The immunoregulatory effects of some anti-cancer drugs have important role in their anti-tumor mechanisms. Our results showed that doxorubicin (DXR) of 0.04 mg ?L-1 could enhance the interleukin 2 (IL-2) release and induction of lymphokine-activated killer (LAK) activity of human fetal thymocytes(HFT). Higher concentration of this drug (4 mg ?L-1) exhibited inhibition on IL-2 release but no effect on LAK activity. These data suggest that lower concentration of DXR have some immunopotentiation effects on HFT.

Objective To develop a knowledge-attitude-practice scale of elder abuse for caregiver.Methods The elder abuse related knowledge-attitude-practice scale was established by literature review,in-depth interview,expert consultation and discussion among focus group.200 caregivers were selected conveniently for investigation.T-test,correlation analysis,factor analysis,etc.were used to select items.Results Three sub-scales were built which were knowledge,attitude and practice respectively.The number of items of each sub-scales were 22,14 and 15 respectively through item selection.Conclusions The scale,which has good representativeness,applicability and operability,can be used for measuring the caregiver elder abuse knowledge-attitude-practice and providing an objective evidence for the health education to the caregiver.

Objective To establish a multiplex PCR targeting the intergenic spacer regions (IGS) for the identification of Cryptococcus neoformans var.grubii,var.neoformans and Cryptococcus gattii.Methods Primers were designed by using the software ClustalW2 and Oligo 6 based on the sequence of IGS1 region,which shows high sequence variability in the genome of Cryptococcus neoformans and Cryptococcus gattii.,for the multiplex PCR.Then,the developed multiplex PCR was performed to identify 51 Cryptococcus neoformans strains representing genotypes VNI-VNIV and VNB as well as 41 Cryptococcus gattii strains representing genotypes VGI-VGIV.The identification results were compared with those from common PCR by using primers GPA1A,CLA4D and SODlgattii specific to Cryptococcus neoformans var.grubii,var.neoformans and Cryptococcus gattii,respectively,as well as with those from the canavanine-glycine-bromothymol blue (CGB) medium-based culture.Results The developed multiplex PCR successfully identified the 92 Cryptococcus neoformans and Cryptococcus gattii.strains,and yielded negative results from the other tested pathogenic yeasts,which revealed a high specificity of the designed primers.False positive results were observed in the identification of two Cryptococcus gattii strains with GPA1A primer-based PCR,one Cryptococcus gattii strain with CLA4D primer-based PCR,one var.grubii strain and one var.neoformans strain with CGB culture,while no false negative results were observed in the detection of these Cryptococcus strains by any of these methods.Conclusions The developed multiplex PCR in this study can rapidly and accurately identify Cryptococcus neoformans var.grubii,var.neoformans,AD hybrid,and Cryptococcus gattii,with superior performance in comparison with common PCR and CGB medium-based culture.

Objective To establish a PCR method for rapid identification and sequence typing of VG Ⅱ allele of the intergenic spacer region (IGS) of Cryptococcus gattii.Methods Since IGS1 was of high sequence variation,multiple alignments were conducted by ClustalX 2 in IGS1 of Cryptococcus gattii and Cryptococcus neoformans,and then primer sets specific to genotype VG Ⅱ was designed for PCR analysis.The specificity of the primer pair was detected by amplification of the other genotypes in Cryptococcus gattii,Cryptococcus neoformans,and other pathogenic yeasts.The amplified fragments from VG Ⅱ genotype were sequenced and subtyped.Results Using the PCR analysis developed in this study,all VG Ⅱ genotype strains tested were amplified,whereas no amplification was obtained from other genotypes or yeast species involved herein.Three polymorphic nucleotide sites at 72,79 and 104 bp in the fragment amplified could be used to distinguish sub-genotypes within VG Ⅱ genotype.Conclusions The PCR analysis developed in this study can be used for rapid identification of genotype VG Ⅱ of Cryptococcus gattii.The sequence typing based on the amplified fragment from IGS1 may be performed for screening the highly virulent sub-genotype VGⅡ a.

To study bioadhesive property of carbomer 934 in dog alimentary tract, carbomer 934 and ethylcellulose were radiolabelled with technetium-99 m. The gastrointestinal emptying rate of these materials was measured by the technique of gamma scintiscan. The results showed that the empty rate of adhesive material (carbomer 934) was remarkably slower in dog alimentary tract compared to nonadhesive material (ethylcellulose). It is concluded that, in dog, the interaction between gastrointestinal mucus layer and adhesive material or nonadhesive material was significantly different. Carbomer 934 had stronger bioadhesive property in vivo than that of ethylcellulose.
Acrylic Resins ; pharmacokinetics ; Animals ; Cellulose ; analogs & derivatives ; pharmacokinetics ; Digestive System ; diagnostic imaging ; Dogs ; Gamma Cameras ; Gastric Emptying ; Intestinal Mucosa ; metabolism ; Radioimmunodetection

Objective:To investigate the clinical significance of inflammatory factors in bacterial infection children with glucose-6-phosphate dehydrogenase (G6PD) deficiency in PICU.Methods:A prospective cohort study was carried out from June 2014 to December 2017. 77 bacterial infection children with pediatric critical illness score less than 80 who were admitted to the PICU, were recruit in the study.The patient diagnosed as other basic diseases,with history of high-dose glucocorticoid use, discharged or died within 24 hours were excluded.The recruited patients were divided into G6PD deficiency group (observation group with 36 cases) and non-G6PD deficiency group (control group with 41 cases) according to the presence or absence of G6PD deficiency.Blood samples were taken at admission, 12 hand 24 h after hospitalization to detect the concentrations of tumor necrosis factor (TNF-α), interleukin 6 (IL-6), interleukin 10 (IL-10) andC-reactive protein (CRP). T test, χ2 test and Fisher exact test were used to analyze the changes of the above inflammatory factors, complications, prognosis, PICU stay time and hospitalization costs. Results:The levels of inflammatory factors in the observation group were significantly higher than those in the control group at admission, 12 and 24 hours after hospitalization, the differences were statistically significant (all P< 0.05). There was no statistically significant difference in thechangerate of inflammatory factors between the two groups during treatment; The PICU stay time of observation group was longer [(7.98 ± 6.55) vs (5.01 ± 6.21)] and the hospitalization cost (yuan) was higher [(36 634.09 ± 11 876.67) vs (31 571.42 ± 10 245.80)], P<0.05; Compared to the control group, the incidence ofsevere sepsis, septic shock, MODS increased significantly, and the curative rate decreasedsignificantly in observation group( P<0.05). Conclusions:G6PD-deficient children with bacterial infections had serious inflammatory reactions with poor prognosis and higher hospitalization costs and were susceptible to the occurrence of severe sepsis, septic shock and MODS.

Objective:To explore the serum levels of inflammatory cytokines and prognosis in severe acute infection children with glucose-6-phosphate dehydrogenase(G6PD) deficiency.Methods:A total number of 160 children with severe acute infections admitted to PICU of Guangxi Zhuang Autonomous Region Maternal and Child Health Hospital from June 2014 to December 2017 were selected as subjects in this study, including 80 children with G6PD deficiency(observation group) and 80 children without G6PD deficiency(control group). The changes of TNF-α, IL-6, IL-10 and CRP were dynamically monitored at 0-hour, 12-hour and 24-hour after admision, and the occurrences of sepsis, multiple organ dysfunction syndrome(MODS) were prospectively analyzed.Results:The levels of serum cytokines and CRP in the observation group were significantly higher than those in the control group at admission[TNF-α: (65.57±19.09) pg/ml vs.(46.53±20.34) pg/ml; IL-6: (98.90±29.02) pg/ml vs.(89.89±25.54) pg/ml; IL-10: (87.66±21.84) pg/ml vs.(76.34±19.01) pg/ml; CRP: (60.18±22.24) mg/L vs.(41.43±19.51) mg/L, respectively], and the differences between two groups were statistically significant( P<0.05). The levels of cytokines and CRP in the observation group were higher than those in the control group at 12 h and 24 h after treatment( P<0.01). Compared with the control group, the incidences of sepsis(82.50% vs 67.50%) and MODS(73.75% vs 58.75%) in the observation group increased, and the recovery rate(81.25% vs 92.50%) decreased, with statistical significance between two groups( P<0.05). Conclusion:Children with G6PD deficiency need to be paid more attention to inflammation, sepsis, MODS and the difficulty of treatment when they are infected.The potential mechanism may be related to oxidative stress.

A phospholipid-based injectable gel was developed for the sustained delivery of leuprolide acetate (LA). The gel system was prepared using biocompatible materials (SPME), including soya phosphatidyl choline (SPC), medium chain triglyceride (MCT) and ethanol. The system displayed a sol state with low viscosity in vitro and underwent in situ gelation in vivo after subcutaneous injection. An in vitro release study was performed using a dialysis setup with different release media containing different percentages of ethanol. The stability of LA in the SPME system was investigated under different temperatures and in the presence of various antioxidants. In vivo studies in male rats were performed to elucidate the pharmacokinetic profiles and pharmacodynamic efficacy. A sustained release of LA for 28 days was observed without obvious initial burst in vivo. The pharmacodynamic study showed that once-a-month injection of LA-loaded SPME (SPME-LA) led to comparable suppression effects on the serum testosterone level as observed in LA solution except for the onset time. These findings demonstrate excellent potential for this novel SPME system as a sustained release delivery system for LA.

Cell-penetrating peptides (CPPs) have been widely used to enhance the membrane translocation of various carriers for many years, but the non-specificity of CPPs seriously limits their utility in vivo. In this study, cholesterol-anchored, reduction-sensitive PEG (first synthesized by our laboratory) was applied to develop a co-modified liposome with improved tumor targeting. Following optimization of the formulation, the in vitro and in vivo properties of the co-modified liposome were evaluated. The co-modified liposome had a much lower cellular uptake and tumor spheroid uptake, but a much higher tumor accumulation compared to CPP-modified liposome, indicating the non-specific penetration of CPPs could be attenuated by the outer PEG coating. With the addition of exogenous reducing agent, both the in vitro and in vivo cellular uptake was markedly increased, demonstrating that the reduction-sensitive PEG coating achieved a controllable detachment from the surface of liposomes and did not affect the penetrating abilities of CPPs. The present results demonstrate that the combination of cholestervsitive PEG and CPPs is an ideal alternative for the application of CPP-modified carriers in vivo.

The T cell co-stimulatory molecule OX40 and its cognate ligand OX40L have attracted broad research interest as a therapeutic target in T cell-mediated diseases. Accumulating preclinical evidence highlights the therapeutic efficacy of both agonist and blockade of the OX40-OX40L interaction. Despite this progress, many questions about the immuno-modulator roles of OX40 on T cell function remain unanswered. In this review we summarize the impact of the OX40-OX40L interaction on T cell subsets, including Th1, Th2, Th9, Th17, Th22, Treg, Tfh, and CD8 T cells, to gain a comprehensive understanding of anti-OX40 mAb-based therapies. The potential therapeutic application of the OX40-OX40L interaction in autoimmunity diseases and cancer immunotherapy are further discussed; OX40-OX40L blockade may ameliorate autoantigen-specific T cell responses and reduce immune activity in autoimmunity diseases. We also explore the rationale of targeting OX40-OX40L interactions in cancer immunotherapy. Ligation of OX40 with targeted agonist anti-OX40 mAbs conveys activating signals to T cells. When combined with other therapeutic treatments, such as anti-PD-1 or anti-CTLA-4 blockade, cytokines, chemotherapy, or radiotherapy, the anti-tumor activity of agonist anti-OX40 treatment will be further enhanced. These data collectively suggest great potential for OX40-mediated therapies.