Systematic proteome-wide Mendelian randomization using the human plasma proteome to identify therapeutic targets for lung adenocarcinoma.

BACKGROUND: Lung adenocarcinoma (LUAD) is the predominant histological subtype of lung cancer and the leading cause of cancer-related mortality. Identifying effective drug targets is crucial for advancing LUAD treatment strategies. METHODS: This study employed proteome-wide Mendelian randomization (MR) and colocalization analyses. We collected data on 1394 plasma proteins from a protein quantitative trait loci (pQTL) study involving 4907 individuals. Genetic associations with LUAD were derived from the Transdisciplinary Research in Cancer of the Lung (TRICL) study, including 11,245 cases and 54,619 controls. We integrated pQTL and LUAD genome-wide association studies (GWASs) data to identify candidate proteins. MR utilizes single nucleotide polymorphisms (SNPs) as genetic instruments to estimate the causal effect of exposure on outcome, while Bayesian colocalization analysis determines the probability of shared causal genetic variants between traits. Our study applied these methods to assess causality between plasma proteins and LUAD. Furthermore, we employed a two-step MR to quantify the proportion of risk factors mediated by proteins on LUAD. Finally, protein-protein interaction (PPI) analysis elucidated potential links between proteins and current LUAD medications. RESULTS: We identified nine plasma proteins significantly associated with LUAD. Increased levels of ALAD, FLT1, ICAM5, and VWC2 exhibited protective effects, with odds ratios of 0.79 (95% CI 0.72-0.87), 0.39 (95% CI 0.28-0.55), 0.91 (95% CI 0.72-0.87), and 0.85 (95% CI 0.79-0.92), respectively. Conversely, MDGA2 (OR, 1.13; 95% CI 1.08-1.19), NTM (OR, 1.12; 95% CI 1.09-1.16), PMM2 (OR, 1.35; 95% CI 1.18-1.53), RNASET2 (OR, 1.15; 95% CI 1.08-1.21), and TFPI (OR, 4.58; 95% CI 3.02-6.94) increased LUAD risk. Notably, none of the nine proteins showed evidence of reverse causality. Bayesian colocalization indicated that RNASET2, TFPI, and VWC2 shared the same variant with LUAD. Furthermore, NTM and FLT1 demonstrated interactions with targets of current LUAD medications. Additionally, FLT1 and TFPI are currently under evaluation as therapeutic targets, while NTM, RNASET2, and VWC2 are potentially druggable. These findings shed light on LUAD pathogenesis, highlighting the tumor-promoting effects of RNASET2, TFPI, and NTM, along with the protective effects of VWC2 and FLT1, providing a significant biological foundation for future LUAD therapeutic targets. CONCLUSIONS: Our proteome-wide MR analysis highlighted RNASET2, TFPI, VWC2, NTM, and FLT1 as potential drug targets for further clinical investigation in LUAD. However, the specific mechanisms by which these proteins influence LUAD remain elusive. Targeting these proteins in drug development holds the potential for successful clinical trials, providing a pathway to prioritize and reduce costs in LUAD therapeutics.

IL20Rb aggravates pulmonary fibrosis through enhancing bone marrow derived profibrotic macrophage activation.

Idiopathic pulmonary fibrosis (IPF) is one of the most fatal chronic interstitial lung diseases with unknown pathogenesis, current treatments cannot truly reverse the progression of the disease. Pulmonary macrophages, especially bone marrow derived pro-fibrotic macrophages, secrete multiple kinds of profibrotic mediators (SPP1, CD206, CD163, IL-10, CCL18…), thus further promote myofibroblast activation and fibrosis procession. IL20Rb is a cell-surface receptor that belongs to IL-20 family. The role of IL20Rb in macrophage activation and pulmonary fibrosis remains unclear. In this study, we established a bleomycin-induced pulmonary fibrosis model, used IL4/13-inducing THP1 cells to induce profibrotic macrophage (M2-like phenotype) polarization models. We found that IL20Rb is upregulated in the progression of pulmonary fibrosis, and its absence can alleviate the progression of pulmonary fibrosis. In addition, we demonstrated that IL20Rb promote the activation of bone marrow derived profibrotic macrophages by regulating the Jak2/Stat3 and Pi3k/Akt signaling pathways. In terms of therapeutic strategy, we used IL20Rb neutralizing antibodies for animal administration, which was found to alleviate the progression of IPF. Our results suggest that IL20Rb plays a profibrotic role by promoting profibrotic macrophage polarization, and IL20Rb may become a potential therapeutic target for IPF. Neutralizing antibodies against IL20Rb may become a potential drug for the clinical treatment of IPF.

Exploring the optimal indicator of short-term peridiagnosis weight dynamics to predict cancer survival: A multicentre cohort study.

BACKGROUND: Body weight and its changes have been associated with cancer outcomes. However, the associations of short-term peridiagnosis weight dynamics in standardized, clinically operational time frames with cancer survival remain largely unknown. This study aimed to screen for and evaluate the optimal indicator of short-term peridiagnosis weight dynamics to predict overall survival (OS) in patients with cancer. METHODS: This multicentre cohort study prospectively collected data from 7460 patients pathologically diagnosed with cancer between 2013 and 2019. Body weight data were recorded 1 month before, at the time of and 1 month following diagnosis. By permuting different types (point value in kg, point height-adjusted value in kg/m2, absolute change in kg or relative change in percentage) and time frames (prediagnosis, postdiagnosis or peridiagnosis), we generated 12 different weight-related indicators and compared their prognostic performance using Harrell's C-index, integrated discrimination improvement, continuous net reclassification improvement and time-dependent C-index. We analysed associations of peridiagnosis relative weight change (RWC) with OS using restricted cubic spine (RCS), Kaplan-Meier analysis and multivariable-adjusted Cox regression models. RESULTS: The study enrolled 5012 males and 2448 females, with a median age of 59 years. During a median follow-up of 37 months, 1026 deaths occurred. Peridiagnosis (1 month before diagnosis to 1 month following diagnosis) RWC showed higher prognostic performance (Harrell's C-index = 0.601, 95% confidence interval [CI] = [0.583, 0.619]) than other types of indicators including body mass index (BMI), absolute weight change, absolute BMI change, prediagnosis RWC and postdiagnosis RWC in the study population (all P < 0.05). Time-dependent C-index analysis also indicated that peridiagnosis RWC was optimal for predicting OS. The multivariable-adjusted RCS analysis revealed an N-shaped non-linear association between peridiagnosis RWC and OS (PRWC < 0.001, Pnon-linear < 0.001). Univariate survival analysis showed that the peridiagnosis RWC groups could represent distinct mortality risk stratifications (P < 0.001). Multivariable survival analysis showed that, compared with the maintenance group (weight change < 5%), the significant (gain >10%, hazard ratio [HR] = 0.530, 95% CI = [0.413, 0.680]) and moderate (gain 5-10%, HR = 0.588, 95% CI = [0.422, 0.819]) weight gain groups were both associated with improved OS. In contrast, the moderate (loss 5-10%, HR = 1.219, 95% CI = [1.029, 1.443]) and significant (loss >10%, HR = 1.280, 95% CI = [1.095, 1.497]) weight loss groups were both associated with poorer OS. CONCLUSIONS: The prognostic performance of peridiagnosis RWC is superior to other weight-related indicators in patients with cancer. The findings underscore the importance of expanding the surveillance of body weight from at diagnosis to both past and future, and conducting it within clinically operational time frames, in order to identify and intervene with patients who are at risk of weight change-related premature deaths.

MICAL2 implies immunosuppressive features and acts as an independent and adverse prognostic biomarker in pancreatic cancer.

At present, clinical outcomes of pancreatic cancer patients are still poor. New therapeutic targets for pancreatic cancer are urgently needed. Previous studies have indicated that Microtubule Associated Monooxygenase, Calponin and LIM Domain Containing 2 (MICAL2) is highly expressed in many tumors and promotes tumor progression. However, the role played by MICAL2 in pancreatic cancer remains unclear. Based on gene expression and clinical information from multiple datasets, we used comprehensive bioinformatics analysis in combination with tissue microarray to explore the function and clinical value of MICAL2. The results showed that MICAL2 was highly expressed in pancreatic cancer tissue and exhibited potential diagnostic capability. High expression of MICAL2 was also associated with poor prognosis and acted as an independent prognostic factor. MICAL2, mainly expressed in fibroblasts of pancreatic cancer, was closely related to metastasis and immune-related features, such as epithelial-mesenchymal transformation, extracellular cell matrix degradation, and inflammatory response. Furthermore, higher MICAL2 expression in pancreatic cancer was also associated with an increase in cancer-associated fibroblasts as well as M2 macrophage infiltration, and a reduction in CD8 + T cell infiltration, thereby facilitating the formation of an immunosuppressive microenvironment. Our results helped elucidate the clinical value and function in metastasis and immunity of MICAL2 in pancreatic cancer. These findings provided potential clinical strategies for diagnosis, targeted therapy combination immunotherapy, and prognosis in patients with pancreatic cancer.

[A Prognostic Model of Elderly Patients with Non-small Cell Lung Cancer 
Based on Geriatric Nutritional Risk Index].

BACKGROUND: The relationship between nutritional status and prognosis of cancer patients has emerged as a hotspot for research. The aim of this study is to explore the application value of the geriatric nutritional risk index (GNRI) in assessing the prognosis of elderly patients with non-small cell lung cancer (NSCLC), and establish a Nomogram to predict the prognosis of elderly patients with NSCLC. METHODS: The data of patients with NSCLC aged ≥65 years who were initially treated in the First Affiliated Hospital of Zhengzhou University from January 2016 to December 2019 were retrospectively analyzed. To determine the optimal cut-off value for GNRI, receiver operating characteristic (ROC) curve was constructed, and the patients were divided into high and low GNRI groups. Kaplan-Meier curve and Log-rank test were used to compare overall survival (OS) of the two groups. Univariate and multivariate Cox regression was used to analyze the risk factors for poor prognosis in elderly patients with NSCLC. Nomogram predicting survival in elderly patients with NSCLC was constructed and validated by using R software. RESULTS: Statistically significant differences in age, gender, body mass index (BMI), histological type, albumin, treatment methods, neutrophil to lymphocyte ratio (NLR), prognostic nutritional index (PNI), systemic immune-inflammation index (SII) and cytokeratin 19 fragment (CYFRA21-1) were observed between the high and low GNRI groups (P<0.05). The Kaplan-Meier curve showed a shorter OS in the low-GNRI group. Multivariate Cox regression analysis showed that CYFRA21-1>3.3 ng/mL was an independent risk factor for the development of OS in patients with NSCLC, and GNRI>97.09 was a protective factor [hazard ratio (HR)=0.52, 95% confidence interval (CI): 0.34-0.79, P<0.05]. Patients in the stage IV had a 1.98-fold increased risk of death compared with patients in the stage I (95%CI: 1.02-3.86, P<0.05). The risk of death was 3.58 times higher in patients receiving chemotherapy alone compared with those receiving combination therapy (95%CI: 2.03-6.32, P<0.05). A Nomogram constructed on the basis of GNRI, which predicted the OS of elderly patients with NSCLC with a concordance index (C-index) of 0.70 (95%CI: 0.65-0.76), and the area under the curve (AUC) for 1 and 2-year survival rates to be 0.93 (95%CI: 0.87-0.98) and 0.72 (95%CI: 0.63-0.80), respectively, and the calibration curve has a good coincidence of prediction. CONCLUSIONS: High GNRI scores are significantly associated with improved survival in elderly patients with NSCLC, and reliance on cut-off values may provide the appropriate timing for nutritional support. The Nomogram constructed in this study can be used as an effective tool to predict the survival rate of elderly patients with NSCLC, which has strong clinical practicability.

Predicting anticancer drug sensitivity on distributed data sources using federated deep learning.

Drug sensitivity prediction plays a crucial role in precision cancer therapy. Collaboration among medical institutions can lead to better performance in drug sensitivity prediction. However, patient privacy and data protection regulation remain a severe impediment to centralized prediction studies. For the first time, we proposed a federated drug sensitivity prediction model with high generalization, combining distributed data sources while protecting private data. Cell lines are first classified into three categories using the waterfall method. Focal loss for solving class imbalance is then embedded into the horizontal federated deep learning framework, i.e., HFDL-fl is presented. Applying HFDL-fl to homogeneous and heterogeneous data, we obtained HFDL-Cross and HFDL-Within. Our comprehensive experiments demonstrated that (i) collaboration by HFDL-fl outperforms private model on local data, (ii) focal loss function can effectively improve model performance to classify cell lines in sensitive and resistant categories, and (iii) HFDL-fl is not significantly affected by data heterogeneity. To summarize, HFDL-fl provides a valuable solution to break down the barriers between medical institutions for privacy-preserving drug sensitivity prediction and therefore facilitates the development of cancer precision medicine and other privacy-related biomedical research.

PIEZO2 promotes cell proliferation and metastasis in colon carcinoma through the SLIT2/ROBO1/VEGFC pathway.

BACKGROUND: The PIEZO2 may be involved in the occurrence and development of tumors. OBJECTIVES: To explore the potential mechanism and effect of PIEZO2 on colon cancer. MATERIAL AND METHODS: We assessed the expression and prognostic role of PIEZO2 in patients with colon cancer. The role of PIEZO2 in SW480 cell proliferation, migration and invasion in vitro was investigated using cell counting kit-8 (CCK-8), wound healing, and transwell and cell invasion assays, respectively. The effect of PIEZO2 on SW480 cells in vivo was also explored. The potential mechanisms of PIEZO2 in SW480 cells were detected using quantitative reverse-transcription polymerase chain reaction (qRT-PCR) and western blot. RESULTS: The PIEZO2 was significantly increased in colon cancer tissues and the PIEZO2 high expression group was associated with a lower overall survival (OS) rate. Furthermore, PIEZO2 knockdown weakened the proliferation, migration and invasion of SW480 cells. The PIEZO2 knockdown was related to a lower expression of SLIT2, ROBO1, HIF-1α, and VEGFC. Finally, the tumors in control SW480 cells grew faster and larger than those in mice inoculated with si-PIEZO2 SW480 cells. Moreover, the si-PIEZO2 SW480 cell group showed a reduced expression of Ki67 and VEGFC and, at the same time, a significantly higher apoptosis index of tumor cells compared to the control group. The expression of PIEZO2 was higher in cancer-associated fibroblasts (CAFs) of colon cancer. CONCLUSIONS: The PIEZO2 was increased in colon cancer tissues and was an unfavorable gene in patients with colon cancer, promoting colon cell proliferation, migration and invasion through the SLIT2/ROBO1/VEGFC pathway.

Invasive Pulmonary Aspergillosis Diagnosis via Peripheral Blood Metagenomic Next-Generation Sequencing.

Invasive pulmonary aspergillosis (IPA) is one of the major causes of morbidity and mortality in immunocompromised patients such as hematological malignancies, hematopoietic stem cell transplantation, and solid organ transplantation. The diagnosis of IPA in these patients is still difficult because it has no obvious specificity in clinical symptoms, signs and imaging, and test sensitivity of blood 1,3-ß-d-glucan test, galactomannan are low. Therefore, we still need to explore more diagnostic methods. In our study, via peripheral blood metagenomic next-generation sequencing (mNGS), five patients were tested positive for Aspergillus DNA and then quickly diagnosed as IPA. Out of the 5 cases, 1 was proven and 4 were probable IPA. The underlying diseases of the 5 patients were myelodysplastic syndrome (2 cases), acute myeloid leukemia (2 cases), and renal transplantation (1 case). Then they were diagnosed as IPA using other methods such as lung histopathology, bronchoalveolar lavage fluid (BALF) mNGS, and sputum culture or sputum mNGS. In case 1, sputum culture suggested Aspergillus flavus. In case 2, both Grocott methenamine silver (GMS) stain of lung histopathology and lung tissue mNGS suggested Aspergillus infection. In cases 3 and 4, BALF-mNGS suggested Aspergillus infection. In case 5, sputum mNGS suggested Aspergillus infection. In conclusion, detecting the cfDNA of Aspergillus via peripheral blood mNGS can be used to diagnose IPA and is a rapid and non-invasive diagnosis method.

Circ_0006006 facilitates non-small cell lung cancer progression by modulating miR-924/SRSF7 axis.

BACKGROUND: Non-small cell lung cancer (NSCLC) is an aggressive tumor with high mortality. Circular RNAs played crucial roles in the development of cancers, including NSCLC. In the present study, the action of circ_0006006 in NSCLC was investigated. METHODS: Using a real-time quantitative polymerase chain reaction, the relative gene expression was detected. The structure of circ_0006006 was identified using RNase R digestion and actinomycin D treatment. The functional role of circ_0006006 in cell proliferation, migration, invasion, apoptosis and angiogenesis was explored using cell counting kit-8, 5-ethynyl-2'-deoxyuridine, colony formation, wound healing, transwell, flow cytometry and tube formation assays, respectively. Using western blotting, the relative proteins expression was measured. Dual-luciferase reporter and RNA immunoprecipitation assays were employed to verify the correlation between microRNA-924 (miR-924) and circ_0006006 or serine/arginine-rich splicing factor 7 (SRSF7). Xenograft tumor experiment was used to investigate the effect of circ_0006006 on tumor growth in vivo. An immunohistochemistry assay was performed to detect Ki-67, Bax, Bcl-2 and SRSF7 expression in tissues of mice. RESULTS: Circ_0006006 was increased in NSCLC tissues and cells. Loss-of-function assays demonstrated that circ_0006006 silencing repressed proliferative ability, cell migration and invasion, and angiogenesis, as well as promoted cell apoptosis, in A549 and H1299 cells. Follow-up mechanism experiments depicted that circ_0006006 sponged miR-924 and miR-924 inhibitor rescued the circ_0006006 knockdown-mediated inhibition effect on the progression of NSCLC. Additionally, the inhibition effect of circ_0006006 knockdown on SRSF7 expression was reversed by miR-924 inhibitor. Moreover, the suppressive effect of miR-924 on NSCLC progression was reversed by SRSF7 overexpression. Xenograft tumor experiment unveiled that circ_0006006 knockdown inhibited tumor growth in vivo. CONCLUSIONS: Circ_0006006 stimulated NSCLC progression by targeting miR-924 to regulate SRSF7 expression.

Characteristics of Mucormycosis in Hematological Patients and a Death Prediction Model.

Mucormycosis is an angioinvasive fungal infection, associated with high mortality. The aim of our study was to explore the high-risk factors and predict the death of hematological disease complicated with mucormycosis. We retrospectively analyzed clinical data of 31 patients with hematological disease complicated with mucormycosis, adopted random forest to establish the death prediction model, and validated the model in another 15 patients. The median age of the 31 cases was 46 (28-51) years, male to female ratio 1.38:1, and 90-day mortality rate 54.8%. The most common underlying disease was acute myeloid leukemia (58.1%). The main clinical symptoms were fever (100%), cough (87.1%), sputum (80.6%), chest pain (61.3%), and hemoptysis (19.4%). Reversed halo sign (83.9%) was the most common computed tomography sign. A total of 48.4% of patients also had aspergillus or bacterial infections. Discriminative models were constructed by random forest with 17 non-survivors and 14 survivors. Procalcitonin, the duration of intravenous administration of amphotericin B or amphotericin B liposomes, and neutropenia at death or 90 days of survival were the leading risk factors for poor prognosis, with area under the curve of 0.975 (95% CI 0.934-1). We chose 0.6775 as death prediction threshold (with 82.3% sensitivity and 100% specificity) and validated the model successfully in another 15 patients. Chest pain and reversed halo sign are specific clinical and image signs of hematological disease complicated with mucormycosis. Neutropenia, elevated procalcitonin, and insufficient use time of amphotericin B or amphotericin B liposomes are risk factors for death.

The sesquiterpene lactone eupatolide induces apoptosis in non-small cell lung cancer cells by suppressing STAT3 signaling.

We aimed to evaluate the role of a natural sesquiterpene lactone, eupatolide, in non-small-cell lung cancer (NSCLC) and further explore its underlying mechanism on regulating the activation of signal transducer and activator of transcription 3 (STAT3), which is thought to have carcinogenic function in a variety of malignancies including lung cancer. Cell survival was measured by Cell Counting Kit-8 assay. in vivo experiments were performed by inoculating NSCLC cells into nude mice. Western blot and qRT-PCR were applied to detect the activation level of STAT3 and the mRNA levels of anti-apoptotic markers. The cell apoptosis was measured by Annexin V-FITC/PI Apoptosis Detection Kit. Our results showed that eupatolide suppressed the survival of NSCLC cells in a dose and time dependent manner. Furthermore, eupatolide increased the anti-tumor activity of the chemotherapeutic drugs cisplatin and 5-Fluoracil (5-FU). The xenograft study revealed that eupatolide suppressed tumor growth of NSCLC cells in vivo. Furthermore, eupatolide induced apoptosis by suppressing the activation of STAT3 in NSCLC cells. Sustained activation or knockdown of STAT3 suppressed and enhanced the activity of eupatolide, respectively. This paper is the first to report that eupatolide could effectively inhibit NSCLC progression, suggesting that eupatolide might be utilized as a novel STAT3 inhibitor for treating NSCLC.

Effects of Selenium Nanoparticles Combined With Radiotherapy on Lung Cancer Cells.

OBJECTIVE: To investigate the effects of selenium nanoparticles (nano-Se) combined with radiotherapy on the proliferation, migration, invasion, and apoptosis of non-small cell lung cancer (NSCLC) A549 and NCI-H23 cells. METHODS: Nano-Se was synthesized and characterized by transmission electron microscope (TEM), X-ray diffractometer, and Ultraviolet-visible (UV)-Vis Spectroscopy, separately. The uptake of nano-Se by lung cancer cells was detected by flow cytometry. Cell counting kit-8 (CCK-8) method was used to detect the antiproliferative activity of nano-Se combined with radiotherapy. Wound healing tests and transwell assay were used to detect the migration and invasion ability of the cells. Annexin V-fluorescein isothiocyanate (FITC)/Propidium iodide (PI) staining by flow cytometry was used to detect apoptosis. The expression of Cyclin D1 (CCND1), c-Myc, matrix metalloproteinase 2 (MMP2), MMP9, cleaved Caspase-3, and cleaved Caspase-9 were detected by Western blot. RESULTS: The average diameter of nano-Se was 24.39 nm and the wavelength of nano-Se increased with the increase of radiation dose under UV-Vis Spectroscopy. The uptake of nano-Se in lung cancer cells was increased with the increase of nano-Se concentration. The nano-Se combined with radiotherapy decreased the proliferation activity of NSCLC cell lines A549 and NCI-H23 in a dose-dependent manner (all P < 0.05). Compared with the Control group, nano-Se combined with radiotherapy could significantly inhibit the migration and invasion of lung cancer cells (all P < 0.05), and the effects of the combination of nano-Se and radiotherapy was better than that of a single application (all P < 0.05). Furthermore, nano-Se combined with radiotherapy could induce apoptosis of lung cancer cells (P < 0.05) and nano-Se combined with radiotherapy could significantly inhibit the expression of proliferation-related proteins CCND1, c-Myc, invasion and migration-related proteins MMP2 and MMP9, but conversely promoted the expression of apoptosis-related proteins cleaved caspase-3 and cleaved caspase-9. Conclusion: This study found that nano-Se combined with radiotherapy plays an anti-cancer role in lung cancer cells by inhibiting cell proliferation, migration, and invasion, as well as inducing apoptosis, suggesting that nano-Se may be used as a radiosensitizer in the clinical treatment of lung cancer, but further research is still needed.

Apatinib as an optional treatment in metastatic colorectal cancer.

Antiangiogenic therapy has shown clinical benefit in metastatic colorectal cancer (mCRC). We aimed to evaluate the efficacy and safety of apatinib in patients who failed standard treatment and to explore potential factors related to its efficacy.A total of 47 patients were enrolled in this retrospective study. Patients who received apatinib therapy after failure of standard therapy from December 2014 and February 2018 were included. Progression-free survival (PFS), overall survival (OS), objective response rate (ORR), and treatment-related adverse events were recorded and evaluated.The median PFS was 3.717 months (95% confidence interval [CI], 3.198-4.235), and the median OS was 7.335 months (95% CI, 6.738-7.932). The disease control rate was 72.34%, and the ORR was 8.51%. The most common grade 3 to 4 adverse reactions were hypertension, proteinuria, hand-foot syndrome, and diarrhea. Multivariate analysis indicated previous antiangiogenic therapy and baseline elevated neutrophil-to-lymphocyte ratio (NLR) as independent prognostic factors.Apatinib might be a reasonable treatment option with a controlled safety profile for patients with mCRC who have failed standard therapy. Patients who previously received antiangiogenic therapy and who have baseline elevated NLR are more likely to benefit from apatinib.

Distribution of serum neuron-specific enolase and the establishment of a population reference interval in healthy adults.

BACKGROUND: Neuron-specific enolase (NSE) is an important tumor marker in the serum of patients with lung cancer. Elevated serum NSE levels are also associated with many other diseases. However, there is no unified population reference interval for serum NSE. This study aimed to investigate the distribution of serum NSE in healthy Chinese adults aged 20-79 years and to establish its reference interval in Chinese population. METHODS: A total of 10 575 healthy subjects were in line with the requirements of this study. The concentration of serum NSE was detected by a fully automated Cobas e602 analyzer with matching reagents. The population reference interval for serum NSE was established using the unilateral 95th percentile (P95 ) according to standard guidelines. RESULTS: The distributions of serum NSE were not significantly different between males and females (P > 0.05) and also did not differ by age (P > 0.05). Therefore, the population reference interval for serum NSE was established as upper limit 25.4 ng/mL (90% confidence interval: 24.5-26.2 ng/mL). CONCLUSIONS: We established the first population reference interval for serum NSE in a large healthy Chinese adult cohort, which was higher than that recommended by Roche Diagnostics GmbH. This new reference interval is more practical and applicable in Chinese adults.

The rs3850641 polymorphism of the TNFSF4 gene increases the risk of myocardial infarction in a Chinese Han population.

Tumor necrosis factor superfamily member 4 (TNFSF4), also known as Ox40 ligand (Ox40l), plays an important role in atherosclerosis development. Several studies reported the association between the rs3850641 polymorphism of the TNFSF4 gene and the risk of myocardial infarction (MI). However, the results are inconsistent. In order to explore the relationship between the rs3850641 polymorphism of the TNFSF4 gene and MI, we conducted a case-control study including 454 cases and 512 controls in a Chinese Han population. Genotyping was performed using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. The present study found that AA genotype (AA vs. GG: odds ratio (OR) & 95% confidence interval (CI), 2.00(1.04,3.86), P=0.039; AA vs. AG+GG: OR & 95% CI, 1.93(1.00,3.70), P=0.049) or A allele carriers (A vs. G: OR & 95% CI, 1.27(1.00,1.60), P=0.047) of the rs3850641 polymorphism of the TNFSF4 gene increased the risk of MI. In conclusion, this case-control study confirms that the rs3850641 polymorphism of the TNFSF4 gene increases the risk of MI.

Serum miR-21 level: a potential diagnostic and prognostic biomarker for non-small cell lung cancer.

Because lung cancer is the most common cause of cancer death among both men and women, focused efforts are necessary to identify and develop biomarkers that aid in the detection and treatment of this serious disease. Recent research has been aimed at understanding the roles of microRNAs (miRNAs) in tumorigenesis and their utility as cancer biomarkers. Here, miR-21 was investigated as a potential serum biomarker for non-small cell lung cancer (NSCLC). The relative expression level of miR-21 was detected by real-time PCR in the sera of 80 NSCLC patients; sera were also collected from 60 healthy people as a control. The most suitable cut-off value and the prognostic value of serum miR-21 levels were analyzed using a receiver-operating curve. The relative serum miR-21 level in NSCLC patients was significantly higher than that in healthy people (P<0.05). For relative miR-21 expression, the area under the ROC curve was 0.812 (95% CI: 0.736-0.888) with a sensitivity of 73.8% and a specificity of 71.7%, based on a cut-off value of 1.22. NSCLC patients were divided into two groups based on miR-21 expression; those with higher relative expression (≥1.22) had significantly lower survival time than those in the lower expression group (P<0.05). Further, serum miR-21 level and survival time were negatively correlated in NSCLC patients (P<0.05). Thus, miR-21 may be useful as a diagnostic and prognostic indicator of NSCLC.

Hepatitis B surface antigen (HBsAg) and core antigen (HBcAg) combine CpG oligodeoxynucletides as a novel therapeutic vaccine for chronic hepatitis B infection.

Hepatitis B virus infection is a non-cytopathic hepatotropic virus which can lead to chronic liver disease and hepatocellular carcinoma. Traditional therapies fail to provide sustained control of viral replication and liver damage in most patients. As an alternative strategy, immunotherapeutic approaches have shown promising efficacy in the treatment of chronic hepatitis B patients. Here, we investigated the efficacy of a novel therapeutic vaccine formulation consisting of two HBV antigens, HBsAg and HBcAg, and CpG adjuvant. This vaccine formulation elicits forceful humoral responses directed against HBsAg/HBcAg, and promotes a Th1/Th2 balance response against HBsAg and a Th1-biased response against HBcAg in both C57BL/6 and HBV transgenic mice. Vigorous cellular immune response was also detected in HBV transgenic mice, for a significantly higher number of HBs/HBc-specific IFN-γ secreting CD4+ and CD8+ T cells was generated. Moreover, vaccinated mice elicited significantly intense in vivo CTL attack, reduced serum HBsAg level without causing liver damage in HBV transgenic mice. In summary, this study demonstrates a novel therapeutic vaccine with the potential to elicit vigorous humoral and cellular response, overcoming tolerance in HBV transgenic mice.

Two new macrosporin dimers from the fungus Alternaria sp. XZSBG-1.

Two new macrosporin dimers (1-2) along with four known compounds (3-6) were isolated from the extracts of the fungal strain Alternaria sp. XZSBG-1 from the sediment of the salt lake in the Bange, Tibetan, China. Their structures were determined by spectroscopic methods, mainly by 2D NMR spectra. Compounds 1 and 2 are new macrosporin dimers with symmetric chemical structures. In the cytotoxicity assay and inhibited alpha-glucosidase activity assay, all these compounds showed no notable inhibitory activity.