Chronic myeloid leukaemia: Biology and therapy.

Chronic myeloid leukaemia (CML) is caused by BCR::ABL1. Tyrosine kinase-inhibitors (TKIs) are the initial therapy. Several organizations have reported milestones to evaluate response to initial TKI-therapy and suggest when a change of TKI should be considered. Achieving treatment-free remission (TFR) is increasingly recognized as the optimal therapy goal. Which TKI is the best initial therapy for which persons and what depth and duration of molecular remission is needed to achieve TFR are controversial. In this review we discuss these issues and suggest future research directions.

The transcriptional control of LcIDL1-LcHSL2 complex by LcARF5 integrates auxin and ethylene signaling for litchi fruitlet abscission.

At the physiological level, the interplay between auxin and ethylene has long been recognized as crucial for the regulation of organ abscission in plants. However, the underlying molecular mechanisms remain unknown. Here, we identified transcription factors involved in indoleacetic acid (IAA) and ethylene (ET) signaling that directly regulate the expression of INFLORESCENCE DEFICIENT IN ABSCISSION (IDA) and its receptor HAESA (HAE), which are key components initiating abscission. Specifically, litchi IDA-like 1 (LcIDL1) interacts with the receptor HAESA-like 2 (LcHSL2). Through in vitro and in vivo experiments, we determined that the auxin response factor LcARF5 directly binds and activates both LcIDL1 and LcHSL2. Furthermore, we found that the ETHYLENE INSENSITIVE 3-like transcription factor LcEIL3 directly binds and activates LcIDL1. The expression of IDA and HSL2 homologs was enhanced in LcARF5 and LcEIL3 transgenic Arabidopsis plants, but reduced in ein3 eil1 mutants. Consistently, the expressions of LcIDL1 and LcHSL2 were significantly decreased in LcARF5- and LcEIL3-silenced fruitlet abscission zones (FAZ), which correlated with a lower rate of fruitlet abscission. Depletion of auxin led to an increase in 1-aminocyclopropane-1-carboxylic acid (the precursor of ethylene) levels in the litchi FAZ, followed by abscission activation. Throughout this process, LcARF5 and LcEIL3 were induced in the FAZ. Collectively, our findings suggest that the molecular interactions between litchi AUXIN RESPONSE FACTOR 5 (LcARF5)-LcIDL1/LcHSL2 and LcEIL3-LcIDL1 signaling modules play a role in regulating fruitlet abscission in litchi and provide a long-sought mechanistic explanation for how the interplay between auxin and ethylene is translated into the molecular events that initiate abscission.

Structure-based design and synthesis of anti-fibrotic compounds derived from para-positioned 3,4,5-trisubstituted benzene.

Liver fibrosis is an abnormal wound-healing response to liver injuries. It can lead to liver cirrhosis, and even liver cancer and liver failure. There is a lack of treatment for liver fibrosis and it is of great importance to develop anti-fibrotic drugs. A pivotal event in the process of developing liver fibrosis is the activation of hepatic stellate cells (HSCs), in which the nuclear receptor Nur77 plays a crucial role. This study aimed to develop novel anti-fibrotic agents with Nur77 as the drug target by modifying the structure of THPN, a Nur77-binding and anti-melanoma compound. Specifically, a series of para-positioned 3,4,5-trisubstituted benzene ring compounds with long-chain backbone were generated and tested for anti-fibrotic activity. Among these compounds, compound A8 was with the most potent and Nur77-dependent inhibitory activity against TGF-ß1-induced activation of HSCs. In a crystal structure analysis, compound A8 bound Nur77 in a peg-in-hole mode as THPN did but adopted a different conformation that could interfere the Nur77 interaction with AKT, which was previous shown to be important for an anti-fibrotic activity. In a cell-based assay, compound A8 indeed impeded the interaction between Nur77 and AKT leading to the stabilization of Nur77 without the activation of AKT. In a mouse model, compound A8 effectively suppressed the activation of AKT signaling pathway and up-regulated the cellular level of Nur77 to attenuate the HSCs activation and ameliorate liver fibrosis with no significant toxic side effects. Collectively, this work demonstrated that Nur77-targeting compound A8 is a promising anti-fibrotic drug candidate.

Glycine Decarboxylase (GLDC) Plays a Crucial Role in Regulating Energy Metabolism, Invasion, Metastasis and Immune Escape for Prostate Cancer.

Glycine decarboxylase (GLDC) is one of the core enzymes for glycine metabolism, and its biological roles in prostate cancer (PCa) are unclear. First, we found that GLDC plays a central role in glycolysis in 540 TCGA PCa patients. Subsequently, a metabolomic microarray showed that GLDC enhanced aerobic glycolysis in PCa cells, and GLDC and its enzyme activity enhanced glucose uptake, lactate production and lactate dehydrogenase (LDH) activity in PCa cells. Next, we found that GLDC was highly expressed in PCa, was directly regulated by hypoxia-inducible factor (HIF1-α) and regulated downstream LDHA expression. In addition, GLDC and its enzyme activity showed a strong ability to promote the migration and invasion of PCa both in vivo and in vitro. Furthermore, we found that the GLDC-high group had a higher TP53 mutation frequency, lower CD8+ T-cell infiltration, higher immune checkpoint expression, and higher immune exclusion scores than the GLDC-low group. Finally, the GLDC-based prognostic risk model by applying LASSO Cox regression also showed good predictive power for the clinical characteristics and survival in PCa patients. This evidence indicates that GLDC plays crucial roles in glycolytic metabolism, invasion and metastasis, and immune escape in PCa, and it is a potential therapeutic target for prostate cancer.

Survival analysis of surgical versus nonsurgical treatment in stage I to III small cell lung cancer in the last 20 years: A systematic review and meta-analysis.

More and more patients with small cell lung cancer (SCLC) have received surgical treatment in the last 20 years. This meta-analysis compared whether surgical treatment can bring greater survival benefits to patients with stage I-III SCLC compared with chemotherapy, radiotherapy and chemoradiotherapy. Pubmed, Embase, Web of Science, Cochrane library database, and ClinicalTrials were searched for relevant articles. The main outcomes were overall survival (OS), reported as hazard ratios (HRs), and 95% confidence intervals (CIs). A total of 19 articles containing 30 185 patients (3940 patients receiving surgical treatment and 26 245 patients receiving nonsurgical treatment) were included in this study. Surgical resection significantly improved OS when compared to nonsurgical treatment in retrospective studies (HR: 0.55, 95% CI: 0.47-0.64, p < 0.01). In the subgroup analysis for retrospective studies, surgical resection was associated with superior OS in stage I (HR: 0.42, 95% CI: 0.24-0.71, p < 0.01), stage II (HR: 0.61, 95% CI: 0.52-0.73, p < 0.01), and stage III diseases (HR: 0.66, 95% CI: 0.51-0.86, p < 0.01). Sublobar resection resulted in worse OS than a lobectomy (HR: 0.78,95% CI: 0.60-1.00, p < 0.01) for patients undergoing surgical resection. Compared with nonsurgical treatment, surgical treatment can indeed bring more significant survival benefits to patients with stage I-III SCLC, and lobectomy can bring longer survival compared with sublobectomy. More prospective studies are needed to confirm these findings.

The investigation on the hypercoagulability of hepatocellular carcinoma-related cerebral infarction with thromboelastography.

AIM: To investigate the hypercoagulability of hepatocellular carcinoma (HCC)-related cerebral infarction (HCRCI) with thromboelastography (TEG). METHODS: A multicenter prospective study was conducted in HCRCI patients, HCC patients without cerebral infarction, and acute cerebral infarction (ACI) patients without HCC between January 2016 and December 2019. TEG parameters and laboratory and clinical data were collected and compared among the three groups. To confirm the independent risk factors of HCRCI, multivariate analyses were conducted. Receiver operating characteristic (ROC) curves were utilized to evaluate the area under the curve (AUC) plotted by each independent risk factor. RESULTS: There were 38 patients recruited in the HCRCI group, and 152 patients were recruited to the HCC group and the ACI group. The levels of plasma neutrophil count, D-dimer, α-fetoprotein (AFP), carcinoembryonic antigen, and maximum amplitude (MA)-a parameter of TEG-were significantly higher in the HCRCI group than HCC and ACI groups. Multivariate logistic regression analysis showed that increased neutrophile count, D-dimer, AFP, and MA were independently associated with HCRCI. ROC curve analysis showed first that AUC of MA for HCRCI was .875, which was larger than the other risk factors, and second that the optimal cutoff value for MA was 61.35, with a sensitivity of 89.50% and specificity of 66.40%. CONCLUSION: It was suggested that TEG disclosed that the pathogenesis of HCRIC is exactly related to the hypercoagulability. And with a cutoff value of MA equaling to 61.35, TEG facilitates clinicians to identify HCC patients at high risk of HCRIC.

Endovascular treatment versus medical management for mild stroke with acute anterior circulation large vessel occlusion: a meta-analysis.

BACKGROUND: The effectiveness of endovascular treatment (EVT) in patients with mild stroke (National Institutes of Health Stroke Scale score ≤5) and acute anterior circulation large vessel occlusion (AACLVO) remains unknown. OBJECTIVE: To conduct a meta-analysis to compare the efficacy and safety of EVT in patients with mild stroke and AACLVO. METHODS: EMBASE, Cochrane Library, PubMed, and Clinicaltrials.gov databases were searched until October 2022. Both retrospective and prospective studies which compared the clinical outcomes between EVT and medical treatment were included. ORs and 95% confidence intervals (CIs) for excellent and favorable functional outcomes, symptomatic intracranial hemorrhage (ICH), and mortality were pooled using a random-effects model. A propensity score (PS)-based methods adjusted analysis was also performed. RESULTS: 4335 patients from 14 studies were included. In patients with mild stroke and AACLVO, EVT presented no marked differences in excellent and favorable functional outcomes and mortality compared with medical treatment. A higher risk of symptomatic ICH (OR=2.79; 95% CI 1.49 to 5.24; P=0.001) was observed with EVT. Subgroup analysis revealed that EVT had potential benefit for proximal occlusions with excellent functional outcomes (OR=1.68; 95% CI 1.01 to 2.82; P=0.05). Similar results were observed when PS-based methods adjusted analysis was used. CONCLUSION: EVT did not significantly benefit clinical functional outcomes in comparison with medical treatment in patients with mild stroke and AACLVO. However, it may improve functional outcomes when treating patients with proximal occlusion, despite being associated with an increased risk of symptomatic ICH. Stronger evidence from ongoing randomized controlled trials is required.

Upregulation of CCNB2 and Its Perspective Mechanisms in Cerebral Ischemic Stroke and All Subtypes of Lung Cancer: A Comprehensive Study.

Cyclin B2 (CCNB2) belongs to type B cell cycle family protein, which is located on chromosome 15q22, and it binds to cyclin-dependent kinases (CDKs) to regulate their activities. In this study, 103 high-throughput datasets related to all subtypes of lung cancer (LC) and cerebral ischemic stroke (CIS) with the data of CCNB2 expression were collected. The analysis of standard mean deviation (SMD) and summary receiver operating characteristic (SROC) reflecting expression status demonstrated significant up-regulation of CCNB2 in LC and CIS (Lung adenocarcinoma: SMD = 1.40, 95%CI [0.98-1.83], SROC = 0.92, 95%CI [0.89-0.94]. Lung squamous cell carcinoma: SMD = 2.56, 95%CI [1.64-3.48]. SROC = 0.97, 95%CI [0.95-0.98]. Lung small cell carcinoma: SMD = 3.01, 95%CI [2.01-4.01]. SROC = 0.98, 95%CI [0.97-0.99]. CIS: SMD = 0.29, 95%CI [0.05-0.53], SROC = 0.68, 95%CI [0.63-0.71]). Simultaneously, protein-protein interaction (PPI) analysis indicated that CCNB2 is the hub molecule of crossed high-expressed genes in CIS and LC. Through Multiscale embedded gene co-expression network analysis (MEGENA), a gene module of CIS including 76 genes was obtained and function enrichment analysis of the CCNB2 module genes implied that CCNB2 may participate in the processes in the formation of CIS and tissue damage caused by CIS, such as "cell cycle," "protein kinase activity," and "glycosphingolipid biosynthesis." Afterward, via single-cell RNA-seq analysis, CCNB2 was found up-regulated on GABAergic neurons in brain organoids as well as T cells expressing proliferative molecules in LUAD. Concurrently, the expression of CCNB2 distributed similarly to TOP2A as a module marker of cell proliferation in cell cluster. These findings can help in the field of the pathogenesis of LC-related CIS and neuron repair after CIS damage.

Weighted Gene Co-Expression Network Analysis to Identify Potential Biological Processes and Key Genes in COVID-19-Related Stroke.

The purpose of this research was to explore the underlying biological processes causing coronavirus disease 2019- (COVID-19-) related stroke. The Gene Expression Omnibus (GEO) database was utilized to obtain four COVID-19 datasets and two stroke datasets. Thereafter, we identified key modules via weighted gene co-expression network analysis, following which COVID-19- and stroke-related crucial modules were crossed to identify the common genes of COVID-19-related stroke. The common genes were intersected with the stroke-related hub genes screened via Cytoscape software to discover the critical genes associated with COVID-19-related stroke. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis for common genes associated with COVID-19-related stroke, and the Reactome database was used to annotate and visualize the pathways involved in the key genes. Two COVID-19-related crucial modules and one stroke-related crucial module were identified. Subsequently, the top five genes were screened as hub genes after visualizing the genes of stroke-related critical module using Cytoscape. By intersecting the COVID-19- and stroke-related crucial modules, 28 common genes for COVID-19-related stroke were identified. ITGA2B and ITGB3 have been further identified as crucial genes of COVID-19-related stroke. Functional enrichment analysis indicated that both ITGA2B and ITGB3 were involved in integrin signaling and the response to elevated platelet cytosolic Ca2+, thus regulating platelet activation, extracellular matrix- (ECM-) receptor interaction, the PI3K-Akt signaling pathway, and hematopoietic cell lineage. Therefore, platelet activation, ECM-receptor interaction, PI3K-Akt signaling pathway, and hematopoietic cell lineage may represent the potential biological processes associated with COVID-19-related stroke, and ITGA2B and ITGB3 may be potential intervention targets for COVID-19-related stroke.

Abiraterone, Orteronel, Enzalutamide and Docetaxel: Sequential or Combined Therapy?

Objective: To summarize the current therapeutic status using chemotherapeutic agent docetaxel and endocrine therapeutic agents (ARAT, abiraterone, orteronel or enzalutamide) for the treatment of metastatic castration-resistant prostate cancer (mCRPC), including sequential therapy and combined therapy, to promote the consensus on the optimal regimen for achieving superior treatment efficacy. Methods: Through literature search in PubMed, articles with the following relevant keywords were collected and anlyzed: CRPC, abiraterone, orteronel and enzalutamide, median survival, overall survival, prostate specific antigen (PSA), PSA response rate and median radiologic progression-free survival. Results: Fifty-eight articles were obtained and analyzed in this review. These articles included androgen axis-targeting agents after docetaxel, docetaxel after androgen axis-targeting agents, Triple sequential and combination therapy, covering four current drugs for mCRPC treatment: docetaxel, abiraterone, orteronel, and enzalutamide. It was found that there may be some cross-resistance between androgen axis-targeting agents, which will reduce the efficacy of subsequent drug treatment. Although neither of the studies of using combination therapy showed serious drug toxicity, the efficacy of sequential therapy was not as good as expected. Most adverse reactions after treatment were reported to be level 1-2. Conclusion: Based on the results of the current studies, abiraterone followed by enzalutamide treatment is the best sequential treatment for most docetaxel-naïve patients. This treatment achieves not only good OS, but also PFS and PSA response rates. In addition, for patients who have previously failed docetaxel treatment, enzalutamide is the best choice as the subsequent treatment.

The Index of Esophageal Cancer Related Ischemic Stroke: A Retrospective Patient Control Study.

Purpose: To investigate independent risk factors for esophageal cancer-related ischemic stroke (ECIS) and to use them to develop an index of ECIS to help clinicians identify patients at high risk for ECIS or to identify ECIS from other types of ischemic stroke. Methods: We retrospectively enrolled active esophageal cancer (EC) patients with acute ischemic stroke (ECIS group) and patients with active EC without ischemic stroke (EC group), age- and sex-matched with ECIS patients, at seven centers from January 2011 to December 2020. Clinical data and laboratory and imaging findings were collected. Univariate and multivariate analyses were performed to analyze the independent risk factors for ECIS. Optimal cutoffs for sensitivities and specificities were obtained by Youden's J statistic following a receiver operator characteristic (ROC) analysis of each risk factor and the product of the risk factors. Results: A total of 91 ECIS patients and 91 EC patients were included. Elevated levels of carcinoembryonic antigen (CEA) [odds ratio (OR) = 0.105, 95% confidence interval (CI): 1.051-1.174, P < 0.001], D-dimer (DD) (OR = 0.003, 95% CI: 1.002-1.004, P < 0.001), and neutrophil count (OR = 0.857, 95% CI: 1.628-3.407, P < 0.001) were independent risk factors for ECIS. The area under the curve (AUC) of each independent risk factor and the product of the three independent risk factors were calculated by a receiver operator characteristic (ROC) curve, and the cutoff value from the largest AUC was called the ECIS index. Conclusion: It was suggested that elevated plasma DD and CEA levels and increased neutrophils in EC patients may altogether contribute to the development of ECIS. The index of ECIS may facilitate clinicians to identify patients at high risk for ECIS or to identify ECIS from other etiologic types of ischemic stroke.

Cancer Related Subarachnoid Hemorrhage: A Multicenter Retrospective Study Using Propensity Score Matching Analysis.

OBJECTIVE: To investigate the clinical features, risk factors and underlying pathogenesis of cancer related subarachnoid hemorrhage (SAH). METHODS: Clinical data of SAH in patients with active cancer from January 2010 to December 2020 at four centers were retrospectively reviewed. Patients with active cancer without SAH were matched to SAH patients with active cancer group. Logistic regression was applied to investigate the independent risk factors of SAH in patients with active cancer, after a 1:1 propensity score matching (PSM). A receiver operator characteristic curve was configured to calculate the optimal cut-off value of the joint predictive factor for cancer related SAH. RESULTS: A total of 82 SAH patients with active cancer and 309 patients with active cancer alone were included. Most SAH patients with cancer had poor outcomes, with 30-day mortality of 41.5%, and with 90-day mortality of 52.0%. The PSM yielded 75 pairs of study participants. Logistic regression revealed that a decrease in platelet and prolonged prothrombin time were the independent risk factors of cancer related SAH. In addition, receiver operator characteristic curve of the joint predictive factor showed the largest AUC of 0.8131, with cut-off value equaling to 11.719, with a sensitivity of 65.3% and specificity of 89.3%. CONCLUSION: Patients with cancer related SAH often have poor outcomes. The decrease in platelet and prolonged prothrombin time are the independent risk factors of cancer related SAH, and the joint predictive factor with cutoff value equal to 11.719 should hence serve as a novel biomarker of cancer related SAH.

Direct endovascular treatment versus bridging therapy in patients with acute ischemic stroke eligible for intravenous thrombolysis: systematic review and meta-analysis.

OBJECTIVE: In this review and meta-analysis we sought to compare the efficacy and safety of direct endovascular thrombectomy (EVT) and bridging therapy for intravenous thrombolysis (IVT)-eligible patients with acute ischemic stroke caused by large vessel occlusions (AIS-LVO). METHODS: We searched Medline, Embase, and the Cochrane Library for published randomized clinical trials (RCTs) and observational studies providing outcomes of patients with IVT-eligible AIS-LVO who have undergone EVT with or without IVT. The primary outcome was the proportion of patients achieving a modified Rankin Scale (mRS) score of 0-2 at 90 days. The secondary outcomes included the rates of (1) an excellent outcome defined as an mRS score of 0 or 1 at 90 days, (2) mortality at 90 days, (3) symptomatic intracranial hemorrhage (sICH), (4) any type of intracranial hemorrhage (ICH), (5) successful recanalization, and (6) clot migration. RESULTS: We included three RCTs and six observational studies (4 of which were propensity score-adjusted studies) with a total of 3133 patients. In unadjusted and adjusted analyses, no differences in the rates of mRS scores 0-2, mRS scores 0-1, mortality at 90 days, sICH or successful recanalization were detected between patients with AIS-LVO who underwent direct EVT or bridging therapy. The patients treated with direct EVT had a lower risk ratio for any type of ICH and clot migration than did the patients treated with bridging therapy. CONCLUSION: Compared with bridging therapy, direct EVT may be equally effective and yield a lower rate of ICH and clot migration in patients with AIS. TRAIL REGISTRATION NUMBER: PROSPERO: CRD42021236691.

BMI1 activates P-glycoprotein via transcription repression of miR-3682-3p and enhances chemoresistance of bladder cancer cell.

Chemoresistance is the most significant reason for the failure of cancer treatment following radical cystectomy. The response rate to the first-line chemotherapy of cisplatin and gemcitabine does not exceed 50%. In our previous research, elevated BMI1 (B-cell specific Moloney murine leukemia virus integration region 1) expression in bladder cancer conferred poor survival and was associated with chemoresistance. Herein, via analysis of The Cancer Genome Atlas database and validation of clinical samples, BMI1 was elevated in patients with bladder cancer resistant to cisplatin and gemcitabine, which conferred tumor relapse and progression. Consistently, BMI1 was markedly increased in the established cisplatin- and gemcitabine-resistant T24 cells (T24/DDP&GEM). Functionally, BMI1 overexpression dramatically promoted drug efflux, enhanced viability and decreased apoptosis of bladder cancer cells upon treatment with cisplatin or gemcitabine, whereas BMI1 downregulation reversed this effect. Mechanically, upon interaction with p53, BMI1 was recruited on the promoter of miR-3682-3p gene concomitant with an increase in the mono-ubiquitination of histone H2A lysine 119, leading to transcription repression of miR-3682-3p gene followed by derepression of ABCB1 (ATP binding cassette subfamily B member 1) gene. Moreover, suppression of P-glycoprotein by miR-3682-3p mimics or its inhibitor XR-9576, could significantly reverse chemoresistance of T24/DDP&GEM cells. These results provided a novel insight into a portion of the mechanism underlying BMI1-mediated chemoresistance in bladder cancer.

Comprehensive signature analysis of drug metabolism differences in the White, Black and Asian prostate cancer patients.

The drug response sensitivity and related prognosis of prostate cancer varied from races, while the original mechanism remains rarely understood. In this study, the comprehensive signature including transcriptomics, epigenome and single nucleotide polymorphisms (SNPs) of 485 PCa cases- including 415 Whites, 58 Blacks and 12 Asians from the TCGA database were analyzed to investigate the drug metabolism differences between races. We found that Blacks and Whites had a more prominent drug metabolism, cytotoxic therapy resistance, and endocrine therapy resistance than Asians, while Whites were more prominent in drug metabolism, cytotoxic therapy resistance and endocrine therapy resistance than Blacks. Subsequently, the targeted regulation analysis indicated that the racial differences in cytotoxic therapy resistance, endocrine therapy resistance, might originate from drug metabolisms, and 19 drug metabolism-related core genes were confirmed in the multi-omics network for subsequent analysis. Furthermore, we verified that CYP1A1, CYP3A4, CYP2B6, UGT2B17, UGT2B7, UGT1A8, UGT2B11, GAS5, SNHG6, XIST significantly affected antineoplastic drugs sensitivities in PCa cell lines, and these genes also showed good predictive efficiency of drug response and treatment outcomes for PCa in this cohort of patients. These findings revealed a comprehensive signature of drug metabolism differences for the Whites, Blacks and Asians, and it may provide some evidence for making individualized treatment strategies.

Clinical features of intracerebral hemorrhage in patients with colorectal cancer and its underlying pathogenesis.

BACKGROUND: The diagnosis of both cancer and intracerebral hemorrhage (ICH) in the same patient is not uncommon, but the clinical features and pathogenesis of patients with colorectal cancer (CRC) and ICH are still not well known. AIM: To investigate the clinical features and underlying pathogenesis of ICH in patients with CRC. METHODS: A retrospective review of CRC patients complicated with ICH from three centers between January 2014 and December 2020 was performed. Clinical data such as laboratory examinations, imaging features, prognosis, and underlying pathogenesis were analyzed. RESULTS: Of 16673 identified CRC patients, 20 (0.12%) suffered from ICH. There were 13 males and 7 females, with an average age (mean ± SD) of 68.45 ± 10.66 years. Fourteen patients (70%) had distant metastases and most patients (85%) showed an elevation of one or more cancer biomarkers. The hemorrhagic lesions in 13 patients (65%) were in the intracerebral lobe. Four patients were completely dependent and 4 died within 30 days after hemorrhage. Intratumoral hemorrhage (50%) and coagulopathy (50%) accounted for the majority of hemorrhages. CONCLUSION: Patients with ICH and CRC often have clinical features with lobar hemorrhage, distant metastases and poor prognosis. Intratumoral hemorrhage and coagulopathy are the main causes of ICH in patients with CRC.

The independent risks and specific biomarker of breast cancer-related ischemic stroke.

AIM: This retrospective study was designed to investigate the independent risks and specific biomarker for breast cancer-related ischemic stroke (BCRS). METHODS: Clinical features and laboratory findings were compared between BCRS group and breast cancer group without stroke, and further multivariate analyses were performed to predict independent risks factors for BCRS patients. A receiver operator characteristic (ROC) curve analysis was configured to estimate the diagnostic efficacy of each independent risk and the product of these risks and to obtain the optimal cut-off value of diagnosis, which was termed the BCRS Index. RESULTS: BCRS patients had elevated plasma D-dimer and CA153 levels and platelet-to-lymphocyte ratio (PLR), as well as more patients received endocrine therapy (all p ＜ 0.05). Moreover, multivariate analysis revealed that D-dimer levels (odds ratio [OR]: 1.002; 95% confidence interval [CI]: 1.001-1.003; p = 0.000), CA153 levels (OR: 1.005; 95% CI: 1.001-1.008; p = 0.007), PLR (OR: 1.010; 95% CI: 1.004-1.015; p = 0.001), and endocrine therapy (OR: 1.268; 95% CI: 1.087-1.479; p = 0.003) were identified as independent risks of BCRS. Furthermore, ROC analysis displayed that the product of risks had the best diagnostic efficacy, of which the area under the curve was 0.846 ± 0.28. The optimum cut-off point was 2.37 × 106/mL, which was termed the BCRS Index with higher diagnostic accuracy and validity. CONCLUSIONS: Endocrine therapy, as well as elevated plasma D-dimer and CA153 levels and PLR values may be independent risks for BCRS. Furthermore, BCRS Index should be served as a novel specific biomarker for BCRS, which is useful to distinguish BCRS for clinicians.

Wiser Reasoning and Less Disgust Have the Potential to Better Achieve Suicide Prevention.

Background: High school and university teachers need to advise students against attempting suicide, the second leading cause of death among 15-29-year-olds. Aims: To investigate the role of reasoning and emotion in advising against suicide. Method: We conducted a study with 130 students at a university that specializes in teachers' education. Participants sat in front of a camera, videotaping their advising against suicide. Three raters scored their transcribed advice on "wise reasoning" (i.e., expert forms of reasoning: considering a variety of conditions, awareness of the limitation of one's knowledge, taking others' perspectives). Four registered psychologists experienced in suicide prevention techniques rated the transcripts on the potential for suicide prevention. Finally, using the software Facereader 7.1, we analyzed participants' micro-facial expressions during advice-giving. Results: Wiser reasoning and less disgust predicted higher potential for suicide prevention. Moreover, higher potential for suicide prevention was associated with more surprise. Limitations: The actual efficacy of suicide prevention was not assessed. Conclusion: Wise reasoning and counter-stereotypic ideas that trigger surprise probably contribute to the potential for suicide prevention. This advising paradigm may help train teachers in advising students against suicide, measuring wise reasoning, and monitoring a harmful emotional reaction, that is, disgust.

Utility of Thromboelastography to Identify Hypercoagulability in Lung Cancer Related Ischemic Stroke Patients.

Lung cancer related hypercoagulability could increase the risk of ischemic stroke. Routine coagulation tests may have limited capacity in evaluating hypercoagulability. The aim of this study was to investigate the ability of thromboelastography (TEG) in the identification of hypercoagulability in patients with lung cancer and cryptogenic ischemic stroke (LCIS). Between January 2016 and December 2018, whole citrated blood from LCIS patients (n = 35) and age- and gender-matched lung cancer patients and healthy volunteers were used for TEG and routine coagulation tests. The coagulation indicator and clinical data were compared among the 3 groups. There were 27/35 (77.14%) on TEG and 18/35 (51.43%) on routine coagulation tests of LCIS patients who had evidence of hypercoagulability. The detection rate of hypercoagulability by TEG in LCIS patients was higher than routine coagulation tests (P = 0.018). Comparing with lung cancer patients and healthy controls, LCIS patients have a significantly higher maximum amplitude (MA), fibrinogen, and D-dimer. Multivariate analysis showed that D-dimer and MA were significantly associated with ischemic stroke in lung cancer patients. ROC curve showed that the area under the curve of TEG (0.790 ± 0.048, 95% CI: 0.697-0.864) was significantly higher than routine coagulation tests (0.673 ± 0.059, 95% CI: 0.572-0.763) (P = 0.04) in identifying hypercoagulability in LCIS patients. Therefore, TEG could identify hypercoagulability in LCIS patients and healthy controls. Identification of hypercoagulability in lung cancer patients by TEG may be helpful to prevent the occurrence of LCIS.

Profiling of the Risk Factors and Designing of a Model to Identify Ischemic Stroke in Patients with Non-Hodgkin Lymphoma: A Multicenter Retrospective Study.

BACKGROUND: The occurrence of ischemic stroke in patients with non-Hodgkin lymphoma (NHL) is not well understood. This study aimed to determine independent risk factors to identity ischemic stroke in non-Hodgkin lymphoma-associated ischemic stroke (NHLAIS) patients. METHODS: This retrospective study was conducted on NHLAIS patients and age- and gender-matched NHL patients. We collected clinical data of patients in both groups and used multiple logistic regression analysis to identify independent risk factors for NHLAIS. A receiver operating characteristic (ROC) analysis was used to establish an identification model based on potential risk factors of NHLAIS. RESULTS: Sixty-three NHLAIS patients and 63 NHL patients were enrolled. Stage III/IV (58/63, 92.1%) and multiple arterial infarcts (44/63, 69.8%) were common among NHLAIS patients. Notably, NHLAIS patients had higher levels of serum fibrinogen (FIB), D-dimer, and ferritin (SF) and prolonged thromboplastin time and prothrombin time (PT) compared with NHL patients (all p < 0.05). Elevated FIB, D-dimer, and SF and prolonged PT were independent risk factors for NHLAIS. The area under the ROC curve of the identification model of NHLAIS patients was largest compared to that of other risk factors (0.838, 95% confidence interval: 0.759-0.899) (p < 0.05). CONCLUSION: This study reveals that elevated serum FIB, D-dimer, and SF and prolonged PT are potential independent risk factors of NHLAIS. The identification model established in this study may help monitor NHL patients who are at high risk of developing NHLAIS.