Predictive Role of a Novel Ferroptosis-Related lncRNA Pairs Model in the Prognosis of Papillary Thyroid Carcinoma.

This study aimed to evaluate the potential prognostic value of ferroptosis-related long non-coding RNAs (lncRNAs) in papillary thyroid carcinoma (PTC). Based on The TCGA database, lncRNAs and ferroptosis-related genes with differential expression levels in PTC tumors vs. normal tissues were screened. After the co-expression network construction, ferroptosis-related lncRNAs (FRLs) were screened. Kaplan-Meier analysis was conducted to compare the survival performance of patients with PTC in the high- and low-risk groups. Furthermore, a nomogram was created to enhance PTC prognosis. CIBERSORT was used to investigate the infiltration of various immune cells in high- and low-risk groups. In total, 10 lncRNA pairs with differential expression levels were obtained. There were significant differences in the histological subtype and pathological stage between the high- and low-risk groups, and age (P = 7.39E-13) and FRLM model status (P = 1.09E-04) were identified as independent prognostic factors. Subsequently, the nomogram survival model showed that the predicted one-, three-, and five-year survival rates were similar to the actual one- (c-index = 0.8475), three- (c-index = 0.7964), and five-year (c-index = 0.7555) survival rates. Subjects in the low-risk group had significantly more CD4 + memory T cells and resting myeloid dendritic cells, and subjects in the high-risk group had more plasma B cells and monocytes. The risk assessment model constructed using FRLs showed good predictive value for the prognosis of patients with PTC.

Laser hemorrhoidoplasty vs. rubber band ligation: a randomized trial comparing 2 mini-invasive treatment for grade II hemorrhoids.

PURPOSE: As a minimally invasive procedure, laser hemorrhoidoplasty (LHP) can not only relieve the symptoms of hemorrhoids, but also protect the anal cushion structure. This study aimed to investigate the clinical efficacy of LHP in the treatment of grade II hemorrhoids. METHODS: A total of 70 patients with grade II hemorrhoids were randomly assigned to receive LHP or Rubber Band Ligation (RBL) (n = 35 per group) in 2019 from a single center. The postoperative pain, bleeding, feeling of anal distension(local falling, swelling, foreign body sensation, stool) and postoperative recurrence rate were compared between the two groups. RESULTS: The postoperative pain, bleeding, and feeling of anal distension in the LHP group were improved significantly as compared with the RBL group within 2 weeks after surgery (P < 0.01). Both methods can relieve the symptoms of grade II hemorrhoids. There was no difference in the recurrence rate between the two groups at 1 year after surgery (P > 0.05). The patients in LHP group took less time to return to normal activities (P < 0.001). CONCLUSIONS: As a minimally invasive treatment, LHP is easy and not traumatic and results in mild postoperative pain and few complications. It is an ideal choice for grade II hemorrhoids.

Lasiodiplodiapyrones A and B, Pyrone-Preussomerin Adducts with Highly Strained Polycyclic Ring Systems from Lasiodiplodia pseudotheobromae.

Lasiodiplodiapyrones A and B (1 and 2), two new preussomerin derivatives, possessing an unexpected 6-methyl-4H-furo[3,2-c]pyran-4-one moiety and a highly functionalized conjoint and complicated polycyclic ring system, along with two known congeners (3 and 4), were isolated from the fungus Lasiodiplodia pseudotheobromae. Their structures including absolute configurations were determined by spectroscopic analyses, Mosher's method, and ECD calculations. A biosynthetic pathway was proposed to explain the origin of lasiodiplodiapyrones A and B as well as their relationship with preussomerins. Compounds 1-4 showed suppressive effects on the production of NO with IC50 values of 4.8 ± 0.3, 8.5 ± 1.1, 5.9 ± 0.8, and 12.8 ± 1.3 µM, respectively.

Clinical factors of PICC-RVT in cancer patients: a meta-analysis.

PURPOSE: There is a lack of studies that systematically evaluate the clinical factors of PICC-RVT such as treatment, tumor stage, metastasis, and chemotherapy drugs in cancer patients. This study, therefore, aims to evaluate the clinical factors of catheter-related venous thrombosis in cancer patients with indwelling PICC to provide a basis for the clinical prevention and reduction of thrombosis. METHODS: Relevant studies were retrieved from major databases (PubMed, Embase, Web of Science, China National Knowledge Infrastructure (CNKI), WanFang Data, and China Biology Medicine disc (CMB)) and searched from their earliest available dates until July 2022. If two or more studies had the same outcome, a meta-analysis using RevMan 5.4.1 was performed. This systematic review was registered at PROSPERO (number CRD42022358426). RESULTS: A total of 19 articles involving 19,824 patients were included for quantitative analysis. Meta-analysis of these studies indicated that a history of chemotherapy, tumor type, tumor stage, presence or absence of metastasis, and use of fluorouracil, etoposide, platinum drugs, and taxane were all risk factors for PICC catheter thrombosis in cancer patients. CONCLUSION: In clinical PICC catheter thrombosis prevention, patients with the above characteristics should be watched more closely than other patients, as they have a higher risk for PICC catheter thrombosis. Based on the present evidence at hand, radiotherapy cannot be considered to be related to the formation of PICC-RVT in cancer patients.

Anthropometric measures and physical examination could be used to assess phenotypic GLIM (Global leadership initiative on malnutrition) criteria in heart failure patients.

BACKGROUND AND AIMS: The assessment of muscle mass using technology-based methods is less commonly performed when applying the Global Leadership Initiative on Malnutrition (GLIM) criteria due to the lack of skilled clinical nutrition practitioners and/or equipment. Based on the predictive validity of poor health outcomes and feasibility in clinical practice, this study aimed to analyze whether the measurement of calf circumference (CC), mid-upper arm circumference (MAC), and the physical examination could be used as substitutes for muscle mass assessment, as well as handgrip strength (HGS) used as a substitution when applying the GLIM criteria in hospitalized HF patients. METHODS AND RESULTS: From June 2022 to January 2023, a single-center prospective study including 216 patients was performed. Additionally, covariates were identified by a directed acyclic graph. The multivariate logistic regression analysis was also used to analyze and compare the association between poor health outcomes and malnutrition (based on 5 types of GLIM criteria). Cohen-kappa coefficient and TELOS-feasibility score were calculated. The prevalence of malnutrition ranged from 35.2% to 42.6%, depending on the tool used. After adjusting for covariates, malnutrition assessed using CC, MAC, or physical examination within the GLIM criteria was independently associated with poor clinical outcomes (90-day HF-related readmission or all-cause mortality and prolonged hospital stay) but not with HGS. CONCLUSION: CC, MAC and results from physical examination but not HGS may serve as a substitutive metric of muscle mass contained in the GLIM criteria to diagnose malnutrition and predict poor clinical outcomes among HF patients. REGISTRATION NUMBER: This study was registered at Chinese Clinical Trial Registry. (ChiCTR2200057876) on 20 Mar. 2022.

Lysine 2-hydroxyisobutyrylation orchestrates cell development and aflatoxin biosynthesis in Aspergillus flavus.

Lysine 2-hydroxyisobutyrylation (Khib ) is a recently identified post-translational modification (PTM) that regulates numerous cellular metabolic processes. In pathogenic microorganism, although glycolysis and fungal virulence are regulated by Khib , its potential roles in fungi remain to be elusive. Our preliminary results showed that levels of Khib fluctuate over time in Aspergillus flavus, which frequently contaminates crops and produces carcinogenic aflatoxins. However, the perception of Khib function in A. flavus is limited, especially in mycotoxin-producing strains. Here, we performed a comprehensive analysis of Khib in A. flavus, and 7156 Khib sites were identified in 1473 proteins. Notably, we demonstrated that Khib of AflM, a key enzyme in aflatoxin biosynthesis, affected conidia production and sclerotia formation. Furthermore, aflM deletion impaired aflatoxin biosynthesis, and more importantly, strains in which Khib was mimicked by K to T mutation at K49, K179 and K180 sites showed reduced aflatoxin production compared with wild type and ΔaflM complementation strains. These results indicate that Khib at these sites of AflM negatively regulates aflatoxin biosynthesis in A. flavus. In summary, our study revealed the potential roles of Khib in A. flavus, and particularly shed light on a new way to regulate aflatoxin production via Khib .

Prediction of all-cause mortality with malnutrition assessed by nutritional screening and assessment tools in patients with heart failure：a systematic review.

BACKGROUND AND AIMS: In the absence of a gold standard or scientific consensus regarding the nutritional evaluation of heart failure (HF) patients, this study aimed to summarize and systematically evaluate the prognostic value of nutritional screening and assessment tools used for all-cause mortality in HF patients. METHODS AND RESULTS: Relevant studies were retrieved from major databases (PubMed, Embase, Web of Science, China National Knowledge Infrastructure (CNKI), WanFang Data, and China Biology Medicine disc (CMB)) and searched from the earliest available date until July 2021. If three or more studies used the same tool, meta-analysis using RevMan 5.3 was performed. This systematic review was registered at PROSPERO (number CRD42021275575). A total of 36 articles involving 25,141 HF patients were included for qualitative analysis and 31 studies for quantitative analysis. Meta-analysis of these studies indicated, poor nutritional status evaluated by using 5 nutritional screening tools (Prognostic Nutritional Index (PNI), Geriatric Nutritional Risk Index (GNRI), Controlling Nutritional Status Score (CONUT), Nutritional Risk Index (NRI), and Short Form Mini Nutritional Assessment (MNA-SF)) or 2 nutritional assessment tools (the Mini Nutritional Assessment (MNA) and Generated Subjective Global Assessment (SGA)) predicted all-cause mortality in HF patients. Of all tools analyzed, MNA had the maximum HR for mortality [HR = 2.62, 95%CI 1.11-6.20, P = 0.03] and MNA-SF [HR = 1.94, 95%CI 1.40-2.70, P＜0.001] was the best nutritional screening tools. CONCLUSION: Poor nutritional status predicted all-cause mortality in HF patients. MNA may be the best nutritional assessment tool, and MNA-SF is most recommended for HF patient nutritional screening. The application value of MNA, especially in patients with reduced left ventricular ejection fraction (LVEF), needs to be further confirmed. The clinical application value of Mini-Nutrition Assessment Special for Heart Failure (MNA-HF) and Global Leadership Initiative on Malnutrition (GLIM) in HF patients needs to be confirmed.

Incidence of workplace violence against nurses among Chinese hospitals: A meta-analysis.

AIMS: To explore the incidence of workplace violence against nurses in Chinese hospitals. BACKGROUND: Previous systematic reviews on the incidence of workplace violence against Chinese health care workers did not include many articles published in Chinese. Although several studies have investigated cases of violence against health care providers in China, no meta-analysis has been conducted to assess the incidence of violence against Chinese nurses. EVALUATION: In this study, relevant data were retrieved from studies published up to July 2020. A meta-analysis was conducted using R software (Version 4.0). KEY FINDINGS: The 12-month incidence of workplace violence among Chinese nurses was 71% (95% CI 67%-75%), and verbal violence was the most common sub-type of violence (63%, 95% CI 58%-67%). CONCLUSION: Chinese nurses are at a high risk of violence at workplace. Hospital managers should explore ways to reduce violence against their employees, especially the younger nurses who work in secondary hospitals. IMPLICATIONS FOR NURSING MANAGEMENT: The findings of this study highlight the need to enhance the legal system in terms of laws meant to effectively mitigate violence against nurses in Chinese hospitals. Measures should be particularly taken to protect younger nurses who work in secondary hospitals.

Overcoming Spectral Dependence: A General Strategy for Developing Far-Red and Near-Infrared Ultra-Fluorogenic Tetrazine Bioorthogonal Probes.

Bioorthogonal fluorogenic dyes are indispensable tools in wash-free bioimaging of specific biological targets. However, the fluorogenicity of existing tetrazine-based bioorthogonal probes deteriorates as the emission wavelength shifts towards the NIR window, greatly limiting their applications in live cells and tissues. Herein, we report a generalizable molecular design strategy to construct ultra-fluorogenic dyes via a simple substitution at the meso-positions of various far-red and NIR fluorophores. Our probes demonstrate significant fluorescence turn-on ratios (102 -103 -fold) in the range 586-806 nm. These results will greatly expand the applications of bioorthogonal chemistry in NIR bioimaging and biosensing.

Surface Charge Density Inside a Silicon Nitride Nanopore.

Surface charges inside a nanopore determine the zeta potential and ion distributions and play a significant role in affecting ion transport and the sensitivity of detecting biomolecules. It is of great importance to study the fluctuation of surface charges with the salt concentration and pH in various applications of nanopores. Herein, we proposed a theoretical model to predict the surface charge density of a Si3N4 nanopore, in which both silanol and amine groups were taken into account. It was demonstrated that the surface charge density in the Si3N4 nanopore changes not only with pH but also with the salt concentration. The theoretical model could well predict the experimental results with different salt concentrations, pH values, and pore sizes. The effect of surface functional groups on the isopotential point (pHiep) of the Si3N4 nanopore was also systematically studied. The results indicated that the silanol groups are major determinants of the surface charge, but the influences of the amine groups should not be ignored because the small number of amine groups can change pHiep dramatically. The pHiep value of the Si3N4 nanopore was measured as 4.1, and the ratio of amine over silanol was ascertained as 0.013.

Astragaloside IV alleviates mouse slow transit constipation by modulating gut microbiota profile and promoting butyric acid generation.

Gut microbiota and short-chain fatty acids (SCFAs) are associated with the development of various human diseases. In this study, we examined the role of astragaloside IV in modulating mouse gut microbiota structure and the generation of SCFAs, as well as in slow transit constipation (STC). An STC model was established by treating mice with loperamide, in which the therapeutic effects of astragaloside IV were evaluated. The microbiota community structure and SCFA content were analysed by 16S rRNA gene sequencing and gas chromatography-mass spectrometry, respectively. The influence of butyrate on STC was assessed using a mouse model and Cajal cells (ICC). Astragaloside IV promoted defecation, improved intestinal mobility, suppressed ICC loss and alleviated colonic lesions in STC mice. Alterations in gut microbiota community structure in STC mice, such as decreased Lactobacillus reuteri diversity, were improved following astragaloside IV treatment. Moreover, astragaloside IV up-regulated butyric acid and valeric acid, but decreased isovaleric acid, in STC mouse stools. Butyrate promoted defecation, improved intestinal mobility, and enhanced ICC proliferation by regulating the AKT-NF-κB signalling pathway. Astragaloside IV promoted intestinal transit in STC mice and inhibited ICC loss by regulating the gut microbiota community structure and generating butyric acid.

Relationship between metformin therapy and risk of colorectal cancer in patients with diabetes mellitus: a meta-analysis.

OBJECTIVE: At present, there are many studies on metformin and the risk of colorectal cancer in patients with diabetes, but the conclusions are contradictory. Our aim is to comprehensively collect the published literature and systematically evaluate the relationship between metformin and the risk of colorectal cancer in patients with diabetes. METHODS: We systematically searched the MEDLINE, EMBASE, and CENTRAL databases up to March 2020. We adopted adjusted estimates and their 95% confidence intervals (CI) to calculate summary effect estimates using either a fixed-effects or a random-effects model. RESULTS: A total of 17 articles were included in this study, with a total of 1,092,074 patients with diabetes. Meta-analysis of observational studies showed that metformin treatment could significantly reduce the incidence of colorectal cancer in diabetic patients (adjusted RR = 0.884, 95%CI = 0.829-0.943), and there was heterogeneity between studies (p = 0.013, I2 = 47.9%). Subgroup analysis showed that metformin treatment was significantly associated with a significantly reduced risk of colorectal cancer in diabetics in America and Europe (adjusted RR = 0.852, 95%CI = 0.786-0.924; adjusted RR = 0.900, 95%CI = 0.845-0.958). Patients with diabetes treated with metformin had a significantly lower risk of colorectal cancer compared with patients who had never been treated with metformin or sulfonamide monotherapy (adjusted RR = 0.863, 95%CI = 0.776-0.960; adjusted RR = 0.911, 95%CI = 0.882-0.941). CONCLUSIONS: Metformin therapy is associated with a significantly reduced risk of colorectal disease in patients with diabetes, and it is necessary to conduct larger, more standardized clinical studies to verify this conclusion.

Discrimination of single-stranded DNA homopolymers by sieving out G-quadruplex using tiny solid-state nanopores.

Nanopore sensor has been developed as a promising technology for DNA sequencing at the single-base resolution. However, the discrimination of homopolymers composed of guanines from other nucleotides has not been clearly revealed due to the easily formed G-quadruplex in aqueous buffers. In this work, we report that a tiny silicon nitride nanopore was used to sieve out G tetramers to make sure only homopolymers composed of guanines could translocate through the nanopore, then the 20-nucleotide long ssDNA homopolymers could be identified and differentiated. It is found that the size of the nucleotide plays a major role in affecting the current blockade as well as the dwell time while DNA is translocating through the nanopore. By the comparison of translocation behavior of ssDNA homopolymers composed of nucleotides with different volumes, it is found that smaller nucleotides can lead to higher translocation speed and lower current blockage, which is also found and validated for the 105-nucleotide long homopolymers. The studies performed in this work will improve our understanding of nanopore-based DNA sequencing at single-base level.

Pose Prediction of Autonomous Full Tracked Vehicle Based on 3D Sensor.

Autonomous vehicles can obtain real-time road information using 3D sensors. With road information, vehicles avoid obstacles through real-time path planning to improve their safety and stability. However, most of the research on driverless vehicles have been carried out on urban even driveways, with little consideration of uneven terrain. For an autonomous full tracked vehicle (FTV), the uneven terrain has a great impact on the stability and safety. In this paper, we proposed a method to predict the pose of the FTV based on accurate road elevation information obtained by 3D sensors. If we could predict the pose of the FTV traveling on uneven terrain, we would not only control the active suspension system but also change the driving trajectory to improve the safety and stability. In the first, 3D laser scanners were used to get real-time cloud data points of the terrain for extracting the elevation information of the terrain. Inertial measurement units (IMUs) and GPS are essential to get accurate attitude angle and position information. Then, the dynamics model of the FTV was established to calculate the vehicle's pose. Finally, the Kalman filter was used to improve the accuracy of the predicted pose. Compared to the traditional method of driverless vehicles, the proposed approach was more suitable for autonomous FTV. The real-world experimental result demonstrated the accuracy and effectiveness of our approach.

Application of humic acid changes the microbial communities and inhibits the expression of tetracycline resistance genes in 4-chlorophenol wastewater treatment.

The occurrence and spread of antibiotic resistance genes (ARGs) are concerns that have threatened public health for many years. However, the effects of humic acid (HA) application on the expression of ARGs in chlorophenols wastewater treatment are rarely reported. In this study, we investigated the sludge performance, including the removal of pollutants, changes in the microbial communities, and the expression of tetracycline resistance genes (TRGs), to explore the function of HA in 4-chlorophenol (4-CP) wastewater treatment at different HA concentrations. The results showed that HA application did not significantly stimulate the removal of pollutants, other than the removal of PO43--P. High-throughput sequencing analysis indicated that the application of HA influenced the microbial communities and changed the expression level of TRGs. Quantitative real-time PCR analysis showed that the expression of numerous TRGs (tetC, tetG, tetW, tetX, and intI1) was significantly inhibited by the application of HA (25 mg L-1) during 4-CP wastewater treatment. In summary, HA application played an important role in treating chlorophenols wastewater and reducing the expression of TRGs. This work aimed to provide an efficient method of reducing the expression level of ARGs in industrial wastewater treatment, which has inevitable environmental significance.

Effects of 4-chlorophenol toxicity on sludge performance and microbial community in sequencing batch reactors.

In this study, the effects of 4-chlorophenol (4-CP) influent concentrations ranging from 10 to 100 mg L-1 on sludge toxicity, enzymatic activity and microbial community, along with their correlations, were investigated in a sequencing batch bioreactor (SBR), which was defined as the acclimated SBR. Another SBR was set as a control group that did not receive the influent 4-CP. The results showed that the sludge toxicity increased as the influent 4-CP increased, exhibiting a positive correlation with 4-CP loads. The enzymatic activity was stimulated after long-term acclimation with 4-CP and was positively related to the 4-CP loads and sludge toxicity. During the stable operational stages of the acclimated SBR, the microbial diversity first increased and then decreased as the 4-CP loads increased, while the similarity of the microbial community between the acclimated and control SBRs decreased with increasing 4-CP loads. The aim of this study is to provide theoretical support for reducing sludge toxicity in industrial wastewater treatment.

KLF4 protects brain microvascular endothelial cells from ischemic stroke induced apoptosis by transcriptionally activating MALAT1.

In this study, we investigated the expression profile and functional role of Kruppel-like family of transcription factor 4 (KLF4) in mouse cerebral microvascular endothelial cells (MECs) after focal cerebral ischemia and in cultured b.End3 cells after oxygen-glucose deprivation (OGD). Its downstream regulation was also studied. Our data showed that KLF4 was significantly upregulated in the cerebral MECs after transient ischemic insult and in cultured b.End3 cells after 24 h OGD exposure. In in vitro b.End3 cell model, KLF4 shRNA significantly increased OGD-induced activation of caspase-3 and also increased OGD-induced b.End3 cell death. KLF4 shRNA substantially enhanced OGD induced Bim and Bax expression at mRNA and protein levels and also aggravated OGD induced upregulation of E-selectin, MCP-1 and IL-6. Bioinformatic analysis suggested that MALAT1 promoter has a possible KLF4 binding site. In this study, we validated this possible binding site and also demonstrated that enforced KLF4 expression increased MALAT1 transcription. Functionally, knockdown of MALAT1 phenocopied the effect of KLF4 shRNA on enhancing OGD induced cell apoptosis and OGD induced upregulation of pro-apoptotic factors and pro-inflammatory cytokines. Based on these findings, we infer that MALAT1 is a transcriptional target of KLF4 in its protective role in cerebral MECs after ischemic insult.

Preoperative platelet-to-lymphocyte ratio is a valuable prognostic biomarker in patients with hepatocellular carcinoma undergoing curative liver resection.

The Platelet to lymphocyte ratio (PLR) has been reported to predict prognosis of patients with hepatocellular carcinoma (HCC). This study examined the prognostic potential of stratified PLR for HCC patients undergoing curative liver resection. Medical records were retrospectively analyzed for 778 HCC patients undergoing curative liver resection at the Affiliated Tumor Hospital of Guangxi Medical University and the First People's Hospital of Changde between April 2010 and October 2013. Patients were stratified based on quintile analysis of their preoperative PLR, and patients in different quintiles were analyzed for overall survival (OS) and disease-free survival (DFS) using Kaplan-Meier analysis. Independent predictors of death or recurrence were explored using multivariable Cox proportional hazard regression. Higher PLR quintiles were significantly associated with poorer overall survival (p < 0.001). Multivariate analysis showed PLR to be an independent risk factor for OS (p = 0.003). Patients in PLR quintile 5 had lower overall survival than in quintile 1 (hazard ratio (HR) = 2.780, 95% confidence interval (CI): 1.769-4.367, p < 0.001). Although patients in PLR quintile 5 had significantly lower disease-free survival (DFS) than in quintile 1 (HR = 1.534, 95% CI: 1.112-2.117, p = 0.009), this association was not significant after multivariable adjustment (p = 0.220). Subgroup analysis also showed that PLR quintiles were significantly associated with poor OS in patients positive for HBsAg or with cirrhosis (both p < 0.001). Similar results were obtained when PLR was analyzed as a dichotomous variable with cut-off values of 110 and 115. Elevated preoperative PLR may be independently associated with poor OS and DFS in HCC patients following curative resection.

Stratified aspartate aminotransferase-to-platelet ratio index accurately predicts survival in hepatocellular carcinoma patients undergoing curative liver resection.

The aspartate aminotransferase-to-platelet ratio index has been reported to predict prognosis of patients with hepatocellular carcinoma. This study examined the prognostic potential of stratified aspartate aminotransferase-to-platelet ratio index for hepatocellular carcinoma patients undergoing curative liver resection. A total of 661 hepatocellular carcinoma patients were retrieved and the associations between aspartate aminotransferase-to-platelet ratio index and clinicopathological variables and survivals (overall survival and disease-free survival) were analyzed. Higher aspartate aminotransferase-to-platelet ratio index quartiles were significantly associated with poorer overall survival (p = 0.002) and disease-free survival (p = 0.001). Multivariate analysis showed aspartate aminotransferase-to-platelet ratio index to be an independent risk factor for overall survival (p = 0.018) and disease-free survival (p = 0.01). Patients in the highest aspartate aminotransferase-to-platelet ratio index quartile were at 44% greater risk of death than patients in the first quartile (hazard ratio = 1.445, 95% confidence interval = 1.081 - 1.931, p = 0.013), as well as 49% greater risk of recurrence (hazard ratio = 1.49, 95% confidence interval = 1.112-1.998, p = 0.008). Subgroup analysis also showed aspartate aminotransferase-to-platelet ratio index to be an independent predictor of poor overall survival and disease-free survival in patients positive for hepatitis B surface antigen or with cirrhosis (both p < 0.05). Similar results were obtained when aspartate aminotransferase-to-platelet ratio index was analyzed as a dichotomous variable with cutoff values of 0.25 and 0.62. Elevated preoperative aspartate aminotransferase-to-platelet ratio index may be independently associated with poor overall survival and disease-free survival in hepatocellular carcinoma patients following curative resection.

Overexpression of microRNA-21 strengthens stem cell-like characteristics in a hepatocellular carcinoma cell line.

BACKGROUND: Liver cancer stem cells (LCSCs) have been shown to express higher levels of microRNA-21 (miR-21). Here, we examine the possible contributions of miR-21 to the phenotype of LCSCs in culture and in xenograft tumors in nude mice. METHODS: The hepatocellular carcinoma cell line MHCC-97H was stably transformed with a retroviral vector to establish cells overexpressing miR-21, while a cell line transformed with empty vector served as a negative control. RT-PCR and Western blotting were used to evaluate the effects of miR-21 overexpression on the expression of various LCSC markers, a Transwell assay was used to assess the effects on cell migration and invasion, and a spheroid formation assay was used to examine the effects on clonogenesis. The effects of miR-21 overexpression were also examined in tumors in nude mice. RESULTS: An MHCC-97H cell line was constructed that stably overexpresses miR-21 at 7.78 ± 1.51-fold higher levels than the negative control cell line. Expression of the LCSC markers CD13, Ep-CAM, CD90, and OCT4 was significantly higher in the miR-21-overexpressing cell line than in the negative control at both mRNA and protein levels. The overexpressing cell line formed larger, tighter, and more numerous spheroids. Overexpression of miR-21 was associated with greater cell migration and invasion. Tumors of overexpressing cells in nude mice had a significantly larger mean volume after 34 days of growth (773.62 ± 163.46 mm3) than tumors of negative control cells (502.79 ± 33.94 mm3, p = 0.048), as well as greater mean weight (0.422 ± 0.019 vs. 0.346 ± 0.006 g, p = 0.003). CONCLUSIONS: Overexpression of miR-21 strengthens the phenotype of LCSCs, facilitating invasion, migration, and tumorigenesis in hepatocellular carcinoma.