Objective To determine the roles of MyD88 and Trif,critical adaptor proteins for TLR signaling,in production of donor-specific antibodies (DSA) and memory T cells in a presensitized mouse cardiac transplant model.Methods Skin grafts from Balb/c mice were transplanted into either wild type B6 mice or B6 Myd88 and Trif double knockout mice (Myd88/Trif DKO).The recipients were subsequently transplanted heterotopically with cardiac grafts from the same donors two weeks after skin transplantation.Plasma DSA levels and spleen phenotypical analysis were performed prior to heart transplant or at time of cardiac rejection by using flow cytometry.Results Recipients presensitized with skin grafts developed accelerated cardiac allograft rejection in the absence of Myd88 and Trif.However,plasma DSA,especially IgG2,was significantly decreased (P＜0.05) in Myd88/Trif DKO mice,compared to that in Wild Type mice at 2nd week after skin transplantation.The production of DSAs including all IgG subtypes was further reduced 3 days following heart transplantation in the Myd88/Trif DKO.In addition,MyD88/Trif DKO mice had impaired ability to generate memory T cells,as percentages of both CD44hi CD4+ and CD44hi CD8+ were significantly lower in the DKO than in Wild Type mice (P＜0.01,P＜0.05).Conclusion Simultaneous ablation of MyD88 and Trif in recipients significantly decreases the production of serum DSAs and spleen memory T cells following allogeneic skin and heart transplantation,supporting a crucial role of TLR signaling in adaptive immune responses in organ transplantation.

Objective　To investigate the diagnose and therapy of patients with smooth muscle tumors (SMTs) of gstrointestinal tract (GI). Methods　A retrospective analysis was made on the clinical and pathological data of 92 patients with SMTs of GI admitted from 1982 to 1999 in Nanfang Hospital. Results　Location of the lesion: 41 cases in stomach, 44 in small intestine, and 7 in large bowel. Adjuvant examinations: BUS was performed on 63 cases with positive findings in 31; CT on 27 cases with positive findings in 20; DSA on 29 cases with positive findings in 27; barium series on 45 with positive findings in 28; and small intestinoscopy on 11 cases with pasitive findings in 2. Conclusions　DSA is the most effective method in diagnoses of SMTs of GI, especially for small intestinal leiomyoma. The primary treatment of GI-SMTs is surgical resection.

Objective To investigate the relationship between isolated nocturnal hypertension and left ventricular hypertrophy. Methods In the inhabitants of 14 villages in Jingning County, Zhejiang Province, we performed 24-hour ambulatory blood pressure monitoring with SpaceLab monitors and measured 12-lead resting electrocardiogram using an electronic recording system of GE company, Left ventrieular hypertrophy was diagnosed with the criteria of Sokolow-Lyon voltage amplitude and Cornell product. Isolated nocturnal hypertension was defined as a nighttime ( from 22:00 to 4:00) blood pressure of ≥ 120/70 mm Hg( 1 mm Hg = 0. 133 kPa). Isolated daytime ( from 8:00 to 18:00) hypertension was a diurnal blood pressure of ≥ 135/85 nun Hg. When both conditions were present or absent, subjects were classified either as having combined day-night hypertension or as normotensive on ambulatory measurement. Analysis of variance and multiple regressions were used for statistical analysis. Results 647 participants (53.9% being female,average age 47. 8 years) included 72 patients with isolated nocturnal hypertension, 33 with isolated daytime hypertension and 248 with day-night sustained hypertension. Compared with normotensive subjects, patients with isolated nocturnal hypertension and day-night sustained hypertension had a higher Sokoiow-Lyon voltage amplitude and Comell product. However, after adjustment for sex, age, body mass index, drinking and smoking habits, serum total cholesterol, fasting blood glucose and the use of antihypertensive drugs, only day-night hypertensive patients had a significantly higher Sokolow-Lyon voltage (32. 8 mV, P =0. 0003 ) and Cornell product (1371 mV×ms, P =0.0004) than normotensive subjects (29.0 mV, 1114 mV×ms).Regardless of whether Sokolow-Lyon or Cornell criteria were used, both nighttime and daytime systolic and diastolic blood pressure were independent risk factors of left ventricular hypertrophy (P < 0. 01 ). However,the prevalence of left ventricular hypertrophy in patients with isolated nocturnal hypertension ( 23.6% ) study was not statistically different from that in normotensives ( 17.4%, P = 0. 24). Conclusion In our current cross-sectional study, isolated nocturnal hypertension was not independently related to left ventricular hypertrophy diagnosed with ECG criteria.

Objective To discuss the curative effect of transplantation using donation after cardiac death (DCD) according with Chinese standard Ⅲ (C-Ⅲ).Methods The organs were obtained from 4 DCDs from 2011 to 2012,and the clinical data of DCD transplantation were retrospectively analyzed.Withdrawal of life support occurred in the operating room.Donor warm ischemia time was 7-15 min.Results The biopsy of liver was performed on the 3rd DCD.Eight cases were subjected to renal transplantations,and 3 to liver transplantations.One patient exhibited delayed graft function of the kidney from the 4th DCD.All patients made an uneventful recovery and were discharged from the hospital without rejection or surgical complication.They were followed up in outpatient department.Conclusion The use of DCD according with C-Ⅲ is an effective way to increase the number of organs available for transplantation,and can obtain satisfactory effects.

Objective To explore the expression level of Tim-3,the marker of activated T_H 1 cells.in T lymphocytes in different sites from recipients with acute rejection.Methods The model of cervical heterotopic heart transplantation was established in mice Two groups were get up:the isograft group(C57BL/6→C57BL/6) and the allograft group (Balb/c→C57BL/6).Lymphocytes were isolated from peripheral blood,spleens,draining lymph nodes and grafts 3 or 6 days after transplantation.The expression of TIM-3 in CD4~+ and CD8~+ T subsets was detected by flow cytometry.Results There was no significant difference in Tim-3~+/CD4~+ and Tim-3~+/CD8~+ ratio in peripheral blood or spleens between two groups.As compared with the isograft group,the proportion of Tirn-3~+/CD4~+ cells was slightly elevated in draining lymph node(P<0.05),but the percentage of Tim-3~+/CD4~+ cells had no significant change between 3 days and 6 days in the allograft group(P>0.05).The expression of Tim-3 in CD4~+ and CD8~+ of graft infiltrating T cells was obviously increased in allograft group(P<0.01),and it was significantly (P<0.01) up-regulated on the 6th day as compared with that on the 3rd day.Conclusion The dynamic changes of Tim-3 expression in T lymphocytes in draining lymph node and graft were correlated with the progresston oi acute rejection in mice.

Objective To investigate the effects of T. gondii soluble tachyzoite antigen (STAgs) on the survival time of mouse heart allograft and the possible mechanism. Methods The STAgs were prepared by pulverizing T. gondii tachyzoite with ultrasound on ice. Cervical heterotopic heart transplantations were done by using Balb/c mice as donors, and C57BL/6 mice as recipients.The recipients were classified randomly into three groups: syngeneic group, acute rejection group and STAgs-treated group. The recipients in acute rejection group and STAgs-treated group were injected subcutaneously with 0. 1 ml PBS and 0. 1 ml (5 μg) STAgs at the 4th day before transplantation respectively, and those in syngeneic group were not subjected to any treatment. The grafts were observed daily by cervical palpation, and the total cessation of cardiac contraction was defined as the endpoint. The heart allografts were harvested at the 7th day after transplantation for pathological examination and immunohistochemical staining for CD4+ T, CD8+ T. Results The recipients in syngeneic group were all alive at the 100th day after transplantation. The average survival time in acute rejection group and STAgs-treated group was (6.7± 0.5) days and (70.8± 3.5) days,respectively (P＜0.05). HE staining showed that the rejection on the 7th day after transplantation in syngeneic group, acute rejection group and STAgs-treated group was fallen into 0 degree, Ⅲ-Ⅳ degree and 0- Ⅰ degree, respectively. Immunohistochemical staining revealed that the CD4+ T and CD8+T were markedly down-regulated in STAgs-treated group as compared with those in acute rejection group. Conclusion T. gondii STAgs can significantly prolong the survival time of mouse heart allograft and inhibit the rejection probably by changing the ratio of TH1/TH2, or inhibiting the effect of dendritic cells by inducing the lipoxin A4.

Hemoglobin-loaded nano-sized particles with oxygen carrying capacity were prepared. All experiments were performed using biodegradable polymer poly (polyepsilon-caprolactone) (PCL) as matrix polymer. Optimized preparation parameters led to nanoparticles with well-defined characteristics such as size <200 nm, P50 27 mmHg and high encapsulation efficiency up to 99.4%. The results of in vitro and vivo studies suggested that Hb-loaded particles did not activate complements. After the nanoparticles suspension was injected into the mice via tail vein, the particles did not cause significant changes in total platelet counts. Apparently, the hemoglobin-loaded nanoparticles can serve as a potential candidate in substitution for red cells.
Animals ; Biocompatible Materials ; chemistry ; Blood Substitutes ; chemical synthesis ; chemistry ; Cattle ; Hemoglobins ; chemistry ; Materials Testing ; Mice ; Nanoparticles ; chemistry ; Particle Size ; Polyesters ; chemistry

The progress of researches on drug-loaded nanoparticles was summarized in this review. The major emphasis was laid on the selection of wall polymers, technology of preparation, surface modification, investigation of release in vitro and biocompatibility evaluation. Additionally, we envisioned a perspective regarding the development in this field. With the development of synthesis of biodegradable polymer, with the appearance of novel equipment, and with the deep-going studies on modification of nanoparticles surface method, on fabrication of nanoparticles art as well as on evaluation of drug release and reaction between drug and organ, further researches in this field will open up the way to applications of drug-loaded nanoparticles in larger field.
Capsules ; administration & dosage ; Delayed-Action Preparations ; Drug Carriers ; chemistry ; pharmacokinetics ; Drug Compounding ; trends ; Nanomedicine ; trends ; Nanoparticles ; administration & dosage ; chemistry ; Polyesters ; chemistry

On the basis of previous researches, we have prepared Bovine hemoglobin-loaded nanoparticles (HbP), using the double emulsion method. More mild dispersing treatment was employed during the primary and secondary emulsion; over 97% encapsulation efficiency (EE%) and an average size about 286 nm were achieved by using surfactants, screening solvents, as well as avoiding the traditional strong dispersing process. The value of Hydrophile-lipophile balance in oil phase exerted a significant effect on EE% and led to higher EE% when matched with the surfactants in outer aqueous phase. When compared with the sole solvent Span80, the mixed surfactants such as Poloxemer188/Span80 stabilized the emulsion more efficiently and increased the EE%. The higher concentration of surfactants resulted in higher EE% and narrower size distribution. But over some amount, the surfactants had no significant effect on EE%, resulting in larger size and polydispersity index (PDI). The appropriate removal rate of solvents contributes to higher EE%, smaller size and PDI.
Animals ; Biocompatible Materials ; Blood Substitutes ; chemical synthesis ; chemistry ; Cattle ; Emulsions ; Hemoglobins ; chemistry ; Humans ; Nanoparticles ; Particle Size ; Solvents ; chemistry ; Surface-Active Agents ; chemistry

Bovine Hb-loaded nanoparticles with modulated size of pores, for use as blood substitutes, were prepared and a nonenzymatic reduction system including two-step-reduction and process optimization was established to control the metHb level in the present study. After the first-step-reduction procedure was performed, the raw BHb, being oxidized severely, was encapsulated to form nanoparticles by the modified double emulsion method. The binary solvent of dichloromethane (DCM) and acetonitrile (Aci) showed properties such as minimizing Hb oxidation and enlarging the pores of nanopartilces. Based on the size of pores o f nanoparticles evaluated by the diffusion of various substances wi thdifferent molecular weights, reducing agents such as ascorbic acid and glutathione present in the plasma were selected to perform the second-step-reduction, i. e. to further reduce the metHb in nanoparticles. The metHb level was reduced from over 90% in the raw materials to 1.25% by the two-step-reduction and controlled preparation; this is near the level of native blood, possessing the ability of carrying/releasing oxygen.
Animals ; Biocompatible Materials ; chemistry ; Blood Substitutes ; chemistry ; Cattle ; Hemoglobins ; chemistry ; metabolism ; Humans ; Methemoglobin ; analysis ; chemistry ; Nanoparticles ; chemistry ; Porosity