Role and mechanisms of CHI3L1 in coronary artery lesions in a mouse model of Kawasaki disease-like vasculitis / 中国当代儿科杂志

OBJECTIVES@#To explore the role and potential mechanisms of chitinase-3-like protein 1 (CHI3L1) in coronary artery lesions in a mouse model of Kawasaki disease (KD)-like vasculitis.@*METHODS@#Four-week-old male SPF-grade C57BL/6 mice were randomly divided into a control group and a model group, with 10 mice in each group. The model group mice were intraperitoneally injected with 0.5 mL of lactobacillus casei cell wall extract (LCWE) to establish a mouse model of KD-like vasculitis, while the control group mice were injected with an equal volume of normal saline. The general conditions of the mice were observed on the 3rd, 7th, and 14th day after injection. Changes in coronary artery tissue pathology were observed using hematoxylin-eosin staining. The level of CHI3L1 in mouse serum was measured by enzyme-linked immunosorbent assay. Immunofluorescence staining was used to detect the expression and localization of CHI3L1, von Willebrand factor (vWF), and α-smooth muscle actin (α-SMA) in coronary artery tissue. Western blot analysis was used to detect the expression of CHI3L1, vWF, vascular endothelial cadherin (VE cadherin), Caspase-3, B cell lymphoma-2 (Bcl-2), Bcl-2 associated X protein (Bax), nuclear factor κB (NF-κB), and phosphorylated NF-κB (p-NF-κB) in coronary artery tissue.@*RESULTS@#The serum level of CHI3L1 in the model group was significantly higher than that in the control group (P<0.05). Compared to the control group, the expression of CHI3L1 in the coronary artery tissue was higher, while the expression of vWF was lower in the model group. The relative expression levels of CHI3L1, Bax, Caspase-3, NF-κB, and p-NF-κB were significantly higher in the model group than in the control group (P<0.05). The relative expression levels of vWF, VE cadherin, and Bcl-2 were lower in the model group than in the control group (P<0.05).@*CONCLUSIONS@#In the LCWE-induced mouse model of KD-like vasculitis, the expression levels of CHI3L1 in serum and coronary arteries increase, and it may play a role in coronary artery lesions through endothelial cell apoptosis mediated by inflammatory reactions.

Serum YKL-40 levels in patients with multiple sclerosis / Níveis séricos de YKL-40 em pacientes com esclerose múltipla

ABSTRACT Background: Multiple sclerosis (MS) is a chronic inflammatory disease affecting the central nervous system. The YKL-40 protein, which is secreted from various cells that contribute to inflammation and infection, plays a role in immune regulation. Objective: This study investigated the serum YKL-40 levels of patients with clinically isolated syndrome (CIS) and MS. Methods: The participants was divided into three groups: 1) patients with CIS (n = 20); 2) patients with relapsing-remitting MS (RRMS; n = 39); and 3) healthy individuals (n = 35). The YKL-40 levels in serum samples obtained from the participants were measured using enzyme-linked immunoassays. Results: The median serum YKL-40 level was 20.2 ng/mL (range 9.8-75.9 ng/mL) in the patients with CIS, 22.7 ng/mL (range 13.4-57.9 ng/mL) in the patients with RRMS and 11.0 ng/mL (range 10.0-17.3 ng/mL) in the control group (p < 0.001). The serum YKL-40 levels in the patients with RRMS were correlated with the patients' expanded disability status scale scores and ages (p < 0.05). No relationships were determined between the serum YKL-40 levels and the other variables (p > 0.05). The serum YKL-40 levels were higher in the CIS group than in the MS group. These findings show that the serum YKL-40 levels were high even at the beginning of the disease. The serum YKL-40 levels were also not involved in the progression to clinically definite MS. Conclusions: The findings from this study suggested that YKL-40 may be a useful marker for the inflammatory process of MS.

RESUMO Contexto: A Esclerose Múltipla (EM) é uma doença inflamatória crônica que afeta o sistema nervoso central. A proteína UKL-40, secretada de várias células que participam de processos inflamatórios e infecciosos, desempenha um importante papel na regulação imunológica. Objetivo: Este estudo investigou níveis séricos de YKL-40 em pacientes com Síndrome Clinicamente Isolada (SCI) e EM. Métodos: Os participantes foram divididos em três grupos: 1) pacientes com SCI (n = 20); 2) pacientes com EM recorrente-remitente (EMRR; n = 39); e 3) indivíduos saudáveis (n = 35). Os níveis de YKL-40 em amostras séricas obtidas dos participantes foram medidos usando-se imunoensaios ligados a enzimas. Resultados: O nível sérico médio de YKL-40 foi 20.2 ng/mL (range 9.8-75.9 ng/mL) em pacientes com CIS, 22.7 ng/mL (intervalo entre 13.4-57.9 ng/mL) em pacientes com EMRR e 11.0 ng/mL (intervalo entre 10.0-17.3 ng/mL) no grupo controle (p < 0.001). Os níveis séricos de YKL-40 em pacientes com EMRR estavam correlacionados às pontuações e idades dos pacientes na EDSS (p < 0.05). Não foram determinadas relações entre os níveis séricos de YKL-40 e outras variáveis (p > 0.05). Os níveis séricos de YKL-40 no grupo SCI estavam mais elevados do que no grupo EM. Estes resultados demonstram que os níveis séricos de YKL-40 estavam mais elevados até mesmo no início da doença. Os níveis séricos de YKL-40 também não estavam associados à progressão da EM clinicamente definida. Conclusões: A partir deste estudo, os resultados sugeriram que a proteína YKL-40 pode ser um indicador útil no processo inflamatório da EM.

Biomarcadores gliais da doença de Alzheimer / Glial biomarkers of Alzheimer's disease

Introdução: A neuroinflamação associada às células gliais é um elemento importante do processo patológico da doença de Alzheimer (DA). Este estudo apresenta uma revisão dos marcadores gliais quitinase 3-like 1 (YKL-40), do receptor desencadeado expresso nas células mieloides 2 (Triggering receptor expressed on myeloid cells 2 ­ TREM2), da proteína acídica fibrilar glial (GFAP) e da proteína B S100 ligante de cálcio (S100B). Métodos: Nesta revisão são analisados os marcadores gliais YKL-40, TREM2, GFAP e S100B presentes em sangue e/ou líquido cefalorraquidiano (LCR), a partir de estudos publicados até 2020 nos bancos de dados do PubMed, Medline e Periódicos Capes. Resultados: Foram recuperados 233 documentos, dentre os quais foram incluídos 60. Todos os marcadores se encontram aumentados na DA em LCR ­ YKL-40 e TREM2 solúvel (sTREM2), já na fase pré-clínica ­, e em sangue, e estão correlacionados ao declínio cognitivo. No entanto, nenhum dos marcadores analisados apresentou grande potencial para o diagnóstico diferencial. Além da proteína TREM2 solúvel no LCR, no sangue também se pode identificar alteração nos níveis do RNAm de TREM2. GFAP sanguíneo mostra ser o melhor em distinguir controles de pacientes com Alzheimer. Há evidências de um efeito protetivo da ativação glial em reação ao acúmulo amiloide. Conclusão: Os marcadores gliais no geral têm pouca utilidade para o diagnóstico diferencial, mas podem auxiliar no prognóstico e como biomarcadores inespecíficos para doenças neurodegenerativas. (AU)

Introduction: Glial cell-associated neuroinflammation is a driving force for the pathological process of Alzheimer's disease (AD). This study is a systematic review aimed to analyze the following glial markers: chitinase-3-like protein 1 (YKL-40), triggering receptor expressed on myeloid cells 2 (TREM2), glial fibrillary acidic protein (GFAP) and S100 calcium-binding protein B (S100B). Methods: The PubMed, MEDLINE and CAPES Journals databases were searched for studies published until 2020 that addressed blood and/or cerebrospinal fluid (CSF) levels of YKL-40, TREM2, GFAP and S100B. Results: A total of 233 articles were retrieved, of which 60 were included in this study. All CSF ­ YKL-40 and soluble TREM2 (sTREM2) in preclinical stage ­ and blood biomarker levels were elevated for AD and were correlated to cognitive decline. None of the analyzed biomarkers showed promising results for differential diagnosis. Besides CSF sTREM2 levels, blood TREM2 mRNA levels were also altered in AD. Blood GFAP levels seem to be the best option for distinguishing controls from AD patients.' There is evidence of a protective role of glial activation in amyloid accumulation. Conclusion: Glial markers in general are of little use for differential diagnosis but can assist in prognosis and as nonspecific biomarkers of neurodegenerative diseases. (AU)

Value of serum YKL-40 in the diagnosis of anti-MDA5-positive patients with dermatomyositis complicated with severe pulmonary injury / 北京大学学报(医学版)

OBJECTIVE@#To investigate the value of serum and bronchoalveolar lavage fluid (BALF) chitinase-3-like-1 protein (YKL-40) in the diagnosis of anti-melanoma differentiation-associated gene 5 (MDA5)-positive dermatomyositis (DM) patients complicated with serious pulmonary injury, including rapidly progressive interstitial lung disease (RP-ILD) and pulmonary infection.@*METHODS@#Anti-MDA5 antibodies positive patients with DM who were hospitalized in the Department of Rheumatology of China-Japan Friendship Hospital from 2013 to 2018 were involved in this study. Demographic information, clinical, laboratory and imaging data were retrospectively collected. ELISA was used to detect the serum and BALF levels of YKL-40. The receiver operating characteristic (ROC) curve was drawn, and the area under ROC curve (AUC) was used to evaluate the diagnostic value of serum YKL-40 for pulmonary injury.Interstitial lung disease (ILD) was confirmed by chest high-resolution CT (HRCT). RP-ILD was defined as progressive respiratory symptoms such as dyspnea and hypoxemia within 3 months, and/or deterioration of interstitial changes or appearace of new pulmonary interstitial lesions on chest HRCT. Pulmonary infection was considered as positive pathogens detected in qualified sputum, blood, bronchoalveolar lavage fluid or lung biopsy specimens.@*RESULTS@#A total of 168 anti-MDA5-positive DM patients including 108 females and 60 males were enrolled in the study. Of these patients, 154 had ILD, and 66(39.3%) of them presented RP-ILD. Seventy patients with pulmonary infection were confirmed by etiology. In the patients with RP-ILD, 39 (59.1%) of them were complicated with pulmonary infection. While only 31 cases(30.4%) had pulmonary infection in the non-RP-ILD patients. The incidence of pulmonary infection in the patients with RP-ILD was significantly higher than that of those with non-RP-ILD (P < 0.001). The serum YKL-40 levels in the RP-ILD patients with pulmonary infection were the highest compared with RP-ILD without pulmonary infection, non-RP-ILD with pulmonary infection and non-RP-ILD without pulmonary infection groups among all the patients [83 (42-142) vs. 42 (21-91) vs. 43 (24-79) vs. 38 (22-69), P < 0.01].The sensitivity, specificity and AUC of serum YKL-40 in the diagnosis of RP-ILD complicated with pulmonary infection were 75%, 67%, and 0.72, respectively. The AUC of diagnosed of anti-MDA5 positive DM patients complicated with RP-ILD and pulmonary infection was higher than that of patients complicated with only RP-ILD and only pulmonary infection (0.72 vs. 0.54 and 0.55, Z=2.10 and 2.11, P < 0.05).@*CONCLUSION@#The prognosis of anti-MDA5-positive DM patients with RP-ILD and pulmonary infection were poor. Serum YKL-40 level can be used as a helpful tool for the diagnosis of coexistence of these conditions in the patients.

Value of chitinase-like protein YKL-40 in bronchoalveolar lavage fluid for predicting refractory / 中国当代儿科杂志

OBJECTIVE@#To evaluate the value of chitinase-like protein YKL-40 in bronchoalveolar lavage fluid (BALF) for predicting refractory @*METHODS@#A total of 50 children with common @*RESULTS@#Compared with the common MPP group, the RMPP group had significantly higher incidence rates of fever, shortness of breath, lung consolidation, and pleural effusion (@*CONCLUSIONS@#There is an increase in the level of YKL-40 in BALF in children with RMPP, and the level of YKL-40 in BALF has a certain value for predicting RMPP.

Association of YKL-40 in bronchoalveolar lavage fluid with airway damage in children with Mycoplasma pneumoniae pneumonia / 中国当代儿科杂志

OBJECTIVE@#To investigate the association of YKL-40 in bronchoalveolar lavage fluid (BALF) with airway damage in children with Mycoplasma pneumoniae pneumonia (MPP).@*METHODS@#A total of 60 children with MPP who were admitted to the hospital were enrolled as the MPP group, and 12 children with bronchial foreign bodies were enrolled as the control group. According to the imaging findings, the MPP group was further divided into 3 subgroups: pulmonary patchy shadow (n=34), pulmonary consolidation (n=19) and pulmonary ground-glass opacity (n=7). According to the bronchoscopic findings, the MPP group was further divided into 3 subgroups: mucosal congestion/edema (n=38), mucous secretion (n=18) and plastic bronchitis (n=4). The clinical manifestations and laboratory characteristics of the children with MPP were analyzed, the expression of YKL-40 in BALF was measured.@*RESULTS@#The MPP group had significantly higher levels of serum lactate dehydrogenase and BALF YKL-40 than the control group (P<0.05). The pulmonary consolidation subgroup had significantly higher levels of serum C-reactive protein and lactate dehydrogenase than the pulmonary patchy shadow subgroup (P<0.05), and the pulmonary consolidation and pulmonary ground-glass opacity subgroups had a significantly higher level of BALF YKL-40 than the pulmonary patchy shadow subgroup (P<0.05). The plastic bronchitis subgroup had a significantly higher level of BALF YKL-40 than the mucous secretion and mucosal congestion/edema subgroups (P<0.05). The mucous secretion and plastic bronchitis subgroups had a significantly higher proportion of children with shortness of breath than the mucosal congestion/edema subgroup (P<0.05). The plastic bronchitis subgroup had significantly higher serum levels of C-reactive protein and lactate dehydrogenase than the mucosal congestion/edema subgroup (P<0.05).@*CONCLUSIONS@#The level of BALF YKL-40 is associated with airway damage and disease severity in children with MPP.

Change of Inflammatory Factors in Patients with Acute Coronary Syndrome / 中华医学杂志(英文版)

<p><b>Background</b>Acute coronary syndrome (ACS) is closely related to unstable plaques and secondary thrombosis. The inflammatory cells in plaques and their inflammatory products may be the cause for plaque instability and ruptures. The study aimed to disclose the changes of inflammatory factors including serum intracellular adhesion molecule-1 (ICAM-1), chitinase-3-like protein 1 (YKL-40), and lipoprotein-associated phospholipase A2 (Lp-PLA2) in patients with ACS and its clinical significance.</p><p><b>Methods</b>A total of 120 patients with coronary heart disease (CHD) were categorized into 2 groups: 69 with ACS and 51 with stable angina pectoris (SAP); 20 patients with chest pain and normal angiography served as a control group. The 120 patients with CHD were categorized into single-vessel disease group, double-vessel disease group, and three-vessel disease group based on the number of coronary artery stenosis. The severity of coronary artery stenosis was quantified based on coronary angiography using Gensini score. They were further divided into mild CHD group with its Gensini score <26 (n = 36), moderate CHD group with its Gensini score being 26-54 (n = 48) and severe CHD group with its Gensini score >54 (n = 36). Serum levels of ICAM-1, YKL-40, and Lp-PLA2 of different groups were determined by enzyme-linked immunosorbent assay. Correlation between ICAM-1, YKL-40, Lp-PLA2, and Gensini score was analyzed.</p><p><b>Results</b>The levels of serum inflammatory factors ICAM-1, YKL-40, and Lp-PLA2 were significantly higher in the ACS group than those in control group and SAP group (all P < 0.05); and compared with control group, no significant difference was observed in terms of the serum ICAM-1, YKL-40, and Lp-PLA2 levels in the SAP group (P > 0.05).The levels of serum ICAM-1, YKL-40, and Lp-PLA2 were not significantly different among control group, single-vessel disease group, double-vessel disease group, and three-vessel disease group (all P > 0.05). The levels of serum ICAM-1, YKL-40, and Lp-PLA2 were not significantly different among control group, mild CHD group (Gensini score <26), moderate CHD group (Gensini score 26-54), and severe CHD group (Gensini score >54) (all P > 0.05). Nonparametric Spearman correlation analysis showed that the levels of serum ICAM-1, YKL-40, and Lp-PLA2 were not correlated with the Gensini score in CHD patients (r = 0.093, r = -0.149, and r = -0.085, all P > 0.05; respectively).</p><p><b>Conclusions</b>The serum levels of ICAM-1, YKL-40, and Lp-PLA2 were correlated with different clinical types of CHD, but not well correlated the severity and extent of artery stenosis, suggesting that ICAM-1, YKL-40, and Lp-PLA2 might be involved in occurrence of instability of atherosclerotic plaque, and might reflect the severity of CHD mostly through reflecting the plaque stability.</p>

Correlation between molecular features and genetic subtypes of Glioblastoma: critical analysis in 109 cases / Correlação entre as características moleculares e os subtipos genéticos dos glioblastomas: análise crítica de 109 casos

OBJECTIVE: Glioblastoma, the most common and lethal brain tumor, is also one of the most defying forms of malignancies in terms of treatment. Integrated genomic analysis has searched deeper into the molecular architecture of GBM, revealing a new sub-classification and promising precision in the care for patients with specific alterations. METHOD: Here, we present the classification of a Brazilian glioblastoma cohort into its main molecular subtypes. Using a high-throughput DNA sequencing procedure, we have classified this cohort into proneural, classical and mesenchymal sub-types. Next, we tested the possible use of the overexpression of the EGFR and CHI3L1 genes, detected through immunohistochemistry, for the identification of the classical and mesenchymal subtypes, respectively. RESULTS: Our results demonstrate that genetic identification of the glioblastoma subtypes is not possible using single targeted mutations alone, particularly in the case of the Mesenchymal subtype. We also show that it is not possible to single out the mesenchymal cases through CHI3L1 expression. CONCLUSION: Our data indicate that the Mesenchymal subtype, the most malignant of the glioblastomas, needs further and more thorough research to be ensure adequate identification.

OBJETIVO: O glioblastoma (GBM), o tumor cerebral mais comum e mais letal, é também um dos tipos de tumores de mais difícil tratamento. Análises genômicas integradas têm contribuído para um melhor entendimento da arquitetura molecular dos GBMs, revelando uma nova subclassificação com a promessa de precisão no tratamento de pacientes com alterações específicas. Neste estudo, nós apresentamos a classificação de uma casuística brasileira de GBMs dentro dos principais subtipos do tumor. MÉTODO: Usando sequenciamento de DNA em larga escala, foi possível classificar os tumores em proneural, clássico e mesenquimal. Em seguida, testamos o possível uso da hiperexpressão de EGFR e CHI3L1 para a identificação dos subtipos clássico e mesenquimal, respectivamente. RESULTADOS: Nossos resultados deixam claro que a identificação genética dos subtipos moleculares de GBM não é possível utilizando-se apenas um único tipo de mutação, em particular nos casos de GBMs mesenquimais. Da mesma forma, não é possível distinguir os casos mesenquimais apenas com a expressão de CHI3L1. CONCLUSÃO: Nossos dados indicam que o subtipo mesenquimal, o mais maligno dos GBMs, necessita de uma análise mais aprofundada para sua identificação.

Validity of Klotho, CYR61 and YKL-40 as ideal predictive biomarkers for acute kidney injury: review study / Validade de Klotho, CYR61 e YKL-40 como biomarcadores preditivos ideais para lesão renal aguda: estudo de revisão

ABSTRACT CONTEXT AND OBJECTIVE: Acute kidney injury (AKI) is still a headache for clinicians and scientists as a possible reason for increased death among intensive care unit (ICU) patients after invasive cardiac surgery. Furthermore, the diagnostic process for AKI using conventional biomarkers is not sufficient to ensure early warning of this condition because of the morbid influence of non-renal factors that definitively delay the time for the prognosis. These imposed limitations have led to significant amounts of research targeted towards identifying novel biomarkers for AKI with a sustained degree of sensitivity and specificity. Here, we reviewed previous studies conducted on the Klotho, CYR61 and YKL-40 biomarkers in relation to AKI. DESIGN AND SETTING: Review of the literature conducted in the Institute of Clinical Chemistry & Biochemistry, Ljubljana University Medical Center, Slovenia. METHODS: The literature was searched in PubMed and the Cochrane Library. From the database of this specialty, we selected 17 references that matched our context for detailed analysis and further investigation. RESULTS: The studies reviewed showed notable differences in their results relating to the diagnostic impact of Klotho, CYR61 and YKL-40 on early prediction of AKI. CONCLUSIONS: The results regarding the Klotho, CYR61 and YKL-40 biomarkers showed markedly equivocal performance in the previous studies and did not fulfill the expectations that these factors would form valid possible biomarkers for AKI.

RESUMO CONTEXTO E OBJETIVO: A lesão renal aguda (LRA) ainda é uma dor de cabeça para os clínicos e cientistas como possível razão para o aumento da mortalidade entre os pacientes de unidade de terapia intensiva (UTI) após cirurgia cardíaca invasiva. Além disso, o processo de diagnóstico para LRA usando biomarcadores convencionais não é suficiente para garantir um alerta precoce desta condição, devido à influência mórbida de fatores não renais que podem retardar o tempo para o prognóstico. Essas limitações geraram quantidades significativas de pesquisas orientadas para identificar novos biomarcadores para LRA com um grau adequado de sensibilidade e especificidade. Revisamos estudos anteriores realizados sobre os biomarcadores Klotho, CYR61, YKL-40 para LRA. TIPO DE ESTUDO E LOCAL: Revisão da literatura realizada no Instituto de Química Clínica e Bioquímica, Centro Médico da Universidade de Ljubljana, Eslovênia. MÉTODOS: A literatura foi pesquisada no PubMed e Cochrane Library. A partir da base de dados da especialidade, selecionamos 17 referências que combinavam com o contexto para uma análise detalhada e mais investigação. RESULTADOS: Os estudos revisados mostraram diferenças notáveis nos resultados sobre o impacto diagnóstico de Klotho, CYR61 e YKL-40 sobre a detecção precoce do LRA. CONCLUSÃO: Os resultados em relação aos biomarcadores Klotho, CYR61 e YKL-40 mostraram desempenho marcadamente equívoco nos estudos anteriores e não cumpriram as expectativas de que estes fatores constituam possíveis biomarcadores válidos para LRA.

Changes in serum YKL-40 level and humoral immune function and their significance in children with recurrent pneumonia / 中国当代儿科杂志

<p><b>OBJECTIVE</b>To investigate the changes in serum YKL-40 level and humoral immune function and their significance in children with recurrent pneumonia.</p><p><b>METHODS</b>Blood samples were collected from 30 children with recurrent pneumonia (recurrent pneumonia group), 30 children with acute pneumonia (acute pneumonia group), and 30 healthy children (control group). Serum YKL-40 levels were measured by enzyme-linked immunosorbent assay. The correlation between serum YKL-40 level and laboratory indices related to humoral immune function was analyzed. The receiver operating characteristic (ROC) curve was used to analyze the diagnostic value of serum YKL-40 level for recurrent pneumonia.</p><p><b>RESULTS</b>The recurrent pneumonia group had a significantly higher serum YKL-40 level than the acute pneumonia and control groups (P<0.05). The acute pneumonia group had a significantly higher serum YKL-40 level than the control group (P<0.05). Serum levels of IgG and complement 4 in the recurrent pneumonia group were significantly lower than in the acute pneumonia group (P<0.05). Serum YKL-40 level was negatively correlated with serum IgG level (r=-0.309, P=0.047) and serum complement 4 level (r=-0.324, P=0.039). The area under the ROC curve of serum YKL-40 level for diagnosing recurrent pneumonia was 0.958 (95%CI: 0.921-0.994).</p><p><b>CONCLUSIONS</b>Humoral immune function is low in children with recurrent pneumonia. Serum YKL-40 may be involved in the occurrence of recurrent pneumonia and can be used as a reference index for diagnosing recurrent pneumonia.</p>

Expression of YKL-40 and TLR4 in patients with chronic rhinosinusitis / 中华耳鼻咽喉头颈外科杂志

<p><b>OBJECTIVE</b>To explore the expression of YKL-40, TLR4 and NF-κB in chronic rhinosinusitis (CRS) with or without nasal polyps (CRSwNP and CRSsNP), and to investigate their expressional correlation and the potential role in pathogenesis of CRS.</p><p><b>METHODS</b>The specimens were obtained from sinus mucosa and inferior turbinate mucosa of the patients with informed consent. The different expression of YKL-40, TLR4 and NF-κB among each group was detected by real time RT-PCR and immunohistochemistry (S-P method). SPSS 17.0 software was used to analyze the data.</p><p><b>RESULTS</b>mRNA level: The relative expression of YKL-40 in CRSwNP group (0.91±0.17) was higher than those in the control group (0.49±0.09), the difference was significant (t=2.12, P<0.05). The relative expression of TLR4 in CRSsNP group (0.88±0.19) and CRSwNP group (0.67±0.13) were lower than those in control group (1.48±0.14), the differences were significant (t value was -4.11, -2.48, all P<0.05). The relative expression of NF-κB in CRSsNP group (0.69±0.13) and CRSwNP group (0.72±0.14) were lower than those in control group (1.20±0.15), the differences were significant (t value was 2.33, 2.27, all P<0.05). Protein level: The expression of YKL-40 in CRSwNP group was stronger than that in CRSsNP group and control group (U value was 72.5 and 73, all P<0.01). The expression of TLR4 in CRSwNP group and CRSsNP group was weaker than that in control group (U value was 62 and 38, all P<0.01). There was a negative correlation between YKL-40 and TLR4 (rmRNA=-0.741, P<0.01; rprotein=-0.46, P<0.05) in CRSwNP group.</p><p><b>CONCLUSIONS</b>The expression of YKL-40 in pantients with CRSwNP is higher than those in healthy control and CRSsNP patients. There was a negative correlation between YKL-40 and TLR4. Both of them may be involved in the pathogenesis of CRSwNP.</p>

Expression of serum YKL-40 in anaphylactic rhinitis patients and association of serum YKL-40 with serum IL-4 and IFN-γ / 临床耳鼻咽喉头颈外科杂志

OBJECTIVE@#This study intends to preliminarily discuss the expression and the clinical meaning of serum YKL-40 in anaphylactic rhinitis by comparing the different expressions of serum YKL-40 in types of anaphylactic rhinitis, and to preliminarily discuss possible mechanism of having anaphylactic rhinitis involved with serum YKL-40 by associating it with serum IL-4 and IFN-γ in anaphylactic rhinitis.@*METHOD@#Firstly, each select 20 people in our hospital who have anaphylactic rhinitis respectively according to different levels--mild intermittent, mild persistent, moderate-severe interminttent, moderate-severe persistent as the experimental groups, while 20 healthy people as the nomal control. Secondly, test the levels of serum YKL-40, IL-4 and IFN-γ respectively in each group by the ELISA method. Thirdly, statistically analyze and discuss the collected data.@*RESULT@#(1) There was a rise in the expression of serum YKL-40 between the experimental groups and the nomal control group, which contained a statistical significance (P 0.05). (2) There was a rise in the expression of serum IL-4 between the experimental groups and the nomal control group, which contained a statistical significance (P 0.05). (3) There was a reduction in the expression of serum IL-4 be- tween the experimental groups and the nomal control group, which contained a statistical significance (P 0.05). (4) The corelation between serum YKL-40 and IL-4 in anaphylactic rhinitis was positive, while the corelation between serum YKL-40 and IFN-γ was negative.@*CONCLUSION@#(1) Allergic rhinitis serum YKL-40 expression was increased. The corelation between serum YKL-40 and IL-4 in anaphylactic rhinitis was positive, while the corelation between serum YKL-40 and IFN-γ was negative,suggesting that YKL-40 may regulate the differentiation of Th cells, Promote Th1 to Th2 immune shift, through this mechanism involved in the pathogenesis of allergic rhinitis. (2) Compared with patients with intermittent allergic rhinitis, persistent allergic rhinitis serum YKL-40 expression was increased, suggesting that YKL-40 may promote the continuous attacks of the symptoms of allergic rhinitis.

Association between CHI3L1 SNPs and susceptibility to childhood asthma / 中国当代儿科杂志

<p><b>OBJECTIVE</b>To investigate the association between CHI3L1 single nucleotide polymorphisms (SNPs) and the susceptibility to childhood asthma.</p><p><b>METHODS</b>A total of 316 children diagnosed with asthma between January 2011 and October 2013 and 297 healthy children were selected as asthma group and control group respectively. Peripheral blood samples were collected from all subjects. Chemiluminescence and flow cytometry were applied to measure total IgE level and the percentage of eosinophils. ELISA was used to measure YKL-40 level. Genomic DNA was extracted from peripheral blood hemocytes, and the genotype and allele frequencies at CHI3L1 SNPs rs4950928, rs10399805, and rs883125 were determined by MALDI-TOP mass spectrometry.</p><p><b>RESULTS</b>The total IgE and YKL-40 levels were significantly higher in the asthma group than in the control group (P<0.05), while the percentage of eosinophils showed no significant difference between the two groups (P>0.05). The frequency of GG genotype at rs883125 in the asthma group was significantly higher than that in the control group (P<0.05). For rs4950928, the asthma group had a significantly lower frequency of CC genotype (P<0.05) but a significantly higher frequency of CG genotype (P<0.05) compared with the control group. In the asthma group, the patients with GG and CG genotypes at rs4950928 had significantly increased total IgE and YKL-40 levels compared with those with CC genotype at this locus (P<0.05).</p><p><b>CONCLUSIONS</b>YKL-40 is a potential molecular biomarker for the primary diagnosis of childhood asthma. CHI3L1 SNPs rs4950928 and rs883125 may be associated with childhood asthma. G allele at rs4950928 may increase the risk of childhood asthma.</p>

Effects of Guizhi Fuling Decoction on YKL-40 and hs-CRP of patients with non-ST segment elevation acute coronary syndrome / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To investigate the changes of serum levels of chitinase-3-like-1 protein (YKL-40) and high-sensitivity C-reactive protein (hs-CRP) in patients with non-ST segment elevation acute coronary syndrome (ACS), to explore its correlation with its severity, and to observe the effects of Guizhi Fuling Decoction (GFD) on levels of blood lipids, YKL-40, and hs-CRP.</p><p><b>METHODS</b>Recruited were 72 patients with unstable angina (UA) or non-ST segment elevation myocardial infarction (NSTEMI) at Department of Integrative Medicine, First Affiliated Hospital of Xinxiang Medical College from August 2010 to June 2011. They were randomly assigned to the treatment group (36 cases) and the control group (36 cases). All patients were treated by routine treatment, but patients in the treatment group took GFD additionally. The course of treatment was four weeks. According to the severity degree, all patients were graded to four ranks: low-risk group of UA, medium-risk group of UA, high-risk group of UA, and NSTEMI. The levels of YKL-40 and hs-CRP, and the correlation of severity degree were analyzed. Before and after treatment levels of triglyceride (TG), total cholesterol (TC), high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C) were measured. Before treatment, at two weeks, and after treatment the serum levels of YKL-40 and hs-CRP were detected. The relationship of YKL-40, hs-CRP and the severity of the disease were analyzed.</p><p><b>RESULTS</b>Levels of YKL-40 and hs-CRP were positively correlated with the severity of the disease respectively (r = 0.729, P < 0.05; r = 0.655, P < 0.05). The positive correlation also existed between YKL-40 and hs-CRP (r = 0.848, P < 0.05). There was no statistical difference in the levels of blood lipids, YKL-40, or hs-CRP between the two groups before treatment (P > 0.05). Compared with before treatment, the levels of YKL-40 and hs-CRP significantly decreased in both groups after two weeks of treatment (P < 0.05). The levels of TG, TC, LDL-C, YKL-40, and hs-CRP significantly decreased, while the HDL-C level increased in both groups after treatment (P < 0.05). The level of HDL-C in the treatment group was higher, while levels of YKL-40 and hs-CRP were lower after treatment, when compared with the control group (all P < 0.05).</p><p><b>CONCLUSION</b>On the basis of anti-inflammation and adjusting blood lipids by Western medicine, GFD could further reduce the serum levels of YKL-40 and hs-CRP of ACS patients, elevate the HDL-C level, and play anti-atherosclerosis effects.</p>

Association between serum YKL-40 levels and endothelial function in hypertensive patients / 中华心血管病杂志

<p><b>OBJECTIVE</b>To explore the relationship between serum YKL-40 levels and endothelial function in patients with essential hypertension (EH).</p><p><b>METHOD</b>Sixty EH patients [34 male, aged between 43 - 76 years, mean (59 ± 7) years] and 30 healthy subjects [17 male, mean age (57 ± 5) years] were enrolled in this study. Serum YKL-40 levels were measured by enzyme immunoassay (ELISA). Endothelial function [endothelin-1 (ET-1), nitric oxide (NO), flow-mediated dilatation (FMD)] was also measured. EH patients were further divided to no metabolic syndrome and metabolic syndrome group.</p><p><b>RESULTS</b>Serum uric acid, ET-1, hs-CRP were significantly higher while serum NO, FMD and NMD were significantly lower in EH group than in control group (all P < 0.05). YKL-40 was significantly higher in EH group than in the control group [51.7 (35.6 - 341.9) µg/L vs. 33.2 (23.3 - 167.3) µg/L, P < 0.05] and significantly higher in EH patients with metabolic syndrome than in EH patients without metabolic syndrome (152.3 µg/L vs. 94.2 µg/L, P < 0.05). In this cohort, serum YKL-40 level was positively correlated with SBP, DBP, BMI, TG and hsCRP(r = 0.360, 0.303, 0.281, 0.216, 0.530, all P < 0.05)but not correlated with FMD, ET-1 and NO (all P > 0.05).</p><p><b>CONCLUSIONS</b>Serum YKL-40 levels are increased compared to normal controls and positively correlated with blood pressure level but not with endothelial function parameters in hypertensive patients. Serum YKL-40 level might thus be used as a biomarker reflecting inflammation status other than endothelium function in hypertensive patients.</p>

An overview of biomarkers in Alzheimer's disease / 药学学报

Alzheimer's disease (AD), also called presenile dementia, is one of the most common neurodegenerative diseases in elderly people. The main pathological features of AD include senile plaques (SPs), neurofibrillary tangles (NFTs) and neuron loss. A biomarker is a characteristic that can be objectively measured and evaluated as an indicator of normal biological processes, pathogenic processes, or pharmacological responses to a therapeutic intervention. Class biomarkers of AD such as Abeta and phosphorylated tau have been widely used in clinical diagnosis of AD patients. Recently, novel technologies like proteomics, genomics, and imaging techniques have expanded the role of a biomarker from early diagnosis to monitoring the progression of diseases and evaluating the response to various treatments. In this article, we will review the progress of various biomarkers of AD.