Identification and validation of the potential early diagnostic biomarkers of infliximab non-response to treatment of rheumatoid arthritis based on autophagy / 西安交通大学学报(医学版)

【Objective】 The purpose of this study was to perform bioinformatics analysis of infliximab （IFX） treatment of rheumatoid arthritis （RA） non-responders and responders gene data chip based on autophagy， and to screen out the characteristic autophagy-related genes， carry out a preliminary experiment on the role of characteristic genes， and explore the possible mechanism of IFX treatment of RA non-response. 【Methods】 R language was used to analyze the differential expressions of autophagy-related genes on the selected gene expression omnibus database （GEO） data set. Univariate logistic regression， least absolute shrinkage and selection operator （Lasso） regression， and multiple logistic regression analyses were made to screen out the characteristic autophagy-related genes； receiver operating characteristic curve （ROC） was used to assess the diagnostic value of the characteristic autophagy-related genes. Real-time PCR was used to detect the expressions of characteristic autophagy-related genes in RA clinical samples， and Western blot was used to detect the role of characteristic autophagy-related genes in autophagy in RA synovial cell line MH7A cells. 【Results】 Part of autophagy-related genes were differentially expressed between non-responders and responders to IFX treatment of RA （P<0.05）， and autophagy-related gene sets were mainly expressed in non-responders. Hepatocyte growth factor-regulated tyrosine kinase substrate （HGS） and autophagy related 4 homolog B （ATG4B） were screened out as characteristic genes of non-response to IFX treatment of RA. The ROC showed that the predictive model constructed using the selected markers had good discrimination ability in the internal validation data set GSE78068 （AUC=0.708， P<0.05） and the external validation data set GSE58795 （AUC=0.719， P<0.05）. The Real-time PCR results showed that the expression of HGS was increased in peripheral blood leukocytes in the non-responders. After overexpression of HGS in MH7A cells， the ratio of LC3BⅡ/LC3BⅠ was increased while the expression of P62 was decreased， indicating that autophagy increased. 【Conclusion】 The autophagy-related gene expression profiles were different between IFX-treated RA non-responders and responders， suggesting that the non-response of IFX treatment of RA may be related to autophagy. The prediction model constructed with HGS and ATG4B had a certain ability to predict IFX-treated RA non-response， and HGS promoted autophagy in MH7A cells， which provides a new idea for future research on the molecular mechanism of IFX in treating RA non-response.

Extraction, separation, and in vitro dissolution of HgS micro & nano-particles from Mongolian medicine Menken Usu / 中草药

Objective To study the extraction, separation, and in vitro dissolution method of HgS micro & nano-particles from Mongolian medicine Menken Usu. Methods The Soxhlet extraction method was used to investigate the sulfur from Menken Usu effectively, and the optimum time of extraction was determined by investigating the influence of different extraction time on the extraction rate of sulfur in the Menken Usu. Then, the mercuric sulfide particles were separated by differential centrifugation. The mercuric sulfide micro & nano-particles with different particle sizes can be obtained by controlling the concentration of PVP, molar ratio, centrifuge speed, and other factors. Scanning electron microscopy (SEM) and X-ray diffraction (XRD) were used to analyze the morphology and composition of the particles. Using dithizone colorimetric method to determine and compare the dissolution of HgS particles with different sizes, Menken Usu original herbs, and Menken Usu-18 in simulated human gastric and small intestinal. Results The SEM results showed that the obtained six mercuric sulfide particle samples have a uniform size distribution: Uniform size were 2 000-4 000, 800-2 000, 200-800, 80-200, 50-80, and 20-50 nm. The main components in the extracted samples were α-HgS and β-HgS. As the particle size of HgS gradually became smaller, the dissolution of mercury was increased, which indicated that the size of HgS particle was inversely related to the dissolution of mercury. At the same time, the dissolution of mercury is also affected by sulfur, pH, and compounds. Conclusion This is a simple and efficient method for the separation of mercuric sulfide particles, and provides the basis for the pharmacokinetics and pharmacological study of mercuric sulfide nanoparticles with different particle size.

Effect of Zuotai and HgS on gene expression of drug-metabolizing enzymes in livers of mice / 中国中药杂志

Zuotai and cinnabar(96%HgS) are contained in many traditional medicines. To examine their potential effects on drug metabolism genes, mice were orally given Zuotai or HgS at doses of 10, 30, 100, 300 mg•kg⁻¹ for 7 days. HgCl2(33.6 mg•kg⁻¹) was gavaged for control. Twenty-four hour later after the last administration, livers were collected, and expressions of genes related to metabolic enzymes and transporters were examined. Zuotai and HgS had no effects on major phase-1, phase-2 and transporter genes; HgCl2 increased the expressions of CYP2B10, CYP4A10, OATP1A4, UGT1A1, UGT2A3, SULT1A1, SULT2A1, MRP1, MRP3 and MRP4; expression of OATP1A1 was decreased by HgCl2, but not by Zuotai and HgS. Therefore, Zuotai and HgS have different adverse effects on drug-metabolizing genes from HgCl2.

Quality Study on Cinnabar-analysis of Dyeing Status for Cinnabar / 中国药房

OBJECTIVE:To analyze the dyeing status of cinnabar and its pieces,and provide reference for its quality clinical safetey appicaton. METHODS:TLC was used for the qualitative identification of amaranth,carmine,erythrosine,acid red 73, 808 udan and indirubin. HPLC-MS was used to detect the 808 udan :HPLC conditions were as follows,column was Acquity UPLC BEH C18 with mobile phase of cetonitrile-0.1% formic acid(70∶30,V/V)at a flow rate of 0.3 ml/min,the detection wave-length was 520 nm;MS conditions were as follows,ion source was electrospray ionization source,scanning mode was positive ion scanning with full scanning tandem mass spectrometry,nebulizer pressure was 30 psi,drying gas was nitrogen,ion spray voltage was 4 000 V,collision energy was 30 V,and the injection volume was 5 μl. The volumetric method was used for content determi-nation of HgS. RESULTS:TLC spots of amaranth,carmine,erythrosine,acid red 73,808 udan and indirubin were clear and well-separated. 4 batches of 808 udan dyeing were included in the 18 batches of samples,6 batches had non-compliance contents (including 3 batches of 808 udan dyeing). CONCLUSIONS:Dyeing-doped and other quality problems exist in the cinnabaris in markets,which should be noticed.

Gingivoestomatitis herpética primaria: Conducta odontológica / Primary herpetic gingivostomatitis. conduct dental

Se funda como premisa que el cuidado periodontal es, en esencia, labor del odontólogo general y que éste no puede pasar por alto la responsabilidad de proveer atención a todo paciente. La incidencia excesivamente elevada de los problemas periodontales entre las población, dificulta que un número reducido de especialistas los pueda enfrentar. En la cavidad bucal se producen variedades de enfermedades de etiología infecciosa viral, específicamente en las infecciones herpesvirus la presentación frecuente, la gingivoestomatitis herpética, sea primaria o recidivante, llamadas comúnmente GEH, la cual constituye una urgencia en Odontología, actualmente, aparece con mayor frecuencia en lactantes y niños menores de 6 años pero también puede verse en adolescentes y adultos. Se plantea que el 70 por ciento de los casos de GEH aparecen en pacientes con menos de 3 años y con igual frecuencia en ambos sexos. Es importante que el odontólogo, las identifique, así como las consecuencias que ocasiona si no se previenen o tratan a tiempo, así como las complicaciones. El propósito de esta revisión bibliográfica es describir las diferentes presentaciones clínicas, su etiología, diagnósticos diferenciales y diferentes métodos de tratamiento, además de la interconsulta con diferentes áreas, para valorar sus complicaciones y cuidados postoperatorios. Para ello se realizó basado en los lineamientos de la investigación descriptiva documental, una revisión de la literatura nacional e internacional.

It is primordial for the general practitioner dentists the periodontal care of their patients. Among the population the periodontal diseases are very common and only a reduced number of specialists can treat them. Among the variety of pathologic entities that affect the oral mucosa, they exist them of etiologic infectious viral, specifically in the infections herpesvirus Of very frequent presentation, herpetic gingivostomatitis, primary or recurrent, called commonly  HGS, it is considered one of the emergencies in dentistry, nowadays, it appears with major frequency in nursing and 6-year-old minor children,  but also it can it turns in teenagers and adults. It appears that 70 percent of HGS cases appears in patients with less than 3 years and with equal frequency in both sexes. Is important that the general dentist, identify this pathologies  and the consequences that might bring along if prevention is not done time. The purpose of this research is to describe the different clinical describe the etiologic, differential diagnoses, clinical features and treatment of this disease and also to recommend the multidisciplinary attention to these patient. For this paper was made a study based on the lineaments of the descriptive documental research, mainly with scientific bibliographic references literature national and international presentations.

Quality Standard for Huisheng Diyidan Tablet / 中成药

AIM:To establish the method for quality control of Huisheng Diyidan Tablet(Eupolyphagea seu Steleophaga;Radix Angelicae sinensis,Sanguis Draconis,etc.). METHODS: Radix Angelicae sinesis,Eupolyphaga seu Steleophaga,Chinnabaris,Moschus,Boswellia carterii were identified by microscope.Sanguis Draconis was identified by TLC,Pyritum was identified by general identified reaction;The content limitation of cinnabaris(HgS) was determined by titration.Ferulic acid content of Radix Angelicae sinensis was determined by HPLC. RESULTS: Every part of the tablet was identified,the content limitation of cinnabaris(HgS) and ferulic acid content of Radix Angelicae sinensis were determined. CONCLUSION: The method showed that the characteristic for identification is distinct and highly specific,quantitative assay is simple,accurate,reliable and can be used for quality control of Huisheng Diyidan Tablet effectively.