Acute Toxicity and Hepatotoxicity of Aqueous Extracts of Taxilli Herba from Different Hosts in Zebrafish Model / 中国实验方剂学杂志

Objective:To explore the acute toxicities and hepatotoxicities of aqueous extracts of Taxilli Herba from <italic>Morus alba</italic>， <italic>Toxicodendron</italic> <italic>trichocarpum</italic>， <italic>Camellia oleifera</italic>， <italic>Salix babylonica</italic>， <italic>Melia azedarach</italic>， and <italic>Nerium indicum</italic> against zebrafish model and the effect of different hosts on the toxicity of Taxilli Herba， hoping to provide a theoretical basis for the safe use of Taxilli Herba. Method:The normally developed AB zebrafish at 3-day post fertilization was selected for acute toxicity study. According to the results of preliminary toxicity experiments， the zebrafishes were treated with aqueous extracts of Taxilli Herba from different hosts at six doses， and their mortality was calculated 72 h later. GraphPad Prism 6.0 was used for plotting the dose-toxicity curve， followed by the calculation of their median lethal concentration （LC₅₀） and 10% lethal concentration （LC₁₀）. The gz15Tg/+（AB） liver fluorescent protein transgenic zebrafish with normal development at 4-day post fertilization was applied for the hepatotoxicity study. The zebrafishes were divided into the low-， medium-， and high-dose groups of aqueous extracts of Taxilli Herba from six hosts， the positive control （acetaminophen） group， and the blank （embryo amniotic fluid） group， and then treated with the corresponding drugs. Seventy-two hours later， the liver morphology and fluorescent area changes in zebrafish were observed. And the activities of alanine aminotransferase （ALT） and aspartate aminotransferase （AST） were detected. Result:The results of acute toxicity test demonstrated that the LC₅₀ values of water extracts of Taxilli Herba from <italic>M. alba</italic>， <italic>T.</italic> <italic>trichocarpum</italic>， <italic>C. oleifera</italic>， <italic>S. babylonica</italic>， <italic>M. azedarach</italic>， and <italic>N. indicum</italic> were 1.24， 0.94， 0.51， 0.38， 0.11， 0.09 g·L^-1， respectively， and the LC₁₀ values were 0.70， 0.60， 0.35， 0.28， 0.08， 0.07 g·L^-1， respectively. As revealed by hepatotoxicity test， compared with the blank group， the positive control group exhibited liver morphological changes， decreased fluorescent area （<italic>P</italic><0.01）， and elevated ALT and AST activities （<italic>P</italic>< 0.01）， suggesting that acetaminophen was hepatotoxic to zebrafish. However， there was no change in the liver morphology or fluorescent area of zebrafish in the low-， medium-， and high-dose groups of water extracts of Taxilli Herba from <italic>M. alba</italic>， and the ALT and AST activities were decreased. By contrast， the liver morphology and fluorescent areas in the medium- and high-dose groups of water extracts of Taxilli Herba from <italic>T.</italic> <italic>trichocarpum</italic>， <italic>C. oleifera</italic>， <italic>S. babylonica</italic>， <italic>M. azedarach</italic>， and <italic>N. indicum</italic> changed to varying degrees （<italic>P</italic><0.05， <italic>P</italic><0.01）. Besides， the activities of both ALT and AST were also enhanced. These indicated that Taxilli Herba from <italic>M. alba</italic> had no hepatotoxicity to zebrafish， while that from <italic>T.</italic> <italic>trichocarpum</italic>， <italic>C. oleifera</italic>， <italic>S. babylonica</italic>， <italic>M. azedarach</italic>， and <italic>N. indicum</italic> showed varying degrees of hepatotoxicity to zebrafish. Conclusion:The toxicity of Taxilli Herba is host-dependent. Taxilli Herba from <italic>M. alba</italic> has no hepatotoxicity， but that from the other five hosts shows varying degrees of hepatotoxicity. Standardizing the host source may be an important measure to realize the medication safety of Taxilli Herba.

Analysis of Serum Transcriptome Characteristics of Patients with Yin and Yang Syndromes of Acute Ischemic Stroke / 中国实验方剂学杂志

Objective:To obtain the regulatory relationship between genes by screening the differentially expressed long non-coding ribonucleic acid(lncRNA), microRNA(miRNA) and messenger RNA(mRNA) in serum of patients with Yin and Yang syndromes of acute ischemic stroke, and to discuss the material basis and biological mechanism of formation of Yin and Yang syndromes of acute ischemic stroke from the transcriptome level. Method:The microarray chips were adopted to detect expression of lncRNA, mRNA and miRNA in serum of ischemic stroke patients with Yin and Yang syndromes and non-stroke subjects(10 cases each). Differential expression profiles related to Yin and Yang syndromes were selected by conjoint analysis. Further, the obtained differential genes were subjected to antisense lncRNA and mRNA co-expression analysis, gene ontology(GO) and Kyoto encyclopedia of genes and genomes(KEGG) functional pathway analysis, and the intergenic regulatory relationship was obtained to predict the target genes of lncRNA. Partial differential genes in 40 patients(10 with Yang syndrome and 30 with Yin syndrome) were verified by real-time fluorescence quantitative polymerase chain reaction(Real-time PCR). Result:The expression of 227 lncRNA, 54 mRNA and 4 miRNA were closely related to Yang syndrome, 394 lncRNA and 206 mRNA were closely related to Yin syndrome. Antisense lncRNA RP11-647P12.1 and RP11-677M14.2 may regulate the expression of neuron-derived neurotrophic factor(NDNF) and neurogranin(NRGN) by up-regulating the expression level in Yang syndrome. The differential expression of mRNA between Yin syndrome and Yang syndrome was mainly related to neurotransmitter receptor activity regulation, endocrine hormone regulation, inflammatory response, renin-angiotensin system and other pathways. Conclusion:There are differences in the expression profiles of lncRNA, miRNA and mRNA between Yin syndrome and Yang syndrome in acute ischemic stroke, which may be regulated by multiple pathways, such as blood pressure regulation, adrenergic receptor regulation, renin-angiotensin system and γ-aminobutyric acid(GABA). The transcriptome characteristics provide scientific basis for studying the biological basis of Yin syndrome and Yang syndrome in acute ischemic stroke.

Under-5-mortality rate and causes of death in China, 2000 to 2010 / 中华流行病学杂志

Objective To assess the changes and the leading cause of deaths for children under 5 years old,in China,during 2000-2010,with the aim of evaluation on the progress in achieving the relative goal set by "National Program of Action for Child Development in China (2001-2010)",and understanding the related challenges.Methods Data used in this study were collected from the population-based National Maternal and Child' s Health Surveillance Network of China.Infant Mortality Rate (IMR),Under-5-mortality rate (U5MR) and the leading cause of deaths for under-5 children were analyzed.Results Nationwide IMR and U5MR in 2010 dropped by 59.3％and 58.7％ respectively,compared to that in 2000.Decreases by 50.8％ and 47.1％ in IMR and U5MR were observed in urban areas,and 56.5％ and 56.0％ in rural areas during this period.Compared with data from 2000,the leading causes-specific U5MR in 2010 had significantly declined.The top 5 leading causes of death in 2010 were premature birth/low birth weight,pneumonia,birth asphyxia,congenital heart disease and accidental suffocation,but were different in urban and rural areas.In 2010,both IMR and U5MR from the rural areas were 2.8-folds than that of the urban areas.In addition,IMRs in the Middle and Western parts of China were 1.5 and 2.3-folds respectively of that in the East,and U5MR in Middle and West was 1.5 and 2.2-folds respectively of that in East.Conclusion IMR,U5MR and the leading causes specific mortality rate in China declined remarkably from 2000 to 2010,and the goal set by "National Program of Achon for Child Development in China (2001-2010)" had been successfully achieved.However,the disparity on child' s health in regions and in urban or rural areas,still remained a challenge.

Analysis on the diarrhea mortality rate, pre-death diagnosis and treatment of children under-5 in China, 1996-2006 / 中华流行病学杂志

Objective To understand the trends of diarrhea mortality rate, pre-death diagnosis and treatment of children under-5 in China, from1996 to 2006. Methods We used data obtained from the 1996 to 2006 national child mortality surveillance network, including 116 counties (cities) throughout China, to evaluate the under 5 mortality rate (U5MR) due to diarrhea in different geographical areas, and related factors of under 5 children mortality due to diarrhea. Results Data from the national U5MR due to diarrhea fell from 249.8 in 1996 to 75.6 per 100 000 live births, in 2006. The U5MR due to diarrhea in urban reduces from 11.6 in 1996 to 6.1 per 100 000 live births in 2006, with a reduction of 47.4%. The U5MR due to diarrhea in rural decreased from 304.7 in 1996 to 94.3 per 100 000 live births in 2006, with a reduction of 69.1%. The U5MR due to diarrhea in coastal,inland and remote areas fell from 48.9, 178.9 and 566.9 in 1996 to 6.2,30.4 and 199.2 per 100 000live births in 2006, with a reduction of 87.3%, 83.0% and 64.9%, respectively. Among the rural children died of diarrhea, about 37.9% were diagnosed in a village clinic, 15.1% never received any diagnostic procedure. Nearly 20% of the patients had not been treated, with 50%-60% of them had only been treated in an outpatient department. Conclusion During 1996-2006, the U5MR due to diarrhea showed a substantially downward trend in China but the disparities between urban and rural,remote and coastal, areas were increasing.

Analysis on under-5 mortality rate and the leading kinds of diseases in China, from 2000 to 2006 / 中华流行病学杂志

Objective To study the changing pattern of infant mortality and under-5 mortality rate in China from 2000 to 2006, and to evaluate China's progress in achieving the United Nations' Millennium Development Goal 4. Methods A population-based survey was conducted through a nationwide multi-level surveillance network. The mortality rate and the proportion of death for children under 5 were analyzed. Results The infant mortality rate (IMR), under-5 mortality rate (U5MR) in China dropped to 17.2, 20.6 per 1000 live births in 2006, respectively, comparing to 32.2 and 39.7 per 1000 live births in 2000. In urban areas, IMR, U5MR dropped to 8.0, 9.6 per 1000 live births in 2006, respectively while they were 11.8 and 13.8 per 1000 live births respectively in 2000. In rural areas, IMR, USMR dropped to 19.7 and 23.6 per 1000 live births in 2006, respectively but they were 37.0 and 45.7 per 1000 live births respectively in 2000. During this period, the mortality rates due to pneumonia and diarrhea had dropped sharply. The proportion of deaths due to pneumonia, diarrhea also dropped from 19.5%, 4.9% in 2000 to 15.6%, 3.7% in 2006, respectively. In urban areas, the proportion of deaths due to pneumonia dropped from 9.9% in 2000 to 9.8% in 2006, In rural areas, the proportion of deaths due to pneumonia, diarrhea dropped from 20.1%, 5.2% in 2000 to 16.2%, 4.0% in 2006, respectively. Conclusion The U5MR in China remarkably dropped from 2000 to 2006. Based on data through the surveillance program, China should be able to accomplish the Millennium Development Goals 4 of the United Nations as planned.

DNA mismatch repair enzyme hMSH2 genetic polymorphism in southern Chinese Han population / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To study hMSH2 genetic polymorphism in southern Chinese Han population.</p><p><b>METHODS</b>The basic materials and blood samples from 163 southern Chinese were collected. The mutations of exon 6 and exon 7 of hMSH2 gene were investigated by PCR-SSCP, followed by DNA sequencing.</p><p><b>RESULTS</b>Fragments of 250 bp including exon 6 and fragments of 323 bp including exon 7 of hMSH2 gene were amplified by multiple PCR. The allele frequencies of C18, A82 and B39 type mutations were 0.0184, 0.0031, 0.0031, respectively. The gene frequencies and gene type frequencies of three polymorphism sites in normal population accorded with Hardy-Weinberg equilibrium (P>0.05). The heterozygosity of C18 type mutation (0.0361) was the highest.</p><p><b>CONCLUSION</b>There were three polymorphism sites in exon 7 of hMSH2 gene in southern Chinese Han population, among which the genotype frequency of C18 type was the highest, suggesting that C18 type mutation be a useful genetic mark.</p>