Alzheimer’ s disease ( AD) is one of the most common dementia of neurodegenerative disorders, which results from the deposition of amyloid-beta ( Aβ) and there are no curative treatments for this disease at present.It had been proved that prion protein is the receptor for Aβand it plays a key role in the progress of AD with dual-side effects. Prion protein can not only transfer neurotoxicity to neurons but also protect them from neurotoxicity of Aβ.The polymor-phisms of prion protein encoding gene ( PRNP) affect the AD incubation period and clinical symptoms in humans and other animals.The discovery of PRNP mutational mouse fills the gaps of existing AD mouse models in this research area, which is potential for the studies of pathogenesis, new drugs design and testing aspects.The role and effects of prion protein in AD pathogenesis were summarized in this paper, furthermore, the discovery and utility of PRNP gene mutational mouse in research on AD and/or amyloid diseases were reviewed, and in order to provide some guidance for AD animal model study.

myocytes.In aging mice induced by D-galactose experiment.TP has anti-apoptosis and anti-oxidation effect in a dose-dependant manner.

OBJECTIVETo observe the efficacy of combination therapy of clomiphene and Chinese drugs for nourishing Shen and activating blood circulation (NSABC) in treating Stein-Leventhal syndrome caused sterility.

METHODSSixty-two patients with anovulation caused sterility were randomly divided into the treated group (n = 32) and the control group (n = 30). The treated grop was treated with the combination therapy and the control group treated by the same dosage of clomiphene alone.

RESULTSAfter treatment, when comparing with that before treatment, the endocrine hormones in the treated group improved significantly, showing a markedly decrease of androgen and luteotropic hormone, and increase of estrogen (P < 0.001). The periodic ovulation rate in the treated group reached 87%, the total pregnancy rate being 65.6%, with no occurrence of ovarian hyperstimulation syndrome (OHSS) and luteinized unruptured follicle syndrome (LUFS), while in the control group, the periodic ovulation rate was 66%, the total pregnancy rate 36.6%, with LUFS occurred in 4 patients. Comparison of the therapeutic effects between the two groups showed significant difference (P < 0.05).

CONCLUSIONThe combination therapy of clomiphene and NSABC has a better therapeutic effect in treating Stein-Leventhal syndrome caused sterility than that of using clomiphene alone.

Adult ; Androgens ; blood ; Anovulation ; blood ; etiology ; Clomiphene ; therapeutic use ; Drug Therapy, Combination ; Drugs, Chinese Herbal ; therapeutic use ; Female ; Humans ; Infertility, Female ; blood ; drug therapy ; etiology ; Ovarian Hyperstimulation Syndrome ; prevention & control ; Ovulation Induction ; Phytotherapy ; Polycystic Ovary Syndrome ; blood ; complications ; drug therapy ; Progestins ; blood

OBJECTIVETo study the mechanism of reversal effect of Curcuma Wenyujin n-Butyl alcohol extract (CWNAE) on multiple drugs resistance (MDR) of SGC7901/VCR cells.

METHODSSGC7901/VCR cells were co-culured with different concentrations CWNAE (80, 40, and 20 μg/mL) and Verapamil (VP, 10 μg/mL) for 24 h, and then acted with Adriamycin (ADM) for 1, 2, and 4 h, respec- tively. SGC7901/VCR cells with no intervention were taken as the vehicle control group. SGC7901/VCR cells treated with ADM alone were taken as the control group. The effect of CWNAE on intracellular ADM concentration was detected by flow cytometry (FCM). Cells were treated as mentioned before without any intervention of ADM. SGC7901/VCR with no ADM intervention were taken as the control group. The effect of CWNAE on the expression of P-glycoprotein (P-gp), lung resistance protein (LRP), and glu- cosylceramide synthase (GCS) was studied by Western blot. The effect of CWNAE on the location and expression quantity of P-gp was further illustrated by immunohistochemistry (IHC).

RESULTSCompared with the ADM group, the expression ratio obviously increased in the W80, W40, W20, and VP10 groups with statistical difference (all P < 0.05). The comparative expression quantity of P-gp, GCS, and LRP in SGC7901/VCR cells was obviously higher than that of non-MDR with statistical difference (all P < 0.05). The expression quantity of P-gp and GCS could be obviously down-regulated by 80 and 40 μg/mL CWN- AE, and 10 μg/mL VP, with no effect on the expression of LRP. Results of IHC proved that P-gp was mainly expressed on the cytomembrane or in the plasma, and it was also expressed on the nuclear membrane. P-gp in different locations could all be down-regulated by CWNAE.

CONCLUSIONSCWNAE could reverse the MDR of SGC7901/VCR cell line probably by inhibiting the expression of P-gp and GCS. CWNAE had no effect on LRP that also highly expressed on SGC7901/VCR. So we supposed that CWNAE could become a potential drug to reverse MDR of highly expressed P-gp and GCS.

ATP-Binding Cassette, Sub-Family B, Member 1 ; Cell Line, Tumor ; Curcuma ; Doxorubicin ; Drug Resistance, Multiple ; drug effects ; Drug Resistance, Neoplasm ; drug effects ; Drugs, Chinese Herbal ; pharmacology ; therapeutic use ; Humans ; Stomach Neoplasms

OBJECTIVETo explore effects and action mechanism of warm moxibustion on regulation of blood lipids and anti-atherosclerosis.

METHODSForty-one male Japanese big-ear white rabbits were randomly divided into a blank group (10 rabbits), a model group (10 rabbits), a moxibustion group (10 rabbits) and a medication group (11 rabbits). Normal diet was applied in the blank group while high-cholesterol diet combined with injection of bovine serum albumin were applied in the rest groups to establish rabbit model of atherosclerosis. After establishment, the model group was not intervened and warm moxibustion was applied in the moxibustion group at "Zusan-li" (ST 36) and "Shenque" (CV 8), 10 min per acupoint per day for continuous 4 weeks. The medication group was treated with intragastric administration of lovastatin capsule (3.6 mg/kg) for continuous 4 weeks. The level of blood lipids, such as total cholesterol (TC), triglyceride (TG), and content of CD40 ligand (CD40L), soluble CD40 ligand (sCD40L) and expression of nuclear factor NF-kappaB were tested after 4 weeks.

RESULTSCompared with the model group, the moxibustion group and medication group could effectively reduce the contents of TC and low density lipoprotein (all P < 0.05), lower the level of sCD40L [(8.310 +/- 1.221) ng/mL in the model group, (7.097 +/- 0.846) ng/mL in the moxibustion group and (7.354 +/- 0.631) ng/mL in the medication group], reduce expression of CD40L [(0.235 +/- 0.179) mm2 in the model group, (0.072 +/- 0.079) mm2 in the moxibustion group and (0.039 +/- 0.015) mm2 in the medication group] and NF-kappaB [(0.145 +/- 0.052)mm2 in the model group, (0.052 +/- 0.012) mm2 in the moxibustion group and (0.036 +/- 0.013) mm2 in the medication group], indicating the significant difference (P < 0.05, P < 0.001). There was no statistical difference between the moxibustion group and medication group (all P > 0.05).

CONCLUSIONThe warm moxibustion has great effect on regulation of blood lipids and anti-atherosclerosis, in which lowering expression of CD40-CD40L could be one of possible mechanisms to take effect of anti-atherosclerosis.

Animals ; Atherosclerosis ; blood ; therapy ; CD40 Antigens ; blood ; CD40 Ligand ; blood ; Humans ; Lipids ; blood ; Male ; Moxibustion ; methods ; Rabbits

Objective To investigate the relationship between disease severity and enzyme-linked immunosorbent assay (ELISA) index values of anti-desmoglein (Dsg) 1 and-Dsg3 antibodies in 56 patients with pemphigus,and to characterize fluctuations in anti-Dsg1 and-Dsg3 antibodies in different forms of pemphigus.Methods Fifty-six patients with pemphigus (including 36 cases of pemphigus vulgaris (PV) and 20 cases of pemphigus foliaceus (PF)) were enrolled in this study.Blood samples were obtained from these patients before treatment and at the following four time points:when the condition was relieved and the taper of glucocorticoids began,the dose of glucocorticoids was tapered to half of their initial dose,the maintenance treatment started,and when the duration of maintenance treatment reached two years.ELISA was performed to determine the levels of anti-Dsg1 and-Dsg3 antibodies in these serum samples.Spearman correlation analysis was carried out to assess the relationship between disease severity and ELISA index values,and independent sample's t test to compare the levels of anti-Dsg antibodies among these time points.Results The severity of pemphigus was correlated with anti-Dsg antibody ELISA index values.Both anti-Dsg1 and anti-Dsg3 ELISA index values were significantly reduced at the remission of pemphigus compared with those before treatment (all P ＜ 0.01).At the end of the two-year maintenance treatment,10 (50％) patients with PF and 7 (19.4％) patients with PV became negative for anti-Dsg1 ELISA,whereas only 1 (2.7％) patient with PV became negative for anti-Dsg3 ELISA.Conclusions Anti-Dsg antibody ELISA index value is correlated with disease severity in patients with pemphigus,which may serve as a useful marker for assessing disease severity and activity as well as evaluating therapeutic efficacy.

Background:Resistance of Helicobacter pylori(Hp)to antibiotics is the primary reason for failure of Hp eradication therapies. It has been reported that there are regional differences in the resistance rate of Hp to commonly used antibiotics. Monitoring the regional Hp resistance status is helpful for improving the eradication rate in local area. Aims:To investigate the resistant spectrum of clinical Hp strains to commonly used antibiotics in Jiaxing Area,Zhejiang Province. Methods:A total of 17 402 patients who underwent gastroscopy from Jan. 2009 to Dec. 2013 at Jiaxing First Hospital were recruited for Hp culturing by using gastric antral biopsies. Then a drug sensitive test was performed for the Hp strains obtained from the culturing. Sensitivity of these Hp strains to metronidazole,amoxicillin,gentamicin,furazolidone,clarithromycin and levofloxacin was determined. Results:Among the 17 402 cases of gastric antral biopsies,5 898(33. 9% )were positive for Hp culturing. Drug sensitive test revealed that the resistance rate of metronidazole was extremely high in all year and age groups;the resistance rates of clarithromycin and levofloxacin were increasing by years;and the resistance rates of furazolidone,amoxicillin and gentamicin were considerably low in all year and age groups. When two antibiotics were combined,amoxicillin and gentamicin accounted for the lowest resistance rate,and the next were amoxicillin and furazolidone,and gentamicin and furazolidone,respectively. Conclusions:The clinical Hp strains isolated from all age groups in Jiaxing Area,Zhejiang Province are highly resistant to metronidazole,therefore it is not recommended to be used in first line eradication regimen. Amoxicillin combined with gentamicin/ furazolidone is an ideal antibiotic combination for patients with Hp infection in all age groups;and combination of gentamicin and furazolidone is recommended to patients who are allergic to penicillin.

Objective To investigate effects of bone marrow mesenchymal stem cells (MSC) on severe acute pancreatitis (SAP) in rats.Methods A total of 60 rats were randomly divided into normal group (n =10),the model of SAP group (n =10),the transplantation of the MSC group (n =20),the combination of the MSC and the granulocyte colony-stimulating factor (G-CSF) group (n =20).The conversion rate of MSC was detected by using immunofluorescence methods,and the level of amylase in serum was assayed by using biochemical methods.Simultaneously,the level of interleukin-6 (IL-6) in serum was determined by using enzyme linked immunosorbent assay (ELISA).Results The conversion rates of the MSC increased,and consequently,the levels of amylases and interleukin-6 in serum were reduced (P ＜ 0.05).When a small amount of the G-CSF was added to MSC,the therapeutic effects of the two different kinds of cells were synergistically strengthened.In the contrary,when a large number of the G-CSF was added to MSC,the antagonism resulted between these two different kinds of cells gives rise to harmful effects on SAP.Conclusions The bone marrow mesenchymal stem cells have therapeutic effects on SAP.When the number of the bone marrow mesenchymal stem cells increases,the protective effects are enhanced.

Objective To investigate condition of single drug or multiple drug resistance and sensitivities of different combinations of antibiotics in Helicobacter pylori (H.pylori) infected patients of different ages in Jiaxing City,Zhejiang Province.Methods From January 2007 to December 2011,a total of 6280 patients underwent gastroendoscopy examination were enrolled,the average age of them was 50.8 years old.Among them,129 cases were less than 20 years old,1802 cases were between 20 and 40,3016 cases were between 40 and 60,and 1333 cases were over 60.The mucosa of gastric antrum was collected for H.pylori culture.Drug sensitivity of isolated H.pylori strains was tested with metronidazole,amoxicillin and gentamycin,furazolidone,clarithromycin and levofloxacin.x2 test was performed for the comparison of drug resistance among different age groups.Results Among 6280 specimens,H.pylori culture of 2311 cases was positive (positive rate 36.80％).The positive rate of patients aged between 40 and 60 was the highest (38.43％,1159/3016),and that of patients over 60 was the lowest (33.76％,450/1333).The drug resistance rate of metronidazole in patients between 20 and 40 years reached 98.02％ (644/657) and was the highest.The drug resistance rate of clarithromycin in patents over 60 years old was the highest,which was 22.67％(102/450).The drug resistance rates of the levofloxacin,furazolidone,amoxicillin and gentamicin were low of all ages.Mixed resistance of two antibiotic appeared in 586 strains,mixed resistance rate of metronidazole and clarithromycin was the highest (259 strains,15.23 ％).Mixed resistance of three drugs appeared in 49 strains,mixed resistance rate of metronidazole,clarithromycin and levofloxacin was the highest (32 strains,12.88％).A total of 1691 strains were sensitive to the combination of amoxicillin and gentamycin,the sensitive was rate 99.41％.The sensitive rate of the combination of amoxicillin and furazolidone,gentamycin and furazolidone was both 94.24％.Conclusions Metronidazole presented high drug resistance of all ages,and should not be chosen.The combination use of amoxicillin and gentamicin is the ideal antibiotic combination for different ages.The combination of gentamycin and furazolidone is recommended for patients who are allergic to penicillin.

In this study, plate transparent circle by Davis method was introduce firstly screening ?-Rhamnosidase high-yield strain. The spore-sprouted Aspergillus niger 8-hour were mutagenized by ethyl methane sulphonate and pre-screened via transparent circle. 11% mutants yield 40% higher of ?-rhamnosidase than the original strain. A high-yield strain, T-226 with the highest ?-rhamnosidase activity of 373.4 U/mL was finally selected from these potential high-yield mutants after rescreened by shake flask fermentation twice. When the T-226 strain was fermented in 5 L bioreactor, the enzyme activity could reach to 631.9 U/mL after 84 h. Thus, the established screening method is highly efficient to isolate ?-rhamnosidase high-yield mutant of A. niger.