Development and validation of a risk prediction model for community-acquired pressure injury in a cancer population: A case-control study.

BACKGROUND: Patients with cancer are susceptible to pressure injuries, which accelerate deterioration and death. In patients with post-acute cancer, the risk of pressure injury is ignored in home or community settings. OBJECTIVE: To develop and validate a community-acquired pressure injury risk prediction model for cancer patients. METHODS: All research data were extracted from the hospital's electronic medical record system. The identification of optimal predictors is based on least absolute shrinkage and selection operator regression analysis combined with clinical judgment. The performance of the model was evaluated by drawing a receiver operating characteristic curve and calculating the area under the curve (AUC), calibration analysis and decision curve analysis. The model was used for internal and external validation, and was presented as a nomogram. RESULTS: In total, 6257 participants were recruited for this study. Age, malnutrition, chronic respiratory failure, body mass index, and activities of daily living scores were identified as the final predictors. The AUC of the model in the training and validation set was 0.87 (95 % confidence interval [CI], 0.85-0.89), 0.88 (95 % CI, 0.85-0.91), respectively. The model demonstrated acceptable calibration and clinical benefits. CONCLUSIONS: Comorbidities in patients with cancer are closely related to the etiology of pressure injury, and can be used to predict the risk of pressure injury. IMPLICATIONS FOR PRACTICE: This study provides a tool to predict the risk of pressure injury for cancer patients. This suggests that improving the respiratory function and nutritional status of cancer patients may reduce the risk of community-acquired pressure injury.

A mitochondria-targeting dihydroartemisinin derivative as a reactive oxygen species -based immunogenic cell death inducer.

Immunogenic cell death (ICD) can activate the anticancer immune response and its occurrence requires high reliance on oxidative stress. Inducing mitochondrial reactive oxygen species (ROS) is a desirable capability for ICD inducers. However, in the category of ICD-associated drugs, numerous reported ICD inducers are a series of anthracyclines and weak in ICD induction. Herein, a mitochondria-targeting dihydroartemisinin derivative (T-D) was synthesized by conjugating triphenylphosphonium (TPP) to dihydroartemisinin (DHA). T-D can selectively accumulate in mitochondria to trigger ROS generation, leading to the loss of mitochondrial membrane potential (ΔΨm) and ER stress. Notably, T-D exhibits far more potent ICD-inducing properties than its parent compound. In vivo, T-D-treated breast cancer cell vaccine inhibits metastasis to the lungs and tumor growth. These results indicate that T-D is an excellent ROS-based ICD inducer with the specific function of trigging vigorous ROS in mitochondria and sets an example for incorporating artemisinin-based drugs into the ICD field.

Association between polymorphisms in connexin 40 gene (Cx40) and risk of atrial fibrillation: a meta-analysis based on 3,452 subjects.

INTRODUCTION: Atrial fibrillation (AF) is a common cardiac arrhythmia that is associated with heart failure and stroke, leading sometimes to death. But the pathogenesis of AF remains unclear. Numerous studies have investigated whether the connexin 40 (Cx40) polymorphisms influences the risk of AF, but the results are controversial. METHODS: We searched English and Chinese databases and calculated the odds ratio (OR) and 95% confidence interval (CI) to examine the existence of genetic associations between the Cx40 polymorphisms and the risk of AF. All relevant studies were screened and meta-analyzed using Review Manager 5.0. RESULTS: A total of 12 studies, including 10 studies for -44 polymorphism (rs35594137) and 4 studies for -26 polymorphism (rs10465885), were identified for the meta-analysis. For -44 polymorphism, the results showed a significantly increased risk of AF in the five genetic models in the overall analysis. Furthermore, in subgroup analysis, increased AF risks were also observed in Asian and non-Asian populations. For -26 polymorphism, the overall OR revealed an increased risk of AF in dominant model. In subgroup analysis, increased AF risk was only found in recessive genetic model of the Asian population. CONCLUSIONS: The Cx40 polymorphisms were positively associated with AF in both populations, especially on -44 polymorphism.

Effective treatment of high-voltage pulsed radiofrequency combined with oxygen-ozone injection in acute zoster neuralgia.

INTRODUCTION: Postherpetic neuralgia (PHN) is the most common and severe complication of acute herpes zoster. Early treatment of herpes zoster neuralgia is of great significance to reduce the incidence of PHN. This retrospective study evaluated the efficacy and safety of the combination of high-voltage pulsed radiofrequency (PRF) and oxygen-ozone(O2-O3) injection in patients with acute zoster neuralgia (AZN) who failed to respond to conservative treatment. METHODS: One-hundred patients diagnosed with AZN were classified into two groups (high-voltage PRF group [HP group, n = 50] and high-voltage PRF combined with O2-O3 injection group [HPO group, n = 50]) based on different treatment methods. Therapeutic effectiveness was assessed using a numerical rating scale (NRS) and the Pittsburgh Sleep Quality Index (PSQI). The dosages of gabapentin and tramadol (mg/d) before treatment and after 1 week and 1, 3, and 6 months of treatment were measured. The incidence of clinically meaningful PHN after treatment was also recorded. RESULTS: Pain intensity and sleep quality in both groups at all time points improved after treatment compared to before treatment (P < 0.05). After 1 week and 1 month of treatment, NRS and PSQI scores in both groups decreased, but the differences were not statistically significant (P > 0.05). NRS, PSQI scores, and the dosages of gabapentin and tramadol decreased more significantly in the HPO group than those in the HP group after 3 months (P < 0.05). The incidence of PHN was significantly lower in the HPO group than in the HP group (P < 0.05). There were no significant differences in adverse events between the groups. CONCLUSIONS: High-voltage PRF is a safe and effective method for treating AZN. The combination of high-voltage PRF and O2-O3 injection is superior to high-voltage PRF alone for treating late-stage AZN. This approach could be recommended as an alternative treatment for patients with refractory AZN and could significantly reduce the risk of PHN.

Development and Validation of a Risk Nomogram Model for Predicting Community-Acquired Pressure Injury Among the Older Adults in China: A Case-Control Study.

Purpose: A predictive model of community-acquired pressure injury (CAPI) was established and validated to allow the early identification of the risk of pressure injuries by family caregivers and community workers. Patients and Methods: The participants were hospitalized patients 65 years and older from two branches of a tertiary hospital in China, one for model training set and the other for validation set. This study was a case-control study based on hospital electronic medical records. According to the presence of pressure injury at admission, patients were divided into a case group and a control group. In the model training set, LASSO regression was used to select the best predictors, and then logistic regression was used to construct a nomogram. The performance of the model was evaluated by drawing the receiver operating characteristic curve (ROC) and calculating the area under the curve (AUC), calibration analysis, and decision curve analysis. The model used a 10-fold crossover for internal and external validation. Results: The study included a total of 20,235 subjects, including 11,567 in the training set and 8668 in the validation set. The prevalence of CAPI in the training and validation sets was 2.5% and 1.8%, respectively. A nomogram was constructed including eight variables: age ≥ 80, malnutrition status, cerebrovascular accidents, hypoproteinemia, respiratory failure, malignant tumor, paraplegia/hemiplegia, and dementia. The AUC of the prediction model in the original model, internal validation, and external validation were 0.868 (95% CI: 0.847, 0.890), mean 0.867, and 0.840 (95% CI: 0.807,03.873), respectively. The nomogram showed acceptable calibration and clinical benefit. Conclusion: We constructed a nomogram to predict CAPI from the perspective of comorbidity that is suitable for use by non-specialists. This nomogram will help family caregivers and community workers with the early identification of PI risks.

Unexpected Dynamic Binding May Rescue the Binding Affinity of Rivaroxaban in a Mutant of Coagulation Factor X.

A novel coagulation factor X (FX) Tyr319Cys mutation (Y99C as chymotrypsin numbering) was identified in a patient with severe bleeding. Unlike the earlier reported Y99A mutant, this mutant can bind and cleave its specific chromogenetic substrate at a normal level, suggesting an intact binding pocket. Here, using molecular dynamics simulations and MM-PBSA calculations on a FX-rivaroxaban (RIV) complex, we confirmed a much stronger binding of RIV in Y99C than in Y99A on a molecular level, which is actually the average result of multiple binding poses in dynamics. Detailed structural analyses also indicated the moderate flexibility of the 99-loop and the importance of the flexible side chain of Trp215 in the different binding poses. This case again emphasizes that binding of ligands may not only be a dynamic process but also a dynamic state, which is often neglected in drug design and screening based on static X-ray structures. In addition, the computational results somewhat confirmed our hypothesis on the activated Tyr319Cys FX (Y99C FXa) with an impaired procoagulant function to bind inhibitors of FXa and to be developed into a potential reversal agent for novel oral anticoagulants (NOAC).

Novel m.4268T>C mutation in the mitochondrial tRNAIle gene is associated with hearing loss in two Chinese families.

BACKGROUND: Herein, we report the genetic, clinical, molecular and biochemical features of two Han Chinese pedigrees with suggested maternally transmitted non-syndromic hearing loss. AIM: To investigate the pathophysiology of hearing loss associated with mitochondrial tRNA mutations. METHODS: Sixteen subjects from two Chinese families with hearing loss underwent clinical, genetic, molecular, and biochemical evaluations. Biochemical characterizations included the measurements of tRNA levels using lymphoblastoid cell lines derived from five affected matrilineal relatives of these families and three control subjects. RESULTS: Three of the 16 matrilineal relatives in these families exhibited a variable seriousness and age-at-onset (8 years) of deafness. Analysis of mtDNA mutation identified the novel homoplasmic tRNAIle 4268T>C mutation in two families both belonging to haplogroup D4j. The 4268T>C mutation is located in a highly conserved base pairing (6U-67A) of tRNAIle. The elimination of 6U-67A base-pairing may change the tRNAIle metabolism. Functional mutation was supported by an approximately 64.6% reduction in the level of tRNAIle observed in the lymphoblastoid cell lines with the 4268T>C mutation, in contrast to the wild-type cell lines. The reduced level of tRNA was below the proposed threshold for normal respiration in lymphoblastoid cells. However, genotyping analysis did not detect any mutations in the prominent deafness-causing gene GJB2 in any members of the family. CONCLUSION: These data show that the novel tRNAIle 4268T>C mutation was involved in maternally transmitted deafness. However, epigenetic, other genetic, or environmental factors may be attributed to the phenotypic variability. These findings will be useful for understanding families with maternally inherited deafness.

Quantitative elucidation of associations between nucleotide identity and physicochemical properties of amino acids and the functional insight.

Studies on codon property would deepen our understanding of the origin of primitive life and enlighten biotechnical application. Here, we proposed a quantitative measurement of codon-amino acid association and found that seven out of 13 physicochemical properties have stronger associations with the nucleotide identity at the second codon position, indicating that protein structure and function may associate more closely with it than the other two sites. When extending the effect of codon-amino acid association to protein level, it was found that the correlation between the second codon position (measured by the relative frequencies of nucleobase T and A at this codon site) and hydrophobicity (by the form of GRAVY value) became stronger with 96% genomes having R > 0.90 and p < 1e-60. Furthermore, we revealed that informational genes encoding proteins have lower GRAVY values than operational proteins (p < 3e-37) in both prokaryotic and eukaryotic genomes. The above results reveal a complete link from codon identity (A2 versus T2) to amino acid property (hydrophilic versus hydrophobic) and then to protein functions (informational versus operational). Hence, our work may help to understand how the nucleotide sequence determines protein function.

Genome-wide characterization and expression profiling of B3 superfamily during ethylene-induced flowering in pineapple (Ananas comosus L.).

BACKGROUND: The B3 superfamily (B3s) represents a class of large plant-specific transcription factors, which play diverse roles in plant growth and development process including flowering induction. However, identification and functional surveys of B3 superfamily have not been reported in ethylene-induced pineapple flowering (Ananas comosus). RESULTS: 57 B3 genes containing B3 domain were identified and phylogenetically classified into five subfamilies. Chromosomal localization analysis revealed that 54 of 57 AcB3s were located on 21 Linkage Groups (LG). Collinearity analysis demonstrated that the segmental duplication was the main event in the evolution of B3 gene superfamily, and most of them were under purifying selection. The analysis of cis-element composition suggested that most of these genes may have function in response to abscisic acid, ethylene, MeJA, light, and abiotic stress. qRT-PCR analysis of 40 AcB3s containing ethylene responsive elements exhibited that the expression levels of 35 genes were up-regulated within 1 d after ethephon treatment and some were highly expressed in flower bud differentiation period in stem apex, such as Aco012003, Aco019552 and Aco014401. CONCLUSION: This study provides a basic information of AcB3s and clues for involvement of some AcB3s in ethylene-induced flowering in pineapple.

Transcriptomic model-based lncRNAs and mRNAs serve as independent prognostic indicators in head and neck squamous cell carcinoma.

Head and neck squamous cell carcinoma (HNSC) is one of most common types of cancer worldwide, and mRNAs and long non-coding RNAs (lncRNAs) have been identified as prognostic biomarkers in HNSC. In the present study, using gene expression datasets from multiple platforms, survival-associated genes in HNSC were identified. Subsequently, a combination of 17 genes (14 mRNAs and 3 lncRNA) was optimized using random forest variable hunting and a risk score model for HNSC prognosis was developed using a cohort from The Cancer Genome Atlas. Patients with high-risk scores tend to have earlier disease recurrence and lower survival rates, compared with those with low-risk scores. This observation was further validated in three independent datasets (GSE41613, GSE10300 and E-MTAB-302). Association analysis revealed that the risk score is independent of other clinicopathological observations. On the basis of the results depicted in the nomogram, the risk score performs better in 3-year survival rate prediction than other clinical observations. In summary, the lncRNA-mRNA signature-based risk score successfully predicts the survival of HNSC and serves as an indicator of prognosis.

Bone marrow mesenchymal stem cells could reduce the toxic effects of hexavalent chromium on the liver by decreasing endoplasmic reticulum stress-mediated apoptosis via SIRT1/HIF-1α signaling pathway in rats.

This study focused on the effect of bone marrow mesenchymal stem cells (BMSCs) on the repair of rat liver injury induced by Cr (VI). Twenty-four Wistar rats were randomly divided into the control, model and cell therapy group, with 8 rats in each group. Potassium dichromate solution containing 0, 0.4 and 0.4 mg/kg·bw Cr (VI) was administered 5 times a week for 30 days. At the end of treatment, rats in the cell therapy group were administered 1 × 107 BMSCs. Two weeks later, serum alanine and aspartate aminotransferase levels in the cell therapy group were significantly improved compared with those in the model group, CM-Dil-labeled BMSCs were localized in rat livers. Compared with the model group, in the cell therapy group the number of apoptotic hepatocytes by TUNEL assay, MDA content, the expression of HIF-1α, endoplasmic reticulum (ER) stress-mediated apoptosis-related proteins including Grp78, CHOP, Cleaved-Caspase-12, ATF6, and Bax was significantly lower, and SOD activity, the expression of SIRT1 and Bcl-2 was significantly higher. It is suggested that BMSCs are localized in livers and reduce the toxic effects of Cr (VI) on the liver, and the possible mechanism may be related to the mechanisms of BMSCs decreasing ER stress-mediated hepatocyte apoptosis via the SIRT1/HIF-1α signaling pathway.

Bone marrow mesenchymal stem cells repair Cr (VI)- injured kidney by regulating mitochondria-mediated apoptosis and mitophagy mediated via the MAPK signaling pathway.

The present study aimed to explore the repair effect and mechanism of bone marrow mesenchymal stem cells (BMSCs) transplantation on injured kidneys caused by hexavalent chromium (Cr (VI)). Wistar rats were intraperitoneally injected with 0.4 mg/kg•bw Cr (VI) ion solution. After 30 days, 1 × 107 BMSCs were transplanted into rats. After cell transplantation for 2 weeks, there was no significant difference in the chromium content between the model and BMSCs-therapy group by atomic absorption spectrometry. In BMSCs-therapy group, the renal organ index, the serum levels of blood urea nitrogen (BUN) and creatinine (CRE), malonaldehyde (MDA) content were significantly decreased, superoxide dismutase (SOD) activity was significantly elevated, and the pathological changes were improved compared with the model group. The results of immunohistochemical and western blot assays showed that the expressions of apoptosis-related proteins Bax, Cytochrome c, and Caspase-3, as well as autophagy-associated proteins Beclin 1, PINK1, Parkin, p-Parkin, LC3B, and the MAPK signaling pathway, including the ratio of p-p38 to p38 and p-JNK to JNK were all significantly decreased, Bcl-2 and p62 expressions, and the ratio of p-ERK to ERK were significantly elevated in BMSCs-therapy group compared with the model group. These results suggested that BMSCs repaired Cr (VI)-injured kidney through decreasing mitochondria-mediated apoptosis and mitophagy mediated by downregulating phosphorylation of p38 and JNK, upregulating phosphorylation of ERK.

Seven LncRNA-mRNA based risk score predicts the survival of head and neck squamous cell carcinoma.

Dysregulation of mRNAs and long non-coding RNAs (lncRNAs) is one of the most important features of carcinogenesis and cancer development. However, studies integrating the expression of mRNAs and lncRNAs to predict the survival of head and neck squamous cell carcinoma (HNSC) are still limited, hitherto. In current work, we identified survival related mRNAs and lncRNAs in three datasets (TCGA dataset, E-TABM-302, GSE41613). By random forest, seven gene signatures (six mRNAs and lncRNA) were further selected to develop the risk score model. The risk score was significantly associated with survival in both training and testing datasets (E-TABM-302, GSE41613, and E-MTAB-1324). Furthermore, correlation analyses showed that the risk score is independent from clinicopathological features. According to Cox multivariable hazard model and nomogram, the risk score contributes the most to survival than the other clinical information, including gender, age, histologic grade, and alcohol taking. The Gene Set Enrichment Analysis (GSEA) indicates that the risk score is associated with cancer related pathways. In summary, the lncRNA-mRNA based risk score model we developed successfully predicts the survival of 755 HNSC samples in five datasets and two platforms. It is independent from clinical information and performs better than clinical information for prognosis.

[Cloning and bioinformatics analysis of 1-hydroxy-2-methyl-2-(E)-butenyl 4-diphosphate reductase（PcHDR1）gene in Phlegmarirus carinatus].

The open reading frame of 1-hydroxy-2-methyl-2-(E)-butenyl 4-diphosphate reductase (HDR) was cloned from Phlegmarirus carinatus by RT-PCR method and the sequence was analyzed by bioinformatics tools. After searching the transcriptome dataset of P. carinatus, one unique sequence encoding 1-hydroxy-2-methyl-2-(E)-butenyl 4-diphosphate reductase was discovered. The primers were designed according to the cDNA sequence of 1-hydroxy-2-methyl-2-(E)-butenyl 4-diphosphate reductase from the dataset. And then, the open reading frame (ORF) of 1-hydroxy-2-methyl-2-(E)-butenyl 4-diphosphate reductase, named as PcHDR1 (GenBank Accession number：JQ957845), was cloned by RT-PCR strategy with the template of mixed RNA extracted from roots, stem and leaf of P. carinatus. The bioinformatic analysis of this gene and its corresponding protein was performed. The ORF of PcHDR1 consisted of 1 437 base pairs (bp), encoding one polypeptide with 478 amino acids. The sequence comparison showed that PcHDR1 is closest with GbHDR (Ginkgo biloba),and the sequence homology was up to 78%. Bioinformatics prediction and analysis indicated that PcHDR1 protein contained a conserved domain of LytB, without transmembrane region and signal peptides. This study cloned and analyzed 1-hydroxy-2-methyl-2-(E)-butenyl 4-diphosphate reductase from P. carinatus. The result will provide a foundation for exploring the function of PcHDR1 involved in terpene biosynthesis in P. carinatus plants.

[Synthesis of 6-benzyl-1-[(benzyloxy)methyl]-3-hydroxy-5-(hydroxymethyl)pyrimidine-2,4(1H,3H)-dione].

OBJECTIVE: To find the best synthesis method of 6-benzyl-1-[(benzyloxy)methyl]-3-hydroxy-5-(hydroxymethyl) pyrimidine-2,4(1H,3H)-dione e for observing the change of its biological activity after N-3 hydroxylation. METHODS: After trying some N-hydroxylation methods, the target compound was successfully synthesized via one-pot oxidizing process by sodium hydride (NaH) and 3-chloroperbenzoic acid(m-CPBA); the anti-HIV reverse transcriptase (RT) activity and integrase (IN) activity of the target compound was assayed via enzyme-linked immunesorbent assay (ELISA) and phosphorylation of DNA package method. RESULTS: The target compound could be obtained through the improved m-CPBA oxidative method by only one step, and the yield of the reaction could reach 60%-70%. And the structure of this compound was identified by 1H NMR, 13C NMR and MS; The activity result showed it added the anti-HIV IN activity after N-3 hydroxylation as well as retained the anti-HIV RT activity. CONCLUSION: The improved m-CPBA oxidative method is a convenient and efficient way to prepare the compound 6-benzyl-1-[(benzyloxy)methyl]-3-hydroxy-5-(hydroxymethyl)pyrimidine-2,4(1H,3H)-dione e which has both anti-HIV RT and IN activity.

[Improved synthesis process of diethyl N-[4-[(2,4-diaminopyrido[3,2-d]pyrimidin-6-yl)methylamino]benzoyl]-L-glutamate].

OBJECTIVE: To establish a new approach to synthesis of diethyl N-[4-[(2,4-diaminopyrido[3,2-d]pyrimidin-6-yl)methylamino]benzoyl]-L-glutamate. METHODS: Target compound (5) was synthesized by the use of (2,4-dioxo-tetrahydropyridopyrimidin-6-yl)methyl acetate (1) as starting material via hydrolysis, chlorination, condensation with diethyl (p-aminobenzoyl)glutamate and aminolysis. RESULTS: A new approach to synthesis of diethyl N-[4-[(2,4-diaminopyrido[3,2-d]pyrimidin-6-yl)methylamino]benzoyl]-L-glutamate was established. This synthetic route has hydrolysis reaction, chlorination, diethyl N-(p-aminobenzoyl)-L-glutamate condensation reaction and ammonolysis reaction. The total yield is 36.7%.The structures of those compounds have identified by 1H nuclear magnetic resonance, 13C nuclear magnetic resonance and mass spectrometry. This synthetic route avoid the unstable brominated reaction product and improves the harsh condition of ammonolysis reaction. CONCLUSION: The new synthetic route has improved the reaction condition and the stability of the intermediate, and increased the extent of the derivative compounds, which has great significance to anti-folic acid of anti-tumor inhibitor synthesis.

The prognostic value of plasma soluble CD40 ligand levels in patients with nasopharyngeal carcinoma.

BACKGROUND: Serum soluble CD40 ligand (sCD40L) concentrations are increased in patients with nasopharyngeal carcinoma (NPC). This study further evaluated the relationship between plasma sCD40L concentrations and long-term survival of NPC. METHODS: Plasma sCD40L concentrations of 312 patients and 312 healthy controls were determined using an ELISA. The associations of plasma sCD40L concentrations with 5-year overall survival, progression-free survival, distant metastasis-free survival, and locoregional relapse-free survival were investigated by univariate and multivariate analyses. RESULTS: Plasma sCD40L concentrations were substantially higher in patients than in healthy subjects and also correlated highly with tumor classification, lymph node classification and tumor node metastasis stage. sCD40L emerged as an independent predictor for 5-year overall survival, progression-free survival, distant metastasis-free survival, and locoregional relapse-free survival using univariate and multivariate Cox regression analysis. CONCLUSIONS: High plasma sCD40L concentration is correlated with stage progression of NPC as well as associated with poor survival of NPC. It is suggested that sCD40L should have the potential to be a prognostic biomarker for NPC.

Isolation and molecular characterization of 1-aminocyclopropane-1-carboxylic acid synthase genes in Hevea brasiliensis.

Ethylene is an important factor that stimulates Hevea brasiliensis to produce natural rubber. 1-Aminocyclopropane-1-carboxylic acid synthase (ACS) is a rate-limiting enzyme in ethylene biosynthesis. However, knowledge of the ACS gene family of H. brasiliensis is limited. In this study, nine ACS-like genes were identified in H. brasiliensis. Sequence and phylogenetic analysis results confirmed that seven isozymes (HbACS1-7) of these nine ACS-like genes were similar to ACS isozymes with ACS activity in other plants. Expression analysis results showed that seven ACS genes were differentially expressed in roots, barks, flowers, and leaves of H. brasiliensis. However, no or low ACS gene expression was detected in the latex of H. brasiliensis. Moreover, seven genes were differentially up-regulated by ethylene treatment. These results provided relevant information to help determine the functions of the ACS gene in H. brasiliensis, particularly the functions in regulating ethylene stimulation of latex production.

Plasma adrenomedullin levels and nasopharyngeal carcinoma prognosis.

BACKGROUND: Adrenomedullin has been identified as a tumor growth factor. However, few studies have reported its relationship with cancer survival. We evaluated the prognostic value of pretreatment plasma adrenomedullin levels in nasopharyngeal carcinoma (NPC). METHODS: Plasma adrenomedullin levels of 258 NPC patients and 100 healthy controls were determined using enzyme-linked immunosorbent assay. Adverse event was defined as tumor progression or death from any cause during 5-year follow-up. The relationships between plasma adrenomedullin levels and 5-year mortality, adverse event, tumor-free survival and overall survival were evaluated using multivariate analysis. RESULTS: Pretreatment plasma adrenomedullin levels were substantially higher in patients than in healthy subjects and were correlated highly with tumor classification, lymph node classification and tumor node metastasis stage positively. Adrenomedullin was identified as an independent predictor of 5-year mortality, adverse event, tumor-free survival and overall survival. Based on receiver operating characteristic curve analysis, pretreatment plasma adrenomedullin level had high predictive value for 5-year mortality and adverse event and had high diagnostic value for NPC. CONCLUSIONS: Adrenomedullin may be a reliable biomarker for predicting the long-term prognosis of patients with NPC and also has potential diagnostic utility for NPC.