OBJECTIVEThis paper aims to assess the interaction between common variations in catalase (CAT) polymorphic gene and environmental factors for antioxidant defense enzyme in modulating individual susceptibility to colorectal cancer (CRC).

METHODSA case-control study with 880 colorectal cancer cases and 848 controls was conducted to investigate whether variations in the catalase (CAT) gene, one of the genes involved in scavenging oxidative stress, influenced susceptibility to CRC.

RESULTSThe interaction between life style and genotypes as well as with their effects on colorectal cancer was deduced from the present study. Significant difference (P = 0.01) was identified in the distribution of CAT genotype between the colorectal cancer cases and the controls. The CRC cases had significantly lower mean activity than the controls (P < 0.01). Correlation analyses revealed statistically significant correlations between CAT activity and CAT genotype (P < 0.01).

CONCLUSIONThe risk of CRC was associated with smoking, low vegetable consumption, high pork and poultry consumptions, and low or high BMI. This is the first study reporting an association of polymorphism CAT-21A > T with colorectal cancer. Low CAT activity was associated with an increased risk of CRC; however, no evidence was found to support an association between CAT-21A > T polymorphism and CRC risk.

Adult ; Aged ; Case-Control Studies ; Catalase ; genetics ; Colorectal Neoplasms ; enzymology ; epidemiology ; metabolism ; Female ; Genotype ; Humans ; Male ; Middle Aged ; Oxidative Stress ; Polymerase Chain Reaction

AIMTo explore the effects of calcitonin-gene-related peptide (CGRP) on LPS-induced MMP-9 secretion by alveolar macrophages (AM) in vitro.

METHODSThe supernatant of LPS-induced Wistar rat AM from different intervention groups were collected to measure the activity by gelatin zymography.

RESULTS(Only secreting a small amount of MMP-9 with unstimulated AM, LPS stimulated MMP-9 production in a concentration-dependent manner (p < 0.01). (2) The activity of MMP-9 in CGRP intervention groups at different levels were significantly lower than those in non-intervention group (p < 0.01). (3) The inhibiting effects of CGRP were diminished by H-7 and W-7, an antagonist of protein kinase C (PKC) and calmodulin (CaM) (p < 0.05).

CONCLUSIONThese data suggested that CGRP involved in the MMP-9 secretion by AM, partly, via PKC and CaM pathway.

Animals ; Cells, Cultured ; Female ; Lipopolysaccharides ; adverse effects ; Macrophages, Alveolar ; secretion ; Male ; Matrix Metalloproteinase 9 ; metabolism ; Rats ; Rats, Wistar ; Receptors, Calcitonin Gene-Related Peptide ; metabolism

Objective To explore the effects of intensive antiplatelet therapy for patients with high on-treatment platelet reactivity(HPR)after coronary stent implantation.Methods Between March 2009 and February 2011,a total of 3316 consecutive acute coronary syndrome patients undergoing drug-eluting stent implanting from 3 hospitals were enrolled.Among them,840 patients(25.3％)were identified as HPR (defined as 20 μmol/L adenosine diphosphate induced platelet aggregation of ≥ 55％ at 24 hours after administration of 300 mg clopidogrel loading dose and 300 mg aspirin).The HPR patients were randomly assigned to receive standard(aspirin 300 mg/d and clopidogrel 75 mg/d,n =280)or intensified(n =560)antiplatelet therapy by the ratio of 1: 2.Patients in the intensive group were initially treated with a double maintenance dose of clopidogrel(150 mg/d)and aspirin(300 mg/d).After 3 days,patients with unsolved HPR received additional cilostazol treatment(50-100 mg,bid).The reversion rate of HPR and clinical events were observed.Results In the intensive group,HPR reversed in 304 out of 560 patients(54.3％)at 3 days post therapy and the remaining 256 patients with HPR were treated with additional cilostazol regimen for another 3 days and the total reversion rate of HPR was 81.1％(454/560).The reversion rate of HPR at 30 days in the intensified group was significantly higher than that of the standard grooup(69.9％ vs.55.7％,P =0.000).At 30 days after percutaneous coronary infervention,l patient suffered from subacute stent thrombosis(0.2％)in intensified group and no stent thrombosis was observed in standard group(P =1.000).There were no death,major or minor bleeding in both two groups.Minimal bleeding was also similar in the two groups(intensive: 4.28％ vs.standard: 2.14％,P =0.166).Conclusions The intensified antiplatelet therapy regimens could significantly increase the reversion rate of HPR in acute coronary syndrome patients undergoing coronary stenting without increasing the risk of bleeding.The clinic impact of this strategy needs to be elucidated by long term follow-up outcome studies.

BACKGROUNDHepatic arterial infusion chemotherapy for liver metastases is under evaluation because of the high target dose and low general toxicity. To investigate the efficacy and safety of a Folfox4 regimen administered through a combined hepatic arterial and systemic infusion for the first-line treatment of colorectal cancer (CRC) with unresectable liver metastases.

METHODSTwenty-seven CRC patients with unresectable hepatic metastases and no prior chemotherapy were enrolled into the study. They received a Folfox4 regimen; 1st day: HAI of oxaliplatin 85 mg/m(2) and L-folinic acid 200 mg/m(2), followed by a bolus hepatic arterial injection of 5-fluorouracil 400 mg/m(2), then continuous HAI of 5-FU 600 mg/m(2); 2nd day: infusion of L-folinic acid 200 mg/m(2) i.v. followed by an intravenous bolus injection of 5-Fluorouracil 400 mg/m(2), then continuous infusion of 5-fluorouracil 600 mg/m(2) i.v. The patients received HAI during the odd cycles, and the intravenous administration of the same Folfox4 regimen during the even cycles.

RESULTSA total of 236 treatment cycles were given with a median of 10 cycles. The therapy generated the following results after six treatment cycles: complete response (CR) 1/27 (3.7%), partial response (PR) 17/27 (63.0%), stable disease (SD) 6/27 (22.2%), and progress disease (PD) 3/27 (11.1%). Five patients had hepatectomy. The serum levels of both carcinoembryonic antigen (CEA) and CA19-9 were significantly reduced (P < 0.05). A median time to progression of 11 months and a median overall survival of 24 months were documented. The major adverse events included grade 1/2 nausea/vomiting, upper abdominal pain, peripheral neuropathy, and neutropenia/thrombocytopenia.

CONCLUSIONSThe Folfox4 regimen administered through combined hepatic arterial and systemic infusions is efficacious and safe for the treatment of CRC with unresectable liver metastases, and it facilitates the control of local lesions.

Adult ; Aged ; Aged, 80 and over ; Antineoplastic Combined Chemotherapy Protocols ; administration & dosage ; adverse effects ; CA-19-9 Antigen ; blood ; Carcinoembryonic Antigen ; blood ; Colorectal Neoplasms ; drug therapy ; mortality ; pathology ; Female ; Fluorouracil ; administration & dosage ; adverse effects ; Hepatic Artery ; Humans ; Infusions, Intra-Arterial ; Leucovorin ; administration & dosage ; adverse effects ; Liver Neoplasms ; drug therapy ; secondary ; Male ; Middle Aged ; Organoplatinum Compounds ; administration & dosage ; adverse effects

To screen the anti-inflammatory active fraction of unripe Forsythiae Fructus, and elucidate the action mechanism, water decoction, ethyl acetate portion, n-butanol portion and residue water extracts of unripe Forsythiae Fructus were administered into rats for continuously 15 days. The acute lung injury inflammatory model was established to observe the section structure of lung tissues. Levels of IL-6, TNF-α, IL-1β and IL-10 in bronchoalveolar lavage fluid were determined by ELISA kits, and changes in endogenous metabolites in serum were analyzed based on 1H-NMR metabolomics. The results showed that ethyl acetate portion of unripe Forsythiae Fructus had a better anti-inflammatory activity against acute lung injury, and could suppress the release of inflammatory factors of IL-6, TNF-α, IL-1β, significantly reduce contents of creatine, β-OH-butyrate, succinate, lysine, valine, isoleucine and glutamine, and elevate the content of GPC in serum. Ethyl acetate portion was proved to be the main fraction of anti-inflammatory activity from the perspective of endogenous metabolites in serum, and played an anti-inflammatory role by regulating creatine metabolism, choline metabolism, branched-chain amino acid metabolism and TCA cycles. This study could lay a foundation for studying pharmacodynamic material basis of unripe Forsythiae Fructus.

Objectives To understand the risk factors of cystic echinococcosis in Tibetan population,so as to provide the reference for development of prevention and control strategies.Methods Four cystic echinococcosis highly-prevalent townships were selected from Naqu County of Tibet and Shiqu County of Sichuan Province,which had similar environmental and altitude conditions,from August to September,2017.Applying the 1:1 case-control study,a household survey was conducted to investi-gate the risk factors of echinococcosis in humans. Results A total of 378 residents were investigated,of which the numbers of cases and non-cases were both 189.The univariate analysis showed that the years of keeping dogs(OR=1.032,P<0.05),the number of keeping dogs(OR=1.260,P<0.05),the way of raising dogs(OR=1.434,P<0.05),feeding with raw viscera (OR=1.531,P<0.05),and there being stray dogs around(OR=1.946,P<0.05)were the risk factors of echinococcosis.As a result of the multivariate logistic regression analysis,only three risk factors,feeding with raw viscera,there being stray dogs around,and drinking water resource,were included in the regression model.Conclusion Feeding with raw viscera,there be-ing stray dogs around,and drinking water resource are the risk factors of echinococcosis in humans.

OBJECTIVETo investigate the protective effect of Exosomes from human adipose-derived mesenchymal stem cells (hAMSCs) in neural injury induced by glutamate and its possible mechanism.

METHODSCharacteristics of Exosomes from hAMSCs were identified by electron microscopy and Western blot analysis. Cytokines that might play a major role in the protective effect were tested by enzyme-linked immunosorbent assay (ELISA). The protective action of Exosome and its possible signaling pathway were researched by the in vitro neural injury induced by glutamate, including control group (without Glu), Glu group (dealing with Glu), Glu+Exo group (dealing with Glu +100 ng/ml Exo), Glu+Exo+Akt group (dealing with Glu+100 ng/ml Exo+10 μmol/L Akt), Glu+Exo+Erk group (dealing with 100 ng/ml Glu+100 ng/ml Exo+10 μmol/L Erk), and Glu+Exo+TrkB group (dealing with Glu+100 ng/ml Exo +10 μmol/L TrkB).

RESULTSExosomes from hAMSCs had similar sizes to those isolated from other kinds of cells, and expressed the characteristic proteins such as CD63, CD81, HSP70, and HSP90. Cytokines that had neurotrophic effects on Exosomes were mainly insulin-like growth factor and hepatocyte growth factor, with the concentration being 9336.49±258.63 and 58,645.50±16,014.62, respectively; brain derived neurotrophic factor, nerve growth factor,and vascular endothelial growth factor had lower levels, with the concentration being 1928.25±385.47, 1136.94±5.99, and 33.34±9.43, respectively. MTS assay showed that the PC12 cell survival rates were 0.842±0.047, 0.306±0.024, 0.566±0.026, 0.461±0.016, 0.497±0.003, and 0.515±0.034 in the control group, Glu group, Glu+Exo group, Glu+Exo+Akt group, Glu+Exo+Erk group, and Glu+Exo+TrkB group; obviously, it was significantly lower in Glu group than in control group (P=0.02), significantly higher in Glu+Exo group than in Glu group (P=0.01), and significantly lower in Glu+Exo+Akt group than in Glu+Exo group (P=0.01).

CONCLUSIONExosomes secreted from hAMSCs have protective effect against neuron damage induced by glutamate, which may be mediated through activating the PI3/K-Akt signalling pathway.

Animals ; Central Nervous System ; injuries ; Exosomes ; Glutamic Acid ; Humans ; Mesenchymal Stromal Cells ; PC12 Cells ; Rats ; Vascular Endothelial Growth Factor A

BACKGROUNDData on the epidemiology of hypertension in Chinese non-dialysis chronic kidney disease (CKD) patients are limited. The aim of the present study was to investigate the prevalence, awareness, treatment, and control of hypertension in the non-dialysis CKD patients through a nationwide, multicenter study in China.

METHODSThe survey was performed in 61 tertiary hospitals in 31 provinces, municipalities, and autonomous regions in China (except Hong Kong, Macao, and Taiwan). Trained physicians collected demographic and clinical data and measured blood pressure (BP) using a standardized protocol. Hypertension was defined as systolic BP ≥ 140 mmHg and/or diastolic BP ≥ 90 mmHg, and/or use of antihypertensive medications. BP < 140/90 mmHg and < 130/80 mmHg were used as the 2 thresholds of hypertension control. In multivariate logistic regression with adjustment for sex and age, we analyzed the association between CKD stages and uncontrolled hypertension in non-dialysis CKD patients.

RESULTSThe analysis included 8927 non-dialysis CKD patients. The prevalence, awareness, and treatment of hypertension in non-dialysis CKD patients were 67.3%, 85.8%, and 81.0%, respectively. Of hypertensive CKD patients, 33.1% and 14.1% had controlled BP to < 140/90 mmHg and < 130/80 mmHg, respectively. With successive CKD stages, the prevalence of hypertension in non-dialysis CKD patients increased, but the control of hypertension decreased (P < 0.001). When the threshold of BP < 130/80 mmHg was considered, the risk of uncontrolled hypertension in CKD 2, 3a, 3b, 4, and 5 stages increased 1.3, 1.4, 1.4, 2.5, and 4.0 times compared with CKD 1 stage, respectively (P < 0.05). Using the threshold of < 140/90 mmHg, the risk of uncontrolled hypertension increased in advanced stages (P < 0.05).

CONCLUSIONSThe prevalence of hypertension Chinese non-dialysis CKD patients was high, and the hypertension control was suboptimal. With successive CKD stages, the risk of uncontrolled hypertension increased.

Adult ; Aged ; Awareness ; Female ; Humans ; Hypertension ; complications ; epidemiology ; therapy ; Male ; Middle Aged ; Prevalence ; Renal Insufficiency, Chronic ; complications

Fenofibrate, an agonist for peroxisome proliferator-activated receptor alpha (PPAR-α), lowers blood pressure, but whether this action is mediated via baroreflex afferents has not been elucidated. In this study, the distribution of PPAR-α and PPAR-γ was assessed in the nodose ganglion (NG) and the nucleus of the solitary tract (NTS). Hypertension induced by drinking high fructose (HFD) was reduced, along with complete restoration of impaired baroreceptor sensitivity, by chronic treatment with fenofibrate. The molecular data also showed that both PPAR-α and PPAR-γ were dramatically up-regulated in the NG and NTS of the HFD group. Expression of the downstream signaling molecule of PPAR-α, the mitochondrial uncoupling protein 2 (UCP2), was up-regulated in the baroreflex afferent pathway under similar experimental conditions, along with amelioration of reduced superoxide dismutase activity and increased superoxide in HFD rats. These results suggest that chronic treatment with fenofibrate plays a crucial role in the neural control of blood pressure by improving baroreflex afferent function due at least partially to PPAR-mediated up-regulation of UCP2 expression and reduction of oxidative stress.
Afferent Pathways ; drug effects ; Animals ; Antihypertensive Agents ; pharmacology ; Baroreflex ; drug effects ; Blood Pressure ; drug effects ; Fenofibrate ; pharmacology ; Male ; Oxidative Stress ; drug effects ; PPAR gamma ; drug effects ; metabolism ; Rats, Sprague-Dawley ; Signal Transduction ; drug effects ; Transcriptional Activation ; drug effects ; Uncoupling Protein 2 ; drug effects ; metabolism ; Up-Regulation

Objective: To investigate the association between peripheral blood mitochondrial DNA copy number (mtDNAcn) and incident risk of liver cancer. Methods: At the baseline of Dongfeng-Tongji (DFTJ) cohort, 27 009 retirees were recruited from Dongfeng Motor Corporation in 2008. After excluding people without baseline DNA, with current malignant tumor and loss of follow-up, 1 173 participants were randomly selected into a sub-cohort by age-and gender-stratified sampling method at a proportion of 5% among all retirees. A total of 154 incident liver cancer cases identified from the cohort before December 31, 2018 (4 cases had been selected into the sub-cohort) were selected to form the case cohort of liver cancer. For the above 1 323 participants, their baseline levels of mtDNAcn in peripheral blood cells were measured by using quantitative real-time PCR method. The restricted cubic spline analysis was used to fit the shape of the association between baseline mtDNAcn and incident risk of liver cancer. The weighted Cox proportional hazards model was used to estimate the hazard ratio (HR) and 95%CI. Results: In this case-cohort study, the median follow-up time was 10.3 years. The restricted cubic spline analysis indicated that the relationship between peripheral blood mtDNAcn and incident risk of liver cancer followed a U-shaped pattern (P_non-linear<0.05). All case-cohort population were divided into four subgroups by sex-specific quartiles of mtDNAcn levels among sub-cohort participants, when compared to participants in the Q₂ subgroup of mtDNAcn, those in the Q₁ subgroup (HR=2.00,95%CI:1.08-3.70) and Q₄ subgroup (HR=4.11,95%CI:2.32-7.26) both had a significantly elevated risk of liver cancer, while those in the Q₃ subgroup (HR=1.05,95%CI:0.54-2.05) had not. There were no significant multiply interaction effects of aging, gender, tobacco smoking, alcohol drinking and history of chronic hepatitis on the above association (P_interaction>0.05). Conclusion: Both extremely low and high baseline level of mtDNAcn in peripheral blood cells are associated with an increased risk of incident liver cancer, but the underlying mechanisms need to be further clarified.
Cohort Studies ; DNA Copy Number Variations ; DNA, Mitochondrial/genetics* ; Female ; Humans ; Liver Neoplasms/genetics* ; Male ; Mitochondria