Optimization of preparation technology and in vitro release of baicalin-glycyrrhizic acid solid nanocrystals / 中国药房

OBJECTIVE To optimize the preparation technology of baicalin （BCN）-glycyrrhizic acid （GA） solid nanocrystals （BCN-GA-SN）， to characterize them and investigate their in vitro release characteristics. METHODS According to the compatibility ratio of classic couplet medicinals “Scutellaria baicalensis-Glycyrrhiza uralensis”， the compatibility ratio of BCN and GA was determined as 6∶1 （m/m）； BCN-GA nanosuspension was prepared by precipitation method combined with high-pressure homogenization method. The preparation technology of BCN-GA nanosuspension was optimized by using mean particle size and polydispersity index （PDI） as indexes and with types and dosage of stabilizers， stirring speed and time， high-pressure homogenization pressure and frequency as factors. The freeze-dried consolidation process of BCN-GA nanosuspension was optimized to prepare BCN-GA-SN using average particle size， PDI and redispersibility index （RDI） as indicators， with the type and dosage of freeze-dried protective agents as factors； then， the physicochemical properties and in vitro release of BCN-GA-SN were investigated. RESULTS The optimal preparation technology of BCN-GA-SN was as follows： BCN-GA nanosuspension was prepared by using 15% sodium dodecyl sulfate as a stabilizer， stirring at 1 000 r/min for 15 minutes， and homogenizing at 100 MPa for 20 times； then， BCN-GA nanosuspension was freeze-dried and solidified with 5% mannitol （corresponding to the dosage of BCN）. The average particle size of prepared BCN-GA-SN was （442.2±5.7） nm with PDI of 0.225±0.015 and RDI of 1.055± 0.013. The prepared BCN-GA-SN presented as the irregularly spherical shape with more uniform size； the drug-loading amount of BCN in the nanocrystal was （62.5±0.7）%， and that of GA was （9.4±0.2）%； the in vitro release results showed that the cumulative dissolution of BCN-GA-SN was higher than that of the physical mixture of BCN and GA. CONCLUSIONS BCN-GA-SN is prepared successfully in this study with uniform particle size and even distribution， which can effectively improve the dissolution of BCN.

Research advances in traditional Chinese medicine regulation of autophagy in treatment of liver cancer / 临床肝胆病杂志

Autophagy has become a research hotspot in the prevention and treatment of tumor in recent years. With the help of the bidirectional regulatory effect of autophagy, it can not only provide energy and a stable internal environment for normal and tumor cells by clearing misfolded proteins and damaged organelles in cells, but also induce autophagic death of tumor cells. Traditional Chinese medicine has advantages over Western medicine in better mediating autophagy to inhibit tumor development and progression, with the features of low toxicity, multiple targets, and multiple pathways. With an increasing number of studies on autophagy in traditional Chinese medicine, this article reviews the research advances in the effect of traditional Chinese medicine in autophagy in liver cancer in the past 10 years and explores and analyzes existing problems, hoping to provide a reference and new ideas for subsequent research on liver cancer.

Non-coding RNA and pancreatic cancer / 中南大学学报(医学版)

Non-coding RNA could regulate gene expression, involved in epigenetic modification, and participate in the cell differentiation, proliferation, apoptosis, and other life activities. Noncoding RNA also plays a crucial role in cancer occurrence, cancer cell invasion and distant metastases. Through mediating genome hyper-methylation, transcriptional regulation, regulation of transposable sequences, maintenance of genomic imprinting and DNA damage repair, noncoding RNA could regulate the growth and apoptosis of pancreatic cancer cells. Understanding the molecular mechanism of non-coding RNA in the development process of pancreatic cancer has important theoretical and practical value in the diagnosis, treatment and prognosis.

Gene detection and clinical study of rhinovirus isolated from children with acute low respiratory tract infection in Shanghai / 中华传染病杂志

Objective To understand human rhinovirus (HRV) etiology of acute lower respiratory tract infection (ALRTI) in children in Shanghai area and establish a nested reverse transcription- polymerase chain reaction (nested RT-PCR) assay.Methods Three hundred and forty-two naso- pharyngeal secretion (NPS) samples from ALRTI cases who were hospitalized were collected during January 2005—December 2005.Nested RT-PCR techniques were used to detect HRV-specific RNA.The PCR products were sequenced and data of nucleotides were analyzed.The proportion of HRV infection in children with ALRTI,the distribution of gender,age and season,and clinical char- acteristics were also investigated.Results Forty-six (13.5%) of 342 samples were HRV positive detected by nested RT-PCR.The sequences of 15 positive samples shared high homology of 83%- 97% with HRV sequence in GenBank.Within the 15 positive samples,nucleotide homology varied from 64.4% to 98.4%,and the ratio of genetic variation was from 1.6% to 48.3%./00.These 15 ampli- cons attribute to the two branches of HRV cladogram.The sequences of 15 amplieons were highly varied,in which single nucleotide mutation and several nearby nueleotides mutations were found. Ribonucleotide deletion and insertion in the nucleotide sequence was also found.HRV positive sam- ples were detected in 33 boys and 13 girls,respectively.The ratio of infection cases between boys and girls was 2.5:1.Of 46 HRV infected cases,27 (58.7%) were less than 12 months of age and 38 (82.6%) were less than 3 years old.HRV infected ALRTI occured all the year round and peaked from March to May.Of the patients whose NPS samples were HRV positive detected by nested RT-PCR,45 patients were diagnosed with bronchopneumonia and 1 was diagnosed with asthmatic bronchitis.Fever of most patients was moderate.The peripheral blood leukocyte counts in thirty-nine (84.8%) patients were less than 10?10~9/L.Neutrophil percentages in thirty-seven (80.4%) patients were less than 0.50.C-reactive protein of thirty-six (78.3%) patients were less than 8 mg/L. All of these features were the characteristics of viral pneumonia.The complications were not common and conditions of most patients were not severe.All the children were cured.Conclusions This nes- ted RT-PCR technique is highly specific,rapid and convenient for the detection of HRV RNA in NPS of patients with ALRTI and the genome of HRV viruses is highly variable.The incidence of HRV infection predominates in children in Shanghai area.ALRTI of HRV is short of specificity and condi- tions of most patients are not severe and their prognoses are fine.

Relationship between cytokine gene polymorphism and susceptibility to hepatitis B virus intrauterine infection / 中华流行病学杂志

<p><b>OBJECTIVE</b>To explore the possible relationship between cytokines (TNF-alpha, IFN-gamma, IL-4 and IL-10), which were expressed abnormal quantity in the peripheral blood to intrauterine HBV infectious children, gene single nucleotide polymorphism (SNP) and susceptibility to HBV intrauterine infection.</p><p><b>METHODS</b>A cross sectional study on molecular epidemiology was carried out. The subjects were selected from outpatients of the hepatitis B vaccine special clinics of our hospital. According to intrant criteria, children under high risk of HBV intrauterine infection were divided into immuno-failure group (group I) and immuno-effective group (group II) while children without high risk were included in the control group. Four gene SNP sites of TNF-alpha-238, IFN-gamma + 874, IL-4-590 and IL-10-1082 region were determined by real-time quantitative fluorescent PCR.</p><p><b>RESULTS</b>Significant differences of TNF-alpha-238 A allele frequency were found between group I and group II (chi(2) = 6.797, P < 0.05) as well as between group I and control group (chi(2) = 9.513, P < 0.05). No evident difference of TNF-alpha-238 A was found between group II and control group (chi(2) = 0.047, P > 0.05). Significant differences of IFN-gamma + 874 A allele frequency were found between group I and group II (chi(2) = 7.238, P < 0.05), and between group I and the controls (chi(2) = 5.199, P < 0.05) but no significant difference was found between group II and control group (chi(2) = 0.602, P > 0.05). Significant differences of IL-4-590 C/T allele frequency were not found between group I and group II (chi(2) = 0.632, P > 0.05), group I and control group (chi(2) = 0.584, P > 0.05), or between group II and control group (chi(2) = 0.004, P > 0.05) respectively. Significant differences of IL-10-1082 G allele frequency were found between group II and group I (chi(2) = 10.359, P < 0.001), and between group II and the controls (chi(2) = 35.418, P < 0.001), but not found between group I and control group (chi(2) = 1.759, P > 0.05).</p><p><b>CONCLUSION</b>This study suggested the possibility that TNF-alpha-238 A allele and IFN-gamma + 874 A allele were associated with HBV intrauterine infection. There was no evident relationship between IL-4-590 C/T allele SNP and susceptibility to HBV intrauterine infection, but the IL-10-1082 G allele seemed to be associated with preventive efficacy to HBV intrauterine infection.</p>

Relationship between cytokines gene polymorphism and susceptibility to hepatitis B virus intrauterine infection / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>The influences of genomic background are confirmed in more diseases. Immunologic tolerance after intrauterine infection of hepatitis B virus is considered to occur in T cells. Cytokines work effectively in eliminating virus by immune system after hepatitis B virus infection. To explore the relationship between cytokines (tumor necrosis factor-alpha, interferon-gamma, interleukin-4 and interleukin-10), which expressed abnormal quantity in the peripheral blood to intrauterine hepatitis B virus infectious children, gene single nucleotide polymorphism (SNP) and susceptibility to hepatitis B virus intrauterine infection.</p><p><b>METHODS</b>This is a cross sectional study of molecular clinical epidemiology. The subjects in this study were selected from outpatients of hepatitis B vaccine follow-up special clinics of our hospital in the period. According to intrant criteria, the high risk children of hepatitis B virus (HBV) intrauterine infection were divided into immune failure group (group I); and immune effective group (group II) and non high risk children belonged to the control group. Four gene SNP sites of TNF-alpha -238, IFN-gamma +874, IL-4 -590 and IL-10 -1082 were determined by real-time quantitative fluorescent polymerase chain reaction (PCR).</p><p><b>RESULTS</b>The significant differences of TNF-alpha -238 A allele frequency were found between group I and group II (chi(2) = 6.797, P < 0.05) and between group I and the control group (chi(2) = 9.513, P < 0.05). No evident differences of TNF-alpha -238 A were found between group II and control group (chi(2) = 0.047, P > 0.05); the significant differences of IFN-gamma +874 A allele frequency were found between group I and group II (chi(2) = 7.238, P < 0.05), and between group I and the control group (chi(2) = 5.199, P < 0.05). No evident differences were found between group II and the control group (chi(2) = 0.602, P > 0.05); the significant differences of IL-4 -590 C/T allele frequency were not found between group I and group II (chi(2) = 0.632, P > 0.05), also group I and the control group (chi(2) = 0.584, P > 0.05), and the group II and the control group (chi(2) = 0.004, P > 0.05) respectively; The significant differences of IL-10 -1082 G allele frequency were found between group II and group I (chi(2) = 10.359, P < 0.001), and between group II and the controls (chi(2) = 35.418, P < 0.001), but the significant differences were not found between group I and the control group (chi(2) = 1.759, P > 0.05).</p><p><b>CONCLUSIONS</b>This study suggested the possibility that the TNF-alpha -238 A allele and IFN-gamma +874 A allele were associated with HBV intrauterine infection. There was no evident relationship between IL-4 -590 C/T allele SNP and susceptibility to HBV intrauterine infection, but the IL-10 -1082 G allele was associated with preventive efficacy to HBV intrauterine infection.</p>