Ticagrelor versus Clopidogrel in the Dual Antiplatelet Regimen for Unruptured Intracranial Aneurysm Treated with Stent-Assisted Coil Embolization: A Single-Center Cohort Study.

BACKGROUND: Dual antiplatelet therapy (DAPT) of aspirin plus clopidogrel is commonly used in patients with unruptured intracranial aneurysms treated with stent-assisted coil (SAC) embolization. However, the unpredictable clopidogrel efficacy of the 5%-55% nonresponders limits its use. Ticagrelor, as a potential alternative of clopidogrel, is an antiplatelet agent with low resistance rates but uncertain efficacy and safety in these patients. METHODS: A single-center cohort study was performed to compare the efficacy and safety of ticagrelor with clopidogrel in the DAPT regimen in patients with unruptured intracranial aneurysms and treated with SAC. The patients with clopidogrel resistance identified as inadequate adenosine diphosphate inhibition rate determined by thromboelastography were treated with ticagrelor instead, and both drugs achieved adequate suppression of platelet aggregation when stents were implanted. The occurrence of major adverse cardiovascular and cerebrovascular events (MACCE) and bleeding events was recorded through 6 months follow-up. RESULTS: Data from 86 patients with 99 unruptured intracranial aneurysms and treated by SAC with clopidogrel were compared with those from 108 patients with 111 aneurysms and treated with ticagrelor. Neither the baseline characteristics nor the incidence of the MACCE or bleeding events differed between the groups. Ticagrelor exerted significantly higher adenosine diphosphate inhibition rate than that of the clopidogrel. Multivariable logistic regression analysis showed that the incidence of MACCE was related to hematocrit and fibrinogen levels. CONCLUSIONS: Ticagrelor seemed to be as effective and safe as clopidogrel for SAC in unruptured intracranial aneurysms. Hematocrit and fibrinogen levels were independent risk factors for the incidence of MACCE.

Clinical Course and Outcome Patterns of Acute-on-chronic Liver Failure: A Multicenter Retrospective Cohort Study.

BACKGROUND AND AIMS: Acute-on-chronic liver failure (ACLF) is acute decompensation of liver function in the setting of chronic liver disease, and characterized by high short-term mortality. In this study, we sought to investigate the clinical course of patients at specific time points, and to propose dynamic prognostic criteria. METHODS: We assessed the clinical course of 453 patients with ACLF during a 12-week follow-up period in this retrospective multicenter study. The clinical course of patients was defined as disease recovery, improvement, worsening or steady patterns based on the variation tendency in prothrombin activity (PTA) and total bilirubin (TB) at different time points. RESULTS: Resolution of PTA was observed in 231 patients (51%) at 12 weeks after the diagnosis of ACLF. Among the remaining patients, 66 (14.6%) showed improvement and 156 (34.4%) showed a steady or worsening course. In patients with resolved PTA, the clinical course of TB exhibited resolved pattern in 95.2%, improved in 3.9%, and steady or worse in 0.8%. Correspondingly, in patients with improved PTA, these values for TB were 28.8%, 27.3%, and 43.9%, respectively. In patients with steady or worsening PTA, these values for TB were 5.7%, 32.3%, and 65.6%, respectively. Dynamic prognostic criteria were developed by combining the clinical course of PTA/TB and the clinical outcomes at 4 and 12 weeks after diagnosis in ACLF patients. CONCLUSIONS: We propose the following dynamic prognostic criteria: rapid progression, slow progression, rapid recovery, slow recovery, and slow persistence, which lay the foundation for precise prediction of prognosis and the improvement of ACLF therapy.

Lactobacillus plantarum surface-displayed influenza antigens (NP-M2) with FliC flagellin stimulate generally protective immune responses against H9N2 influenza subtypes in chickens.

The H9N2 avian influenza virus (AIV) causes serious economic losses to the poultry industry every year. Vaccines that induce a mucosal immune response may be successful against influenza virus infection because its transmission occurs primarily in the mucosa. To develop novel and potent oral vaccines based on Lactobacillus plantarum (L. plantarum) to control the spread of AIV in poultry industry, in the present study, we constructed and expressed fusions of the influenza antigens NP and M2 with the Salmonella Typhimurium flagellinprotein FliC on the surface of L. plantarum. Oral immunization of chicks was performed, and serum antibodies, mucosal antibodies, and specific cellular immunity were detected. Immunizing chicks with avian influenza virus was evaluated. The results showed high levels of IgG in addition to high levels of secretory immunoglobulin A (sIgA) in chickens orally administered recombinant L. plantarum. In addition, the fusion may significantly increase the levels of NP- and M2-specific T cell-mediated immunity in the case of mucosal administration of NC8-pSIP409-pgsA'-NP-M2-FliC. Recombinant NC8-pSIP409-pgsA'-NP-M2-FliC mediated effectively protected chickens against influenza virus and reduced virus titers in the lung. Our study outcomes indicate that the expression of influenza NP-M2 and a mucosal adjuvant (FliC), by L. plantarum could generate a mucosal vaccine candidate for animals in the future to defend against AIVs.

Tuning the properties of atomically precise gold nanoclusters for biolabeling and drug delivery.

A structure-determined gold-levonorgestrel nanocluster, Au10(C21H27O2)10 (Au10NC), has been obtained via solvent induced crystal transformation from Au8(C21H27O2)8 (Au8NC), accompanied by a fluorescence color change from green to yellow. A cationic polymer, poly(allylamine hydrochloride) (PAH), was chosen to assemble with Au10NC to prepare monodisperse and stable particles (Au10NC-PAH) with an increased quantum yield of 49.8%. The as-fabricated Au10NC-PAH realized effective antibody-mediated actin imaging and sustained drug release.

Relationship between high dietary fat intake and Parkinson's disease risk: a meta-analysis.

OBJECTIVE: To assess whether dietary fat intake influences Parkinson's disease risk. DATA SOURCES: We systematically surveyed the Embase and PubMed databases, reviewing manuscripts published prior to October 2018. The following terms were used: ("Paralysis agitans" OR "Parkinson disease" OR "Parkinson" OR "Parkinson's" OR "Parkinson's disease") AND ("fat" OR "dietary fat" OR "dietary fat intake"). DATA SELECTION: Included studies were those with both dietary fat intake and Parkinson's disease risk as exposure factors. The Newcastle-Ottawa Scale was adapted to investigate the quality of included studies. Stata V12.0 software was used for statistical analysis. OUTCOME MEASURES: The primary outcomes included the relationship between high total energy intake, high total fat intake, and Parkinson's disease risk. The secondary outcomes included the relationship between different kinds of fatty acids and Parkinson's disease risk. RESULTS: Nine articles met the inclusion criteria and were incorporated into this meta-analysis. Four studies scored 7 and the other five studies scored 9 on the Newcastle-Ottawa Scale, meaning that all studies were of high quality. Meta-analysis results showed that high total energy intake was associated with an increased risk of Parkinson's disease (P = 0.000, odds ratio (OR) = 1.49, 95% confidence interval (CI): 1.26-1.75); in contrast, high total fat intake was not associated with Parkinson's disease risk (P = 0.123, OR = 1.07, 95% CI: 0.91-1.25). Subgroup analysis revealed that polyunsaturated fatty acid intake (P = 0.010, OR = 1.03, 95% CI: 0.88-1.20) reduced the risk of Parkinson's disease, while arachidonic acid (P = 0.026, OR = 1.15, 95% CI: 0.97-1.37) and cholesterol (P = 0.002, OR = 1.09, 95% CI: 0.92-1.29) both increased the risk of Parkinson's disease. Subgroup analysis also demonstrated that, although the results were not significant, consumption of n-3 polyunsaturated fatty acids (P = 0.071, OR = 0.88, 95% CI: 0.73-1.05), α-linolenic acid (P = 0.06, OR = 0.86, 95% CI: 0.72-1.02), and the n-3 to n-6 ratio (P = 0.458, OR = 0.89, 95% CI: 0.75-1.06) were all linked with a trend toward reduced Parkinson's disease risk. Monounsaturated fatty acid (P = 0.450, OR = 1.06, 95% CI: 0.91-1.23), n-6 polyunsaturated fatty acids (P = 0.100, OR = 1.15, 95% CI: 0.96-1.36) and linoleic acid (P = 0.053, OR = 1.11, 95% CI: 0.94-1.32) intakes were associated with a non-significant trend toward higher PD risk. Saturated fatty acid (P = 0.619, OR = 1.01, 95% CI: 0.87-1.18) intake was not associated with Parkinson's disease. CONCLUSION: Dietary fat intake affects Parkinson's disease risk, although this depends on the fatty acid subtype. Higher intake of polyunsaturated fatty acids may reduce the risk of Parkinson's disease, while higher cholesterol and arachidonic acid intakes may elevate Parkinson's disease risk. However, further studies and evidence are needed to validate any link between dietary fat intake and Parkinson's disease.

MnO2@Corncob Carbon Composite Electrode and All-Solid-State Supercapacitor with Improved Electrochemical Performance.

Two corncob-derived carbon electrode materials mainly composed of micropores (activated carbon, AC) and mesopores/macropores (corncob carbon, CC) were prepared and studied after the anodic electrodeposition of MnO2. The capacity of the MnO2/activated carbon composite (MnO2@AC) electrode did not noticeably increase after MnO2 electrodeposition, while that of the MnO2/corncob carbon composite (MnO2@CC) electrode increased up to 9 times reaching 4475 mF cm-2. An asymmetric all-solid-state supercapacitor (ASC) was fabricated using AC as the anode, MnO2@CC as the cathode, and polyvinyl alcohol (PVA)/LiCl gel as the electrolyte. An ultrahigh specific capacitance of 3455.6 mF cm-2 at 1 mA cm-2, a maximum energy density of 1.56 mW h cm-2, and a long lifetime of 10,000 cycles can be achieved. This work provides insights in understanding the function of MnO2 in biomass-derived electrode materials, and a green path to prepare an ASC from waste biomass with excellent electrochemical performance.

Prediction of occult lymph node metastasis using SUV, volumetric parameters and intratumoral heterogeneity of the primary tumor in T1-2N0M0 lung cancer patients staged by PET/CT.

OBJECTIVE: The aim of this study was to identify whether PET/CT-related metabolic parameters of the primary tumor could predict occult lymph node metastasis (OLM) in patients with T1-2N0M0 NSCLC staged by 18F-FDG PET/CT. METHODS: 215 patients with clinical T1-2N0M0 (cT1-2N0M0) NSCLC who underwent both preoperative FDG PET/CT and surgical resection with the systematic lymph node dissection were included in the retrospective study. Heterogeneity factor (HF) was obtained by finding the derivative of the volume-threshold function from 40 to 80% of the maximum standardized uptake value (SUVmax). Univariate and multivariate stepwise logistic regression analyses were used to identify these PET parameters and clinicopathological variables associated with OLM. RESULTS: Statistically significant differences were detected in sex, tumor site, SUVmax, mean SUV (SUVmean), metabolic tumor volume (MTV), total lesion glycolysis and HF between patients with adenocarcinoma (ADC) and squamous cell carcinoma (SQCC). OLM was detected in 36 (16.7%) of 215 patients (ADC, 27/152 = 17.8% vs. SQCC, 9/63 = 14.3%). In multivariate analysis, MTV (OR = 1.671, P = 0.044) in ADC and HF (OR = 8.799, P = 0.023) in SQCC were potent associated factors for the prediction of OLM. The optimal cutoff values of 5.12 cm3 for MTV in ADC, and 0.198 for HF in SQCC were determined using receiver operating characteristic curve analysis. CONCLUSIONS: In conclusion, MTV was an independent predictor of OLM in cT1-2N0M0 ADC patients, while HF might be the most powerful predictor for OLM in SQCC. These findings would be helpful in selecting patients who might be considered as candidates for sublobar resection or new stereotactic ablative radiotherapy.

Aneurysmal Subarachnoid Hemorrhage Onset Alters Pyruvate Metabolism in Poor-Grade Patients and Clinical Outcome Depends on More: A Cerebrospinal Fluid Metabolomic Study.

Cerebral metabolism alterations influence cerebrospinal fluid (CSF) composition and are sensitive to brain injury. In subarachnoid hemorrhage (SAH) patients, Fisher scale, Hunt-Hess scale, and World Federation of Neurological Societies (WFNS) grading scale evaluating SAH severity are inadequate to predict long-term outcome; therefore, in an effort to determine metabolite pattern disparity and discover corresponding biomarkers, we designed an untargeted CSF metabolomic study covering a broad range of metabolites of SAH patients with different severity and outcome. The present study demonstrated the SAH altered the cerebrospinal fluid metabolome involving carbohydrate, lipid, and amino acid metabolism. Pyruvate metabolism was enhanced in SAH patients with Hunt-Hess scale above III, and the CSF pyruvate level was significantly associated with WFNS grading scale above III. There is no significant variation among CSF metabolome in SAH patients with merely different amounts and distribution of bleeding. SAH patients with unfavorable outcome present upregulated CSF amino acids level and enhanced lipid biosynthesis. The present study provides a novel possibility of early identification of patients who might possess unfavorable outcome and further clarification of the underlying pathophysiology.

Prediction of Occult Lymph Node Metastasis Using Tumor-to-Blood Standardized Uptake Ratio and Metabolic Parameters in Clinical N0 Lung Adenocarcinoma.

PURPOSE: We aimed to investigate whether the tumor-to-blood SUV ratio (SUR) and metabolic parameters of F-FDG uptake could predict occult lymph node metastasis (OLM) in clinically node-negative (cN0) lung adenocarcinoma. MATERIALS AND METHODS: We retrospectively reviewed 157 patients with cN0 lung adenocarcinoma who underwent both preoperative F-FDG PET/CT and surgical resection with the systematic lymph node dissection. The SUVmax, SUVmean, MTV, and total lesion glycolysis (TLG) of the primary tumor was measured on the PET/CT workstation. SURmax, SURmean, and TLGsur were derived from each of them divided by descending aorta SUVmean. These PET parameters and clinicopathological variables were analyzed for OLM. RESULTS: In our study, OLM was detected in 31 (19.7%) of 157 patients. Significantly higher values of tumor size, SUVmax, SUVmean, MTV, TLGsuv, SURmax, SURmean, and TLGsur were found in patients with OLM. In receiver operating characteristic curve analysis, the optimal cutoff values of the above parameters were 29.50, 4.38, 2.45, 6.37, 44.13, 5.30, 1.86, and 28.24, respectively. The multivariate analysis showed that TLGsur (odds ratio, 1.024; P = 0.002) was the most potent associated factor for the prediction of OLM in cN0 lung adenocarcinoma. CONCLUSIONS: TLGsur showed the most powerful predictive performance than the other PET parameters for the prediction of OLM in cN0 lung adenocarcinoma. This normalized volumetric parameter would be helpful in selection of sublobar resection or aggressive tailored treatments in patients with cN0 lung adenocarcinoma.

Regulation of iron metabolism by hypoxia-inducible factors.

Hypoxia-inducible factors (HIFs) are central mediators of cellular adaption to hypoxia. The heterodimeric HIF transcription factors consist of HIF-α and HIF-ß, that form functional HIFs. Mammals contain HIF-1α, HIF-2α, and HIF-3α. HIFs play a key role in iron metabolism by regulating the expression of iron-related proteins, such as divalent metal transporter 1 (DMT1), ferroportin 1 (FPN1), duodenal cytochrome b (Dcytb), and transferrin receptor (TfR). Hepcidin and iron regulatory proteins (IRPs), the central mediators for systematic and intracellular iron homeostasis, are also regulated by HIFs. In this review, we summarized the regulatory effects of HIFs on iron-related proteins, thus providing insights into the control of HIFs as therapeutic strategies for some iron related disorders.

Effect of estrogen on iron metabolism in mammals.

Estrogen is a steroid hormone produced mainly by the ovaries. It combines with the nuclear receptors to exert the biological effects influencing the metabolism of body. Elevated levels of estrogen are often associated with altered iron levels in mammals. Furthermore, the findings of estrogen response element (ERE) have demonstrated that estrogen affects iron metabolism directly in peripheral tissues. In this review, we will briefly summarize the effect of estrogen on iron metabolism in mammals, and discuss recent progress in the mechanisms of estrogen on some iron related proteins in order to provide guidance for clinical use of estrogen. Estrogen and iron metabolism are closely related, but the exact regulatory mechanisms still need further exploration.

[Umbilicus metastasis in patients with epithelial ovarian cancer : clinical features of 21 patients].

OBJECTIVE: To analyze the clinical features, treatments and prognosis of patients with Sister Mary Joseph's nodule of umbilicus (SMJN) from epithelial ovarian cancer (EOC) patients. METHODS: Among a total of 2642 pathologically diagnosed EOC cases, 21 cases with SMJN were histopathologically diagnosed and had an age range of 40-66 years at Sun Yat-sen University Cancer Center between January 1991 and January 2011. Their clinical data were retrospectively analyzed. RESULTS: The incidence of SMJN in EOC was 0.79 %. The 1, 2 and 5-year survival rates were 61.8%, 26.8% and 9.5% respectively. The diagnosis was confirmed via local excision biopsy, fine-needle aspiration biopsy or gross pathological diagnosis. Univariate analysis showed that patients with progressive disease or relapsing with umbilical metastasis after treatment had worse prognosis than those diagnosed at pre-treatment (22 vs 6 months, P < 0.01) . Patients with suboptimal cytoreductive surgery and/or less than 6 circles of chemotherapy or palliative treatment had worse prognosis than those with optional cytoreductive surgery during 6-8 circles of chemotherapy (21 vs. 4 months). Multivariate analysis showed that the time to diagnose and treatment regimen were independent predictors of survival (relative risk = 41.28, P < 0.01). CONCLUSIONS: SMJN is a rare manifestation of EOC. Improving the diagnostic vigilance, optimal debulking surgery plus regular chemotherapy and other new individualized postoperative treatments may arrest the progression of EOC and prolong patient survival.

Expression of c-Src and phospho-Src in epithelial ovarian carcinoma.

Abnormal c-Src expression and activation has been observed in a number of tumors. To determine the therapeutic potential of Src inhibitors for ovarian cancer patients, this study aimed to explore the expression patterns of c-Src and phospho-Src in epithelial ovarian cancer. A total of 82 patients with epithelial ovarian cancer treated at Sun Yat-sen University Cancer Center from January 1999 to December 2005 were enrolled along with 25 patients with benign ovarian lesions; 20 normal ovarian tissues served as controls. Expression of c-Src and phospho-Src (Tyr416) was examined using immunohistochemistry. Survival analyses were performed using Kaplan-Meier curves. As compared to the control group, a significantly greater proportion of ovarian cancer tissues were positive for c-Src and phospho-Src expression (P < 0.001). c-Src expression was associated with age, while phospho-Src expression was significantly associated with age, FIGO stage, histology grade, and residual tumor size after surgery (all P < 0.05). The mean survival time was associated with phospho-Src expression, but not with c-Src expression. The mean survival times of patients with phospho-Src-positive tumors were significantly greater than those with phospho-Src-negative tumors (87.4 months, 95 % CI = 74.3-100.5 months and 91.5 months, 95 % CI = 84.7-98.2 months, respectively; P = 0.013). The increased c-Src expression and activation in epithelial ovarian cancer suggests that ovarian cancer patients may benefit from tyrosine kinase inhibitors such as Dasatinib. Activation of c-Src through phosphorylation at Tyr416 may play a role in the early stages of ovarian cancer development, and evaluation of its expression may be a useful prognostic marker of epithelial ovarian cancer.

[Clinical analysis of 12 cases of ovarian carcinosarcoma].

OBJECTIVE: To evaluate the clinical pathological characteristics, treatment and prognosis of ovarian carcinosarcoma. METHODS: The clinical, pathological and follow-up data of 12 cases of ovarian carcinosarcoma treated in Cancer Center of Sun Yat-sen University from May, 2002 to May, 2009 were analyzed retrospectively. RESULTS: The 12 patients with ovarian carcinosarcoma had a median age of 55 years at diagnosis, among whom 10 were postmenopausal women. The patients sought medical attention for such symptoms as pelvic and/or abdominal pain, abdominal distention and ascites. Ten patients showed elevated serum CA125 level ad admission, and postoperative chemotherapy resulted in lowered CA125 level within normal range in 7 of them; in 8 cases, CA125 level increased with disease recurrence. Pelvic mass was found by such imaging examinations as CT, MRI and ultrasound in all cases. A definite diagnosis was obtained by postoperative pathological examination. All the patients received surgical resection and platinum-based adjuvant chemotherapy. Two patients achieved disease-free survival after the treatment. Disease relapse occurred in 10 cases within 2 years after surgery, among whom 2 showed disease remission after a secondary surgery and/or chemotherapy, and 1 was receiving chemotherapy; death occurred in 5 cases, and 2 cases were lost to the follow-up. CONCLUSIONS: Ovarian carcinosarcoma has a poor prognosis. Primary surgery and platinum-based postoperative adjuvant chemotherapy is the main treatment for ovarian carcinosarcoma. The prognosis of ovarian carcinosarcoma is associated with the residual disease after surgery. The patients with disease recurrence may obtain remission and survival through a secondary surgery and/or chemotherapy. Serum CA125 can be used as a marker for monitoring the chemotherapeutic effect in clinical observation and follow-up visits.