Identifying cancer-related microRNAs based on gene expression data.

MOTIVATION: MicroRNAs (miRNAs) are short non-coding RNAs that play important roles in post-transcriptional regulations as well as other important biological processes. Recently, accumulating evidences indicate that miRNAs are extensively involved in cancer. However, it is a big challenge to identify which miRNAs are related to which cancer considering the complex processes involved in tumors, where one miRNA may target hundreds or even thousands of genes and one gene may regulate multiple miRNAs. Despite integrative analysis of matched gene and miRNA expression data can help identify cancer-associated miRNAs, such kind of data is not commonly available. On the other hand, there are huge amount of gene expression data that are publicly accessible. It will significantly improve the efficiency of characterizing miRNA's function in cancer if we can identify cancer miRNAs directly from gene expression data. RESULTS: We present a novel computational framework to identify the cancer-related miRNAs based solely on gene expression profiles without requiring either miRNA expression data or the matched gene and miRNA expression data. The results on multiple cancer datasets show that our proposed method can effectively identify cancer-related miRNAs with higher precision compared with other popular approaches. Furthermore, some of our novel predictions are validated by both differentially expressed miRNAs and evidences from literature, implying the predictive power of our proposed method. In addition, we construct a cancer-miRNA-pathway network, which can help explain how miRNAs are involved in cancer. AVAILABILITY AND IMPLEMENTATION: The R code and data files for the proposed method are available at http://comp-sysbio.org/miR_Path/ CONTACT: liukeq@gmail.com SUPPLEMENTARY INFORMATION: supplementary data are available at Bioinformatics online.

[Relationship between early blood pressure variability and reperfusion in acute ischemic stroke patients with intravenous thrombolysis].

OBJECTIVE: To investigate the impacts of blood pressure (BP) variability on reperfusion and long-term outcome in patients with acute ischemic stroke after intravenous thrombolysis (IVT). METHODS: The clinical data of 188 patients with acute ischemic stroke receiving IVT in Department of Neurology, the Second Affiliated Hospital, Zhejiang University School of Medicine from June 2009 to September 2014, including hour-to-hour BP measurements, clinical manifestations, laboratory tests and radiologic findings were retrospectively analyzed. The mean 24-h BP values, and BP variability profiles, including standard deviation (sd), average squared difference between successive measurements (sv), average squared difference between rise and drop successive measurements (sv-rise and sv-drop) were calculated. Reperfusion, defined as >50% reduction in Tmax >6 s perfusion lesion volume from baseline to follow-up scans, and clinical neurological outcome based on modified Rankin scale (mRS) at 3 months after onset were also analyzed. The favorable outcome was defined as mRS 0-1 and unfavorable outcome as mRS 2-6. The binary logistic-regression model was performed to determine the independent risk factors of reperfusion and favorable outcome, respectively. RESULTS: Among 188 patients, 114 (60.6%) achieved reperfusion. During the 0-to-24 h blood pressure course, only systolic blood pressure (SBP) variability parameters were negatively correlated with reperfusion (sv: OR=0.421, 95% CI:0.187-0.950, P=0.037; sv-rise: OR=0.311, 95% CI:0.137-0.704, P=0.005) and long-term clinical outcomes (sv: OR=6.381, 95% CI:2.132-19.096, P=0.001; sv-rise: OR=5.615, 95% CI:2.152-14.654, P<0.001; sv-drop: OR=3.009, 95% CI:1.263-7.169, P=0.013). CONCLUSION: SBP variability during the first 24 hours after IVT is negatively associated with cerebral reperfusion and unfavorable neurological outcome in patients with acute ischemic stroke receiving IVT.

[Risk factors of hemorrhagic transformation in different locations and its relation to clinical outcomes of patients with acute ischemic stroke following intravenous thrombolysis].

OBJECTIVE: To investigate the risk factors of hemorrhagic transformation (HT) in different cerebral regions and to explore its relation to clinical outcomes of patients with acute ischemic stroke after intravenous thrombolysis therapy. METHODS: The clinical, laboratory, and radiological data of 292 consecutive acute ischemic stroke patients undergoing intravenous thrombolysis therapy in Second Affiliated Hospital, Zhejiang University School of Medicine from June 2009 to May 2013 was retrospectively analyzed. Deep HT was defined as HT located in basal ganglia, internal capsule, external capsule and thalamus, otherwise the lesion was defined as non-deep HT. Patients were divided into 3 groups [Deep HT(n=47), non-deep HT(n=82), non HT(n=8)] and the differences in clinical and demographic characteristics were compared by using one-way analysis of variance and Ξ2-test. Multivariable logistic regression models were used to determine the independent risk factors of HT in different cerebral regions and clinical outcomes. RESULTS: Age, baseline National Institutes of Health Stroke Scale (NIHSS) score, baseline systolic blood pressure and the frequency of atrial fibrillation were different among three groups. Logistic regression analysis revealed that baseline NIHSS score (OR=1.126, 95%CI:1.063-1.193, P<0.001) and baseline systolic blood pressure (OR=0.982, 95%CI:0.967-0.998, P=0.020) were independent risk factors of deep HT. Multivariate analysis also found that deep HT was an independent predictor of functional outcome after thrombolysis (OR=0.291, 95%CI:0.133-0.640, P=0.002). CONCLUSION: Baseline NIHSS score and systolic blood pressure are predictors for deep hemorrhagic transformation, which indicates the poor functional outcome of patients with acute ischemic stroke following thrombolytic therapy.

Identifying dysregulated pathways in cancers from pathway interaction networks.

BACKGROUND: Cancers, a group of multifactorial complex diseases, are generally caused by mutation of multiple genes or dysregulation of pathways. Identifying biomarkers that can characterize cancers would help to understand and diagnose cancers. Traditional computational methods that detect genes differentially expressed between cancer and normal samples fail to work due to small sample size and independent assumption among genes. On the other hand, genes work in concert to perform their functions. Therefore, it is expected that dysregulated pathways will serve as better biomarkers compared with single genes. RESULTS: In this paper, we propose a novel approach to identify dysregulated pathways in cancer based on a pathway interaction network. Our contribution is three-fold. Firstly, we present a new method to construct pathway interaction network based on gene expression, protein-protein interactions and cellular pathways. Secondly, the identification of dysregulated pathways in cancer is treated as a feature selection problem, which is biologically reasonable and easy to interpret. Thirdly, the dysregulated pathways are identified as subnetworks from the pathway interaction networks, where the subnetworks characterize very well the functional dependency or crosstalk between pathways. The benchmarking results on several distinct cancer datasets demonstrate that our method can obtain more reliable and accurate results compared with existing state of the art methods. Further functional analysis and independent literature evidence also confirm that our identified potential pathogenic pathways are biologically reasonable, indicating the effectiveness of our method. CONCLUSIONS: Dysregulated pathways can serve as better biomarkers compared with single genes. In this work, by utilizing pathway interaction networks and gene expression data, we propose a novel approach that effectively identifies dysregulated pathways, which can not only be used as biomarkers to diagnose cancers but also serve as potential drug targets in the future.

Network pharmacology analysis of the mechanism of Huisheng oral liquid in the treatment of lung cancer.

Background: To study the active ingredient and possible mechanism of Huisheng oral liquid in the treatment of lung cancer by network pharmacology. Methods: The active ingredient and drug targets of Huisheng oral liquid were screened using the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) and Traditional Chinese Medicine Integrated Database (TCMID), and lung cancer targets were screened using the Gene Expression Omnibus (GEO) database. The drug targets of the effective components of Huisheng oral liquid were matched with disease targets and the obtained intersecting targets were imported into the Search Tool for the Retrieval of Interaction Gene/Proteins (STRING) database to construct a protein-protein interaction (PPI) network. R software and the Kyoto Encyclopedia of Genes and Genomes (KEGG) database were used for Gene Ontology (GO) and KEGG enrichment analyses, and Cytoscape software was used to construct a Huisheng oral liquid component target-lung cancer target network. The function and pathway of the therapeutic target of Huisheng oral liquid for lung cancer were analyzed. Results: A total of 1,376 differentially expressed genes (DEGs) of lung cancer were obtained, and 185 potential effective components of Huisheng oral liquid in the treatment of lung cancer were obtained, including quercetin, luteolin, kaempferol, and baicalein. There were 36 intersecting targets between Huisheng oral liquid and lung cancer, and the key targets for lung cancer treatment were CDKN1A, CCNB1, MDM2, CDK1, ErbB2, E2F1, EGFR, etc. Huisheng oral liquid mainly regulates the p53 signaling pathway. Conclusions: The mechanism of Huisheng oral liquid in the treatment of lung cancer is mainly reflected in regulating tumor cell apoptosis, inhibiting angiogenesis, and improving immunity.

Adverse skin reactions induced by sintilimab in advanced lung squamous carcinoma: a case report and review of the literature.

Background: Sintilimab is an immune checkpoint inhibitor (ICI). It can induce immune-related Adverse Events (irAEs). Severe adverse skin reactions are rare, but the mortality rate is high. We report the first case of successful treatment of adverse skin reactions using traditional Chinese medicine (TCM). Case Description: Here we present the case of a 67-year-old male with advanced lung squamous carcinoma. After 8 cycles of chemotherapy, the patient's disease progressed and the treatment regimen was adjusted to sintilimab combined with albumin paclitaxel and cisplatin. Thirty-two days after this cycle, the patient reported a sporadic rash with pruritus on the face, front chest, and both upper limbs. The area of rash was 40%, and the adverse reaction was grade 3. The level of interleukin-related indicators was above normal. The patient's skin symptoms disappeared after treatment with hormones, TCM, and other drugs. The patient's adverse skin reaction was due to an immune-related toxicity caused by sintilimab, so treatment with sintilimab was suspended. The albumin-paclitaxel plus cisplatin regimen was continued to treat lung cancer. Conclusions: Although rare, case of fatal adverse reaction caused by sintilimab have been reported. We recommend early monitoring and recognition of symptoms. During management, high-dose hormones combined TCM may be helpful.

miR-517a is up-regulated in glioma and promotes glioma tumorigenesis in vitro and in vivo.

miR-517a has been reported to act as an oncogenic miRNA in human hepatocellular carcinoma and lung cancer. However, the roles and underlying molecular mechanism of miR-517a in glioma remain unclear. In the present study, the expression of miR-517a in clinical glioma tissues and glioma cell lines was examined by quantitative real-time PCR (qRT-PCR). Transfected with knockdown or forced expression of miR-517a, the effects of miR-517a on cell proliferation, migration, and invasion were detected through in vitro and in vivo tumorigenesis assays. Here, we report that miR-517a expression was up-regulated in glioma tissues when compared with normal brain tissues, and up-regulation of miR-517a level is tightly correlated with the status of pathology classification of glioma. A functional assay found that overexpression of miR-517a in glioma cells markedly promoted or suppressed cell proliferation, colony formation, migration and invasion, respectively. Moreover, we revealed that the knockdown of miR-517a dramatically suppressed glioma cell growth, migration, and invasion in vitro and in vivo Furthermore, we found that knockdown of miR-517a significantly induced apoptosis. Therefore, miR-517a acts an oncogenic miRNA that promotes tumor progression in glioma, and thus may become a promising therapeutic candidate for glioma.

Mechanical Thrombectomy Outcome Predictors in Stroke Patients with M2 Occlusion: A Single-Center Retrospective Study.

BACKGROUND: Mechanical thrombectomy (MT) has demonstrated benefit in patients with acute ischemic stroke due to proximal large-vessel occlusion. However, it is unclear whether these results can be extrapolated to patients with an occlusion of the second segment (M2) of the middle cerebral artery (MCA). We sought to study outcomes in patients with M2 occlusion treated with MT and to better understand clinical predictors of these outcomes. METHODS: We performed a single-center retrospective analysis of consecutive patients with acute MCA M2 segment occlusion who underwent stent retriever MT. We correlated clinical and radiographic outcomes with demographic, clinical, and technical characteristics. RESULTS: Thirty-seven patients were included in the analysis (median admission National Institutes of Health Stroke Scale [NIHSS] score, 15 [12-19], mean age 74 [67-80] years, 48.6% women). Good clinical outcome at 3 months (modified Rankin Scale ≤2) was achieved in 48.6% of patients. Baseline NIHSS was a predictor of clinical outcomes, based on modified Rankin Scale distribution at 3 months after MT (P = 0.015, odds ratio 1.63, 95% confidence interval 1.01-2.43). CONCLUSIONS: The results of our single-institution experience suggest that MT-based endovascular therapy for M2 occlusions is safe and effective. Baseline NIHSS was a predictor of outcomes in patients treated with MT for M2 segment occlusion of the MCA.

Mechanical Thrombectomy Using Solitaire in Acute Ischemic Stroke Patients with Vertebrobasilar Occlusion: A Prospective Observational Study.

BACKGROUND: The safety and effectiveness of endovascular mechanical thrombectomy in patients with acute vertebrobasilar occlusion (VBO) are debatable and undergoing evaluation. We report the clinical outcome and prognostic factors in a prospective cohort of acute ischemic stroke patients with VBO. METHODS: In total, 48 consecutive patients with acute VBO underwent mechanical thrombectomy using Solitaire. We analyzed clinical and imaging data and searched for predictors of good clinical outcome (modified Rankin scale score: 0-3). RESULTS: The median prethrombectomy National Institutes of Health Stroke Scale score was 22.0. The median duration from symptom onset to recanalization was 493.5 minutes. A total of 35.4% of the patients received rescue therapy. Recanalization (modified Thrombolysis In Cerebral Infarction: 2b-3) was successful in all patients. Clinically relevant intracranial hemorrhage was observed in 2 patients. After 90 days, good outcomes were obtained in 27 patients. The baseline National Institutes of Health Stroke Scale score, posterior circulation Acute Stroke Prognosis Early CT Score (pc-ASPECTS), anesthesia type, and posterior communicating artery (PComA) patency were significantly associated with outcomes at 90 days in univariate analysis. Multivariate logistic regression indicated that high pc-ASPECTS at admission and PComA patency were independent predictors of good outcome at 90 days. CONCLUSIONS: Up to 60.4% of the patients reached good outcomes after endovascular treatment and 35.4% of the patients received rescue therapy, suggesting that mechanical thrombectomy using Solitaire in patients with stroke with VBO is safe and effective and that rescue therapy is readily required and employed. High baseline pc-ASPECTS and PComA patency were associated with better outcomes after thrombectomy in these patients.

[Study on the changes of soluble intercellular adhesion molecule-1 level in sera of rats infected with Pneumocystis carinii].

OBJECTIVES: To examine sICAM-1 in Pneumocystis carinii pneumonia (PCP) and the effect of TMP-SMZ therapy on its level and on pathological and immunological changes in rats. METHODS: 50 female Wistar rats were randomly divided into normal group (N group), PCP model group (PCP group) and TMP-SMZ therapy group (SMZ group). 1 mg of dexamethasone was injected intramuscularly twice a week for rats in PCP and SMZ groups to induce PCP. Normal saline was injected for N group in the same way. When the infection was confirmed, TMP-SMZ was given to rats in SMZ group by 25 mg/(kg.d) for 5 days for 3 courses with an interval of 2 weeks. sICAM-1 in serum was detected by ELISA, and the pathological changes in lungs and liver and the Pc in alveoli of lungs were observed. RESULTS: The level of sICAM-1 in PCP and SMZ groups at the 3rd week [(1.847+/-0.50) ng/ml, (1.787+/-0.59) ng/ml] was lower notably than that at 0 week [(2.407+/-0.81) ng/ml, [(2.478+/-0.59) ng/ml respectively] (P<0.05), and then increased gradually. It was significantly higher in PCP group at 9th week [(3.233+/-0.83) ng/ml] and at 12th week [(3.984+/-0.87) ng/ml] than that of 0 week (P<0.05). Its level in SMZ group at 12th week [(3.621+/-l.62) ng/ml] was also higher than that in 0 week [(2.478+/-0.59) ng/ml] (P<0.05). sICAM-1 level in both PCP and SMZ groups at 9th week and 12th week was higher than that of N group (P<0.05, P<0.01). There was no significant difference between SMZ and PCP groups at 9th week and 12th week (P>0.05). CONCLUSION: The sICAM-1 level in rats was low but significantly increases after the induction of PCP.

Risk Factors and Outcomes in Patients With Hypernatremia and Sepsis.

BACKGROUND: Hypernatremia is an uncommon but important electrolyte abnormality in intensive care unit patients. Sepsis is one of the most common causes of intensive care unit admission, but few studies about the role of hypernatremia in sepsis has been published yet. In this study, we aimed to explore the risk factors for developing hypernatremia in patients with sepsis, and the prognosis of patients with sepsis with or without hypernatremia was also assessed. MATERIALS AND METHODS: In this retrospective cohort study of 51 septic intensive care unit patients at a single center, we examined the risk factors for the development of hypernatremia and the association of hypernatremia with clinical outcomes using univariate and multivariable analyses. Clinical outcomes such as mortality and hospital duration of patients with or without hypernatremia were also compared. RESULTS: Acute Physiology and Chronic Health Evaluation II score (odds ratio = 1.15; 95% CI: 1.022-1.294) was found to be the only independent risk factor for hypernatremia in patients with sepsis. Moreover, patients developing hypernatremia during hospitalization showed significantly higher morbidity and mortality. CONCLUSIONS: Acute Physiology and Chronic Health Evaluation II score may be an independent risk factor for hypernatremia in patients with sepsis. Moreover, hypernatremia is strongly associated with worse outcome in sepsis.