Plasma Deoxycholic Acid Levels are Associated with Hemodynamic and Clinical Outcomes in Acute Pulmonary Embolism Patients.

This study aimed to evaluate the correlation of plasma deoxycholic acid (DCA) levels with clinical and hemodynamic parameters in acute pulmonary embolism (APE) patients. Total 149 APE adult patients were prospectively recruited. Plasma DCA levels were measured using rapid resolution liquid chromatography-quadrupole time-of-flight mass spectrometry. Baseline clinical and hemodynamic parameters were evaluated according to plasma DCA levels. The plasma DCA levels were significantly lower in APE patients than in those without APE (P < 0.001). APE patients with adverse events had lower plasma DCA levels (P < 0.001). Low DCA group patients presented more adverse cardiac function, higher NT-proBNP levels (P = 0.010), and higher WHO functional class levels (P = 0.023). Low DCA group also presented with an adverse hemodynamic status, with higher pulmonary vascular resistance levels (P = 0.027) and lower cardiac index levels (P = 0.024). Both cardiac function and hemodynamic parameters correlated well with plasma DCA levels. Kaplan-Meier survival analysis demonstrated that APE patients with lower plasma DCA levels had a significantly higher event rate (P = 0.009). In the univariate and multivariate Cox regression analyses, the plasma DCA level was an independent predictor of clinical worsening events after adjusting for age, sex, WHO functional class, NT-proBNP level, pulmonary vascular resistance, and cardiac index (HR 0.370, 95% CI 0.161, 0.852; P = 0.019). Low plasma DCA levels predicted adverse cardiac function and hemodynamic collapse. A low DCA level was correlated with a higher clinical worsening event rate and could be an independent predictor of clinical outcomes in multivariate analysis.

[Effective constituents of essential oil from Gleditsiae Fructus Abnormalis and anti-cerebral ischemia/reperfusion injury mechanism: based on GC-MS, network pharmacology, and experimental verification].

Based on GC-MS and network pharmacology, the active constituents, potential targets, and mechanism of essential oil from Gleditsiae Fructus Abnormalis(EOGFA) against cerebral ischemia/reperfusion(I/R) injury were explored, and the effective constituents were verified by experiment. To be specific, GC-MS was used identify the constituents of the volatile oil. Secondly, the targets of the constituents and disease were predicted by network pharmacology, and the drug-constituent-target network was constructed, followed by Gene Ontology(GO) term enrichment and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment of the core targets. Molecular docking was performed to investigate the binding affinity between the active constituents and the targets. Finally, SD rats were used for experimental verification. The I/R injury model was established, and the neurological behavior score, infarct volume, and pathological morphology of brain tissue were measured in each group. The content of interleukin-1ß(IL-1ß), interleukin-6(IL-6), and tumor necrosis factor-alpha(TNF-α) was determined by enzyme-linked immunosorbent assay(ELISA), and the protein expression of vascular endothelial growth factor(VEGF) by Western blot. A total of 22 active constituents and 17 core targets were screened out. The core targets were involved in 56 GO terms and the major KEGG pathways of TNF signaling pathway, VEGF signaling pathway, and sphingolipid signaling pathway. Molecular docking showed that the active constituents had high affinity to the targets. The results of animal experiment suggested that EOGFA can alleviate the neurological impairment, decrease the cerebral infarct volume and the content of IL-1ß, IL-6 and TNF-α, and down-regulate the expression of VEGF. The experiment verified the part results of network pharmacology. This study reflects the multi-component, multi-target, and multi-pathway characteristics of EOGFA. The mechanism of its active constituents is related to TNF and VEGF pathways, which provides a new direction for in-depth research on and secondary development of Gleditsiae Fructus Abnormalis.

The prognostic analysis of clinical breast cancer subtypes among patients with liver metastases from breast cancer.

BACKGROUND: To determine whether the inferior outcome noted with triple-negative breast cancer (TNBC) reflects a higher risk population among patients with breast cancer liver metastases. METHODS: A total of 123 patients with breast cancer liver metastases diagnosed at Tianjin Medical University Cancer Hospital were included in this study. Breast cancer subtype was assigned using immunohistochemistry or fluorescence in situ hybridization: hormone receptor (HR) positive (+)/human epidermal growth factor receptor 2 (HER2) negative (-), HR+/HER2+, HR-/HER2+ and triple-negative subtype. Clinical features and survival were evaluated in different subtypes. RESULTS: The median age at breast cancer diagnosis was 47 years (range, 23-67 years). Breast cancer subtype was confirmed in all patients (39.8% with HR+/HER2-, 24.4% with HR+/HER2+, 15.3% with HR-/HER2+ and 20.3% with TNBC). The median overall survival after liver metastases was 29 months (range, 4-89 months), and the overall 1-, 2- and 3-year survival rate was 68.3, 48.0 and 34.1%, respectively. Survival was found to be impacted by breast cancer subtype (P = 0.001), and was shortest for patients with TNBC. Time to liver metastases (TTLM) less than 24 months and liver metastasis lesions ≥3 were found to be important predictors of poor survival after liver metastases (P = 0.009 and 0.001, respectively). CONCLUSIONS: The results indicate that clinical breast cancer subtype remains an independent prognostic predictor among patients with breast cancer liver metastases. Liver metastases arising from TNBC confers the worst prognosis, and novel agents capable of controlling intrahepatic and extrahepatic TNBC are needed.

Comparison of surgical outcomes in patients with colorectal liver metastases versus non-colorectal liver metastases: A Chinese experience.

AIM: To compare the surgical treatment outcomes between patients with colorectal liver metastases (CLM) and non-colorectal liver metastases (NCLM). METHODS: The study population consisted of 132 patients undergoing hepatectomy at Tianjin Medical University Cancer Hospital between January 1996 and December 2008. Survival analyses were used to assess the differences in prognosis and survival between groups. RESULTS: The primary tumor site was colorectal in 60 (45.5%), breast in 16 (12.1%), lung in 14 (10.6%), non-colorectal gastrointestinal in 12 (9.1%), genitourinary in 10 (7.6%), pancreatobiliary tumor (n = 8, 6.1%) and others in 12 (9.1%). A curative liver resection was performed in all patients by pathological findings. After a median follow-up of 32 months, the overall 3- and 5-year survival rate was 44.7 and 29.5% in all patients, respectively. The 3- and 5-year survival rates were 53.3 and 36.7% for liver metastases from colorectal tumors, 62.5 and 43.8% from breast, 60.0 and 40.0% from genitourinary neoplasm, 41.7 and 25.0% from non-colorectal gastrointestinal cancer, 28.5 and 15.0% from lung, 12.5 and 0% from pancreatobiliary malignancies, and 41.7 and 8.3% from other sites, respectively. CONCLUSIONS: Hepatic resection is an effective and safe treatment for liver metastases mainly depending on primary tumor sites. Hepatic metastases from non-colorectal gastrointestinal cancer, pulmonary and pancreatobiliary malignancies have the worst prognosis; those from breast and genitourinary neoplasm show the best prognosis.

Treatment outcome of patients with liver-only metastases from breast cancer after mastectomy: a retrospective analysis.

PURPOSE: To evaluate the efficiency of combined treatment of transcatheter arterial chemoembolization (TACE) and systemic chemotherapy (SC) for liver-only metastases from breast cancer after mastectomy. METHODS: We compared the outcomes of 44 patients who underwent combined treatment of TACE and systemic chemotherapy (TSC) with those of 43 patients who underwent systemic chemotherapy (SC). RESULTS: The median follow-up from the diagnosis of liver metastases was 29 months (range, 0-89 months). Response rates were 59.1% and 34.9% for TSC group and SC group (P < 0.05), respectively. The 1-, 2- and 3-year survival rates for TSC group were 76.2, 66.7 and 47.6%, and those for SC group were 48.1, 29.6 and 7.4% (P = 0.027), respectively. Estrogen receptor (ER)-negative status of primary tumor, disease-free interval from mastectomy to liver metastases (DFI) less than 24 months and patients who received systemic chemotherapy only were independently associated with poor prognosis (P = 0.009; P = 0.023; P = 0.030). CONCLUSIONS: The combined treatment of TACE and systemic chemotherapy may prolong survival for liver metastases in breast cancer after mastectomy.