Abstract:Objective:To evaluate the feasibility of implanting a new self-expanding valved stent for aortic valve implantation and its influence on coronary blood flow. Methods: We designed a self-expanding valved stent made from super-elastic memory nitinol alloy, with a tubular shape and a wide mesh in the cavate middle part. A valvular ring made of nitinol wire was sutured on the lower part. Fresh porcine pericardium was decellularized, treated with 0. 6% glutaraldehyde solution for 36 h, trimmed into leaflets, and sutured by hand into the valvular ring. The valved stent was pulled into a 14-French sheath by a silk and positioned in the left ventricle of isolated pig heart via the ascending aorta, and then deployed over the native aortic valves by pulling back the outer sheath. Water was injected into the ascending aorta by a silicon tube to evaluate the competence of the prosthetic heart valves and its effect on coronary flow. Results: The prepared valved aortic stent could be stably positioned over the native valves and could be removed after deployment. The prosthetic heart valves showed a satisfactory function and had no influence on coronary flow and mitral valve motion. Conclusion: This self-expanding valved stent is well-designed and allows for aortic valve implantation over the native valves without interfering the coronary flow; it can be evaluated further in vivo.

Abstract:Objective:To develop valved aortic stent and to assess the feasibility of its trans-catheter implantation to the ascending aorta in vivo. Methods: We designed self-expandable nitinol stents (15-19 mm in diameter) according to the internal diameter of the ascending aorta of Chinese miniswines. Bovine pericardium was cross-linked with 0. 6% glutaraldehyde solution for 36 hours, and then was shaped and sutured into the stents. Fluid passing test, pre-releasing test and static test of pressure in the tube were performed in all devices. The devices were tried to be inserted percutaneously through common iliac artery to deploy in the ascending aorta in 7 Chinese miniswines. Results: In vitro test showed that the closure of the percutaneous valved aortic stent leaflets was satisfactory, and the fluid flow was not restricted in the opposite direction. The devices could be released through the catheter, expanded completely, and be fixed rapidly in the tube. The devices were deployed using 12F-16F catheter and were inserted through common iliac artery in 6 of the 7 Chinese miniswines. All devices were implanted in the desired position, with 6 expanded completely and fixed rapidly in the ascending aorta. One did not expand completely and was displaced. Animals were executed and dissected after 24 hours. All the devices were fixed in the ascending aorta and there were no thrombus. Conclusion: The function of the percutaneous valved aortic stent is satisfactory. The size of compressed device is suitable for catheterization. It can be successfully implanted into the ascending aorta by using a retrograde method through common iliac artery.

Abstract:Objective:To observe whether transforming growth factor-beta 1 (TGF-β1) can improve the mechanical properties of tissue engineered heart valve (TEHV) prepared by TGF-β1 and myofibroblasts.Methods: Myofibroblasts were isolated,cultured,identified,and seeded onto the decellularized aortic valve leaflet.In the experimental group,TEHV were cultured with DMEM containing 10 ng/ml TGF-β1 for 14 days.In the control group,TEHV were cultured with DMEM only for 14 days.The contents of lysyl oxidase (LOX) and hydroxyproline,the expression of LOX and COLL-1 mRNA,and the mechanical properties of the TEHVs were analyzed in each group.Results: The contents of LOX and hydroxyproline,expression of LOX and COLL-1 mRNA,Max-load,and Max-stress were significantly higher in the experimental group than those in the control group (all P<0.05).However,the experimental and control group showed comparable values of Max-strain and elastic modulus.Conclusion: TGF-β1 can increase expression of LOX and COLL-1 mRNA in the seeded cells during TEHV construction,increasing the production and cross-linking of collagen,and improve the mechanical properties of the TEHV.

Abstract:Objective:To evaluate the surgical efficacy of valve replacement for severe paravalvular leakage(PVL) by echocardiogram. Methods: From June 2000 to December 2007, 26 patients with severe PVL were admittted to our hospital. The patients included 19 males and 7 females, with a mean age of 48 years (ranging 33 to 68 years). Severe PVL was reported in 11 cases after aortic valve replacement and 15 mitral valve replacement. The grades of cardiac function was in NYHA Ⅲ(16 cases) and Ⅳ(10 cases). Preoperation echocardiogram combined with intraoperation findings was the main diagnosis approach. Nineteen patients (73.1%) underwent a second valve replacement (RO group) and 7 (26.9%) were managed conservatively (MC group). Results: One patient died of MODS early after operation in the RO group. During 2 months to 8 years follow-up (mean 2.7 years), one patient had recurrence of paravalvular leakage 2 months later and died of heart failure 5 months later after refusing a second operation. In MC group, one patient died of multiple organ failure in hospital; the rest died within 6 months after operation. Conclusion: Surgical treatment for patients with echocardiogram-diagnosed severe PVL should be performed as early as possible. The mortality and morbidity of conservative therapy are extremely high. Re-operation can greatly improve the long-term survival of the patient and the heart function.

Abstract:Objective:To investigate the surgical procedure for mitral valve prolapse complicated by infective endocarditis.Methods: From June 2000 to December 2007,40 patients with mitral valve prolapse complicated by infective endocarditis received operation in our hospital.The patients included 30 males and 10 females,with a mean age of 39.2 years (ranging 13-63 years).The positive blood culture rate was 42.5% before operation.Combination of echocardiogram with post-operative pathology was the main method for diagnosis.The grades of cardiac function of the patients were in NYHA Ⅱ(15 cases),Ⅲ(21 cases)and Ⅳ(4 cases).Mitral valve repair was performed in 5 patients and mitral valve replacement was done in 35 cases,all with artificial mechanical heart valves.Results: One patient died of renal failure early after operation.One patient had complete AV block and received pacemaker implantation.All the patients had normal body temperature on discharge.During follow-up (mean 2.7 years,ranging 6 months to 8 years),39 patients survived without later mortality,recurrence of endocarditis and paravalvular leakage.Conclusion: Surgical treatment for patients with mitral valve prolapse complicated by progressive moderate or severe mitral regurgitation and infective endocarditis should be performed as early as possible.Radical debridement of the infected tissues and application of sensitive and high dose of antibiotics are the keys for preventing postoperative endocarditis recurrence.Replacement or annuloplasty should be chosen according to the quality of the valve during surgery.The results of mechanical prosthetic valve are excellent.

Abstract:

Abstract:Objective:To study the changes of PTEN gene expression in radiationinduced bystander cells.Methods: The irradiated cells and nonirradiated cells were cocultured in a ratio of 11.The culture medium of irradiated cells was used to culture nonirradiated cells to create two bystander cell models. The expression of PTEN mRNA and protein in the bystander cells,irradiated cells,nonirradiated cells was compared.Results: The protein expression of PTEN in the irradiated cells was negatively associated with the irradiation dose.The downregulation degree of PTEN protein was related to the different treatments of cells.The most prominent downregulation was found in the bystander cells cultured with medium of irradiated cells.The downregulation of PTEN protein in the two kinds of bystander cells was more severe than that in the irradiated cells(P<0.01).Conclusion: PTEN protein expression can be influenced by low dose radiation and the bystander effect of radiation.

Abstract:Objective:To investigate the relationship of chemokine receptor with the development and progression of primary biliary cirrhosis (PBC). Methods: Real-time PCR and flow cytometry were used to examine the mRNA and protein expression of chemokine receptor 1 (CCR1),CCR3 and CCR5 in the peripheral blood mononuclear cells (PBMCs) of 60 patients with PBC,60 patients with hepatitis B-related cirrhosis, and 60 normal controls. Total bilirubin (TBIL) and γ-glutamyltransferase (γ-GT) levels were determined in the patients with PBC and normal controls,and their correlation with chemotactic factors was also analyzed. Results: Both the mRNA and protein expression levels of CCR1,CCR3 and CCR5 in the PBMCs were significantly lower in PBC patients than those in the other two groups (P<0.05), and there were no significant differences between the latter two groups. The mRNA and protein levels of CCR1,CCR3 and CCR5 were significantly lower in patients with stage Ⅲ and Ⅳ PBC than those with stage Ⅰ and Ⅱ PBC. CCR1 protein expression was correlated with TBIL levels in PBC patients(r=- 0.445,P<0.01), but not with γ-GT(r=-0.230,P>0.05). CCR3 protein was not linearly correlated with TBIL level (r=-0.173,P>0.05),but was correlated with γ-GT(r=-0.295,P<0.05). Expression of CCR5 protein was negatively correlated with both TBIL and γ-GT levels(r=-0.531,P<0.01; r=-0.665,P<0.01). Conclusion: CCR1,CCR3 and CCR5 expression is associated with the development and progression of PBC; they may be involved in the regulatory mechanism of PBC,which may cast new lights on the diagnosis and prevention of PBC.

Abstract:Objective:To explore a novel method for cultivation of the endothelial cells(EC) from infantile hemangiomas(IH) in vitro and observe the biological character of cultured endothelial cells.Methods:Fresh operative specimens were obtained from infantile hemangiomas.The endothelial cells of IH were cultured by explant combined with trypsin-digestion technique.Immunohistochemical staining of EnVision method was carried out to identify the cultured cells.The purity of endothelial cell was examined by flow cytometry analysis of FITC-CD34.The biologic characters of endothelial cells were observed under inverted phase contrast microscope.Results:Endothelial cells were successfully cultured from 8 IH specimens of all the 14 explants.The morphology of cultured endothelial cells included two types:polygonal cells and fusifourm cells.The cultured cells were homogenously positive for EC markers-vWF or CD34,indicating their EC origin.Tube formation was found in endothelial cells of IH.The proportion of CD34+ cells was 76.28% in cultured endothelial cells as detected by flow cytometry analysis.Conclusion:ECs can be successfully isolated and cultured from infantile hemangiomas by explant combined with trypsin-digestion technique; the cultured cells have some characters of endothelial cells.

Abstract:Objective:To investigate the acute damage of the nigrastriatal system in SAMP8 mouse after treatment with MPTP and its relationship with microglial activation.Methods: Totally 57 male SAMP8 mice were randomly divided into two groups,control group and MPTP group.Mice were sacrificed (each time 6-9 mice) at 6 h,24 h,3 d,and 8 d after the first injection in each group.Mice were subcutaneously injected with normal saline or MPTP (20 mg/kg) at an interval of 2 h for 4 times.The changes of spontaneous activity of mice were observed after injection.The changes of TH+ (tyrosine hydroxylase positive) neuronal numbers in the substantial nigra,TH-ir (tyrosine hydroxylase immunoreactivity), and microglial activation in striatum were examined by immunohistochemistry; striatal dopamine (DA) levels were determined by HPLC.Results: The spontaneous activity of SAMP8 mice was decreased significantly after the third injection,and recovered at 48 h after the first injection. Compared with the control group,the TH+ neurons in MPTP group decreased by 7.06% at 6 hours (P=0.235),by 12.79% at 24 hours(P<0.05),by 22.49% at 3 days(P<0.01),and by 42.39% at 8 days(P<0.001); there was significant difference in the TH+ neurons between the 3 days and 8 days (P<0.05).The corrected optical densities (COD) of TH-ir in the striatum in MPTP group were significantly lower than those in the control group at different time points (6 h,\[P<0.05\],24 h\[P<0.01\],3 d\[P<0.001\],8 d\[P<0.001\]); there was significant difference between the 24 h and 3 days groups (P<0.05).Compared with the control group,the striatal dopamine (DA) levels decreased by 79.09% at 6 hours ( P<0.001),by 80.3% at 24 hours (P<0.001),by 86.6% at 3 days (P<0.001),and by 81.0% at 8 days (P<0.001); there were no significant difference between the 24 h,3 days,and 8 days.The immunoreactivity of microglial greatly increased at 24 hours,further activated at 3 days,and largely abated at 8 days after MPTP injection.Conclusion: MPTP can cause acute damage to substantia nigra of SAMP8 mice,resulting in reduced spontaneous activity and dopaminergic neurons loss; the activation of microglial might be related to the nigrostriatum damage of MPTP-SAMP8 mice.

Abstract:Objective:To study whether interleukin (IL)-18 is involved in the activation of monocytes through direct contact with T cells and the related intracellular mechanism. Methods: T cells and monocytes were isolated and purified from the peripheral blood of healthy donors by magnetic beads. Phytohemagglutinin (PHA) pre-stimulated T cells were fixed by 1% paraformaldehyde and were then co-cultured with monocytes at a T cellmonocyte ratio of 41. TNF-α and IL-18 levels in the supernatants were assayed by ELISA. Expression of IL-18 receptor α chain (IL-18Rα) on the surface of monocytes was analyzed by flow cytometry.Results: Monocytes activated by PHA-stimulated T cells produced significantly more TNF-α than by unstimulated T cells; non-cultured T cells or monocytes hardly produced any TNF-α. Upon direct cellular contact, PHA pre-stimulated T cells also up-regulated IL-18Rα expression on the surface of monocytes and induced IL-18 production in monocytes, which could be suppressed by nuclear factor (NF)-κB inhibitor (N-acetyl-L-cysteine, NAC) or phosphatidyl-inositol (PI) 3 kinase inhibitor (LY294002), but not by mitogen activated protein kinase (MAPK) inhibitor (SB203580). Neutralizing anti-IL-18 monoclonal antibody dose-dependently inhibited the production of TNF-α by monocyte-stimulated T cells. IL-18 failed to induce TNF-α production by cultured monocytes alone, while dose-dependently enhanced TNF-α production in monocyte-stimulated T cells, which could be inhibited by NAC or LY294002, but not by SB203580.Conclusion: By direct cellular contact T cells can stimulate monocytes to produce TNF-α and IL-18, up-regulate IL-18 receptor expression in monocytes, and activate intracellular NF-κB and PI3 kinase pathways. IL-18 can enhance T cell ability to stimulate TNF-α production by monocytes, which is dependent on the activation of NF-κB and PI3 kinase pathways.

Abstract:Objective:To investigate the changes of vasoconstrictor and vasodilator functions of isolated thoracic aorta in the rats with obstructive jaundice,so as to study the mechanism for the functional changes of the aorta in rats with obstructive jaundice.Methods: Sixty male SD rats were randomly divided into bile duct ligation (BDL) group and sham operation (SO) group.The thoracic aortas were isolated at 3,7 and 14 d after surgery and the vasoconstrictor responses induced by high potassium,norepinephrine (NE) and phenylephrine (PE) gradient and the vasodilator response to SNP were tested.Another 40 male SD rats were randomly divided into BDL three-day group,BDL seven-day group,BDL 14-day group and sham operation (SO) group.The expression of α1D -AR protein in the thoracic aorta was assessed by Western blotting.Results: The vasoconstrictor responses of thoracic aorta rings in high potassium,NE,PE,and BDL rats were weaker than those in the SO group.The vasodilator response induced by SNP in the BDL group was greater than that in the SO group.The expression of α1D -AR protein in the BDL group was weaker than that in the SO group,and the expression decreased with the prolongation of obstructive time.Conclusion: The systolic and diastolic functions of isolated thoracic aorta rings are changed in cholestatic rats; the weakened systolic function might be a result of decreased expression of α1D-AR albumen.

Abstract:Objective:The imaging diagnosis of early liver abscess is difficult.This study is to evaluate the diagnostic value of DWI,T2WI and dynamic enhanced MR imaging for early liver abscess.Methods: DWI,T2WI and dynamic enhanced imaging scans were performed in 17 patients with 17 early liver abscesses.The signal intensities and ADC values of necrotic area,non-necrotic area and normal liver were measured and compared.Results: The ADC value of the necrotic areas of liver abscesses (\[0.88±0.09\] mm2/s) was significantly lower than those of normal liver (\[1.31±0.12\] mm2/s,P<0.05) and non-necrotic area of liver abscesses (\[1.43±0.18\] mm2/s,P<0.05); there was also significant difference between the ADC values of the normal liver and non-neocrotic area (P<0.05).The necrotic areas had a hyperintensity characteristic on DWI,T2WI and a hypointensity characteristic on T1WI; no enhancement was found on dynamic enhanced imaging.The non-necrotic areas had moderate hyperintensity on DWI,T2WI and hypointensity on T1WI; there was obvious enhancement on dynamic enhanced imaging.Conclusion: The early liver abscess is characterized on magnetic resonance imaging.The DWI scan is helpful for diagnosis of early liver abscess.

Abstract:Objective:To explore a scientific,complicated sampling method and corresponding formulas for sensitive question survey.Methods:Cochran W.G.’s classic sampling theories,two randomized response technique(RRT) models,total probability formulas, and properties of mean and variance were used in this study.Results:Formulas for the estimation of the population proportion and its variance for dichotomous sensitive questions on Greenberg model in cluster sampling and stratified cluster sampling were deduced.Formulas for the estimation of the population mean and its variance for quantitative sensitive question on the additive constant model in cluster sampling and stratified cluster sampling were deduced.Our survey methods and formulas were successfully applied in surveying the pre-marriage sex and cheating in examination in Soochow University.Conclusion:Our survey methods and formulas on two RRT models for sensitive question survey in cluster sampling and stratified cluster sampling have high reliablility.

Abstract:Objective:To assess the safety and efficacy of simultaneous intravenous plus intracoronary administration of tirofiban bolus for patients with acute ST-elevation myocardial infarction(STEMI) undergoing primary percutaneous coronary intervention (PCI).Methods: Forty-three patients with acute STEMI ready to receive primary PCI were randomly divided into tirofiban IV group (intravenous tirofiban bolus only before stent deployment,n=22) or tirofiban IV&IC group (intravenous plus intracoronary administration of tirofiban bolus simultaneously,n=21).The thrombolysis in myocardial infarction trial and perfusion of the myocardium were observed before and after PCI.Major adverse cardiovascular event (MACE),hemorrhage event,and thrombocytopenia were observed during hospital stay; MACE was also observed 30 days after PCI.Results: The clinical characteristics and baseline angiographic findings were similar in the two groups.After PCI,no difference was observed in the final TIMI flow grade 3,CTFC≤27,sumSTR≥70% between the two groups (P=0.951,0.933,0.666,respectively).There was no significant difference in the frequencies of MACE (P=0.101) and the left ventricular ejection fraction between the two groups (P=0.694).No major hemorrhage or severe thrombocytopenia were found in the two groups during hospital stay.The total rate of bleeding was also similar in the two groups (P=0.558).The frequencies of MACE were similar in the two groups 30 days after operation.Conclusion: Simultaneous intravenous and intracoronary administration of tirofiban bolus is safe for STEMI patients undergoing primary PCI; the short-term efficacy is similar to that of intravenous administration only. PCI，and the short-term efficacy is similar to intravenouse administration only.

Abstract:Objective:To observe the effect of Rosiglitazone (RGTZ) on oxygen free radical and biochemical parameters of aged rats,so as to establish a basis for anti-aging study.Methods:The 24-month-old naturally aged SD rats were randomly divided into the control group (CONT),the RGTZ group and the caloric restriction group(CR).The RGTZ group was given intragastric administration of RGTZ (4 mg·kg-1·d-1) and the CR group was given 60% of the diet that of the CONT group.The rats were killed 12 weeks later and the serum malondialdehyde(MDA) content,superoxide dismutase(SOD) activity and the blood biochemistry parameters were examined.Results:The blood glucose (GLU),aspartate transaminase(AST), alamine transaminase(ALT),serum creatinine (SCr),and blood urea nitrogen(BUN) were within the normal range in all groups.Compared with the CONT group,blood cholesterol (CH) in RGTZ group was lower,but with no significant difference.The serum triglyceride(TG) of both RGTZ and CONT groups decreased markedly than those in the CONT group(P＜0.05).The activities of SOD and MDA were improved in RGTZ and CR group compared with the control group.Conclusion:RGTZ can regulate the lipid metabolism and attenuate the oxidative damage in aged rats,indicating its anti-aging effect.

Abstract:Objective:To observe the clinical effect and adverse reaction of capecitabine as first-line monotherapy in elderly patients with stage Ⅱa breast cancer.Methods: From June 2002 to June 2005,71 elderly patients with stage Ⅱa breast cancer received chemotherapy(different scheme: capecitabine group and CEF group) after operation.The efficacies and adverse reactions were evaluated and compared between the two groups.Results: The 3-year and 5-year survival rates of patients in capecitabine group were 97.06％ and 94.12％,respectively; the relapse rate was 5.88%; all were comparable to those of CEF group. One of the advantages of capecitabine was its oral administration. The adverse effect of capecitabine was mainly hand-foot syndrome,with an incidence of 82.35%,but was tolerable. The gastrointestinal reaction and bone marrow repression in capecitabine group were significantly lower than those in the CEF group(P<0.01). There was no giving up of treatment due to adverse reactions or fear of chemotherapy in our group. Conclusion: Capecitabine is effective and safe in the treatment of elderly patients with stage Ⅱa breast cancer; it is easy to take,with less adverse effects and better patient compliance.

Abstract:Objective:To develop a new method for the simultaneous determination of two hydrophilic components and two lipophilic components of Radix et Rhizoma Salviae Miltiorrhizae.Methods: The HPLC-DAD method was employed using a column of Agilent Zorbax TC C18 (4.6 mm×250 mm, 5 μm) with a mobile phase of methanol -2% acetic acid.The gradient elution program was as follow:0-15 min, 30% B-40% B; 15-20 min, 40% B-60% B; 20-25 min, 60% B-90% B;25-40 min, 90% B.The detection wavelength was set at 281 nm and the temperature was 35℃.Results: The linearity was obtained over 3.76-120.20 μg·ml-1(r=0.999 9) for rosmarinic acid, 34.20-109 4.5 μg·ml-1(r=0.999 9) for salviamolic acid B, 0.64-20.32 μg·ml-1(r=0.999 9) for clyptotanshinon,and 1.02-32.72 μg·ml-1(r=0.999 6) for tanshinone ⅡA.The RSDs of precision and stability of the sample were both less than 1% in 48 hours.The average recovery was between 99.72%-100.63%.Conclusion: The present method is simple and has satisfactory efficacy; it can simultaneously determine multiple hydrophilic and lipophilic bioactive components in Salvia miltiorrhiza from different areas.

Abstract:Objective:To isolate and identify phenolic glycosides and lignans from the rhizomes of Curculigo orchioides Gaertn.Methods: Phenolic glycosides and lignans were isolated by silica gel,Sephadex LH-20 chromatography and semi-preparative HPLC methods.The structures of the isolated compounds were identified by physiochemical and spectral analysis/Results: Five phenolic glycosides,one lignan and one sitosterol were isolated and identified from Curculigo orchioides Gaertn,namely, 2,6-dimethoxy benzolic acid(1),curculigoside A(2),curculigoside B(3),curculigine A(4),4-dichlorine-5-hydroxyl-3-methylphenol-1-O-β-D-glucopyranosyl-(1→6)-β-D-gluco-pyranosede(5),3,3′,5,5′-tetramethoxy-7,9′:7′,9 -diepoxylignan -4,4′-di-O-β-D-glucopyranoside(6),and β-sitosterol(7).Conclusion: Seven compounds have been isolated from Curculigo orchioides Gaertn; compound 5 is a new chlorine-containing phenol,and is named as curculigine D.

Abstract:Objective:To study the antifungal activity of triazole alcohols by introduction of cyclopropyl as side chain.Methods: Nine title compounds were synthesized and characterized by 1HNMR,MS spectra and element analysis.Eight fungi were used for in vitro anti-fungal test.Results: All of the title compounds showed antifungal activities of different extents,especially to the deep infection ones,and they had a MIC value < 0.125 μg/ml against Candida albicans,showing an anti-fungal activity 4 times higher than that of fluconzole and similar to that of totraconazaole.Conclusion: 1-(1H-1,2,4-triazole-1-yl)-2-(2,4-difluoro-phenyl)-3-\[N-cyclopropyl-N-(3,4-dichlorobenzyl) amino\]-2-propanols(6f) has a better activity ratio and is worth further studying.

Abstract:Objective:To prepare and characterize nobilisideA freeze-dried liposome. Methods: The nobilisideA liposomes were prepared using a film dispersion method followed by a freeze-dried technique. The freeze-dried liposomes were characterized with regard to the drug content, entrapment efficiency, the particle size, ζ potential, and its stability and hemolytic rate in glucose transfusion. Results: Through optimized technique, the prepared nobilisideA freeze-dried liposome, with sucrose as protective agent, had satisfactory structure and redissolubility. The contents of nobilisideA liposome before and after freeze-drying were 108.3% and 108.6%, the entrapment efficiency were 98.4% and 97.8%, the particle sizes were 89.9 nm and 115.8nm, and the ζ potentials were -19.9mV and -15.9mV, respectively. The liposome content, entrapment efficiency, particle size and hemolytic rate were stable within 8 h during glucose transfusion. Conclusion: NobilisideA freeze-dried liposomes have a narrow size distribution range, a high entrapment efficiency and a stable character, making it a promising candidate for nobilisidesA liposome.

Abstract:Amyotrophic lateral sclerosis is a chronic neurodegenerative disorder characterized by selective death of motor neurons and progressive paralysis. Many hypotheses have been proposed to explain its pathogenesis. In recent years, one of the most studied hypotheses was the inflammatory response accompanying the motor neuron death. Microglia and its interactions with motor neurons play important roles in the development and progression of the inflammatory responses and the disease itself, which results in different new and potent therapeutic strategies of great clinical value.

Abstract:As a tropical infectious disease,the dengue fever is now one of the most important arthropod-borne diseases from a medical and public health perspective.Antibody-dependent enhancement of dengue virus infection and the unclear pathogenesis mechanism hamper the prevention and treatment of the disease.No efficient preventative and therapeutic drugs are available now,but much progress has been made in the last few years in the drug prevention and therapy of dengue fever.To better understand the current situation,this article reviews the recent advances in the development of anti-dengue vaccines,small-molecule drugs,monoclonal antibodies and the relevant problems.

Abstract:Objective:To introduce a new method which can avoid the interference of ABCD1 pseudogenes in the molecular diagnosis of X-linked adrenoleukodystrophy. Methods:The coding regions of ABCD1 gene of 3 unrelated Chinese patients with X-linked adrenoleukodystrophy were amplified from the total RNA of peripheral blood by long distance RTPCR; the product was further amplified in 4 segments in a second round PCR; and the PCR products were purified and directly sequenced.To confirm the mutations,the genomic DNA from peripheral blood cells of the patients was analyzed by direct sequencing after amplification of the ABCD1 genes by nested PCR,in which the product of the first round PCR covered the fragment starting from exon 6 and ending at 3′UTR of the ABCD1 gene.Results:The 3 Chinese patients with X-linked adrenoleukodystrophy had 3 different base substitutions(2235C>T,2065C>T and 2190A>T)in the ABCD1 genes of the 3 probands and their mothers,which resulted in 2 missense mutations (R617C and P560L) and one nonsense mutation (K602X).Conclusion:Nested PCR can rapidly and efficiently avoid the interference of ABCD1 pseudogenes in the molecular diagnosis of X-ALD.

Abstract:目的:通过动物体内实验研究羟基丁酸-羟基戊酸共聚物(PHBV)在小鼠体内的降解行为和组织相容性,进一步探讨生物可降解材料PHBV作为生物医用材料的应用。方法:将PHBV(其中HV含量为9.5%)和对照材料聚乳酸(PLA)植入28只KM小鼠皮下,分别于术后1、2、4、6、8及13周取出2组植入材料,一组行肉眼观察,取组织切片后行H-E染色,然后在光学显微镜下观察;另一组进行扫描电镜(SEM)观察。结果:PHBV组在植入56 d后动物体内炎症反应已经消失,组织相容性较同期PLA组良好。90 d内机体未对PHBV膜造成严重的侵蚀和破坏,而且在植入PHBV材料的部位均无脓肿形成及组织坏死发生。结论:PHBV在动物体内降解速率缓慢,具有良好的组织相容性。

Abstract:目的:建立HPLC-MS法测定人体血浆中多奈哌齐的药物浓度,研究口服盐酸多奈哌齐分散片在健康人体的生物等效性。方法:20名健康志愿者单剂量交叉口服受试制剂盐酸多奈哌齐分散片或参比制剂盐酸多奈哌齐片5 mg。采用HPLC-MS测定其不同时间点血药浓度,计算主要药代动力学参数及相对生物利用度,判断其是否具有生物等效性。结果:在0.1~16 ng·ml-1范围内,线性关系良好,最低定量限为0.1 ng·ml-1。受试制剂和参比制剂的主要药代动力学参数:t1/2分别为(57.38±15.27)、(59.27±27.02) h; Tmax分别为(3.4±1.42)、(3.75±2.73) h; Cmax分别为(9.56±2.4)、(9.54±2.73) ng·ml-1 ;AUC0-t分别为(602.94±190.43)、(623.25±299.76) ng·h·ml-1。受试制剂的相对生物利用度为(105.2±43.2)%。两制剂的主要药代动力学参数无显著性差异。结论:2种制剂具有生物等效性。

Abstract:目的:建立LC-MS法测定人血中硫普罗宁的药物浓度,并对2种制剂进行生物等效性评价。方法:20例健康受试者单剂量交叉口服400 mg硫普罗宁供试制剂或参比制剂后,采用LC-MS测定人血中不同时间点硫普罗宁的浓度,计算其药代动力学参数和相对生物利用度,评价两制剂的生物等效性。结果:硫普罗宁供试制剂和参比制剂主要药代动力学参数如下:Cmax分别为(2.31±0.64)、(2.33±0.83) μg/ml,AUC0-15分别为(6.70±1.57)、(6.68±1.53) μg·h·ml-1,Tmax分别为(3.1±0.7)、(3.7±0.6) h,t1/2分别为(3.08±0.86)、(2.90±0.84) h。本方法在0.04～10.0 μg/ml浓度范围内线性关系良好。最低定量浓度为0.04 μg/ml,两制剂主要药动学参数经统计学检验无显著性差异。结论:本方法简单、快速、准确,2种制剂具有生物等效性。

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