Effects of titanium dioxide nanoparticles on circRNA expression profiles in human hepatocellular carcinoma cells HepG2 / 北京大学学报(医学版)

OBJECTIVE@#To investigate the effect of titanium dioxide nanoparticles (TiO2 NPs) on the expression profile of circular ribonucleic acid (circRNA) in human hepatocytes through in vitro cell experiments, and to attempt to understand the potential mechanism of hepatotoxicity through bioinformatics analysis.@*METHODS@#TiO2 NPs were characterized from the aspects of particle size, shape and agglomeration state. The cell counting kit-8 (CCK8) was used to detect the cytotoxicity of TiO2 NPs against human hepatocellular carcinoma cells (HepG2) after exposure to 0, 1.56, 3.13, 6.25, 12.5, 25, 50, 100, and 200 mg/L TiO2 NPs for 24 h or 48 h. The cells were treated at doses of 0 mg/L TiO2 NPs (control group) and 100 mg/L TiO2 NPs (treatment group), and collected after exposure for 48 h, and then RNA from the extracted cell samples was collected and sequenced. The differential circRNAs between the control and the TiO2 NPs treatment groups were screened, and then the enrichment pathway of the differential circRNA target gene was analyzed by multivariate statistics. According to the sequencing results, significantly altered genes and important genes in the significant enrichment pathways were screened, and real-time reverse transcription-polymerase chain reaction (real-time RT-PCR) was performed to verify the results.@*RESULTS@#TiO2 NPs were spherical anatase with a hydrated particle size of (323.50±85.44) nm and a Zeta potential of (-21.00±0.72) mV in a serum-free medium. The results of the CCK8 cytotoxicity assay showed that with the increase of TiO2 NPs concentration, cell viability gradually decreased. A total of 11 478 circRNAs were found by RNA sequencing. Compared with the control groups, TiO2 NPs treatment groups (100 mg/L) had a total of 89 differential circRNAs, of which 59 were up-regulated and 30 were down-regulated. Analysis of the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway showed that the targeted genes of differential circRNAs were mainly enriched in fatty acid degradation, Fanconi anemia pathway, and fatty acid metabolism. The expression levels of circRNA.6730, circRNA.3650 and circRNA.4321 were significantly different between the TiO2 NPs treatment group and the control group, which were consistent with the sequencing results.@*CONCLUSION@#TiO2 NPs can induce changes in circRNA expression profile, and epigenetics may play an important role in the mechanism of hepatotoxicity.

Characteristics of informative biomarkers for strength training in volleyball athletes / Características dos biomarcadores informativos para treinamento de força nos atletas de voleibol / Características de los biomarcadores informativos para el entrenamiento de fuerza en atletas de voleibol

ABSTRACT Introduction The relevance in studying the characteristics of biochemical markers on the training process of volleyball players is conditioned to the specificity of these parameters for such sport, considering the degree and nature of physical activity mostly in open kinetic chain. Objective To select the most relevant biomarkers for strength training in volleyball athletes and to verify their consistency with other biochemical status parameters. Methods A review of the scientific and methodological literature in the field of volleyball training was performed and the biochemicals were tested with statistical-mathematical methods. The optimal set of biochemical markers for an effective control of the training process in open kinetic chain sport was established, which can be used to evaluate the tolerability of training loads in several of its stages. Results Effective clinical and laboratory tests were determined to solve medical and biological monitoring tasks in the training process. The possibility of using biochemical control data to assess the prospects of a high level of functional status in the pre-competition period was demonstrated. Conclusion The results obtained can be used as part of the medical and biological support in the training process of volleyball athletes, and can be introduced in national medical and biological subject cycles. Evidence level II; Therapeutic studies - outcomes research.

RESUMO Introdução A relevância no estudo das características dos marcadores bioquímicos sobre o processo de treinamento dos jogadores de voleibol está condicionada à especificidade desses parâmetros para tal esporte, considerando o grau e a natureza da atividade física majoritariamente em cadeia cinética aberta. Objetivo Selecionar os biomarcadores mais relevantes para treinamento de força em atletas de voleibol e verificar a sua consistência com outros parâmetros do status bioquímico. Métodos Efetuou-se uma análise da literatura científica e metodológica no campo do ensino do voleibol e os bioquímicos foram testados com métodos estatístico-matemáticos. Foi estabelecido o conjunto ideal de marcadores bioquímicos para um controle eficaz do processo de treinamento no esporte de cadeia cinética aberta, que pode ser usado para avaliar a tolerabilidade das cargas de treinamento em várias de suas etapas. Resultados Foram determinados testes clínicos e laboratoriais eficazes para resolver tarefas de monitoramento médico e biológico no processo de treinamento. Foi demonstrada a possibilidade de utilizar dados de controle bioquímico para avaliar as perspectivas de um alto nível de estado funcional no período pré-competição. Conclusão Os resultados obtidos podem ser utilizados como parte do suporte médico e biológico no processo de treinamento de atletas de vôlei, podendo ser introduzidos em ciclos de disciplinas médicas e biológicas nacionais. Evidência nível II; Estudos terapêuticos - pesquisa de resultados.

RESUMEN Introducción La relevancia en el estudio de las características de los marcadores bioquímicos sobre el proceso de entrenamiento de los jugadores de voleibol está condicionada a la especificidad de estos parámetros para dicho deporte, considerando el grado y la naturaleza de la actividad física sobre todo en cadena cinética abierta. Objetivo Seleccionar los biomarcadores más relevantes para el entrenamiento de fuerza en deportistas de voleibol y verificar su consistencia con otros parámetros del estado bioquímico. Métodos Se realizó una revisión de la literatura científica y metodológica en el campo del entrenamiento del voleibol y se comprobaron los bioquímicos con métodos estadístico-matemáticos. Se estableció el conjunto ideal de marcadores bioquímicos para un control eficaz del proceso de entrenamiento en el deporte de cadena cinética abierta, que puede utilizarse para evaluar la tolerabilidad de las cargas de entrenamiento en varias de sus etapas. Resultados Se determinaron pruebas clínicas y de laboratorio eficaces para resolver las tareas de seguimiento médico y biológico en el proceso de formación. Se demostró la posibilidad de utilizar los datos de control bioquímico para evaluar las perspectivas de un alto nivel de estado funcional en el período previo a la competición. Conclusión Los resultados obtenidos pueden ser utilizados como parte del apoyo médico y biológico en el proceso de entrenamiento de los atletas de voleibol, y pueden ser introducidos en los ciclos de las disciplinas médicas y biológicas nacionales. Nivel de evidencia II; Estudios terapéuticos - investigación de resultados.

Protective effect of breviscapine on acute lung injury in rats with infectious shock

Acute lung injury (ALI), during the progression of infectious shock, leads to systemic inflammatory response syndromewith increased pulmonary capillary membrane permeability due to pulmonary inflammation and uncontrolled inflammatoryresponses. It may cause fatality in patients. Here, we evaluated the protective effect of breviscapine on ALI in rats withinfectious shock. Sprague-Dawley (SD) rats were assigned into Sham, model [lipopolysaccharide (LPS) group], andbreviscapine treatment groups (LPS + breviscapine group) and weighed. The lung coefficient, and the wet-to-dry weightratio (W/D) and moisture content of lung tissues were calculated. The pathological changes of the lung tissues were detectedusing hematoxylin-eosin (HE) staining, and the protein expressions of interleukin-1 beta (IL-1?), IL-6, and tumor necrosisfactor-alpha (TNF-?) were determined by enzyme-linked immunosorbent assay. Western blotting was conducted to measurethe protein expressions of toll-like receptor-9 (TLR-9) and nuclear factor-kappa B (NF-?B) (p65). Compared with LPSgroup, breviscapine significantly lowered the lung coefficient and the W/D and moisture content of lung tissues, relieved thepathological changes of lung tissues, reduced the protein expression levels of IL-1?, IL-6, and TNF-?, weakened theactivation of NF-?B (p65) in lung tissues, and repressed the protein expressions of TLR-9 and NF-?B (p65).

Expression Level and Significance of Tim-3 in CD4+ T Lymphocytes in Peripheral Blood of Patients with Coronary Heart Disease

Abstract Objective: To investigate the expression level and significance of T cell immunoglobulin and mucin-domain containing molecules-3 (Tim-3) and interleukin-7 (IL-7) in CD4+ T lymphocytes in peripheral blood of patients with coronary heart disease (CHD). Methods: 75 patients with CHD treated at our hospital were selected and classified as mild group (25 cases), moderate group (25 cases) and severe group (25 cases), according to the severity of illness. Twenty-five healthy volunteers who underwent a physical examination at our hospital during the same period were selected as the control group. The expression level of Tim-3 in CD4+ T lymphocytes in peripheral blood of patients in four groups was detected by flow cytometry and quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR). The expression level of IL-7 in peripheral blood serum was measured by enzyme-linked immunosorbent assay (ELISA). Correlation analyses of Tim-3 and IL-7, Tim-3 and disease severity and IL-7 and disease severity were performed, respectively. Results: Flow cytometry and qRT-PCR demonstrated that the expression of Tim-3 in CD4+ T lymphocytes in peripheral blood of patients with CHD increased with the aggravation of the disease. ELISA showed that the tendency of IL-7 expression in peripheral blood serum was consistent with the expression of Tim-3, and the expression of Tim-3 had a positive correlation with IL-7. The expression levels of both Tim-3 and IL-7 were positively correlated with the Gensini score. Conclusion: The expression of Tim-3 and IL-7 in peripheral blood of patients with CHD was upregulated and increased with the aggravation of CHD.

A comparative study of the morphology of suboccipital cavernous sinus using magnetic resonance imaging and cast specimens / Un estudio comparativo de la morfología del seno cavernoso suboccipital utilizando imágenes de resonancia magnética y muestras de yeso

SUMMARY: A comparative study of the morphology of suboccipital cavernous sinus (SCS) using MRI and cast specimens was performed. The present retrospective study analysed the craniocervical magnetic resonance venography (MRV) imaging data of 61 patients. Three-dimensional reconstruction was performed using Mimics 19.0. The SCS left-right diameter(d1), distance from the midline (d2), supero-inferior diameter(d3), anteroposterior diameter (d4), distance from posterior diameter to skin (d5), and diameter of the SCS at different parts (d6-d8) were measured. Comparison between MRV images and cast specimens, the SCS, marginal sinus, anterior condylar vein, and vertebral artery venous plexus were symmetrical and could be bilaterally displayed, whereas the presence of extra condylar vein and posterior condylar vein exhibited different types. The adjacency between the SCS and its communicating vessels and changes in its communicating vessels corresponded well with the MRV images and cast specimens. Many types of the presence of left and right lateral condylar and posterior condylar veins were found in the cast specimens, which could be divided into the bilateral presence of posterior condylar and lateral condylar veins, unilateral presence of posterior condylar veins, and unilateral presence of lateral condylar vein. A total of 61 cases analysed using MRV images revealed the bilateral presence of posterior condylar and lateral condylar veins (77.1 %), the unilateral presence of posterior condylar vein (18.0 %), and the unilateral presence of lateral condylar vein (9.8 %), of which the bilateral presence of posterior condylar and lateral condylar veins accounted for the largest proportion. MRV images and cast specimens of the SCS showed its normal morphological structure and adjacency, thus providing accurate and complete Three-dimensional imaging anatomical data of the SCS and its communicating vascular structures. This study enriches the Chinese SCS imaging anatomy data and may be valuable in clinical practice.

RESUMEN: Se realizó un estudio comparativo de la morfología del seno cavernoso suboccipital (SCS) mediante resonancia magnética y muestras de yeso. El presente estudio retrospectivo analizó los datos de imágenes de venografía por resonancia magnética (RNM) craneocervical de 61 pacientes. La reconstrucción tridimensional se realizó con Mimics 19.0. Se midió: el diámetro izquierdo-derecho del SCS (d1), la distancia desde la línea mediana (d2), el diámetro superoinferior (d3), el diámetro anteroposterior (d4), la distancia desde el diámetro posterior hasta la piel (d5) y el diámetro del SCS en diferentes partes (d6-d8). En la comparación entre las imágenes RNM y las muestras de yeso, el SCS, el seno marginal, la vena condilar anterior y el plexo venoso de la arteria vertebral eran simétricos y se observaron bilateralmente, mientras que la presencia de la vena extracondilar y la vena condilar posterior presentaba tipos diferentes. La proximidad del SCS y sus vasos comunicantes y los cambios en sus vasos comunicantes se correspondieron bien con las imágenes de RNM y los especímenes moldeados. Se encontraron muchos tipos de venas condilares laterales y condilares posteriores izquierda y derecha en las muestras de yeso, que podrían dividirse en presencia bilateral de venas condilares posteriores y condilares laterales, presencia unilateral de venas condilares posteriores y presencia unilateral de venas condilares laterales. Un total de 61 casos analizados mediante imágenes MRV revelaron la presencia bilateral de venas condilares posteriores y condilares laterales (77,1 %), la presencia unilateral de venas condilares posteriores (18,0 %) y la presencia unilateral de venas condilares laterales (9,8 %) de los cuales la presencia bilateral de las venas condilar posterior y condilar lateral representó la mayor proporción. Las imágenes de RNM y las muestras de yeso del SCS mostraron su estructura morfológica y adyacencia normales, lo que proporcionó datos anatómicos de imágenes tridimensionales precisos y completos del SCS y sus estructuras vasculares comunicantes. Este estudio enriquece los datos de anatomía de imágenes de SCS chino y puede ser valioso en la práctica clínica.

Identification of Escherichia coli β-glucuronidase inhibitors from Polygonum cuspidatum Siebold & Zucc

Abstract Gut bacterial β-glucuronidase (GUS) can reactivate xenobiotics that exert enterohepatic circulation- triggered gastrointestinal tract toxicity. GUS inhibitors can alleviate drug-induced enteropathy and improve treatment outcomes. We evaluated the inhibitory effect of Polygonum cuspidatum Siebold & Zucc. and its major constituents against Escherichia coli GUS (EcGUS), and characterized the inhibitory mechanism of each of the components. Trans-resveratrol 4'-O-β-D-glucopyranoside (HZ-1) and (-)-epicatechin gallate (HZ-2) isolated from P. cuspidatum were identified as the key components and potent inhibitors. These two components displayed strong to moderate inhibitory effects on EcGUS, with Ki values of 9.95 and 1.95 μM, respectively. Results from molecular docking indicated that HZ-1 and HZ-2 could interact with the key residues Asp163, Ser360, Ile 363, Glu413, Glu504, and Lys 568 of EcGUS via hydrogen bonding. Our findings demonstrate the inhibitory effect of P. cuspidatum and its two components on EcGUS, which supported the further evaluation and development of P. cuspidatum and its two active components as novel candidates for alleviating drug-induced damage in the mammalian gut.

Effects of nano titanium dioxide on gut microbiota based on human digestive tract microecology simulation system in vitro / 北京大学学报(医学版)

OBJECTIVE@#To explore the effects of oral exposure to titanium dioxide nanoparticles (TiO2 NPs) on the composition and structure of human gut microbiota.@*METHODS@#The particle size, shape, crystal shape and degree of agglomeration in ultrapure water of TiO2 NPs were characterized. The in vitro human digestive tract microecological simulation system was established by simulating the fluid environment and physical conditions of stomach, small intestine and colon, and the stability of the simulation system was evaluated. The bacterial communities were extracted from human feces and cultured stably in the simulated system. They were exposed to 0, 20, 100 and 500 mg/L TiO2 NPs, respectively, and the bacterial fluids were collected after 24 h of exposure. The effect of TiO2 NPs on the composition and structure of human gut microbiota was analyzed by 16S rRNA sequencing technology. Linear discriminant analysis effect size (LEfSe) was used to screen differential bacteria, and the Kyoto encyclopedia of genes and genomes (KEGG) database for functional prediction.@*RESULTS@#The spherical and anatase TiO2 NPs were (25.12±5.64) nm in particle size, while in ultra-pure water hydrated particle size was (609.43±60.35) nm and Zeta potential was (-8.33±0.22) mV. The in vitro digestive tract microecology simulation system reached a relatively stable state after 24 hours, and the counts of Enterococci, Enterobacte-rium, and Lactobacillus reached (1.6±0.85)×107, (5.6±0.82)×107 and (2.7±1.32)×107, respectively. 16S rRNA sequencing results showed that compared with the control group, the number and evenness of gut microbiota were not significantly affected at phylum, class, order, family and genus levels in TiO2 NPs groups (20, 100 and 500 mg/L). The relative abundance of some species was significantly changed, and a total of 42 different bacteria were screened between the TiO2 NPs groups (20, 100 and 500 mg/L) and the control group [linear discriminant analysis(LDA) score>3], represented by Enterobacter, Bacteroidaceae, Lactobacillaceae, Bifidobacteriaceae and Clostridium. Further predictive analysis of gut microbiota function showed that TiO2 NPs might affect oxidative phosphorylation, energy meta-bolism, phosphonate and phosphonate metabolism, and methane metabolism (P < 0.05).@*CONCLUSION@#In human digestive tract microecological simulation system, TiO2 NPs could significantly change the composition and structure of human gut microbiota, represented by Enterobacter and probiotics, and may further affect a variety of metabolism and function of the body.

Identification of a new azoreductase driven prodrug from bardoxolone methyl and 5-aminosalicylate for the treatment of colitis in mice / 中国天然药物

For local treatment of ulcerative colitis, a new azoreductase driven prodrug CDDO-AZO from bardoxolone methyl (CDDO-Me) and 5-aminosalicylate (5-ASA) was designed, synthesized and biologically evaluated. It is proposed that orally administrated CDDO-AZO is stable before reaching the colon, while it can also be triggered by the presence of azoreductase in the colon to fragment into CDDO-Me and 5-ASA, generating potent anti-colitis effects. Superior to olsalazine (OLS, a clinically used drug for ulcerative colitis) and CDDO-Me plus 5-ASA, CDDO-AZO significantly attenuated inflammatory colitis symptoms in DSS-induced chronic colitis mice, which suggested that CDDO-AZO may be a promising anti-ulcerative colitis agent.

Awareness of the Three Level Social-psychological Service in Zhejiang Province / 预防医学

Objective@#To learn the awareness of the Three Level Social-psychological Service in Zhejiang Province and its influencing factors, so as to provide the basis for promoting the construction of social-psychological service system.@*Methods@#The counties (cities, districts) in Zhejiang Province were divided into three levels: high, medium and low, according to economic development. The residents are selected by multistage stratified random sampling method. A questionnaire survey was conducted to collect the general information of residents and their awareness of the Three Level Social-psychological Service.The influencing factors for the awareness were analyzed by multivariate logistic regression model. @*Results @#Of 7 114 questionnaires sent out, 6 577 valid ones were recovered, with the response rate of 92.45%. The overall awareness rates of the Three Level Social-psychological Service and service sites was 63.02% and 59.91%, respectively. The multivariate logistic regression analysis showed that the age of 40-<50 years ( OR=1.376, 95%CI: 1.077-1.758 ), permanent residence ( OR=1.474, 95%CI: 1.319-1.647 ), being the national pilots ( OR=1.200, 95%CI: 1.079-1.334 ) and having the experience of seeking mental health services before 2018 (OR=1.323, 95%CI: 1.191-1.469) were the influencing factors for the awareness of the Three Level Social-psychological Service; under 50 years old ( OR: 0.610-0.768, 95%CI: 0.423-0.991 ), permanent residence ( OR=1.571, 95%CI: 1.407-1.755 ), being the national pilots ( OR=1.368, 95%CI: 1.232-1.519 ) and having the experience of seeking mental health services before 2018 ( OR=0.733, 95%CI: 0.661-0.812 ) were the influencing factors for the awareness of the Three Level Social-psychological Service sites. @*Conclusions@#It is necessary to improve the awareness of the Three Level Social-psychological Service among Zhejiang residents. Age, permanent residence, being the national pilots, seeking mental health service experience before 2018 are associated with the awareness of the Three Level Social-psychological Service.

Design, synthesis, and biological evaluation of ligustrazine/resveratrol hybrids as potential anti-ischemic stroke agents / 中国天然药物

To search for potent anti-ischemic stroke agents, a series of tetramethylpyrazine (TMP)/resveratrol (RES) hybrids 6a-t were designed and synthesized. These hybrids inhibited adenosine diphosphate (ADP)- or arachidonic acid (AA)-induced platelet aggregation, among them, 6d, 6g-i, 6o and 6q were more active than TMP. The most active compound 6h exhibited more potent anti-platelet aggregation activity than TMP, RES, as well as positive control ticlopidine (Ticlid) and aspirin (ASP). Furthermore, 6h exerted strong antioxidative activity in a dose-dependent manner in rat pheochromocytoma PC12 cells which were treated with hydrogen peroxide (HO) or hydroxyl radical (·OH). Importantly, 6h significantly protected primary neuronal cells suffered from oxygen-glucose deprivation/reoxygenation (OGD/R) injury, comparable to an anti-ischemic drug edaravone (Eda). Together, our findings suggest that 6h may be a promising candidate warranting further investigation for the intervention of ischemic stroke.

Influence of oxidative/antioxidative biomarkers and inflammatory cytokines on rats after sub-acute orally administration of titanium dioxide nanoparticles / 北京大学学报(医学版)

OBJECTIVE@#To evaluate the sub-acute oral effect of titanium dioxide (TiO2) nanoparticles on the oxidation/antioxidation biomarkers and inflammatory cytokines in blood, liver, intestine, and colon in rats.@*METHODS@#Twenty four 4-week-old clean-grade Sprague Dawley (SD) rats were randomly devided into 4 groups by body weight (n=6, control, low, middle, and high), in which the rats were orally exposed to TiO2 nanoparticles at doses of 0, 2, 10 and 50 mg/kg body weight/day for 28 consecutive days separately. Food intake, body weight and abnormal behaviors during the experiment were recorded. The rats were euthanized on the 29th day. The blood was collected via abdominal aortic method and centrifuged to collect the serum. Tissues from liver, intestine and colon were collected and homogenated. Then enzyme-linked immunosorbent assay (ELISA) and microwell plate methods were used to detect oxidation/antioxidation biomarkers including superoxide dismutase (SOD), glutathione (GSH), glutathione peroxidase (GSH-Px), total mercapto (T-SH), glutathione disulfide (GSSG), malomdialdehvde (MDA) and inflammatory cytokines including interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) in the serum, liver, intestine and colon in the rats.@*RESULTS@#Compared with the control group, no significant differences in body weight, food intake and organ coefficients were observed in all the three groups after TiO2 gavage. No significant changes in GSH, GSH-Px, T-SH, and IL-6 were observed. Compared with the control group, significant increase of SOD activity in serum in high dose group, signi-ficant increase of GSSG concentration in intestine in middle and high dose group and significant increase of MDA concentration in liver in low and high dose group were observed. Compared with the control group, a significant increase of TNF-α in liver in middle and high dose group was observed.@*CONCLUSION@#TiO2 nanoparticle can increase antioxidant enzymes activities in blood, increase oxidative biomarkers in liver and intestine, increase inflammatory cytokines in liver in rats after a 28-day sub-acute orally administration. Among blood, liver, intestine, and colon, liver is most sensitive to the toxicity induced by TiO2 nanoparticles, followed by intestine, blood, and colon in sequence.

Effects of titanium dioxide nanoparticles on fecal metabolome in rats after oral administration for 90 days / 北京大学学报(医学版)

OBJECTIVE@#To explore the effects and related mechanisms of oral exposure titanium dioxide nanoparticles (TiO2 NPs) for 90 days on the intestinal and the gut microbiota of rats, through fecal metabolomics.@*METHODS@#Twelve 4-week-old clean-grade Sprague Dawley (SD) rats were randomly de-vided into 2 groups by body weight, treated with TiO2 NPs at dose of 0 or 50 mg/kg body weight everyday respectively for 90 days. The solution of each infection was freshly prepared and shocked fully by ultrasonic. Characterization of the particle size, crystal form, purity, and specific surface area of TiO2 NPs was conducted. And the fresh feces of the rats were collected on the 90th day. After lyophilized and hydrophilic phase extraction, ultra performance liquid chromatography-Q-exactive orbitrap-high-resolution mass spectrometry system (UPLC-QEMS) was utilized for non-targeted determination of fecal meta-bolites. The metabolites were identified and labeled through Compound Discoverer 3.0 software, and used for subsequent metabolomics analysis. Bioinformatics analysis was carried out including unsupervised principal component analysis and supervised orthogonal projection to latent structure discriminant analysis for the differential metabolites between the two groups. The differential metabolites were followed-up for Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis.@*RESULTS@#Compared with the control group, the body weight of the rats was significantly reduced (P<0.05) in the treatment group. A total of 22 metabolites in fecal metabolomics showed significant changes. Among them, xanthine, 1-methyladenine, 3-hydroxypyridine, methionine sulfoxide, pyridoxine, 1,5-isoquinolinediol, N-acetylornithine, N-acetyl-D-galactosamine, L-citrulline, L-methionine, leucine, DL-tryptophan, L-ornithine, 4-methyl-5-thiazoleethanol, and L-glutamic acid totaled 15 metabolites increased significantly. N-acetylhistamine, D-pipecolinic acid, imidazolelactic acid, L-valine, 2,3,4,6-tetramethylpyrazine, caprolactam, and histamine totaled 7 metabolites decreased significantly. N-acetylhistamine, L-valine and methionine sulfoxide were changed more than 16 times. Analysis of KEGG pathway revealed that the two metabolic pathways arginine biosynthesis and aminoacyl-tRNA biosynthesis were significantly changed (false discover rate < 0.05, pathway impact > 0.1).@*CONCLUSION@#Oral exposure to TiO2 NPs for 90 days could disrupt the metabolism of the intestine and gut microbiota, causing significant changes in metabolites and metabolic pathways which were related to inflammatory response, oxidative stress, glucose homeostasis, blood system and amino acid homeostasis in rat feces. It is suggested that the toxic effect of TiO2 NPs on rats may be closely related to intestinal and gut microbiota metabolism.

Effect of subchronic combined oral exposure of titanium dioxide nanoparticles and glucose on levels of serum folate and vitamin B12 in young SD rats / 北京大学学报(医学版)

OBJECTIVE@#To explore the effect of subchronic combined oral exposure of titanium dioxide nanoparticles and glucose on levels of serum folate and vitamin B12 in young SD rats.@*METHODS@#At first, the physical and chemical properties of titanium dioxide nanoparticles, such as particle size, shape, crystal form and agglomeration degree in solution system, were characterized in detail. Eighty 4-week-old young SD rats were randomly divided into 8 groups (10 rats in each group, half male and half female). The rats were exposed to titanium dioxide nanoparticles through intragastric administration at 0, 2, 10 and 50 mg/kg body weight with or without 1.8 g/kg glucose daily for 90 days. At last, the concentrations of serum folate and vitamin B12 were detected.@*RESULTS@#Titanium dioxide nanoparticles were anatase crystals, closely spherical shape, with an average particle size of (24±5) nm. In male young rats, compared with the control group, the serum folate concentration was significantly increased when exposed to titanium dioxide nanoparticles (10 mg/kg) and glucose. The difference was statistically significant (P<0.05). However, in female and male young rats, compared with glucose (1.8 g/kg) exposure group, titanium dioxide nanoparticles (50 mg/kg) and glucose significantly reduced the serum folate concentration. The difference was statistically significant (P<0.05). Through statistical analysis of factorial design and calculation of interaction, obvious antagonistic effect was observed between titanium dioxide nanoparticles and glucose on the serum folate concentration in the young female SD rats. The combined oral exposure of titanium dioxide nanoparticles and glucose had little effect on the concentration of serum vitamin B12 in the young SD rats, with no significant interaction between the two substances. It was only found that titanium dioxide nanoparticles (2 mg/kg) and glucose significantly increased the serum vitamin B12 concentration, compared with glucose (1.8 g/kg) exposure group. The difference was statistically significant (P<0.05).@*CONCLUSION@#Subchronic combined oral exposure of titanium dioxide nanoparticles and glucose had an obvious antagonistic effect on serum folate concentrations in young SD rats.

Association between different parent-child separation types and emotion regulation strategies among preschool children / 中国学校卫生

Objective@#To understand effects of timing and duration of separation experiences from parents on emotion regulation of left-behind preschoolers,and to provide the reference for phychological instruction and intervention among the special groups of children.@*Methods@#Children’s emotion regulation strategy and the relevant information among 1 373 left-behind preschool children from Funan county in Fuyang.Qianshan county in Anqing,Changfeng county and Fexi county inFeixi were investigated.@*Results@#Children with left-behind experiences younger than 18 months old tend to use less cognitive restructuring (P=0.03) and alternative action strategies (P=0.00) than non-left behind children. Children separated from father less than 47 months (median) and 36 months (median) from mother tend to use less cognitive restructuring (P=0.00) and alternative action strategies (P=0.00) than non-left behind children.@*Conclusion@#Separation experiences from parents younger than 18 months old exert severe damage on children’s emotional regulation. With the duration of separation increases, children show resilience of emotion regulation, which might be a protective factor for negative emotion due to parent-child separation.

miR-424 modulates radio-sensitivity of breast cancer cells via targeting HMGA1 / 中国肿瘤生物治疗杂志

@# Objective: To explore the effect of miR-424/HMGA1 (high mobility proteinA1) axis on the radio-sensitivity of breast cancer cells and the possible mechanism. Methods:Atotal of 50 cases of breast cancer tissues from patients, who underwent surgical resection at the Department of Oncological Radiotherapy, Wuxi Fourth People’s Hospital from April 2014 to April 2017, were collected for this study. Real-time quantitative polymerase chain reaction (qPCR) and Western blotting were performed to evaluate the mRNA and protein expressions of miR-424 and HMGA1 in breast cancer tissues of radiation sensitive and insensitive patients. After being treated with different doses of 60Co γ-ray radiation (0, 2, 4, 6 and 8 Gy), the expression changes of miR-424 and HMGA1 in breast cancer MDA-MB-468 cells were observed. Subsequently, miR-424 mimic/inhibitor and pcDNA-HMGA1 were transfected into MDA-MB-468 cells, and the effect of miR-424 on cell proliferation, invasion and apoptosis of radiation-treated MDA-MB-468 cells were evaluated by colony formation assay, MTT assay, Transwell assay and Annexin V-FITC/PI double staining flow cytometry assay, respectively. Furthermore, dual luciferase reporter gene assay was used to verify whether HMGA1 was a target gene of miR-424. Results: The patients in radio-sensitive group exhibited higher miR-424 expression but lower HMGA1 expression than the patients in insensitive group (all P<0.01). Compared with the cells treated with 0, 2 and 4 Gy radiation, the cells treated with 6 and 8Gy radiation exhibited significantly higher apoptosis rate and miR-424 expression but lower HMGA1 expression and cell invasion (all P<0.01). Moreover, luciferase reporter gene assay confirmed that miR-424 down-regulated HMGA1 expression. Mechanistically, miR-424 significantly inhibited cell proliferation, invasion and induced apoptosis of MDA-MB-468 cells (all P<0.01) via targeted down-regulating HMGA1, and further upregulated the radio-sensitivity of breast cancer cells. Conclusion: miR-424/HMGA1 axis regulates the radio-sensitivity of breast cancer, and over-expression of miR-424 may increase the sensitivity of MDA-MB-468 cells to γ-ray radiation therapy.

MiR-106a aggravates sepsis-induced acute kidney injury by targeting THBS2 in mice model

Abstract Purpose To investigate the role and related mechanisms of miR-106a in sepsis-induced AKI. Methods Serum from sepsis and healthy patients was collected, sepsis mouse model was established by cecal ligation and puncture (CLP). TCMK-1 cells were treated with lipopolysaccharide (LPS) and transfected with THBS2-small interfering RNA (siTHBS2), miR-106a inhibitor, miR-106a mimics and their negative controls (NCs). The expression of miR-106a, thrombospondin 2 (THBS2), Bax, cleaved caspase-3 and Bcl-2, cell viability, relative caspase-3 activity and TNF-α, IL-1β, IL-6 content were respectively detected by quantitative real-time polymerase chain reaction (qRT-PCR), western blotting, Cell Counting Kit-8 (CCK-8) and enzyme linked immunosorbent assay (ELISA). The relationship between miR-106a and THBS2 was confirmed by dual luciferase reporter assay. Results MiR-106a was up-regulated in serum of sepsis patients, CLP-induced mice models and LPS-induced TCMK-1 cells. LPS reduced cell viability and Bcl-2 expression, and increased caspase-3 activity, Bax expression, the content of TNF-α, IL-1β, IL-6. THBS2 was a target of miR-106a. The decreases of caspase-3 activity, TNF-α, IL-1β, IL-6, Bax expression and the increases of cell viability, Bcl-2 expression caused by miR-106a knockdown were reversed when THBS2 silencing in LPS-stimulated TCMK-1 cells. Conclusion MiR-106a aggravated LPS-induced inflammation and apoptosis of TCMK-1 cells via regulating THBS2 expression.

Anatomical parameters of the rectus capitis posterior minor muscle based on a new magnetic resonance scan method / Parámetros anatómicos del músculo recto posterior menor de la cabeza basado en un nuevo método de escaner con resonancia magnética

The past findings confirm that the Rectus Capitis Posterior minor (RCPmi) is connected to the cervical spinal dura mater via the Myodural Bridge (MDB) through the posterior antlanto-occipital interspace. It is hypothesized to perform some functions. Furthermore, some clinical studies found that the pathology of RCPmi might be related to chronic headaches. But few studies were related to the morphological parameters of the RCPmi. It would be conducive to performing clinical researches on the RCPmi and MDB. To explore the optimal section for measuring the RCPmi by MRI and provide imaging anatomy parameters of the RCPmi for clinical research. The RCPmi was measured in the dissection of 10 formalin-fixed cadaver specimens. The morphological parameters of the RCPmi were obtained. Based on these parameters, T2-weighted images of the RCPmi were collected from 109 healthy adults by using the MRIs with different oblique sagittal scanning angles. The parameters of length and area of the RCPmi on the scanning sections were measured using MRI workstation and Mimics software. The length of RCPmi reached a maximum at 30 degrees scanning leaned from the posterior median line through the dens of the axis in oblique sagittal section. At this scanning section, the length of RCPmi was 21.2 ± 2.6 mm in males and 19.3 ± 2.4 mm in females and the area of RCPmi was 91.9 ± 27.2 mm2 in males and 73.3 ± 22 mm2 in females. These parameters of RCPmi were present with significant gender differences (P < 0.05) but was not age related. Thirty degrees leaned from the median line was suggested to be the optimum scanning angle to display the RCPmi in oblique sagittal section. The reference values of length and area of the RCPmi were established for studies of hypertrophy or amyotrophy of the RCPmi.

Hallazgos previos confirman que el músculo rector posterior menor de la cabeza (mRPMC) está conectado a la duramadre cervical por medio del puente miodural (PMD) a través del espacio intermedio antlanto-occipital posterior. Se plantea la hipótesis de su capacidad para realizar algunas funciones. Además, estudios clínicos encontraron que la patología del mRPMC podría estar relacionada con dolores de cabeza crónicos. Sin embargo, pocos estudios se relacionaron con los parámetros morfológicos del mRPMC. Se buscará realizar investigaciones clínicas sobre el mRPMC y el PMD, además de explorar la sección óptima que permita medir el mRPMC por resonancia magnética (RM) y que permita obtener la imagen adecuada para la identificación de los parámetros anatómicos del mRPMC en la investigación clínica. Se midió el mRPMC durante la disección de 10 especímenes, correspondientes a cadáveres fijados con formalina. Se obtuvieron los parámetros morfológicos del mRPMC. Basándose en estos parámetros, se estudiaron imágenes ponderadas en T2 del mRPMC de 109 adultos sanos, utilizando las resonancias magnéticas con diferentes ángulos de exploración sagital oblicua. Los parámetros de longitud y área del mRPMC en las secciones de exploración se midieron utilizando la estación de trabajo del equipo de RM y el software Mimics. La longitud del mRPMC alcanzó un máximo de 30 grados de exploración, inclinado desde la línea mediana posterior, a través del eje en la sección sagital oblicua. En esta sección la longitud del mRPMC fue 21,2 ± 2,6 mm en los hombres y 19,3 ± 2,4 mm en las mujeres, y el área del mRPMC fue 91,9 ± 27,2 mm2 en los hombres y 73,3 ± 22 mm2 en las mujeres. Se observaron diferencias significativas de sexo en estos parámetros del mRPMC (P <0,05) sin embargo estos no estaban relacionados con la edad. Se sugirieron 30 grados inclinados a partir de la línea mediana como el ángulo óptimo de exploración para mostrar el mRPMC en la sección sagital oblicua. Los valores de referencia de longitud y área del mRPMC se establecieron para estudios de hipertrofia o amiotrofia del mRPMC.

Glycemic Index, Glycemic Load, and Glycemic Response to Pomelo in Patients with Type 2 Diabetes / 华中科技大学学报（医学）（英德文版）

Food intake has a great influence on blood glucose in patients with diabetes.This study was to determine the glycemic index (GI) and glycemic load (GL) of a particular pomelo named Majia pomelo and its effects on postprandial glucose (PPG) in patients with type 2 diabetes (T2D).Twenty healthy subjects and 20 T2D patients (controlled on lifestyle measures and/or metformin) were tested on 2 separate days with 50 g of glucose and 50 g equivalent of carbohydrates from Majia pomelo for GI measurement.To test effects of Majia pomelo on PPG,19 hospitalized T2D patients (controlled on insulin therapy) were selected for a 9-day study.The dose of insulin for each patient was adjusted on the first 3 days.A total of 100 mg Majia pomelo was consumed per meal in the last 3 tested days.Blood glucose was measured to evaluate the glycemic excursions.The GIs for Majia pomelo in healthy individuals and T2D patients were 78.34± 1.88 and 72.15±1.95 respectively.The value of GL was as low as 4.23 in diabetic patients with serving size of 100 g pomelo,indicting Majia pomelo as a high GI but low GL fruit.Consumption of Majia pomelo in hospitalized T2D patients did not cause significant glucose fluctuation.It was concluded that high GI pomelo can serve as a low GL fruit if it is consumed with a limited daily amount and thus can be supplied to diabetic patients.These results may mean more varieties of food choices for T2D patients.

Synthesis and evaluation of 2-cyano-3, 12-dioxooleana-1, 9(11)-en-28-oate-13β, 28-olide as a potent anti-inflammatory agent for intervention of LPS-induced acute lung injury / 中国天然药物

The present study was designed to synthesize 2-Cyano-3, 12-dioxooleana-1, 9(11)-en-28-oate-13β, 28-olide (1), a lactone derivative of oleanolic acid (OA) and evaluate its anti-inflammatory activity. Compound 1 significantly diminished nitric oxide (NO) production and down-regulated the mRNA expression of iNOS, COX-2, IL-6, IL-1β, and TNF-α in lipopolysaccharide (LPS)-stimulated RAW264.7 cells. Further in vivo studies in murine model of LPS-induced acute lung injury (ALI) showed that 1 possessed more potent protective effects than the well-known anti-inflammatory drug dexamethasone by inhibiting myeloperoxidase (MPO) activity, reducing total cells and neutrophils, and suppressing inflammatory cytokines expression, and thus ameliorating the histopathological conditions of the injured lung tissue. In conclusion, compound 1 could be developed as a promising anti-inflammatory agent for intervention of LPS-induced ALI.

Synthesis and anti-hepatocellular carcinoma activity of novel O-vinyl diazeniumdiolate-based nitric oxide-releasing derivatives of oleanolic acid / 中国天然药物

Considering that high levels of nitric oxide (NO) exert anti-cancer effect and the derivatives of oleanolic acid (OA) have shown potent anti-cancer activity, new O-vinyl diazeniumdiolate-based NO releasing derivatives (5a-l, 11a-l) of OA were designed, synthesized, and biologically evaluated in the present study. These derivatives could release different amounts of NO in liver cells. Among them, 5d, 5i, 5j, 11g, 11h, and 11j released more NO in SMMC-7721 cells and displayed stronger proliferative inhibition against SMMC-7721 and HepG2 cells than OA and other tested compounds. The most active compound 5j showed almost 20-fold better solubility than OA in aqueous solution, released larger amounts of NO in liver cancer cells than that in normal ones, and exhibited potent anti-hepatocellular carcinoma activity but little effect on the normal liver cells. The inhibitory activity against the cancer cells was significantly diminished upon addition of an NO scavenger, suggesting that NO may contribute, at least in part, to the activity of 5j.