Objective To retrospectively analyze the outcomes and adverse effects of sequential therapy of BTD and MPT regimen for the newly-diagnosed multiple myeloma patients no eligible for high dose chemotherapy and stem cell transplantation. Methods Thirty-six patients were involved in this study and the patients were treated with tandem therapy of BTD and MPT regimen. The patients were treated with BTD regimen as induced therapy no less than 2 cycles. When the patients got PR or above PR,they were treated with MPT regimen as consolidation therapy which was no less than 2 cycles. Then,the patients who achieved PR or partial PR were received MPT chemotherapy regimen as consequent treatment. After that,low dose thalidomide was used as maintenance therapy. The outcomes and adverse effects were retrospectively evaluated. Results Thirty-six patients were treated with BTD regimen as induced therapy. The results were that 7 patients (19.4 %) achieved CR,8 (22.2 %) VGPR,14 (38.9 %) PR and the OR rate was 80.6 %. The patients (n=29) who achieved no less than PR was treated with MPT regimen as consequent therapy. The results were that four patients were in progression and the others were stable. Twenty-five patients were treated with low dose thalidomide as maintenance therapy. The median progression-free survival (PFS) did not reached yet until last follow-up (median follow-up time was 16.5 months). One-year overall survival rate was expected 86.0 % and 3-year expected overall survival rate was 77.0 %. The main regimen-associated toxicities included thrombocytopenia,peripheral neuropathy (PN),Herpes Zoster,gastrointestinal symptoms,anemia,neutropenia,constipation,fatigue,rash and so on. The incidence of grade 3 and 4 adverse events was low. Conclusion Sequential therapy of BTD and MPT regimen can be used as the front-line therapy for the newly-diagnosed multiple myeloma patients no eligible for high dose chemotherapy and stem cell transplantation.

ObjectiveTo observe the expressions of PPAR-γ protein during the course of pancreatic fibrosis of chronic pancreatitis (CP) in Wistar rats and its significance.Methods Bibutyltin dichloride ( DBTC,8 mg/kg body weight) in a volume of 200 ml solvent was injected into the tail vein to establish the CP rat's model.Wistar rats were randomly divided into control group and 1,3,5,7,14,42 d group according to weights.Pancreatic tissue underwent routine pathological examination,and collagen accumulation in pancreatic sections was determined by staining for Sirius Red.Pancreatic myeloperoxidase (MPO)activity was determined.Expressions of α-SMA and PPAR-γ proteins were assessed by immunohistochemical method.Results Light microscopy showed signs of acute pancreatitis with interstitial edema and infiltration of neutrophilic granulocytes 7 d after DBTC injection.Acinar cells necrosis,atrophy,lymphocytes and monocytes infiltration,fibrosis within lobule and peri-lobule as well as pancreatic duct changes were found,which was in accord with the course from AP to CP.One days after induction,the activity of MPO,expressions of α-SMA was significantly increased[ (0.78 ±0.71) vs (0.15 ±0.05)U/g,6.67 ±3.14 vs 0,P＜0.05],then it did not increase with time of induction.Seven days after induction,collagen level reached the peak [ (45.42 ±15.99)％ ],which was significantly higher than that in control group [ (10.87 ± 2.28 )％,P ＜ 0.05 ].Collagen fibers accumulated from periductal to intra-acinar and/or inter-acinar areas.In control rats,the expression of PPAR-γ protein was positive only in vessel walls,and the expression level was 0.17±0.41 and increased with time of induction,then reached the peak of 4.83 ± 2.71 at 42 d.ConclusionsDuring the course of pancreatic fibrosis in rats,the expression of PPAR-γ protein is gradually increased,and plays a limited anti-inflammation and anti-fibrosis role.

Objective To investigate the effect of α-tocopherol on fibrosis of chronic pancreatitis (CP) rat and explore its mechanism.MethodsMale Wistar rats were randomly divided into control group,acute necrotizing pancreatitis (ANP) group,α-tocopherol group.CP was induced by dibutyltindich loride ( 8 mg/kg) infusion into the tail vein.Gastric lavage of α-tocopherol (800 mg/kg body weight,daily) was started 24 hours after dibutyhindich loride infusion for 4 weeks.The rats in ANP and control group received 0.6 ml salad oil gastric lavage.The rats were sacrificed 4 weeks later.Pancreatic tissue was harvested for histological examination and collagen staining,and measurement of the levels of hydroxyproline and malondialdehyde (MDA) of the pancreas were performed.The mRNA expression of transforming growth factor (TGF)-β１ was measured by real time PCR.ResultsAfter gastric lavage for 4 weeks,the pancreatic tissue inflammation,fiber deposition and abnormal structure in rats of α-tocopherol group were greatly reduced.The levels of MDA and hydroxyproline in rats of α-tocopherol group were significantly lower than those in ANP group [ (0.40 ±0.20) vs (1.07 ±0.41) nmol/100mg,(402.49 ±27.62) vs (664.92 ±29.04) μg/g,P＜0.05].The expressions of TGF-β1 mRNA in rats of o-tocopherol group were significantly lower than those in ANP group (2.24 ± 0.89 vs 3.35 ± 0.66,P ＜ 0.05 ).Conclusions Tocopherol gamma can improve pancreatic inflammation and fibrosis by reducing the oxidative stress level and down-regulating the expression of TGFβ1mRNA in rats with CP.

Objective To survey knowledge of the local people's understanding of Brucellosis,and to explore the risk factors for brucellosis infection,and to determine the key issue of next comprehensive health promotion intervention.Methods Two counties,Yanggao and Guangling,which are old endemic areas with Brucellosis in history,and with epidemic rebounding in recent years,were selected.The survey was carried out by two stage stratified cluster sampling method.The questionnaires included respondents' demographic data(gender,age,education level,etc.),Brucellosis (hereinafter referred to as Brucellosis) knowledge of the investigation and behavior and attitude of people toward the measure for control of Brucellosis.Results A total of 5372 people were investigated in two counties of which 62.7％(3362/5372) of farmers.The investigated crowd had low culture level.The awareness of Brucellosis infection route of Yanggao and Guangling counties were 84.03％ (2379/2831) and 333％(847/2541 ).The average awareness of Brucellosis infection route was 18.60％(6001/32 260).In the investigation of knowledge on Brucellosis prevention of the two counties,29％ believed that it was necessary to wear gloves to process flow product,and 70％ of people answered do not know.For farmers on how to deal with dead animals,results showed that 79.1％(664/839) in Yanggao choose to sell dead animals to the market; 61.2％ (267/361) in Guangling choose to kill and bury,there were inappropriate treatment on handling of ill and dead animals in the two counties.Conclusions Spread of Brucellosis is caused mainly due to emphasis on the disease is not enough,and inappropriate handling of dead livestock.Measures like strengthening health education and behavioral intervention,increasing public awareness of the disease prevention and ability to change the incorrect way of life and cognitive concepts,can effectively reduce human infection and the spread of Brucellosis.

OBJECTIVETo investigate the vascular activity of extract from mulberry leaves (EML) on rat thoracic aorta and the underlying mechanism.

METHODSIsolated thoracic rings of Sprague-Dawley rats were mounted on the organ bath and the tension of the vessel was recorded.

RESULT(1) EML produced a concentration-dependent vasorelaxation of aorta preconstricted by high K(+) (60 mmol/L) or 10(-6) mol/L phenylephrine (PE) in endothelium-intact and endothelium-denuded arteries. (2) EML at EC(50) concentration reduced the calcium dose-response curve. (3) After incubation of aorta with verapamil, EML induced vasocontraction of aorta preconstricted by PE, which was abolished by ruthenium red.

CONCLUSIONThe vascular effect of EML is biphasic, the vasorelaxation is greater than the vasocontraction. The vasorelaxation induced by EML may be mediated by inhibition of voltage-and receptor-dependent calcium channels in vascular smooth muscle cells, while the vasocontraction is via activation of ryanodine receptor in endoplasmic reticulum.

Acetates ; isolation & purification ; pharmacology ; Animals ; Aorta, Thoracic ; drug effects ; physiology ; Dose-Response Relationship, Drug ; In Vitro Techniques ; Male ; Morus ; chemistry ; Plant Extracts ; isolation & purification ; pharmacology ; Plant Leaves ; chemistry ; Potassium ; pharmacology ; Rats ; Rats, Sprague-Dawley ; Ryanodine Receptor Calcium Release Channel ; physiology ; Vasoconstriction ; drug effects ; Vasodilation ; drug effects

OBJECTIVETo investigate whether activation of mitochondrial aldehyde dehydrogenase 2 (ALDH2) and inhibition of mitochondrial permeability transition pore (mitoPTP) were involved in the cardioprotection of ethanol postconditioning in isolated rat heart.

METHODSHearts isolated from male Sprague-Dawley rats were perfused on a langendorff apparatus and subjected to 30 min of regional ischemia (occlusion of left anterior descending artery) followed by 120 min of reperfusion. The ventricular hemodynamic parameters and lactate dehydrogenase (LDH) release during reperfusion were measured. Infarct size was measured by TTC staining method and the expression of ALDH2 at mRNA level of left anterior myocardium was detected by RT-PCR.

RESULTIn contrast to ischemia and reperfusion, ethanol postconditioning improved the recovery of left ventricular developed pressure, maximal rise/fall rate of left ventricular pressure during reperfusion, reduced LDH release and infarct size. The expression of ALDH2 mRNA level was increased. Administration of mitoPTP activator atractyloside attenuated the effect of ethanol postconditioning, LDH release and infarct size were increased, and the recovery of hemodynamic parameters was inhibited. The expression of ALDH2 mRNA was decreased.

CONCLUSIONEthanol postconditioning has cardioprotection effect, which may be associated with upregulating mitochondrial ALDH2 mRNA expression and inhibiting the opening of mitochondrial permeability transition pore.

Aldehyde Dehydrogenase ; drug effects ; genetics ; metabolism ; Aldehyde Dehydrogenase, Mitochondrial ; Animals ; Ethanol ; pharmacology ; In Vitro Techniques ; Ischemic Postconditioning ; L-Lactate Dehydrogenase ; metabolism ; Male ; Mitochondria, Heart ; drug effects ; metabolism ; Mitochondrial Membrane Transport Proteins ; drug effects ; metabolism ; Mitochondrial Proteins ; drug effects ; genetics ; metabolism ; Myocardial Reperfusion Injury ; metabolism ; pathology ; prevention & control ; Myocardium ; metabolism ; pathology ; RNA, Messenger ; genetics ; Rats ; Rats, Sprague-Dawley

Objectives To explore the expression of the receptor for advanced glycation end products (RAGE) in pancreas and the serum concentration of RAGE in rats with acute necrotizing pancreatitis (ANP).Methods Sixty four male Spraque-Dawley rats were randomly divided into control group,ANP 6,18,24,36,48,72,96 h group with 8 rats in each group.The rat model of ANP was established by injecting 20％ L-arginine intraperitoneally at the dose of 250mg/100g body weight for twice at the interval of 1 h.Rats in control group were injected intraperitoneally with the same amount of saline.The pancreas samples were histologically examined by light microscope and scored.The amount of ascites,levels of serum amylase and RAGE was determined; Real-time PCR was performed to detect the expression of RAGE mRNA in pancreatic tissue.Results Pancreatic injuries aggravated with time.The amount of ascites increased from ( 1.98 ± 0.64) ml at 6h to (8.69 ±0.62)ml at 96 h.Serum amylase level began to increase at 6h after L-arginine intraperitoneal injection and reached the peak value at 18 h[(5069.88 ± 603.25 ) U/L],and returned to normal at 36 h.The serum concentration of RAGE and RAGE mRNA expression in pancreatic tissue were ( 18.33 ± 2.99) ng/ml and 0.41 ±0.13 in the control group.The corresponding values increased at 6 h in ANP group,which were (30.31 ±5.03) ng/ml and 1.57 ±0.19,and they were significantly higher than those in the control group (P ＜0.05) ; they reached the peak value at 24 h[( 105.41 ±21.31 ) ng/ml and 4.23 ±0.73],which were significantly higher than those in other ANP groups ( P ＜ 0.05 ) ; at 96 h they decreased to the lowest point [( 33.54 ± 6.96) ng/ml and 1.19 ± 0.19],which were still significantly higher than those in the control group (P ＜ 0.05 ).Conclusions The expression levels of RAGE in pancreatic tissues and serum level of RAGE increase within 36 h of ANP onset,then decrease gradually,but they are always higher than normal values.

Objective To investigate the effect of donepezil on subventricular zone ( SVZ) neuro-genesis related neurotrophic factors after cerebral infarction. Methods Mice were randomly assigned into three groups: vehicle-treated sham group (Sham+vehicle,n=18),vehicle-treated middle cerebral artery oc-clusion (MCAO) group (MCAO + vehicle,n=30) and donepezil-treated MCAO group (MCAO+donepezil, n=30). Middle cerebral artery occlusion( MCAO) was induced by thread-occlusion method. Nissl staining was used to measure the infarct volume and the modified neurological severity score(mNSS) was used to as-sess neurologic function and brain water content was detected to assess brain edema degree. Proliferative cells and neuroblasts were labeled with 5-bromodeoxyuridine ( BrdU) and doublecortin ( DCX). The SVZ BrdU+/DCX+cells were detected by immunofluorescence. The expression of glial cell line-derived neurotro-phic factor (GDNF),brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) were detec-ted by Western blot. Results The infarct volume of MCAO + donepezil group ((13. 33±4. 55)%) was sig-nificantly lower than that of MCAO + vehicle group ((31. 33±3. 93)%,t=7. 34,P<0. 05). The neurologic deficits were significantly ameliorated after donepezil treatment,and the brain water content of MCAO + done-pezil group ((71. 82±10. 18)%)was significantly less than that of MCAO + vehicle group ((85. 93± 7. 54)%,F=13. 480,P<0. 05). All differences were statistically significant (P<0. 05). The area of BrdU+/DCX+cells within SVZ of MCAO + vehicle group ((6. 16±1. 79)%) was significantly larger than that of sham + vehicle group ((2. 25±1. 09)%),and was fewer than that of MCAO+donepezil group ((16. 19± 2. 16)%,F=102. 756,P<0. 05). MCAO significantly promoted the expression of GDNF,BDNF and NGF within SVZ compared with sham operation,and donepezil increased these protein levels(F=15. 114,27. 121, 27. 398,P<0. 05). Conclusion Donepezil regulates neurogenesis via increasesing the expression of GDNF, BDNF and NGF within SVZ after cerebral infarction.

Objective To investigate the role of Src signaling pathway in neurogenesis promoted by choline acetyltransferase (CHAT) + neurons in the subventricular zone (SVZ) after ischemic stroke.Methods The eighty-four mice were randomly assigned into four groups:sham-operated mice treated with vehicle (Sham+vehicle,n=18),middle cerebral artery occlusion (MCAO)-operated mice treated with vehicle (MCAO+vehicle,n=22),MCAO mice treated with donepezil (MCAO+donepezil,n=21),MCAO mice treated with donepezil and Src inhibitor KX2-391 (MCAO+donepezil+KX2-391,n=23).Mice were subjected to the temporary MCAO model of ischemic stroke.Modified neurological severity score (mNSS) was used to assess neurologic function of the mice.Proliferative cells were labeled with Ki67,and neuroblasts with doublecortin (DCX).The expression of Ki67+/DCX+ in the SVZ was detected by immunofluorescence.The expression of Ki67,phospho-epidermal growth factor receptor (p-EGFR),p-Raf,Src and p-Akt in the SVZ were quantified by Western blot.Results MCAO+donepezil+KX2-391 group showed worse performance in the mNSS test than MCAO+donepezil group (P＜0.05).Ten days after MCAO,the number of Ki67+/DCX+ cells in the SVZ of MCAO+donepezil group was 125.33± 13.71/area,which was 71.67± 18.35/area in MCAO+ donepezil+KX2-391 group (P＜0.05).What's more,the expression of proteins Ki67,p-EGFR,p-Raf,Src and p-Akt in mice of MCAO+donepezil group was markedly increased,which was (1.39±0.23),(1.42±0.19),(0.88±0.13),(1.14±0.19),(1.04±0.18) and it was decreased in MCAO+donepezil+KX2-391 group,which was 0.84±0.26,0.94±0.26,0.73±0.15,0.71±0.18,0.81±0.19(P＜0.05).Conclusion CHAT+ neurons in SVZ may promote neurogenesis after stroke via Src-epidermal growth factor receptor (EGFR) signaling pathway.

To investigate the adjuvant effect of granulocyte macrophage colony stimulating factor (GM-CSF) in Flaviviridae virus DNA vaccines. After DNA immunization, the antibody levels of serum from mice were detected by ELISA and indirect immunofluorescence assay. Co-immunization of GM-CSF suppressed the immune responses induced by DV1 and DV2 candidate vaccines whereas enhanced the immune response induced by HCV C and E1 DNA vaccines. As genetic adjuvant for DNA vaccines, GM-CSF might display complex diversity on the immune responses: an augmentation or suppression due to different immunogens. Therefore, GM-CSF should be used with some cautions in clinic.
Adjuvants, Immunologic ; administration & dosage ; Animals ; Antibodies, Viral ; immunology ; DNA, Viral ; administration & dosage ; genetics ; immunology ; Dengue ; immunology ; prevention & control ; virology ; Dengue Vaccines ; administration & dosage ; genetics ; immunology ; Dengue Virus ; genetics ; immunology ; Female ; Granulocyte-Macrophage Colony-Stimulating Factor ; administration & dosage ; immunology ; Hepacivirus ; genetics ; immunology ; Hepatitis C ; immunology ; prevention & control ; virology ; Humans ; Immunization ; Mice ; Mice, Inbred BALB C ; Vaccines, DNA ; administration & dosage ; genetics ; immunology ; Viral Vaccines ; administration & dosage ; genetics ; immunology