Many studies have shown that chronic inflammation occurs in the brain of patients with Alzheimer's disease (AD). It is well known that long-term administration of non-steroidal anti-inflammatory drugs (NSAIDs) can alleviate the cognitive decline of AD patient and elderly. Several inflammatory cytokines produced in the metabolism of arachidonic acid (AA) are closely related to inflammatory diseases. Lipoxygenases (LOXs) and cyclooxygenases (COXs) play a crucial role in the AA network, the products eicosanoids have an important impact on the progression of AD. Although there are many arguments and conflicting evidence, currently LOXs and COXs are still the hot topics in the research on AD pathogenesis and drug development. Here, we review the progress in research on COXs and LOXs, including their actions on CNS and their association with AD, and explore the feasibility of LOXs and COXs as targets for the drugs to prevent and/or treat AD.
Alzheimer Disease ; drug therapy ; enzymology ; prevention & control ; Amyloid beta-Peptides ; metabolism ; Animals ; Anti-Inflammatory Agents, Non-Steroidal ; pharmacology ; therapeutic use ; Arachidonic Acid ; metabolism ; Brain ; metabolism ; Cyclooxygenase 1 ; metabolism ; Cyclooxygenase 2 ; metabolism ; Cyclooxygenase Inhibitors ; therapeutic use ; Humans ; Lipoxygenase Inhibitors ; therapeutic use ; Lipoxygenases ; metabolism ; Prostaglandin H2 ; metabolism ; Prostaglandin-Endoperoxide Synthases ; metabolism

Background and purpose:Rectal small cell carcinoma is high malignant tumor and prone to early metastasis. It is rare in the clinical and its prognosis is poor. The aim of this article was to analyze clinical characteristics and summarize the diagnosis,treatment and prognosis of rectal small cell carcinoma.Methods:Clinical data of 16 cases with rectal small cell carcinoma conifrmed by pathology from Jan. 2001 to Jan. 2013 in the Tumor Hospital Affiliated to Zhengzhou University Hospital were analyzed retrospectively.Results:Among the 16 rectal small cell carcinoma patients (mean age is 58.5 years), 9 were male, 7 were female; 4 cases in stageⅡ, 7 cases in stageⅢ and 5 cases in stageⅣ. Ten cases underwent surgical treatment, of which 6 cases underwent radical surgery, 4 cases underwent palliative surgery;6 cases received chemotherapy alone, 2 cases received chemoradiotherapy, 2 cases did not receive any treatment postoperatively. Five cases were lost opportunity for operation, of which 3 cases underwent chemotherapy alone and 2 cases underwent chemoradiotherapy. One case did not receive any treatment. Among 10 cases of resection of the lesions, 5 cases had vascular invasion and 7 cases had local lymph node metastasis. All patients received 7-65 months of follow-up. The median survival was 15.4 months. The 6 months, 1 year, 2 years, 3 years and 5 years survival rates were 58.4%, 46.2%, 26.6%, 13.1% and 6.2% respectively. The prognosis of patients was associated with tumor staging, presence of vascular invasion and lymph node metastasis, and type of operation (P<0.05); but not related to age, gender and tumor size (P>0.05).Conclusion:The biologic behavior of rectal small cell carcinoma which is a rare disease and similar to small cell lung cancer, and its prognosis is poor. Treatment methods include surgery, radiotherapy and chemotherapy. The overall result is poor.

Background and purpose:The recurrence and metastasis of gastric cancer seriously affect survival in patients.SOX gene as a regulatory factor of the classical Wnt pathway, may play an important role in the process. This study was to explore the expression of stem cell marker SOX-2 and β-catenin in gastric cancer and to analyze the relationship with recurrence and metastasis after operation.Methods:Immunohistochemistry was used to detect the expression of SOX-2 and β-catenin in 71 tumor samples from 71 cases after surgery for gastric cancer. The correlation between SOX-2 and β-catenin expression and the clinicopathological characteristics of gastric cancer and disease-free survival was analyzed.Results:The SOX-2 protein expression was associated with metastasis, lymph node inifltration or differentiation (P=0.011,P=0.036,P=0.034) in the 71 gastric cancer, but not with gender, age or T stage. β-catenin expression was correlated with metastasis, lymph node invasion or T stage (P=0.025,P=0.014,P=0.026), but was not related to differentiation, gender or age. The survival analysis showed that SOX-2 and β-catenin expression was closely associated with prognosis of patients, and metastatic rate in positive expression was higher than that in negative expression.Conclusion:The expression of SOX-2 and β-catenin is associated with the development, recurrence, metastasis of gastric cancer and may be used as a useful prognostic parameter to predict overall survival.

OBJECTIVETo study the physiopathologic basis of Weikangfu Granule (WKFG) in treating precancerosis of gastric mucosa in patients of chronic gastritis with Pi-deficiency syndrome (CG-PDS).

METHODSOne hundred and fifteen patients of CG-PDS who suffered from intestinal metaplasia (IM) and atypical hyperplasia (ATHP) of gastric mucosa, were divided into two groups. The treated group (n = 61) was treated by WKFG with its ingredients modified according to the syndrome type of patients. The control group (n = 54) was treated with Weishu granule. The histopathological and subcellular ultrastructural changes were detected by optical microscope, screening electronic microscope, transmission electronic microscope and histochemical staining; the nuclear and mitochondrial ultrastructure of gastric mucosa were analyzed with energy dispersion X-ray analyser and image analysis system. And the changes of cAMP, lipid peroxide (LPO), superoxide dismutase (SOD) before and after treatment in the treated group were measured and compared with those of the health control group consisting of 15 volunteers.

RESULTSThe symptomatic and pathological therapeutic effect in the treated group were significantly superior to those in the control group (P < 0.05). The contents of Zn, Cu, cAMP, SOD and (3)H-TdR LCT in gastric mucosa of the treated group before treatment were all lower than those of the healthy control group, yet all these indexes markedly increased after treatment, while serum LPO level, which increased before treatment was lowered after treatment. All the changes showed statistical significance (P < 0.05 or P < 0.01).

CONCLUSIONWKFG can reverse IM and ATHP in patients of CG-PDS, and the effect may be realized by way of increasing the level of Zn, Cu, cAMP and SOD in gastric mucosa, promoting cell differentiation, enhancing cellular immunity and reducing oxygen free radicals and lipid peroxidation.

Adult ; Aged ; Antineoplastic Agents ; pharmacology ; therapeutic use ; Chronic Disease ; Copper ; analysis ; Cyclic AMP ; analysis ; Drugs, Chinese Herbal ; therapeutic use ; Gastric Mucosa ; chemistry ; pathology ; ultrastructure ; Gastritis, Atrophic ; pathology ; Humans ; Lipid Peroxides ; analysis ; Male ; Medicine, Chinese Traditional ; Middle Aged ; Precancerous Conditions ; pathology ; Stomach Neoplasms ; pathology ; Superoxide Dismutase ; analysis ; Syndrome ; Yang Deficiency ; complications ; Zinc ; analysis

OBJECTIVETo investigate the influence of class III forces in craniofacial morphology and sutural histology in Rhesus monkeys.

METHODSSix male Rhesus monkeys in mixed dentition were employed in this study, two as 90-day experimental group, two as 45-day experimental group and the other two as control respectively. The experimental monkeys were casted magnetic orthopedic appliance-III (MOA-III), the control monkeys received no treatment. Intraoral photographs, casts and cephalometric radiographs of each animal were obtained at the beginning and at the end of the experiment. Fluorescent and haematoxylin-eosin staining were used to observe the histological changes in craniofacial sutures. RESULTS; In experimental groups, the maxillomandibular relationship changed more significantly in 90-day experimental group than 45-day experimental animals. But changes were scarcely noted in the control. The bony depositions of the sutures were distinctly found during the experimental period, especially in zygomaticomaxillary, transverse palatine, pterygopalatine and zygomaticotemporal sutures.

CONCLUSIONThis study indicates that this kind of magnetic appliance could cause skeletal and dental changes of maxilla and mandible, and change the arrangement of connective tissues in craniofacial sutures, and lead to significant new bone deposition in craniofacial sutures.

Animals ; Cephalometry ; Macaca mulatta ; Magnetic Phenomena ; Male ; Mandible ; Maxilla ; Skull

Objective: To analyze the clinical characteristics and long-term outcomes with multicenter study for acute lymphoblastic leukemia (ALL) in children over 10 years old and adolescents. Method: Newly diagnosed ALL patients aged from 10 to 18 years old in three hospitals were included in the study from May 1(st) 2005 to April 30(th) 2015. They were received ALL-2005/2009 protocol following up to December 31(st) 2016. The clinical characteristics, outcomes and the prognostic analysis were evaluated between the two protocols. Results: Totally, 237 patients were involved in the study, 76 cases for ALL-2005 and 161 cases for ALL-2009 protocol. Complete remission (CR) after induction therapy was 94.5%. 64 (28.6%) patients relapsed with a median time of 14.5 months and 70 (29.5%) patients passed away during the following time. In long-term follow-up, the 5-year event-free survival (EFS) and 5-year overall survival (OS) of ALL patients were (63.1±3.3)% and (68.4±3.2)%. The 7-year EFS and OS were (61.0±3.5)% and (67.6±3.3)%.The 5-year EFS of intermediate risk group in ALL-2005 and ALL-2009 protocol were (73.6±6.1)% and (71.7±4.3)% with no difference (χ(2)=0.064, P=0.801). The 5-year EFS of high risk group in two protocols were (27.6±9.6)% and (33.9±9.3)%, showing no significant difference (χ(2)=0.296, P=0.586). Five years relapsed rate of two protocols were (33.8±5.7)% and (32.6±4.1)% with no difference (χ(2)=0.055, P=0.815). The mortalities were 36.8% and 29.8% separately (χ(2)=2.869, P=0.090). Univariate analysis indicated that age, male, risk, BCR/ABL translocation/t(9;22) and resistant to induction were risk prognostic factors in long-term survival (χ(2)=4.764, 4.796, 46.410, 9.560, 25.450; P=0.029, 0.029, <0.001, 0.049, <0.001). Cox multivariate analysis showed male, risk and resistant to induction were independent risk prognostic factors (RR=1.790, 2.727, 2.719; P=0.021, 0.000, 0.012). Conclusion: Protocol ALL-2009 enhanced the chemotherapy intensity in intermediate risk group with no benefit of survival. BCR-ABL fusion or t(9;22) translocation was still the risk factor of prognosis. TKI inhibitor used in these patients could improve survival. EFS rate was increased a little and death rate was decreased in ALL-2009 protocol with no significant lower relapsed rate comparing with ALL-2005 protocol.
Adolescent ; Antineoplastic Combined Chemotherapy Protocols ; Child ; Disease-Free Survival ; Humans ; Male ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; Prognosis ; Remission Induction ; Risk Factors ; Translocation, Genetic

BACKGROUNDIbutilide has been commonly used for pharmacologic cardioversion of atrial fibrillation and flutter in clinical settings. The objective of this study was to investigate the effects of ibutilide on the defibrillation threshold (DFT), restitution properties, dispersion of refractoriness and activation patterns during ventricular fibrillation (VF).

METHODSIbutilide was administrated intravenously in six open-chest beagles. Before and after the drug administration, 20-second episodes of VF were electrically induced and recorded with a 10×10 unipolar electrode plaque sutured on the lateral epicardium of the left ventricle. DFT and VF activation patterns, including type of epicardial activation maps, VF cycle length (VF-CL), conduction velocity, wavelength (WL) and reentry incidence, were measured. Restitution properties and dispersion of refractoriness were estimated from activation recovery intervals (ARI) during pacing.

RESULTSCompared to baseline, ibutilide markedly decreased the DFT by 31% ((491 ± 14) V vs. (337 ± 59) V, P < 0.01). The drug significantly reduced the maximal slope of the restitution curve (1.34 ± 0.08 vs. 0.76 ± 0.06, P < 0.01) and its epicardial dispersion (0.36 ± 0.09 vs. 0.21 ± 0.06, coefficient of variation, P = 0.03). The dispersion of refractoriness was enhanced at the pacing cycle length of 300 ms to 160 ms by ibutilide. The drug significantly increased the VF-CL ((96 ± 19) ms vs. (112 ± 20) ms, P < 0.01) and the WL ((41 ± 9) mm vs. (52 ± 14) mm, P = 0.02) during VF, and reduced the reentry incidence by 25% (0.08 ± 0.02 vs. 0.06 ± 0.02, P < 0.01). In the epicardial activation maps, ibutilide significantly reduced the percentage of more complex activation maps during VF.

CONCLUSIONSIntravenous ibutilide significantly decreased the DFT. It might be due to reduction of activation pattern complexity during VF.

Animals ; Anti-Arrhythmia Agents ; therapeutic use ; Dogs ; Pericardium ; drug effects ; Sulfonamides ; therapeutic use ; Ventricular Fibrillation ; drug therapy ; physiopathology

Ischemia-reperfusion injury (IRI) is a major complication in liver transplantation (LT) and it is closely related to the recovery of grafts' function. Researches has verified that both innate and adaptive immune system are involved in the development of IRI and Kupffer cell (KC), the resident macrophages in the liver, play a pivotal role both in triggering and sustaining the sterile inflammation. Damage-associated molecular patterns (DAMPs), released by the initial dead cell because of the ischemia insult, firstly activate the KC through pattern recognition receptors (PRRs) such as toll-like receptors. Activated KCs is the dominant players in the IRI as it can secret various pro-inflammatory cytokines to exacerbate the injury and recruit other types of immune cells from the circulation. On the other hand, KCs can also serve in a contrary way to ameliorate IRI by upregulating the anti-inflammatory factors. Moreover, new standpoint has been put forward that KCs and macrophages from the circulation may function in different way to influence the inflammation. Managements towards KCs are expected to be the effective way to improve the IRI.
Cytokines ; Hand ; Immune System ; Inflammation ; Ischemia* ; Kupffer Cells ; Liver Transplantation* ; Liver* ; Macrophages* ; Receptors, Pattern Recognition ; Reperfusion Injury* ; Reperfusion* ; Toll-Like Receptors

Objective To evaluate the role of preoperative serological indexes in predicting long-term survival and tumor recurrence of hepatocellular carcinoma (HCC) patients after liver transplantation, aiming to explore its significance in expanding the Milan criteria. Methods Clinical data of 669 recipients undergoing liver transplantation for HCC were retrospectively analyzed. The optimal cut-off value was calculated by the receiver operating characteristic (ROC) curve. The risk factors affecting the overall survival and recurrence-free survival rates of HCC patients after liver transplantation were identified by univariate and multivariate regression analyses. The correlation between preoperative serum liver enzymes and pathological characteristics in HCC patients was analyzed. The predictive values of alpha-fetoprotein (AFP) combined with γ -glutamyl transferase (GGT) and different liver transplant criteria for the survival and recurrence of HCC patients after liver transplantation were compared. Results Exceeded Milan criteria, total tumor diameter (TTD) > 8 cm, AFP > 200 ng/mL and GGT > 84 U/L were the independent risk factors for the overall survival and recurrence-free survival rates of HCC patients after liver transplantation (all P < 0.05). Correlation analysis showed that preoperative serum GGT level was correlated with TTD, number of tumor, venous invasion, microsatellite lesions, capsular invasion, tumor, node, metastasis (TNM) stage, Child-Pugh score and exceeded Milan criteria (all P < 0.05). Milan-AFP-GGT-TTD (M-AGT) criteria were proposed by combining Milan criteria, TTD with serum liver enzyme indexes (AFP and GGT). The 5-year overall survival and recurrence-free survival rates of HCC recipients who met the M-AGT criteria (111 cases of exceeded Milan criteria) were significantly higher than those who met Hangzhou criteria (both P < 0.05), whereas had no significant difference from their counterparts who met the University of California at San Francisco (UCSF) criteria (both P > 0.05). Conclusions Preoperative serological indexes of AFP and GGT could effectively predict the long-term survival and tumor recurrence of HCC patients after liver transplantation. Establishing the M-AGT criteria based on serological indexes contributes to expanding the Milan criteria, which is convenient and feasible.

BACKGROUNDSerum high sensitive C-reactive protein (hs-CRP), adiponectin levels and urine albumin excretion rate (UAER) are probably associated with inflammation and atherosclerosis. The aim of this study was to determine the three markers in coronary artery disease (CAD) subjects with different glucose tolerance status in a Chinese population and further explore the levels of the three markers in these subjects and the possible association of these markers with CAD risk factors and the severity of CAD as well.

METHODSA total of 242 subjects with angiographically documented CAD were recruited, and then assigned to three groups: the normal glucose tolerance (NGT) + CAD group, including 100 CAD patients with NGT; the impaired glucose tolerance (IGT) + CAD group, 40 CAD patients with IGT; the type 2 diabetes mellitus (T2DM) + CAD group, 102 CAD patients with T2DM. Serum hs-CRP, adiponectin levels as well as UAER were measured in all subjects.

RESULTSSerum hs-CRP levels were increased in the T2DM + CAD group compared with the NGT + CAD group (4.71 +/- 2.59) vs (3.60 +/- 2.46) mg/L, P = 0.037. Serum adiponectin levels were gradually decreased from the NGT + CAD to IGT + CAD to T2DM + CAD groups, (5.99 +/- 1.84), (5.82 +/- 1.72) and (4.65 +/- 1.71) mg/L, P = 0.002 and 0.040 for NGT + CAD and IGT + CAD groups vs T2DM + CAD group, respectively. While the UAER was gradually increased from the NGT + CAD to IGT + CAD to T2DM + CAD groups, (6.42 +/- 2.51), (6.89 +/- 2.94) and (15.03 +/- 4.22) microg/min (P < 0.001) for NGT + CAD and IGT + CAD groups vs T2DM + CAD group. Multiple linear stepwise regression analysis showed that waist-hip ratio (WHR) and low density lipoprotein cholesterol (LDL-C) were the significant determinants of serum hs-CRP levels; triglyceride (TG), high density lipoprotein cholesterol (HDL-C), age, WHR, T2DM, 2-hour serum insulin (2hINS), sex, and apolipoprotein B were the significant determinants of serum adiponectin levels; and systolic blood pressure (SBP), T2DM, and hemoglobin A1c (HbA1c) were the significant determinants of UAER in all subjects (R(2) = 0.070, 0.352, and 0.214, respectively). However, no significant correlation was seen for hs-CRP, adiponectin and UAER with the severity of CAD. Hs-CRP levels were significantly correlated with UAER.

CONCLUSIONSThere was a trend of increased serum hs-CRP levels from the NGT + CAD to IGT + CAD to T2DM + CAD groups, though it only showed significance in the T2DM + CAD group compared with the NGT + CAD group. Serum adiponectin levels were decreased and UAER was increased from the NGT + CAD to IGT + CAD to T2DM + CAD groups. Increased UAER and serum hs-CRP, and decreased adiponectin levels were associated with traditional CAD risk factors but failed to be correlated with the severity of CAD. Hs-CRP levels were significantly correlated with UAER.

Adiponectin ; blood ; Aged ; Albuminuria ; urine ; C-Reactive Protein ; metabolism ; Coronary Artery Disease ; blood ; metabolism ; physiopathology ; urine ; Female ; Glucose Intolerance ; blood ; urine ; Humans ; Male ; Middle Aged