A novel intronic variant causing aberrant splicing identified in two deaf Chinese siblings with enlarged vestibular aqueducts.

OBJECTIVE: We aimed to evaluate the genotype-phenotype relationship in two Chinese family members with enlarged vestibular aqueduct (EVA). METHODS: We collected blood samples and clinical data from each pedigree family member. Genomic DNA was isolated from peripheral leukocytes using standard methods. Targeted next-generation sequencing and Sanger sequencing were performed to find the pathogenic mutation in this family. Minigene assays were used to verify whether the novel intronic mutation SLC26A4c.765+4A>G influenced mRNA splicing. RESULTS: Hearing loss in the patients with EVA was diagnosed using auditory tests and imaging examinations. Two pathogenic mutations, c.765+4A>G and c.919-2A>G were detected in SLC26A4. In vitro minigene analysis confirmed that c.765+4A>G variant could cause aberrant splicing, resulting in skipping over exon 6. CONCLUSIONS: The SLC26A4c.765+4A>G mutation is the causative variant in the Chinese family with EVA. Particular attention should be paid to intronic variants.

Integrated approaches for increasing plant yield under salt stress.

Salt stress affects large cultivated areas worldwide, thus causing remarkable reductions in plant growth and yield. To reduce the negative effects of salt stress on plant growth and yield, plant hormones, nutrient absorption, and utilization, as well as developing salt-tolerant varieties and enhancing their morpho-physiological activities, are some integrative approaches to coping with the increasing incidence of salt stress. Numerous studies have been conducted to investigate the critical impacts of these integrative approaches on plant growth and yield. However, a comprehensive review of these integrative approaches, that regulate plant growth and yield under salt stress, is still in its early stages. The review focused on the major issues of nutrient absorption and utilization by plants, as well as the development of salt tolerance varieties under salt stress. In addition, we explained the effects of these integrative approaches on the crop's growth and yield, illustrated the roles that phytohormones play in improving morpho-physiological activities, and identified some relevant genes involve in these integrative approaches when the plant is subjected to salt stress. The current review demonstrated that HA with K enhance plant morpho-physiological activities and soil properties. In addition, NRT and NPF genes family enhance nutrients uptake, NHX1, SOS1, TaNHX, AtNHX1, KDML, RD6, and SKC1, maintain ion homeostasis and membrane integrity to cope with the adverse effects of salt stress, and sd1/Rht1, AtNHX1, BnaMAX1s, ipal-1D, and sft improve the plant growth and yield in different plants. The primary purpose of this investigation is to provide a comprehensive review of the performance of various strategies under salt stress, which might assist in further interpreting the mechanisms that plants use to regulate plant growth and yield under salt stress.

Divergent Synthesis of Pentacyclic Isoindolinones Enabled by Sequential Insertion of Two Different Isocyanides and Acid Promoted Cyclization of Ketenimines.

A palladium-catalyzed multicomponent reaction involving o-bromobenzaldehydes and two different isocyanides was developed to assemble series of isoindolinones with spiroindolenine or azepinoindole skeletons. This sequential insertion reaction features mild conditions, a wide substrate scope, and high efficiency. Preliminary mechanistic study indicated that the difference in steric hindrance between isocyanide components is crucial when regulating the reaction sequence, whereas the ligand also played an important role during the whole process.

Effects of gradient high-field static magnetic fields on diabetic mice.

Although 9.4 T magnetic resonance imaging (MRI) has been tested in healthy volunteers, its safety in diabetic patients is unclear. Furthermore, the effects of high static magnetic fields (SMFs), especially gradient vs. uniform fields, have not been investigated in diabetics. Here, we investigated the consequences of exposure to 1.0-9.4 T high SMFs of different gradients (>10 T/m vs. 0-10 T/m) on type 1 diabetic (T1D) and type 2 diabetic (T2D) mice. We found that 14 h of prolonged treatment of gradient (as high as 55.5 T/m) high SMFs (1.0-8.6 T) had negative effects on T1D and T2D mice, including spleen, hepatic, and renal tissue impairment and elevated glycosylated serum protein, blood glucose, inflammation, and anxiety, while 9.4 T quasi-uniform SMFs at 0-10 T/m did not induce the same effects. In regular T1D mice (blood glucose ≥16.7 mmol/L), the >10 T/m gradient high SMFs increased malondialdehyde ( P<0.01) and decreased superoxide dismutase ( P<0.05). However, in the severe T1D mice (blood glucose ≥30.0 mmol/L), the >10 T/m gradient high SMFs significantly increased tissue damage and reduced survival rate. In vitro cellular studies showed that gradient high SMFs increased cellular reactive oxygen species and apoptosis and reduced MS-1 cell number and proliferation. Therefore, this study showed that prolonged exposure to high-field (1.0-8.6 T) >10 T/m gradient SMFs (35-1 380 times higher than that of current clinical MRI) can have negative effects on diabetic mice, especially mice with severe T1D, whereas 9.4 T high SMFs at 0-10 T/m did not produce the same effects, providing important information for the future development and clinical application of SMFs, especially high-field MRI.

[4 + 1 + 1] Tandem Cyclization Reaction Involving Isocyanides: Access to 2-(Trifluoromethyl)quinazolin-4(3H)-imines.

A palladium-catalyzed three-component reaction of isocyanides, 2,2,2-trifluoro-N-(2-iodophenyl)acetimidoyl chlorides, and amines for the one-pot synthesis of 2-(trifluoromethyl)quinazolin-4(3H)-imines was described. The protocol features a wide substrate scope, high efficiency, and readily available raw materials.

Familial Temperature-Sensitive Auditory Neuropathy: Distinctive Clinical Courses Caused by Variants of the OTOF Gene.

Objective: To investigate the clinical course and genetic etiology of familial temperature-sensitive auditory neuropathy (TSAN), which is a very rare subtype of auditory neuropathy (AN) that involves an elevation of hearing thresholds due to an increase in the core body temperature, and to evaluate the genotype-phenotype correlations in a family with TSAN. Methods: Six members of a non-consanguineous Chinese family, including four siblings complaining of communication difficulties when febrile, were enrolled in this study. The clinical and audiological profiles of the four siblings were fully evaluated during both febrile and afebrile episodes, and the genetic etiology of hearing loss (HL) was explored using next-generation sequencing (NGS) technology. Their parents, who had no complaints of fluctuating HL due to body temperature variation, were enrolled for the genetics portion only. Results: Audiological tests during the patients' febrile episodes met the classical diagnostic criteria for AN, including mild HL, poor speech discrimination, preserved cochlear microphonics (CMs), and absent auditory brainstem responses (ABRs). Importantly, unlike the pattern observed in previously reported cases of TSAN, the ABRs and electrocochleography (ECochG) signals of our patients improved to normal during afebrile periods. Genetic analysis identified a compound heterozygous variant of the OTOF gene (which encodes the otoferlin protein), including one previously reported pathogenic variant, c.5098G > C (p.Glu1700Gln), and one novel variant, c.4882C > A (p.Pro1628Thr). Neither of the identified variants affected the C2 domains related to the main function of otoferlin. Both variants faithfully cosegregated with TSAN within the pedigree, suggesting that OTOF is the causative gene of the autosomal recessive trait segregation in this family. Conclusion: The presence of CMs with absent (or markedly abnormal) ABRs is a reliable criterion for diagnosing AN. The severity of the phenotype caused by dysfunctional neurotransmitter release in TSAN may reflect variants that alter the C2 domains of otoferlin. The observations from this study enrich the current understanding of the phenotype and genotype of TSAN and may lay a foundation for further research on its pathogenesis.

Divergent Reaction of Isocyanides with o-Bromobenzaldehydes: Synthesis of Ketenimines and Lactams with Isoindolinone Cores.

A divergent reaction of isocyanides with o-bromobenzaldehydes for the synthesis of isoindolinone-derived ketenimines and lactams was disclosed. The reaction features readily available reactants, relatively mild conditions, and high yields of products. Ketenimines could be applied in further transformations for access to other functional molecules. A mechanism study showed that the palladium-migration/imine-insertion process was the key step in this reaction.

Targeted next-generation sequencing identified a novel variant of SOX10 in a Chinese family with Waardenburg syndrome type 2.

OBJECTIVE: Waardenburg syndrome type 2 (WS2) is an autosomal dominant syndrome, characterized by bright blue eyes, hearing loss, and depigmented patches of hair and skin. It exhibits high phenotypic and genetic heterogeneity. We explored the molecular etiology in a Chinese family with WS2. METHODS: We recruited a three-generation family with three affected members. Medical history was obtained from all family members who underwent detailed physical examinations and audiology tests. Genomic DNA was extracted from peripheral blood of each individual, and 139 candidate genes associated with hearing loss were sequenced using Illumina HiSeq 2000 (Illumina Inc., San Diego, CA, USA) and verified by Sanger sequencing. RESULTS: Genetic evaluation revealed a novel nonsense heterozygous variant, NM_006941.4: c.342G>A (p.Trp114Ter) in exon 2 of the SOX10 gene in the three affected patients; no unaffected family member carried the variation. We did not detect the variation in 500 Chinese individuals with normal hearing or in 122 unrelated Chinese families with hearing loss, suggesting that it was specific to our patients. CONCLUSIONS: We identified a novel heterozygous nonsense variation in a family with syndromic hearing loss and WS2. Our findings expand the pathogenic spectrum and strengthen the clinical diagnostic role of SOX10 in patients with WS2.

Metabolic profiling of rats poisoned with paraquat and treated with Xuebijing using a UPLC-QTOF-MS/MS metabolomics approach.

Xuebijing (XBJ) is a compound Chinese medicine that contains Paeoniae Radix Rubra, ChuanXiong Rhizoma, Salvia Miltiorrhiza Radix et Rhizoma, Carthami Flos, and Angelicae Sinensis Radix. It is widely used in China to treat sepsis. Previous studies have demonstrated that XBJ can decrease mortality in patients with moderate paraquat poisoning. However, the mechanism by which it exerts this effect is not completely clear. In this study, an ultra-performance liquid chromatography quadrupole time-of-flight mass spectrometry (UPLC-QTOF-MS/MS)-based metabolomics approach was used to perform a metabolic profiling analysis. Principal component analysis (PCA), random forest (RF), and partial least squares discriminant analysis (PLS-DA) were used to identify metabolites to clarify the mechanism of XBJ's activity. XBJ clearly alleviated lung injury in a Sprague Dawley (SD) rat model of paraquat (PQ) poisoning. Seven metabolites related to four pathways, including those involved in sphingolipid and phospholipid metabolism, amino acid metabolism, unsaturated fatty acid metabolism, and pantothenic acid and CoA biosynthesis, were present at different levels in PQ-poisoned rats treated with XBJ compared with untreated rats. XBJ can ameliorate the effects of PQ poisoning in SD rats. Using a metabolomics approach enabled us to gain new insight into the mechanism underlying this effect.

Assessment of a biofluid mechanics-based model for calculating portal pressure in canines.

BACKGROUND: Portal hypertension is a severe complication caused by various chronic liver diseases. The standard methods for detecting portal hypertension (hepatic venous pressure gradient and free portal pressure) are available in only a few hospitals due to their technical difficulty and invasiveness; thus, non-invasive measuring methods are needed. This study aimed to establish and assess a novel model to calculate free portal pressure based on biofluid mechanics. RESULT: Comparison of each dog's virtual and actual free portal pressure showed that a biofluid mechanics-based model could accurately predict free portal pressure (mean difference: -0.220, 95% CI: - 0.738 to 0.298; upper limit of agreement: 2.24, 95% CI: 1.34 to 3.14; lower limit of agreement: -2.68, 95% CI: - 3.58 to - 1.78; intraclass correlation coefficient: 0.98, 95% CI: 0.96 to 0.99; concordance correlation coefficient: 0.97, 95% CI: 0.93 to 0.99) and had a high AUC (0.984, 95% CI: 0.834 to 1.000), sensitivity (92.3, 95% CI: 64.0 to 99.8), specificity (91.7, 95% CI: 61.5 to 99.8), positive likelihood ratio (11.1, 95% CI: 1.7 to 72.8), and low negative likelihood ratio (0.08, 95% CI: 0.01 to 0.6) for detecting portal hypertension. CONCLUSIONS: Our study suggests that the biofluid mechanics-based model was able to accurately predict free portal pressure and detect portal hypertension in canines. With further research and validation, this model might be applicable for calculating human portal pressure, detecting portal hypertensive patients, and evaluating disease progression and treatment efficacy.

The mutation frequencies of GJB2, GJB3, SLC26A4 and MT-RNR1 of patients with severe to profound sensorineural hearing loss in northwest China.

OBJECTIVE: To expose the spectrum and frequency of GJB2, GJB3, SLC26A4 and MT-RNR1 in northwest China and to investigate the underlying causative genes in patients without common mutations. METHODS: We analyzed the mutation screening results of GJB2, GJB3, SLC26A4 and MT-RNR1 in 398 unrelated severe-to-profound probands with bilateral, symmetrical sensorineural hearing loss. Subsequently, we selected 10 probands with a significant family history of inherited hearing loss (HL) that did not have the above four common gene mutations to perform next-generation sequencing (NGS) of 139 known deafness genes, followed by co-segregation analysis of all available family members. RESULTS: Among the 398 patients, 69 (17.34%) had the biallelic GJB2 gene mutations, and the most common mutations were c.235delC, c.109G>A and c.299_300delAT, with allele frequencies of 12.31%, 3.38% and 3.89%, respectively. A total of 63 (15.83%) cases with biallelic SLC26A4 mutations were detected, and the most common pathogenic alleles were c.919-2A>G, c.2168A>G and c.1174A>T, with allele frequencies of 9.17%, 2.26% and 0.88%, respectively. Mitochondrial gene mutations were detected in 9 (2.26%) patients, with 5 cases of mitochondrial DNA (mtDNA) m.1555A>G mutation and 4 cases of mtDNA m.1095T>C mutation. In 10 probands with a clear family history of HL, NGS showed two novel pathogenic variants in 2 families, including c.4129C>T/c.3268C>T in LOXHD1, c.334G>A/c.2968G>T in CDH23. Sanger sequencing confirmed that these variants segregated with the HL in each family. CONCLUSIONS: Our results showed that GJB2 and SLC26A4 were the two major HL-causing genes in northwest China. The most common mutation alleles in GJB2 were c.235delC, c.109G>A and c.299_300delAT, and those in SLC26A4 were c.919-2A>G, c.2168A>G and c.1174A>T. In addition, both genes and their loci can be used as the first selection of deafness gene screening. Additionally, for patients who did not have mutations of these common genes, NGS provided an efficient diagnosis for increasing known deafness genes.

Targeted next-generation sequencing identifies a novel frameshift EYA1 variant causing branchio-otic syndrome in a Chinese family.

OBJECTIVE: To evaluate the genotype-phenotype correlation of branchio-otic syndrome (BOS) in a Chinese family. METHODS: The proband in this study was an 18-month-old boy with hearing loss, preauricular pit, and branchial fistula without a renal anomaly. We collected blood samples from 6 family members, including 4 who were affected by the syndrome. Targeted next-generation sequencing and Sanger sequencing were performed to identify pathogenic mutations in this family. RESULTS: Pedigree analysis indicated that the mode of inheritance in the family was consistent with the autosomal dominant pattern. Hearing loss was the most common manifestation, occurring in 4 patients. Other findings included preauricular pits (n=2), cervical fistulas (n=3) and abnormal pinnae (n=4). None of the patients had renal anomalies. Evaluation by pure-tone audiometry and temporal bone imaging demonstrated bilateral mixed hearing loss, as well as middle ear and inner ear deformities, in two patients. Mutational analysis of candidate genes in the selected patients led to the identification of a novel frameshift variant NM_000503.4: c.1075_1077delinsAT (p.Gly359Ilefs*7) in the EYA1 gene. CONCLUSIONS: The EYA1 c.1075_1077delinsAT mutation is the causative variant in the Chinese family with BOS, although the penetrance is variable within patients.

Recommendations for head and neck surgical oncology practice in a setting of acute severe resource constraint during the COVID-19 pandemic: an international consensus.

The speed and scale of the global COVID-19 pandemic has resulted in unprecedented pressures on health services worldwide, requiring new methods of service delivery during the health crisis. In the setting of severe resource constraint and high risk of infection to patients and clinicians, there is an urgent need to identify consensus statements on head and neck surgical oncology practice. We completed a modified Delphi consensus process of three rounds with 40 international experts in head and neck cancer surgical, radiation, and medical oncology, representing 35 international professional societies and national clinical trial groups. Endorsed by 39 societies and professional bodies, these consensus practice recommendations aim to decrease inconsistency of practice, reduce uncertainty in care, and provide reassurance for clinicians worldwide for head and neck surgical oncology in the context of the COVID-19 pandemic and in the setting of acute severe resource constraint and high risk of infection to patients and staff.

Posttreatment Non-Improved Vocal Cord Mobility Indicates the Need of Salvage Surgery for Hypopharyngeal Carcinomas.

INTRODUCTION: We aimed to analyze the relationship between the changed status of vocal cord mobility and survival outcomes. METHODS: Seventy-eight patients with dysfunctional vocal cords and hypopharyngeal carcinomas accepted non-surgical treatment as the initial therapy between May 2009 and December 2016. Vocal cord mobility was assessed before and after the initial non-surgical treatment. The cord mobility status was classified as normal, impaired, and fixed. Patients with improved mobility (IM) (n =56) were retrospectively analyzed for disease-free survival (DFS), recurrence-free survival (RFS), and overall survival (OS) and compared with 22 patients with non-improved mobility (non-IM). RESULTS: Fifty-six (71.8%) patients had improved cord mobility after the initial non-surgical treatment. The non-improved cord mobility was significantly associated with shortened DFS (P=0.005), RFS (P=0.002), and OS (P<0.001). If non-improved cord mobility was regarded as an indicator for local-regional recurrence within 1 year, the sensitivity and the specificity were 60.9%, 87.5% respectively. The multivariate analysis showed that improved cord mobility (P=0.006) and salvage surgery (P=0.015) were both independent protective factors for OS. CONCLUSION: Changes in cord mobility are a key marker for predicting prognosis. Non-improved cord mobility may indicate a high possibility of a residual tumor, therefore, patients whose cord mobility remains dysfunctional or worsens after non-surgical treatment might need an aggressive salvage strategy.

Establishment and assessment of the hepatic venous pressure gradient using biofluid mechanics (HVPGBFM): protocol for a prospective, randomised, non-controlled, multicentre study.

INTRODUCTION: Portal hypertension (PH) is a severe disease with a poor outcome. Hepatic venous pressure gradient (HVPG), the current gold standard to detect PH, is available only in few hospitals due to its invasiveness and technical difficulty. This study aimed to establish and assess a novel model to calculate HVPG based on biofluid mechanics. METHODS AND ANALYSIS: This is a prospective, randomised, non-controlled, multicentre trial. A total of 248 patients will be recruited in this study, and each patient will undergo CT, blood tests, Doppler ultrasound and HVPG measurement. The study consists of two independent and consecutive cohorts: original cohort (124 patients) and validation cohort (124 patients). The researchers will establish and improve the HVPG using biofluid mechanics (HVPGBFM)model in the original cohort and assess the model in the validation cohort. ETHICS AND DISSEMINATION: The study was approved by the Scientific Research Projects Approval Determination of Independent Ethics Committee of Shanghai Ninth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine (approval number 2017-430 T326). Study findings will be disseminated through peer-reviewed publications and conference presentations. TRIAL REGISTRATION NUMBER: NCT03470389.

Selective impairment of musical emotion recognition in patients with amnesic mild cognitive impairment and mild to moderate Alzheimer disease.

BACKGROUND: Patients with Alzheimer disease (AD) and amnesic mild cognitive impairment (aMCI) have deficits in emotion recognition. However, it has not yet been determined whether patients with AD and aMCI also experience difficulty in recognizing the emotions conveyed by music. This study was conducted to investigate whether musical emotion recognition is impaired or retained in patients with AD and aMCI. METHODS: All patients were recruited from the First Affiliated Hospital of Anhui Medical University between March 1, 2015 and January 31, 2017. Using the musical emotion recognition test, patients with AD (n = 16), patients with aMCI (n = 19), and healthy controls (HCs, n = 16) were required to choose one of four emotional labels (happy, sad, peaceful, and fearful) that matched each musical excerpt. Emotion recognition scores in three groups were compared using one-way analysis of variance (ANOVA) test. We also investigated the relationship between the emotion recognition scores and Mini-Mental State Examination (MMSE) using Pearson's correlation analysis test in patients with AD and aMCI. RESULTS: Compared to the HC group, both of the patient groups showed deficits in the recognition of fearful musical emotions (HC: 7.88 ±â€Š1.36; aMCI: 5.05 ±â€Š2.34; AD: 3.69 ±â€Š2.02), with results of a one-way ANOVA confirming a significant main effect of group (F(2,50) = 18.70, P < 0.001). No significant differences were present among the three groups for the happy (F(2,50)=2.57, P = 0.09), peaceful (F(2,50) = 0.38, P = 0.09), or sad (F(2,50) = 2.50, P = 0.09) musical emotions. The recognition of fearful musical emotion was positively associated with general cognition, which was evaluated by MMSE in patients with AD and aMCI (r = 0.578, P < 0.001). The correlations between the MMSE scores and recognition of the remaining emotions were not significant (happy, r = 0.228, P = 0.11; peaceful, r = 0.047, P = 0.74; sad, r = 0.207, P = 0.15). CONCLUSION: This study showed that both patients with AD and aMCI had decreased ability to distinguish fearful emotions, which might be correlated with diminished cognitive function.

Combined preoperative albumin-bilirubin (ALBI) and serum γ-glutamyl transpeptidase (GGT) predicts the outcome of hepatocellular carcinoma patients following hepatic resection.

Background: Liver function is an important prognostic factor for patients with hepatocellular carcinoma. The purpose of this study was to develop and validate a nomogram integrating the albumin-bilirubin (ALBI) and serum γ-glutamyl transpeptidase (GGT) level to predict postoperative overall survival (OS) and disease-free survival (DFS) of hepatocellular carcinoma (HCC). Methods: The effect of combined of ALBI and GGT on HCC prognosis was investigated using univariate and multivariate Cox analyses. The nomogram for OS and DFS were developed, respectively, and their predictive ability was compared with other conventional staging systems, including the American Joint Commission on Cancer (AJCC), Barcelona Clinic Liver Cancer (BCLC) and the Cancer of the Liver Italian Program (CLIP). Results: Combined ALBI and GGT was highly associated with OS (P<0.001) and DFS (P<0.001) of HCC patients treated with hepatic resection. In addition, the C-index of the OS (0.706±0.034) or DFS (0.674±0.032) nomogram in the training cohort was larger than AJCC, BCLC and CLIP. The Akaike information criterion (AICs) of the OS (2178.405) or DFS (2961.018) nomogram in the training cohort was smaller than above staging systems. The results suggested that the OS or DFS nomogram was the most powerful model to predict HCC prognosis. The similar trend was observed in the validation cohort. Conclusion: The novel nomogram integrating ALBI and GGT was highly associated with OS and DFS of postoperative HCC patients.

Palladium Catalyzed Insertion Reaction of Isocyanides with 3-Arylisoxazol-5(4H)-ones: Synthesis of 4-Aminomethylidene Isoxazolone Derivates.

A palladium catalyzed insert reaction of isocyanides to 3-arylisoxazol-5(4H)-ones for the construction of 4-aminomethylidene isoxazolone derivates is reported. In this transformation, only the C-H bond of the methylene group was involved while the remaining ring structure was retained. In general, this work provided a new protocol for the synthesis of 4-aminomethylidene isoxazolones.

Mn(III)-Mediated Cascade Cyclization of 3-Isocyano-[1,1'-biphenyl]-2-carbonitrile with Arylboronic Acid: Construction of Pyrrolopyridine Derivatives.

A Mn(III) mediated cascade cyclization of new designed multifunctionalized 3-isocyano-[1,1'-biphenyl]-2-carbonitrile with arylboronic acid to construct pyrrolopyridine derivatives is developed. A series of pyrroloporidine compounds have been constructed through the formation of two new C-C bonds and one C-N bond via a radical pathway.

The discovery of a novel eight-mRNA-lncRNA signature predicting survival of hepatocellular carcinoma patients.

Increasing evidence indicates that the expressions of messenger RNAs (mRNAs) and long non-coding RNAs (lncRNAs) undergo a frequent and aberrant change in carcinogenesis and cancer development. But some research was carried out on mRNA-lncRNA signatures for prediction of hepatocellular carcinoma (HCC) prognosis. We aimed to establish an mRNA-lncRNA signature to improve the ability to predict HCC patients' survival. The subjects from the cancer genome atlas (TCGA) data set were randomly divided into two parts: training data set (n = 246) and testing data set (n = 124). Using computational methods, we selected eight gene signatures (five mRNAs and three lncRNAs) to generate the risk score model, which were significantly correlated with overall survival of patients with HCC in both training and testing data set. The signature had the ability to classify the patients in training data set into a high-risk group and low-risk group with significantly different overall survival (hazard ratio = 4.157, 95% confidence interval = 2.648-6.526, P < 0.001). The prognostic value was further validated in testing data set and the entire data set. Further analysis revealed that this signature was independent of tumor stage. In addition, Gene Set Enrichment Analysis suggested that high risk score group was associated with cell proliferation and division related pathways. Finally, we developed a well-performed nomogram integrating the prognostic signature and other clinical information to predict 3- and 5-year overall survival. In conclusion, the prognostic mRNAs and lncRNAs identified in our study indicate their potential role in HCC biogenesis. The risk score model based on the mRNA-lncRNA may be an efficient classification tool to evaluate the prognosis of patients' with HCC.