There is a broad and urgent need for the clinical application of anticancer nanomedicine in tumor therapy, but the complex biological barrier in solid tumors has always been the main obstacle to infiltrating nanomedicine into the tumor. The traditional design of nanomedicine based on enhanced permeability and retention (EPR) effect still has some limitations in tumor permeability, it is urgent to find other design theories. Therefore, this review summarizes two novel strategies, active transcytosis and immune cell-mediated tumor penetration, for promoting tumor penetration of anticancer nanomedicine.

Acupuncture Therapy ; Female ; Humans ; Middle Aged ; Ventricular Premature Complexes ; therapy

ObjectiveTo summarize the nursing measures for patients with nasal facial soft tissue defect treated with transplantation of free foot skin flap.MethodThe clinical data of 13 patients with transplantation were reviewed to summarize the nursing measures.ResultAll skin flaps of the 13 patients survived.ConclusionEnough preoperative preparation,active psychological nursing and careful postoperative observation are critical for the success of the operation.

Objective To observe the corneal nerve fibres damage in different stage of diabetic retinopathy (DR) with type 2 diabetes.Methods A cross-sectional study.One hundred and twenty eyes of 120 patients with type 2 diabetes served as diabetes group.According to International Clinical Diabetic Retinopathy Disease Severity Scales (2002),diabetes patients were classified into 4 subgroups:patients without diabetic retinopathy (NDR),patients with mild or moderate non-proliferative diabetic retinopathy (mNPDR),patients with severe non-proliferative diabetic retinopathy (sNPDR) and patients with proliferative diabetic retinopathy (PDR),each subgroup has 30 eyes of 30 patients.Another 30 eyes of 30 healthy participants served as control group.All eyes were scanned with HRT3 in vivo corneal confocal microscopy.Images of sub-basal nerve plexus were quantified including nerve fiber length (NFL),nerve fiber density (NFD),nerve fiber branch density (NFB),and nerve tortuosity (NT).The correlations of corneal nerve fiber with age,duration of diabetes and glycated hemoglobin (HbA1 c) were analyzed using Spearman correlation analysis.Results NFL,NFD and NFB were found to be significantly lower in diabetic patients (F=147.315,142.586,65.898;P=0.000,0.000,0.000),NT was significantly greater in diabetic patients (F=39.431,P=0.000),when compared to control group.In diabetic patients,NFL,NFD and NFB were gradually reduced with DR severity,NT was gradually increased with DR severity.While the difference ofNFL,NFD,NFB,NT was not statistically significant between sNPDR and PDR subgroups (P＞.0.05),but was statistically significant between other subgroups (P＜0.05).Spearman correlation analysis results showed that age (r=-0.071,-0.080,0.001,0.100;P=0.391,0.328,0.991,0.224) and HbAlc (r=-0.109,-0.115,-0.126,0.025;P=0.238,0.211,0.169,0.781) had no correlation with NFL,NFD,NFB,NT.Duration of diabetes was negatively correlated with the NFL,NFD (r=-0.212,-0.264;P=0.020,0.004),positive correlated with NT (r=0.261,P=0.004),and had no correlation with NFB (r=-0.119,P=0.194).Conclusions Corneal nerve fiber loss and nerve tortuosity increased were found in patients with type 2 diabetes,and even without diabetic retinopathy.The progress of corneal neuropathy was correlated with the severity of DR,but it was not change significantly between sNPDR and PDR.

Objective To observe the clinical significance and laboratory diagnostic values of Pre-S1 antigens (Pre-S1)and its relativity to HBeAg and HBV-DNA after using interferon in association with kurarinone.Methods The content of Pre-S1 and HBV-M was detected by ELISA and the levels of HBV-DNA were detected by flores- cence quantitative PCR(FQ-PCR)in 100 serum samples of patients with HBV infection and patients after an antivi- ral treatment.Results Matched control in 50 serum of HBsAg-positive and detectable HBV-DNA cases,both 29 samples in 30 HBeAg-positive cases and 17 samples in 20 HBeAg-negative cases Pre-S1s were positive.Treatment set 50 serum of patients after taking two courses of an antiviral treatment for HBV infection,drawing blood to observe related markers,5 cases of effect set were turned into negative for serologic markers and virologic markers.19 cases of valid set,serologic markers were various and the HBV-DNA copies descended 2-3 orders of magnitude.26 cases of invalid set,serologic markers were not various,and 30 % samples of the HBV-DNA copies descended 1～2 orders of magnitude.Conclusion It was supplementary for Pre-S1 to indicate HBV expression when the HBeAg varied.It also provided detcctable laboratory markers in HBV infectivity,replication and therapeutic efficiency evaluation.

Thymus,a main organ for T cell development,plays a pivotal role in adaptive immune response and dealing with the threaten from pathogens and tumors.With the deep understanding of the thymus,people have been realizing that the thymus is extremely sensitive to acute and chronic injuries as well as involution with age.Thymus regeneration can recover its function to a certain level.Up to now,these methods including adoptive thymic epithelial progenitor cells immunotherapy,injection of IL-2 and angiogenesis factor and regulation of c-Met signal are able to promote thymus recovery and T cell regeneration.

Objective To investigate the variations of the expression and activity of phosphatidyl inositol-3 kinase(PI-3K)in the adipose tissue of pregnant women with gestational diabetes mellitus(GDM)and to explore its relationship with insulin resistance(IR)in these women.Methods The expression of PI-3K p85aprotein and mRNA in adipose tissue were detected by Western blot and Semi quantitative reverse transcription polymerase chain reaction(RT-PCR)in 20 GDM women(GDM group)and 20 normal pregnant women(normal group).The activity of PI-3K was determined by ELISA and IR index was calculated using homeostasis model assessment(HOMA)according to the results of fasting insulin(FINS)and fasting plasma glucose(FPG),which measured by oxidase assay and immunoradioassay,respectively.Results The expressions of PI-3K p85αmRNA and PI-3K p85a protein were markedly increased in the adipose tissue of GDM group than in the normal group(mRNA:0.83±0.03 vs 0.53±0.07,P＜0.01;protein:0.93±0.04 vs 0.71±0.06,P＜0.01).However,the PI-3K activity in the GDM groups was significantly down-regulated compared with the normal group(1.7±0.6 vs 5.2±0.5,P＜0.01).The levels of FPG and FINS (HOMA-IR)in the GDM group were all significantly higher than the normal group[FPG:(5.8±0.2)mmol/L vs(4.7±0.3)mmol/L;FINS:(14.8±0.2)mmol/L vs(11.2±0.3)mmol/L;HOMA-IR:1.3±0.4 vs 0.9±0.3,a11 P＜0.01]. Conclusions The decreased activity of PI-3K in the adipose tissue may be one of the molecular mechanisms for IR in GDM.

Objective To investigate the expression and tyrosine phosphorylation of insulin receptor substrate-1 (IRS-1) and in the adipose tissue of patients with gestational diabetes mellitus (GDM), and to explore molecular mechanisms of insulin resistance in GDM. Methods The serum and adipose tissue were sampled from patients with GDM (GDM group, n = 20) and normal pregnant women (control group, n = 20). Fasting plasma glucose was measured by glucose oxidase assay. The expressions of IRS-1 protein and mRNA were determined by Western blot and semi-quantitative RT-PCR. The tyrosine phosphorylation of IRS-1 was measured by immunoprecipitation. Results Compared with control group, in GDM group, the expression of IRS-1 mRNA was markedly decreased (0.61 ±0.06 vs 1.12 ± 0.17, P < 0.01), the expression of IRS-1 protein was significantly decreased (0.57 ±0.08 vs O. 83 ±0.07, P <0.01) and tyrosine phosphorylation was significantly reduced (0.23 ± O. 06 vs O. 62 ±0.04, P < 0.01) in the adipose tissue. Conclusion The decline of protein expression and tyrosine phosphorylation of IRS-1 in the adipose tissue of gestational diabetes appears to be one of the moleculemechanisms of insulin resistance in patients with GDM.

A method for the real-time polymerase chain reaction ( PCR ) coupled with high specific invader assay to detect single nucleotide polymorphism ( SNP) was established. To reduce the background signal, the amount of flap endonuclease 1 ( FEN1 enzyme ) and wild-type detection probe was optimized. Under the optimum conditions including 0. 05 μmo/L invasive oligonucleotide probe, 0. 125 μmol/L wild-type detection probe, 0. 5 μmol/L mutation detection probe, 0. 25 μmol/L each fluorescence resonance energy transfer (FRET) probe and 1. 5 U FEN1, the background signal of wild-type sample and mutation sample was dramatically decreased and the background interference to the detecting results was thus eliminated. A total of 21 cases of aldehyde dehydrogenase-2*2 ( ALDH2*2 ) , 19 cases of cytochrome p450 2 C19*2 ( CYP2 C19*2 ) and 19 cases of CYP2C19*3 were analyzed with the established method, and the genotypes of ALDH2*2 were 10 cases of GG homozygote, 8 cases of GA heterozygote and 3 cases of AA homozygote; the genotypes of CYP2C19*2 were 9 cases of GG homozygote, 8 cases of GA heterozygote and 2 cases of AA homozygote;and the genotypes of CYP2C19*3 were 18 cases of GG homozygote and 1 case of GA heterozygote. These results were consistent with those by pyrosequencing. The established method was specific, simple, short time-consuming and low cost, and could be used for the detection of SNP genotyping with non-polluting in single closed tube.

Background:Tryptophan(TRP)is an essential amino acid,and can produce 5-hydroxytryptamine(5-HT)via 5-HT signal pathway and kynurenine( KYN)metabolic pathway under the catalysis of enzyme,thereby participating in the pathogenesis of visceral hypersensitivity in diarrhea-predominant irritable bowel syndrome(IBS-D). Aims:To investigate the relationship between visceral sensitivity and TRP metabolic pathway in patients with IBS-D. Methods:Thirty patients with IBS-D and 30 healthy controls from June 2012 to January 2014 at Guangdong Provincial TCM Hospital were enrolled. Score of gastrointestinal symptom rating scale( GSRS)was evaluated. Visceral sensitivity was measured by anorectal manometry. RT-PCR and Western blotting were used to detect mRNA and protein expressions of colon mucosal IDo, respectively. Serum 5-HT,5-HIAA,TRP,IDo,KYN,KYNA concentrations and IDo activity,KAT activity were determined by high performance liquid chromatography assay. Results:Compared with control group,GSRS score was significantly increased(P < 0. 05),initial perception threshold,defecation threshold,pain threshold were significantly decreased(P < 0. 05),anorectal constriction pressure was significantly increased( P < 0. 05),serum 5-HT,5-HIAA concentrations were significantly increased(P < 0. 05),mRNA and protein expressions of IDo were significantly increased (P < 0. 05),serum KYN was significantly increased(P < 0. 05),KYNA was significantly decreased(P < 0. 01),IDo activity was significantly incseased(P < 0. 01),and KAT activity was significantly decreased in IBS-D group(P < 0. 01). Correlation analysis showed that initial perception threshold,defecation threshold,pain threshold and anorectal constriction pressure were correlated with 5-HT,5-HIAA,TRP,KYN,KYNA,IDo activity and KAT activity in patients with IBS-D (P < 0. 05). Conclusions:TRP metabolic pathway is correlated with visceral hypersensitivity in patients with IBS-D.