Consensus ; Humans ; Insomnia, Fatal Familial ; diagnosis ; Mutation ; Pedigree

Objective To investigate the effect of CYP46A1 on the pathogenesis of Alzheimer's disease.Methods Recombinant lentiviral vectors which including anthropogenic CYP46A1 were injected into bilateral hippocampus of 3-monthold male 5XFAD transgenic mice,while empty vectors were injected into the corresponding position of the control group.After two months,the ability of learning and memory were tested by Morris water maze and T maze experiments,and amyloid plaque and inflammatory infiltration in the brain were detected by immunohistochemical staining and ELISA respectively.Results Compared with the control group,CYP46A1 virus injection significantly increased the CYP46A1 mRNA and protein expression in hippocampus.In addition,CYP46A1 overexpression significantly decreased the latency to find the platform in Morris water maze test and increased the correct rate to choose in T maze test.Aβ immunohistochemical staining and plaques area statistics demonstrated that the amyloid plaque area of hippocampus in CYP46A1 overexpression mice was significantly reduced,and there was a significantly decrease of hippocampal astrocytes expression by means of GFAP staining.Furthermore,hippocampal CYP46A1 overexpression significantly decreased the expression level of Aβ40,Aβ42,IL-1β and TNF-α,while compare with the control group.Conclusion CYP46A1 overexpression in hippocampus can promote the cognitive impairment,as well as ameliorate the brain inflammatory infiltration in 5XFAD transgenic mice,suggesting that CYP46A1 has anti-Alzheimer's disease like effects.

Objective To investigate the effect of emodin on the gemci-tabine-resistant pancreatic cancer cell line SW1990/Gemcitabine (GEM),and explore the potential mechanism of its action .Methods The pancreatic cancer cell line SW1990 was treated by intermittently in-creasing the concentration of gemcitabine in the culture medium for 10 months, and SW1990/GEM cells were obtained.This experiment was di-vided into control group ,emodin group,gemcitabine group and combina-tion group ( emodin +gemcitabine ) .SW1990/GEM and SW1990 cells were treated with emodin ( 10 μmol · L-1) and gemcitabine ( 20 μmol· L-1) alone or those two together in three groups for 48 h, in con-trol group cells were treated with 0.1%DMSO for 48 h.Cell proliferation was analyzed by MTT.Reverse transcription -polymerase chain reaction was performed to analyze the protein and gene expression of multidrug re-sistance gene-1 ( MDR-1) .Flow cytometric was applied to analyze the function of the P-glycoprotein(P-gp).The Rhodamine l23 efflux experiment was applied to assay P -gp function in SW1990/Gemcitabine cells.Results Compared with gemcitabine group , the combination group could significantly inhibit the proliferation of SW1990/GEM cells.Treatment of SW1990/GEM and SW1990 cells with gemcitabine alone could inhibit 13.34%and 36.52%of cell viability,there was significant difference between the two group (P＜0.05). The results showed that the SW1990 /GEM cell line had an obvious resistance to gemcitabine compared with the cell line SW 1990.While SW 1990/GEM and SW 1990 cells were treated with gemcitabine combined with emodin , cell via-bility was inhibited to 40.45%and 43.87%, there was no significant difference between the two group .The emodin could enhance the anti -proliferative effect of gemcitabine on drug -resistance cell SW1990/GEM.Compared with gemcitabine group, the combination group could significantly inhibit the expression of MDR-1 gene,and the difference was statistically significant (P＜0.05).Conclusion Effect of emodin can down -regulate the expression of MDR -1 and then improve the drug resistance of gemcitabine in pancreatic cancer .

BACKGROUNDEpigallocatechin-3-gallate (EGCG) has exhibited antitumor properties in several types of cancers, including nasopharyngeal carcinoma (NPC), but the molecular mechanisms underlying this function remain incompletely understood. The aim of the present study was to characterize the global impact of EGCG on the expression of microRNAs (miRNAs) in NPC cells.

METHODSUsing microarray analysis, the alterations of miRNA expression profiles were investigated in EGCG-treated CNE2 cells. Furthermore, the target genes and signaling pathways regulated by EGCG-specific miRNAs were identified using target prediction program and gene ontology analysis.

RESULTSA total of 14 miRNAs exhibited >2-fold expression changes in a dose-dependent manner after treatment with 20 μmol/L and 40 μmol/L EGCG. Totally 43, 49, and 52 target genes from these differentially expressed miRNAs were associated with the apoptosis, cell cycle regulation, and cell proliferation, respectively. A total of 66 signaling pathways, primarily involved in cancer development and lipid and glucose metabolism, were shown to be regulated by EGCG-specific miRNAs.

CONCLUSIONEGCG induces considerable alterations of miRNA expression profiles in CNE2 cells, which provides mechanistic insights into cellular responses and antitumor activity mediated by EGCG.

Antineoplastic Agents ; pharmacology ; Carcinoma ; Catechin ; analogs & derivatives ; pharmacology ; Cell Line, Tumor ; Computational Biology ; Gene Expression ; drug effects ; genetics ; Humans ; MicroRNAs ; genetics ; metabolism ; Nasopharyngeal Neoplasms ; genetics ; Real-Time Polymerase Chain Reaction ; Signal Transduction ; drug effects ; genetics

An optimal therapy for pulmonary embolism (PE) was explored by comparing three different methods in order to alleviate the sufferings of PE patients and reduce the mortality. Eighty patients with PE diagnosed by computed tomography angiography (CTA) were treated with thrombolysis, anticoagulation only, or surgery/intervention. The clinical efficacy of different treatments were compared and analyzed. Twenty-four out of the 26 patients (92%) in anticoagulation only group showed improvement in CTA and clinical presentations, which was significantly higher than that in the thrombolysis group (87%, n=39, P<0.05). However, there was no significant difference in the rate of mortality between thrombolysis group and anticoagulation only group. In the surgery/interventional group (n=15), the success rate was 47%, and the mortality rate was 14%. Both of them were significantly different from those in thrombolysis and anticoagulation only groups (both P<0.05). Log-rank analysis of the data of 5-year follow-up revealed that the survival time in surgery/intervention group was significantly shorter than in the other two groups (P<0.05). It was suggested that it is of importance to choose the appropriate therapeutic regimen for PE patients. Mortality may be reduced and prognosis may be improved with anticoagulation only and thrombolysis therapy.
Adolescent ; Adult ; Aged ; Aged, 80 and over ; Anticoagulants ; adverse effects ; therapeutic use ; Female ; Humans ; Male ; Middle Aged ; Postoperative Complications ; Pulmonary Embolism ; drug therapy ; surgery ; Pulmonary Surgical Procedures ; adverse effects ; Survival Analysis ; Thrombolytic Therapy ; adverse effects

OBJECTIVETo investigate the effect of premature rupture of the membrane (PROM) on neonatal complications in premature infants.

METHODSThe registration information of 7684 preterm infants with gestational age <37 weeks were collected from the cooperative units in the task group between January 1, 2014 to December 31, 2014. Specially trained personnel from each cooperative units filled in the unified form in a standardized format to record the gender, gestational age, birth weight, PROM, placental abruption, antenatal corticosteroid, Apgar score, amniotic fluid pollution, and complications of the infants. The data were analyzed comparatively between the cases with PROM and those without (control).

RESULTSThe preterm mortality rate was significantly lower but the incidences of ICH, NEC, ROP and BPD were significantly higher in PROM group than in the control group (P<0.05). The 95% confidence interval of the OR value was <1 for mortality, and was >1 for ICH, NEC, ROP and BPD. After adjustment for gestational age, birth weight, gender, mode of delivery, placental abruption, placenta previa, prenatal hormones, gestational diabetes mellitus (GDM), gestational period hypertension and 5-min Apgar score <7, the incidences of NEC, ROP and BPD were significantly different between the two groups (P<0.05) with 95% confidence interval of OR value >1, but the mortality rate and incidence of ICH were not significantly different between the two groups (P>0.05).

CONCLUSIONPROM is a risk factor for NEC, ROP and BPD in preterm infants, and adequate intervention of PROM can reduce the incidences of such complications as NEC, ROP and BPD in the infants.

Apgar Score ; Birth Weight ; Female ; Fetal Membranes, Premature Rupture ; pathology ; Gestational Age ; Humans ; Incidence ; Infant, Newborn ; Infant, Newborn, Diseases ; etiology ; Infant, Premature ; Pregnancy ; Risk Factors