Impact of Folic Acid on the Resistance of Non-small Cell Lung Cancer Cells to Osimertinib by Regulating Methylation of DUSP1 / 中国肺癌杂志

BACKGROUND@#Drug resistance is the main cause of high mortality of lung cancer. This study was conducted to investigate the effect of folic acid (FA) on the resistance of non-small cell lung cancer (NSCLC) cells to Osimertinib (OSM) by regulating the methylation of dual specificity phosphatase 1 (DUSP1).@*METHODS@#The OSM resistant NSCLC cell line PC9R was establishd by gradually escalation of OSM concentration in PC9 cells. PC9R cells were randomly grouped into Control group, OSM group (5 μmol/L OSM), FA group (600 nmol/L FA), methylation inhibitor decitabine (DAC) group (10 μmol/L DAC), FA+OSM group (600 nmol/L FA+5 μmol/L OSM), and FA+OSM+DAC group (600 nmol/L FA+5 μmol/L OSM+10 μmol/L DAC). CCK-8 method was applied to detect cell proliferation ability. Scratch test was applied to test the ability of cell migration. Transwell assay was applied to detect cell invasion ability. Flow cytometry was applied to measure and analyze the apoptosis rate of cells in each group. Real-time fluorescence quantitative polymerase chain reaction (RT-qPCR) method was applied to detect the expression level of DUSP1 mRNA in cells. Methylation specific PCR (MSP) was applied to detect the methylation status of the DUSP1 promoter region in each group. Western blot was applied to analyze the expression levels of DUSP1 protein and key proteins in the DUSP1 downstream mitogen-activated protein kinase (MAPK) signaling pathway in each group.@*RESULTS@#Compared with the Control group, the cell OD450 values (48 h, 72 h), scratch healing rate, number of cell invasions, and expression of DUSP1 in the OSM group were obviously decreased (P<0.05); the apoptosis rate, the methylation level of DUSP1, the expression of p38 MAPK protein, and the phosphorylation level of extracellular regulated protein kinases (ERK) were obviously increased (P<0.05); the cell OD450 values (48, 72 h), scratch healing rate, number of cell invasions, and expression of DUSP1 in the DAC group were obviously increased (P<0.05); the apoptosis rate, the expression of p38 MAPK protein, the phosphorylation level of ERK, and the methylation level of DUSP1 were obviously reduced (P<0.05). Compared with the OSM group, the cell OD450 values (48, 72 h), scratch healing rate, number of cell invasions, and expression of DUSP1 in the FA+OSM group were obviously decreased (P<0.05); the apoptosis rate, the methylation level of DUSP1, the expression of p38 MAPK protein, and the phosphorylation level of ERK were obviously increased (P<0.05). Compared with the FA+OSM group, the cell OD450 values (48, 72 h), scratch healing rate, number of cell invasions, and expression of DUSP1 in the FA+OSM+DAC group were obviously increased; the apoptosis rate, the methylation level of DUSP1, the expression of p38 MAPK protein, and the phosphorylation level of ERK were obviously reduced (P<0.05).@*CONCLUSIONS@#FA may inhibit DUSP1 expression by enhancing DUSP1 methylation, regulate downstream MAPK signal pathway, then promote apoptosis, inhibit cell invasion and metastasis, and ultimately reduce OSM resistance in NSCLC cells.

Development and verification of an ELISA method for detection of process-specific residual host protein in biological preparation / 中国生物制品学杂志

@#Objective To develop and verify a double-antibody sandwich ELISA method for the detection of process-specific E.coli residual protein in recombinant biological preparations.Methods Taking the production and purification process of glucagon-like peptide(GLP)expressed by E.coli as the specific process model,the same process was used to intercept the residual protein of empty E.coli(normal E.coli that does not express recombinant protein). One female New Zealand white rabbit and six female Kunming mice were immunized with the residual protein as the immunogen. Using the IgG antibody purified from rabbit immune serum as the coating antibody,mouse immune serum as the second sandwich antibody,and antimouse IgG-HRP as the enzyme-labeled secondary antibody,a double antibody sandwich ELISA method for process-specific residual protein of E.coli was established. The specificity,accuracy and precision of the method were verified,and the limit of detection(LOD)was determined. Simultaneously,the developed method and the commercial E.coli host protein residue detection kit were used to quantitatively determine the residual protein of purified GLP preparation.Results After a series of gradient dilution of process-specific residual protein with known concentration,the sensitivity of this ELISA method reached 338 pg/mL. No cross reaction occurred in the detection of CHO and yeast cell lysis protein by this method,the recoveries of samples with low,medium and high concentrations were all in the range of 80% — 120%,and the intra-assay and inter-assay CVs of the empty E.coli interception standard with low,medium and high concentrations were all less than15%. For the residual protein in GLP preparation,about 62% of the residual proteins were not detected by the commercial non-process-specific ELISA kit compared with the total amount of residual proteins detected by the developed method,and these residual proteins should be the process-specific residual proteins.Conclusion The double antibody sandwich ELISA method developed in this study has high sensitivity,strong specificity,good accuracy and precision for the detection of process-specific E.coli residual protein,which can meet the detection requirements that the residual protein is less than0. 01% — 0. 1% in biological preparations.

Rendimiento diagnóstico de once indicadores para resistencia a la insulina en una muestra de pobladores peruanos

Introducción: La resistencia a la insulina (RI) es una de las principales causas del desarrollo de patologías crónicas. Es indispensable su detección temprana, por ello es importante estudiar métodos más asequibles y menos costosos como los biomarcadores. Objetivo: Determinar la precisión diagnóstica de once biomarcadores para RI en una muestra de pobladores peruanos. Metodología: Estudio de pruebas diagnósticas. Análisis de base de datos secundario del estudio PERU MIGRANT. Para medir RI se utilizó como referencia la evaluación del modelo homeostático (HOMA-IR) ≥ 2,8. Los biomarcadores se basaron en la ratio de lípidos, los indicadores de lípido visceral, los indicadores con triglicéridos y glucosa (TyG), y los indicadores con cintura abdominal. Para la precisión se utilizó el análisis de la curva de características operativas del receptor y el área bajo la curva (AUC) con sus respectivos intervalos de confianza al 95% (IC95%). Resultados: Se estudió a 938 participantes. La prevalencia de RI fue del 9,91%. En relación con el análisis ROC, el índice TyG - índice de masa corporal (TyG - IMC) tuvo el mayor AUC, tanto en hombres: AUC=0,85 (0,81 - 0,90), corte=241,55; sens=92,5 (79,6 - 98,4) y esp=78,3 (73,9 - 82,2); como en mujeres: AUC=0,81 (0,76 - 0,85), corte=258,77; sens=79,2 (70,3 - 86,5) y esp= 82,1 (78,0 - 85,8). Discusión: Según los datos analizados, el índice TyG-IMC es el mejor indicador para medir RI. Es un índice simple que se puede tomar de manera rutinaria en la práctica clínica diaria. Es conveniente añadir futuros estudios prospectivos que confirmen su capacidad predictiva.

Introduction: Insulin resistance (IR) is one of the main causes of chronic disease. Early detection is essential, which is why it is important to study more affordable and less expensive methods, such as biomarkers. Objective: To determine the diagnostic accuracy of 11 biomarkers of IR in a sample of Peruvian residents. Method: diagnostic tests. Secondary Database Analysis of the PERU-MIGRANT Study. To measure RI, a homeostatic model evaluation (HOMA-IR) ≥ 2.8 was used as a reference. Biomarkers were based on the lipid ratio, visceral lipid indicators, indicators of triglycerides and glucose (TyG), and indicators of abdominal waist. For precision, the receiver operating characteristic curve and area under the curve (AUC) with their respective 95% confidence intervals (95%CI) were used. Results: A total of 938 participants were studied. The prevalence of IR was 9.91%. In relation to the ROC analysis, the TyG index - body mass index (TyG - BMI) had the highest AUC, both in men: AUC=0.85 (0.81 - 0.90), cut-off=241.55; sens=92.5 (79.6 - 98.4) and sp=78.3 (73.9 - 82.2); as in women: AUC=0.81 (0.76 - 0.85), cut-off=258.77; sens=79.2 (70.3 - 86.5) and esp= 82.1 (78.0 - 85.8). Discussion: According to the data analyzed, the TyG-IMC index is the best indicator for measuring IR. It is a simple index that can be routinely used in clinical practice. Future prospective studies are needed to confirm its predictive capacity.

Instrumentos para la evaluación del riesgo de lesiones por presión en adultos en estado crítico: scoping review / Risk assessment instruments for pressure ulcer in adults in critical situation: a scoping review / Instrumentos para a avaliação do risco de lesões por pressão para adultos em situação crítica: scoping review*

Objetivo: mapear los instrumentos para la evaluación del riesgo de lesiones por presión en adultos en situación crítica en una unidad de terapia intensiva; identificar los indicadores de desempeño de los instrumentos y la apreciación de los usuarios con respecto al uso/limitaciones de los instrumentos. Método: scoping review. Para redactar el estudio se utilizó la extensión Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews. La investigación se realizó mediante la herramienta de búsqueda EBSCOhost en 8 bases de datos, resultando 1846 estudios, de los cuales 22 conforman la muestra. Resultados: se identificaron dos grandes grupos de instrumentos: los generalistas [Braden, Braden (ALB), Emina, Norton-MI, RAPS y Waterlow]; y los específicos (CALCULATE, Cubbin & Jackson, EVARUCI, RAPS-ICU, Song & Choi, Suriaidi y Sanada y el índice COMHON). En cuanto al valor predictivo, EVARUCI y CALCULATE mostraron los mejores resultados de indicadores de desempeño. En cuanto a las apreciaciones/limitaciones señaladas por los usuarios, destaca la escala CALCULATE, seguida de la EVARUCI y la RAPS-ICU, aunque aún necesitan ajustes futuros. Conclusión: el mapeo mostró que las evidencias son suficientes para indicar uno o más instrumentos para la evaluación del riesgo de lesiones por presión en adultos críticos en una unidad de cuidados intensivos.

Objective: to map the instruments for risk assessment of pressure ulcers in adults in critical situation in intensive care units; identify performance indicators of the instrument, and the appreciation of users regarding the instruments' use/limitations. Method: a scoping review. We used the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews in the writing of the study. We carried out the searches in the EBSCOhost search tool for 8 databases, resulting in 1846 studies, of which 22 studies compose the sample. Results: we identified two big instrument groups: generalist [Braden, Braden (ALB), Emina, Norton-MI, RAPS, and Waterlow]; and specific (CALCULATE, Cubbin & Jackson, EVARUCI, RAPS-ICU, Song & Choi, Suriaidi and Sanada, and COMHON index). Regarding the predictive value, EVARUCI and CALCULATE presented better results for performance indicators. Concerning appreciation/limitations indicated by users, we highlight the CALCULATE scale, followed by EVARUCI and RAPS-ICU, although they still need future adjustments. Conclusion: the mapping of the literature showed that the evidence is sufficient to indicate one or more instruments for the risk assessment of pressure ulcers for adults in critical situation in intensive care units.

Objetivo: mapear os instrumentos para avaliação do risco de lesões por pressão nos adultos em situação crítica em unidade de cuidados intensivos; identificar os indicadores de desempenho dos instrumentos e a apreciação dos utilizadores quanto ao uso/às limitações dos instrumentos. Método: scoping review. O Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews foi utilizado para a redação do estudo. A pesquisa foi realizada na ferramenta de busca EBSCOhost em oito bases de dados, resultando em 1846 estudos, dos quais 22 compõem a amostra. Resultados: identificaram-se dois grandes grupos de instrumentos: os genéricos [Braden, Braden (ALB), Emina, Norton-MI, RAPS e Waterlow]; e os específicos (CALCULATE, Cubbin & Jackson, EVARUCI, RAPS-ICU, Song & Choi, Suriaidi e Sanada e o índice de COMHON). Quanto ao valor preditivo, a EVARUCI e a CALCULATE apresentaram os melhores resultados de indicadores de desempenho. Em relação à apreciação/às limitações apontadas pelos utilizadores, destacam-se a escala CALCULATE, seguindo-se da EVARUCI e da RAPS-ICU, embora ainda necessitem de ajustes futuros. Conclusão: o mapeamento mostrou que as evidências são suficientes para indicar um ou mais instrumentos para avaliação do risco de lesões por pressão nos adultos em situação crítica em unidade de cuidados intensivos.

Escala predictiva de los resultados adversos en la hemorragia digestiva alta no varicosa / It not climbs predictiva of the adverse results in the high digestive hemorrhage varicose

Introducción: Existen varios sistemas de puntuación para predecir los resultados adversos en los pacientes con hemorragia digestiva alta no varicosa, pero no se han validado lo suficiente y cada uno pertenece a distintas poblaciones fuentes. Objetivo: Demostrar la utilidad de una escala propuesta para predecir las probabilidades de resangrado, de mortalidad y de necesidad de cirugía en los pacientes con hemorragia digestiva alta no varicosa. Métodos: Se realizó un estudio retrospectivo de una prueba diagnóstica en el hospital de Prenda, Luanda, Angola desde enero del 2021 hasta mayo del 2022. El universo estuvo formado por 93 pacientes atendidos durante ese período con el criterio de inclusión de tener el diagnóstico de hemorragia digestiva alta de origen no varicoso. Resultados: De un total de 93 pacientes se obtuvo como desenlace primario una recurrencia del sangrado de 18 pacientes para un 19,35 por ciento del total, seguido con 12 fallecidos para un 12,90 por ciento del total y cuatro fallecidos para un 4,40 por ciento del total. Los valores predictivos de la escala de forma general fueron, al ser aplicada una sensibilidad de 0,91, la especificidad de un 0,92, el valor predictivo negativo de un 0,95 y el valor predictivo negativo de un 0,86. Conclusiones: La escala propuesta tiene una sensibilidad y especificidad adecuada para predecir, en los pacientes con hemorragia digestiva alta no varicosa, la probabilidad de resangrado, de mortalidad y la necesidad de cirugía(AU)

Introduction: Several scoring systems exist to predict adverse outcomes in patients with nonvariceal upper gastrointestinal bleeding, but they have not been sufficiently validated and each pertains to different source populations. Objective: To demonstrate the usefulness of a proposed scoring scale to predict the probability of rebleeding, mortality, and need for surgery in patients with nonvariceal upper gastrointestinal bleeding. Methods: A retrospective study of a diagnostic test was performed at the hospital of Prenda, Luanda, Angola, from January 2021 to May 2022. The study universe consisted of 93 patients attended during that period, with the inclusion criterion of having a diagnosis of upper gastrointestinal bleeding of nonvariceal origin. Results: From a total of 93 patients, the primary outcome was a recurrence of bleeding in 18 patients, accounting for 19.35 percent of the total; followed by 12 deaths, representing 12.90 percent of the total, and four deaths, accounting for 4.40 percent of the total. After the scale was applied, the following general predictive values were obtained: sensitivity of 0.91, specificity of 0.92, negative predictive value of 0.95 and negative predictive value of 0.86. Conclusions: The proposed scale presents adequate sensitivity and specificity for predicting the probability of fatal rebleeding and the need for surgery in patients with nonvariceal upper gastrointestinal bleeding(AU)

Validation studies on migraine diagnostic tools for use in nonclinical settings: a systematic review / Estudos de validação de ferramentas de diagnóstico de enxaqueca (migrânea) para uso em ambientes não clínicos: uma revisão sistemática

Abstract Background Migraine underdiagnosis and undertreatment are so widespread, that hence is essential to diagnose migraine sufferers in nonclinical settings. A systematic review of validation studies on migraine diagnostic tools applicable to nonclinical settings can help researchers and practitioners in tool selection decisions. Objective To systematically review and critically assess published validation studies on migraine diagnostic tools for use in nonclinical settings, as well as to describe their diagnostic performance. Methods A multidisciplinary workgroup followed transparent and systematic procedures to collaborate on this work. PubMed, Medline, and Web of Science were searched for studies up to January 17, 2022. The QUADAS-2 was employed to assess methodological quality, and the quality thresholds adopted by the Global Burden Disease study were used to tail signaling questions. Results From 7,214 articles identified, a total of 27 studies examining 19 tools were eligible for inclusion. There has been no high-quality evidence to support any tool for use of migraine diagnosis in nonclinical settings. The diagnostic accuracy of the ID-migraine, structured headache and HARDSHIP questionnaires have been supported by moderate-quality evidence, with sensitivity and specificity above 70%. Of them, the HARDSHIP questionnaire has been the most extensively validated. The remaining 16 tools have provided poor-quality evidence for migraine diagnosis in nonclinical populations. Conclusions Up till now, the HARDSHIP questionnaire is the optimal choice for diagnosing migraine in nonclinical settings, with satisfactory diagnostic accuracy supported by moderate methodological quality. This work reveals the crucial next step, which is further high-quality validation studies in diverse nonclinical population groups.

Resumo Antecedentes O sub-diagnóstico e o subtratamento da enxaqueca são tão difundidos que, portanto, é essencial para diagnosticar os portadores de enxaqueca em ambientes não-clínicos. Uma revisão sistemática dos estudos de validação das ferramentas de diagnóstico da enxaqueca aplicáveis a ambientes não-clínicos pode ajudar os pesquisadores e profissionais nas decisões de seleção de ferramentas. Objetivo Revisar sistematicamente e avaliar criticamente estudos de validação publicados sobre ferramentas de diagnóstico da enxaqueca para uso em ambientes não-clínicos, bem como descrever seu desempenho diagnóstico. Métodos Um grupo de trabalho multidisciplinar seguiu procedimentos transparentes e sistemáticos para colaborar neste trabalho. PubMed, Medline e Web of Science foram pesquisados por estudos até 17 de janeiro de 2022. O QUADAS-2 foi empregado para avaliar a qualidade metodológica, e os limites de qualidade adotados pelo estudo da Global Burden Disease foram usados para responder a questões de sinalização. Resultados De 7.214 artigos identificados, um total de 27 estudos examinando 19 ferramentas foram elegíveis para inclusão. Não houve evidência de alta qualidade para apoiar qualquer ferramenta para o uso de diagnóstico de enxaqueca em ambientes não clínicos. A precisão diagnóstica do ID-Migraine, questionário de dor de cabeça estruturada e questionário HARDSHIP foram apoiados por evidências de qualidade moderada, com sensibilidade e especificidade acima de 70%. Deles, o questionário HARDSHIP foi o mais amplamente validado. As 16 ferramentas restantes forneceram provas de má qualidade para o diagnóstico de enxaqueca em populações não-clínicas. Conclusões Até agora, o questionário HARDSHIP é a escolha ideal para o diagnóstico da enxaqueca em ambientes não-clínicos, com precisão diagnóstica satisfatória apoiada por uma qualidade metodológica moderada. Este trabalho revela o próximo passo crucial, que é a realização de mais estudos de validação de alta qualidade em diversos grupos populacionais não-clínicos.

Phenotypic and molecular characterization of Staphylococcus aureus isolates conducted in nares of psoriatic patients attending a public hospital in Argentina / Caracterización fenotípica y molecular de aislamientos de Staphylococcus aureus portados en narinas de pacientes con psoriasis que concurren a un hospital público en Argentina

Abstract Although Staphylococcus aureus increases its relative abundance in psoriasis when compared with the microbiome of healthy subjects, it is not the most important microorganism underlying this disease. However, there is scant data on the role and molecular features of S. aureus strains in psoriasis; therefore, the aim of this study was to evaluate nasal carriage of this microorganism, its phenotypic and molecular characteristics as well as the impact of host factors on its carriage in psoriatic patients. The presence of S. aureus was analyzed in nasal swabs from 46 healthy volunteers and 50 psoriatic patients by conventional microbiology techniques. Nasal carriage of S. aureus was higher in psoriatic patients than in the control group (37.24% vs 22.98%, respectively), being associated to sex (male), age (adults) and severity of the disease (more frequent in moderate and severe cases). Determination of antibiotic resistance detected 12% of (-lactam resistant isolates, with variable accompanying resistance to macrolides, aminoglycosides and fluoroquinolones. No resistance to rifampicin, vancomycin, mupirocin or trimethoprim/sulfamethoxazole was found. A preliminary molecular characterization of the isolates was performed by PCR amplification of virulence genes. Molecular characterization of the strains did not reveal a predominant strain in psoriatic patients. Although we established host factors related to increased carriage of S. aureus in psoriatic patients, we could not establish the predominance of one type of strain. Genomic and transcriptomic analysis of the isolated strains would be necessary to address this point.

Resumen A pesar de que Staphylococcus aureus incrementa su abundancia relativa en la psoriasis cuando se compara con el microbioma de personas sanas, no es el microorganismo más importante subyacente a la enfermedad. Sin embargo, existen pocos datos sobre el papel y las características moleculares de las cepas de S. aureus en pacientes con psoriasis. Nuestro objetivo fue evaluar la portación nasal de este microorganismo, sus características fenotípicas y moleculares, y el impacto de factores del hospedador sobre dicha portación en estos pacientes. Se analizó la presencia de S. aureus en hisopados nasales de 46 voluntarios sanos y 50 pacientes con psoriasis mediante técnicas microbiológicas convencionales. Se encontró mayor portación en pacientes con psoriasis que en el grupo control (37,24% vs. 22,98%, respectivamente) y esta estuvo asociada al sexo (masculino), la edad (adultos) y la gravedad de la enfermedad (más frecuente en casos moderados a graves). El 12% de los aislamientos de S. aureus mostraron resistencia a betalactámicos, con resistencia acompañante a macrólidos, aminoglucósidos y fluoroquinolonas en grado variable. No se encontró resistencia a rifampicina, vancomicina, mupirocina o trimetroprima/sulfametoxazol. Se realizó una caracterización molecular preliminar de los aislamientos por amplificación de genes de virulencia mediante PCR. Si bien se identificaron factores relacionados con el hospedador que incrementan la portación nasal de S. aureus en pacientes con psoriasis, la caracterización molecular de las cepas no reveló ninguna característica genotípica predominante asociada a esta afección. Se necesitan más estudios genómicos y transcriptómicos para profundizar en esta caracterización.

Precisión diagnóstica de una versión abreviada de las pruebas de patrones de frecuencia y patrones de duración para la evaluación del ordenamiento auditivo temporal / Diagnostic accuracy of an abbreviated version of the frequency pattern and duration pattern tests for the evaluation of auditory temporal ordering

Introducción: Las pruebas de patrones de frecuencia y patrones de duración son consideradas los gold standard de evaluación del ordenamiento auditivo temporal. A pesar de su amplia difusión, la extensión y duración de estas pruebas dificultan su utilización dentro de baterías de evaluación del procesamiento auditivo. Sin embargo, dadas sus características estructurales, pareciera ser posible reducirlas sin perder su precisión diagnóstica. Objetivo: Determinar las propiedades diagnósticas de versiones abreviadas de las pruebas de patrones de frecuencia y patrones de duración. Material y Método: Se realizó un estudio transversal de diseño observacional analítico. Se evaluaron 166 oídos de 88 sujetos con edades entre 18 y 33 años, los cuales fueron clasificados con normalidad o alteración del ordenamiento auditivo temporal. Se utilizaron las pruebas originales de Auditec de 30 ítems por oído como referencia y los primeros 10 ítems de cada oído como versión abreviada. Resultados: La versión abreviada de la prueba de patrones de frecuencia obtuvo una sensibilidad de un 94,33%, una especificidad del 94,29% y un área bajo la curva ROC de 0,980. La versión abreviada de la prueba de patrones de duración obtuvo una sensibilidad de un 89,58%, especificidad del 71,88% y un área bajo la curva ROC de 0,916. Ambas versiones tuvieron un índice de concordancia adecuado. Conclusiones: Las versiones abreviadas de la prueba de patrones de frecuencia y patrones de duración cuentan con excelentes propiedades diagnósticas para la evaluación del ordenamiento auditivo temporal y pueden ser utilizadas de manera intercambiable con las versiones originales.

Introduction: The frequency and duration pattern tests are considered the gold standard for assessing auditory temporal ordering. Despite their wide dissemination, the length and duration of these tests make it difficult to use them within auditory processing assessment batteries. However, given their structural characteristics, reducing them without losing their diagnostic accuracy seems possible. Aim: Determine the diagnostic properties of abbreviated versions of the Frequency Patterns and Duration Patterns tests. Material and Method: A cross-sectional study with an analytical observational design was carried out. 166 ears of 88 subjects aged between 18 and 33 years were evaluated, classified as normal or altered in temporal auditory order. The original Auditec tests of 30 items per ear were used as a reference, and the first 10 items of each ear as an abbreviated version. Results: The abbreviated version of the frequency patterns test obtained a sensitivity of 94.33%, a specificity of 94.29%, and an area under the ROC curve of 0.980. The abbreviated version of the duration pattern test obtained a sensitivity of 89.58%, a specificity of 71.88%, and an area under the ROC curve of 0.916. Both versions had an adequate concordance index. Conclusion: The abbreviated versions of the frequency patterns and duration patterns test have excellent diagnostic properties for assessing auditory temporal ordering and can be used interchangeably with the original versions.

Predictive Values of Systemic Immune-Inflammation Index in New-Onset Atrial Fibrillation Following Coronary Artery Bypass Grafting

ABSTRACT Introduction: We investigated the relationship between the newly-defined systemic immune-inflammation index and the new-onset atrial fibrillation in patients undergoing coronary artery bypass grafting. Method: This study included 392 patients who underwent coronary artery bypass grafting. We divided the participants into two groups as those with and without new-onset atrial fibrillation. Prior to coronary artery bypass grafting, we evaluated blood samples, including systemic immune-inflammation index, and other laboratory parameters of the patients. We formulized the systemic immune-inflammation index score as platelet × neutrophil/lymphocyte counts. Results: The findings revealed that new-onset atrial fibrillation occurred in 80 (20.4%) of 392 patients during follow-ups. Such patients had higher systemic immune-inflammation index, neutrophil/lymphocyte ratio, and C-reactive protein levels than those who did not develop new-onset atrial fibrillation (P<0.001, P<0.001, P=0.010, respectively). In receiver operating characteristic curve analysis, systemic immune-inflammation index levels > 712.8 predicted new-onset atrial fibrillation with a sensitivity of 85% and a specificity of 61.2% (area under the curve: 0.781, 95% confidence interval: 0.727-0.835; P<0.001). Conclusion: Overall, systemic immune-inflammation index, a novel inflammatory marker, may be used as a decisive marker to predict the development of atrial fibrillation following coronary artery bypass grafting.

Diagnosis of fibromyalgia: diagnostic feasibility and accuracy of thermography

INTRODUCTION: Studies have suggested using thermography as a resource to diagnose fibromyalgia, although there has been no evidence confirming this hypothesis so far. OBJECTIVE: To evaluate the sensitivity and specificity of computerized infrared thermography as an auxiliary method for diagnosing fibromyalgia. METHODS: It is a diagnostic accuracy studywith cross-sectional design. One hundred and three individuals were evaluated for global pain using the Visual Analogue Scale. The measurement of pain at tender points was assessed by algometry, and skin temperature was assessed by thermography. To evaluate sensitivity and specificity, the analysis was performed using the Receiver Operating Characteristic Curve, measured by the area under the curve with their respective confidence intervals. RESULTS: Thermography has not been very sensitive or specific for pain (tender points) and diagnosis of fibromyalgia, according to the evaluation of the Receiver Operating Characteristic Curve, with an area under the curve equal to or lower than 0.75. CONCLUSION: In this study the thermography was not sensitive and specific as a tool for diagnosing the fibromyalgia syndrome. This study highlights important clinical implications concerning the current methods for diagnosing it, which, despite all efforts, are still subjective and poorly reproducible.

Bacterial vaginosis and trichomoniasis: prevalence, associated factors, and performance of diagnostic tests

Introduction: Bacterial vaginosis and vaginal trichomoniasis are frequent causes of health care demand. Objective: To estimate the prevalence, identify associated factors, and investigate the performance of diagnostic tests for bacterial vaginosis and trichomoniasis. Methods: Cross-sectional study with participants over 18 years old. All of them were submitted to an interview and gynecological examination with evaluation of vaginal secretion, pH verification, collection of material for Pap smear, wet mount test, Whiff test, bacterioscopy, and polymerase chain reaction for trichomoniasis detection. Logistic regression analysis was applied to identify associated factors with bacterial vaginosis. Diagnostic performance for bacterial vaginosis was evaluated following Amsel criteria, the Ison and Hay score, and the Pap smear, considering the Nugent score as the gold standard. As for trichomoniasis, diagnostic performance was evaluated through the Pap smear and the wet mount test, using the polymerase chain reaction as the gold standard. Results: The prevalence of bacterial vaginosis was 33.7%, and for trichomoniasis, 0.5%. The complaint of abnormal vaginal secretion was associated with the diagnosis of bacterial vaginosis (odds ratio 2.2). The diagnostic accuracy by Amsel criteria, the Ison and Hay score, and the Pap smear was 35.6, 97.0, and 84.2%, respectively. The sensitivity for trichomoniasis through wet mount test was 0.0%, and through the Pap smear, 100%. Conclusion: The prevalence of bacterial vaginosis was high, and trichomoniasis was low. The only associated factor with bacterial vaginosis was the report of abnormal vaginal secretion. The methods with the most accurate diagnostic performance for bacterial vaginosis were the Ison and Hay score and the Pap smear and, for trichomoniasis, the Pap smear

Evaluation of AIIMS Modified INCLEN Tool for Diagnosis of Epilepsy

Objectives: To evaluate the AIIMS Modified INCLEN tool for the diagnosis of epilepsy. Methods: This cross-sectional study enrolled 250 children aged 1 month to 18 years presenting with complaints of abnormal body movements to either the pediatric or neurology outpatient departments in our institution between October 1, 2018 and June 30, 2020. The All India Institute of Medical Sciences (AIIMS) modified International Clinical Epidemiology Network (INCLEN) diagnostic tool for epilepsy (AIIMS modified INDT-EPI) was administered and a diagnosis was made, which was further verified by a pediatrician or a neurologist. Specificity, sensitivity, positive predictive value (PPV) and negative predictive value (NPV) were calculated. Results: The study tool had a sensitivity of 87.6% and specificity of 84.0%. The PPV and NPV of the study tool were 86.8% and 84.9%, respectively. Conclusion: The study tool has good psychometric properties for physician assessment with regard to diagnosis of epilepsy.

Comparison of frailty assessment and related tools in elderly hospitalized patients with atrial fibrillation / 中华老年医学杂志

Objective:We evaluated frailty in elderly hospitalized patients with atrial fibrillation and analyzed the relevance, consistency, and diagnostic power of different frailty tools.Methods:From September 2018 to April 2019, a total of 197 elderly patients with atrial fibrillation aged ≥ 65 years in Beijing Hospital, Chinese PLA General Hospital, and Beijing Tsinghua Changgung Hospital were prospectively enrolled.Five frailty tools, including the clinical frailty scale(CFS), FRAIL scale(FRAIL), Fried frailty phenotype(Fried), Edmonton frail scale(EFS), and comprehensive geriatric assessment-frailty index(CGA-FI), were used for frailty assessment.Results:A total of 197 hospitalized elderly patients with atrial fibrillation were enrolled, with an average age of(77.5±7.1)years old(57.4% male). The prevalence of frailty, according to the five frailty tools, were 25.4%(FRAIL), 27.9%(EFS), 34.5%(Fried), 40.6%(CFS), and 42.6%(CGA-FI), respectively.CFS had a good correlation(correlation coefficient 0.80)and and consistency(Kappa value 0.71, 95% CI 0.61~0.81)with CGA-FI.The combined frailty index was used as the gold standard for frailty diagnosis.The results showed that CFS and CGA-FI had high diagnostic sensitivity(95.9 % and 98.0 %, respectively)and specificity(77.7 % and 75.7 %, respectively). Conclusions:Frailty is common in elderly hospitalized patients with atrial fibrillation, showing multidimensional features, and physical weakness is not prominet.CFS and CGA-FI are recommended for the assessment of frailty in patients with atrial fibrillation, which had good correlation and consistency.

Clinical analysis of sIgG antibody in children with food intolerance in Qingdao / 中华健康管理学杂志

Objective:To analyze food intolerance status in children in Qingdao by detecting the serum levels of food-specific IgG (sIgG).Methods:In this cross-sectional study, a total of 4 249 children aged 0 to 14 years (all were permanent residents of Qingdao City) admitted to Women and Children′s Hospital Affiliated to Qingdao University from May 2017 to December 2020 for suspected food intolerance were selected as the study objects with the whole sampling method. According to the age, the objects were divided into 4 groups: 0-<1 year group (440 cases), 1-<3 years group (1 761 cases), 3-<6 years group (1 193 cases), and ≥6 years group (855 cases). Positive condition of serum sIgG antibodies of 14 kinds of food in the children were detected by enzyme-linked immunosorbent assay. Chi-square test was used to compare the positive rate of the antibodies among different foods, gender and age groups.Results:The total positive rate of food sIgG antibody in 4 249 children was 95.32% (4 050/4 249), the highest positive rate was found in eggs (81.50%) and the lowest positive rate was found in pork (1.15%). The positive rates of sIgG antibody in milk (54.98% vs 49.69%, χ2=11.627), crab (5.59% vs 3.71%, χ2=8.049) and shrimp (4.62% vs 2.75%, χ2=9.784) in boys were significantly higher than those in girls, and the positive rates of sIgG antibody in tomato (49.19% vs 45.54%, χ2=5.510), cod (8.53% vs 5.96%, χ2=10.512) and beef (2.58% vs 1.70%, χ2=3.959) in girls were significantly higher than those in boys (all P<0.05). The total positive rate of sIgG antibody in 14 foods was the lowest in 0-<1 year group (89.09%), and it was the highest in 3-<6 years group (96.98%) ( χ2=63.950, P<0.001). The highest positive rate in 0-<1 year group was found in tomato (56.36%), and it was eggs (85.29%, 88.94%, 85.50%) in all the other 3 groups. The positive rates of corn and beef decreased with age ( χ2=44.098, 20.106, P<0.001), while those of cod and mushroom increased with age ( χ2=32.315, 40.338, P<0.001). The positive rate of wheat (57.13%, χ2=42.273), tomato (57.01%, χ2=209.862), soybean (24.99%, χ2=92.580), crab (6.81%, χ2=33.201), shrimp (6.25%, χ2=47.863) were all the highest in 1-<3 years group among the 4 groups (all P<0.001), and the positive rate of chicken was the highest in 3-<6 years group (7.88%, χ2=29.875; P<0.001). Conclusions:Children in Qingdao have a high level of food intolerance, and the highest positive rate is for eggs. Milk, crab and shrimp should be focused on for boys, while tomatoes, cod and beef shoud be paid more attention to for girls. Children of different ages have different kinds of food intolerance, and their diets should be adjusted reasonably according to the characteristics.

The role of a simple Nomogram model in evaluating the severity of mycoplasma pneumonia pneumonia in adults / 中国基层医药

Objective:To investigate the role of a simple Nomogram model in evaluating the severity of mycoplasma pneumoniae pneumonia (MPP) in adults.Methods:The clinical data of 162 patients with MPP who received treatment in Wenzhou Central Hospital from March 2015 to October 2022 were retrospectively analyzed. These patients were divided into a severe group ( n = 67) and a common group ( n = 95) according to whether they were diagnosed with severe MPP. The clinical data of patients were recorded. Fourteen clinical variables were screened, including age, sex, onset season, fever, heat peak, fever duration, cough duration, white blood cell count, percentage of neutrophils, percentage of lymphocytes, hemoglobin, platelet count, C-reactive protein, and procalcitonin. Multivariate logistic regression analysis of statistically significant variables in univariate analysis was performed. The Nomogram model was constructed with the R language software package (version 3.6.2). The model was verified with a calibration curve and receiver operating characteristic curve. Results:Univariate analysis results showed that in the severe group, the fever peak ( Z = 5.03, P < 0.001) was higher, fever duration ( χ2 = 27.55, P < 0.001), and cough duration ( χ2 = 28.72, P < 0.001) were longer, white cell count ( t = 2.93, P = 0.004), percentage of neutrophils ( t = 9.08, P < 0.001), C-reactive protein ( t = 35.05, P < 0.001), and procalcitonin level ( t = 15.09, P < 0.001) were greater compared with the common group. The percentage of lymphocytes ( t = 1.16, P < 0.001), hemoglobin level ( t = 1.22, P < 0.001), and platelet count ( t = 2.82, P < 0.001) in the severe group were significantly lower than those in the common group. Multivariate logistic regression analysis results showed that heat peak, cough duration, and C-reactive protein were positively correlated with the severity of MPP (all P < 0.05). The percentage of lymphocytes, hemoglobin concentration, and platelet count were negatively correlated with the severity of MPP (all P < 0.05). The establishment and validation results of the Nomogram model showed that the accuracy of the model was good, with a sensitivity of 88.73%, a specificity of 77.61%, and a C-index of 0.904. Conclusion:Heat peak, cough duration, percentage of lymphocytes, platelet count, and C-reactive protein are closely related to the severity of early MPP. A simple Nomogram model can be one of the tools for early assessment of the severity of MPP.

Qualitative and staging diagnosis of rectal tumors with dual contrast-enhanced ultrasonography and interventional biopsy / 中国基层医药

Objective:To investigate the clinical efficacy of qualitative and staging diagnosis of rectal tumors with dual contrast-enhanced ultrasonography and interventional biopsy.Methods:A total of 300 patients with rectal tumors who received treatment in The First People's Hospital of Huzhou from December 2019 to March 2022 were included in this study. All patients underwent dual contrast-enhanced ultrasonography and interventional biopsy followed by focus resection. Taking the postoperative histopathological test results as the gold standard, the efficacy of dual contrast-enhanced ultrasonography and interventional biopsy in the localization, qualitative analysis, and staging of rectal tumors was analyzed.Results:The compliance rate of dual contrast-enhanced ultrasonography and interventional biopsy in the localization of rectal tumors was 100%. The sensitivity, specificity, and accuracy of the dual contrast-enhanced ultrasonography and interventional biopsy for qualitative diagnosis of rectal tumors were 94.8%, 97.8%, and 96.7%, respectively. The Kappa value used for assessing agreement in the qualitative diagnosis of rectal tumors between dual contrast-enhanced ultrasonography and interventional biopsy and postoperative tissue pathological examination results was 0.947. The area under the curve plotted for qualitative diagnosis of rectal tumors was 0.974. The sensitivity, specificity, and sensitivity of dual contrast-enhanced ultrasonography and interventional biopsy for diagnosis of stage I-III rectal cancer were 94.1%-97.8%. The Kappa values used for assessing agreement in staging diagnosis of stage I-III rectal cancer between dual contrast-enhanced ultrasonography and interventional biopsy and postoperative tissue pathological examination results were 0.923, 0.912, and 0.927, respectively. The areas under the curve plotted for staging diagnosis of rectal cancer were 0.961, 0.955, and 0.970, respectively.Conclusion:Dual contrast-enhanced ultrasonography and interventional biopsy have a high efficacy in the localization, qualitative diagnosis, and staging diagnosis of rectal tumors.

Analysis on optimal cut-off values for prediction of lumbar spinal stenosis using lumbar pedicle thickness / 中国基层医药

Objective:To investigate the optimal cut-off values for the prediction of lumbar spinal stenosis using lumbar pedicle thickness.Methods:The clinical data of 64 patients with lumbar spinal stenosis (patient group) admitted to Binzhou Center Hospital from November 2019 to April 2021 and 48 healthy volunteers (healthy control group) who concurrently received routine physical examination involving lumbar spine MRI examination in the same hospital were retrospectively analyzed. Lumbar pedicle thickness was measured on T 2 weighted images of the L 5 vertebral body in the axial projection. Lumbar pedicle thickness was compared between groups using the independent sample t-test. The relationship between lumbar pedicle thickness and age change was analyzed using a one-way analysis of variance. The efficacy of lumbar pedicle thickness in the diagnosis of lumbar spinal stenosis was evaluated using the receiver operating characteristic (ROC) curve, optimal cut-off values, sensitivity, specificity, and the area under the ROC curve. Results:There was no significant correlation between lumbar pedicle thickness and age change ( P > 0.05). Lumbar pedicle thickness of patients with lumbar spinal stenosis was significantly higher than that of healthy controls [(13.25 ± 1.73) mm vs. (8.54 ± 1.88) mm, t = 13.75, P < 0.05]. ROC curve results showed that the optimal cut-off value was 10.50 mm, with a sensitivity of 95.3% and a specificity of 85.4. The area under the ROC curve was 0.963 (95% CI 0.928-0.998). Conclusion:The increase in lumbar pedicle thickness is related to the increase in the incidence of lumbar spinal stenosis. Lumbar pedicle thickness is an accurate, objective, and clear morphological parameter for the prediction of lumbar spinal stenosis. Application of lumbar pedicle thickness to predict lumbar spinal stenosis is innovative and scientific.

Value of serum IgG4 and IgG4/IgG ratio in differential diagnosis of autoimmune diseases / 中国基层医药

Objective:To investigate the value of immunoglobulin G4 (IgG4) and IgG4/ immunoglobulin G (IgG) ratio in the differential diagnosis of IgG4-related diseases (IgG4-RD) and other autoimmune diseases.Methods:A total of 35 patients with IgG4-RD and 937 patients with autoimmune diseases who received treatment in Beijing Hospital from January 2021 to July 2022, and 200 subjects who concurrently underwent health checkups in the same hospital were included in this study. The IMMAGE 800 and BN II automatic special protein analyzers were used to detect IgG and IgG4. The receiver operating characteristic (ROC) curve of IgG4 and IgG4/IgG ratio was plotted.Results:Serum IgG4 level and IgG4/IgG ratio in the IgG4-RD group were 2.83 (2.01, 5.07) g/L and 25% (18%, 43%) respectively, which were higher than 0.35 (0.16, 0.72) g/L, 3% (1%, 6%) in the autoimmune disease group and 0.27 (0.14, 0.49) g/L, 2% (1%, 4%) in the healthy control group ( U = 795.50, 82.50, 1 744.50, 205.50, all P < 0.001). Taking IgG4 ≥ 1.35 g/L as the standard, patients with IgG4 ≥ 1.35 g/L in the three groups were screened out. There was a statistically significant difference in IgG4/IgG ratio between the IgG4-RD group and the non-IgG4-RD group ( U = 453.50, P < 0.001). The ROC curve of IgG4 and IgG4/IgG ratio showed that when IgG4 was 1.47 g/L, the sensitivity was 91.7%, the specificity was 83.5%, and the area under the ROC curve was 0.96. When IgG4/IgG was 12.5%, the sensitivity was 91.4%, the specificity was 85%, and the area under the ROC curve was 0.96. Taking IgG4 ≥ 1.47 g/L and IgG4/IgG ≥ 12.5% as the diagnostic criteria of IgG4-RD, the sensitivity was 94.3%, the specificity was 85.9%, and the area under the ROC curve was 0.96, which were higher than the sensitivity (87.2%) and diagnostic specificity (82.6%) provided by IgG4 alone. Conclusion:Because non-IgG4-RD diseases can also have the phenomenon of increased IgG4, when IgG4 ≥ 1.47 g/L is taken as the diagnostic criteria, its diagnostic sensitivity and specificity are the highest. Combined detection of IgG4 and IgG4/IgG ratio can increase the diagnostic efficacy of IgG4-RD.

Research progress on linear ubiquitin chain assembly complex and OTU deubiquitinase with linear linkage specificity in tumor / 药学实践杂志

Linear ubiquitination is an important post-translational modification that has been discovered in recent years. The linear ubiquitin chain is formed by the linkage of glycine residue of one ubiquitin protein to the methionine residue of another ubiquitin. This process is regulated by the linear ubiquitin chain assembly complex (LUBAC) and the OTU deubiquitinase with linear linkage specificity (OTULIN). Linear ubiquitination is involved in various biological processes, including immune response, inflammation, and cell apoptosis. Recent studies have shown that linear ubiquitination is closely related to the occurrence, development, and drug resistance of tumors by affecting signaling pathways such as NF-κB and Wnt/β-catenin. The research progress on the function of LUBAC and OTULIN in tumors was reviewed in this paper.

Correlation of anti-phosphatidylserine/prothrombin antibodies with unexplained recurrent miscarriages / 北京大学学报(医学版)

OBJECTIVE@#To investigate whether anti-phosphatidylserine/prothrombin antibodies and its IgG or IgM subtypes were correlated with unexplained recurrent miscarriages.@*METHODS@#In our a single-center retrospective study, 283 patients with at least one unexplained miscarriage who visited the Third Hospital of Peking University between January 2021 and August 2023, aged between 18-40 years, and tested for anti-phosphatidylserine/prothrombin antibodies IgG or IgM subtypes, were included. The patients with either positive IgG or IgM anti-phosphatidylserine/prothrombin antibody were regarded as positive for anti-phosphatidylserine/prothrombin antibody. SPSS 26.0 software was used for statistical analysis. Chi-square test and Logistic regression analysis were used to study the correlation of anti-phosphatidylserine/prothrombin antibodies and its IgG or IgM subtypes with unexplained recurrent miscarriages. And the diagnostic sensitivity, specificity, the positive predictive value, the negative predictive value of anti-phosphatidylserine/prothrombin antibodies and its IgG or IgM subtypes in unexplained miscarriages was calculated with four-fold table.@*RESULTS@#Chi-square analysis showed that anti-phosphatidylserine/prothrombin antibodies and its IgM subtypes were correlated with recurrent miscarriages (both P < 0.05), while the IgG subtype was not correlated with recurrent miscarriages (P>0.05). After adjusting with anticardiolipin antibodies, anti-β2 glycoprotein antibodies, lupus anticoagulants, antinuclear antibodies, and age by Logistic regression analysis, anti-phosphatidylserine/prothrombin antibodies were correlated with unexplained recurrent miscarriages (OR=2.084, 95%CI 1.045-4.155, P < 0.05), and anti-phosphatidylserine/prothrombin antibody IgM subtypes were correlated with unexplained recurrent miscarriages (OR=2.368, 95%CI 1.187-4.722, P < 0.05).The sensitivity of anti-phosphatidylserine/prothrombin antibody in recurrent miscarriage was 65.43%, the specificity was 48.51%, the positive predictive value was 33.76%, and the negative predictive value was 77.78%. In the patients with recurrent miscarriages with negative classical antiphospholipid antibodies, the sensitivity of anti-phosphatidylserine/prothrombin antibody was 59.09%, the specificity was 63.23%, the positive predictive value was 40.63%, and the negative predictive value was 78.40%. The sensitivity of the anti-phosphatidylserine/prothrombin antibody IgM subtype for the diagnosis of recurrent miscarriage was 65.43%, the specificity was 50.99%, the positive predictive value was 34.87%, and the negative predictive value was 78.63%.@*CONCLUSION@#Anti-phosphatidylserine/prothrombin antibody and IgM subtype antibody are correlated with unexplained recurrent miscarriages in patients with at least one unexplained miscarriage. Whether positive anti-phosphatidylserine/prothrombin antibody or IgM subtype could predict future unexplained recurrent miscarriages warrants a prospective study.