Metallomics is a frontier interdisciplinary subject at its vigorous development stage. Its goal is to systematically study the content, distribution, chemical species, structural characteristics and functions of metal elements in biological system. It is also a comprehensive discipline to study the existing state and function of free or complex metal elements in life. Metallomics is an ideal tool to study the biological behavior of inorganic elements, which can be used to solve many problems in the research of mineral Chinese medicine(MCM). It provides a strong theoretical basis and technical support for the research of MCM. Its theory and methods provide re-ference and enlightenment for the in-depth study of MCM, and also provide new ideas and open up new ways for the research of MCM. The application of metallomics theory and methods in the research of MCM is of great significance to reveal the material basis and mec-hanism of MCM, promote the process of basic research on MCM, fully exploit and utilize medicinal mineral resources and carry forward the traditional MCM treasure in China. In this paper, we introduced the concept, academic development, research content and research methods of metallomics, and discussed the application prospects of metallomics in the analysis of inorganic element composition characteristics and quality control, material basis and mechanism of MCM, so as to provide reference for further researches on MCM.
China ; Drugs, Chinese Herbal ; Medicine, Chinese Traditional ; Minerals ; Quality Control

Objective To analyze the prognosis of pediatric burns and its influencing factors. Methods Clinical data of 1 737 children with burns from January 2013 to December 2017 in the First Affiliated Hospital of Anhui Medical University was analyzed by retrospective method. The demographic, clinical features, and related factors affecting prognosis . Results Log-binominal regression model showed that the care rate was higher in children aged 1- and 3- compared with children aged 7-12 (all P<0.05); Boiling water burns had a higher care rate than electric shock and flame burns (including chemical burn) (all P<0.05); Moderate and severe burns had a higher care rate than heavy severe burns (all P<0.05); The unhealed rate of pediatric burns in summer was higher than burned in winter (RR=0.861,95% CI:0.690-1.074); Children without complications had a higher care rate (P<0.05); Children lived in rural areas have a higher unhealed rate than lived in urban areas (RR=0.713，95% CI:0.618-0.824). Conclusions The care rate of pediatric burns was 51.1%. Major influencing factors included children aged 7-12, burned by electric and flame (including chemical burns), burned severe extraordinarily, burned in summer, and with complications, lived in rural.

Based on the distribution information of 110 samples and 55 environmental factors, Maxent model was used to predict the ecology suitability regions of Trollius chinensis. The study aims at providing theory basis for the cultivation of T. chinensis. The results showed that the Maxent model prediction result was good (AUC>0.9) and the main factors effecting the ecology suitability regions of T. chinensis were precipitation in July, standard deviation of seasonal variation of temperature, annual mean temperature, precipitation in August and altitude. The ecology suitable regions of T. chinensis mainly concentrated in Shanxi, Hebei, east of Inner Mongolia, west of Jilin and Liaoning, north of Shaanxi, south of Ningxia, east and south of Gansu, and east of Qinghai. The results indicated that except for traditional distribution regions, north of Shaanxi, south of Ningxia, east and south of Gansu, and east of Qinghai could selected as the regions for cultivation of T. chinensis. It provides theory basis for selecting suitable regions to cultivate T. chinensis.

Objective To explore the characteristics and components of recurrent papillary thyroid cancer in patients with metabolic syndrome .Methods We retrospectively reviewed the information of the patients with recurrent papillary thyroid cancer after initial surgery during January 1st ,2010 and December 31st ,2015 in the First Affiliated Hospital of Zhengzhou University .We compared tumor size ,lymph node metastasis ,recurrence time and postoperative invasion rate in metabolic syndrome and non-metabolic syndrome groups . Results Totally 82 patients were included with 34 men and 48 women .There was no significant difference between patients with and those without metabolic syndrome grouped by the classic diagnosis approach .However ,the lymph node metastasis grade of recurrent papillary thyroid cancer patients who also suffered from at least two metabolic disorders ,was lower ,especially in women (P=0 .002) .Moreover ,patients with metabolic disorders had shorter recurrence time (Pdiabetes=0 .034 , Pdyslipidemia =0 .037 , PBMI =0 .004 , PMetS2 =0 .036) .Conclusion Papillary thyroid cancer patients with metabolic disorder ,especially with two or more components of metabolic syndrome and overweight and/or obesity ,may have an increasing risk of recurrence .

Objective To investigate the neuroprotective effect and mechanism of levofloxacin (LEV) on acute cerebral ischemia-reperfusion injury in mice.Methods A total of 30 C57BL/6J mices were randomly divided into sham operation group (n =6),experimental group (n =18) and control group (n =6).According to the intervention time,experimental group was divided into 0,3,6 h experimental group,6 mices in each group.The model of middle cerebral artery occlusion (MCAO) was established by modified Longa method,sham operation group did not block the middle cerebral artery,experimental group was given LEV 10 mg · kg-1 by tail vein at 0,3,6 h after modeling,sham opera tion group and control group were given 0.9％ NaC1.The neurological score was measured by Longa score;the infarct volume was measured by 2,3,5-triphenyte-trazoliumchloride (TTC) staining;the neuronal apoptosis was detected by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) method,apoptosis index (AI) was calculated;the positive expression of B-lymphoma-2 gene-related X protein (Bax) and caspase-3 was detected by immunohistochemistry.Results The Longa scores in sham operation group,control group and 0,3,6 h experimental group were 0,(2.88 ± 1.03),(1.77 ± 0.56),(2.21 ± 0.96),(2.66 ± 1.03) points.Compared with control group,the Longa score of 0 h group was significantly reduced (P ＜ 0.05),but there was no significant difference among 0,3 and 6 h groups (P ＞ 0.05).The cerebral infarct volume in sham operation group,control group and 0,3,6 h experimental group were 0,(21.03 ± 0.25),(13.14 ± 0.44),(13.21 ± 0.53),(16.86 ± 0.65) mm3.The AI in sham operation group,control group and 0,3,6 h experimental group were 1.16 ±0.32,36.51 ±2.44,18.45 ±0.46,20.15 ±0.69,26.49 ±0.77.Compared with control group,the cerebral infarct volume and AI of experimental groups were significantly decreased (P ＜ 0.01).The cerebral infarct volume in 0,3 h experimental group were significantly lower than 6 h experimental group (P ＜0.01).The cerebral infarct volume and AI increased gradually with the prolong of LEV duration,and the difference was significant in 3 groups (P ＜ 0.01).The Bax in sham operation group,control group and0,3,6 h experimental group were 2.63 ±1.04,20.76±1.75,18.13 ±0.42,19.05 ±0.71,19.25 ±1.32,caspase-3 were 5.15 ±2.02,60.13 ±2.41,34.31±2.36,36.25 ±2.01,52.13 ±2.23.Compared with control group,the caspase-3 in experimental groups were significantly lower (P ＜0.05,P ＜0.01).The expression of caspasc-3 in mice gradually increased with the prolongation of LEV,there was no significant difference in Bax expression among 3 groups (P ＞ 0.05).Conclusion LEV can inhibit the expression of apoptotic protein Bax and caspase-3 after cerebral ischemia reperfusion injury,so as to inhibit the apoptosis of nerve cells and play a role in brain protection.

BACKGROUNDThe efficacy and safety of telmisartan combined with clopidogrel, leflunomide, or both drugs for immunoglobulin A nephropathy (IgAN) are unclear. This study was designed to evaluate the efficacy and safety of telmisartan combined with clopidogrel, leflunomide, or both drugs for IgAN.

METHODSIt is a multicenter, prospective, double-dummy randomized controlled trial. Primary IgAN patients were recruited in 13 renal units across Beijing, China, from July 2010 to June 2012. After a 4-week telmisartan (80 mg/d) wash-in, 400 patients continuing on 80 mg/d telmisartan were randomly assigned to additionally receive placebo (Group A), 50 mg/d clopidogrel (Group B), 20 mg/d leflunomide (Group C), or 50 mg/d clopidogrel and 20 mg/d leflunomide (Group D). The 24-week intervention was completed by 360 patients. The primary endpoint was change in 24-h proteinuria at 24 weeks. A linear mixed-effect model was used to analyze the changes at 4, 12, and 24 weeks. Generalized estimating equations were used to evaluate changes in hematuria grade. This trial was registered at the Chinese Clinical Trial Registry.

RESULTSThe effects of telmisartan combined with leflunomide on changes in proteinuria (0.36 [95% confidence interval (CI) 0.18-0.55] g/d, P < 0.001), in serum uric acid (76.96 [95% CI 57.44-96.49] μmol/L, P < 0.001), in serum creatinine (9.49 [95% CI 6.54-12.44] μmol/L, P < 0.001), and in estimated glomerular filtration rate (-6.72 [95% CI-9.46 to -3.98] ml·min-1·1.73 m-2, P < 0.001) were statistically significant, whereas they were not statistically significant on changes in systolic and diastolic blood pressure and weight (P > 0.05). Telmisartan combined with clopidogrel had no statistical effect on any outcome, and there was no interaction between the interventions. No obvious adverse reactions were observed.

CONCLUSIONSTelmisartan combined with leflunomide, not clopidogrel, is safe and effective for decreasing proteinuria in certain IgAN patients.

TRIAL REGISTRATIONchictr.org.cn, ChiCTR-TRC-10000776; http://www.chictr.org.cn/showproj.aspx?proj=8760.

Adolescent ; Adult ; Benzimidazoles ; adverse effects ; therapeutic use ; Benzoates ; adverse effects ; therapeutic use ; Blood Pressure ; drug effects ; China ; Creatinine ; blood ; Female ; Glomerular Filtration Rate ; drug effects ; Glomerulonephritis, IGA ; blood ; drug therapy ; Humans ; Isoxazoles ; adverse effects ; therapeutic use ; Kidney Function Tests ; Male ; Middle Aged ; Prospective Studies ; Ticlopidine ; adverse effects ; analogs & derivatives ; therapeutic use ; Treatment Outcome ; Uric Acid ; blood ; Young Adult

In the present study, the complete genomes of four common (4/EV71/Wenzhou/CHN/2014, 15/ EV71/Wenzhou/CHN/2014, 116/EV71/Wenzhou/ CHN/2014, and 120/EV71/Wenzhou/CHN/2014) and two virulent (11/EV71/Wenzhou/CHN/2014 and 109/EV71/Wenzhou/CHN/2014) enterovirus 71 (EV71) isolates were sequenced and described. They are 7405 bp in length and belong to EV71 sub-genotype C4 (C4a cluster). Nucleotide sequence alignment revealed six nucleotide variations (GP151→TP151, GP199→AP199, GP261→TP261, AP328→CP328, GP422→AP422, and GP437→TP437) in the two virulent isolates within the 5'UTR of the IRES element. RNA secondary structure predictions of IRES and FCE indicated that the common isolates shared similar structures, which were different from those of the virulent isolates. Moreover, the GP114→CP114 and GP151→TP151 mutations in the virulent isolates contributed to the formation of the unique RNA secondary structures in SL II. Furthermore, nucleotide/amino acid sequence alignments of 82 EV71 isolates indicated that six sites (TP488 and CP577 in the 5'UTR; AsnP57 in 2A; IleP56 in 3C; CP10 and AP47 in the 3'UTR) are potentially associated with the neurovirulence of EV71. Finally, the 3D structures of 2A were analogous, whereas the structures of VP1 and 3C were variable.
Base Sequence ; Central Nervous System ; virology ; Enterovirus A, Human ; classification ; genetics ; isolation & purification ; pathogenicity ; Enterovirus Infections ; virology ; Genome, Viral ; Genomics ; Genotype ; Humans ; Molecular Sequence Data ; Nucleic Acid Conformation ; Phylogeny ; RNA, Viral ; chemistry ; genetics ; Virulence

OBJECTIVETo investigate the in vitro effect of caffeic acid phenethyl ester (CAPE), a NF-κB inhibitor, on the apoptosis of osteoarthritic (OA) chondrocytes and on the regulation of the gelatinases matrix metalloproteinase 2 (MMP-2) and matrix metalloproteinase 9 (MMP-9).

METHODSAnnexin V-FITC/propidium iodide (PI) labeling and western blotting were used to observe and determine the apoptosis in TNFα-stimulated primary cultured osteoarthritic chondrocytes. Also, gelatin zymography was applied to examine MMP-2 and MMP-9 activities in supernatants.

RESULTSIt was confirmed by both flow cytometry and western blotting that chondrocytes from OA patients have an apoptotic background. Use of CAPE in combination with 10 ng/mL of TNFα for 24 h facilitated the apoptosis. MMP-9 in the supernatant could be autoactivated (from proMMP-9 to active MMP-9), and the physiologic calcium concentration (2.5 mmol/L) could delay the autoactivation of MMP-9. The activities of MMP-2 and MMP-9 in the fresh supernatant increased significantly in response to stimulation by 10 ng/mL of TNFα for 24 h. The stimulatory effect of TNFα just on proMMP-9 was counteracted significantly by CAPE.

CONCLUSIONNF-κB could prevent chondrocytes apoptosis though its activation was attributed to the increase of proMMP-9 activity induced by TNFα (a pro-apoptotic factor). Therefore, therapeutic NF-κB inhibitor was a 'double-edged swords' to the apoptosis of chondrocytes and the secretion of MMP-9.

Aged ; Apoptosis ; drug effects ; Caffeic Acids ; pharmacology ; therapeutic use ; Calcium ; physiology ; Cells, Cultured ; Chondrocytes ; drug effects ; enzymology ; secretion ; Drug Evaluation, Preclinical ; Female ; Humans ; Matrix Metalloproteinase 2 ; metabolism ; Matrix Metalloproteinase 9 ; metabolism ; Middle Aged ; NF-kappa B ; antagonists & inhibitors ; Osteoarthritis ; drug therapy ; enzymology ; Phenylethyl Alcohol ; analogs & derivatives ; pharmacology ; therapeutic use ; Tumor Necrosis Factor-alpha ; pharmacology

Objective To study the expressions of Piwil2 protein and mRNA in papillary thyroid carcinoma(PTC) and the relationship between Piwil2 and the invasion and metastasis of PTC. Methods Immunohistochemistry and in situ hybridization were used to detect the expression of Piwil2 protein and mRNA in 60 cases of PTC with the matched adjacent non-cancerous epithelium (NCE). Results The positive rates of Piwil2 protein expression in PTC and NCE were 88.3% (53/60) and 10.0% (6/60)respectively, with significant difference ( x2 = 73. 654,P ＜ 0.01 ). The positive rates of Piwil2 mRNA expression in PTC and NCE were 85.0% (51/60) and 6. 7% (4/60) respectively, also with significant difference (x2 =74. 148 ,P ＜0.01 ). Up-regulated expressions of Piwil2 protein and mRNA were related to the invasion and metastasis of PTC (P ＜ 0.05 ). Conclusion Piwil2 may play a role in the invasion and metastasis of PTC.

Objective To study the relationship between status of methylation of human runt-related transcription factor 3 ( RUNX3 ) gene promoter in papillary thyroid carcinoma ( PTC). Methods Methylation-specific PCR and immunohistochemical SP technique were used to detect the methylation of RUNX3 gene promoter and expression of its protein in 56 cases of PTC and their matched adjacent non-carceious epithelium(NCE). Results In NCE, there was no methylation of RUNX3 gene promoter, while in PTC the methylation rate was 35.1% (20/56), which was related to the tumor TNM stage, pathological grade and lymph node metastasis (P<0. 05). The positive rates of RUNX3 protein expression in NCE and PTC were 100. 0% and 60. 7% , respectively, with a significant difference ( χ2 = 27. 378, P < 0. 05). In PTC, the positive rates of RUNX3 protein expression in grade I and grade II were 70.0% and 37.5% , respectively ( P < 0. 05 ); the rates were 46.7% and 76.9% in lymph node metastasis group and no metastasis group, respectively ( P < 0. 05 ). Moreover, there was a distinct correlation between methylation of RUNX3 gene promoter and expression of its protein (χ 2= 21. 62, P < 0. 01). Conclusions Methylation of promoter might be one of the important factors of inactivation of RUNX3 gene, and might play an important role in carcinogenesis and progression of PTC.