OBJECTIVES: To explore the cytotoxicity of four wild mushrooms involved in a case of Yunnan sudden unexplained death (YNSUD), to provide the experimental basis for prevention and treatment of YNSUD. METHODS: Four kinds of wild mushrooms that were eaten by family members in this YNSUD incident were collected and identified by expert identification and gene sequencing. Raw extracts from four wild mushrooms were extracted by ultrasonic extraction to intervene HEK293 cells, and the mushrooms with obvious cytotoxicity were screened by Cell Counting Kit-8 (CCK-8). The selected wild mushrooms were prepared into three kinds of extracts, which were raw, boiled, and boiled followed by enzymolysis. HEK293 cells were intervened with these three extracts at different concentrations. The cytotoxicity was detected by CCK-8 combined with lactate dehydrogenase (LDH) Assay Kit, and the morphological changes of HEK293 cells were observed under an inverted phase contrast microscope. RESULTS: Species identification indicated that the four wild mushrooms were Butyriboletus roseoflavus, Boletus edulis, Russula virescens and Amanita manginiana. Cytotoxicity was found only in Amanita manginiana. The raw extracts showed cytotoxicity at the mass concentration of 0.1 mg/mL, while the boiled extracts and the boiled followed by enzymolysis extracts showed obvious cytotoxicity at the mass concentration of 0.4 mg/mL and 0.7 mg/mL, respectively. In addition to the obvious decrease in the number of HEK293 cells, the number of synapses increased and the refraction of HEK293 cells was poor after the intervention of Amanita manginiana extracts. CONCLUSIONS The extracts of Amanita manginiana involved in this YNSUD case has obvious cytotoxicity, and some of its toxicity can be reduced by boiled and enzymolysis, but cannot be completely detoxicated. Therefore, the consumption of Amanita manginiana is potentially dangerous, and it may be one of the causes of the YNSUD.
Humans ; HEK293 Cells ; Sincalide ; China ; Amanita ; Death, Sudden

OBJECTIVE: To investigate the therapeutic effect of Epothilone D on traumatic optic neuropathy (TON) in rats. METHODS: Forty-two SD rats were randomized to receive intraperitoneal injection of 1.0 mg/kg Epothilone D or DMSO (control) every 3 days until day 28, and rat models of TON were established on the second day after the first administration. On days 3, 7, and 28, examination of flash visual evoked potentials (FVEP), immunofluorescence staining and Western blotting were performed to examine the visual pathway features, number of retinal ganglion cells (RGCs), GAP43 expression level in damaged axons, and changes of Tau and pTau-396/404 in the retina and optic nerve. RESULTS: In Epothilone D treatment group, RGC loss rate was significantly decreased by 19.12% (P=0.032) on day 3 and by 22.67% (P=0.042) on day 28 as compared with the rats in the control group, but FVEP examination failed to show physiological improvement in the visual pathway on day 28 in terms of the relative latency of N2 wave (P=0.236) and relative amplitude attenuation of P2-N2 wave (P=0.441). The total Tau content in the retina of the treatment group was significantly increased compared with that in the control group on day 3 (P < 0.001), showing a consistent change with ptau-396/404 level. In the optic nerve axons, the total Tau level in the treatment group was significantly lower than that in the control group on day 7 (P=0.002), but the changes of the total Tau and pTau-396/404 level did not show an obvious correlation. Epothilone D induced persistent expression of GAP43 in the damaged axons, detectable even on day 28 of the experiment. CONCLUSION Epothilone D treatment can protect against TON in rats by promoting the survival of injured RGCs, enhancing Tau content in the surviving RGCs, reducing Tau accumulation in injured axons, and stimulating sustained regeneration of axons.
Animals ; Disease Models, Animal ; Epothilones ; Evoked Potentials, Visual ; Nerve Regeneration/physiology* ; Optic Nerve Injuries/metabolism* ; Rats ; Rats, Sprague-Dawley ; Retinal Ganglion Cells/physiology*

OBJECTIVES: To explore the possible mechanism of Yunaconitine poisoning by studying the changes of urine metabolic profile in rats chronically poisoned by Yunaconitine via non-targeted metabolomics. METHODS: A rat model of Yunaconitine poisoning was established, and a metabolomics method based on UPLC-QTOF-MS technology was used to obtain the urine metabolic profile. Principal component analysis (PCA), orthogonal projections to latent structures-discriminant analysis (OPLS-DA), variable importance in projection (VIP) value greater than 1, fold change (FC) value greater than 3 or less than 0.33 and P value less than 0.05 were used to screen potential biomarkers related to the toxicity of Yunaconitine. The metabolic pathway analysis was performed through the MetaboAnalyst website and pathological changes of related tissues were observed. RESULTS: Sixteen potential biomarkers including L-isoleucine were screened, which mainly involved six metabolic pathways including the biosynthesis and degradation of valine, leucine and isoleucine, pentose and glucuronate interconversions, and propanoate metabolism, alanine, aspartate and glutamate metabolism, tyrosine metabolism. Pathological studies showed that rat toxic change in nervous system, liver and cardiac caused by Yunaconitine. CONCLUSIONS Yunaconitine may cause neurotoxicity, hepatotoxicity and cardiotoxicity by affecting amino acid and glucose metabolism.
Aconitine/analogs & derivatives* ; Animals ; Biomarkers/metabolism* ; Chromatography, High Pressure Liquid ; Metabolome ; Metabolomics ; Rats

Leaf miner is one of the major pests on safflower, which causes yield loss and poor quality seriously. "Weihonghua", "nine safflower varieties" and "three chemical insecticides" as materials that used to evaluate variety and regularity of leaf miner, safflower resistant level, and different proportions insecticides in field efficiency test. The results showed that Liriomyza sativae and L. huidobrensis accounted for 80%, the peak period of two pests was all in July; but Phytomyza horticola is relative less, its peak period occured in June. Three were great difference of resistance to leaf miner among safflower varieties, FQ12 and YJ65 expressed higher resistibility to leaf miner by ratio method. With abamectin 2% emulsifiable concentrate diluted for 2 000 times, or the mixture three insecticides(bifenthrin 20% water emulsions, thiamethoxam 25% water dispersible granule, abamectin 2% emulsifiable concentrate=1∶1∶1) diluted for 3 000 times, which were sprayed on leaves at squaring stage and lethal rate was 96% after 48 h in the study. Through comparative study on the variety and regularity of leaf miner, screen for resistant varieties to leaf miner and for high efficiency pesticide. The study provides theoretical basis and reference for integrated pest management of leaf miner.
Animals ; Carthamus tinctorius ; Diptera ; Insecticides ; Pesticides ; Thiamethoxam

Objective To explore the association of cardiac disease associated genetic variants and the high incidence of Yunnan sudden unexplained death （YNSUD） in Yi nationality. Methods The genomic DNA was extracted from peripheral blood samples collected from 205 Yi villagers from YNSUD aggregative villages （inpatient group） and 197 healthy Yi villagers from neighboring villages （control group）. Fifty-two single nucleotide variants （SNVs） of 25 cardiac disease associated genes were genotyped using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry （MALDI-TOF-MS）. The SPSS 17.0 was used to analyze data. The pathogenicities of variants with differences between the two groups that have statistical significance were predicted by protein function prediction software PolyPhen-2 and SIFT. All villagers from inpatient group were given electrocardiogram （ECG） examination using a 12-lead electrocardiograph. Results The allele frequency and the genotype frequency of missense mutation DSG2 （rs2278792, c.2318G>A, p.R773K） of pathogenic genes of arrhythmogenic right ventricular cardiomyopathy （ARVC） in inpatient group was higher than that in control group （P<0.05）. Abnormal ECG changes were detected in 71 individuals （34.6%） in the inpatient group, among which 54 individuals carried R773K mutation, including clockwise （counterclockwise） rotation, left （right） axis deviation, ST segment and T wave alteration and heart-blocking. Conclusion Definite pathogenic mutations have not been found in the 52 cardiac disease genes associated SNVs detected in Yi nationality in regions with high incidence of YNSUD. The cause of high incidence of YNSUD in Yi nationality needs further study.
Arrhythmogenic Right Ventricular Dysplasia ; China/epidemiology* ; Death, Sudden/etiology* ; Death, Sudden, Cardiac/etiology* ; Ethnicity/genetics* ; Humans ; Incidence ; Mutation

Objective To explore the correlation between 4 tag single nucleotide polymorphisms （Tag SNP） sites （rs7721799, rs32897, rs7718461, rs10062367） of corticotropin releasing hormone binding protein （CRHBP） and schizophrenia and aggressive behavior in the Yunnan Han population. Methods Case-control correlation analysis was used to establish a complex amplification system. Improved multiplex ligase detection reaction （iMLDR） technology was used to detect the genotypes of 4 SNP sites of CRHBP gene of 163 Han schizophrenic patients （including 81 patients with aggressive behavior, 82 patients without aggressive behavior） and 345 healthy Han individuals, which were analyzed statistically by SPSS 19.0, Haploview 4.2 and PHASE 2.1 software. Results There was no correlation between the 3 SNP sites of CRHBP gene and the onset of schizophrenia except for the rs7718461 site （P>0.05）. The relative risk of aggressive behavior of patients carrying GG or GA genotype at rs7718461 site were 4.903 times higher than those carrying AA genotype （P<0.05）. Conclusion The CRHBP gene may not be associated with the occurrence of schizophrenia in Yunnan Han population, but AA genotype of rs7718461 may reduce the risk of aggressive behavior in schizophrenia patients.
Asian People/genetics* ; Carrier Proteins/genetics* ; China ; Gene Frequency ; Genetic Predisposition to Disease ; Genotype ; Humans ; Polymorphism, Single Nucleotide ; Schizophrenia/genetics*

OBJECTIVE: CDKN2B-AS1 polymorphisms were shown to associate with the risk of stroke in European. The goal of this study was to evaluate the contribution of CDKN2B-AS1 rs1333049 to the risk of hemorrhagic stroke (HS) and brain tumor (BT) in Han Chinese. METHODS: A total of 142 HSs, 115 BTs, and 494 controls were included in the current association study. The genotyping test was performed using the melting temperature shift method. RESULTS: We failed to validate the association of CDKN2B-AS1 rs1333049 with the risk of brain disease. Significantly higher levels of low-density lipoprotein cholesterol (LDL-C) (p=0.027), high-density lipoprotein cholesterol (HDL-C) (p<0.001) and total cholesterol (TC) (p<0.001) were found in HSs in the genotype GG/GC carriers, but not the genotype CC carriers (p>0.05). The meta-analysis of 10 studies among 133,993 individuals concluded that rs1333049 of CDKN2B-AS1 gene was likely to increase a 16% incidence rate of cerebrovascular disease (CD) among various populations (odds ratio 1.16, 95% confidence interval 1.08–1.25; p<0.0001, random-effect method). CONCLUSION: Our case-control study identified rs1333049 genotypes showed different association with the concentration of the LDL-C, HDL-C and TC in the HS patients. Meta-analysis supported the association between rs1333049 and CD risk in various populations, although we were unable to observe association between rs1333049 and the risk of HSs in Han Chinese.
Asian Continental Ancestry Group ; Brain Diseases* ; Brain Neoplasms ; Brain* ; Case-Control Studies* ; Cerebrovascular Disorders ; Cholesterol ; Freezing ; Genotype ; Humans ; Incidence ; Lipoproteins ; Methods ; Stroke

Human xanthine oxidase is considered to be a target for therapy of hyperuricemia. Cichorium intybus is a Chinese plant medicine which widely used in Xinjiang against various diseases. In order to screen the inhibitors of xanthine oxidase from C. intybus and to explore main pharmacological actions of cichory a compound collection of C. intybus was built via consulting related references about chemical research on cichory. The three-dimensional crystal structure of xanthine oxidase (PDB code: 1N5X) from Protein Data Bank was downloaded.. Autodock 4.2 was employed to screen the inhibitors of xanthine oxidase from cichory 70 compounds were found to possess quite low binding free energy comparing with TEI (febuxostat). C. intybus contains constituents possessing potential inhibitive activity against xanthine oxidase. It can explain the main pharmacological actions of cichory which can significantly lower the level of serum uric acid.
Chicory ; chemistry ; Databases, Protein ; Drugs, Chinese Herbal ; chemistry ; Enzyme Inhibitors ; chemistry ; Humans ; Molecular Docking Simulation ; Molecular Structure ; Xanthine Oxidase ; antagonists & inhibitors ; metabolism

OBJECTIVETo explore the integrated application of sales of child-specific over-the-counter (OTC) cold related medications in retail pharmacies and healthcare visits of children for influenza-like illness (ILI) in surveillance and early warning of influenza among children.

METHODSAn integrated surveillance system (ISS) was implemented since 2012 in Qianjiang County, a rural area in Hubei Province of China. The daily information from August 1, 2012 to February 28, 2013 of health care visits of children for ILI reported by 80 health facilities and sales of 14 child-specific over-the-counter (OTC) cold related medications reported by 11 pharmacies were extracted from ISS database. Cumulative sums (CUSUM) model was conducted to analyze the degree of fitting and the early warning signal generated; the correlationship was then analyzed further.

RESULTSIn 212 days, 983 visits of children for ILI and 12 819 sales by person of child-specific OTC were reported. Conducting CUSUM model, the fitting degree was in the acceptable range, 31 warning signals were generated from ILI data series with 3 peak periods and 14 from OTC data series with 2 peak periods. A similar time trend of two data series was observed with a correlation(r = 0.497, P < 0.05), but without any spatial clustering. And the optimal correlation(r = 0.505, P < 0.05) appeared at a time offset of 4 days preceded by OTC sales.

CONCLUSIONThe availability of integrated surveillance system for symptoms could be applied for surveillance of influenza among children; while it could explore the possibility of real epidemic in the very early stage.

Child ; China ; epidemiology ; Disease Outbreaks ; prevention & control ; Humans ; Influenza, Human ; epidemiology ; prevention & control ; Nonprescription Drugs ; Population Surveillance

BACKGROUNDThe optimal revascularization strategy in patients with heart failure with preserved ejection fraction (HFPEF) remains unclear. The aim of the present study was to compare the effects of percutaneous coronary intervention (PCI) and coronary artery bypass grafting (CABG) in patients with HFPEF.

METHODSFrom July 2003 through September 2005, a total of 920 patients with coronary artery disease (CAD) and HFPEF (ejection fraction ≥ 50%) underwent PCI (n = 350) or CABG (n = 570). We compared the groups with respect to the primary outcome of mortality, and the secondary outcomes of main adverse cardiac and cerebral vascular events (MACCE), including death, myocardial infarction, stroke and repeat revascularization, at a median follow-up of 543 days.

RESULTSIn-hospital mortality was significantly lower in the PCI group than in the CABG group (0.3% vs. 2.5%, adjusted P = 0.016). During follow-up, there was no significant difference in the two groups with regard to mortality rates (2.3% vs. 3.5%, adjusted P = 0.423). Patients receiving PCI had higher MACCE rates as compared with patients receiving CABG (13.4% vs. 4.0%, adjusted P < 0.001), mainly due to higher rate of repeat revascularization (adjusted P < 0.001). Independent predictors of mortality were age, New York Heart Association (NYHA) class and chronic total occlusion.

CONCLUSIONAmong patients with CAD and HFPEF, PCI was shown to be as good as CABG with respect to the mortality rate, although there was a higher rate of repeat revascularization in patients undergoing PCI.

Aged ; Angioplasty, Balloon, Coronary ; mortality ; Coronary Artery Bypass ; mortality ; Female ; Heart Failure ; physiopathology ; therapy ; Hospital Mortality ; Humans ; Male ; Middle Aged ; Stents