of BRAF fusion is gradually increasing, but there is a lack of effective therapeutic strategies for BRAF fusion. In this paper, we review the clinical characteristics, mechanism of action, and clinical treatment of BRAF fusion to provide a basis for the treatment of BRAF fusion in NSCLC patients.
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Comparison of Diagnostic Performance Between PI-RADS v2.1 and PI-RADS v2 for Prostate Cancer: A Meta-analysis / 肿瘤防治研究

Objective To compare the diagnostic performance of PI-RADS v2.1 and PI-RADS v2 in the detection of clinically significant prostate cancer(csPCa) by Meta-analysis. Methods The major biomedical databases were searched (CNKI, CBM, Medline, and Embase) with the keywords "PIRADS v2.1" or "PI-RADS v2.1". The Quality Assessment of Diagnostic Accuracy Studies Tool v2 (QUADAS-2) was used to evaluate literature quality. Meta-analysis was performed using STATA17.0 and ReMan5.4 software. Forest plots were used to represent the sensitivity and specificity of PI-RADS v2.1 and PI-RADS v2 for each study. Sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, and diagnostic odds ratio were combined, and diagnostic performance was evaluated using asummary receiver operating characteristic curve (SROC). Subgroup analysis was performed on three covariables: tumor location, threshold, and the nationality of authors. Results A total of 12 studies were included, involving 3 158 patients and 3 243 lesions. Forall zones and the whole gland, PI-RADS v2.1 had a larger area under the SROC curve (AUC) for csPCa performance, compared with PI-RADS v2. Subgroup analysis: PI-RADS v2.1 also had a larger area under the SROC (AUC) to detect transitional zone csPCa. Different diagnostic thresholds: when a score of 4 was used for the threshold, PI-RADS v2.1 had the maximum area under SROC (AUC) for csPCa performance detection. Author nationality: Researches of PI-RADS v2.1 in Chinese authors had the largest area under the SROC (AUC) in detecting csPCa performance. Conclusion Compared with PI-RADS v2, the diagnostic performance of PI-RADS v2.1 in detecting csPCa is not obviously improved and overall specificity is still low.

Diagnostic value of thyroid imaging report and data system combined with BRAF V600E mutation detection for thyroid fine needle puncture cytological uncertain nodules / 肿瘤研究与临床

Objective:To investigate the diagnostic value of thyroid imaging report and data system (TIRADS) combined with BRAF V600E mutation detection in differentiating uncertain thyroid nodules by using fine needle aspiration cytology (FNAC), and to analyze the role of TIRADS classification in screening the nodules needed to be routinely detected for BRAF V600E mutation.Methods:The clinicopathological data of 337 thyroid nodules patients diagnosed with TIRADS classification, FNAC Bethesda classification, BRAF V600E mutation detection and postoperative histopathology from the Second Hospital of Hebei Medical University between January 2018 and August 2021 were retrospectively analyzed. The role of TIRADS classification, FNAC Bethesda classification and BRAF V600E mutation detection alone and the combined detection in the differentiation of benign and malignant thyroid nodules was also analyzed.Results:The postoperative histopathological result was regarded as the gold standard. The sensitivity of TIRADS classification, FNAC Bethesda classification and BRAF V600E mutation for thyroid cancer diagnosis was 76.0%, 88.1% and 80.4% respectively, and the corresponding specificity was 84.0%, 96.0% and 100.0%, respectively. Histologically, 37 (62.7%) of 59 nodules with FNAC uncertainty were malignant nodules after the surgery. The sensitivity and accuracy of BRAF V600E mutation detection in the diagnosis of FNAC uncertain nodules were 51.4% and 69.5%, respectively, while the sensitivity and accuracy of BRAF V600E mutation detection combined with TIRADS classification were 86.5% and 84.7%, respectively. The sensitivity and accuracy of BRAF V600E mutation detection combined with TIRADS classification were both improved ( P values were 0.002 and 0.049, respectively). The positive rate of BRAF V600E mutation in thyroid nodules increased step by step with the rise of risk degree in TIRADS classification, and the type 3 cases were lower than those in type 4a cases [14.3% (1/7) vs. 68.6% (24/35), P = 0.012], and there were no statistically significant differences among the adjacent groups above 4a (all P > 0.05). Conclusions:TIRADS combined with BRAF V600E mutation detection can improve the sensitivity and accuracy in the diagnosis of FNAC uncertain thyroid nodules. The BRAF V600E mutation rate of TIRADS 4a and above nodules is high, so routine detection is recommended.

Research progress of m 6A methylation modification in respiratory viruses replication and host immune response / 中华临床感染病杂志

N 6-methyladenosine (m 6A) modification is the most prevalent internal modification of eukaryotic mRNA and is dynamically regulated by a variety of m 6A modifying enzymes, including methylation transferases, demethylases and specific binding proteins. Respiratory viral infections have received much attention in recent years, and the process of virus replication and metabolism in host cells is regulated by m 6A. This article reviews the mechanism of m 6A-regulated enzymes, the roles of m 6A modifications in respiratory viruses replication and the host immune response to viruses, including adenovirus, influenza A virus, severe acute respiratory syndrome coronavirus 2, respiratory syncytial virus, and human metapneumovirus. It would provide a reference for exploring the regulatory role of viral episodic transcriptome modifications and antiviral targets or vaccine development.

A study on the suitability of HD-V2 film in ultra-high dose-rate electron beam dosimetry / 中华放射肿瘤学杂志

Objective:To evaluate the usability of Gafchromic HD-V2 film for dose dosimetry in the ultra-high dose-rate (UD) electron beam from a modified medical linac, and to investigate the response between the energy and dose-rate dependence to the film.Methods:The HD-V2 film was utilized to measure the average dose-rate of the UD electron beam. The measured result was compared with those by advanced Markus chamber and alanine pellets. And characteristics of the UD electron beam were also measured by HD-V2 film. Energy dependence of HD-V2 film at three beam energies (6 MV X-ray, 9 MeV and 16 MeV electron beam) was investigated by obtaining and comparing the calibration curves based on the clinical linear accelerator in the dose range of 10-300 Gy. The dose-rate dependence of HD-V2 film was also studied by varying the dose rate among 0.03 Gy/s, 0.06 Gy/s and 0.1 Gy/s, and range of 100-200 Gy/s.Results:The measured average maximum dose-rate of 9 MeV UD electron beam at source skin distance (SSD) 100 cm was approximately 121 Gy/s using HD-V2 film, consistent with the results by advanced Markus chamber and alanine pellets. The measured percentage depth dose (PDD) curve parameters of the UD electron beam were similar to the conventional 9 MeV beam. The off-axis dose distribution of the UD electron beam showed the highest central axis, and the dose was gradually decreased with the increase of off-axis distance. The energy dependence of HD-V2 film had no dependency of 6 MV and 9, 16 MeV while measuring the dose in the range from 20 to 300 Gy. The HD-V2 film had no significant dose-rate dependency at the dose rate of 0.03 Gy/s, 0.06 Gy/s and 0.1 Gy/s for the clinical linear accelerator. Likewise, there was also no dose-rate dependence in the range 100-200 Gy/s in the modified machine.Conclusion:HD-V2 film is suitable for measuring ultra-high dose rate electron beam, independent of energy and dose rate.

Preliminary study on the distribution of T cell receptor β chain in patients with Takayasu arteritis / 中华风湿病学杂志

Objective:To investigate the diversity of T cell receptor repertoire in patients with Takayasu arteritis and analyze the side chain gene expression and distribution pattern of V、J gene rearrangement of T cell receptors.Methods:The peripheral blood samples of 8 patients with Takayasu arteritis and 4 healthy controls were collected. After constructing the library, high-throughput sequencing was performed with Illumina hiseq X10 sequencer. Bioinformatics analysis was conducted to obtain the sequences and compared with the reference sequences. the frequency information of V/D/J genes, and extraction of CDR region sequenceswere compared. The diversity of the TCR repertoire was also evaluated, and the comparative analysis and cluster analysis between groups and within samples were carried out. The data were analyzed by R language statistical software. Comparisons between two groups were analyzed by Mann-Whitney U test. Results:There was no significant difference in D50 index and Shannon entropy of chain CDR3 between Takayasu arteritis group and healthy control group. There was no significant difference in high-frequency cloning between the two groups. However, a total of 21 gene rearrangement fragments were different between the two groups. The expression of 14 V/J gene rearrangement fragments such as TRBV15-TRBJ2-3 [0.31 (0.27, 0.70) ], TRBV26-TRBJ2-6[0.30 (0.23, 0.57) ], TRBV28-TRBJ1-4[179 (139, 412) ], TRBV28-TRBJ1-6[362 (253, 419) ] in the patient group was significantly higher than that in the control group ( Z score were 2.65, 2.08, 2.27, 2.27, 2.27, 2.08, 2.65, 2.08, 2.27, 2.27, 2.08, 2.08, 2.46 and 2.22 respectively, P<0.05). The expression of seven V/J gene rearrangement fragments such as TRBV10-1-TRBJ1-2 [7.49 (4.9, 12.1) ],TRBV29-1-TRBJ2-2[10.5 (4.0, 12.8) ], TRBV-4-2-TRBJ2-6 [3.31 (1.8, 5.8) ] in the patients with Takayasu arteritis group was significantly lower than that in the control group ( Z score were -2.08, -2.27, -2.08, -2.08, -2.27, -2.08 and -2.29, P<0.05). Conclusion:Although there is no significant decrease in the diversity of peripheral blood TCR repertoire in patients with Takayasu arteritis, there are differences in the expression of chain V and J genes of TCR genes, and there is unique V/J rearrangement clones.