Noncanonical mutations in ribosome nascent peptide exit tunnel confer clarithromycin resistance in Mycobacterium abscessus complex.

Mycobacterium abscessus is a non-tuberculous mycobacterial pathogen known to cause pulmonary and skin infections worldwide. Renowned for its multidrug resistance, M. abscessus infections often result in unfavorable clinical outcomes. Clarithromycin plays a pivotal role in treating M. abscessus infections, with resistance commonly leads to treatment failure. While canonical mutations in 23S rRNA residue 2270/2271 are recognized as a major mechanism for acquired clarithromycin resistance, resistant isolates devoid of such mutations have been widely reported. In this study, we conducted a comprehensive investigation into acquired clarithromycin resistance using spontaneous mutants derived from two parental strains characterized by erm(41) T28 and C28 sequevars respectively. A total of 135 resistant mutants were selected from the parental strains. Sequencing of the 78 mutants lacking canonical 2270/2271 mutations identified mutations within the peptidyl-transferase center and in hairpin loops 35, 49, and 74 of the 23S rRNA. Moreover, these noncanonical mutations were identified in 57 out of 1875 genomes of clinical isolates. Thirteen representative mutations were introduced into the bacterial genome via site-directed mutagenesis, and their contribution to macrolide resistance was verified. Mapping these mutations onto the three-dimensional structure of 23S rRNA revealed their localization at the entrance of the nascent peptide exit tunnel, potentially contributing to resistance by disrupting the macrolide binding pocket. The identification of these noncanonical 23S rRNA mutations advances our understanding of macrolide resistance in M. abscessus and underscores their importance as potential markers for detecting clarithromycin resistance.

Lipoproteins and metabolites in diagnosing and predicting Alzheimer's disease using machine learning.

BACKGROUND: Alzheimer's disease (AD) is a chronic neurodegenerative disorder that poses a substantial economic burden. The Random forest algorithm is effective in predicting AD; however, the key factors influencing AD onset remain unclear. This study aimed to analyze the key lipoprotein and metabolite factors influencing AD onset using machine-learning methods. It provides new insights for researchers and medical personnel to understand AD and provides a reference for the early diagnosis, treatment, and early prevention of AD. METHODS: A total of 603 participants, including controls and patients with AD with complete lipoprotein and metabolite data from the Alzheimer's disease Neuroimaging Initiative (ADNI) database between 2005 and 2016, were enrolled. Random forest, Lasso regression, and CatBoost algorithms were employed to rank and filter 213 lipoprotein and metabolite variables. Variables with consistently high importance rankings from any two methods were incorporated into the models. Finally, the variables selected from the three methods, with the participants' age, sex, and marital status, were used to construct a random forest predictive model. RESULTS: Fourteen lipoprotein and metabolite variables were screened using the three methods, and 17 variables were included in the AD prediction model based on age, sex, and marital status of the participants. The optimal random forest modeling was constructed with "mtry" set to 3 and "ntree" set to 300. The model exhibited an accuracy of 71.01%, a sensitivity of 79.59%, a specificity of 65.28%, and an AUC (95%CI) of 0.724 (0.645-0.804). When Mean Decrease Accuracy and Gini were used to rank the proteins, age, phospholipids to total lipids ratio in intermediate-density lipoproteins (IDL_PL_PCT), and creatinine were among the top five variables. CONCLUSIONS: Age, IDL_PL_PCT, and creatinine levels play crucial roles in AD onset. Regular monitoring of lipoproteins and their metabolites in older individuals is significant for early AD diagnosis and prevention.

Phenotypes of patients with systemic sclerosis in the Chinese Han population: a cluster analysis.

OBJECTIVE: Systemic sclerosis (SSc) is a heterogeneous connective tissue disease that is commonly subdivided into limited cutaneous SSc (lcSSc) and diffuse cutaneous SSc (dcSSc) based on the extent of skin involvement. This subclassification may not reflect the full range of clinical phenotypic variation. This study aimed to investigate clinical features and aggregation of patients with SSc in Chinese based on SSc manifestations and organ involvements, in order to achieve precise treatment of SSc early prevention of complications. METHODS: In total 287 SSc patients were included in this study. A cluster analysis was applied according to 13 clinical and serologic variables to determine subgroups of patients. Survival rates between obtained clusters and risk factors affecting prognosis were also compared. RESULT: In this study, six clusters were observed: cluster 1 (n = 66) represented the skin type, with all patients showing skin thickening. In cluster 2 (n = 56), most patients had vascular and articular involvement. Cluster 3 (n = 14) individuals mostly had cardiac and pulmonary involvement. In cluster 4 (n = 52), the gastrointestinal type, 50 patients presented with stomach symptoms and 28 patients presented with esophageal symptoms. In cluster 5 (n = 50), patients barely had any major organ involvement. Cluster 6 (n = 49) included 46% of all patients presenting with renal crisis. CONCLUSION: The results of our cluster analysis study implied that limiting SSc patient subgroups to those based only on skin involvement might not capture the full heterogeneity of the disease. Organ damage and antibody profiles should be considered when identifying homogeneous patient groups with a specific prognosis. Key Points • Provides a new method of categorizing SSc patients. • Can better explain disease progression and guide subsequent treatment.

Effect of Hypoxia Conditioning on Body Composition in Middle-Aged and Older Adults: A Systematic Review and Meta-Analysis.

BACKGROUND: The effects of hypoxia conditioning, which involves recurrent exposure to hypoxia combined with exercise training, on improving body composition in the ageing population have not been extensively investigated. OBJECTIVE: This meta-analysis aimed to determine if hypoxia conditioning, compared to similar training near sea level, maximizes body composition benefits in middle-aged and older adults. METHODS: A literature search of PubMed, EMBASE, Web of Science, Scopus and CNKI (China National Knowledge Infrastructure) databases (up to 27th November 2022) was performed, including the reference lists of relevant papers. Three independent reviewers extracted study characteristics and health outcome measures. Search results were limited to original studies of the effects of hypoxia conditioning on body composition in middle-aged and older adults. RESULTS: Twelve studies with a total of 335 participants were included. Hypoxia conditioning induced greater reductions in body mass index (MD = -0.92, 95%CI: -1.28 to -0.55, I2 = 0%, p < 0.00001) and body fat (SMD = -0.38, 95%CI: -0.68 to -0.07, I2 = 49%, p = 0.01) in middle-aged and older adults compared with normoxic conditioning. Hypoxia conditioning improved lean mass with this effect not being larger than equivalent normoxic interventions in either middle-aged or older adults (SMD = 0.07, 95%CI -0.12 to 0.25, I2 = 0%, p = 0.48). Subgroup analysis showed that exercise in moderate hypoxia (FiO2 > 15%) had larger effects than more severe hypoxia (FiO2 ≤ 15%) for improving body mass index in middle-aged and older adults. Hypoxia exposure of at least 60 min per session resulted in larger benefits for both body mass index and body fat. CONCLUSION: Hypoxia conditioning, compared to equivalent training in normoxia, induced greater body fat and body mass index improvements in middle-aged and older adults. Adding hypoxia exposure to exercise interventions is a viable therapeutic solution to effectively manage body composition in ageing population.

Differences in the pathogenetic characteristics of prostate cancer in the transitional and peripheral zones and the possible molecular biological mechanisms.

Since the theory of modern anatomical partitioning of the prostate was proposed, the differences in the incidence and pathological parameters of prostate cancer between the peripheral zone and transition zone have been gradually revealed. It suggests that there are differences in the pathogenic pathways and molecular biology of prostate cancer between different regions of origin. Over the past decade, advances in sequencing technologies have revealed more about molecules, genomes, and cell types specific to the peripheral and transitional zones. In recent years, the innovation of spatial imaging and multiple-parameter magnetic resonance imaging has provided new technical support for the zonal study of prostate cancer. In this work, we reviewed all the research results and the latest research progress in the study of prostate cancer in the past two decades. We summarized and proposed several vital issues and focused directions for understanding the differences between peripheral and transitional zones in prostate cancer.

Individual surveillance by competing risk model for patients with hepatocellular carcinoma occurrence in all-cause cirrhosis.

PURPOSE: It was of great significance to identify someone with a high risk of hepatocellular carcinoma (HCC) occurrence and make a diagnosis as early as possible. Therefore, we aimed to develop and validate a new, objective, and accurate prediction model, and convert it into a nomogram to make a personalized prediction of cancer occurrence in cirrhotic patients with different etiologies. METHODS: The present study included 938 patients with cirrhosis from January 1, 2011, to December 31, 2012. Patients were prospectively followed-up until January 1, 2018. We used a competing risk model and the Fine-Gray test to develop and validate the prediction model and to plot a nomogram based on the model established. RESULTS: At the end of follow-up, 202 (21.5%) patients developed HCC, with a 5-year incidence of 19.0% (corrected for competing risk model). Based on the competing risk regression method, we built a prediction model including age, gender, etiology, lymphocyte, and A/G ratio. Three groups with different risks were generated on account of tertiles of the 5-year risk predicted by the model. The cumulative 1-, 3-, and 5-year incidences of HCC were 2.0%, 20.8%, and 42.3% in high-risk group, 0.9%, 10.1%, and 17.7% in medium-risk group, and 0%, 2.0%, 8.5% in low-risk group (P < 0.001). The model showed excellent discrimination and calibration in predicting the risk of HCC occurrence in patients with all-cause cirrhosis. CONCLUSION: The model could make an individual prediction of cancer occurrence and stratify patients based on predicted risk, regardless of the causes of cirrhosis.

Comparison of NK cell subsets, receptors and functions induced by radiofrequency ablation and microwave ablation in HBV-associated primary hepatocellular carcinoma.

Background: Topical therapy has been shown to induce an immune response in patients with hepatocellular carcinoma (HCC). In this study, a prospective parallel group control experiment was conducted to compare the differences between radiofrequency ablation and microwave ablation in inducing the immune regulation of NK cells. Methods: Sixty patients with clinically and pathologically confirmed hepatitis B-associated hepatocellular carcinoma (HCC) were selected for thermal ablation. Patients were randomly assigned into the MWA group (n = 30) and the RFA group (n = 30). Patient's peripheral blood was isolated on days D0, D7, and month M1. NK cell subsets, receptors, and killing function were detected by flow cytometry and LDH. Student t test and rank sum test were used to compare the statistical differences between the RFA (radio frequency) and MWA (microwave) groups. The Kaplan-Meier curve and log-rank test were used to calculate the difference between the two survival curves. Results: Comparison of the frequency of CD3-CD56+ and CD3-CD56+CD16+ in NK cells between the RFA and WMA groups showed that there was no difference in the D0, D7, M1, D7-D0, M1-D0, and M1-D7 groups. The changes of the inhibitory NK cell receptor CD159A were significantly different at D7 (P<0.05). CD107a were compared between the RFA and WMA groups, indicating that CD107a changes induced by NK cells were significantly different at D7-D0 (P<0.05). Comparison of NK cell lysis activity of target K562 cells between the RFA and WMA groups showed that there was no difference at D0, D7, D7-D0. There was no difference in recurrence-free survival (RFS) between the RFA and WMA groups (P=0.11). Conclusions: The difference between MWA and RFA-induced NK cell changes was mainly manifested in the inhibitory receptors CD159a and CD107a 1 week after surgery, with microwave-induced changes being more severe. Comparison of the NK cell lysis activity of the target K562 cells between the RFA and WMA groups showed that there was no difference in D0, D7, D7- D0. Survival analysis showed that these differences did not affect the recurrence-free survival (RFS) in the two groups.

Single-cell omics traces the heterogeneity of prostate cancer cells and the tumor microenvironment.

Prostate cancer is one of the more heterogeneous tumour types. In recent years, with the rapid development of single-cell sequencing and spatial transcriptome technologies, researchers have gained a more intuitive and comprehensive understanding of the heterogeneity of prostate cancer. Tumour-associated epithelial cells; cancer-associated fibroblasts; the complexity of the immune microenvironment, and the heterogeneity of the spatial distribution of tumour cells and other cancer-promoting molecules play a crucial role in the growth, invasion, and metastasis of prostate cancer. Single-cell multi-omics biotechnology, especially single-cell transcriptome sequencing, reveals the expression level of single cells with higher resolution and finely dissects the molecular characteristics of different tumour cells. We reviewed the recent literature on prostate cancer cells, focusing on single-cell RNA sequencing. And we analysed the heterogeneity and spatial distribution differences of different tumour cell types. We discussed the impact of novel single-cell omics technologies, such as rich omics exploration strategies, multi-omics joint analysis modes, and deep learning models, on future prostate cancer research. In this review, we have constructed a comprehensive catalogue of single-cell omics studies in prostate cancer. This article aimed to provide a more thorough understanding of the diagnosis and treatment of prostate cancer. We summarised and proposed several key issues and directions on applying single-cell multi-omics and spatial transcriptomics to understand the heterogeneity of prostate cancer. Finally, we discussed single-cell omics trends and future directions in prostate cancer.

Effect of HBsAg expression in liver tissue on prognosis of hepatocellular carcinoma after minimally invasive interventional therapy.

Background: The aim of this study was to investigate the association between pathologic markers and prognosis in patients with hepatocellular carcinoma who received transcatheter chemoembolization combined with locoregional ablation therapy. Methods: This retrospective study included 111 hepatitis B virus (HBV)-associated hepatocellular carcinoma (HCC). All patients underwent transcatheter arterial chemoembolization (TACE) combined with locoregional ablation therapy, and received core needle biopsy before therapy in Beijing You 'an Hospital affiliated to Capital Medical University from January 1, 2013 to December 31, 2016. Demographic, pathological indicators and clinical laboratory data were collected. The cumulative recurrence-free survival (RFS) and overall survival (OS) were calculated and compared by Kaplan-Meier method and Log-rank test, and Cox proportional risk model was used to screen for independent predictors of recurrence and long-term prognosis in HCC patients. Results: There was a correlation between HBsAg expression in liver tissue and prognosis of HCC patients. Patients with negative HBsAg expression had longer 1-,3- and 5-year RFS rates than positive HBsAg expression (78.3%, 43.5%, 30.4% and 58.5%, 24.5%, 17.0%, P=0.018). Meanwhile,the postoperative 1-,3-and 5-year OS rates of HCC patients in the negative HBsAg expression group were significantly higher than those of HCC patients in the positive HBsAg expression group (100%, 89.1%, 80.4% and 100%, 75.5%, 58.5%, P=0.008). Conclusions: The prognosis of patients with hepatocellular carcinoma with negative HBsAg expression was better than that with positive HBsAg expression. Accordingly, the expression of the liver HBsAg before combined therapy was a prognostic indicator for OS and RFS. For patients with liver HBsAg positive, follow-up should be strengthened and corresponding intervention measures should be taken to improve prognosis.

Drug Resistance of Mycobacterium tuberculosis Based on Whole-Genome Sequencing in the Yi Ethnic Group, Sichuan Province, China.

This study investigated drug-resistant tuberculosis (DR-TB) in the Yi ethnic group. The study was designed to identify risk factors for DR-TB and its relationship with HIV/AIDS. To establish the resistance to antituberculosis drugs, whole-genome sequencing (WGS) was performed using culture-positive Mycobacterium tuberculosis samples collected from people of the Yi ethnic group from March 2019 to March 2021. Baseline characteristics were obtained from China's tuberculosis surveillance system. A total of 116 M. tuberculosis strains were included in the final analysis. Lineage 2.2 (75.86%) was the dominant sublineage, followed by lineage 4.5 (18.97%) and lineage 4.4 (5.17%). The rates of rifampicin-resistant (RR-TB), multidrug-resistant (MDR-TB), and preextensively drug-resistant TB (pre-XDR-TB) were 18.97%, 10.34%, and 6.03%, respectively. Drug-resistant strains were not found in the elderly (age ≥ 65 years). The proportions of RR/MDR-TB and pre-XDR-TB cases among re-treatment patients were higher than those among new patients (χ 2 = 12.155, P = 0.003; χ 2 = 22.495, P = 0.001, respectively). The pre-XDR-TB case proportions were higher among female patients than among males and higher among referred patients (χ 2 = 5.456, P = 0.032; χ 2 = 15.134, P = 0.002, respectively). The rates of RR/MDR-TB and pre-XDR-TB did not differ appreciably among groups with different HIV infection statuses nor lineage populations. DR-TB poses a serious challenge to the Yi ethnic group. Re-treatment patients, women, and referred patients were at high risk of MDR/RR-TB or pre-XDR-TB while HIV and lineage 2 had negligible association with drug resistance. Whole-genome sequencing should be used to guide the design of treatment regimens and to tailor public interventions.

Comparison of mortality and complications between urgent-start peritoneal dialysis and urgent-start hemodialysis: A systematic review and meta-analysis.

The advantages of urgent-start peritoneal dialysis (PD) vis-à-vis urgent-start hemodialysis (HD) are not clear. We performed a systematic review and meta-analysis of studies comparing the two modalities. Databases of PubMed, Embase, Ovoid, and Google Scholar were searched up to November 1, 2020. The primary outcome was mortality, and secondary outcomes were dialysis-related infectious complications and mechanical complications. Risk ratios (RRs) were calculated for all outcomes. Seven studies were included. The pooled analysis revealed a statistically significant reduced risk of all-cause mortality in patients undergoing urgent-start PD as compared to urgent-start HD (RR: 0.61, 95% confidence interval [CI] [0.40, 0.94], I2  = 56.34%). A meta-analysis of dialysis-related infectious complications indicated no statistically significant difference between the two modalities (RR: 0.66, 95% CI [0.29, 1.50], I2  = 69.62%). Our analysis revealed a statistically significant reduced risk of mechanical complications in patients undergoing urgent-start PD (RR: 0.54, 95% CI [0.40, 0.73], I2  = 0%). To conclude, unadjusted data from observational studies are indicative of lower mortality and lower risk of mechanical complications with urgent-start PD versus urgent-start HD. The risk of infectious complications was not different between the two groups. Further studies with a larger sample size using propensity-matched cohorts are needed to strengthen current evidence.

Chondroblastoma of mandibular condyle: Case report and literature review.

Chondroblastoma is one of the uncommon benign bone tumors, particularly when located in the mandibular condyle. Such a location makes its diagnosis difficult when based on only its clinical presentation and radiographic features. Herein the current report presents a case of chondroblastoma of the mandibular condyle: its clinical presentation, radiographic features, and immediate condylar reconstruction after resection. Additionally, the relevant literature is discussed to provide clinical recommendations for its diagnosis and treatment. Chondroblastoma has been reported so infrequently in the temporomandibular joint (TMJ), more common entities should first be considered in the differential diagnosis of masses in this location. Osteochondroma is the most frequent bone neoplasm in the TMJ. Since a correct diagnosis is difficult, additional tools, such as magnetic resonance imaging (MRI) and immunohistochemical analyses, should be used for diagnostics and surgical planning.

[Retracted] MicroRNA-33b suppresses the proliferation and metastasis of hepatocellular carcinoma cells through the inhibition of Sal-like protein 4 expression.

Following the publication of this paper, it was drawn to the Editors' attention by a concerned reader that certain of the Transwell cell migration data shown in Figs. 2D and 4C were strikingly similar to data appearing in different form in other articles by different authors. Owing to the fact that the contentious data in the above article had already been published elsewhere, or were already under consideration for publication, prior to its submission to International Journal of Molecular Medicine, the Editor has decided that this paper should be retracted from the Journal. The authors were asked for an explanation to account for these concerns, but the Editorial Office did not receive any reply. The Editor apologizes to the readership for any inconvenience caused. [the original article was published in International Journal of Molecular Medicine 38: 1587­1595, 2016; DOI: 10.3892/ijmm.2016.2754].

Detection of Mycobacterium kansasii using a combination of loop-mediated isothermal amplification (LAMP) and lateral flow biosensors.

Mycobacterium kansasii is an opportunistic pathogen that causes both intrapulmonary and extrapulmonary infections. The symptoms of the pulmonary diseases caused by M. kansasii closely resemble Mycobacterium tuberculosis. Rapid and accurate differentiation of M. kansasii from M. tuberculosis, as well as other mycobacteria, is crucial for developing effective therapeutics and disease treatment. In this study, we combined loop-mediated isothermal amplification (LAMP) with lateral flow biosensors (LFB) to detect M. kansasii, by targeting the species-specific sequence of rpoB, a gene which encodes the ß subunit of bacterial RNA polymerase. The assay was validated to ensure that it was highly selective by testing M. kansasii, M. tuberculosis, other species of respiratory bacteria, and other nontuberculous mycobacteria. The detection limit of the assay was 1 fg/µL of DNA and 50 CFU of bacilli in sputum. The M. kansasii-LAMP-LFB assay is a fast, cheap, and accurate method for detecting M. kansasii by constant temperature amplification and simple interpretation.

Exploring the Dynamics of Hemorrhagic Fever with Renal Syndrome Incidence in East China Through Seasonal Autoregressive Integrated Moving Average Models.

OBJECTIVE: The purpose of this study was to explore the dynamics of incidence of hemorrhagic fever with renal syndrome (HFRS) from 2000 to 2017 in Anqiu City, a city located in East China, and find the potential factors leading to the incidence of HFRS. METHODS: Monthly reported cases of HFRS and climatic data from 2000 to 2017 in the city were obtained. Seasonal autoregressive integrated moving average (SARIMA) models were used to fit the HFRS incidence and predict the epidemic trend in Anqiu City. Univariate and multivariate generalized additive models were fit to identify and characterize the association between the HFRS incidence and meteorological factors during the study period. RESULTS: Statistical analysis results indicate that the annualized average incidence at the town level ranged from 1.68 to 6.31 per 100,000 population among 14 towns in the city, and the western towns exhibit high endemic levels during the study periods. With high validity, the optimal SARIMA(0,1,1,)(0,1,1)12 model may be used to predict the HFRS incidence. Multivariate generalized additive model (GAM) results show that the HFRS incidence increases as sunshine time and humidity increases and decreases as precipitation increases. In addition, the HFRS incidence is associated with temperature, precipitation, atmospheric pressure, and wind speed. Those are identified as the key climatic factors contributing to the transmission of HFRS. CONCLUSION: This study provides evidence that the SARIMA models can be used to characterize the fluctuations in HFRS incidence. Our findings add to the knowledge of the role played by climate factors in HFRS transmission and can assist local health authorities in the development and refinement of a better strategy to prevent HFRS transmission.

Biosafety threats of the rapidly established labs for SARS-CoV-2 tests in China.

To increase the capacity of identifying coronavirus disease 2019 (COVID-19) infection, many Biosafety Level 2 (BSL-2) labs have been established in a short period of time for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) nucleic acid tests all over the world. However, their biosafety has not been evaluated, which could have been the first gateway to SARS-CoV-2 transmission. During 9-11 March 2020, the first comprehensive evaluation of the biosafety in all 89 labs qualified for conducting SARS-CoV-2 tests in Sichuan Province of China was conducted. The degree of compliance with 39 criteria in five categories was evaluated: biosafety requirements for lab activities (14 criteria), sample transfer, acceptance and management (6 criteria), waste management (9 criteria), personnel training and protection (4 criteria), and lab environmental disinfection, emergency plans and accident handling (6 criteria). Our results revealed that, although an overall median compliance rate of 94.6% for 39 criteria, only four of 89 labs met all of them. Criteria in personnel training and protection have been most satisfactorily met, followed by lab environmental disinfection, emergency plans and accident handling. The most severe risk was the lack of automatic doors at the main entrance or in core operation areas, especially among labs in CDC and hospitals. This risk, together with failure for keeping pressure in the core operation areas 25 ± 5 Pa (mainly among labs in the third-party testing agencies), may cause accidental exposure to biological agents from lab activities. Other severe risk included failure for standard labeling of SARS-CoV-2 wastes and lacking regular monitoring of sterilization effects. Our findings would provide experiences and lessons for strengthening lab biosafety in other Chinese provinces, and also serve as an important reference for many other countries where such labs are being or will be quickly built for fighting the COVID-19. The information of lab safety should be considered to be internally linked to the national intelligent syndromic surveillance system (NISSS), for better improving the safety of the labs at the greatest need and facilitating more comprehensive surveillance of risk for disease outbreak.

MiR-6803-5p Promotes Cancer Cell Proliferation and Invasion via PTPRO/NF-κB Axis in Colorectal Cancer.

Accumulated studies have implicated microRNAs (miRNAs) exert modifying effects on colorectal cancer (CRC). Protein tyrosine phosphatase, receptor type O (PTPRO) has been identified as a tumor suppressor in several kinds of cancer, including CRC. Previously, we have found that exosome-encapsulated miR-6803-5p is increased in CRC. However, the mechanism of miR-6803-5p in CRC is not clear yet. This study is aimed at elucidating the effect of miR-6803-5p in colorectal carcinogenesis. Expression of miR-6803-5p and PTPRO mRNA in peripheral blood mononuclear cells of CRC patients is estimated by real-time PCR. PTPRO protein in CRC cells is detected by western blot. To verify the association of miR-6803-5p with PTPRO, luciferase reporter assay is performed. CCK-8 and EdU assays are conducted to assess cell proliferation. Real-time PCR and ELISA are applied to detect cytokine expression in CRC cells. Cell invasion and migration assays are evaluated by transwell and scratch tests. Immunofluorescence is carried out to determine the activation of NF-κB in HCT116 cells. Negative correlation is demonstrated between miR-6803-5p and PTPRO in CRC. PTPRO is demonstrated to be a direct target of miR-6803-5p. miR-6803-5p can promote cancer cell proliferation and invasion and enhance inflammation through PTPRO/NF-κB axis in CRC, which serves as a useful target for CRC.

Efficacy of ultrasound-, computed tomography-, and magnetic resonance imaging-guided radiofrequency ablation for hepatocellular carcinoma.

PURPOSES: This study aimed to investigate the efficacy of ultrasound (US)-, computed tomography (CT)-, and magnetic resonance imaging (MRI)-guided radiofrequency ablation (RFA) for the treatment of hepatocellular carcinoma (HCC). MATERIALS AND METHODS: This retrospective study included 141 patients with HCC who were treated with US-guided (n = 29), CT-guided (n = 50), or MRI-guided RFA (n = 62). The primary endpoint was progression-free survival (PFS). The secondary endpoints included overall survival (OS), technique success (TS), and technique efficacy (TE). Cox model and logistic regression were used to determine the risk factors for tumor recurrence and TE. RESULTS: The US, CT, and MRI groups did not show a significant difference in terms of baseline variables. The three groups did not differ significantly in PFS rate (P = 0.072) and OS rate (P = 0.231). The PFS rates at 3 years for the US, CT, and MRI groups were 40.90%, not reached, and 14.80%, respectively. The OS rates at 3 years were 94.70%, 97.50%, and 85.50% for US, CT, and MRI groups, respectively. No significant differences were observed between the three groups in terms of TS rate (P = 0.113) and TE rate (P = 0.682). In multivariate analysis, liver cirrhosis (P = 0.001), level of alpha-fetoprotein (AFP, P = 0.004), and number of tumors (P = 0.012) were independent risk factors for PFS. For TE, the level of AFP (P = 0.018) was an independent factor. CONCLUSION: US-, CT-, and MRI-guided RFA was effective for treating HCC patients. Liver cirrhosis, AFP level, and tumor number were associated with tumor recurrence, and the level of AFP was an independent risk factor affecting TE.

Prediction early recurrence of hepatocellular carcinoma eligible for curative ablation using a Radiomics nomogram.

BACKGROUND: Predicting early recurrence (ER) after radical therapy for HCC patients is critical for the decision of subsequent follow-up and treatment. Radiomic features derived from the medical imaging show great potential to predict prognosis. Here we aim to develop and validate a radiomics nomogram that could predict ER after curative ablation. METHODS: Total 184 HCC patients treated from August 2007 to August 2014 were included in the study and were divided into the training (n = 129) and validation(n = 55) cohorts randomly. The endpoint was recurrence free survival (RFS). A set of 647 radiomics features were extracted from the 3 phases contrast enhanced computed tomography (CECT) images. The minimum redundancy maximum relevance algorithm (MRMRA) was used for feature selection. The least absolute shrinkage and selection operator (LASSO) Cox regression model was used to build a radiomics signature. Recurrence prediction models were built using clinicopathological factors and radiomics signature, and a prognostic nomogram was developed and validated by calibration. RESULTS: Among the four radiomics models, the portal venous phase model obtained the best performance in the validation subgroup (C-index = 0.736 (95%CI:0.726-0.856)). When adding the clinicopathological factors to the models, the portal venous phase combined model also yielded the best predictive performance for training (C-index = 0.792(95%CI:0.727-0.857) and validation (C-index = 0.755(95%CI:0.651-0.860) subgroup. The combined model indicated a more distinct improvement of predictive power than the simple clinical model (ANOVA, P < 0.0001). CONCLUSIONS: This study successfully built a radiomics nomogram that integrated clinicopathological and radiomics features, which can be potentially used to predict ER after curative ablation for HCC patients.

THBS2 is a biomarker for AJCC stages and a strong prognostic indicator in colorectal cancer.

PURPOSE: To investigate the expression of thrombospondin 2 (THBS2) in colorectal cancer (CRC) and its relationship with clinicopathological features and prognosis. METHODS: THBS2 expression was evaluated with tissue microarrays (TMAs) immunohistochemistry (IHC) staining in 100 CRC samples. RESULTS: High THBS2 expression was found in 73 patients (45 male and 28 female). THBS2 expression was significantly correlated to TNM stages (p=4.1×10-5), T classification (p=0.005), lymph node metastasis (p=3×10-4) and AJCC stages (p=0), while no significant association was found in gender, age, distant metastasis or tumor size. In both univariate and multivariate analyses, THBS2 showed statistically prognostic significance [p<0.001, HR (hazard ratio) = 0.237, 95% CI (0.101-0.557) and p<0.001, HR=0.158, 95% CI (0.062-0.401)]. Kaplan-Meier survival analysis further confirmed that THBS2 expression was significantly correlated with clinical outcomes (p<0.001). CONCLUSIONS: All the results indicated THBS2 expression might become a prognostic marker for CRC.