Research progress on programmed death 1 and its ligand as markers of immune tolerance after liver transplantation / 中华肝胆外科杂志

Programmed death 1 (PD-1)/PD-1 ligand (PD-L1) are important signaling molecules that mediate immunosuppression. This signaling pathway leads to the evading of tumor cells from immune surveillance and plays an adverse affect on anti-tumor immunity. For grafts, the activation of PD-1/PD-L1 signaling pathway also plays an important role in the its evasion from host immune attack and the formation of immune tolerance. PD-1/PD-L1 has been shown to regulate immune tolerance in corneal, heart and lung transplantation. Its role in liver transplantation, however, has yet to be elaborated. This article reviews the potential of PD-1/PD-L1 as a marker of immune tolerance after liver transplantation.

Gastric cancer risk assessment based on serum pepsinogen / Монголын Анагаах Ухаан

Introduction@#Cases of gastric cancer have been declining worldwide in recent years. However, gastric cancer incidence increased in the last decade in Mongolia. In Mongolia, over 80% of gastric cancer cases are diagnosed during the late stage. Several studies have revealed that serum pepsinogens (PGs) level reflects, indirectly, histological and functional characteristics of the gastric mucosa.@*Goal@#We aimed to evaluate the risk of gastric cancer and its precancerous condition based on serum PGI, PGI/II biomarkers.@*Materials and Methods@#This case-control study enrolled 114 subjects, including patients with gastric cancer (n=36), atrophic gastritis (n=40) and healthy controls (n=138). The questionnaires were obtained to determine risk factors. Serum PGI, PGII, and H. pylori IgG levels were measured by ELISA (Pepsinogen I ELISA; Pepsinogen II ELISA; H.Pylori IgG ELISA; BIOHIT Plc, Helsinki, Finland). PGI to PGII ratio was calculated. Patients were classified into the ABC(D) group according to Miki K approach. Also, we developed new scoring system based on some risk factors and serum PGI, PGI/II ratio. Logistic regressions were performed to evaluate risk and expressed by odds ratio (OR) and 95% confidence intervals (95%CI).@*Results@#Mean age of the subjects was 60±10.9 years. H.Pylori was positive in 67 subjects. The serum PGI and PGI/II ratio levels were significantly decreased in gastric cancer and atrophic gastritis groups compared to the healthy control. According to classification ABC(D), group D (OR 5.04, 95% CI 1.13-22.50) had higher proportion of atrophic gastritis cases, group C (OR 6.19, 95% CI 1.04-36.78) had higher proportion of gastric cancer cases than others. Additionally, we created a risk prediction scoring system with a score ranging from 0 to 7, based on variables age, family history of gastric cancer, prior disease history, PGI and PGI/II ratio levels. For the atrophic gastritis patients, 17 (42.5%) were classified into medium-risk category (OR 4.49, 95% CI 1.38-14.58) and 17 (42.5%) were classified into high-risk category (OR 7.69, 95% CI 2.16-27.43). Whereas, 11 (30.6%) patients with gastric cancer were classified into medium-risk category (OR 4.35, 95% CI 1.13-16.85), 21 (58.3%) were classified into high-risk category (OR 14.25, 95% CI 3.60-56.43).@*Conclusion@#The methods based on serum PGI and PGI/II may identify a high risk population of gastric cancer and atrophic gastritis.

Research progress on the correlation between T cell subsets and prognosis of diffuse large B-cell lymphoma / 中国肿瘤临床

Diffuse large B-cell lymphoma(DLBCL)is the most common type of non-Hodgkin lymphoma,and is characterized by great hetero-geneity.The use of rituximab in treatment regimens has increased the patient survival rate,but some patients experience poor efficacy.It thus remains necessary to find new prognostic indicators to screen high-risk patients and provide targeted treatment.In recent years,many studies have confirmed correlations between T cell subsets and prognosis in DLBCL patients.This article will review the effects of different T cells on the prognosis in DLBCL patients.

Recent advance of procalcitonin in central nervous system diseases / 中华神经科杂志

Procalcitonin, as a biological marker of bacterial infection, has been widely used in clinical diagnosis of various infectious diseases. With the development of basic and clinical research, it has been found that procalcitonin not only plays a cascading and amplifying role in systemic inflammatory response, but also exerts an important effect on assessment, diagnosis, and prognosis in some central nervous system diseases. In this article, "procalcitonin" "bacterial meningitis""marker" and "central nervous system diseases" were used to search the relevant literatures published from 1993 to 2021 in the databases of Pubmed, Wanfang Medicine and China Knowledge Network. The roles of procalcitonin in central nervous system diseases were systemically reviewed for assisting the diagnosis and treatment of central nervous system diseases.

Mucina y Enfermedad Periodontal / Mucin and periodontal disease

La enfermedad periodontal (EP) es una patología que afecta principalmente los tejidos que rodean a la pieza dentaria (PD) y se caracteriza, en la mayoría de los casos, por una exposición bacteriana que favorece una respuesta destructiva e inflamatoria del huésped, que conduce a la pérdida de inserción periodontal de la PD, provocando una marcada reabsorción ósea y la posible pérdida de las PD. El diagnóstico de EP implica evaluaciones clínicas y radiográficas, en la actualidad se están realizando diversas investigaciones para evaluar posibles compuestos en los fluidos orales a través de lo cual puede ser posible evaluar la presencia y gravedad de estas enfermedades, como así también el riesgo en los pacientes. Hay evidencias de la interacción de macromoléculas salivales, como las mucinas, con microorganismos específicos. De esta manera las mucinas, junto con otros productos de la saliva, ayudan a modular tanto el número como el tipo de proliferación de ciertos organismos y provocar la disminución de otros. La revisión de la literatura actual concluye que las mucinas salivales pueden servir como un parámetro bioquímico de la inflamación del periodonto (AU)

Periodontal disease (PD) is a pathology that mainly affects the tissues surrounding the tooth (PD) and is characterized, in most cases, by a bacterial exposure that favors a destructive and inflammatory response of the host, which leads to the loss of periodontal insertion of the PD, causing a marked bone resorption and the possible loss of the PD. The diagnosis of PD involves clinical and radiographic evaluations, at present several investigations are being carried out to evaluate possible compounds in oral fluids through which it may be possible to evaluate the presence and severity of these diseases, as well as the risk in patients. There is evidence of the interaction of salivary macromolecules, such as mucins, with specific microorganisms. In this way, mucins, together with other saliva products, help modulate both the number and type of proliferation of certain organisms and cause the decrease of others. The review of the current literature concludes that salivary mucins can serve as a biochemical parameter of inflammation of the periodontium (AU)

Correlação entre marcadores bioquímicos e medida ultrassonográfica do comprimento do colo uterino na predição do trabalho de parto pré-termo / Correlation between biochemical markers and ultrasound measurement of cervical length in predicting preterm labor

Objetivo: Avaliar a medida ultrassonográfica do colo uterino e os níveis séricos maternos (colesterol total e frações, triglicérides e arginina dimetil assimétrica), isolados ou em associação, como preditores de parto pré-termo. Métodos: Trata-se de um estudo longitudinal, prospectivo, de correlação entre variáveis bioquímicas e medida ultrassonográfica do colo com a idade gestacional do parto (< ou ≥ 37 semanas). Entre 2015 e 2016, foram avaliadas 145 gestantes portadoras de fatores de risco para parto pré-termo, entre 20 e 24 semanas de gestação, através da medida ultrassonográfica do colo uterino e dos níveis séricos dos biomarcadores. Foram excluídas as gestantes com idade inferior a 18 anos, as que utilizaram progesterona como prevenção de um possível parto prétermo e os casos de prematuridade terapêutica. Este estudo foi aprovado pelo Comitê de Ética e Pesquisa da UFMG (CAAE: 51489715.6.0000.5149). Foi realizada análise de correlação entre os biomarcadores e a medida do colo pelo teste de correlação de Spearman. A curva ROC foi utilizada para determinar a acurácia das variáveis. Foram calculadas sensibilidade e especificidade para a variável que foi considerada preditiva para parto pré-termo, com diferentes pontos de corte. Toda a análise considerou o nível de significância de 0,05, e o software utilizado foi o SPSS versão 20.0. Resultados: Apenas a medida ultrassonográfica do colo apresentou significância estatística como um preditor de parto pré-termo (AUC curva de ROC 0,698 - IC 0,540; 0,856). Colesterol total, HDL, fração não HDL, triglicérides e ADMA apresentaram baixos valores de área sob a curva ROC. Conclusão: A medida ultrassonográfica do colo uterino menor que 2,5 cm entre 20 e 24 semanas de gestação associa-se com a ocorrência de parto pré-termo em gestantes de risco, com especificidade de 98%. Os biomarcadores analisados, isolados ou em associação com a medida do colo, não apresentaram correlação.

Objective: To evaluate the measurement of uterine cervix and maternal serum levels of total cholesterol and fractions, triglycerides and asymmetric arginine di-methyl (ADMA), isolated or in association, as predictors of preterm delivery. Methods: This longitudinal, prospective study of correlation among variables and gestational age at birth (=37 weeks) was previously approved by the local Ethics Committee (CAAE:51489715.6.0000.5149). Between 2015 to 2016, 145 pregnant women with risk factors for preterm labor, from 20 to 24 weeks' gestation, were evaluated through the ultrasound measurement of the cervix and serum levels of the biomarkers. Pregnant women younger than 18 years, those who used progesterone as prevention of a possible preterm delivery and cases of therapeutic prematurity were excluded. A correlation analysis was performed among the biomarkers and the cervix measurement by the Spearman correlation test. The ROC Curve was used to determine the accuracy of the variables. Sensitivity and specificity were calculated for the variable that was considered predictive for preterm delivery, with different cut-off points. Statistical analysis was carried employing the SPSS 20.0 and a value of P<0.05 was considered statistically significant. Results: Considering the significance level of 5%, the cervix length show an area under the ROC curve of 0.698 (CI 0.540;0.856). Total cholesterol, HDL, non-HDL, triglycerides and ADMA presented low values of the area under the ROC curve. No significant correlation between these biomarkers and the outcome evaluated (preterm labor) was observed. Conclusion: Only the uterine cervix below 2.5cm, measured by ultrasound, between 20-24 weeks gestation was associated with the occurrence of preterm birth in pregnant women at risk, with specificity of 98%.

miR-148b-3p, miR-190b, and miR-429 Regulate Cell Progression and Act as Potential Biomarkers for Breast Cancer / 한국유방암학회지

PURPOSE: Breast cancer is the most frequently diagnosed malignancy in women worldwide. MicroRNAs (miRNAs) are thought to serve as potential biomarkers in various cancers, including breast cancer. METHODS: We evaluated the miRNA expression profiles in 1,083 breast cancer samples and 104 normal breast tissues from The Cancer Genome Atlas database. We used the edgeR package of R software to analyze the differentially expressed miRNAs in normal and cancer tissues, and screened survival-related miRNAs by Kaplan-Meier analysis. A receiver operating characteristic curve was generated to evaluate the accuracy of these miRNAs as molecular markers for breast cancer diagnosis. Furthermore, the functional role of these miRNAs was verified using cell experiments. Targets of candidate miRNAs were predicted using 9 online databases, and Gene Ontology (GO) functional annotation and pathway analyses were conducted using Database for Annotation, Visualization and Integrated Discovery online tool. RESULTS: A total of 68 miRNAs showed significantly different expression patterns between the groups (p < 0.001), and 13 of these miRNAs were significantly associated with poor survival (p < 0.05). Three miRNAs with high specificity and sensitivity, namely, miR-148b-3p, miR-190b, and miR-429, were selected. In vitro experiments showed that the overexpression of these 3 miRNAs significantly promoted the proliferation and migration of MDA-MB-468 and T47D cells and reduced the apoptosis of T47D cells. GO and pathway enrichment analyses revealed that the targets of these dysregulated miRNAs were involved in many critical cancer-related biological processes and pathways. CONCLUSION: The miR-148b-3p, miR-190b, and miR-429 may serve as potential diagnostic and prognostic markers for breast cancer. This study demonstrated the roles of these 3 miRNAs in the initiation and progression of breast cancer.

Los movimientos oculares como medida de control ejecutivo en niños con trastorno por déficit de atención con hiperactividad / Eye movements as a measure of executive control in children with Attention Deficit Hyperactivity Disorder

El Trastorno por Déficit de Atención con Hiperactividad (TDAH) está relacionado con dificultades a nivel de control ejecutivo. Nuevas formas de explorar este constructo contribuyen a la precisión diagnóstica, disminuir la prevalencia y la construcción de un consenso objetivo sobre los criterios del TDAH. El objetivo fue establecer las diferencias en el control ejecutivo de un grupo de niños con TDAH (N=22), con respecto al grupo control (N=15), de ambos géneros y de entre 7 y 12 años de edad, escolarizados de la ciudad de Medellín, Colombia. Se implementaron tres parámetros oculares: fijaciones, antisacadas y prosacadas, los cuales fueron registrados continuamente en un equipo de rastreo visual (Tobii T120). Los resultados indicaron un menor tiempo para el grupo con TDAH en fijaciones oculares (p<,001) que miden control de la interferencia. Un mayor número de errores de dirección en el parámetro antisacadas relacionados con el control inhibitorio. Respecto a las prosacadas, que miden la capacidad para iniciar una respuesta motora, no se encontraron diferencias significativas. Se concluyó que la población con TDAH presenta alteración en el control ejecutivo al utilizar el paradigma de rastreo ocular. Se propusieron, además, los movimientos oculares como posible marcador biológico para detectar una población en riesgo de padecer dicho trastorno.

Attention Deficit Hyperactivity Disorder (ADHD) is related to difficulties at the level of the executive control. New ways of exploring this construct contribute to diagnostic accuracy, decrease the prevalence and build an objective consensus on ADHD criteria. The aim of the study was to establish the differences in the executive control of a group of children with ADHD (N=22), with respect to the control group (N=15), of both genders and between 7 and 12 years old, attending school in the city of Medellin, Colombia. Three ocular parameters were implemented: fixings, antisaccade, and prosaccades, which were recorded continuously in a visual tracking equipment (Tobii T120). The results indicated a shorter time for the group with ADHD in ocular fixations (p<0.001) that measure interference control. A greater number of address errors in the antisaccade parameter related to inhibitory control. Regarding the prosaccades, which measure the capacity to initiate a motor response, no significant differences were found. It was concluded that the population with ADHD presents alteration in the executive control when using the eye tracking paradigm. Eye movements were also proposed as a possible biological marker to detect a population at risk of suffering from this disorder.

Research progress on role of exosomes in acute kidney injury / 上海交通大学学报（医学版）

Exosomes are extracellular vesicles with plasma membrane. They are produced intracellularly and then secreted out of the cells. Almost all types of cells in human bodies can produce and excrete exosomes. Exosomes carry a variety of signal proteins, mRNA, miRNA, lncRNA and their degradation fragments. Due to the protection of lipid membrane, these components have biological activity and get involved in the process of cell migration, apoptosis and proliferation, and can modulate the function of the recipient cells. As an important cell-cell signal carrier, exosomes are involved in the development of many kidney diseases. This article reviewed the biological characteristics of exosomes and their roles in acute kidney injury.

Circular RNA and ischemia brain damage related to circular RNA / 国际儿科学杂志

Circular RNAs (circRNAs) are a class of highly stable,long non-coding RNAs (lncRNAs),which shows greater conserved across species and highly specific in different tissue and development stage.There are numerous circRNAs in the central nervous system,which are not only closely related to development,differentiation and biological function of neuronal cells,also play a crucial role in nerve lesions and dysfunction after brain injury.Specific circular RNA could contribute to the regulation of gene expression by acting as miRNA sponges,involving in the protection against apoptosis in neurons and regeneration after brain injury.A comprehensive understanding of the specific circular RNA function and its underlying mechanism in the brain can provide a new strategy for the prevention,diagnosis,and treatment of brain injury at gene level.

The MAKE Biomarker Discovery for Enhancing anTidepressant Treatment Effect and Response (MAKE BETTER) Study: Design and Methodology

OBJECTIVE: Depression is associated with a major disease burden, and many individuals suffer from depressive symptoms due to an insufficient response to ostensibly adequate antidepressant treatment. Therefore, it is important to identify reliable treatment response predictors for use in developing personalized treatment strategies. METHODS: The MAKE Biomarker discovery for Enhancing anTidepressant Treatment Effect and Response (MAKE BETTER) study was performed to identify predictors of antidepressant response using a 2-year naturalistic prospective design. Participants in the MAKE BETTER study were consecutively recruited from patients who visited the Psychiatry Department of Chonnam National University Hospital, Gwangju, South Korea for treatment of a depressive disorder. Data on demographic and clinical characteristics, genetic markers measured by whole-exome sequencing, and blood markers were obtained. The types and doses of antidepressants were determined based on the clinical judgment of the psychiatrist, and the treatment outcomes (e.g., depressive and other psychiatric symptoms and issues related to safety) were assessed. RESULTS: We will be able to use the data collected in this study to develop a treatment-response prediction index composed of biomarkers. CONCLUSION: The MAKE BETTER study will provide an empirical basis for a personalized medicine approach to depression by enabling the prediction of antidepressant treatment response according the characteristics of each patient. It will thereby support evidencebased decision-making that decreases the use of a trial-and-error approach to the treatment of depressive disorders.

Correlation analysis between the expression of 5-hydroxymethyl-cytosine and invasion, metastasis and prognosis of melanoma / 中华皮肤科杂志

Objective To detect the level of 5-hydroxymethyl-cytosine (5-hmc)in melanoma tissues,and to analyze the correlation between 5-hmc and the invasion,metastasis and prognosis of melanoma.Methods A streptavidin-peroxidase immunohistochemical method was used to detect the level of 5-hmc in 67 melanoma tissues and 20 pigmented nevi tissues.Univariate and multivariate analyses were performed with the Cox's proportional hazards regression model to analyze the correlation between the expression of 5-hmc and the prognosis of melanoma.Results The expression rate of 5-hmc was significantly lower in melanoma tissues than in pigmented nevus tissues (40.30％ [27/67] vs.75％ [15/20],22 =7.428,P =0.006).According to American Joint Committee on Cancer (AJCC) TNM staging system,the expression level of 5-hmc was significantly lower in the stage Ⅳ melanoma tissues than in the stage Ⅱ and stage Ⅲ melanoma tissues (x2 =4.416,P =0.036).Patients with lymph node metastasis showed significantly lower expression of 5-hmc compared with those without lymph node metastasis (x2 =5.902,P =0.015),and the level of 5-hmc expression significantly decreased along with the increase of Clark grade (x2 =4.828,P =0.028).There were no significant differences in the level of 5-hmc expression between patients of different ages,genders or nationalities (P ＞ 0.05).Multivariate Cox regression analysis showed that distant lymph node metastasis (HR:2.67,95％ CI:1.22-5.84),not receiving surgical resection (HR:0.41,95％ CI:0.18-0.95),and low expression of 5-hmc (HR:3.54,95％ CI:1.09-11.43)were independent risk factors for poor prognosis of melanoma.Conclusion 5-Hmc may participate in the invasion and metastasis of melanoma,and be associated with the prognosis of melanoma.

Plasma CRABP2 as a Novel Biomarker in Patients with Non-Small Cell Lung Cancer

BACKGROUND: Lung cancer is the most common cause of cancer-related mortality worldwide. We previously reported the identification of a new genetic marker, cellular retinoic acid binding protein 2 (CRABP2), in lung cancer tissues. The aim of this study was to assess plasma levels of CRABP2 from patients with non-small cell lung cancer (NSCLC). METHODS: Blood samples that were collected from 122 patients with NSCLC between September 2009 and September 2013 were selected for the analysis, along with samples from age- (± 5 years), sex-, and cigarette smoking history (± 10 pack-years [PY])-matched controls from the Korea Biobank Network. The control specimens were from patients who were without malignancies or pulmonary diseases. We measured plasma levels of CRABP2 using commercially available enzyme-linked immunosorbent assay kits. RESULTS: The mean age of the NSCLC patients was 71.8 ± 8.9 years, and the median cigarette smoking history was 32 PY (range, 0–150 PY). Plasma CRABP2 levels were significantly higher in patients with NSCLC than in the matched controls (37.63 ± 28.71 ng/mL vs. 24.09 ± 21.09 ng/mL, P < 0.001). Higher plasma CRABP2 levels were also correlated with lower survival rates in NSCLC patients (P = 0.014). CONCLUSION: Plasma CRABP2 levels might be a novel diagnostic and prognostic marker in NSCLC.

Unhas das mãos como biomarcador para fluorose dentária / Fingernails as a biomarker for dental fluorosis

INTRODUCTION: Biomarkers indicate levels of a particular chemical agent in the environment studied, which may be useful for monitoring health status, and nails may be major indicators of fluoride. OBJECTIVE: To evaluate fluoride concentration in the fingernails of children as a biomarker for fluoride exposure. METHODS: Twenty students were selected, aged 4-5 years old. Their nails were cut at 15 and 45 days (two collections), and the fluoride concentration in the nails was analyzed with the ion-specific electrode (Orion 9409) after rapid diffusion with HDMS. RESULTS: The total fluoride mean of the samples was 3.68 μg F/g (sd 1.44), ranging from 1.39 μg F/g to 7.81 μg F/g. Eleven children (55%) brush their teeth three times a day, but only three children (15%) swallow toothpaste. CONCLUSION: There is a high prevalence of fluoride exposure in the fingernails of the children studied, presenting risk of developing dental fluorosis in permanent teeth.

INTRODUÇÃO: Os biomarcadores indicam níveis de determinado agente químico no meio estudado, os quais podem ser úteis ao monitoramento do estado de saúde, podendo as unhas serem importantes indicadores de flúor. OBJETIVO: Avaliar a concentração de flúor nas unhas das mãos de crianças como biomarcador de exposição ao flúo.r MÉTODO: Foram selecionadas 20 escolares, com idade entre 4 e 5 anos. As unhas foram cortadas aos 15 e 45 dias (duas coletas) e a concentração de flúor nas unhas foi analisada com o eletrodo íon específica (Orion 9409), após difusão facilitada por HDMS RESULTADOS: A média total de flúor das amostras foi de 3,68 µg F/g (dp 1,44), variando de 1,39 µg F/g a 7,81 µg F/g. Onze crianças (55%) escovam os dentes três vezes por dia, porém, somente três crianças (15%), engolem dentifrício. CONCLUSÃO: Há uma alta prevalência de exposição ao flúor nas unhas das mãos das crianças investigada com risco de desenvolver fluorose dentária nos dentes permanentes.

Elevated serum CA 19-9 levels in patients with pulmonary nontuberculous mycobacterial disease

Abstract Increased serum CA 19-9 levels in patients with nonmalignant diseases have been investigated in previous reports. This study evaluates the clinical significance of serum CA 19-9 elevation in pulmonary nontuberculous mycobacterial disease and pulmonary tuberculosis. The median CA 19-9 level was higher in patients with pulmonary nontuberculous mycobacterial disease than in patients with pulmonary tuberculosis (pulmonary nontuberculous mycobacterial disease: 13.80, tuberculosis: 5.85, p < 0.001). A multivariate logistic regression analysis performed in this study showed that Mycobacterium abscessus (OR 9.97, 95% CI: 1.58, 62.80; p = 0.014) and active phase of pulmonary nontuberculous mycobacterial disease (OR 12.18, 95% CI: 1.07, 138.36, p = 0.044) were found to be risk factors for serum CA 19-9 elevation in pulmonary nontuberculous mycobacterial disease. The serum CA 19-9 levels showed a tendency to decrease during successful treatment of pulmonary nontuberculous mycobacterial disease but not in pulmonary tuberculosis. These findings suggest that CA 19-9 may be a useful marker for monitoring therapeutic responses in pulmonary nontuberculous mycobacterial disease, although it is not pulmonary nontuberculous mycobacterial disease-specific marker.

Cocaine-induced Psychosis and Brain-derived Neurothrophic Factor in Patients with Cocaine Dependence: Report of Two Cases

Brain-derived neurotrophic factor (BDNF) is linked to numerous brain functions. In addition, BDNF alterations contribute to neurological, mental, and addictive disorders. Cocaine dependence has received much attention recently due to its prevalence and psychological effects. Symptoms of psychosis are one of the most serious adverse events precipitated by cocaine use. It is particularly important to identify patients at risk of developing cocaine-induced psychosis (CIP). We described two cases of patients with cocaine dependence who presented with CIP and had changes in their BDNF levels during the psychotic episode. BDNF levels were initially low in both patients, and then decreased by more than 50% in association with CIP. The relationship between BDNF and psychosis is described in the literature. These cases revealed that BDNF levels decreased during a CIP episode and, thus, it is necessary to investigate BDNF and its relationship with CIP further.

Early diagnostic value of neutrophil gelatinase-associated lipocalin and interleukin-18 in patients with sepsis-induced acute kidney injury / 中华危重病急救医学

Objective To evaluate the early diagnosis value of blood neutrophil gelatinase-associated lipocalin (NGAL) and interleukin-18 (IL-18) in patients with sepsis-induced acute kidney injury (AKI). Methods A prospective case controlled study was conducted. Fifty-six patients with sepsis but without renal disease admitted to intensive care unit (ICU) of Shanxi People's Hospital from April 2014 to April 2015 were enrolled. Blood lactic acid and acute physiology and chronic health evaluation Ⅱ (APACHE Ⅱ) score at ICU admission were recorded. The urine output, blood urea nitrogen (BUN), serum creatinine (SCr), NGAL, IL-18 and tumor necrosis factor-α (TNF-α) were continuously monitored for 48 hours. The patients were divided into AKI group and non-AKI group according to the diagnostic criteria of Kidney Disease: Improving Global Outcomes (KDIGO). The changes trend in above parameters between the two groups at different time points were compared. The early diagnostic value of NGAL, IL-18, and SCr for sepsis-induced AKI was evaluated by receiver operating characteristic curve (ROC). Results Compared with non-AKI group, with the time prolongation after ICU admission, the traditional parameters reflecting AKI urine output in sepsis-induced AKI group was decreased gradually, BUN and SCr were gradually increased, and a statistically significant difference was found at 12 hours between the two groups [BUN (mmol/L): 11.8±3.5 vs. 8.2±3.5, SCr (μmol/L): 88.6±11.3 vs. 74.0±11.0, both P < 0.01]; but the new indicators NGAL and IL-18 reflecting AKI had a statistically significant difference at 6 hours [NGAL (μg/L): 426.7±90.7 vs. 382.3±67.9, IL-18 (ng/L): 75.7±9.3 vs. 70.9±7.3, both P < 0.05]. It was shown that in AKI group, NGAL and IL-18 compared with BUN and SCr increased at least 6 hours ahead of schedule. The area under ROC curve (AUC) of 6-hour NGAL and IL-18 in patients with sepsis-induced AKI were 0.821 [95% confidence interval (95%CI) = 0.713-0.931] and 0.719 (95%CI = 0.584-0.853) respectively, superior to SCr (AUC = 0.677, 95%CI = 0.528-0.825). The cutoff value of NGAL was 363.58 μg/L, and the sensitivity and specificity were 88.0% and 86.7% respectively. Conclusions NGAL and IL-18 in the early prediction of sepsis patients with AKI are better than SCr, and NGAL was most sensitive. Therefore, NGAL can be used as an early biomarker for the diagnosis of AKI in patients with sepsis.

Kallikrein-related peptidases in pancreatic cancer: expression and significance / 国际外科学杂志

Pancreatic cancer is a one of the most malignant digestive cancer.Because the lack of effective methods for early diagnosis,most patients have been ineligible for surgical resection when diagnosed.Kallikrein family is a group of serine proteases,because of its ability to decompose the extracellular matrix proteins,it may be closely related to the invasion and metastasis of various cancers.And some members of kallikrein family may become cancer diagnostic biomarkers.This paper reviews all the recent articles about kallikrein family study in pancreatic cancer.

Biomarkers of therapeutic responses in chronic Chagas disease: state of the art and future perspectives

The definition of a biomarker provided by the World Health Organization is any substance, structure, or process that can be measured in the body, or its products and influence, or predict the incidence or outcome of disease. Currently, the lack of prognosis and progression markers for chronic Chagas disease has posed limitations for testing new drugs to treat this neglected disease. Several molecules and techniques to detect biomarkers in Trypanosoma cruzi-infected patients have been proposed to assess whether specific treatment with benznidazole or nifurtimox is effective. Isolated proteins or protein groups from different T. cruzi stages and parasite-derived glycoproteins and synthetic neoglycoconjugates have been demonstrated to be useful for this purpose, as have nucleic acid amplification techniques. The amplification of T. cruzi DNA using the real-time polymerase chain reaction method is the leading test for assessing responses to treatment in a short period of time. Biochemical biomarkers have been tested early after specific treatment. Cytokines and surface markers represent promising molecules for the characterisation of host cellular responses, but need to be further assessed.

PHH3 as an Ancillary Mitotic Marker in Gastrointestinal Stromal Tumors

BACKGROUND: Counting mitoses is subjective and time-consuming. The adjunctive diagnostic utility of a recently reported mitotic marker, phosphohistone H3 (PHH3), was investigated in gastrointestinal stromal tumors (GISTs). METHODS: We reviewed 77 GISTs for several proliferative indices. These included the mitotic count per 50 high power fields (HPFs), the immunohistochemical Ki-67 labeling index and the immunohistochemical PHH3 mitotic index (MI). For comparison, Spearman's rank correlation and interclass correlation coefficient were used. RESULTS: Mitotic counts ranged from 0-138 (mean, 7.57+/-2.34) and the PHH3 MI ranged from 0-126 per 50 HPFs (mean, 9.61+/-2.27). We found a positive correlation between mitotic counts and PHH3 MI (r=0.810, p<.001). The inter-observer correlation coefficient for three participants was 0.975 for mitotic counts and 0.940 for the PHH3 MI. When using the PHH3 MI instead of mitotic counts in the Armed Forces Institute of Pathology (AFIP) stratification criteria, 10 cases were reclassified. In one patient with a mitotic count of 2 and a PHH3 MI of 6 per 50 HPFs, distant metastasis occurred. CONCLUSIONS: In GISTs, the PHH3 MI correlated adequately with mitotic counts and can be used as a useful adjunctive to count mitotic figures efficiently.