Kikuchi disease: A case report about Sintilimab-induced Kikuchi histiocytic necrotizing lymphadenitis and literature review.

Immune checkpoint inhibitors have become one of the effective means of solid tumor treatment, among which anti-programmed death-1 (PD-1) antibodies are more maturely applied and can effectively inhibit tumor immune escape, thus enhancing the anti-tumor effect, but it can also lead to a series of immune-related adverse events (irAEs) in the process of clinical use. Here, we report a Patient with pancreatic solid pseudopapilloma treated with Sintilimab for the fifteenth cycles who developed chills, fever, and lymph node enlargement. Considering that the patient did not have infection, without history of autoimmune disease, we diagnosed the patient with Sintilimab-induced histiocytic necrotizing lymphadenitis (Kikuchi disease). The symptoms are alleviated after rapid use of glucocorticoids. Histiocytic necrotizing lymphadenitis (Kikuchi lymphadenitis) with anti-programmed death-1 (PD-1) antibody is a rare immune-related adverse events (irAEs).

NR_103776.1 as a novel diagnostic biomarker for systemic lupus erythematosus.

BACKGROUND: With the development of sequencing technologies, there is increasing evidence that long noncoding RNAs (lncRNAs) are involved in systemic lupus erythematosus (SLE). The level of NR_103776.1 expression in SLE and its clinical associations are still not well defined. OBJECTIVE: To identify differentially expressed lncRNAs and explore their functional roles in SLE. METHODS: Transcriptome sequencing was used to screen differentially expressed lncRNAs and mRNAs. Expression validation of clinical samples was performed by QRT-PCR. Bioinformatics was used to analyze its prognostic value and potential function. RESULTS: Of the 231 significantly differentially expressed lncRNAs, NR_103776.1 could be used to distinguish not only SLE patients and rheumatoid arthritis patients but also active SLE patients, stable SLE patients, and healthy controls. NR_103776.1 was significantly and negatively correlated with inflammatory indexes (CRP and ESR). NR_103776.1 dysregulation might contribute to the metabolism of RNA and proteins in SLE patients. CONCLUSIONS: This study not only provided a transcriptome profile of lncRNAs aberrantly expressed in individual nucleated cells of SLE patients but also suggested NR_103776.1 as a novel potential diagnostic biomarker.

The association between metabolic dysfunction-associated steatotic liver disease, cardiovascular and cerebrovascular diseases and the thickness of carotid plaque.

BACKGROUND: The relationship between metabolic dysfunction-associated steatotic liver disease (MASLD) and atherosclerosis has been controversial, which has become a hit of recent research. The study aimed to explore the association between MASLD, cardiovascular and cerebrovascular diseases (CCVD), and the thickness of carotid plaque which was assessed by ultrasound. METHODS: From September 2018 to June 2019, 3543 patients were enrolled. We asked participants to complete questionnaires to obtain information. All patients underwent liver ultrasound and bilateral carotid ultrasound to obtain carotid intima-media thickness (IMT) and maximum carotid plaque thickness (CPT). Hepatic steatosis was quantified during examination according to Hamaguchi's ultrasonographic score, from 0 to 6 points. A score < 2 was defined as without fatty liver, and a score ≥ 2 was defined as fatty liver. Information about blood lipids was collected based on the medical records. RESULTS: We found common risk factors for CCVD events, MASLD, and atherosclerosis. There was a significant correlation between MASLD and carotid plaque, but not with CPT. No association was found between MASLD and CCVD events. CPT and IMT were thicker in CCVD patients than in non-CCVD patients. No significant difference was found between IMT and CPT in MASLD patients and non-MASLD patients. CCVD was independently and consistently associated with higher IMT, and free fatty acid (FFA). CONCLUSIONS: According to our results, we recommend carotid ultrasound examination of the patients when FFA is increased, regardless of the presence of risk factors and MASLD. Due to the distribution of CPT of both CCVD and MASLD patients in the CPT 2-4 mm group, contrast-enhanced ultrasound is necessary to assess the vulnerability of the plaque when CPT ≥ 2 mm. Timely treatment of vulnerable plaques may reduce the incidence of future CCVD events.

Misdiagnosis of Systemic Lupus Erythematosus Combined with Urinary Tuberculosis Leading to Tuberculous Meningitis: A Case Report and Literature Review.

Purpose: To explore the lessons learned from the misdiagnosis of systemic lupus erythematosus (SLE) combined with urinary tuberculosis leading to tuberculous meningitis (TBM) and the diagnosis and treatment of TBM through case reports and review of the literature. Methods: We report a case of an SLE patient presenting with urinary tuberculosis infection misdiagnosed as interstitial cystitis and complex urinary tract infection, who developed neurological infection after a cystocentesis biopsy and was eventually diagnosed with TBM. In addition, all cases of SLE combined with TBM from January 1975 to February 2022 were summarised and reviewed to compare current diagnostic and treatment strategies for the disease. Results: The patient suddenly developed neurological symptoms after cystocentesis biopsy, and we detected Mycobacterium tuberculosis in the macrogenomic next-generation sequence (mNGS) of the cerebrospinal fluid. We therefore excluded interstitial cystitis and neuropsychiatric lupus to confirm the diagnosis of Mycobacterium tuberculosis infection leading to urinary tract tuberculosis and TBM. Conclusion: SLE is complicated by urological tuberculosis, surgery triggering hematogenous dissemination leading to tuberculous meningitis. At the same time, the lack of specificity in the clinical presentation of patients makes it easy to misdiagnose neuropsychiatric lupus and delay treatment, so timely and accurate diagnosis and effective anti-tuberculosis treatment are essential.

Systemic lupus erythematosus complicated with cryptococcal meningitis: A case report.

RATIONALE: Patients with systemic lupus erythematosus (SLE) complicated with cryptococcal meningitis (CM) are easy to be misdiagnosed as neuropsychiatric lupus or tuberculous meningitis due to the lack of specificity of clinical symptoms, which may delay treatment. Through this case, we considered early improvement of India ink stain of cerebrospinal fluid (CSF) and metagenomic next generation sequences to determine whether there is microbial infection, and gave the idea of empirical anti-infection therapy, so as to make early diagnosis and slow down the progression of the disease. PATIENT CONCERNS: We report the case of a 40-year-old female with SLE for 10 years. Five days ago she came down with a fever and a headache. DIAGNOSIS, INTERVENTIONS, AND OUTCOMES: India ink stain of CSF in patients with SLE shows Cryptococcus neoformans growth. Combined with imaging findings, the patient was diagnosed with CM. The patient improved after 3 weeks of antifungal therapy with amphotericin B 42 mg/d and flucytosine 6000 mg/d. LESSONS: The possibility of CM should be considered when SLE patients have sudden headache and fever. India ink stain of CSF and metagenomic next generation sequences should be actively improved in the early stage of the disease to identify whether there is microbial infection, and early empirical anti-infection treatment should be given to reduce mortality.

The Clinical Application of Artificial Intelligence Assisted Contrast-Enhanced Ultrasound on BI-RADS Category 4 Breast Lesions.

RATIONALE AND OBJECTIVES: To propose a novel deep learning method incorporating multiple regions based on contrast-enhanced ultrasound and grayscale ultrasound, evaluate its performance in reducing false positives for Breast Imaging Reporting and Data System (BI-RADS) category 4 lesions, and compare its diagnostic performance with that of ultrasound experts. MATERIALS AND METHODS: This study enrolled 163 breast lesions in 161 women from November 2018 to March 2021. Contrast-enhanced ultrasound and conventional ultrasound were performed before surgery or biopsy. A novel deep learning model incorporating multiple regions based on contrast-enhanced ultrasound and grayscale ultrasound was proposed for minimizing the number of false-positive biopsies. The area under the receiver operating characteristic curve (AUC), sensitivity, specificity, and accuracy were compared between the deep learning model and ultrasound experts. RESULTS: The AUC, sensitivity, specificity, and accuracy of the deep learning model in BI-RADS category 4 lesions were 0.910, 91.5%, 90.5%, and 90.8%, respectively, compared with those of ultrasound experts were 0.869, 89.4%, 84.5%, and 85.9%, respectively. CONCLUSION: The novel deep learning model we proposed had a diagnostic accuracy comparable to that of ultrasound experts, showing the potential to be clinically useful in minimizing the number of false-positive biopsies.

The Role of a Deep Learning-Based Computer-Aided Diagnosis System and Elastography in Reducing Unnecessary Breast Lesion Biopsies.

OBJECTIVES: Ultrasound examination has inter-observer and intra-observer variability and a high false-positive rate. The aim of this study was to evaluate the value of the combined use of a deep learning-based computer-aided diagnosis (CAD) system and ultrasound elastography with conventional ultrasound (US) in increasing specificity and reducing unnecessary breast lesions biopsies. MATERIALS AND METHODS: Conventional US, CAD system, and strain elastography (SE) were retrospectively performed on 216 breast lesions before biopsy or surgery. The area under the receiver operating characteristic curve (AUC), sensitivity, specificity, and biopsy rate were compared between conventional US and the combination of conventional US, SE, and CAD system. RESULTS: Of 216 lesions, 54 were malignant and 162 were benign. The addition of CAD system and SE to conventional US increased the AUC from 0.716 to 0.910 and specificity from 46.9% to 85.8% without a loss in sensitivity while 89.2% (66 of 74) of benign lesions in Breast Imaging Reporting and Data System (BI-RADS) category 4A lesions would avoid unnecessary biopsies. CONCLUSION: The addition of CAD system and SE to conventional US improved specificity and AUC without loss of sensitivity, and reduced unnecessary biopsies.

Elastography Assisted BI-RADS in the Preoperative Breast Magnetic Resonance Imaging 4a Lesions in China.

OBJECTIVES: A considerable number of benign lesions, especially category 4a lesions on Breast Imaging Reporting and Data System Magnetic Resonance Imaging (BI-RADS-MRI), were biopsied according to BI-RADS-MRI, which was a diagnostic imaging challenge. This study aimed to evaluate the diagnostic performance of ultrasound elastography (UE) assisted Breast Imaging Reporting and Data System (BI-RADS) for BI-RADS-MRI category 4a lesions. METHODS: Between January 2017 and December 2019, 228 breast lesions categorized as BI-RADS-MRI 4a were included. Conventional ultrasound (US) and UE were performed to evaluate each lesion. Pathology results were used as the gold standard. The diagnostic performances of different UE methods and our re-assessment proposal were evaluated. RESULTS: When BI-RADS-MRI category 4a, BI-RADS-US category 3-4a, the stiffness of soft or intermediate in elasticity assessment according to the fifth edition of the BI-RADS atlas, strain ratio < 1.335, age ≤ 52 years, and the maximum diameter of lesion ≤20 mm were simultaneously met, an ultrasound-guided empty needle biopsy was not recommended, but short-term ultrasound follow-up for 3-6 months was recommended, and biopsy was performed after changes in evaluation. In this way, 95 of 228 BI-RADS-MRI category 4a lesions avoided biopsies, and the number of patients with biopsies decreased by 41.7%. CONCLUSIONS: UE offers benefits in the characterization of BI-RADS-MRI category 4a lesions. Ultrasound and elastography can help optimize therapy recommendations for BI-RADS-MRI category 4a lesions by our re-assessment proposal.

Clinical use and adjustment of ultrasound elastography for breast lesions followed WFUMB guidelines and recommendations in the real world.

Objective: This study aimed to explore the value of strain elastography (SE) and shear wave elastography (SWE) following the World Federation of Ultrasound in Medicine and Biology (WFUMB) guidelines and recommendations in the real world in distinguishing benign and malignant breast lesions and reducing biopsy of BI-RADS (Breast Imaging Reporting and Data System) 4a lesions. Methods: This prospective study included 274 breast lesions. The elastography score (ES) by the Tsukuba score, the strain ratio (SR) for SE, and Emax for SWE of the lesion(A) and the regions(A') included the lesion and the margin (0.5-5 mm) surrounding the lesion were measured. The sensitivity, specificity, and AUC were calculated and compared by the cutoff values recommended by WFUMB guidelines. Results: When scores of 1 to 3 were classified as probably benign by WFUMB recommendation, the ES was significantly higher in malignant lesions compared to benign lesions (p < 0.05) in all lesions. For the cohort by size >20 mm, the sensitivity was 100%, and the specificity was 45.5%. ES had the highest AUC: 0.79(95% CI 0.72-0.86) with a sensitivity of 96.2%, and a specificity of 61.8% for the cohort by size ≤20 mm. For the Emax-A'-S2.5mm, when the high stiffness would be considered with Emax above 80 kPa in SWE, the malignant lesions were diagnosed with a sensitivity of 95.8%, a specificity of 43.3% for all lesions, a sensitivity of 88.5% for lesions with size ≤20 mm, and sensitivity of 100.0% for lesions with size >20 mm. In 84 lesions of BI-RADS category 4a, if category 4a lesions with ES of 1-3 points or Emax-A'-S2.5 less than 80 kPa could be downgraded to category 3, 52 (61.9%) lesions could be no biopsy, including two malignancies. If category 4a lesions with ES of 1-3 points and Emax-A'-S2.5 less than 80kPa could be downgraded to category 3, 23 (27.4%) lesions could be no biopsy, with no malignancy. Conclusions: The elastography score for SE and Emax-A' for SWE after our modification were beneficial in the diagnosis of breast cancer. The combination of SWE and SE could effectively reduce the biopsy rate of BI-RADS category 4a lesions.

Multi-region radiomics for artificially intelligent diagnosis of breast cancer using multimodal ultrasound.

PURPOSE: The ultrasound (US) diagnosis of breast cancer is usually based on a single-region of a whole breast tumor from a single ultrasonic modality, which limits the diagnostic performance. Multiple regions on multimodal US images of breast tumors may all have useful information for diagnosis. This study aimed to propose a multi-region radiomics approach with multimodal US for artificially intelligent diagnosis of malignant and benign breast tumors. MATERIALS AND METHODS: Firstly, radiomics features were extracted from five regions of interest (ROIs) on B-mode US and contrast-enhanced ultrasound (CEUS) images, including intensity statistics, gray-level co-occurrence matrix texture features and binary texture features. The multiple ROIs included the whole tumor region, strongest perfusion region, marginal region and surrounding region. Secondly, a deep neural network, composed of the point-wise gated Boltzmann machine and the restricted Boltzmann machine, was adopted to comprehensively learn and select features. Thirdly, the support vector machine was used for classification between benign and malignant breast tumors. Finally, five single-region classification models were generated from five ROIs, and they were fused to form an integrated classification model. RESULTS: Experimental evaluation was conducted on multimodal US images of breast from 187 patients with breast tumors (68 malignant and 119 benign). Under five-fold cross-validation, the classification accuracy, sensitivity, specificity, Youden's index and area under the receiver operating characteristic curve (AUC) with our model were 87.1% ± 3.3%, 77.4% ± 11.8%, 92.4% ± 7.2%, 69.8% ± 8.6% and 0.849 ± 0.043, respectively. Our model was significantly better than single-region single-modal methods in terms of the AUC and accuracy (p < 0.05). CONCLUSION: In addition to the whole tumor region, the other regions including the strongest perfusion region, marginal region and surrounding region on US images can assist breast cancer diagnosis. The multi-region multimodal radiomics model achieved the best classification results. Our artificially intelligent model would be potentially useful for clinical diagnosis of breast cancer.

Carotid artery vulnerable plaque model for cerebrovascular events by conventional ultrasound & contrast-enhanced ultrasound: A preliminary study.

BACKGROUND: Conventional ultrasound and contrast-enhanced ultrasound play an important role in the application of carotid plaque. AIMS: To establish carotid artery vulnerable plaques model by conventional ultrasound combined with contrast-enhanced ultrasound, identify high-risk plaques that may lead to cerebrovascular events, and provide clinical risk warning of high-risk plaques of stroke. METHODS: 205 cases of patients selected in 5053 patients with symptoms from 2018 to 2019 who were verified carotid plaques by conventional ultrasound and contrast-enhanced ultrasound image characteristics, 147 cases as a training set, establishing the carotid artery plaque model, analyzing the characteristic of the plaques and the relationship between cerebrovascular event, with 58 cases as a test set, verify the model. Routine carotid ultrasound and contrast-enhanced carotid ultrasound were performed in all enrolled patients. RESULTS: The gray-level characteristics of conventional ultrasound in the training concentration showed statistical differences in plaque morphology, fibrous cap morphology, uniformity and calcification degree in cerebrovascular events. The contrast enhanced ultrasound characteristics of plaques showed statistical differences in neovascularization and perfusion mode in cerebrovascular events. In the test set, there were statistical differences in the above conventional gray scale features and CEUS features. CONCLUSION: The vulnerable plaque model established by conventional ultrasound combined with contrast-enhanced ultrasound has good diagnostic value for the characteristic plaque of carotid artery with cerebrovascular events.

Analysis of Clinical Pathway for Patients With Cleft Lip and Palate.

AIM: To evaluate the implementation of a clinical pathway (CP) and identify clinical factors affecting the CP for cleft lip and palate (CLP) patients. METHODS: A specific CP for CLP patients was developed at CLP Medical Center of Stomatological Hospital affiliated to Nanjing Medical University in 2008. The authors reviewed the collected data of 1810 consecutive patients using the CP for repairing cleft lip, cleft palatal, and alveolar cleft. The patients were treated between January 2008 and December 2019. The rate of completion and risk factors affecting dropout from the CP were analyzed. RESULTS: The completion rates of the CP in cleft lip, cleft palate and alveolar cleft patients were 68.3% (n = 345), 82.4% (n = 785) and 76.1% (n = 268), respectively. The overall completion rate was 77.2% (n = 1398). The main reasons for dropping out were pre-operation events (n = 212, 11.7%) and post-operation events (n = 188, 10.4%). Among the factors of dropout of CP, laboratory test abnormalities accounted for the majority of pre- and post-operation events (n = 179, 9.9%). In statistical analysis, the combined abnormities and events associated with operations were significant risk factors affecting the dropout rate from CP. CONCLUSION: The use of CP for CLP patients was reliable but the completion rate was relatively low because of perioperative events. These results provided some evidence of risk factors which should be considered when modifying the protocol of CP for CLP patients in order to achieve higher completion rate.

A microRNA expression profile for vascular invasion can predict overall survival in hepatocellular carcinoma.

BACKGROUND: The presence of vascular invasion (VI) in pathology specimens is a well-known unfavorable prognostic factor of hepatocellular carcinoma (HCC) recurrence and overall survival (OS). We investigated the vascular invasion related microRNA (miRNA) expression profiles and potential of prognostic value in HCC. METHODS: MiRNA and mRNA expression data for HCC were accessed from The Cancer Genome Atlas (TCGA). LASSO logistic regression models were used to develop a miRNA-based classifier for predicting VI. The predictive capability was accessed by area under receiver operating characteristics (AUC). Concordance index (C-index) and time-dependent receiver operating characteristic (td-ROC) were used to determine its prognostic value. We validated the predictive and prognostic accuracy of this classifier in an external independent cohort of 127 patients. Functionally relevant targets of miRNAs were determined using miRNA target prediction, experimental validation and correlation of miRNA and mRNA expression data. RESULTS: A 16-miRNA-based classifier was developed which identified VI accurately, with AUC of 0.731 and 0.727 in TCGA set and validation cohort, respectively. C-index and td-ROC showed that the classifier was able to stratify patients into risk groups strongly associated with OS. When stratified by tumor characteristics, the classifier was still a clinically and statistically significant prognostic model. The predictive and prognostic accuracy of the classifier was confirmed in validation cohort. Vascular invasion related miRNA/target pairs were identified by integrating expression patterns of predicted targets, which were validated in cell lines. CONCLUSIONS: A multi-miRNA-based classifier developed based on the presence of VI, which could effectively predict OS in HCC.

Neutrophil-lymphocyte ratio predicts hospital-acquired bacterial infections in decompensated cirrhosis.

BACKGROUND: Bacterial infection is a frequent complication and severe burden in cirrhotic patients. We determined the utility of neutrophil-to-lymphocyte ratio (NLR) to predict the hospital-acquired (HA) bacterial infections episode in patients with decompensated cirrhosis. METHODS: We retrospectively included 2066 consecutive decompensated cirrhotic patients from two separate tertiary hospitals, divided into training (n=1377) and validation (n=689) set. All data were collected on admission and all overt bacterial infections occurring after >48h of hospital stay were registered. RESULTS: The incidence of HA bacterial infections in training and validation cohort was 35.87% and 31.05% respectively. Multivariate analysis showed that total bilirubin (TBil), albumin, white blood cell count (WBC) and NLR were independent predictors of HA bacterial infections. We established a Model_NTWA using these four variables and a Model_TWA which did not include NLR. Areas under the curves (AUC) of Model_NTWA (0.859) and NLR (0.824) were higher than which of Model_TWA (0.713), WBC (0.675), TBil (0.593) and Albumin (0.583). Consistent with training cohort, validation cohort showed similar results. Patients with NLR of at least 4.33 had a significantly lower survival (P<0.001). CONCLUSIONS: NLR can be used as a novel noninvasive marker to predict the occurrence of HA bacterial infections in decompensated cirrhotic patients.

C-reactive protein-to-albumin ratio is a predictor of hepatitis B virus related decompensated cirrhosis: time-dependent receiver operating characteristics and decision curve analysis.

BACKGROUND AND AIMS: Hepatitis B virus (HBV) infection remains a major health problem and HBV-related-decompensated cirrhosis (HBV-DC) usually leads to a poor prognosis. Our aim was to determine the utility of inflammatory biomarkers in predicting mortality of HBV-DC. MATERIALS AND METHODS: A total of 329 HBV-DC patients were enrolled. Survival estimates for the entire study population were generated using the Kaplan-Meier method. The prognostic values for model for end-stage liver disease (MELD) score, Child-Pugh score, and inflammatory biomarkers neutrophil/lymphocyte ratio, C-reactive protein-to-albumin ratio (CAR), and lymphocyte-to-monocyte ratio (LMR) for HBV-DC were compared using time-dependent receiver operating characteristic curves and time-dependent decision curves. RESULTS: The survival time was 23.1±15.8 months. Multivariate analysis identified age, CAR, LMR, and platelet count as prognostic independent risk factors. Kaplan-Meier analysis indicated that CAR of at least 1.0 (hazard ratio, 7.19; 95% confidence interval, 4.69-11.03), and LMR less than 1.9 (hazard ratio, 2.40; 95% confidence interval, 1.69-3.41) were independently associated with mortality of HBV-DC. The time-dependent receiver operating characteristic indicated that CAR showed the best performance in predicting mortality of HBV-DC compared with LMR, MELD score, and Child-Pugh score. The results were also confirmed by time-dependent decision curves. CONCLUSION: CAR and LMR were associated with the prognosis of HBV-DC. CAR was superior to LMR, MELD score, and Child-Pugh score in HBV-DC mortality prediction.

Development and validation of a prognostic nomogram for acute-on-chronic hepatitis B liver failure.

BACKGROUND AND AIM: Determining individual risk of short-term mortality in patients with acute-on-chronic hepatitis B liver failure (ACHBLF) is a difficult task. We aimed to develop and externally validate a prognostic nomogram for ACHBLF patients. METHODS: The nomogram was built to estimate the probability of 30-day, 60-day, 90-day, and 60-month survival based on an internal cohort of 246 patients with ACHBLF. The predictive accuracy and discriminative ability of nomogram were determined by a concordance index (C-index), calibration curve, and time-dependent receiver operating characteristics (tdROC), comparing with model for end-stage liver disease (MELD) score. The results were validated using bootstrap resampling and an external cohort of 138 patients. Furthermore, we plotted decision curves to evaluate the clinical usefulness of nomogram. RESULTS: Independent factors derived from multivariable Cox analysis of training cohort to predict mortality were age, total bilirubin, serum sodium, and prothrombin activity, which were all assembled into nomogram. The calibration curves for probability of survival showed optimal agreement between nomogram prediction and actual observation. The C-index of nomogram was higher than that of MELD score for predicting survival (30-day, 0.809 vs 0.717, P < 0.001; 60-day, 0.792 vs 0.685, P < 0.001; 90-day, 0.779 vs 0.678, P < 0.001; 6-month, 0.781 vs 0.677, P < 0.001). Additionally, tdROC and decision curves also showed that nomogram was superior to MELD score. The results were confirmed in validation cohort. CONCLUSIONS: The prognostic nomogram provided an individualized risk estimate of short-term survival in patients with ACHBLF, offering to clinicians to improve their abilities to assess patient prognosis.

Prognostic value of DNA repair based stratification of hepatocellular carcinoma.

Aberrant activation of DNA repair is frequently associated with tumor progression and response to therapy in hepatocellular carcinoma (HCC). Bioinformatics analyses of HCC data in the Cancer Genome Atlas (TCGA) were performed to define DNA repair based molecular classification that could predict the prognosis of patients with HCC. Furthermore, we tested its predictive performance in 120 independent cases. Four molecular subgroups were identified on the basis of coordinate DNA repair cluster (CDRC) comprising 15 genes in TCGA dataset. Increasing expression of CDRC genes were significantly associated with TP53 mutation. High CDRC was significantly correlated with advanced tumor grades, advanced pathological stage and increased vascular invasion rate. Multivariate Cox regression analysis indicated that the molecular subgrouping was an independent prognostic parameter for both overall survival (p = 0.004, hazard ratio (HR): 2.989) and tumor-free survival (p = 0.049, HR: 3.366) in TCGA dataset. Similar results were also obtained by analyzing the independent cohort. These data suggest that distinct dysregulation of DNA repair constituents based molecular classes in HCC would be useful for predicting prognosis and designing clinical trials for targeted therapy.

Dicer interacts with SIRT7 and regulates H3K18 deacetylation in response to DNA damaging agents.

Dicer participates in heterochromatin formation in fission yeast and plants. However, whether it has a similar role in mammals remains controversial. Here we showed that the human Dicer protein interacts with SIRT7, an NAD(+)-dependent H3K18Ac (acetylated lysine 18 of histone H3) deacetylase, and holds a proportion of SIRT7 in the cytoplasm. Dicer knockdown led to an increase of chromatin-associated SIRT7 and simultaneously a decrease of cytoplasmic SIRT7, while its overexpression induced SIRT7 reduction in the chromatin-associated fraction and increment in the cytoplasm. Furthermore, DNA damaging agents promoted Dicer expression, leading to decreased level of chromatin-associated SIRT7 and increased level of H3K18Ac, which can be alleviated by Dicer knockdown. Taken together with that H3K18Ac was exclusively associated with the chromatin, our findings suggest that Dicer induction by DNA damaging treatments prevents H3K18Ac deacetylation, probably by trapping more SIRT7 in the cytoplasm.

Clinical value of integrated-signature miRNAs in colorectal cancer: miRNA expression profiling analysis and experimental validation.

MicroRNA (miRNA) expression profiling of colorectal cancer (CRC) are often inconsistent among different studies. To determine candidate miRNA biomarkers for CRC, we performed an integrative analysis of miRNA expression profiling compared CRC tissues and paired neighboring noncancerous colorectal tissues. Using robust rank aggregation method, we identified a miRNA set of 10 integrated-signature miRNAs. In addition, the qRT-PCR validation demonstrated that 9 miRNAs were consistent dysregulated with the integrative analysis in CRC tissues, 4 miRNAs (miR-21-5p, miR-183-5p, miR-17-5p and miR-20a-5p) were up-regulated expression, and 5 miRNAs (miR-145-5p, miR-195-5p, miR-139-5p, miR-378a-5p and miR-143-3p) were down-regulated expression (all p < 0.05). Consistent with the initial analysis, 7 miRNAs were found to be significantly dysregulated in CRC tissues in TCGA data base, 4 miRNAs (miR-21-5p, miR-183-5p, miR-17-5p and miR-20a-5p) were significantly up-regulated expression, and 3 miRNAs (miR-145-5p, miR-139-5p and miR-378a-5p) were significantly down-regulated expression in CRC tissues (all p < 0.001). Furthermore, miR-17-5p (p = 0.011) and miR-20a-5p (p = 0.003) were up-regulated expression in the III/IV tumor stage, miR-145-5p (p = 0.028) and miR-195-5p (p = 0.001) were significantly increased expression with microscopic vascular invasion in CRC tissues, miR-17-5p (p = 0.037) and miR-145-5p (p = 0.023) were significantly increased expression with lymphovascular invasion. Moreover, Cox regression analysis of CRC patients in TCGA data base showed miR-20a-5p was correlated with survival (hazard ratio: 1.875, 95%CI: 1.088-3.232, p = 0.024). Hence, the finding of current study provides a basic implication of these miRNAs for further clinical application in CRC.

Hepatocellular carcinoma associated microRNA expression signature: integrated bioinformatics analysis, experimental validation and clinical significance.

microRNA (miRNA) expression profiles varied greatly among current studies due to different technological platforms and small sample size. Systematic and integrative analysis of published datesets that compared the miRNA expression profiles between hepatocellular carcinoma (HCC) tissue and paired adjacent noncancerous liver tissue was performed to determine candidate HCC associated miRNAs. Moreover, we further validated the confirmed miRNAs in a clinical setting using qRT-PCR and Tumor Cancer Genome Atlas (TCGA) dataset. A miRNA integrated-signature of 5 upregulated and 8 downregulated miRNAs was identified from 26 published datesets in HCC using robust rank aggregation method. qRT-PCR demonstrated that miR-93-5p, miR-224-5p, miR-221-3p and miR-21-5p was increased, whereas the expression of miR-214-3p, miR-199a-3p, miR-195-5p, miR-150-5p and miR-145-5p was decreased in the HCC tissues, which was also validated on TCGA dataset. A miRNA based score using LASSO regression model provided a high accuracy for identifying HCC tissue (AUC = 0.982): HCC risk score = 0.180E_miR-221 + 0.0262E_miR-21 - 0.007E_miR-223 - 0.185E_miR-130a. E_miR-n = Log 2 (expression of microRNA n). Furthermore, expression of 5 miRNAs (miR-222, miR-221, miR-21 miR-214 and miR-130a) correlated with pathological tumor grade. Cox regression analysis showed that miR-21 was related with 3-year survival (hazard ratio [HR]: 1.509, 95%CI: 1.079-2.112, P = 0.016) and 5-year survival (HR: 1.416, 95%CI: 1.057-1.897, P = 0.020). However, none of the deregulated miRNAs was related with microscopic vascular invasion. This study provides a basis for further clinical application of miRNAs in HCC.