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Purpose: The purpose of this study is to outline a complete picture of Jarisch-Herxheimer reaction (JHR) in the central nervous system among HIV-negative neurosyphilis patients. Methods: A prospective study cohort of 772 cases with almost all stages of neurosyphilis depicted the features of JHR including occurrence rate, risk profiles, clinical manifestations, medical management and prognosis. Results: The total occurrence rate of JHR was 9.3% (95% CI, 7.3-11.4%), including 4.1% (95% CI, 2.7-5.6%) with severe JHR. The reaction started 5 h after treatment initiation, peaked after 8 h, and subsided after 18 h. Patients with severe JHR experienced a longer recovery time (26 h). Patients with general paresis (OR = 6.825), ocular syphilis (OR = 3.974), pleocytosis (OR = 2.426), or a high CSF-VDRL titre (per log2 titre increase, OR = 2.235) were more likely to experience JHR. Patients with general paresis had an 11.759-fold increased risk of severe JHR. Worsening symptoms included cognitive impairment, mania, nonsense speech, and dysphoria, while symptoms of hallucination, urination disorder, seizures, myoclonus, or aphasia appeared as new-onset symptoms. Neurosyphilis treatment did not need to be interrupted in most patients with JHR and could be reinstated in patients with seizures under supportive medication when JHR subsided. Conclusion: Severe JHR displayed a 4.1% occurrence rate and clinicians should pay particular attention to patients at a higher risk of JHR. The neurosyphilis treatment regime can be restarted under intensive observation for patients with severe JHR and, if necessary, supportive medication should be initiated and continued until the end of therapy. [ABSTRACT FROM AUTHOR]

Objective: This study was designed to establish and validate promising and reliable nomograms for predicting the survival of angiosarcoma (AS) patients. Methods: The Surveillance, Epidemiology, and End Results database was queried to collect the clinical information of 785 AS patients between 2004 and 2015. Data were split into a training cohort (n = 549) and a validation cohort (n = 236) without any preference. Univariate Cox and multivariate Cox regression analyses were performed to analyze the clinical parameters. Independent prognostic factors were then identified. Two nomograms were constructed to predict overall survival (OS) and cancer‐specific survival (CSS) at 3 and 5 years. Finally, the models were evaluated using concordance indices (C‐indices), calibration plots, and decision curve analysis (DCA). Results: Based on the inclusion and exclusion criteria, 785 individuals were included in this analysis. Univariate and multivariate Cox regression analyses revealed that age, tumor size, and stage were prognostic factors independently associated with the OS of AS. Tumor site, tumor size, and stage were associated with the CSS of AS. Based on the statistical results and clinical significance of variables, nomograms were built. The nomograms for OS and CSS had C‐indices of 0.666 and 0.654, respectively. The calibration curves showed good agreement between the predictive values and the actual values. DCA also indicated that the nomograms were clinically useful. Conclusion: We established nomograms with good predictive ability that could provide clinicians with better predictions about the clinical outcomes of AS patients. [ABSTRACT FROM AUTHOR]

Aim: To study the expression and prognostic significance of CD80 in patients with gastric adenocarcinoma. Materials & methods: Real-time quantitative PCR, western blot and immunohistochemistry were performed to detect the expression of CD80 in gastric cancer tissues and matched adjacent normal tissues. Double immunohistochemical staining was performed to preliminary examine the relationship between CD80+ cells and CD8+ cytotoxic T lymphocytes. Results: The expression of CD80 was downregulated in tumor tissues compared with normal tissues (p = 0.002). Immunohistochemistry analysis showed that 49 (39.8%) of 123 patients with gastric cancer demonstrated reduced CD80 expression, which was correlated with the tumor differentiation grade. Conclusion: Our data suggest that reduced CD80 expression independently predicts a poor prognosis in patients with gastric adenocarcinoma. [ABSTRACT FROM AUTHOR]

Background Serum chloride concentrations have clinical significance in the prognosis of heart failure (HF). Little is known regarding the prognostic value of serum chloride in patients with chronic heart failure (CHF). This study sought to investigate the prognostic ability of admission serum chloride for long-term mortality in CHF patients. Methods We identified 1021 consecutive patients diagnosed with CHF. Participants were followed up for all-cause mortality at 21 ± 9 months to establish the survival models and analyze the association between admission serum chloride concentrations and death risk. Results Of the 1021 patients, 905(88.6%) available cases were obtained. Admission serum chloride concentrations of patients were independently and inversely associated with long-term mortality (hazard ratio [HR]: 0.890; 95% CI: 0.863 to 0.918; p  < 0.001). After multivariable risk adjustment for age, male sex, history of diabetes, LVEF, loop diuretic use, beta-blocker use, ACEI or ARB use, eGFR and NT-proBNP, chloride concentrations remained independently associated with mortality (HR:0.922; 95% CI:0.887 to 0.958; p  < 0.001) but not independent of sodium concentrations (HR: 0.953; 95% CI: 0.900 to 1.009; p  = 0.095). The optimal cut-off value of chloride concentrations predicting death was 102.8 mmol/l with an area under the curve (AUC) value of 0.686 (95% CI: 0.635 to 0.737; p  < 0.001), with a sensitivity of 62% and specificity of 70%. The lower chloride concentrations could significantly increase the risk ratio of CHF patients in the setting of hyponatremia ( p  < 0.001). The cumulative survival estimates significantly differed across Na/Cl quartiles (log-rank χ 2 19.14, p  < 0.001), with higher mortality for higher Na/Cl ratio. Correlation analysis showed a positive correlation between serum chloride concentrations and sodium concentrations ( r  = 0.598; p  < 0.001). An increased AUC was observed by combining chloride and sodium (AUC = 0.704, 95% CI:0.655–0.754, p  < 0.001) compared to sodium only (AUC = 0.689, 95% CI:0.639–0.739, p  < 0.001). Conclusions In a Chinese Han population, admission serum chloride concentrations are inversely associated with all-cause mortality of CHF patients and provide incremental prognostic information of serum sodium. [ABSTRACT FROM AUTHOR]

Abstract: Surgical results for intrahepatic cholangiocarcinoma (ICC) remain unsatisfactory due to the high rate of recurrence. Here, we investigated that the expression and roles of tripartite motif‐containing protein 44 (TRIM44) in human ICCs. Firstly, TRIM44 expression was analyzed in several kinds of cancers by referring to public Oncomine database, and the expressions of TRIM44 mRNA and protein were tested in ICC and corresponding paratumorous tissues. Secondly, functions and mechanisms of TRIM44 in ICC cells were further evaluated by TRIM44 interference and cDNA transfection. Finally, the prognostic role of TRIM44 was assessed by Kaplan–Meier and Cox regression. We found that TRIM44 expression was upregulated in ICC tissues compared with corresponding paratumorous tissues, which were consistent with the results from the public cancer database. Knockdown of TRIM44 repressed the invasion and migration of ICC cells, while increased the ICC cell apoptosis. Additionally, high level of TRIM44 was shown to induce ICC cell epithelial to mesenchymal transition (EMT). Mechanistically, a high level of TRIM44 was found to activate MAPK signaling, and a MEK inhibitor, AZD6244, reversed cell EMT and apoptosis endowed by TRIM44 overexpression. Clinically, TRIM44 expression was positively associated with large tumor size (P = 0.035), lymphatic metastasis (P = 0.008) and poor tumor differentiation (P = 0.036). Importantly, patients in TRIM44high group had shorter overall survival and higher cumulative rate of recurrence than patients in TRIM44low group. Our results suggest elevated TRIM44 promotes ICC development by inducing cell EMT and apoptosis resistance, and TRIM44 is a valuable prognostic biomarker and promising therapeutic target of ICC. [ABSTRACT FROM AUTHOR]

Background and Aim Downregulation of the WW domain containing oxidoreductase ( WWOX) has been reported to be involved in tumorigenesis in several neoplasms. This study sought to investigate the expression and role of WWOX in intrahepatic cholangiocarcinoma ( ICC). Methods WWOX expression was measured by quantitative real-time polymerase chain reaction ( PCR), immunoblot, immunofluorescence, and immunohistochemistry. The prognostic significance was assessed by Kaplan- Meier and Cox regression analyses. The role of WWOX in proliferation, anchorage-independent growth, gene expression regulation, and tumorigenesis was assessed by WWOX re-expression using lentivirus. Methylation-specific PCR was performed to evaluate the methylation status of the WWOX gene regulatory region. A DNA methyltransferase inhibitor, 5-aza-2′-deoxycytidine ( AZA), was used to activate the endogenous WWOX gene in ICC cells both in vitro and in vivo. Results The expression of WWOX in ICC tissues was much lower than that in nontumorous samples and showed reverse correlation with proliferative status. Restoration of WWOX expression resulted in suppression of the growth of WWOX-deficient ICC cells through activation of the intrinsic apoptotic signaling pathway, but did not affect growth of WWOX-sufficient human intrahepatic biliary epithelial derived non-cancer cells. Multivariate analyses revealed that downregulation of WWOX was an unfavorable predictor for overall survival and cumulative recurrence rates. The WWOX gene regulatory region was frequently methylated in ICC tissues and cell lines, and intratumoral WWOX restoration, through AZA injection, suppressed tumor growth in nude mice. Conclusion Downregulation of WWOX may occur as a result of hypermethylation and implies a poor prognosis in ICC; WWOX re-expression may be a potential molecular therapeutic target for ICC. [ABSTRACT FROM AUTHOR]

Triple-negative breast cancer (TNBC) is a subtype with high rates of metastasis, poor prognosis and limited therapeutic options. The present study aimed to identify the potential pivotal genes for prognosis and treatment in TNBC. A total of two microarray expression datasets, GSE38959 and GSE65212, were downloaded from the Gene Expression Omnibus database, and RNA-sequencing data of breast cancer from The Cancer Genome Atlas database were analyzed to screen out differentially expressed genes (DEGs) between TNBC tissues and normal tissues. The intersection of DEGs was submitted to Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses. A protein-protein interaction (PPI) network was constructed and visualized using Cytoscape software. Furthermore, module, centrality and survival analyses were performed to identify the potential hub genes. Reverse transcription-quantitative (RT-q)PCR analysis was performed to detect the expression levels of key genes in TNBC samples, and 377 DEGs were identified. Functional analysis revealed that the DEGs were significantly involved in cell cycle process, nuclear division and the p53 signaling pathway. A PPI network was constructed with these DEGs, and 66 core genes with high centrality features in module 1 were selected. Relapse-free survival analysis confirmed that high expression levels of five genes [cyclin B1 (CCNB1), GINS complex subunit 2, non-SMC condensin I complex subunit G (NCAPG), minichromosome maintenance 4 (MCM4) and ribonucleotide reductase regulatory subunit M2 (RRM2)] were significantly associated with poor prognosis in TNBC. RT-qPCR analysis demonstrated that CCNB1, NCAPG, MCM4 and RRM2 were significantly upregulated in 25 TNBC tissues compared with adjacent normal breast tissues. Furthermore, gene set enrichment analysis revealed that CCNB1, NCAPG, MCM4 and RRM2 were closely associated with tumor proliferation. Taken together, these results suggest that CCNB1, NCAPG, MCM4 and RRM2 are associated with tumorigenesis and TNBC progression, and thus may act as promising prognostic biomarkers and therapeutic targets for TNBC. [ABSTRACT FROM AUTHOR]

Background: Breast cancer (BC) is the most prevalent cancer among women worldwide. Although advances have been made in the identification of predictive biomarkers, current options for early diagnosis and prognostic analysis are still suboptimal. Recently, transfer-RNA-derived RNA fragments (tRFs) have emerged as a class of small noncoding RNAs that play a role in the cancer progression. The authors aimed to identify a specific class of tRFs as a molecular marker for BC diagnosis and prognosis in clinical management. Methods: The levels of 5′-tRF-His-GTG were quantified in BC tissue (n = 101) and inflammatory normal breast tissue (n = 22) using in situ hybridization. Clinicopathological parameters were obtained, including age, tumor node metastasis stage, hormone receptor status, histopathological grade, lymphovascular invasion, and recurrence. The correlation between the expression of 5′-tRF-His-GTG and these parameters in different BC subtypes was analyzed. Patient death and cancer progression were regarded as clinical endpoints in the survival analysis. Gene Ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were also performed to predict the involvement in pivotal biological process. Results: The expression of 5′-tRF-His-GTG was significantly downregulated in BC tissues and was in connection with T stage in human epidermal growth factor 2-positive and basal-like BC, as well as N stage and histopathological grade in luminal BC. Patients with low expression of 5′-tRF-His-GTG had a poor overall survival rate. Statistics of GO and KEGG pathway revealed that cation channel activity, protein catabolic process, response to temperature stimulus, cell cycle, focal adhesion, and glycerophospholipid metabolism were significantly enriched. Conclusions: This study suggests that the assessment of 5′-tRF-His-GTG expression could serve as a novel biomarker for individual diagnosis and prognosis in BC. [ABSTRACT FROM AUTHOR]

In terms of mortality and survival, pancreatic cancer is one of the worst malignancies. Known as a unique type of programmed cell death, cuprotosis contributes to tumor cell growth, angiogenesis, and metastasis. Cuprotosis programmed-cell-death-related lncRNAs (CRLs) have been linked to PAAD, although their functions in the tumor microenvironment and prognosis are not well understood. This study included data from the TCGA-PAAD cohort. Random sampling of PAAD data was conducted, splitting the data into two groups for use as a training set and test set (7:3). We searched for differentially expressed genes that were substantially linked to prognosis using univariate Cox and Lasso regression analysis. Through the use of multivariate Cox proportional risk regression, a risk-rating system for prognosis was developed. Correlations between the CRL signature and clinicopathological characteristics, tumor microenvironment, immunotherapy response, and chemotherapy sensitivity were further evaluated. Lastly, qRT-PCR was used to compare CRL expression in healthy tissues to that in tumors. Some CRLs are thought to have strong correlations with PAAD outcomes. These CRLs include AC005332.6, LINC02041, LINC00857, and AL117382.1. The CRL-based signature construction exhibited outstanding predictive performance and offers a fresh approach to evaluating pre-immune effectiveness, paving the way for future studies in precision immuno-oncology. [ABSTRACT FROM AUTHOR]

Background: Triple negative breast cancer (TNBC) is a subtype of breast cancer with poor prognosis and lack of effective treatment target. Here we screened differentially expressed lncRNAs through bioinformatics analysis and identified CARMN as a downregulated lncRNA which is lowest expressed in TNBC. We aimed to identify the potential role and molecular mechanisms of CARMN in TNBC. Methods: Predictive value of CARMN was explored in breast cancer cohorts. TNBC cell lines with CARMN overexpression or CARMN silence and were used for in vitro and in vivo experiments. RNA-seq of CARMN overexpressed cells was performed for exploring downstream of CARMN. Results: CARMN is downregulated at different phase of malignant transformation of breast tissue. CARMN can predict both better prognosis and higher response rate of cisplatin-based neoadjuvant chemotherapy in breast cancer. A nomogram is built to predict cisplatin-based chemotherapy response in breast cancer. Through in vitro and in vivo studies, we confirmed CARMN can also inhibit tumorigenesis and enhance sensitivity to cisplatin in TNBC cells. RNA-seq and further experiments revealed CARMN can inhibit DNA replication. MCM5, an important DNA replication initiation factor, is the most downregulated gene in DNA replication pathway following CARMN overexpression. We confirmed CARMN can produce miR143-3p from its exon5 which is DROSHA and DICER dependent, resulting binding and decrease of MCM5. Moreover, suppressing miR143-3p can weaken function of CARMN in suppressing tumorigenesis and promoting chemosensitivity. Conclusions: Our results indicated lncRNA CARMN is a predictive biomarker of better prognosis and enhanced cisplatin sensitivity in TNBC. CARMN is the host gene of miR143-3p which downregulates MCM5, causing inhibited DNA replication. [ABSTRACT FROM AUTHOR]