Elevated proton motive force is a tetracycline resistance mechanism that leads to the sensitivity to gentamicin in Edwardsiella tarda.

Tetracycline is a commonly used human and veterinary antibiotic that is mostly discharged into environment and thereby tetracycline-resistant bacteria are widely isolated. To combat these resistant bacteria, further understanding for tetracycline resistance mechanisms is needed. Here, GC-MS based untargeted metabolomics with biochemistry and molecular biology techniques was used to explore tetracycline resistance mechanisms of Edwardsiella tarda. Tetracycline-resistant E. tarda (LTB4-RTET ) exhibited a globally repressed metabolism against elevated proton motive force (PMF) as the most characteristic feature. The elevated PMF contributed to the resistance, which was supported by the three results: (i) viability was decreased with increasing PMF inhibitor carbonylcyanide-3-chlorophenylhydrazone; (ii) survival is related to PMF regulated by pH; (iii) LTB4-RTET were sensitive to gentamicin, an antibiotic that is dependent upon PMF to kill bacteria. Meanwhile, gentamicin-resistant E. tarda with low PMF are sensitive to tetracycline is also demonstrated. These results together indicate that the combination of tetracycline with gentamycin will effectively kill both gentamycin and tetracycline resistant bacteria. Therefore, the present study reveals a PMF-enhanced tetracycline resistance mechanism in LTB4-RTET and provides an effective approach to combat resistant bacteria.

pts promoter influences antibiotic resistance via proton motive force and ROS in Escherichia coli.

Introduction: Glucose level is related to antibiotic resistance. However, underlying mechanisms are largely unknown. Methods: Since glucose transport is performed by phosphotransferase system (PTS) in bacteria, pts promoter-deleted K12 (Δpts-P) was used as a model to investigate effect of glucose metabolism on antibiotic resistance. Gas chromatography-mass spectrometry based metabolomics was employed to identify a differential metabolome in Δpts-P compared with K12, and with glucose as controls. Results: Δpts-P exhibits the resistance to ß-lactams and aminoglycosides but not to quinolones, tetracyclines, and macrolide antibiotics. Inactivated pyruvate cycle was determined as the most characteristic feature in Δpts-P, which may influence proton motive force (PMF), reactive oxygen species (ROS), and nitric oxide (NO) that are related to antibiotic resistance. Thus, they were regarded as three ways for the following study. Glucose promoted PMF and ß-lactams-, aminoglycosides-, quinolones-mediated killing in K12, which was inhibited by carbonyl cyanide 3-chlorophenylhydrazone. Exogenous glucose did not elevated ROS in K12 and Δpts-P, but the loss of pts promoter reduced ROS by approximately 1/5, which was related to antibiotic resistance. However, NO was neither changed nor related to antibiotic resistance. Discussion: These results reveal that pts promoter regulation confers antibiotic resistance via PMF and ROS in Escherichia coli.

Baicalin attenuated metabolic dysfunction-associated fatty liver disease by suppressing oxidative stress and inflammation via the p62-Keap1-Nrf2 signalling pathway in db/db mice.

Metabolic dysfunction-associated fatty liver disease (MAFLD) is the main cause of chronic liver disease. Baicalin (Bai), a bioactive molecule found in Scutellaria baicalensis Georgi, possesses antioxidant and antiinflammatory properties. These activities suggest Bai could be a promising therapeutic agent against NAFLD; however, its specific effects and underlying mechanism are still not clear. This study aims to explore the effect of Bai to attenuate MAFLD and associated molecular mechanisms. Bai (50, 100 or 200 mg/kg) was orally administered to db/db mice with MAFLD for 4 weeks or db/m mice as the normal control. Bai markedly attenuated lipid accumulation, cirrhosis and hepatocytes apoptosis in the liver tissues of MAFLD mice, suggesting strong ability to attenuate MAFLD. Bai significantly reduced proinflammatory biomarkers and enhanced antioxidant enzymes, which appeared to be modulated by the upregulated p62-Keap1-Nrf2 signalling cascade; furthermore, cotreatment of Bai and all-trans-retinoic acid (Nrf2 inhibitor) demonstrated markedly weakened liver protective effects by Bai and its induced antioxidant and antiinflammatory responses. The present study supported the use of Bai in attenuating MAFLD as a promising therapeutic agent, and its strong mechanism of action in association with the upregulating the p62-keap1-Nrf2 pathway.

Noninvasive prognostic factors and web predictive tools for idiopathic sudden sensorineural hearing loss.

PURPOSE: To friendly predict a reference prognostic outcome for idiopathic sudden sensorineural hearing loss (ISSNHL) patients with or without anxiety, we identified independent prognostic factors and developed practical predictive tools without invasive tests. METHODS: Patients with ISSNHL in our center were enrolled from June 2013 to December 2018. Univariate and multivariate logistic regression analyses were performed to identify independent prognostic factors of the complete recovery and the overall recovery for ISSNHL, which were subsequently utilized to develop the web nomograms. The discrimination, calibration, and clinical benefit were used to evaluate the performance of nomograms for ISSNHL. RESULTS: 704 ISSNHL patients were finally enrolled in this study. Multivariate logistic regression analysis showed that age, time of onset, gender, affected ear, degree, and type of hearing loss were independent prognostic factors of complete recovery. Age, time of onset, affected ear, and type of hearing loss were independent prognostic factors of overall recovery. Web predictive nomograms were developed with excellent discrimination, calibration, and clinical value. CONCLUSION: Based on the patients' data with a considerable size, independent noninvasive prognostic factors of complete recovery and overall recovery of ISSNHL were identified. Integrating these prognostic factors without invasive tests, practical web predictive nomograms were developed. Using web nomograms, clinical doctors could provide reference data (the predicted recovery rate) for supporting prognostic consultation of ISSNHL patients, especially those with anxiety.

The causal association between peripheral blood eosinophils and nasal polyps: a Mendelian randomization study.

OBJECTIVE: Observational studies suggested that peripheral blood eosinophils were associated with the risk of nasal polyps. However, these studies did not confirm the causality. This study aims to apply Mendelian randomization (MR) method to comprehensively assess the potential causal association between peripheral blood eosinophils and nasal polyps. METHODS: Genetic instrumental variables were extracted from the largest available genome-wide association study (GWAS) of European participants, which were used to investigate the relationship between peripheral blood eosinophils and nasal polyps. The inverse variance weighted method, the MR Egger method, and the weighted median method were applied for this analysis. MR-Egger intercept tests, leave-one-out analyses, and funnel plots were performed for the sensitivity analysis. RESULTS: With the inverse variance weighted method, the MR analysis suggested that there was a significant difference between peripheral blood eosinophils and the risk of nasal polyps (ukb-a-97, OR 1.004, 95% CI 1.003-1.005, p < 0.001; ukb-a-541, OR 1.005, 95% CI 1.004-1.006, p < 0.001; ukb-b-7211, OR 1.004, 95% CI 1.003-1.005, p < 0.001; ukb-b-8425, OR 1.004, 95% CI 1.003-1.005, p < 0.001; finn-b-J10_NASALPOLYP, OR 3.089, 95% CI 2.537-3.761, p < 0.001). Consistent results were also proved by using the weighted median method and the MR Egger method. CONCLUSIONS: Our findings reveal the causal effect of peripheral blood eosinophils on the increased risk of nasal polyps.

Apomictic Malus plants exhibit abnormal pollen development.

Apomixis is the asexual reproduction through seeds that leads to the production of genetically uniform progeny. It has become an important tool in plant breeding because it facilitates the retention of genotypes with desirable traits and allows seeds to be obtained directly from mother plants. Apomixis is rare in most economically important crops, but it occurs in some Malus species. Here, the apomictic characteristics of Malus were examined using four apomictic and two sexually reproducing Malus plants. Results from transcriptome analysis showed that plant hormone signal transduction was the main factor affecting apomictic reproductive development. Four of the apomictic Malus plants examined were triploid, and pollen was either absent or present in very low densities in the stamen. Variation in the presence of pollen was associated with variation in the apomictic percentage; specifically, pollen was absent in the stamens of tea crabapple plants with the highest apomictic percentage. Furthermore, pollen mother cells failed to progress normally into meiosis and pollen mitosis, a trait mostly observed in apomictic Malus plants. The expression levels of meiosis-related genes were upregulated in apomictic plants. Our findings indicate that our simple method of detecting pollen abortion could be used to identify apple plants that are capable of apomictic reproduction.

Ampicillin-controlled glucose metabolism manipulates the transition from tolerance to resistance in bacteria.

The mechanism(s) of how bacteria acquire tolerance and then resistance to antibiotics remains poorly understood. Here, we show that glucose abundance decreases progressively as ampicillin-sensitive strains acquire resistance to ampicillin. The mechanism involves that ampicillin initiates this event via targeting pts promoter and pyruvate dehydrogenase (PDH) to promote glucose transport and inhibit glycolysis, respectively. Thus, glucose fluxes into pentose phosphate pathway to generate reactive oxygen species (ROS) causing genetic mutations. Meanwhile, PDH activity is gradually restored due to the competitive binding of accumulated pyruvate and ampicillin, which lowers glucose level, and activates cyclic adenosine monophosphate (cAMP)/cAMP receptor protein (CRP) complex. cAMP/CRP negatively regulates glucose transport and ROS but enhances DNA repair, leading to ampicillin resistance. Glucose and Mn2+ delay the acquisition, providing an effective approach to control the resistance. The same effect is also determined in the intracellular pathogen Edwardsiella tarda. Thus, glucose metabolism represents a promising target to stop/delay the transition of tolerance to resistance.

Postoperative Adjuvant Hepatic Arterial Infusion Chemotherapy With FOLFOX in Hepatocellular Carcinoma With Microvascular Invasion: A Multicenter, Phase III, Randomized Study.

PURPOSE: To report the efficacy and safety of postoperative adjuvant hepatic arterial infusion chemotherapy (HAIC) with 5-fluorouracil and oxaliplatin (FOLFOX) in hepatocellular carcinoma (HCC) patients with microvascular invasion (MVI). PATIENTS AND METHODS: In this randomized, open-label, multicenter trial, histologically confirmed HCC patients with MVI were randomly assigned (1:1) to receive adjuvant FOLFOX-HAIC (treatment group) or routine follow-up (control group). The primary end point was disease-free survival (DFS) by intention-to-treat (ITT) analysis while secondary end points were overall survival, recurrence rate, and safety. RESULTS: Between June 2016 and August 2021, a total of 315 patients (ITT population) at five centers were randomly assigned to the treatment group (n = 157) or the control group (n = 158). In the ITT population, the median DFS was 20.3 months (95% CI, 10.4 to 30.3) in the treatment group versus 10.0 months (95% CI, 6.8 to 13.2) in the control group (hazard ratio, 0.59; 95% CI, 0.43 to 0.81; P = .001). The overall survival rates at 1 year, 2 years, and 3 years were 93.8% (95% CI, 89.8 to 98.1), 86.4% (95% CI, 80.0 to 93.2), and 80.4% (95% CI, 71.9 to 89.9) for the treatment group and 92.0% (95% CI, 87.6 to 96.7), 86.0% (95% CI, 79.9 to 92.6), and 74.9% (95% CI, 65.5 to 85.7) for the control group (hazard ratio, 0.64; 95% CI, 0.36 to 1.14; P = .130), respectively. The recurrence rates were 40.1% (63/157) in the treatment group and 55.7% (88/158) in the control group. Majority of the adverse events were grade 0-1 (83.8%), with no treatment-related death in both groups. CONCLUSION: Postoperative adjuvant HAIC with FOLFOX significantly improved the DFS benefits with acceptable toxicities in HCC patients with MVI.

Recent Advances in Local Thermal Ablation Therapy for Hepatocellular Carcinoma.

Image-guided local thermal ablation (LTA) plays an important role in the treatment of hepatocellular carcinoma (HCC), especially in patients with HCC who are not suitable for hepatectomy. Radiofrequency ablation (RFA) and microwave ablation (MWA) are the most widely used LTA clinically. Radiofrequency ablation can achieve the best result; that is, a similar therapeutic effect as hepatectomy if the tumor ≤3 cm, while MWA can effectively ablate tumors ≤5 cm. Local thermal ablation has an advantage over liver resection in terms of minimally invasive surgery and can achieve a comparable prognosis and efficacy to liver resection. For borderline liver function, selecting LTA as the first-line therapy may bring more benefits to patients with cirrhosis background. In addition, a combination of multiple therapies for HCC is a good choice, such as LTA combined with transcatheter arterial chemoembolization (TACE), which can achieve a better prognosis than single therapy for larger tumors. For patients who are awaiting liver transplantation, LTA is a good choice. The main problem of LTA needed to be solved is to prevent the local tumor recurrence after ablation in patients with HCC.

Pulmonary Function in Metabolic Syndrome: A Meta-Analysis.

Background: This study aims to systematically evaluate the association between metabolic syndrome (MS) and pulmonary function through meta-analysis. Methods: Electronic databases, including PubMed, Embase, Web of Science, and Cochrane Library, were systematically searched to obtain articles associated with MS and lung function published before December 31, 2021. According to the including and excluding criteria, certain studies were obtained and data were extracted. The Newcastle Ottawa Scale was used to evaluate the quality of the studies. A pooled standardized mean difference (SMD) was calculated by means of random-effects meta-analysis. Different effect models were used according to the heterogeneity. Meta-regression and sensitivity analyses were performed to examine the possible sources of heterogeneity. The Begg's funnel plot and Egger's test were used to evaluate publication bias. Analyses were performed using Stata MP, version14.0 (StataCorp LP, College Station, TX, USA). Results: A total of 15 studies, involving 10,285 cases of MS and 25,416 cases of control, were included in this meta-analysis on the relationship between MS and forced vital capacity (FVC). The pooled SMD for FVC was -0.247 (95% CI = -0.327 to -0.2167, P < 0.001) using random effect model, indicating the decrease of FVC in the patients with MS. In the same studies, the pooled SMD for forced expiratory volume in 1 sec (FEV1) was -0.205 (95% CI = -0.3278 to -0.133, P < 0.001), indicating the decrease of FEV1 also existed in the MS cases. A total of 13 studies, involving 8167 cases of MS and 19,788 cases of control, were included in this meta-analysis on the relationship between MS and FEV1/FVC. The pooled SMD for FEV1/FVC was 0.011 (95% CI = -0.072 to 0.093, P = 0.798) using random effect model, indicating that there was no significant difference between the patients with MS and the control. After introducing the diastolic blood pressure and glycemia into the regression model of the relationship between MS and FVC, the variance of the studies (tau2) decreased from 0.0190 to 0.006694 and 0.007205, which could explain 66.70% and 78.04% of the sources of heterogeneity, and the P values were 0.038 and 0.023. The results suggested that hypertension (diastolic pressure) and hyperglycemia were the factors linked to the heterogeneity among the included studies on both FVC and FEV1. The Begg's funnel plot and Egger's test both showed no evidence of publication bias. Conclusions: Our results show that FVC and FEV1 decrease in MS patients, while FEV1/FVC has no significant difference compared with the control group. It indicates that the patients with MS have restrictive ventilatory functional disturbance. Meta-regression analysis suggests that hypertension (diastolic pressure) and hyperglycemia are the factors linked to the heterogeneity among the included studies on both FVC and FEV1.

Global transcriptional regulator FNR regulates the pyruvate cycle and proton motive force to play a role in aminoglycosides resistance of Edwardsiella tarda.

Bacterial metabolism is related to resistance and susceptibility to antibiotics. Fumarate and nitrate reduction regulatory protein (FNR) is a global transcriptional regulator that regulates metabolism. However, the role of FNR in antibiotic resistance is elusive. Here, fnr deletion mutant was constructed and used to test the role in Edwardsiella tarda EIB202 (EIB202). Δfnr exhibited elevated sensitivity to aminoglycosides. The mutant had a globally enhanced metabolome, with activated alanine, aspartate, and glutamate metabolism and increased abundance of glutamic acid as the most impacted pathway and crucial biomarker, respectively. Glutamate provides a source for the pyruvate cycle (the P cycle) and thereby relationship between exogenous glutamate-activated P cycle and gentamicin-mediated killing was investigated. The activated P cycle elevated proton motive force (PMF). Consistently, exogenous glutamate potentiated gentamicin-mediated killing to EIB202 as the similarity as the loss of FNR did. These findings reveal a previously unknown regulation by which FNR downregulates glutamate and in turn inactivates the P cycle, which inhibits PMF and thereby exhibits the resistance to aminoglycosides.

[Effects of temperature on growth, survival, and reproduction of Conogethes punctiferalis feeding on corn kernels]. / 温度对取食玉米籽粒桃蛀螟生长发育、存活和生殖的影响.

In order to examine the effects of temperature on the growth, survival, and reproduction of Conogethes punctiferalis (Lepidoptera: Crambidae) feeding on corn kernels, the life table parameters of C. punctiferalis at 21, 24, 27, 30 ℃ were calculated based on the age-stage two-sex life table theory, and then population dynamics of C. punctiferalis was projected based on these parameters. The results showed that the life cycles of the pest could be finished at all the four temperature treatments. The developmental duration of each stage shortened with increasing temperature, and there were significant differences among treatments. The highest fecundity (116.7 eggs per female), preadult survival rate (84.7%), and proportion of female (0.46) were observed at 24 ℃. The intrinsic rates of increase at 24, 27, 30 ℃ were 0.1059, 0.1101, and 0.1045 d-1, respectively. The finite rates of increase were 1.1117, 1.1164, and 1.1102 d-1, respectively. There was no significant difference among the three treatments, but the r and λ values were significantly higher than those at 21 ℃. The net reproductive rates (R0) at 21, 24, 27, 30 ℃ were 17.3, 53.7, 36.9, and 19.8, respectively. R0 at 24 ℃ was the highest. It suggested that survival rates, fecundities and female proportions of C. punctiferalis population were high at 24-27 ℃, which was the suitable temperature range for its growth, survival, and reproduction.

[Influence of hemoglobin level(Hb) on survival and prognosis of elderly hip fracture at admission].

OBJECTIVE: To analyze the relationship between hemoglobin(Hb) level on admission and survival prognosis of patients with hip fracture. METHODS: From February 2016 to October 2018, 249 elderly patients with hip fracture were surgically treated including 62 males and 187 females;the age ranged from 60 to 91(73.67±10.52) years;the time from injury to operation was (6.79±2.27) d. The clinical and laboratory examination results were collected. The Hb level at admission and the mortality at 30, 90, 180 and 360 days after operation were observed. According to the Hb level at admission, the patients were divided into Hb<120 g/L and Hb≥120 g/L groups. The survival conditions of the two groups at 30, 90, 180 and 360 days after operation were compared and analyzed. Logistic regression was used to analyze the effect of Hb level on death 30, 90, 180 and 360 days after operation. RESULTS: The mortality rates at 30, 90, 180 and 360 days after operation were 5.22%, 9.24%, 16.87% and 20.48% respectively. The level of Hb at admission was a risk factor for prognosis and death 30, 90, 180 and 360 days after operation(P<0.05). The OR(95% CI) were 2.431(1.475-4.006), 2.625(1.468-4.695), 2.276(1.320-3.925) and 2.082(1.221-3.551) respectively. CONCLUSION: The level of Hb at admission can affect the survival and prognosis of elderly patients with hip fracture. We should further study how to manage the level of Hb before operation.

The OPG/RANKL/RANK system modulates calcification of common carotid artery in simulated microgravity rats by regulating NF-κB pathway.

Functional and structural adaptation of common carotid artery could be one of the important causes of postflight orthostatic intolerance after microgravity exposure, the mechanisms of which remain unclear. Recent evidence indicates that long-term spaceflight increases carotid artery stiffness, which might present a high risk to astronaut health and postflight working ability. Studies have suggested that vascular calcification is a common pathological change in cardiovascular diseases that is mainly manifested as an increase in vascular stiffness. Therefore, this study investigated whether simulated microgravity induces calcification of common carotid artery and to elucidate the underlying mechanisms. Four-week-old hindlimb-unweighted (HU) rats were used to simulate the deconditioning effects of microgravity on cardiovascular system. We found that simulated microgravity induced vascular smooth muscle cell (VSMC) osteogenic differentiation and medial calcification, increased receptor activator of nuclear factor κB (NF-κB) ligand (RANKL) and RANK expression, and enhanced NF-κB activation in rat common carotid artery. In vitro activation of the RANK pathway with exogenous RANKL, a RANK ligand, increased RANK and osteoprotegerin (OPG) expression in HU rats. Moreover, the expression of osteogenic markers and activation of NF-κB in HU rats were further enhanced by exogenous RANKL but suppressed by the RANK inhibitor osteoprotegerin fusion protein (OPG-Fc). These results indicated that the OPG/RANKL/RANK system modulates VSMC osteogenic differentiation and medial calcification of common carotid artery in simulated microgravity rats by regulating the NF-kB pathway.

Construction of a novel immune-related lncRNA signature and its potential to predict the immune status of patients with hepatocellular carcinoma.

BACKGROUND: The accuracy of existing biomarkers for predicting the prognosis of hepatocellular carcinoma (HCC) is not satisfactory. It is necessary to explore biomarkers that can accurately predict the prognosis of HCC. METHODS: In this study, original transcriptome data were downloaded from The Cancer Genome Atlas (TCGA) database. Immune-related long noncoding ribonucleic acids (irlncRNAs) were identified by coexpression analysis, and differentially expressed irlncRNA (DEirlncRNA) pairs were distinguished by univariate analysis. In addition, the least absolute shrinkage and selection operator (LASSO) penalized regression was modified. Next, the cutoff point was determined based on the area under the curve (AUC) and Akaike information criterion (AIC) values of the 5-year receiver operating characteristic (ROC) curve to establish an optimal model for identifying high-risk and low-risk groups of HCC patients. The model was then reassessed in terms of clinicopathological features, survival rate, tumor-infiltrating immune cells, immunosuppressive markers, and chemotherapy efficacy. RESULTS: A total of 1009 pairs of DEirlncRNAs were recognized in this study, 30 of these pairs were included in the Cox regression model for subsequent analysis. After regrouping according to the cutoff point, we could more effectively identify factors such as aggressive clinicopathological features, poor survival outcomes, specific immune cell infiltration status of tumors, high expression level of immunosuppressive biomarkers, and low sensitivity to chemotherapy drugs in HCC patients. CONCLUSIONS: The nonspecific expression level signature involved with irlncRNAs shows promising clinical value in predicting the prognosis of HCC patients.

Development and Validation of a Model Including Distinct Vascular Patterns to Estimate Survival in Hepatocellular Carcinoma.

Importance: Because of tumor heterogeneity, traditional clinical variables remain insufficient to predict recurrence, which impairs long-term survival among patients undergoing radical hepatectomy for hepatocellular carcinoma (HCC). Vessels encapsulating tumor clusters (VETC) constitute a novel vascular pattern distinct from microvascular invasion (MVI), representing biological aggressiveness of HCC. Objective: To establish a model to estimate individualized recurrence-free survival (RFS) in HCC by integrating VETC and MVI. Design, Setting, and Participants: This prognostic study included 498 patients undergoing radical hepatectomy for HCC from 5 academic centers in China from January 1, 2013, to December 31, 2016, and consisted of 3 cohorts: training (243 [48.8%]), internal validation (122 [24.5%]), and external validation (133 [26.7%]). Follow-up was completed on March 30, 2020, and the data were analyzed from December 1 to 31, 2020. Exposures: VETC, MVI, tumor number, and maximum tumor size. Main Outcomes and Measures: The primary end point was RFS. The risk score for relative recurrence and nomogram for absolute RFS probability were derived from the final model, which contained variables recommended by multivariate least absolute shrinkage and selection operator Cox proportional hazards regression analysis. Their performance was quantified using the Harrell concordance index (C index), the time-dependent area under the receiver operating characteristic curve, and calibration curves and was compared with 6 prognostic systems. Recurrence-free survival was estimated by the Kaplan-Meier method, and RFS curves were compared using a log-rank test. Results: Among the 498 patients, 432 (86.7%) were men; the mean (SD) age at diagnosis was 51.4 (11.3) years. Independent predictors for RFS identified included VETC, MVI, tumor number, and maximum tumor size, which were incorporated into the multivariate model (VMNS model). The C index (0.702; 95% CI, 0.653-0.752) for the VMNS score of the training cohort was significantly higher than those of 6 conventional systems (0.587 [95% CI, 0.535-0.638] to 0.657 [95% CI, 0.606-0.708]). Different recurrence risk groups defined by the VMNS score showed significantly different 2-year RFS (low-risk group, 81.4% [SE, 0.036]; medium-risk group, 62.1% [SE, 0.054]; high-risk group, 30.1% [SE, 0.079]; P < .001). Calibration curves of the VMNS nomogram showed good agreement between the nomogram-predicted RFS probability and actual RFS proportion. The internal and external validation cohorts confirmed the results. Conclusions and Relevance: The VMNS model enabled individualized prognostication of RFS in patients with HCC undergoing curative resection.

Expression pattern and prognostic value of N6-methyladenosine RNA methylation key regulators in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is still one of the most common malignancies worldwide. The accuracy of biomarkers for predicting the prognosis of HCC and the therapeutic effect is not satisfactory. N6-methyladenosine (m6A) methylation regulators play a crucial role in various tumours. Our research aims further to determine the predictive value of m6A methylation regulators and establish a prognostic model for HCC. In this study, the data of HCC from The Cancer Genome Atlas (TCGA) database was obtained, and the expression level of 15 genes and survival was examined. Then we identified two clusters of HCC with different clinical factors, constructed prognostic markers and analysed gene set enrichment, proteins' interaction and gene co-expression. Three subgroups by consensus clustering according to the expression of the 13 genes were identified. The risk score generated by five genes divided HCC patients into high-risk and low-risk groups. In addition, we developed a prognostic marker that can identify high-risk HCC. Finally, a novel prognostic nomogram was developed to accurately predict HCC patients' prognosis. The expression levels of 13 m6A RNA methylation regulators were significantly upregulated in HCC samples. The prognosis of cluster 1 and cluster 3 was worse. Patients in the high-risk group show a poor prognosis. Moreover, the risk score was an independent prognostic factor for HCC patients. In conclusion, we reveal the critical role of m6A RNA methylation modification in HCC and develop a predictive model based on the m6A RNA methylation regulators, which can accurately predict HCC patients' prognosis and provide meaningful guidance for clinical treatment.