Recent advances of cell membrane-derived biomimetic nanotechnology in cancer targeted drug delivery system / 药学学报

The development of nanotechnology has made it possible to develop safe, efficient, precise and controllable drug delivery system (DDS). Among them, organic or inorganic synthetic nanocarriers have been widely reported and used for the delivery of tumor therapeutic agents. However, some of carriers have several problems, such as easily eliminated by the body's immune system, difficult to preparation or poor safety in vivo. In recent years, with the development of biomedicine, biomimetic technology based biomembrane-mediated nanodrug delivery has organically integrated the low immunogenicity of natural biomembrane, cancer targeting, and the controllable and multifunctional of smart nanocarrier design. It will achieve a new breakthrough of nanotechnology in cancer targeted therapy. Based on the recent advances of cell membrane-derived biomimetic nanotechnology and the nanomedicine in the field of cancer therapy, this review discusses the three aspects including the experimental basis of cell membrane-derived biomimetic nanotechnology, the classification of biomimetic nanodrug delivery platforms, and the application in cancer targeted therapy. Therefore, the review will provide reference for the design of smart drug delivery system and its development in cancer targeted treatment.

Technical Reports of Endoscopic Retrograde Cholangiopancreatography Guidewires on the Basis of Physical Properties

Background/Aims@#Using an appropriate guidewire can increase the success rate of selective cannulation in endoscopic retrograde cholangiopancreatography. The purpose of this technical study was to investigate the characteristics of each guidewire type and to evaluate its efficiency and rapidity of insertion. @*Methods@#We conducted a three-point bending test using a universal testing machine to investigate the flexibility and bending features of each guidewire. 3D-printed silicone tubes with various types of stricture and a hand-made biliary tree silicone model with six-stranded intrahepatic ducts were used to evaluate the success rate and insertion time of each guidewire. @*Results@#In the three-point bending test, the characteristics of each guidewire were classified. We found that the bending strengths and times were independent of shaft thickness. Using two in vitro biliary duct models, we determined that the success rate and total insertion time were better for guidewires with a resilient shaft and angled tip than for other types of guidewires (p<0.001). Although thickness of the guidewire affected the success rate (p<0.05), it did not affect the total insertion time (p≥0.05). @*Conclusions@#Among several types of guidewire, some factors (resilient shaft, highly flexible, and angled tip) appeared to be associated with the efficiency and rapidity of the guidewire insertion.

Application of polygenic risk scores in risk prediction and precision prevention of complex diseases: opportunities and challenges / 中华流行病学杂志

Along with the rapid progress in the field of human genomics, genome-wide association studies have successfully identified numerous risk loci for complex diseases. Polygenic risk scores can predict disease risk by integrating the effects of multiple susceptibility loci, and begin to show good performance for improving risk prediction, screening strategy and precision prevention. This paper briefly reviews the recent progress of polygenic risk scores in disease prevention, and summarizes the opportunities and challenges of its application.

Association between genetic variants in microRNA biosynthesis genes and the risk of head and neck squamous cell carcinoma / 中华流行病学杂志

Objective To investigate the association between genetic variants in microRNA biosynthesis genes and the risk of head and neck squamous cell carcinoma (HNSCC).Methods A case-control study was conducted with 576 HNSCC patients and 1 552 healthy controls matched by factors as age-(± 5 years) and sex.Eight potentially functional single nucleotide polymorphism loci in microRNA biosynthesis genes (DICER1,GEMIN3,and PIWIL1) were genotyped using the Illumina Infinium BeadChip platform.Univariate and multivariate logistic regression models were performed to assess the association between genotypes and HNSCC risk.Results The allele frequencies of rs1106042 (G＞A) in PIWIL1 were significantly different between the cases and controls (P=0.011).After controlling for factors as age,sex,smoking and alcohol intake,the A allele of rs 1106042 showed a decreased risk of HNSCC (additive model:adjusted OR=0.73,95％CI:0.57-0.93,P=0.011).Results from the stratification analysis by age,sex,smoking,alcohol intake and tumor sites showed that the effect of rs1106042 A allele on HNSCC risk was significant in older age groups (≥60),females,nonsmokers,non-alcohol drinkers,and subjects with oral cavity cancer (P＜0.05).Conclusion Potentially,functional single nucleotide polymorphism in PIWIL1 might modify the risk of HNSCC in China.

Association between genetic variants in microRNA biosynthesis genes and the risk of head and neck squamous cell carcinoma / 中华流行病学杂志

Objective To investigate the association between genetic variants in microRNA biosynthesis genes and the risk of head and neck squamous cell carcinoma (HNSCC).Methods A case-control study was conducted with 576 HNSCC patients and 1 552 healthy controls matched by factors as age-(± 5 years) and sex.Eight potentially functional single nucleotide polymorphism loci in microRNA biosynthesis genes (DICER1,GEMIN3,and PIWIL1) were genotyped using the Illumina Infinium BeadChip platform.Univariate and multivariate logistic regression models were performed to assess the association between genotypes and HNSCC risk.Results The allele frequencies of rs1106042 (G＞A) in PIWIL1 were significantly different between the cases and controls (P=0.011).After controlling for factors as age,sex,smoking and alcohol intake,the A allele of rs 1106042 showed a decreased risk of HNSCC (additive model:adjusted OR=0.73,95％CI:0.57-0.93,P=0.011).Results from the stratification analysis by age,sex,smoking,alcohol intake and tumor sites showed that the effect of rs1106042 A allele on HNSCC risk was significant in older age groups (≥60),females,nonsmokers,non-alcohol drinkers,and subjects with oral cavity cancer (P＜0.05).Conclusion Potentially,functional single nucleotide polymorphism in PIWIL1 might modify the risk of HNSCC in China.

Discrimination of alleles in HLA-C*04:01:01G groups / 中国实验血液学杂志

The aim of this study was to investigate the relatively frequencies of alleles in the HLA-C*04:01:01G group and to analyze their relations with HLA-A and -B loci. DNA samples previously typed as HLA-C*04:01:01G were sequentially selected. The sequences for exon 2 to 7 of the HLA-C locus were analyzed by polymerase chain reaction sequence-based typing(PCR-SBT). The HLA-A, -B, -DRB1 and -DQB1 loci were genotyped using PCR-SBT method. The results showed that 178 samples (94.2%) and 11 samples (5.8%) were assigned as HLA-C*04:01:01 and HLA-C*04:82 respectively among 189 samples previously typed as HLA-C*04:01:01G. 72 haplotypes associated with HLA-C*04:01:01 and C*04:82 were found, in which the frequencies of 26 haplotypes were over 0.0050. HLA-C*04:01:01 was strongly related with A*02:03, A*02:07, A*11:01, A*33:03, B*13:01, B*15:01, B*15:05, B*15:27, B*40:01, B*54:01 alleles, while HLA-C*04:82 was related with B*40:01. It is concluded that HLA-C*04:01:01 and HLA-C*04:82 alleles were confirmed in the HLA-C*04:01:01G group, which should be discriminated by the routine HLA genotyping.

Discrimination of alleles in HLA-C*07:01:01G and HLA-C*07:02:01G groups through detection sequences in exons 1 to 7 of HLA-C locus by using polymerase chain reaction sequence-based typing / 中国实验血液学杂志

This study was aimed to discriminate the alleles in the HLA-C*07:01:01G and HLA-C*07:02:01G groups and analyze their associations with HLA-B locus. Samples previously typed as HLA-C*07:01:01G and HLA-C*07:02:01G were collected. The nucleotide sequences in exons 1 to 7 of the HLA-C locus were sequenced by polymerase chain reaction sequence-based typing (PCR-SBT) and HLA-B genotyping was also preformed by PCR-SBT in these samples. The results showed that 4 samples (30.8%) were confirmed as HLA-C*07:01:01 and 9 samples (69.2%) were HLA-C*07:06 among 13 samples previously typed as HLA-C*07:01:01G. Linkage disequilibrium (LD) analysis showed that HLA-C*07:06 allele was strongly related with HLA-B*44:03. All samples were typed as C*07:02:01 among 102 individuals previously typed as C*07:02:01G. LD analysis showed that C*07:02:01 was strongly related with HLA-B*51:01, B*46:01, B*39:01, B*40:01, B*38:02, B*15:02 alleles. It is concluded that HLA-C*07:01:01 and HLA-C*07:06 alleles are confirmed in the HLA-C*07:01:01G group and HLA-C*07:02:01 is a preferred allele in the HLA-C*07:02:01G.

Role of chemokine ligand 2 in spinal eord in a rat model of tibia bone cancer pain / 中华麻醉学杂志

Objective To investigate the role of chemokine ligand 2 (CCL2) in the spinal cord expression in a rat model of tibia bone cancer pain.Methods Eighty-four female SD rats weighing 160-180 g were randomly divided into 3 groups ( n =28):control group (group C),sham operation group (group S) and tibia bone cancer pain group (group P).Tibia bone cancer pain was induced by intra-tibial inoculation of Walker-256 breast cancer cells.Paw withdral threshold to mechanical stimulation (MWT) was measured with von Frey filaments at 1 d before and at 1,3,7,10,14 and 21 d after inoculation.Six rats in each group were sacrificed after the measurement of MWT at 1 d before inoculation and at 7,14 and 21 d after inoculation.Lumbar 4-6 segments of the spinal cord were removed for determination of the expression of CCL2 by ELISA.The coexpression of CCL2 with Iba-1 (a specific marker of microglia),GFAP(a specific marker of astrocyte) and NeuN (a specific marker of neuron) was determined by double immunofluorescence assay after the measurement of MWT at 14 d after inoculation in group P.Results Compared with groups C and S,MWT was significantly decreased from 7 d to 21 d after inoculation,the expressive of CCI-2 in the spinal cord up-regulated at 7,14 and 21 d after inoculation in group P ( P ＜ 0.05).CCL2 was expressed in the microglia and astrocyte but not in neuron in the spinal cord dorsal horn in a rat model of tibia bone cancer pain.Conclusion Release of CCL2 from microglia and astrocytes in the spinal cord was involved in mechanical hyperalgesia in a rat model of tibia bone cancer pain.

Molecular characterization of full-length genome of Japanese encephalitis virus strain patient's cerebrospinal fluid in China / 中华实验和临床病毒学杂志

<p><b>OBJECTIVE</b>To sequence and analyze the whole genome of Japanese encephalitis virus (JEV) strain named 47 which was isolated from patient's cerebrospinal fluid sample in Heilongjiang province in 1950.</p><p><b>METHODS</b>RNA was extracted from the recovery strain 47 and amplified with self-designed JEV genome sequencing primers. The differentiation analysis for nucleotides and coding amino acids and phylogenetic analysis were performed by the software of DNAStar, Modeltest, and Phylip.</p><p><b>RESULTS</b>The whole genome of strain 47 has 10,977 nucleotides. An open reading frame from 95 to 10,391 including 10,296 nucleotides is capable of coding a 3432 amino acid polyprotein. The nucleotide difference between strain 47 and 5 vaccine strains is 2.4%-4.4%, the amino acid difference between strain 47 and 5 vaccine strains is 0.3%-1.1%. The best evolution model for the whole genome is GTR + I + G. Based on the phylogenetic analysis, strain 47 belongs to the genotype III JEV.</p><p><b>CONCLUSION</b>Strain 47 is highly conserved on whole genome nucleotide and amino acid sequence. And it is belongs to the genotype III JEV.</p>

Effects of brucea javanica oil on expression of vascular endothelial growth factor in A549 cell line / 中国中药杂志

<p><b>OBJECTIVE</b>To study the effects of brucea javanica oil on the expression of vascular endothelial growth factor (VEGF) in A549 cell line.</p><p><b>METHOD</b>A549 cells were incubated with different concentrations of brucea javanica oil (0.5, 1.25, 2.5, 5 g x L(-1) for 48 h respectively. VEGF level in supernatant was determined by VEGF ELISA kits and mRNA expression of VEGF was evaluated by RT-PCR. PMN in health volunteers was treated as control groups.</p><p><b>RESULT</b>Supernatant VEGF protein and mRNA expression were significantly elevated in A549 cells compared with the mononuclear cells (120.73 vs 21.21, P < 0.05). Brucea javanica oil (2.5 g x L(-1)) could reduced supernatant VEGF protein in A549 cells (20.30 vs 120.73, P < 0.05), but had no effect on the expression of VEGF mRNA (1.0230 vs 0.9573). It was found that brucea javanica oil (5 g x L(-1)) significantly reduced VEGF mRNA expression (0.4682 vs 0.9573, P < 0.05).</p><p><b>CONCLUSION</b>Brucea javanica oil can depress the VEGF mRNA expression and secretion in A549 cells, which may be one of the mechanisms of its antitumor effect.</p>

Effect of nano-liposome sustained elemene in inducing cell apoptosis of C6 glioma / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To study the effect of nano-liposome sustained elemene in inducing cell apoptosis of C6 glioma and to explore its influence on the expression of caspase-3 gene.</p><p><b>METHODS</b>C6 glioma cells were cultured in medium with the same amount of nano-liposome sustained elemene and common elemene respectively, also in blank medium for control. The status of cell apoptosis was determined by flow cytometry at 0, 48 h and 72 h, and the expression of Caspase-3 protein was measured simultaneously by immunohistochemistry assay.</p><p><b>RESULTS</b>Marked apoptosis presented in cells cultured in the medium with nano-liposome sustained elemene or common elemene at 48 h and 72 h, with the apoptotic rate significantly higher than that in the control. At the same time, Caspase-3 protein expression raised significantly in cells cultured in medium with either kinds of elemene, showing significant difference when compared with that in the control.</p><p><b>CONCLUSION</b>Elemene has significant apoptosis promoting and Caspase-3 protein expression inducing effect on C6 glioma cells, which could be facilitated by nano-liposome bearing.</p>

Sequence analysis of a novel HLA-A * 2459 allele / 中国实验血液学杂志

This study was aimed to investigate the molecular genetics basis of a novel allele HLA-A * 2459 in Chinese population. DNA was extracted from whole blood by PEL-FREEZ DNA extraction kit. The amplification of HLA-A exons 2 - 4 of the proband was preformed by allele specific primer PCR and the amplified product was sequenced bidirectionally with primers. The sequencing results showed HLA-A alleles of the proband as A * 1101 and the novel allele. The sequences of the novel allele have been submitted to GenBank (DQ313255, DQ313256, DQ313257). After Blast HLA analysis, the novel allele showed only one nucleotide differences with HLA-A * 24020101 at nucleotide position 527 T to C in exon 3. This results in an amino acid changes from Val to Ala at codon 152. In conclusion, this allele is a novel one and has been officially named HLA-A * 2459 by the WHO Nomenclature Committee.

Intervention of maiwei dihuang oral liquid on hormonotherapy in treating active systemic lupus erythematosus / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To observe the intervention of Maiwei Dihuang Oral Liquid (MDOL) on hormonotherapy in treating active systemic lupus erythematosus (SLE).</p><p><b>METHODS</b>Sixty SLE patients in active stage were randomly and equally allocated into two groups, and administered with prednisone, which was medicated in initial dose of 0.5-1 mg/kg, and with the dose being reduced conditionally 6-8 weeks. To the 30 patients in the treated group 10 ml MDOL twice daily was given additionally. The therapeutic course was 3 months.</p><p><b>RESULTS</b>The therapeutic effect in the treated group was better than that in the control group (P < 0.05). Systemic lupus erythematosus disease activity index (SLEDAI) was significantly improved in both groups (P < 0.01), but was superior in the treated group (P < 0.05). The dose of prednisone used was significantly reduced (P < 0.01), and the scores of Yin-deficiency fire-flourishing syndrome were obviously decreased (P < 0.01) in the treated group while in the control group, these indexes were unchanged (P > 0.05), the difference between the two groups was significant (P < 0.01). The occurrence of adverse reaction was significantly lower in the treated group than that in the control group (P < 0.05).</p><p><b>CONCLUSION</b>MDOL can obviously improve the effect of hormonotherapy in SLE, it has advantages in reducing the dosage used and antagonizing the adverse reactions of glucocorticoid.</p>

Effect of receptor solution specific conductivity on iontophoresis of tetracaine hydrochloride / 药学学报

<p><b>AIM</b>To examine the quantitative relationship between solution specific conductivity and the permeability of tetracaine HCl, and to investigate the effect of receptor solution specific conductivity on the iontophoretic transport.</p><p><b>METHODS</b>An in vitro study was carried out to determine the iontophoretic permeability of tetracaine hydrochloride through rat skin. Iontophoretic flux of tetracaine hydrochloride through excised rat skin was determined using Valia-Chien two-chamber diffusion cells with a constant d.c. current and Ag/AgCl electrodes. The specific conductivities of donor and receptor solution were also measured.</p><p><b>RESULTS</b>Iontophoretic flux of tetracaine hydrochloride increased with a decrease of anion (chloride ion) concentration in receptor. And the iontophoretic permeability (ER, ER is the enhancement ratio, and ER = iontophoretic flux/passive flux) for tetracaine hydrochloride was directly related to the conductivity of receptor solution when other conditions were held constant. Linear regressions confirmed that ER was related to inverse of overall specific conductivity of donor and receptor solution [1/(ks.d + ks.r), ks.d and ks.r are the specific conductivity of donor and receptor solution].</p><p><b>CONCLUSION</b>The results suggest that specific conductivity of receptor solution may be a important factor for the iontophoretic permeability of a solute.</p>

Effects of Progesterone on Brain Damage in Hypoxia Mouse / 实用儿科临床杂志

Objective To observe the changes of water, potassium and sodium in the hypoxic cerebral tissues in mice and the effects of progesterone on the tissues and investigate the neuroprotective role of progesterone (PROG)in the cerebral anoxia. Methods Thirty - two male mice were divided into control group, simple hypoxia group, lower dosage group and higher dosage group. Progesterone was injected intraperitoneally in the dosage of 4 mg/kg or 8 mg/kg respectively 30 min before hypoxia in the last two groups. The contents of water, potassium and sodium in brain tissues in mice were evaluated at 24 hours after cerebral anoxia. Results The water, potassium and sodium contents in simple hypoxia group were significantly higher than those in control group(P0.05)in higher dosage group(8 mg/kg PROG)compared with those of simple hypoxia group. Conclusions At 24 hours after cerebral anoxia, there are significant increases of water, potassium and sodium in brain tissues. Progesterone may pro-duce neuroprotective role by inbibiting the rise of them.

Influence of Mild Hypothermia on Nervous Cell Apoptosis and Activity of Caspase - 3 after Hypoxia - Ischemia Brain Damage in Neonatal Rats / 实用儿科临床杂志

Objective To study the effects of mild hypothermia on nervous cell apoptosis and activity of Caspase - 3 after hypoxia -ischemia brain damage (HIBD) in neonatal rats. Methods Seven - day SD rats were divided into sham operation group,normothermia HIBD group (HIBD group) and mild hypothermia HIBD group(mild hypothermia group). In HIBD group,the left carotid of rats was ligated and animals were exposed to 8% oxygen for 2 h.and in mild hypothermia group,hypothermia of 31 - 32 1C lasting 8 hours was used just after HIBD. L sing methods of TUNEL and AC - DEVI) - AMC, the apoptotic cell rate and Caspase - 3 activity level were determined in sham operated group, HIBD group and mild hypothermia group separatively. Results The apoptotic cell rate and Caspase - 3 activity level were significantly lower in sham - operated group and mild hypothermia group than those in HIBD group. Conclusion One of the mechanisms of brain protection by mild hypothermia may be contributed to the decrease of neural cell apoptosis and the activity level of Caspase 3 HIBD.

School Bullying and Related Psychopathology in Elementary School Students / 신경정신의학

OBJECTIVE: School bullying, the most prevalent type of school violence, is known to be related to various behavioral, emotional and social problems both in victims and perpetrators. The purpose of the present study is to investigate the prevalence of school bullying and related psychopathology in a community sample of elementary school students. METHOD: Fourth to 6 th graders of two randomly selected classes in two elementary schools in Anyang City participated in a cross-sectional study. Study subjects completed Korean-Peer Nominating Inventory(K-PNI). Parents completed Korean-Child Behavior Checklist(K-CBCL), ADHD Rating Scale(ARS) and Conners Scales for parents, and teachers completed ARS and Conners Scales for teachers. Descriptive statistics, multiple linear and logistic regression were performed. RESULTS: A Total of 532 students participated in this study. Prevalence of victims, perpetrators, and victim-perpetrators were 48%, 45%, and 30% respectively. Extreme victims and perpetrators of school bullying ranged from 2.1-4.1%. Inattention-passivity in teachers' Conners Scale, social immaturity or aggression in K-CBCL were positively associated with victims and victim-perpetrators, and grade was negatively related to school bullying. Conduct problem in Conners Scale for teachers and emotional instability in K-CBCL, and male gender were positively associated with perpetrators. CONCLUSION: School bullying is very common in Korean children of elementary schools. Those who had experienced school bullying, either as victims or as perpetrators, had signifi-cantly more psychopathology than their counterparts. To clarify a causal relationship between psychopathology and school bullying, a longitudinal follow-up study is suggested.