The value of bedside ultrasound and biomarkers in the diagnosis of sepsis-induced myocardial dysfunction and prognosis of septic shock in children / 中国小儿急救医学

Objective:To evaluate the feasibility of using bedside ultrasound and serum biomarkers for the prediction of sepsis-induced myocardial dysfunction(SIMD)and mortality in septic shock patients.Methods:The patients diagnosed as septic shock were enrolled in the study from January 2019 to July 2021 in PICU at Shanghai Children′s Medical Center Affiliated to Shanghai Jiaotong University School of Medicine.Bedside ultrasound results were recorded at day 1, 2, 3, 7 and 10.Blood samples were collected at the same time, markers of myocardial injury were detected, and prognosis was recorded at 28 days.According to the left ventricular ejection fraction (LVEF), children with septic shock were divided into SIMD group and non-SIMD group.Those with LVEF <50% or decreased by ≥10% from baseline level were defined as SIMD.Differences in cardiac ultrasound parameters and biomarkers between two groups were compared.Logistic regression analysis was performed to determine the independent risk factors for SIMD and the independent risk factors for death at 28 days after septic shock.The area under the receiver operating characteristic curve (AUC) was used to evaluate the efficacy of different indicators in predicting SIMD and the death outcome of children with septic shock on 28 days.Results:A total of 57 children were enrolled, including 28 cases in SIMD group and 29 cases in non-SIMD group.Univariate analysis showed that there were statistically significant differences in pediatric critical illness score, N-terminal B-type natriuretic peptide(NT-proBNP), LVEF and left ventricular short axis shortening rate between two groups ( P<0.05). Logistic analysis demonstrated that LVEF( OR=0.890, 95% CI 0.818-0.969, P=0.007)and NT-proBNP ( OR=1.000, 95% CI 1.000-1.000, P=0.015)could independently predict SIMD.There were 42 cases in survival group and 15 in non-survival group according to the prognosis on 28 days.Univariate analysis showed that there were significant differences in pediatric risk mortality score Ⅲ, pediatric sequential organ failure assessment, cardiac troponin I, and mitral annular plane systolic excursion(MAPSE)( P<0.05). Logistic analysis showed that only MAPSE independently predicted mortality( OR=85.670, 95% CI 1.685-4 356.736, P=0.026). Compared with MAPSE(AUC=0.727), MAPSE combined with pediatric risk mortality score Ⅲ, pediatric sequential organ failure assessment, cardiac troponin I(AUC=0.926) could be better to predict the 28 days prognosis of patients with septic shock on 28 days. Conclusion:NT-proBNP increases significantly in the early stage of SIMD.MAPSE shows no difference between SIMD and non-SIMD patients.MAPSE is correlated with the prognosis of patient with septic shock.

Indirect serum biomarkers perform sub optimally in screening for significant liver fibrosis among HIV-infected and uninfected adults in Uganda

ntroduction: Indirect serum biomarkers present an acceptable noninvasive and cheap alternative for screening of significant liver fibrosis (SLF). Evaluation of their use in resource limited settings is important to determine their utility. Methods: We conducted a cross sectional study among 520 HIV infected and HIV uninfected adults attending care clinics in Kampala Uganda. Presence of SLF was determined using Fibroscan® liver stiffness measurement of ≥7.2KPa. The diagnostic value of indirect serum biomarkers for diagnosis of SLF was evaluated using the area under the receiver operating characteristics curve (AUROC) using Fibroscan® as gold standard. Results: Overall AUROC values for Age Platelet Index (API), Aspartate to Alanine Ratio (AAR), AST-to-Platelet Ratio Index (APRI), Fibrosis Index based on 4 Factors (FIB-4) and Gamma glutamyl transferase to Platelet Ratio Index (GPR) were 0.52, 0.49, 0.55, 0.55 and 0.54 respectively. Among HIV-infected participants AUROC values were slightly improved at predicting presence of SLF but still under 70%. Conclusion: Despite APRI and FIB-4 being more likely to identify participants with SLF, the overall diagnostic value of all serum biomarkers was poor with and without stratification by HIV status. We recommend the use of Fibroscan® technology as more accurate non-invasive diagnostic method for screening of SLF

Clinical significance of abnormal inflammatory markers in Mycoplasma pneumoniae pneumonia / 中华实用儿科临床杂志

Mycoplasma pneumoniae pneumonia (MPP) is usually self-limited.However, refractory MPP affects some patients even after the treatment of macrolide antibiotics, leading to clinical or imaging deterioration.In recent years, novel insights in the clinical manifestations of MPP have been largely obtained, especially in the unique epidemiological characteristics of mycoplasma pneumoniae (MP) in 3 to 5 years interval, and the relationship between refractory and severe MP infection, outbreak and epidemic.The rapid laboratory diagnosis of MP and the selection of optimal therapeutic strategy for severe MPP cases are the huge challenges in clinical practice.Therefore, many studies have been performed to explore the early warning role of serum biomarkers in severe cases, as well as their diagnostic and therapeutic potentials.However, the understanding of the exact application value of these inflammatory markers is still limited.The ideal blood biomarkers of MPP should be reliable, rapid, and widely used, which can assist the diagnosis of severe cases, determination of complications, understanding of the pathogenesis and predictions of clinical outcomes or treatment effect.

Diagnostic value of the neutrophil/lymphocyte ratio, platelet/lymphocyte ratio, and thrombocytosis in the preoperative investigation of ovarian masses / Valor diagnóstico das razões neutrófilo/linfócito, plaqueta/ linfócito, e trombocitose na investigação pré-operatória de massas ovarianas

Abstract Objective To evaluate the diagnostic accuracy of cancer antigen 125 (CA125) and complete blood count (CBC) parameters, such as the neutrophil to lymphocyte ratio (NLR), the platelet to lymphocyte ratio (PLR), and thrombocytosis in patients with ovarian masses. Methods The present is a retrospective study conducted at a single tertiary hospital from January 2010 to November 2016. We included consecutive women referred due to suspicious adnexal masses. The CBC and CA125 were measured in the serum of 528 women with ovarian masses before surgery or biopsy. We evaluated the diagnostic performance of the NLR, PLR, platelets (PLTs), CA125, and the associations between them. We tested the clinical utility of the CBC parameters and CA125 in the discrimination of ovarian masses through decision curve analysis (DCA). Results The best balance between sensitivity and specificity was obtained by the associations of CA125 or PLTs ≥ 350/nL, with 70.14% and 71.66%, CA125 or PLTs ≥ 400/ nL, with 67.30% and 81.79%, CA125 or PLR, with 76.3% and 64.87%, and CA125 or NLR, with 71.09% and 73.89% respectively. In the DCA, no isolated CBC parameter presented a higher clinical utility than CA125 alone. Conclusion We showed that no CBC parameter was superior to CA125 in the prediction of the malignancy of ovarian tumors in the preoperative scenario.

Resumo Objetivo Avaliar a acurácia diagnóstica do antígeno de câncer 125 (cancer antigen 125, CA125, em inglês) e dos parâmetros do hemograma como as razões neutrófilo/linfócito (RNL), plaqueta/linfócito (RPL), e trombocitose em pacientes com massas ovarianas. Métodos Este é um estudo retrospectivo realizado em um hospital terciário no período de janeiro de 2010 a novembro de 2016. Foram incluídas de forma consecutiva mulheres encaminhadas por massas anexiais suspeitas. Foram dosados hemogramas e CA125 no soro de 528 mulheres com massas ovarianas antes da cirurgia ou biópsia. Foram avaliados os desempenhos diagnósticos da RNL, da RPL, das plaquetas (PLQs) e do CA125, considerando-os isoladamente e associados entre si. Testamos a utilidade clínica dos parâmetros do hemograma e do CA125 na discriminação das massas ovarianas por análise de curva de decisão (ACD). Resultados Os melhores equilíbrios entre sensibilidade e especificidade foram obtidos por meio das associações do CA125 ou PLQs ≥ 350/nL, com 70,14% e 71,66%, CA125 ou PLQs ≥ 400/nL, com 67,30% e 81,79%, CA125 ou RPL, com76,3% e 64,87%, e CA125 ou RNL, com 71,09% e 73,89%, respectivamente. Conclusão Na ACD, nenhum parâmetro do hemograma isolado se mostrou superior ao CA125 na predição de malignidade de tumores ovarianos no pré-operatório.

Challenges and prospects for early gastrointestinal cancer screening in China / 第二军医大学学报

China is a country with high incidence of gastrointestinal (GI) cancer. Gastric cancer, esophageal cancer and colon cancer seriously threaten the health of people, and leads to heavy medical burdens. This review discusses the current screening protocol of GI cancer and pancreatic cancer. It also interprets the relevant policies issued by the state in recent years, and evaluates the effects of new technologies such as serum pepsinogen combined with gastrin in detecting gastric cancer, fecal and blood gene detection for colon cancer, and "serum liquid biopsy" of pancreatic cancer for early cancer screening. We also point out the difficulties and challenges in cancer screening at early stage, and the significance of promoting early cancer screening to reduce the mortality of GI cancer in China.

The clinical observation of serum specific biomarkers in patients with chronic graft-versus-host disease / 中华血液学杂志

Objective: Chronic graft-versus-host disease (cGVHD) is a major long-term complication after allogeneic hematopoietic stem cell transplantation (allo-HSCT) . It is important to study the changes of serum biomarkers expression in patients for early diagnosis and treatment. Methods: The expression levels of five serum protein markers (IL-1b, IL-16, CXCL9, CCL19, CCL17) in patients with or without cGVHD after allo-HSCT were detected by liquid suspension microarray. Results: Compared with the control group without cGVHD, the expression levels of CXCL9 and CCL17 in serum of patients with cGVHD were significantly increased (P<0.05) . CCL17 was correlated with the severity of cGVHD (P<0.001) . CXCL9 was significantly increased in the serum of patients with skin lesion (P<0.01) , and CCL17 was significantly expressed in cGVHD patients with liver as the target organ (P<0.01) . Conclusion: The combination of CXCL9 and CCL17 can be used as serum biomarkers of cGVHD, which has certain reference value in assisting the diagnosis and evaluation of cGVHD severity.

The clinical observation of serum specific biomarkers in patients with chronic graft-versus-host disease / 中华血液学杂志

Objective@#Chronic graft-versus-host disease (cGVHD) is a major long-term complication after allogeneic hematopoietic stem cell transplantation (allo-HSCT) . It is important to study the changes of serum biomarkers expression in patients for early diagnosis and treatment.@*Methods@#The expression levels of five serum protein markers (IL-1b, IL-16, CXCL9, CCL19, CCL17) in patients with or without cGVHD after allo-HSCT were detected by liquid suspension microarray.@*Results@#Compared with the control group without cGVHD, the expression levels of CXCL9 and CCL17 in serum of patients with cGVHD were significantly increased (P<0.05) . CCL17 was correlated with the severity of cGVHD (P<0.001) . CXCL9 was significantly increased in the serum of patients with skin lesion (P<0.01) , and CCL17 was significantly expressed in cGVHD patients with liver as the target organ (P<0.01) .@*Conclusion@#The combination of CXCL9 and CCL17 can be used as serum biomarkers of cGVHD, which has certain reference value in assisting the diagnosis and evaluation of cGVHD severity.

LC-MS/MS-based screening of new protein biomarkers for cervical precancerous lesions and cervical cancer / 南方医科大学学报

OBJECTIVE@#To screen potential plasma protein biomarkers for the progression of cervical precancerous lesions into cervical carcinoma and analyze their functions.@*METHODS@#Plasma samples obtained from healthy control subjects, patients with low-grade squamous intraepithelial lesion (LSIL), high-grade squamous intraepithelial lesion (HSIL), cervical cancer (CC), and patients with CC after treatment were enriched for low-abundance proteins for liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis. The MS data of the samples were analyzed using Discoverer 2.2 software, and the differential proteins (peptide coverage ≥20%, unique peptides≥2) were screened by comparison of LSIL, HSIL and CC groups against the control group followed by verification using target proteomics technology. Protein function enrichment and coexpression analyses were carried out to explore the role of the differentially expressed proteins as potential biomarkers and their pathological mechanisms.@*RESULTS@#Compared with the control group, both LSIL group and HSIL group showed 9 differential proteins; 5 differentially expressed proteins were identified in CC group. The proteins ORM2 and HPR showed obvious differential expressions in LSIL and HSIL groups compared with the control group, and could serve as potential biomarkers for the progression of cervical carcinoma. The expression of F9 increased consistently with the lesion progression from LSIL to HSIL and CC, suggesting its value as a potential biomarker for the progression of cervical cancer. CFI and AFM protein levels were obviously decreased in treated patients with CC compared with the patients before treatment, indicating their predictive value for the therapeutic efficacy. Protein function enrichment analysis showed that all these differentially expressed proteins were associated with the complement system and the coagulation cascades pathway.@*CONCLUSIONS@#We identified 5 new protein biomarkers (F9, CFI, AFM, HPR, and ORM2) for cervical precancerous lesions and for prognostic evaluation of CC, and combined detection of these biomarkers may help in the evaluation of the development and progression of CC and also in improving the diagnostic sensitivity and specificity of cervical lesions.

Study on serum markers of prostate cancer by nuclear magnetic resonance-based metabolomics / 中华泌尿外科杂志

Objective To investigate the clinical value of serum metabolomic profile of prostate cancer using nuclear magnetic resonance-based metabolomics.Methods The retrospective case control study was adopted.The clinical data of 31 patients with prostate cancer,28 patients of prostatic hyperplasia and 31 healthy volunteers were enrolled in this study from May 2016 to May 2017 at the first affiliated hospital of Xinjiang medical university.In PCa group,the mean age was 66.3 years old,ranging 53-80 years old.In BPH group,the mean age was 59.3 years old,ranging 46-75 years old.In volunteer group,the mean age was 47.8 years old,ranging 35-62 years old..The serum of the 3 groups was measured by 1H-NMR spectroscopy.Multivariate statistical analysis was used to analyze the serum differential metabolism of the 3 groups,including principal components analysis (PCA),partial least squares discriminant analysis (PLS-DA) and orthogonal partial least squares discriminant analysis (OPLS-DA).Results The multivariate statistical analysis of PCA that the rate of the first principal component 1 (PC1) was 53.24％,the second principal component 2 (PC2) was 25.31％ and the cumulative contribution rate was 78.55 ％.Results of PLS -DA showed that partial data overlap of the three groups,but the separation trend was appeared.The variance of X(R2X) and Y(R2Y) matrixes and predictive value Q2 were 0.67,0.60,and 0.42.The results of OPLS-DA showed that the difference among the PCa group and BPH group,healthy group were obvious.The separation trend were appeared and the differential metabolites could be screened effectively.The R2X、R2Y and Q2 was 0.24,0.57,0.21 and 0.30,0.65,0.36.26 different serum metabolites were detected in the 3 groups,including citric acid,arginine,threonine,citrulline,glutamine,lactic acid,alanine,unsaturated fats,glycoprotein etc.Conclusions Compared with BPH group and healthy group,the serum of prostate cancer patients showed significant differences in metabolism.Nuclear magnetic resonance metabolomics analysis can effectively distinguish these serum metabolic differences.

Screening on serum biomarkers in idiopathic pulmonary fibrosis patients by proteomics technology / 中华流行病学杂志

Objective Applying the proteomics technology to identify proteins differentially in serums of idiopathic pulmonary fibrosis patients and normal population.Methods The study included serum samples from idiopathic pulmonary fibrosis group and normal controlled group with 30 cases of each,from the Second Hospital of Shandong University,between October 2014 and October 2015.Proteins differentially expressed in serums were quantified by the isobaric tags for relative and absolute quantization coupled with two-dimensional liquid chromatography/tandem mass spectrometry technology.The proteins were analyzed in terms of molecular function,cell location and biological processes for showing the key protein molecules which were related to the development of idiopathic pulmonary fibrosis.Results A total of 490 kinds of proteins (with confidence coefficient above 95％) were identified by mass spectrometry and 25 kinds of differentially expressed proteins were found.Compared with the control group,we found 4 types of up-regulated proteins and 21 downregulated ones in the serum of idiopathic pulmonary fibrosis patients.Data from the Gene ontology analysis showed that most differentially expressed proteins were in the extracellular region (92％) while pathway enrichment analysis showed that most proteins were involved in the complement and coagulation cascade pathway.Conclusion Proteins related to the complement system coagulation cascade pathway,and the proteins function need to be further studied.

Screening on serum biomarkers in idiopathic pulmonary fibrosis patients by proteomics technology / 中华流行病学杂志

Objective Applying the proteomics technology to identify proteins differentially in serums of idiopathic pulmonary fibrosis patients and normal population.Methods The study included serum samples from idiopathic pulmonary fibrosis group and normal controlled group with 30 cases of each,from the Second Hospital of Shandong University,between October 2014 and October 2015.Proteins differentially expressed in serums were quantified by the isobaric tags for relative and absolute quantization coupled with two-dimensional liquid chromatography/tandem mass spectrometry technology.The proteins were analyzed in terms of molecular function,cell location and biological processes for showing the key protein molecules which were related to the development of idiopathic pulmonary fibrosis.Results A total of 490 kinds of proteins (with confidence coefficient above 95％) were identified by mass spectrometry and 25 kinds of differentially expressed proteins were found.Compared with the control group,we found 4 types of up-regulated proteins and 21 downregulated ones in the serum of idiopathic pulmonary fibrosis patients.Data from the Gene ontology analysis showed that most differentially expressed proteins were in the extracellular region (92％) while pathway enrichment analysis showed that most proteins were involved in the complement and coagulation cascade pathway.Conclusion Proteins related to the complement system coagulation cascade pathway,and the proteins function need to be further studied.

Label-free quantitative proteomics reveals fibrinopeptide B and heparin cofactor II as potential serum biomarkers in respiratory syncytial virus-infected mice treated with Qingfei oral liquid formula / 中国天然药物

Respiratory syncytial virus (RSV) is a leading cause of acute lower respiratory tract infections. Qingfei oral liquid (QFOL), a traditional Chinese medicine, is widely used in clinical treatment for RSV-induced pneumonia. The present study was designed to reveal the potential targets and mechanism of action for QFOL by exploring its influence on the host cellular network following RSV infection. We investigated the serum proteomic changes and potential biomarkers in an RSV-infected mouse pneumonia model treated with QFOL. Eighteen BALB/c mice were randomly divided into three groups: RSV pneumonia model group (M), QFOL-treated group (Q) and the control group (C). Serum proteomes were analyzed and compared using a label-free quantitative LC-MS/MS approach. A total of 172 protein groups, 1009 proteins, and 1073 unique peptides were successfully identified. 51 differentially expressed proteins (DEPs) were identified (15 DEPs when M/C and 43 DEPs when Q/M; 7 DEPs in common). Classification and interaction network showed that these proteins participated in various biological processes including immune response, blood coagulation, complement activation, and so forth. Particularly, fibrinopeptide B (FpB) and heparin cofactor II (HCII) were evaluated as important nodes in the interaction network, which was closely involved in coagulation and inflammation. Further, the FpB level was increased in Group M but decreased in Group Q, while the HCII level exhibited the opposite trend. These findings not only indicated FpB and HCII as potential biomarkers and targets of QFOL in the treatment of RSV pneumonia, but also suggested a regulatory role of QFOL in the RSV-induced disturbance of coagulation and inflammation-coagulation interactions.

Screening of Serum Biomarkers for Distinguishing between Latent and Active Tuberculosis Using Proteome Microarray / 生物医学与环境科学（英文）

<p><b>OBJECTIVE</b>To identify potential serum biomarkers for distinguishing between latent tuberculosis infection (LTBI) and active tuberculosis (TB).</p><p><b>METHODS</b>A proteome microarray containing 4,262 antigens was used for screening serum biomarkers of 40 serum samples from patients with LTBI and active TB at the systems level. The interaction network and functional classification of differentially expressed antigens were analyzed using STRING 10.0 and the TB database, respectively. Enzyme-linked immunosorbent assays (ELISA) were used to validate candidate antigens further using 279 samples. The diagnostic performances of candidate antigens were evaluated by receiver operating characteristic curve (ROC) analysis. Both antigen combination and logistic regression analysis were used to improve diagnostic ability.</p><p><b>RESULTS</b>Microarray results showed that levels of 152 Mycobacterium tuberculosis (Mtb)-antigen- specific IgG were significantly higher in active TB patients than in LTBI patients (P < 0.05), and these differentially expressed antigens showed stronger associations with each other and were involved in various biological processes. Eleven candidate antigens were further validated using ELISA and showed consistent results in microarray analysis. ROC analysis showed that antigens Rv2031c, Rv1408, and Rv2421c had higher areas under the curve (AUCs) of 0.8520, 0.8152, and 0.7970, respectively. In addition, both antigen combination and logistic regression analysis improved the diagnostic ability.</p><p><b>CONCLUSION</b>Several antigens have the potential to serve as serum biomarkers for discrimination between LTBI and active TB.</p>

Label-free quantitative proteomics reveals fibrinopeptide B and heparin cofactor II as potential serum biomarkers in respiratory syncytial virus-infected mice treated with Qingfei oral liquid formula / 中国天然药物

Respiratory syncytial virus (RSV) is a leading cause of acute lower respiratory tract infections. Qingfei oral liquid (QFOL), a traditional Chinese medicine, is widely used in clinical treatment for RSV-induced pneumonia. The present study was designed to reveal the potential targets and mechanism of action for QFOL by exploring its influence on the host cellular network following RSV infection. We investigated the serum proteomic changes and potential biomarkers in an RSV-infected mouse pneumonia model treated with QFOL. Eighteen BALB/c mice were randomly divided into three groups: RSV pneumonia model group (M), QFOL-treated group (Q) and the control group (C). Serum proteomes were analyzed and compared using a label-free quantitative LC-MS/MS approach. A total of 172 protein groups, 1009 proteins, and 1073 unique peptides were successfully identified. 51 differentially expressed proteins (DEPs) were identified (15 DEPs when M/C and 43 DEPs when Q/M; 7 DEPs in common). Classification and interaction network showed that these proteins participated in various biological processes including immune response, blood coagulation, complement activation, and so forth. Particularly, fibrinopeptide B (FpB) and heparin cofactor II (HCII) were evaluated as important nodes in the interaction network, which was closely involved in coagulation and inflammation. Further, the FpB level was increased in Group M but decreased in Group Q, while the HCII level exhibited the opposite trend. These findings not only indicated FpB and HCII as potential biomarkers and targets of QFOL in the treatment of RSV pneumonia, but also suggested a regulatory role of QFOL in the RSV-induced disturbance of coagulation and inflammation-coagulation interactions.

Effect of a Randomized Controlled Trial Walking Program on Walking, Stress, Depressive Symptoms and Cardiovascular Biomarkers in Elderly Korean Immigrants

PURPOSE: Despite well-known benefits of walking on cardiovascular health, no structured walking exercise program has been formally tested on elderly Korean immigrants (EKIs). This pilot randomized controlled trial study assessed the effect of a walking program on walking behavior (pedometer steps count), stress (cortisol), depressive symptoms (CESD-10), and cardiovascular disease biomarkers (hs-CRP and fibrinogen) via venipuncture in EKIs. METHODS: Seventy EKIs recruited from a Korean community were randomly assigned to a 12-week walking group or control group in a 3:2 ratio. The working program included a pedometer, buddy, monthly coffee card, weekly call for goal setting, and physical activity consultation. Walking group EKIs maintained the Centers for Disease Control and Prevention recommended exercise guidelines and good mental health status over 12 weeks. RESULTS: There was no significant difference in the outcomes between control and walking groups. CONCLUSION: Social networking with Koreans in the senior center and church from a well-established Korean community might have positive effects on mental health.

Screening serum biomarkers in gastric cancer by iTRAQ-Coupled 2D-LC-MS/MS / 实用医学杂志

Objective To apply the Isobaric tags for relative and absolute quantitation (iTRAQ) to identify proteins differentially in serums of gastric cancer (GC) patients, gastric mucosal intestinal metaplasia (IM) patients and normal control population. Methods The study included serum samples from GC group, IM group and normal control group with 45 cases each group,Proteins differentially regulated in serums were identified by the iTRAQ coupled with two-dimensional liquid chromatography/tandem mass spectrometry (2D-LC-MS/MS) technology. Results 10 540 unique peptides , of which correspond to a set of 199 proteins were identified , 23 proteins were over expressed and 14 proteins were underexpressed in GC and IM.Nine immune response proteins such as Lipopolysaccharide-binding protein,C-reactive protein and Ficolin-3 were found in the differential proteins, implying a close linkage between immune response and GC. Conclusions iTRAQ technology may help to identify novel serum markers for early diagnosis of GC.

Staging and neuroprogression in bipolar disorder: a systematic review of the literature

INTRODUCTION: The use of clinical staging models is emerging as a novel and useful paradigm for diagnosing severe mental disorders. The term "neuroprogression" has been used to define the pathological reorganization of the central nervous system along the course of severe mental disorders. In bipolar disorder (BD), neural substrate reactivity is changed by repeated mood episodes, promoting a brain rewiring that leads to an increased vulnerability to life stress. METHOD: A search in the PubMed database was performed with the following terms: "staging", "neuroprogression", "serum", "plasma", "blood", "neuroimaging", "PET scan", "fMRI", "neurotrophins", "inflammatory markers" and "oxidative stress markers", which were individually crossed with "cognition", "functionality", "response to treatments" and "bipolar disorder". The inclusion criteria comprised original papers in the English language. Abstracts from scientific meetings were not included. RESULTS: We divided the results according to the available evidence of serum biomarkers as potential mediators of neuroprogression, with brain imaging, cognition, functioning and response to treatments considered as consequences. CONCLUSION: The challenge in BD treatment is translating the knowledge of neuronal plasticity and neurobiology into clinical practice. Neuroprogression and staging can have important clinical implications, given that early and late stages of the disorder appear to present different biological features and therefore may require different treatment strategies.

Transthyretin-down-regulation in sera of cholangiocarcinoma / 中华肝胆外科杂志

Objective As SELDI-TOF-MS (Surface Enhanced Laser Desorption/Ionization Time of Flight Mass Spectrometry) has been broadly used to screen biomarkers for a variety of diseases, the identification and validation of the revealed biomarkers requires more focused attention.Method In this paper, the serum samples from 60 cholangiocarcinoma, 146 lung cancer, 65 LGC and 58 LPC, 49 benign diseases of hepatobiliary and 53 normal individuals were analyzed by SELDI-TOF-MS. Results Among a set of proteins automatically selected as specific biomarkers by Biomarker Wizard software, three protein peaks, with molecular weights of 13. 71 × 103 , 13.83 × 103 and 13. 99 ×103 , were found significantly decreased in cholangiocarcinoma samples. The candidate biomarkers obtained from Tricine-SDS-PAGE gel bands by matching the molecular weight with peaks on CM10 chips were identified by Mass spectrometry as the native transthyretin(native TTR),cysTTR and glutTTR.These preliminary results were further proven by immunoprecipitation using commercial TTR antibodies. This allowed us to re-measure the TTR levels in all the groups more simply by ELISA assay. It showed a firm consistency between ELISA and SELDI analysis. In addition, while TTR levels in cholangiocarcinoma were found to be lower than those in normal healthy controls, TTR levels in benign diseases of the hepatobiliary system were found to be higher than those in healthy controls.Conclusion TTR could be a biomarker that better discriminates cholangiocarcinoma patients from the benign diseases compared to other biomarkers presently available.

Serum protein profiling to identify biomarkers for small renal cell carcinoma.

Diagnostic biomarkers for early detection of renal cell carcinoma (RCC) are in great need. In the present study, we compared the serum protein profiles of patients with small RCC to those of healthy individuals to identify the differentially expressed proteins with potential to serve as biomarkers. Serum samples were collected from 10 patients with small RCC and 10 healthy individuals. The serum protein expression profiles were analyzed by two-dimensional (2-D) gel electrophoresis. Twenty-seven proteins with differences in expression levels between RCC patients and healthy volunteers were identified. Of these, 19 were expressed at different levels and eight were expressed in serum from the RCC group, but not from the control group. Six differentially expressed proteins identified by using mass spectrometry included coagulation factor XIII B, complement C3 and its precursor, misato homolog 1 (isoform CRA_b), hemopexin, and alpha-1-B-glycoprotein. Some of these serum proteins are known regulators of tumor progression in human malignancies. In conclusion, we successfully applied 2-D gel electrophoresis and identified six serum proteins differentially expressed between patients with small RCC and healthy volunteers. These proteins may provide novel biomarkers for early detection and diagnosis of human RCC.