High-Efficiency Effect-Directed Analysis Leveraging Five High Level Advancements: A Critical Review.

Organic contaminants are ubiquitous in the environment, with mounting evidence unequivocally connecting them to aquatic toxicity, illness, and increased mortality, underscoring their substantial impacts on ecological security and environmental health. The intricate composition of sample mixtures and uncertain physicochemical features of potential toxic substances pose challenges to identify key toxicants in environmental samples. Effect-directed analysis (EDA), establishing a connection between key toxicants found in environmental samples and associated hazards, enables the identification of toxicants that can streamline research efforts and inform management action. Nevertheless, the advancement of EDA is constrained by the following factors: inadequate extraction and fractionation of environmental samples, limited bioassay endpoints and unknown linkage to higher order impacts, limited coverage of chemical analysis (i.e., high-resolution mass spectrometry, HRMS), and lacking effective linkage between bioassays and chemical analysis. This review proposes five key advancements to enhance the efficiency of EDA in addressing these challenges: (1) multiple adsorbents for comprehensive coverage of chemical extraction, (2) high-resolution microfractionation and multidimensional fractionation for refined fractionation, (3) robust in vivo/vitro bioassays and omics, (4) high-performance configurations for HRMS analysis, and (5) chemical-, data-, and knowledge-driven approaches for streamlined toxicant identification and validation. We envision that future EDA will integrate big data and artificial intelligence based on the development of quantitative omics, cutting-edge multidimensional microfractionation, and ultraperformance MS to identify environmental hazard factors, serving for broader environmental governance.

Occurrence and Prioritization of Human Androgen Receptor Disruptors in Sewage Sludges Across China.

The global practice of reusing sewage sludge in agriculture and its landfill disposal reintroduces environmental contaminants, posing risks to human and ecological health. This study screened sewage sludge from 30 Chinese cities for androgen receptor (AR) disruptors, utilizing a disruptor list from the Toxicology in the 21st Century program (Tox21), and identified 25 agonists and 33 antagonists across diverse use categories. Predominantly, natural products 5α-dihydrotestosterone and thymidine emerged as agonists, whereas the industrial intermediate caprolactam was the principal antagonist. In-house bioassays for identified disruptors displayed good alignment with Tox21 potency data, validating employing Tox21 toxicity data for theoretical toxicity estimations. Potency calculations revealed 5α-dihydrotestosterone and two pharmaceuticals (17ß-trenbolone and testosterone isocaproate) as the most potent AR agonists and three dyes (rhodamine 6G, Victoria blue BO, and gentian violet) as antagonists. Theoretical effect contribution evaluations prioritized 5α-dihydrotestosterone and testosterone isocaproate as high-risk AR agonists and caprolactam, rhodamine 6G, and 8-hydroxyquinoline (as a biocide and a preservative) as key antagonists. Notably, 16 agonists and 20 antagonists were newly reported in the sludge, many exhibiting significant detection frequencies, concentrations, and/or toxicities, demanding future scrutiny. Our study presents an efficient strategy for estimating environmental sample toxicity and identifying key toxicants, thereby supporting the development of appropriate sludge management strategies.

Effect-directed analysis of androgenic compounds from sewage sludges in China.

The safety of municipal sewage sludge has raised great concerns because of the accumulation of large-scale endocrine disrupting chemicals in the sludge during wastewater treatment. The presence of contaminants in sludge can cause secondary pollution owing to inappropriate disposal mechanisms, posing potential risks to the environment and human health. Effect-directed analysis (EDA), involving an androgen receptor (AR) reporter gene bioassay, fractionation, and suspect and nontarget chemical analysis, were applied to identify causal AR agonists in sludge; 20 of the 30 sludge extracts exhibited significant androgenic activity. Among these, the extracts from Yinchuan, Kunming, and Shijiazhuang, which held the most polluted AR agonistic activities were prepared for extensive EDA, with the dihydrotestosterone (DHT)-equivalency of 2.5 - 4.5 ng DHT/g of sludge. Seven androgens, namely boldione, androstenedione, testosterone, megestrol, progesterone, and testosterone isocaproate, were identified in these strongest sludges together, along with testosterone cypionate, first reported in sludge media. These identified androgens together accounted for 55 %, 87 %, and 52 % of the effects on the sludge from Yinchuan, Shijiazhuang, and Kunming, respectively. This study elucidates the causative androgenic compounds in sewage sludge and provides a valuable reference for monitoring and managing androgens in wastewater treatment.

Thermokarst lake susceptibility assessment using machine learning models in permafrost landscapes of the Arctic.

Ice-rich permafrost thaws in response to rapid Arctic warming, and ground subsidence facilitates the formation of thermokarst lakes. Thermokarst lakes transform the surface energy balance of permafrost, affecting geomorphology, hydrology, ecology, and infrastructure stability, which can further contribute to greenhouse gas emissions. Currently, the spatial distribution of thermokarst lakes at large scales remains a challenging task. Based on multiple high-resolution environmental factors and thermokarst lake inventories, we used machine learning methods to estimate the spatial distributions of present and future thermokarst lake susceptibility (TLS) maps. We also identified key environmental factors of the TLS map. At 1.8 × 106 km2, high and very high susceptible regions were estimated to cover about 10.4 % of the region poleward of 60°N, which were mainly distributed in permafrost-dominated lowland regions. At least 23.9 % of the area of TLS maps was projected to disappear under representative concentration pathway scenarios (RCPs), with increased susceptibility levels in northern Canada. The slope was the key conditioning factor for the occurrence of thermokarst lakes in Arctic permafrost regions. Compared with similar studies, the reliability of the TLS map was further evaluated using probability calibration curve and coefficient of variation (CV). Our results provide a means for assessing the spatial distribution of thermokarst lakes at the circum-Arctic scale but also improve the understanding of their dynamics in response to the climate system.

Enhancing anaerobic digestion in anaerobic integrated floating fixed-film activated sludge (An-IFFAS) system using novel electron mediator suspended biofilm carriers.

Suspended biofilm carriers mediating direct interspecies electron transfer (DIET)-based syntrophic metabolism is a promising strategy to enhance anaerobic digestion and methane production by associating the advantages of conductive suspended biofilm carriers and anaerobic integrated floating fixed-film and activated sludge (An-IFFAS) process. However, the current knowledge of DIET using conductive suspended biofilm carrier is still limited. In this study, novel electron mediator suspended biofilm carriers had been prepared by introducing a series of graphite powders (3 wt%, 5 wt% and 7 wt%) into high-density polyethylene (HDPE), and applied in An-IFFAS reactors. Results showed that An-IFFAS reactors filled with graphite-modified carriers could enhance the degradation of organic matters and the production of methane significantly in comparison with the control reactor filled with conventional HDPE carriers at organic loading rates (OLRs) of 5.9-23.7 kg COD/m3/d. Microbial analysis proved that 7 wt% graphite-modified carrier improved approximately 4.2% abundance of Geobacter and 7.3% abundance of electrotrophic methanogens (Methanothrix) that exchange electron via DIET comparing with that of HDPE carriers, respectively. These findings demonstrated that electron mediator suspended biofilm carrier was able to potentially proceed DIET and enhance the efficiency of anaerobic digestion and recover CH4-related energy.

New technique of pectoral muscle flap reconstruction for 23 patients with deep sternal wound infections / 中国胸心血管外科临床杂志

@#Objective    To study the effect of deep sternal wound infections（DSWIs）treated by the techniques of pectoral major muscular(PM) turnover and non-suture remain after the wound restitution. Method    We retrospectively analyzed the clinical data of 23 patients with DSWIs in our hospital between June 2016 and December 2016. There were 13 males and 10 females at age of 4-73(54.5±19.5) years. There were 8 patients with concomitant diabetes mellitus and 1 patient with chronic obstructive pulmonary disease(COPD) and brain infarction. Eigteen patients were of type Ⅱ, 5 patients of type Ⅲ according to Pairolero’ classification in the DSWIs. Five patients were with remaining abscess cavity in the mediastinum by thoracic compute tomography(CT). Under general anesthesia the DSWIs debrided thoroughly. The PM elevated from the anterior pectoralis major fascia off subcutaneous tissue to lateral to anterior axillary line, the PM cutted off, then made to the muscle flap, turnover PM flap filled and fixed to sternal wound by lighten tensile suture, the subcutaneous tissue and skin sutured by cutting full-thickness. Results    The sternal reconstruction after debridement of the sternal wound was used by bilateral PM flap in the 17 patients, unilateral PM in 6 patients. There were 21(91.3%) patients in stage Ⅰ healing, 2 patients deferment healing of local cut skin without reoperation. There were 22 patients with non-paradoxical breathing during the postoperation. One death resulted from multiple-organ failure of the concomitant disease. The average of hospital day was 10.6 days. The wound healing was good by chest CT at 1 month after the operation. Conclusion    The sternal forming by the technique of the PM flap turnover, without remain of fremde stoffe in wound for DSWIs is distinctive method, evident effect.

Effects of Pectus Excavatum on the Spine of Pectus Excavatum Patients with Scoliosis.

BACKGROUND: There is high risk in the correction surgery of pectus excavatum with scoliosis because of the lack of the correction mechanism of pectus excavatum with scoliosis. This study performed a comprehensive analysis about the impact that pectus excavatum had on scoliosis and elaborated its biomechanical mechanism in pectus excavatum patients with scoliosis. METHODS: 37 pectus excavatum patients were selected. According to age, Haller index of pectus excavatum, offset coefficient, vertical position, sternal torsion angle, and asymmetric index, 37 patients were, respectively, divided into 2 compared groups. The result was statistically calculated. RESULTS: The scoliosis incidence and severity did not correlate with Haller index, offset coefficient, vertical position, sternal torsion angle, and asymmetric index of pectus excavatum, and there was no statistical significance between the two compared groups. CONCLUSIONS: The incidence and severity of scoliosis in PE patients with scoliosis have nothing to do with the geometric parameters of pectus excavatum but correlate with age. The scoliosis will aggravate with the increase of age. The heart may provide an asymmetric horizontal force to push the spines to the right. The mechanism of how the biomechanical factors exert influences on spines needs to be further investigated to keep the spine stable.

Metal-Chelate Affinity Precipitation with Thermo-Responsive Polymer for Purification of ε-Poly-L-Lysine.

ε-Poly-L-lysine (ε-PL) is a natural preservative for food processing industry. A thermo-responsive polymer, attached with Cu2+ or Ni2+, was prepared for metal-chelate affinity precipitation for purification of ε-PL. The low critical solution temperatures (LCSTs) of these polymers were close to the room temperature (31.0-35.0 °C). The optimal adsorption conditions were as follows: pH 4.0, 0 mol/L NaCl, ligand density 75.00 µmol/g, and 120 min. The ligand Cu2+ showed a stronger affinity interaction with ε-PL and the highest adsorption amount reached 251.93 mg/g polymer. The elution recovery of ε-PL could be 98.42% with 0.50 mol/L imidazole (pH = 8.0) as the eluent. The method could purify ε-PL from fermentation broth and the final product was proved as electrophoretic pure by SDS-PAGE. Moreover, these affinity polymers could be recycled after the purification of ε-PL and the recoveries were above 95.00%. Graphical Abstract Scheme for affinity precipitation of ε-PL.

Numerical Simulation and Clinical Verification of the Minimally Invasive Repair of Pectus Excavatum.

OBJECTIVE: In this article we proposed a modeling method by building an assembled model to simulate the orthopedic process of minimally invasive surgery for pectus excavatum and got the clinical verification, which aims to provide some references for clinic diagnoses, treatment, and surgery planning. METHODS: The anterior chest model of a 15-year-old patient was built based on his CT images; and his finite element model and the Nuss bar were created. Coupling of nodal displacement was used to connect bones with cartilages of the anterior chest. Turning the Nuss bar over is completed by rotating displacement of it. By comparing the numerical simulation outcomes with clinical surgery results, the numerical simulation results were verified. RESULTS: The orthopedic process of minimally invasive surgery of pectus excavatum was simulated by model construction and numerical analysis. The stress, displacement fields and distribution of the contact pressure between the Nuss bar and costal cartilages were analyzed. The relationship between correcting force and displacement was obtained. Compared with the of clinical results, the numerical simulation results were close to that of the actual clinical surgery in displacement field, and the final contact position of the Nuss bar and the costal cartilages. CONCLUSION: Compared with the rigid model, the assembled simulation model is in more conformity with the actual clinical practice. The larger curvature results in the maximum equivalent stress, which is the main reason for clinical pain. Soft tissues and muscles should be taken into account in the numerical simulation process.

Depleting NFAT1 expression inhibits the ability of invasion and migration of human lung cancer cells.

BACKGROUND: Nuclear factor of activated T-cells (NFAT) is a general name applied to a family of transcription factors shown to be important in immune response. One or more members of the NFAT family are expressed in most cells of the immune system. NFAT1 is considered to involve in the development of cardiac, skeletal muscle, nervous systems, and tumorigenesis. METHODS: In the current study, we analyzed MEKK1 expression in 159 surgically resection non-small cell lung cancer patient's samples by immunohistochemistry and determined its role in SK-EMS-1 cells via RNAi experiment. RESULTS: The abilities of invasion, motility, and adhesion of SK-EMS-1 cells were detected by transwell assay, wound healing assay and adhesion assay, respectively. The result showed NFAT1 was highly expressed in lung tumor tissues instead of adjacent lung tissues (54.1% vs 8.8%, p < 0.05); its overexpression was positively correlated with lymph node metastasis (p < 0.05). Depleting its expression in SK-EMS-1 cells can inhibit its invasion and migration abilities significantly (p < 0.05); and also can reduce proliferation of lung cancer cells (p < 0.05). CONCLUSION: Our study showed NFAT1 plays an important role in origination, invasion and metastasis of non-small lung cancer cells; its underlying action mechanism needs further study.

Early results of 18 adults, following a modified Nuss operation for recurrent pectus excavatum.

OBJECTIVES: The minimally-invasive Nuss operation has been widely used for correcting pectus excavatum in children. However, a number of adult patients require reoperations for recurrence or other complications. This work aimed to investigate the early results of recurrent pectus excavatum repair using a modified Nuss procedure, which were seldom reported in adult patients. METHODS: A retrospective chart review was conducted on 18 adult patients who underwent modified Nuss procedure in the age range of 18-31 years. The Haller index of the patients ranged from 3.2 to 6.5. In the modified Nuss technique, a small auxiliary incision was made below the xiphoid process and one finger was inserted instead of a thoracoscope. The introducer was guided by the finger, slowly advanced across the mediastinum and raised the sternum and the anterior chest wall to the desired position. The Lorenz correction bar was introduced through the tunnel, placed in position, and turned over so that the convexity faced anteriorly. RESULTS: The operations were performed successfully and no operative mortality occurred. The mean operating time was 68.5 ± 15.5 min. The postoperative results were excellent in 77.8% of patients and good in 22.2%. Early complications were mild and no late complications occurred. CONCLUSIONS: The modified Nuss procedure is an excellent reoperative correction for adult patients and has outstanding early results, considering that it is technically challenging.

[Effectiveness of minimally invasive surgery for pectus excavatum in adults].

OBJECTIVE: To investigate the effect of anterior chest wall depression on the cardiac function and the effectiveness of minimally invasive surgery for pectus excavatum by comparing cardiac function and morphology between pre- and post-operation. METHODS: Between August 2009 and December 2010, 102 adult patients with pectus excavatum were treated with minimally invasive surgery, including the primary operation in 95 cases and the reoperation in 7 cases. There were 84 males and 18 females, aged 18-57 years (mean, 23.4 years). The haller index (HI) was 4.59 +/- 1.51. Of 102 patients, 59 were classified as pectus excavatum type I and 43 as type II; 42 had clinical symptoms and 19 had the physical sign of heart. The preoperative chest CT examination showed cardiac compression in all patients and heart displacement in 74 patients. The left ventricular ejection fraction (LVEF) was 68.9% +/- 6.2%. RESULTS: The procedure was successful in all patients, and no death or serious complication occurred. The patients were followed up 12-28 months (mean, 21 months). The clinical symptoms and cardiac physical sign of the patients disappeared after operation. HI was 2.70 +/- 0.33 at 12 months after operation, showing significant difference when compared with preoperative HI (t = 5.83, P = 0.00). According to Nuss's evaluation method, the results were excellent in 99 patients and good in 3 patients. CT examination showed complete relief of cardiac compression in 101 patients and mild cardiac compression in 1 patient; the heart position was normal at 12 months after operation. Electrocardiogram returned to normal in 4 patients having abnormal electrocardiogram. LVEF was 70.5% + 4.8% after operation, showing no significant difference when compared with preoperative LVEF (t = 1.08, P = 0.30). CONCLUSION; The main effects of pectus excavatum in adults on heart are compression and displacement. Cardiac compression may be relieved efficiently and the patient's clinical symptoms can be abated by minimally invasive surgery.

Acute respiratory distress caused by esophageal duplication canceration in an adult.

Esophageal duplication (ED) in adults is rare, and ED canceration is very rare. We report a case of acute respiratory embarrassment caused by ED with squamous carcinoma in a 39-year-old man and a review of the literature.

A combined biomarker pattern improves the discrimination of lung cancer.

A total of 227 sera were analysed using surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF MS) to find novel serum biomarkers for lung cancer. The results showed that the 11.53, 11.70, 13.78, 13.90 and 14.07 k m/z peaks identified as native serum amyloid A (SAA), SAA with N-terminal Arg cleaved, native transthyretin (TTR) and its two variants significantly differentiated lung cancer sera from normal control sera (p <0.01). A 'biomarker pattern' combining SAA and TTR was tested to distinguish lung cancer patients from normal control individuals, and the diagnostic positive rate of lung cancer was improved to 91.6%.

Association of dynamic changes in serum cytokine levels with the severity of injury in patients suffering from closed chest traumas complicated with pulmonary contusions.

This study aimed to examine the dynamic changes in the serum levels of tumor necrosis factor (TNF)-α, interleukin (IL)-6 and IL-10 in patients suffering from closed chest injuries and concomitant pulmonary contusions and their correlation with the Thoracic Trauma Severity Score (TTS) and Injury Severity Score (ISS). Patients with multiple traumas with an ISS ≥16 (n=41) were evaluated in the study. Patients included 21 individuals with trauma complicated by pulmonary contusion and 20 patients with trauma without contusion. Venous blood samples were collected from the patients on days 1, 2, 3, 5 and 7 following trauma to assess serum levels of TNF-α, IL-6 and IL-10, whose correlation with TTS and ISS was analyzed. Levels of TNF-α, IL-6 and IL-10 remained significantly higher in the patients with trauma complicated by contusion compared to the patients with trauma without contusion (P<0.01). These three cytokines were positively correlated with TTS and ISS in the patients with trauma complicated by contusion. Serum TNF-α, IL-6 and IL-10 levels increased significantly in the patients with trauma complicated by pulmonary contusion. In conclusion, both cytokine assays and TTS facilitate the accurate assessment of the severity of chest injury.

[Selective Expression of Calcium-Binding Protein S100A7 in Lung Cancer.].

BACKGROUND: S100A7 is a member of S100 family and its overexpression has been previously associated with carcinogenesis of certain cancers. The aim of this study is to explore the expression of calcium-binding protein S100A7 in lung cancer. METHODS: In the present study, RT-PCR, Western-blot and immunohistochemistry were used to analyze the different expression of S100A7 in lung cancer tissues and paired noncancerous lung tissues. RESULTS: The specific expression of S100A7 was found in squamous cell carcinomas and large cell lung carcinomas, whereas it was not detected in adenocarcinomas, small cell carcinomas, other cell types of lung cancer and normal lung tissues as well as paired noncancerous lung tissues. CONCLUSIONS: S100A7 was selectively expressed in squamous cell carcinomas and large cell lung carcinomas and may serve as a potential marker for lung cancer diagnosis.

[A new serum biomarker for lung cancer - transthyretin.].

BACKGROUND: Lung cancer is the leading cause of cancer death worldwide and very few specific biomarkers could be used in clinical diagnosis at present. The aim of this study is to find novel potential serum biomarkers for lung cancer using Surface Enhanced Laser Desorption/Ionization (SELDI) technique. METHODS: Serum sample of 227 cases including 146 lung cancer, 13 pneumonia, 28 tuberculous pleurisy and 40 normal individuals were analyzed by CM10 chips. The candidate biomarkers were identified by ESI/MS-MS and database searching, and further confirmed by immunoprecipitation. The same sets of serum sample from all groups were re-measured by ELISA assay. RESULTS: Three protein peaks with the molecular weight 13.78 kDa, 13.90 kDa and 14.07 kDa were found significantly decreased in lung cancer serum compared to the other groups and were all automatically selected as specific biomarkers by Biomarker Wizard software. The candidate biomarkers obtained from 1-D SDS gel bands by matching the molecular weight with peaks on CM10 chips were identified by Mass spectrometry as the native transthyretin (nativeTTR), cysTTR and glutTTR, and the identity was further validated by immunoprecipitation using commercial TTR antibodies. Downregulated of TTR was found in both ELISA and SELDI analysis. CONCLUSIONS: TTRs acted as the potentially useful biomarkers for lung cancer by SELDI technique.

Tumor with watery diarrhoea, hypokalaemia in a 3-year-old girl.

Watery diarrhoea, hypokalaemia and achlorhydria (WDHA) syndrome was caused by vasoactive intestinal polypeptide (VIP)-producing tumour. A 3-year-old Chinese girl with watery diarrhoea, abdominal distension and hypokalaemia due to a thoracic paraspinal VIP-secreting ganglioneuroma is reported. The girl coughed, fevering up to 39 degrees C after a flu-like episode. She had eight to ten abundant stools daily which is not improved by dietary treatment, resulting in an important weight loss. She weighed 6.8 kg (nl P50 at 6 months of age) and is 76 cm (nl P50 at 9 months of age) in height. Blood electrolytes showed 129 mmol/L sodium, 2.42 mmol/L potassium, 94 mmol/L chloride and 18.6 mmol/L bicarbonate; urinary catecholamines were normal. Computed tomography scan evidenced a left side paravertebral mass of 4 x 6 cm in the lower thoracic region leading to the blood determination of vasoactive intestinal polypeptide which amounted 830 pmol/L(normal < 25 pmol/L). Surgical removal showed a ganglioneuroma of 160 g and was associated with disappearance of the diarrhoea and normalization of VIP level below 20 pmol/L. Review of the 63 reported cases in children with WDHA showed that many of the cases presented with non-treatable watery diarrhoea, hypokalaemia. Achlorhydria is not necessarily part of the WDHA syndrome. The male to female ratio is 1:1.5. Ganglioneuroblastoma and ganglioneuroma are the commonest tumours. Location of the tumour is variable: abdomen, chest or neck. Abdominal distension, flushing, episodic hypertension and colonic dilatation, constipation and ataxia were the other associated features. Surgical resection is the treatment of choice of VIP-producing tumours.

[Diagnosis and treatment of pulmonary aspergillosis in patients without immunodeficiency: report of 15 cases].

OBJECTIVE: To study the diagnosis and treatment of pulmonary aspergillosis in patients without immunodeficiency. METHOD: Pulmonary aspergillosis in 15 patients without immunodeficiency was reviewed. RESULTS: Twelve of the patients had underlying lung diseases (lung cancer), 2 showed masses in the lung by radiography and CT halo, and 1 had aspergilloma within the left main bronchus. The diagnosis of intra-cavitary aspergilloma had been made in all the patients with lung cancer before surgery. Only 3 cases were confirmed by fungal examination before surgery. Thirteen patients received surgical removal of the lesions, and the post-operative recovery was uneventful. Antifungal therapy and open drainage were administered in 1 patient with pleural residual cavity infection, but the treatment failed. Anti-cancer therapy alone was given in 1 patient. Sudden death occurred in another patient. CONCLUSION: In suspected cases of aspergillosis, CT halo sign, histology examination are helpful for the diagnosis. Aspergilloma complicated with underlying lung diseases and mass lesions can be cured by surgery.

[Identification and clinical evaluation of lung cancer serum biomarker L-lactate dehydrogenase B].

OBJECTIVE: To identify potential biomarkers related with lung cancer metastasis. METHODS: Conditional media proteins collected from a primary non-small cell lung cancer cell line (NSCLC) NCI-H226 and its brain metastatic subline H226Br were analyzed by SDS-PAGE and MALDI-TOF-MS. Twelve biomarkers were identified, of which LDHB was significantly up-regulated in H226Br cell and was further validated using ELISA in sera including 105 lung cancer samples, 41 pneumonia and pulmonary tuberculosis samples and 65 healthy samples. RESULTS: The levels of LDHB were specifically elevated in NSCLC sera [A value 0.485 (0 - 1.415)] compared with pneumonia and pulmonary tuberculosis [A value 0.187 (0 - 0.609), P < 0.01] and healthy group [A value, 0.159 (0 - 0.524), P < 0.01] and were progressively increased with the clinical stage. At the cutoff point 0.260 (A value) on the ROC curve, the sensitivity, specificity and total accuracy of LDHB were 81%, 70% and 76% respectively. CONCLUSION: These findings demonstrated that secretome could open up a possibility to identify novel biomarkers related with cancer occurrence and metastasis.