Effectiveness of D-dimer in predicting distant metastasis in colorectal cancer.

PURPOSE: Patients with cancer often present with a hypercoagulable state, which is closely associated with tumor progression. The purpose of this study was to assess the diagnostic efficacy of D-dimer in predicting distant metastasis in colorectal cancer (CRC). METHODS: This study included 529 patients diagnosed with CRC at our hospital between January 2020 and December 2022. Plasma coagulation indicators and tumor markers were collected prior to treatment and their diagnostic efficacy for predicting CRC metastasis was assessed by receiver operating characteristic (ROC) curves. Independent risk factors for evaluating tumor metastasis were obtained by multivariate logistic regression analysis. RESULTS: The level of D-dimer in the metastatic group was significantly higher than that in the non-metastatic group (P<0.001). The results of the multiple logistic regression analysis indicated that lower level of prealbumin and platelet, and higher level of glucose, CEA and D-dimer were independent risk factors for distant metastasis in patients with CRC (P<0.05, respectively). The combination of prealbumin, glucose, D-dimer, platelet and tumor markers (PRE2) was found to be significantly more effective in predicting metastasis of CRC when compared to the combination of tumor marker alone (PRE1, P<0.001). CONCLUSION: Plasma D-dimer may be a novel tumor marker for screening metastases of CRC.

Circulating tumor cells are a good predictor of tumor recurrence in clinical patients with gastric cancer.

Circulating tumor cells (CTCs) as a liquid biopsy have great potential in clinical applications and basic cancer research, but their clinical use in gastric cancer remains unclear. This study investigated whether CTCs could be used as a potential prognosis predictor in patients with gastric cancer. A total of 120 patients with pathologically confirmed gastric cancer were enrolled from January 1, 2015, to December 1, 2019. All patients were initially diagnosed without previous treatment, and then the number of CTCs was detected using the NEimFISH method before radical surgical resection. Regular follow-up was performed in all patients, and the correlations between the number of CTCs and clinical endpoints, such as disease-free survival (DFS) and overall survival (OS), were evaluated. The univariate and multivariate hazard ratios were calculated using the Cox proportional hazard model. Based on the number of CTCs, we defined CTCs ≥ 2 per 7.5 mL of whole blood as the positive group and CTCs < 2 as the negative group. Among the 120 patients who underwent CTC detection before surgery, the rate of CTC-positive patients was 64.17% (77/120) of which stage I and II patients accounted for 22.50% and stage III patients accounted for 41.67% (P = 0.014). By detecting CTCs before surgery and at the time of recurrence, the number of CTCs tends to increase concomitantly with disease progression (median: 2 VS 5 per 7.5 mL). Multivariate analysis showed that age (HR, 0.259; 95% CI, 0.101-0.662; P = 0.005), D-dimer (HR, 3.146; 95% CI, 1.169-8.461; P = 0.023), and lymph node metastasis (HR, 0.207; 95% CI, 0.0071-0.603; P = 0.004) were factors correlated with CTCs. In addition, the median follow-up of all the patients was 38.0 months (range of 28-80 months); the DFS in CTC-positive patients was significantly shorter than that of the CTC-negative patients, and a significant difference was found based on the Cox proportional hazard regression model analysis (44.52 ± 2.83 m vs. 74.99 ± 2.78 m, HR = 4.550, P = 0.018). The OS was shorter in the CTC-positive group than in the CTC-negative group before the operation, but the result was not significant based on the Cox proportional hazard regression model analysis (47.58 ± 2.46 m vs. 70.68 ± 3.53 m, HR = 2.261, P = 0.083). The number of CTCs tends to increase concomitantly with disease progression. In addition, the detection of CTCs was an independent predictor of shorter DFS in gastric cancer. However, the relationship between CTCs and OS needs to be determined in future studies.

Validity and predictability of the confusion assessment method for the intensive care unit for delirium among critically ill patients in the intensive care unit: A systematic review and meta-analysis.

OBJECTIVE: To identify the validity and predictability of the confusion assessment method for the intensive care unit (CAM-ICU) for delirium in critically ill patients in the ICU. METHODS: In this systematic review, PubMed, Embase, Cochrane Central Register of Controlled Trials, and MEDLINE databases were searched for observational studies investigating delirium screening tools for ICU patients. In the meta-analysis, we combined the sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, diagnostic odds ratio, and area under the curve (AUC) of SROC to analysis the predictive value of CAM-ICU. RESULTS: Twenty-nine articles met the inclusion criteria. The pooled sensitivity and specificity values were 0.82 (95% confidence interval [CI]: 0.75-0.87) and 0.95 (95% CI: 0.93-0.97), respectively. The AUC point estimate of the SROC curve was 0.96 (95% CI: 0.94-0.97). Race (Asian or Others) could affect the pooled sensitivity and specificity, and the analysis method (Patient- or Scan-based) and study design were not sources of heterogeneity for pooled sensitivity and specificity. CONCLUSIONS: The CAM-ICU is a valid and reliable tool for delirium prediction among ICU patients. When introducing CAM-ICU to assess delirium, it is necessary to localize its language and content to improve its predictive efficacy in different countries and different ethnic groups. RELEVANCE TO CLINICAL PRACTICE: In clinical practice, nurses can use CAM-ICU to evaluate delirium in critically ill patients in ICU. However, it is necessary to debug the language and content according to the application population.

The prevalence of anxiety and depression in cardiac arrest survivors: A systematic review and meta-analysis.

OBJECTIVE: This systematic review aimed to identify the prevalence of anxiety and depression in cardiac arrest (CA) survivors. METHODS: A systematic review and network meta-analysis was performed on observational studies in adult cardiac arrest survivors with psychiatric disorders from PubMed, Embase, Cochrane Library and Web of Science. In the meta-analysis, we combined the prevalence quantitatively and analyzed the subgroup based on the classification indexes. RESULTS: We identified 32 articles that met the inclusion criteria. Regarding anxiety,the pooled prevalence was 24% (95% CI, 17-31%) and 22% (95% CI, 13-26%) in short-term and long-term respectively. The subgroup analysis showed that the pooled incidence in in-hospital cardiac arrest (IHCA) and out-of-hospital cardiac arrests (OHCA) survivors was 14.0% (95%CI, 9.0-20.0%) and 28.0% (95%CI, 20.0-36.0%) for short-term anxiety.The incidence of anxiety measured by, Hamilton Anxiety Rating Scale(HAM-A) and State-Trait Anxiety Inventory(STAI) was higher than other tools(P < 0.01). Regarding depression,the data analysis showed that the pooled incidence of short-term and long-term depression was 19% (95% CI, 13-26%) and 19% (95% CI, 16-25%), respectively. The subgroup analysis showed that the incidence of short-term and long-term depression was 8% (95% CI, 1-19%) and 30% (95% CI, 5-64%) for IHCA survivors, and was 18% (95% CI, 11-26%) and 17% (95% CI, 11-25%) for OHCA survivors. The incidence of depression measured by Hamilton Depression Rating Scale(HDRS) and Symptom check list-90(SCL-90) was higher than other assessment tools(P < 0.01). CONCLUSIONS: The meta-analysis indicated a high prevalence of anxiety and depression in CA survivors, and those symptoms persisted 1 year or more after CA. Evaluation tool is an important factor affecting the measurement results.

Single-cell transcriptomic analysis of normal and pathological tissues from the same patient uncovers colon cancer progression.

The aim of the present study was to elucidate the evolutionary trajectory of colon cells from normal colon mucosa, to adenoma, then to carcinoma in the same microenvironment. Normal colon, adenoma and carcinoma tissues from the same patient were analyzed by single-cell sequencing, which perfectly simulated the process of time-dependent colon cancer due to the same microenvironment. A total of 22 cell types were identified. Results suggest the presence of dominant clones of same cells including C2 goblet cell, epithelial cell subtype 1 (Epi1), enterocyte cell subset 0 (Entero0), and Entero5 in carcinoma. Epi1 and Entero0 were Co-enriched in antibacterial and IL-17 signaling, Entero5 was enriched in immune response and mucin-type O-glycan biosynthesis. We discovered new colon cancer related genes including AC007952.4, NEK8, CHRM3, ANO7, B3GNT6, NEURL1, ODC1 and KCNMA1. The function of TBC1D4, LTB, C2CD4A, AND GBP4/5 in T cells needs to be clarified. We used colon samples from the same person, which provide new information for colon cancer therapy.

Effects of telemedicine interventions on essential hypertension: a protocol for a systematic review and meta-analysis.

INTRODUCTION: Essential hypertension is a major preventable risk factor for early cardiovascular disease, premature death and disability. It has been reported that telemedicine interventions can provide an innovative solution to essential hypertension to overcome the barriers that exist in traditional treatment or control. Nevertheless, this subject has not been thoroughly investigated. The goal of this study is to systematically evaluate and describe the impact of telemedicine interventions on essential hypertension. METHODS AND ANALYSIS: To find relevant research, we will conduct a systematic literature search of three databases (PubMed, Embase and Cochrane Library), with no language limitations, in addition to researching grey literature. Two reviewers will extract the data individually, and any disagreements will be resolved by discussion or by a third reviewer. The randomised controlled trials will be chosen based on predetermined inclusion criteria. Primary outcomes will include systolic blood pressure and diastolic blood pressure after the telemedicine intervention. Secondary outcomes will include medication adherence (eg, the Morisky Medication Adherence Questionnaire), quality of life (eg, the MOS item scale of the Health Survey Short Form 36 questionnaire), blood pressure control rate and adverse events (eg, stroke, chronic renal failure, aortic dissection, myocardial infarction and heart failure). The quality of the included studies will be assessed using the Cochrane risk-of-bias method. The data will be analysed using RevMan V.5.3.5 software and STATA V.16.0 software. If heterogeneity testing reveals little or no statistical heterogeneity, a fixed effect model will be used for data synthesis; otherwise, a random effect model would be employed. We will synthesise the available evidence to perform a high-quality meta-analysis. ETHICS AND DISSEMINATION: This project does not require ethical approval because it will be conducted using publicly available documents. The review's findings will be published in peer-reviewed journals and publications. PROSPERO REGISTRATION NUMBER: CRD42021293539.

D-dimer, a predictor of bad outcome in gastric cancer patients undergoing radical resection.

As a marker of hypercoagulability, plasma D-dimer is associated with progression of many cancers but remains controversial in gastric cancer (GC). We aim to investigate the predictive value of D-dimer for postoperative outcomes after radical gastrectomy of GC patients. We enrolled 903 consecutive patients with GC who underwent radical gastrectomy and the clinicopathological characteristics were compared. Risk factors for overall survival (OS) and disease-free survival (DFS) were determined using multivariate cox regression analysis. We also compared the survival difference based on Kaplan-Meier method after a one-to-one propensity score matching (PSM). Patients with elevated D-dimer had older age (p < 0.001), advanced TNM stage (p < 0.001), larger tumor size (p = 0.005), lower 5-year OS rate (32.8% vs 62.6%, p < 0.001) and DFS (29% vs 59.6%, p < 0.001). In multivariate analysis, elevated D-dimer was independently associated with shorter OS [hazard ratio (HR): 1.633, 95% confidence interval (CI) 1.178-2.264, p = 0.003] and DFS (HR: 1.58, 95% CI 1.151-2.169, P = 0.005). After PSM, the 5-year OS rate of patients with elevated D-dimer was still significantly lower than matched group (32.8% vs 40.6%, p = 0.005), so was DFS (29% vs 36.6%, p = 0.008). Preoperative elevated D-dimer is an independent risk factor for GC patients undergoing curative gastrectomy.

Predictive value of neutrophil-to-lymphocyte ratio for distant metastasis in gastric cancer patients.

As a systemic inflammatory marker, the significance of NLR in predicting tumor prognosis and early lymph node metastasis is well known, including gastric cancer (GC). However, whether NLR can reflect GC metastasis status remains to be explored. We retrospectively enrolled 1667 GC patients treated in our hospital from December 2010 to December 2018. Patients were grouped according to the presence or absence of metastases. Receiver operating characteristics (ROC) curve analysis was used to evaluate the diagnostic efficacy of markers in assessing GC metastasis. Then we conducted a joint ROC curve analysis. The effects of clinicopathological parameters on GC metastasis were assessed using multiple logistic regression analysis. 743 (44.6%) patients were diagnosed with metastatic GC. Patients with GC metastases have younger age, higher CEA, CA19-9, CA72-4 and NLR. Based on the comparison of AUC, NLR has diagnostic efficacy comparable to that of GC markers. The AUC of NLR combined with GC markers had significantly higher predicting efficacy than that without combination for assessing peritoneal metastasis (P = 0.013), osseous metastasis (P = 0.017) and hepatic metastasis (P < 0.001). In multiple logistic regression analysis, age, NLR, CEA, CA19-9 and CA72-4 were found to be independently associated with GC metastasis (all P < 0.05). NLR was a risk factor of GC metastasis. Combining CEA, CA19-9, CA72-4 and NLR could better predict metastases in GC.

Effectiveness of managing suspected metastasis using plasma D-dimer testing in gastric cancer patients.

Tumor metastasis is closely related to the coagulation system. Tumor metastasis and hypercoagulability promote each other through multiple mechanisms. However, whether coagulation indicators can reflect tumor metastasis remains to be explored. Clinical characteristics of a total of 3447 patients from three tertiary referral centers were collected. Then the diagnostic efficacy of FDP, D-dimer and GC tumor markers [Carcinoembryonic antigen (CEA), Carbohydrate antigen 19-9 (CA19-9) and Carbohydrate antigen 72-4 (CA72-4)] for GC metastases was evaluated by the receiver operating characteristic curve (ROC) analyses. Then we conducted a joint ROC curve analysis. The effects of coagulation parameters and tumor markers on gastric cancer metastasis were assessed using multiple logistic regression analysis. 2049 patients were diagnosed with primary GC, 1398 patients with metastatic GC. Based on comparison of AUC, FDP (cutoff, 1.915) had significantly higher diagnostic efficacy than fibrinogen (P<0.001), CEA (P<0.001), CA199 (P<0.001) and CA724 (P<0.001). No significant difference was observed between D-dimer (cutoff, 0.905) and FDP (P=0.158). The AUC of tumor markers combined with coagulation indexes was higher than that without combination (P<0.001). In multiple logistic regression analysis, age, smoking, D-dimer, FDP, CEA, CA19-9, CA72-4 were found to be significantly associated with GC metastasis (all P<0.001, except for smoking P=0.004). We conclude that plasma FDP and D-dimer may be novel clinical biomarkers for screening metastases of GC.

Investigation on the Influencing Factors of Mental Health of Healthcare Workers for Aid in Hubei during the Outbreak of COVID-19.

BACKGROUND: This study aimed to determine the factors that were related to the psychological health status of healthcare workers aid for Hubei after the COVID-19 outbreak. METHODS: A total of 1260 participants completed the Self-Rating Scale of Sleep (SRSS), the Generalized Anxiety Scale (GAD-7), and the 9-item patient health questionnaire (PHQ-9) via the online questionnaires, and their related experiences with COVID-19 were collected. RESULTS: The average SRSS score of all participants (25.13 ± 6.41) indicated a mild sleep problem, and the factors that influenced their sleep were the respondent's gender, whether they had patients who died under their care, their history of psychosis and whether their family members were infected with COVID-19. The average GAD-7 score of all participants (12.37 ± 4.89) indicated a moderate anxiety level. The main factors that influenced anxiety were the respondent's gender, years of work, history of psychosis, self-perceived health status, and whether their family members were infected with COVID-19. The average PHQ-9 score of all participants (8.90 ± 5.42) indicated a mild depression level. The primary factors that influenced depression were whether the respondent had nursed/treated severely ill patients in Hubei and whether they had a history of psychosis. CONCLUSIONS: During the outbreak of COVID-19, the symptoms of anxiety were prominent among healthcare workers in Hubei. Moreover, male workers, those whose patients died during treatment, those with a history of anxiety disorders and those whose family members were infected with COVID-19 reported more serious problems. Therefore, this particular group of healthcare workers needs to be monitored and provided with tailored psychological support.

FOXI1 inhibits gastric cancer cell proliferation by activating miR-590/ATF3 axis via integrating ChIP-seq and RNA-seq data.

FOXI1 plays a key role in the development of gastric cancer. However, the whole genome FOXI1 binding sites and its target genes are unclear. In the present study, we used ChIP-seq and RNA-seq technologies to identify the target gene of FOXI1. Firstly, ChIP-seq data showed that, 4476 unique peaks in the genome region were captured. Most of these binding peaks are located in introns or intergenic regions. We annotated all the peaks to the nearest gene and identified 404 genes as FOXI1 binding genes. KEGG and GO analysis showed that FOXI1 binding gene to be correlated with the cellular process, cell part, cell, binding, single-organism process. Further, we performed FOXI1-overexpressed RNA-seq experiment. We comprehensively analyzed the ChIP-seq and RNA-seq data and take the intersection of two databases, several genes were identified. ATF3 was selected from the intersection since ATF3 was the most enriched mRNA after FOXI1 overexpressed. ChIP-qPCR and luciferase report gene were used to validate that ATF3 was target gene of FOXI1. Intriguely, ATF3 protein was significantly downregulated after FOXI1 overexpressed. We found FOXI1 can also bind to the promoter of miR-590 and active it which directly target ATF3. The binding site between FOXI1 and miR-590 was verified by ChIP-qPCR and luciferase report gene, and the target relationship between miR-590 and ATF3 was confirmed by dual-luciferase reporter gene. In conclusion, our data identified the genome binding sites of FOXI1, and provide evidence that FOXI1 inhibits gastric cancer cell proliferation by activating miR-590/ATF3 axis.

Obesity and metabolic syndrome related macrophage promotes PD-L1 expression in TNBC through IL6/JAK/STAT pathway and can be reversed by telmisartan.

Breast cancer is the most common malignant tumor in women. Its incidence is associated with obesity and metabolic syndrome (MetS), which are highly prevalent world widely and have been identified as poorer prognosis factors in breast cancer including triple-negative breast cancer (TNBC), which has poorer response to chemotherapy, radiotherapy, and endocrine therapy. Programmed death ligand 1 (PD-L1) is one of the immune checkpoints ligands that facilitates tumor escape and progress. Obesity/MetS could cause systemic inflammation and immune disorders, however, whether and how obesity/MetS affect PD-L1 expression in breast cancer had not been clarified. In the present study, we examined the PD-L1 expression profile in breast cancer either in online database or cell lines. We found higher PD-L1 mRNA level but not DNA copy number in breast cancer than normal breast tissue, and higher PD-L1 expression in TNBC than other subtypes. Moreover, we found a positive relationship between PD-L1 expression in TNBC and metabolic complications in patients. Next, obesity/MetS related M1 macrophage was found to promote the expression of PD-L1 in breast cancer cells cocultured with polarized macrophages derived from either monocyte-like cell line THP-1 or Wistar rat models. IL6/JAK/STAT pathway was further identified to be involved in the process. In addition, we discovered that the PD-L1 expression promoted by obesity/MetS could be restored by telmisartan, one of the angiotensin II receptor blockers (ARBs) and could affect macrophage polarization, through its selective peroxisome proliferator-activated receptor-gamma (PPARG) activation and NFKB p65 inhibition and therefore downregulates IL6 secretion from M1 macrophage.

Genomic Risk Predicts Molecular Imaging-detected Metastatic Nodal Disease in Prostate Cancer.

BACKGROUND: The Decipher genomic classifier (GC) is increasingly being used to determine metastasis risk in men with localized prostate cancer (PCa). Whether GCs predict for the presence of occult metastatic disease at presentation or subsequent metastatic progression is unknown. OBJECTIVE: To determine if GC scores predict extraprostatic 68Ga prostate-specific membrane antigen (68Ga-PSMA-11) positron emission tomography (PET) positivity at presentation. DESIGN, SETTING, AND PARTICIPANTS: Between December 2015 and September 2018, 91 PCa patients with both GC scores and pretreatment 68Ga-PSMA-11 PET scans were identified. Risk stratification was performed using the National Comprehensive Cancer Network (NCCN), Cancer of the Prostate Risk Assessment (CAPRA), and GC scores. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Logistic regression was used to identify factors correlated with PSMA-positive disease. RESULTS AND LIMITATIONS: The NCCN criteria identified 23 (25.3%) and 68 patients (74.7%) as intermediate and high risk, while CAPRA scores revealed 28 (30.8%) and 63 (69.2%) as low/intermediate and high risk, respectively. By contrast, only 45 patients (49.4%) had high-risk GC scores. PSMA-avid pelvic nodal involvement was identified in 27 patients (29.7%). Higher GC score was significantly associated with pelvic nodal involvement (odds ratio [OR] 1.38 per 0.1 units; p=0.009) and any PSMA-avid nodal involvement (pelvic or distant; OR 1.40 per 0.1 units; p=0.007). However, higher GC score was not significantly associated with PSMA-avid osseous metastases (OR 1.11 per 0.1 units; p=0.50). Limitations include selection bias for patients able to receive both tests and the sample size. CONCLUSIONS: Each 0.1-unit increase in GC score was associated with an approximate 40% increase in the odds of PSMA-avid lymph node involvement. These data suggest that patients with GC high risk might benefit from more nodal imaging and treatment intensification, potentially via pelvic nodal dissection, pelvic nodal irradiation, and/or the addition of chemohormonal agents. PATIENT SUMMARY: Patients with higher genomic classifier scores were found to have more metastatic lymph node involvement on prostate-specific membrane antigen imaging.

Temperature-insensitive sum frequency generation of 355-nm ultraviolet laser radiation in LiB3O5 by compensating thermally induced phase mismatch.

A temperature-insensitive sum frequency generation method based on thermally induced phase mismatch compensation is proposed to enhance the thermal stability and scale up the output power of ultraviolet (UV) lasers. In the method, three LiB3O5 crystals are cascaded for sum frequency generation of a 355-nm UV laser, and the two crystals at the ends are employed for frequency conversion; the middle one, which is not required to be phase matched and has an opposite sign of first temperature derivative of phase mismatch, compensates the thermally induced phase mismatch generated in the first crystal. The temperature acceptance bandwidth of frequency conversion in the three cascaded crystals is about double that in a single long crystal with the same interaction length.

Different lymph node staging systems for patients with adenocarcinoma of esophagogastric junction.

OBJECTIVE: In addition to the traditional TNM N staging system, lymph node ratio (LNR) and log odds of metastatic lymph nodes (LODDS) staging methods were developed in cancers. This study aimed to examine their relative prognostic performance in patients with adenocarcinoma of the esophagogastric junction (AEG). PATIENTS AND METHODS: Patients who underwent surgical resection for AEG were identified from the Surveillance, Epidemiology, and End Results (SEER) Program and the First Affiliated Hospital of Xi'an Jiaotong University as the training and validation sets, respectively. The Akaike's Information Criterion (AIC), Harrell's C statistic, and ROC curves were utilized for comparison. RESULTS: A total of 735 patients were involved in the training set. LODDS and LNR staging systems had better prognostic performance than the TNM N staging systems (when considered as a categorical variable: C index = 0.728 and 0.712 vs 0.671; AIC: 6247.537 and 6265.996 vs 6320.045; AUC: 0.762 and 0.719 vs 0.692. For the continuous model: C index = 0.675 and 0.686 vs 0.658; AIC = 6243.740 and 6261.027 vs 6355.077; AUC = 0.778 and 0.733 vs 0.693). In the validation set of 183 patients, the TNM N staging scheme outperformed the LODDS and LNR staging systems (C index = 0.788 vs 0.779 and 0.767; AIC = 1014.702 vs 1026.899 and 1025.288; AUC = 0.806 vs 0.787 and 0.791) when considered a categorical variable. However, when considered a continuous variable, the LODDS and LNR staging systems were better than the TNM N staging system (C index = 0.724 and 0.733 vs 0.747; AIC = 1018.075 and 1025.803 vs 1026.085; AUC = 0.811 and 0.810 vs 0.806). CONCLUSIONS: The LNR and LODDS staging schemes could be considered new options for prognostic prediction of AEG with respect to lymph node status, especially when considered as continuous variables.

5'-Triphosphate siRNA targeting MDR1 reverses multi-drug resistance and activates RIG-I-induced immune-stimulatory and apoptotic effects against human myeloid leukaemia cells.

Multi-drug resistance (MDR), immune suppression and decreased apoptosis are important causes of therapy-failure in leukaemia. Short interfering RNAs (siRNAs) down-regulate gene transcription, have sequence-independent immune-stimulatory effects and synergize with other anti-cancer therapies in some experimental models. We designed a siRNA targeting MDR1 with 5'-triphosphate ends (3p-siRNA-MDR1). Treatment of leukaemia cells with 3p-siRNA-MDR1 down-regulated MDR1 expression, reduced-drug resistance and induced immune and pro-apoptotic effects in drug-resistant HL-60/Adr and K562/Adr human leukaemia cell lines. We show mechanisms-of-action of these effects involve alterations in the anti-viral cytosolic retinoic acid-inducible protein-I (RIG-I; encoded by RIG-I or DDX58) mediated type-I interferon signal induction, interferon-gamma-inducible protein 10 (IP-10; encoded by IP10 or CXCL10) secretion, major histocompatibility complex-I expression (MHC-I) and caspase-mediated cell apoptosis. 3p-siRNA-MDR1 transfection also enhanced the anti-leukaemia efficacy of doxorubicin. These data suggest a possible synergistic role for 3p-siRNA-MDR1 in anti-leukaemia therapy.

D-dimer is an essential accompaniment of circulating tumor cells in gastric cancer.

BACKGROUND: Fibrinogen (FIB) is an important source of fibrin, which plays a crucial role in circulating tumor cells (CTCs) extravasation and distant metastasis development. We hypothesize it's stable final product, plasma D-dimer, may be associated with CTCs appearance and can reflect the metastatic phenotype in cancer patients. METHODS: We first verified our hypothesis in different murine gastric cancer metastasis models in vivo, plasma D-dimer and fibrinogen as well as its degradation products were directly examined in three metastasis immune-deficient mouse models and in controls. Next, we gathered and analyzed the result of plasma D-dimer levels and CTCs numbers in 41 advanced primary gastric cancer (GC) patients. A follow-up study was conducted in these patients. RESULTS: In three in vivo murine metastasis models, plasma D-dimer levels were extremely elevated in a hematogenous and intraperitoneal murine model of metastasis compared with a subcutaneous tumor model and the control group, supporting our previous hypothesis. While in 41 GC patients, the result displayed that plasma D-dimer levels were remarkably increased in patients with distant metastases, especially in visceral metastases patients. Additionally, linear association was shown between D-dimer level and CTCs numbers (R 2 = 0.688, p < 0.001), additionally, plasma D-dimer represent a better survival predictor than CTCs. CONCLUSIONS: Plasma D-dimer is an essential accompaniment of CTCs in GC that is easy to measure and lower in cost, and can be used in the detection of hematogenous metastasis.

p38 predicts depression and poor outcome in esophageal cancer.

p38 mitogen-activated protein kinase (MAPK) signaling has been implicated in the cancer development and progression. However, the precise mechanism of this association remains unknown. The aim of the present study was to evaluate the association between p38 and cancer progression, including investigations into the effects on cell proliferation, resistance to thalidomide, indoleamine 2,3-dioxygenase (IDO) expression and prognosis in patients with esophageal cancer. The present retrospective study included patients with stage I-III esophageal cancer. A total of 228 patients with esophageal cancer were recruited to analyze the expression of phosphorylated (p)-p38 and IDO in tumor, and normal tissues through immunohistochemistry. Depression status was measured using the Zung Self-Rating Depression Scale. P38 cDNA was transfected into esophageal cancer cells to assess tumor cell viability, sensitivity to thalidomide treatment and IDO gene expression. Western blotting and flow cytometry was used to analyze protein expression alterations, and apoptosis in esophageal cancer cells. P-p38 protein was expressed in 68.9% of cancer tissues, and was significantly associated with depressive symptoms, tumor recurrence and poor survival of patients. In vitro experiments revealed that the expression of p-p38 induced esophageal cancer Eca-109 and TE-1 cell viability, and resistance to thalidomide treatment, as well as in the expression of IDO without the application of lipopolysaccharides. Further follow-up of patients revealed that depression was also an independent factor for early recurrence and overall survival rate. Altered p38 MAPK expression was associated with poor outcome in patients with esophageal cancer. p38 may be a potential biomarker for the prediction of depressive symptoms and prognosis in patients with esophageal cancer.

The Management and Prognostic Prediction of Adenocarcinoma of Appendix.

Malignant tumours of the appendix are quite rare, especially appendiceal adenocarcinomas, which may be difficult to detect preoperatively or intraoperatively. We collected data for 1404 patients with adenocarcinoma of the appendix from the Surveillance, Epidemiology, and End Results Program (SEER) database to explore the potential associations between clinicopathological factors and overall survival. Furthermore, a novel nomogram for predicting prognosis was developed based on our analysis of the SEER data. The nomogram prediction model included seven prognostic factors derived based on different clinical estimates. When compared with the traditional tumour-node-metastasis (TNM) staging system, the nomogram prediction model showed superior discriminatory power (Harrell's C-index, 0.741 vs. 0.686) and a greater degree of similarity to actual 5-year overall survival after calibration (Akaike Information Criterion index, 5270.781 vs. 5430.141). Finally, we provide recommendations for the management of patients with adenocarcinoma of the appendix. Notably, we found the depth of adenocarcinoma invasion may be used as an indicator to determine the optimal surgical approach. For mucinous adenocarcinomas of the appendix, because these tumours are characterized by unique biological behaviour, intraoperative hyperthermic intraperitoneal chemotherapy (HIPEC) is recommended. However, whether systematic chemotherapy should be administered to patients with adenocarcinoma of the appendix requires further investigation.

Relationships between p14ARF Gene Methylation and Clinicopathological Features of Colorectal Cancer: A Meta-Analysis.

We conducted a meta-analysis to explore the relationships between p14ARF gene methylation and clinicopathological features of colorectal cancer (CRC). Databases, including Pubmed, Embase and Cochrane Library, were searched and, finally, a total of 18 eligible researches encompassing 1988 CRC patients were selected. Combined odds ratios (ORs) with 95% confidence intervals (95% CIs) were evaluated under a fixed effects model for absence of heterogeneity. Significant associations were observed between p14ARF gene methylation and tumor location (OR = 2.35, 95% CI: 1.55-3.55, P = 0.001), microsatellite instability (MSI) status (OR = 3.28, 95% CI: 2.12-5.07, P<0.0001). However, there were no significant associations between p14ARF gene methylation and tumor stage, tumor differentiation. We concluded that p14ARF gene methylation may be significantly associated with tumor location, and MSI status of CRC.