[Effects of Oridonin combined with Capecitabine on the proliferaction of MDA-MB-231 human breast cancer cells].

Objective: To investigate the effects of oridonin combined with capecitabine on the proliferaction of MDA-MB-231 human breast cancer cells. Methods: Effect of different concentrations(10, 20 and 40 µmol/L)of oridonin, capecitabine and their combination on the proliferation of MDA-MB-231 cells after incubation for 24 or 48 h was studied. Then, the effect of 5 µmol/L of oridonin, capecitabine and their combination on cell colony formation was detected. Finally, influence of 20 µmol/L of oridonin, capecitabine and their combination on morphological alteration of nucleus, cell cycle and apoptosis was explored. Results: The inhibition rate on MDA-MB-231 cells after incubation with 20 µmol/L oridonin or capecitabine for 48 h was 49.5% and 58.6%, respectively, while the inhibition rate against proliferation of MDA-MB-231 cells reached 94.6% with combination of 20 µmol/L oridonin and capecitabine. Cells incubated with combination of oridonin and capecitabine formed fewer and smaller colonies (P<0.01). Meanwhile, cells in the combination group arrested at S and G2/M phases at the same time, and combination of two drugs caused more apoptotic cells (P<0.01). Conclusion: Oridonin combined with capecitabine can synergistically inhibit the proliferation of MDA-MB-231 human breast cancer cells.

Involvement of the MAPK pathway in the pressure-induced synovial metaplasia procedure for the temporomandibular joint.

Abnormal pressure is an important factor that contributes to bone adaptation in the temporomandibular joint (TMJ). We determined the effect of the mitogen-activated protein kinases (MAPK) pathway on the pressure-induced synovial metaplasia procedure for the TMJ, both in vitro and in vivo. Synovial fibroblasts (SFs) were exacted from rat TMJs and exposed to different hydrostatic pressures. The protein extracts were analyzed to determine the activation of ERK1/2, JNK, and p38. Surgical anterior disc displacement (ADD) was also performed on Japanese rabbits, and the proteins of TMJ were isolated to analyze pressure-induced MAPK activation after 1, 2, 4, and 8 weeks. The results showed that the activation of ERK1/2 and JNK in SFs significantly changed with increasing hydrostatic pressure, whereas p38 activation did not change. Moreover, p38 was activated in animals 1 week after surgical ADD. The levels of p38 gradually increased after 2 and 4 weeks, and then slightly decreased but remained higher than in the control 8 weeks after surgical ADD. Nevertheless, JNK was rarely activated after the ADD treatment. Our findings suggest the involvement of MAPK activation in the pressure-induced synovial metaplasia procedure with pressure loading in TMJ.

[Expression profile of microRNA secreted by rat condylar chondrocytes under tensile stress].

Objective: To preliminarily explore the mechanism of tensile stress regulating endochondral osteogenesis of condyle by analyzing the expression profiles of significantly different microRNAs (miRNAs) in exosomes of rat mandibular condylar chondrocytes (MCC) under quiescent and cyclic tensile strain (CTS) conditions. Methods: Rat condylar chondrocytes were cultured under static and CTS conditions respectively (10 SD rats, male, 2 weeks old), and exosomes were extracted. The two groups of exosomes were named as control group and CTS group respectively. The differential expression miRNAs were screened by high-throughput sequencing. Bioinformatics analysis and prediction of target genes related to osteogenesis were performed by TargetScan and miRanda website. Results: The exosomes of rat condylar chondrocytes cultured under tensile stress showed a "double concave disc" monolayer membrane structure, the expression of CD9 and CD81 were positive, and the particle size distribution accorded with the characteristics of exosomes, which was consistent with that of static cultured rat condylar chondrocytes. A total of 85 miRNAs with significantly different expression were detected by high-throughput sequencing (P<0.05). The main biological processes and molecular functions of differential miRNAs were biological processes and protein binding, respectively. Kyoto Encyclopedia of Genes and Genomes (KEGG) database pathway enrichment analysis showed that there was significant enrichment in mammalian target of rapamycin (mTOR) signal pathway. The candidate target genes of miR-199a-5p include bone morphogenetic protein 3 (BMP3), endothelin converting enzyme 1, and miR-186-5p may target Smad8 and BMP3 to exert osteogenesis-related functions. Conclusions: Compared with static state, tensile stress stimulation can change the expression of miRNAs such as miR-199a-5p, miR-186-5p in the exocrine body of rat condylar chondrocytes, which can be considered as a mean to regulate the application potential of the exosomes.

[Advances in research of microRNA in the growth and development of mandibular condyle cartilage].

MicroRNA (miRNA) are a class of small non-coding single-stranded RNA that exert their biological effects by binding to target messenger RNA (mRNA). There is new evidence that miRNA may play an important role in regulating the growth and development of mandibular condylar cartilage. In this paper, the production and mechanism of miRNA are reviewed, and the progress of studies on the growth and development of mandibular condylar cartilage, which is helpful to further study the growth and development of mandibular condylar cartilage.

Single-molecule enzymatic dynamics.

Enzymatic turnovers of single cholesterol oxidase molecules were observed in real time by monitoring the emission from the enzyme's fluorescent active site, flavin adenine dinucleotide (FAD). Statistical analyses of single-molecule trajectories revealed a significant and slow fluctuation in the rate of cholesterol oxidation by FAD. The static disorder and dynamic disorder of reaction rates, which are essentially indistinguishable in ensemble-averaged experiments, were determined separately by the real-time single-molecule approach. A molecular memory phenomenon, in which an enzymatic turnover was not independent of its previous turnovers because of a slow fluctuation of protein conformation, was evidenced by spontaneous spectral fluctuation of FAD.

[Advance and review: miniscrew-assisted rapid palatal expansion].

Rapid palatal expansion (RPE) is commonly used to correct transverse maxillary deficiencies and recognized as a reliable orthopedic procedure in children and adolescents. For adults, however, conventional RPE has been considered rarely successful and can produce undesirable dental effects. Along with the development of digital techniques and mini-implant anchorage, a novel method called miniscrew-assisted RPE (MARPE) has become available for the treatment of maxillary transverse deficiency in older patients recently. In this article, the biomechanical principles and indications of MARPE, the advances in device design, the clinical effects, the matters needing attention and limitations of this method, and the stability after expansion are discussed.

Use of magnetic biochars for the immobilization of heavy metals in a multi-contaminated soil.

Modified biochars, including magnetic biochars, have been tested in water for the removal of inorganic pollutants. However, at present it is unknown if they possess benefits over conventional biochar materials in relation to land remediation. A paddy soil was collected near Liantang village in Lechang Pb-Zn mine area in Guangdong Province (China). The soil was polluted with Cd, Cu, Zn and Pb, with total contents of 1.4mg/kg, 80mg/kg, 1638mg/kg and 2463mg/kg, respectively. We prepared magnetic and conventional biochar from two feedstocks (poultry litter and Eucalyptus) at a temperature of 300 and 500°C. A sequential extraction procedure for the speciation of heavy metals and a phytotoxicity test using rice were performed. Acid-soluble Cd in soils amended with PLB was 8 to 10% lower than in the control polluted soil. This figure was 27 to 29% for acid-soluble Zn and 59 to 63% for acid-soluble Cu. In some cases, differences were found between the heavy metal fractionation in samples amended with magnetic and conventional biochars. Plant biomass was unaffected by most treatments, but increased by 32% in the treatments containing magnetic poultry litter biochar. Our study shows that a careful choice of feedstock is of utmost importance for successful containment of heavy metals in a multi-contaminated mining area soil. An appropriate choice of feedstock (in the case of this study poultry litter vs. eucalyptus) was more determinant with respect to the mobility of pollutants than altering pyrolysis temperature or modifying surface properties through magnetization. However, surface modification through magnetization can have a significant impact on plant yield and offer comparative advantages in the management of some degraded landscapes.

[Streptococcal toxic shock syndrome caused by Streptococcus pyogenes: a retrospective study of 15 pediatric cases].

Objective: To improve the understanding of clinical characteristics of streptococcal toxic shock syndrome (STSS) caused by Streptococcus pyogenes (S. pyogenes) in children. Methods: A retrospective study was conducted to analyze the clinical data of STSS caused by S. pyogenes (culture-confirmed) in 7 tertiary hospitals during 2010-2017 in China. Clinical and laboratory data were collected by reviewing the medical records. Results: Fifteen cases of STSS, including 9 males, were confirmed and the ages of the patients ranged from 6 months to 15 years, with median age of 3 years. All cases had the positive blood culture for S. pyogenes and only 3 cases had short course of ß-lactam treatment before blood culture. Medical evaluation was initiated within (5.1±4.6) days after symptom onset. All patients had fever, and 13 patients had multiple organ dysfunction and 10 patients had disseminated intravascular coagulationl (DIC). Twelve cases had severe pneumonia with or without skin and (or) soft tissue infections. Underlying conditions included giant hemangioma of the skin in 2 patients and varicella in 1 patient. All isolated strains in 14 cases were sensitive to penicillin G, ceftriaxone/cefotaxime, vancomycin, but 12 and 13 isolates were resistant to clindamycin and erythromycin, respectively. Eight patients died, and 5 of them died within 24 hours after admission. One patient was lost to follow-up after intended discharge against medical advice. Conclusion: STSS caused by S. pyogenes in children is a severe syndrome with rapid clinical progression and high mortality rate, and thus the pediatricians should be aware of STSS and immediately initiate aggressive treatment for the suspected cases.

[Impact of anchorage implant design factors on its primary stability].

During the past decade, the anchorage implants have been widely used in the orthodontic treatment. Many scholars have studied the influence of different factors on anchorage implant's primary stability, including anchorage implant's material properties, structural design, surgical procedure, bone condition, loading force's magnitude and direction. This article is to review the influence of anchorage implant's shape, dimension, neck design and thread design on its primary stability.

[An analysis of 181 cases with blood stream infection caused by Streptococcus agalactiae in children from 2011 to 2015: a multi-center retrospective study].

OBJECTIVE: To analyze the clinical characteristics of blood stream infection caused by Streptococcus agalactiae in children and the drug-resistance of the isolates. METHOD: All cases with Streptococcus agalactiae growth in blood or cerebrospinal fluid cultures from January 1, 2011 to December 31, 2015 were enrolled by checking the laboratory information system (LIS) from 7 Class 3 Grade A hospitals (4 in Zhejiang, 2 in Shanghai and 1 in Chongqing). Clinical data were collected for analysis. χ(2) test, t test and non parametric test were used in the study. RESULT: One hundred and eighty-one pediatric cases of blood stream infection caused by Streptococcus agalactiae were included in current study. Eighty-six cases (47.5%) were male, and with age range from one day to 9 years (media 13 days). Thirty cases (16.6%) were premature infants and 127 cases (70.2%) were born via vaginal delivery. Seventy-one cases (39.2%) had early onset (<7 d) infections, and 106 cases (58.6%) had late onset (7-89 d) infections. Seventy-eight cases (43.1%) were complicated with purulent meningitis. Incidences of vaginal delivery(81.7%(58/71) vs. 62.3%(66/106)), shortness of breath moaning (43.7%(31/71) vs. 15.1%(16/106)) and preterm premature rupture of membranes (25.4%(18/71) vs. 3.8%(4/106)) were higher in the early onset infection group compared with the late onset group(P all<0.05). However, the number of cases who had fever(25.4%(18/71)vs.85.8%(91/106)) and complicated with purulent meningitis (29.6%(21/71) vs. 53.8%(57/106)) in early onset infections group was less than that in the late onset group(P both<0.05). The blood cultures of most patients (87.8%) were performed before the use of antibiotics. Drug-resistant tests showed that the sensitive rates to penicillin G, ceftriaxone and cefotaxime were 98.9%, 99.0% and 99.0% respectively. All strains were sensitive to vancomucine. The rates of resistance to clindamycin and erythromycin were 68.0% and 34.0%, respectively. Only 39 cases (22.0%) were treated with single antibiotics of either penicillins or cephalosporins, 80 cases (45.2%) were treated with antibiotics containing ß lactamase inhibitor, 61 cases (34.5%) were treated with either meropenem or cefoperazone-sulbactam. One hundred and fifty-four cases were cured, while 19 died (including 13 complicated with purulent meningitis) and 8 lost to follow up after giving up of treatment. CONCLUSION: The incidence and mortality of blood stream infection caused by Streptococcus agalactiae complicated with purulent meningitis are high in children. Penicillin is the first choice in treatment. Antibiotics should be selected accorrding to the drug-resistance test.

Motoneuron-specific expression of NR3B, a novel NMDA-type glutamate receptor subunit that works in a dominant-negative manner.

We have identified a novel glutamate receptor subunit on the human and mouse genome. Cloning of the mouse cDNA revealed a protein consisting of 1003 amino acids encoded by at least nine exons. This protein showed the highest similarity (51%) to the NR3A subunit of the NMDA receptor and therefore was termed NR3B. NR3B has a structure typical of glutamate receptor family members with a signal peptide and four membrane-associated regions. Amino acids forming a ligand-binding pocket are conserved. When coexpressed with NR1 and NR2A in heterologous cells, NR3B suppressed glutamate-induced current similarly to NR3A. Thus members of the NR3 class of NMDA receptors act as dominant-negative subunits in the NMDA receptor complex. NR3B shows very restricted expression in somatic motoneurons of the brainstem and spinal cord. Its expression in other types of motoneurons, including autonomic motoneurons in Onuf's nucleus and oculomotor neurons, is significantly weaker. Our results indicate that NR3B is important as a regulatory subunit that controls NMDA receptor transmission in motoneurons. It may be involved in the pathogenesis of neurodegenerative diseases involving motoneurons as well.

[Mechanism of sini decoction in regulating beta-adrenergic receptor signal transduction in rats with myocardial ischemia].

OBJECTIVE: To investigate the effect of Sini Decoction (SND) on beta-adrenergic receptor (beta-AR) signal transduction in rats with myocardial ischemia. METHODS: After beta-AR had been blocked by propranolol, the myocardial ischemia rats were established by pituitrin injection. The density of beta-AR in myocardial cell membrane was determined by radioligand binding assay, cAMP level in plasma and myocardial tissue was detected by radioimmunoassay (RIA), and the mRNA expression of beta 1-AR and beta 1-AR kinase (beta ARK-1) was measured by quantitative reverse transcriptase polymerase chain reaction (RT-PCR) amplifying assay. RESULTS: In myocardial ischemia group, the density of beta 1-AR was up-regulated and the mRNA expression of beta ARK-1 increased (P < 0.01), but the cAMP level in plasma and myocardium was lower than that in the normal group (P < 0.01 and P < 0.05). SND could promote beta 1-AR mRNA expression and inhibit beta ARK-1 mRNA expression so as to increase the density of beta-AR and cause significant raising of cAMP level in plasma and myocardium. CONCLUSION: SND could reduce the desensitization of beta 1-AR during myocardial ischemia and improve signal transduction of beta-AR.

Prolonged sound exposure has different effects on increasing neuronal size in the auditory cortex and brainstem.

Tone at moderate levels presented to young rats at a stage (postnatal week-4) presumably that has passed the cortical critical period still can enlarge neurons in the auditory cortex. It remains unclear whether this delayed plastic change occurs only in the cortex, or reflects a change taking place in the auditory brainstem. Here we compared sound-exposure effects on neuronal size in the auditory cortex and the midbrain. Starting from postnatal day 22, young rats were exposed to a low-frequency tone (4 kHz at 65 dB SPL) for a period of 3 (postnatal day 22-25) or 7 (postnatal day 22-29) days before sacrifice. Neurons were analyzed morphometrically from 7 µm-thick histological sections. A marked increase in neuronal size (32%) was found at the cortex in the high-frequency region distant from the exposing tone. The increase in the midbrain was even larger (67%) and was found in both the low and high frequency regions. While cell enlargements were clear at day 29, only in the high frequency region of the cortex a slight enlargement was found at day 22, suggesting that the cortical and subcortical changes are synchronized, if not slightly preceded by the cortex. In contrast, no changes in neuronal size were found in the cochlear nucleus or the visual midbrain. Such differential effects of sound-exposure at the auditory centers across cortical and subcortical levels cannot be explained by a simple activity-driven change occurring earlier in the brainstem, and might involve function of other structures as for example the descending auditory system.

[Three dimensional finite element analysis of stress induced by orthodontic forces in the periodontal tissue].

The purpose of this study was to investigate the stress induced in the periodontal tissue of the upper central incisor by application of orthodontic forces. A three dimensional finite element model consist of tooth, periodontal ligament (PDL), cancellous and compact bone was established and the following results were obtained: (1) The highest stresses were observed on the root surface, the intermediate on the alveolar bone and the lowest in the PDL. (2) Stress condition on the surface of root and alveolar bone is very complex. The maximum, intermediate and minimum principle stresses on the same area are quite different, but the three principal stresses in the PDL are similar. (3) Regarding to tipping and torque movement, the stress value varied largely from the cervix to the apex, and there is stress concentration at the cervix and the apex. For bodily movement when M/F is -10.30, the stress induced is homogeneous and the difference of the stress values from the cervix to the apex is little, which seems to be more physiological.

Autologous skeletal muscle, an alternative for cardiac assistance.

Original attempts to use skeletal muscle for cardiac assistance were soon abandoned when the problem of muscle fatigue could not be solved. In the last 2 decades, better understanding of muscle physiology and the development of successful protocols of electrical muscle conditioning have given new impetus to researchers around the world to proceed in the effort to identify useful applications of skeletal muscle to support the heart. More than 100 patients around the world have undergone cardiomyoplasty, mostly for cardiac failure. While subjective improvement in symptoms was noticed in the majority of the patients, only recently favorable hemodynamic changes have been documented. The other alternative that has been pursued in the laboratory is the construction of skeletal muscle ventricles that, after conditioning and vascular delay, have been shown to provide significant cardiac support when used for diastolic counterpulsation or for right heart bypass in animal models.

Experience with human immunodeficiency virus infection in patients with hepatitis B virus and hepatitis delta virus infections in Los Angeles, 1977-1985.

Stored serum specimens from 723 patients with acute hepatitis B and 228 patients with chronic hepatitis B seen between 1977 and 1985 in the Hepatitis Clinic of the Los Angeles County-University of Southern California Medical Center, Los Angeles, CA, were tested for antibody to human immunodeficiency virus (anti-HIV). Risk factors were ordered hierarchically; cases with multiple risk factors were tabulated only in the risk group listed first on the clinic records. Anti-HIV was first detected in 1979, and by 1983 was found in about half of all homosexual men with chronic hepatitis B. The prevalence was significantly lower in patients with acute hepatitis B than in patients with chronic hepatitis B, and in nonhomosexual subjects compared with homosexual subjects. By 1985, 30 per cent of intravenous drug users with chronic hepatitis B were anti-HIV-positive. The highest annual seroconversion rate for anti-HIV, 21 per cent, was found in homosexual men in 1983. A significant association existed between anti-HIV positivity and hepatitis delta virus infection in homosexual men but not in drug abusers. This study provides data on the natural history of the human immunodeficiency virus epidemic in Los Angeles. Further study on the interaction of these different viruses is warranted.

Skeletal muscle ventricles: update after 18 months in circulation.

Skeletal muscle ventricles (SMVs) have been constructed from canine latissimus dorsi muscle and connected to the aorta as aortic diastolic counterpulsators. Presently one dog remains alive and well with an SMV that has been functioning continuously in circulation for 18 months, without evidence of thromboembolic complications. SMVs are able to perform cardiac-type work with an output equal to that of the left ventricle at physiologic preloads, when tested with a mock circulation device in our laboratory. SMVs have been used for right-sided cardiac assist. In acute experiments these ventricles have functioned effectively, bypassing the right side of the heart for up to 8 h. Most recently we have tested SMVs using them chronically to pump blood in the right-sided circulation, and at the time of writing they have been shown to function effectively in this configuration for up to 18 days. SMVs may be used in the future as a method of treating patients with left- or right-sided heart failure.

Cloning and characterization of LUN, a novel ring finger protein that is highly expressed in lung and specifically binds to a palindromic sequence.

We isolated cDNAs encoding a novel RING finger protein (LUN), the mRNAs of which were expressed at high levels in the lung. In situ hybridization revealed that LUN mRNAs were expressed in the alveolar epithelium of the lung. The LUN gene locus was assigned to chromosome 9p21, which contains candidate tumor suppressor genes associated with loss of heterozygosity in more than 86% of small cell lung cancers. We clarified that LUN is localized to the nucleus and reveals Zn(2+)-dependent DNA binding activity. The region from amino acids 51 to 374 of LUN is responsible for DNA binding. Furthermore, we identified a novel palindromic binding consensus (5'-TCCCAGCACTTTGGGA-3') for the LUN binding. Interestingly, this LUN binding palindromic sequence is found in the upstream transcriptional regulatory region of the E-cadherin gene and two intervening regions of the talin gene. Our results suggested that LUN might be an important trans-acting transcriptional regulator for lung cancer-associated genes including E-cadherin and talin genes.