PURPOSE: We previously found that the histone methyltransferase suppressor of variegation, enhancer of zeste, trithorax and myeloid-nervy-deformed epidermal autoregulatory factor-1 domain-containing protein 3 (SMYD3) is a potential independent predictive factor or prognostic factor for overall survival in gastric cancer patients, but its roles seem to differ from those in other cancers. Therefore, in this study, the detailed functions of SMYD3 in cell proliferation and migration in gastric cancer were examined. MATERIALS AND METHODS: SMYD3 was overexpressed or suppressed by transfection with an expression plasmid or siRNA, and a wound healing migration assay and Transwell assay were performed to detect the migration and invasion ability of gastric cancer cells. Additionally, an MTT assay and clonogenic assay were performed to evaluate cell proliferation, and a cell cycle analysis was performed by propidium iodide staining. Furthermore, the expression of genes implicated in the ataxia telangiectasia mutated (ATM) pathway and proteins involved in cell cycle regulation were detected by polymerase chain reaction and western blot analyses. RESULTS: Compared with control cells, gastric cancer cells transfected with si-SMYD3 showed lower migration and invasion abilities (P<0.05), and the absence of SMYD3 halted cells in G2/M phase and activated the ATM pathway. Furthermore, the opposite patterns were observed when SMYD3 was elevated in normal gastric cells. CONCLUSIONS: To the best of our knowledge, this study provides the first evidence that the absence of SMYD3 could inhibit the migration, invasion, and proliferation of gastric cancer cells and halt cells in G2/M phase via the ATM-CHK2/p53-Cdc25C pathway. These findings indicated that SMYD3 plays crucial roles in the proliferation, migration, and invasion of gastric cancer cells and may be a useful therapeutic target in human gastric carcinomas.
Ataxia Telangiectasia ; Blotting, Western ; Cell Cycle ; Cell Proliferation ; G2 Phase Cell Cycle Checkpoints ; Histones ; Humans ; Plasmids ; Polymerase Chain Reaction ; Propidium ; RNA, Small Interfering ; Stomach Neoplasms* ; Transfection ; Wound Healing

OBJECTIVETo investigate the major risk factors for congenital heart disease (CHD) in Chinese neonates and to provide a reference for the prevention of CHD.

METHODSA literature search was performed to collect the case-control studies on the risk factors for CHD in Chinese neonates published in 2001-2016. The relevant data were extracted accordingly. The quality of included studies was assessed by Newcastle-Ottawa Scale. Sensitivity analysis was conducted using different models to analyze the same data. The publication bias was assessed by Egger's test.

RESULTSA total of 17 case-control studies involving 2 930 cases and 4 952 controls were included. The Meta analysis showed that the major risk factors for CHD in Chinese neonates were as follows: mother with advanced age (OR=2.649, 95%CI: 1.675-4.189), cold or fever (OR=4.558, 95%CI: 2.901-7.162), medication use in early pregnancy (OR=3.961, 95%CI: 2.816-5.573), passive smoking (OR=2.766, 95%CI: 1.982-3.859), abnormal childbearing history (OR=2.992, 95%CI: 1.529-5.856), noise exposure (OR=3.030, 95%CI: 1.476-6.217), radiation exposure (OR=2.363, 95%CI: 1.212-4.607), decoration (OR=4.979, 95%CI: 3.240-7.653), gestational diabetes (OR=5.090, 95%CI: 3.132-8.274), and pet raising (OR=2.048, 95%CI: 1.385-3.029).

CONCLUSIONSMothers with advanced age, cold or fever, medication use in early pregnancy, passive smoking, abnormal childbearing history, noise exposure, radiation exposure, decoration, gestational diabetes, and pet raising may increase the risk of CHD in Chinese neonates.

Case-Control Studies ; Heart Defects, Congenital ; etiology ; Humans ; Infant, Newborn ; Risk Factors

Esophagustype cervical spondylosis is easily misdiagnosed or missed diagnosed for its lower incidence. The pathological basis manily concerned with compression of osteophyte for esophageal and tracheal wall and local inflammatory reaction. The diagnosis of disease is generally not difficult. Especially dynamic esophagogram could not only show degree of cervical degeneration and osteophyte shape, but also could clearly observe location and degree of osteophytosis indenting esophageal and tracheal. Recently, the treatment of esophagustype cervical spondylosis has been the focus of attention. It is generally believed that conservative treatment could alleviate disease but could not cure it. More and more scholars tend to treat disease by surgical resection of osteophyte to relieve compression for esophagus, and clinical symptoms could obviously improved. However, long-term follow up is lack, and further follow-up effect is lack of powerful support, anddifferent treatment methods and surgical procedures are lack of comparative research.

OBJECTIVETo evaluate the efficacy and safety of Chinese medicine (CM) plus Western medicine (WM) in the treatment of pediatric patients with severe hand, foot and mouth disease (HFMD) by conducting a prospective, controlled, and randomized trial.

METHODSA total of 451 pediatric patients with severe HFMD were randomly assigned to receive WM therapy alone (224 cases, WM therapy group) or CM [Reduning Injection ( ) or Xiyanping Injection ()] plus WM therapy (227 cases, CM plus WM therapy group) for 7-10 days, according to a web-based randomization system. The primary outcome was fever clearance time, which was presented as temperature decreased half-life time. The secondary outcomes included the rate of rash/herpes disappearance within 120 h, as well as the rate for cough, runny nose, lethargy and weakness, agitation or irritability, and vomiting clearance within 120 h. The drug-related adverse events were also recorded.

RESULTSThe temperature decreased half-life time was 40.4 h in the WM therapy group, significantly longer than 27.2 h in the CM plus WM therapy group (P<0.01). Moreover, the rate for rash/herpes disappearance within 120 h was 43.6% (99/227) in the CM plus WM therapy group, significantly higher than 29.5% (66/224) in the WM therapy group (P<0.01). In addition, the rate for cough, lethargy and weakness, agitation or irritability disappearance within 120 h was 32.6% (74/227) in the CM plus WM therapy group, significantly higher than 19.2% (43/224) in the WM therapy group (P<0.01). No drug-related adverse events were observed during the course of the study.

CONCLUSIONThe combined CM and WM therapy achieved a better therapeutic efficacy in treating severe HFMD than the WM therapy alone. Reduning or Xiyanping Injections may become an important complementary therapy to WM for relieving the symptoms of severe HFMD. (Registration No. NCT01145664).

An HPLC method was established to determine the contents of catalpol, acteoside, rehmaionoside A, rehmaionoside D, leonuride in three part of Rehmanni glutinosa in Beijing No.1 variety R. glutinosa during the growth period, This method, in combination with its HPLC fingerprint was used to evaluate its overall quality characteristics.The results showed that：① the content of main components of R. glutinosa varied in different growth stages ;② there was a great difference of the content of main components between theradial striations and the non-radial striations; ③ the two sections almost have the same content distribution of catalpol, acteoside and rehmaionoside D; ④the content of rehmaionoside A in non-radial striations was higher than that in radial striations,while the content of leonuride in radial striations was higher than that in non-radial striations.; ⑤the HPLC fingerprint of radial striations, non-radial striations and whole root tuber were basically identical, except for the big difference in the content of chemical components. The result of clustering displayed that the radial striations, non-radial striations, and whole root were divided into two groups. In conclusion, there was a significant difference in the quality characteristics of radial striations and non-radial striations of R. glutinosa. This research provides a reference for quality evaluation and geoherbalism of R. glutinosa.

In the daily life, we perceive the world around us by integrating multiple sensory cues (visual, auditory, olfactory, gustatory, tactile, vestibular and proprioceptive) to create a coherent, reliable representation that allows us to interact meaningfully with the environment. The integration of different sensory information is necessary for our perception, motor transformation, decision making, learning and memory. In the past decades, many interdisciplinary researchers have been attracted to the field of multisensory research, and tremendous advances have been made in this field. We review the researches on multisensory integration during self-motion perception in the past decades from the candidate areas, the integration principles and the neural correlation of the behaviors, with the intention to provide a comprehensive source for those interested in understanding the neural substrates for multisensory integration. Meanwhile, we also provide a prospect for the future research in this field.

BACKGROUNDRetinal edema is the major complication of retinal vein occlusion and diabetic retinopathy; it can damage visual function by influencing macular region. This study was to establish a rat retinal edema model and explore the related VEGF expression and observe the responses to anti-VEGF drugs in this model.

METHODSA rat retinal edema model was established by inducing photochemical reaction using a 532 nm laser after the intravenous injection of Erythrosin B. Immediately after the laser treatment, models were given intravitreal injections of Ranibizumab or Conbercept to inhibit VEGF expression, and the changes of retinal thickness were measured. Retinal edema was observed using fundus photography (FP), optical coherence tomography (OCT), and fluoresce in fundus angiography (FFA) at 0, 1, 2, 4, 7 and 14 days after intervention. The retinal VEGF expression was measured using enzyme-linked immunosorbent assay (ELISA) and western blotting at each time point. The rat retinal edema model was also used to verify the function of anti-VEGF polypeptide ZY1.

RESULTSBoth retinal edema and vascular leakage were clearly observed at 1, 2 and 4 days after photochemical induction and the retinal thickness increased notably over the same period. The retinal VEGF expression peaked at day 1 and retina became thickening simultaneously. After the interventions, the VEGF expression of the Ranibizumab and Conbercept groups decreased at each time point compared to the edema group (26.90 ± 3.57 vs. 40.29 ± 6.68, F = 31.269 on day 1 and 22.36 ± 1.12 vs. 29.92 ± 0.93 F = 163.789 on day 2, both P < 0.01); the mean RT (278 ± 4 vs. 288 ± 3, F = 134.190 on day 1 and 274 ± 7 vs. 284 ± 6, F = 64.367 on day 2, both P < 0.05) and vascular leakage in these groups also decreased. The same results were observed in the ZY1 group, particularly at day 2 (P < 0.05).

CONCLUSIONSThis retinal edema model induced by a photochemical reaction is reliable and repeatable. Induced edema increases expression of VEGF. This model can be used to test new drugs.

Angiogenesis Inhibitors ; therapeutic use ; Animals ; Enzyme-Linked Immunosorbent Assay ; Erythrosine ; toxicity ; Fluorescein Angiography ; Intravitreal Injections ; Macular Edema ; chemically induced ; drug therapy ; metabolism ; Ranibizumab ; therapeutic use ; Rats ; Rats, Sprague-Dawley ; Recombinant Fusion Proteins ; therapeutic use ; Tomography, Optical Coherence ; Vascular Endothelial Growth Factor A ; metabolism

BACKGROUNDSmD1-amino-acid 83-119 peptide (SmD183-119) is the major epitope of Smith (Sm) antigen, which is specific for adult systemic lupus erythematosus (SLE). The anti-SmD183-119 antibody has exhibited higher sensitivity and specificity than anti-Sm antibody in diagnosing adult SLE. However, the utility of anti-SmD183-119antibodies remains unclear in children with SLE (cSLE). This study aimed to assess the characteristics of anti-SmD183-119antibody in the diagnosis of cSLE.

METHODSSamples from 242 children with different rheumatological and immunological disorders, including autoimmune diseases (SLE [n = 46] and ankylosing spondylitis [AS, n = 11]), nonautoimmune diseases (Henoch-Schonlein purpura [HSP, n = 60], idiopathic thrombocytopenia purpura [n = 27], hematuria [n = 59], and arthralgia [n = 39]) were collected from Shanghai Children's Medical Center from March 6, 2012 to February 27, 2014. Seventy age- and sex-matched patients were enrolled in this study as the negative controls. All the patients' sera were analyzed for the anti-SmD183-119, anti-Sm, anti-U1-nRNP, anti-double-stranded DNA (dsDNA), anti-nucleosome, anti-SSA/Ro60, anti-SSA/Ro52, anti-SSB, anti-Scl-70, and anti-histone antibodies using the immunoblotting assay. The differences in sensitivity and specificity between anti-SmD183-119 and anti-Sm antibodies were compared by Chi-square test. The correlations between anti-SmD183-119and other auto-antibodies were analyzed using the Spearman's correlation analysis. A value of P< 0.05 was considered statistically significant.

RESULTSThirty-six out of 46 patients with cSLE were found to be positive for anti-SmD183-119, while 12 patients from the cSLE cohort were found to be positive for anti-Sm. Compared to cSLE, it has been shown that anti-SmD183-119 was only detected in 27.3% of patients with AS and 16.7% of patients with HSP. In comparison with anti-Sm, it has been demonstrated that anti-SmD183-119 had a higher sensitivity (78.3% vs. 26.1%, χ2 = 25.1, P< 0.05) and a lower specificity (90.8% vs. 100%, χ2 = 13.6, P< 0.05) in the diagnosis of cSLE. Further analysis revealed that anti-SmD183-119antibodies were positively correlated with anti-dsDNA, anti-nucleosome, and anti-histone antibodies in cSLE. Moreover, it has been clearly shown that anti-SmD183-119 was more sensitive than anti-Sm in discriminating autoimmune diseases from nonautoimmune disorders in patients with arthralgia or hematuria.

CONCLUSIONSMeasurement of anti-SmD183-119in patients with cSLE has a higher sensitivity and a marginally lower specificity than anti-Sm. It has been suggested that inclusion of anti-SmD183-119testing in the integrated laboratory diagnosis of cSLE may significantly improve the overall sensitivity in child populations.

Autoantibodies ; immunology ; Autoantigens ; immunology ; Child ; Female ; Humans ; Immune System Diseases ; immunology ; Immunoblotting ; Lupus Erythematosus, Systemic ; immunology ; Male ; Peptides ; chemistry ; immunology ; snRNP Core Proteins ; immunology

OBJECTIVETo explore the differentiation-inducing potentiality of Pulsatilla saponin A on K562 cells.

METHODSPulsatilla saponin A of different concentrations was used to treat K562 cells; the benzidine staining and the hemoglobinometry were applied to measure the change of hemoglobin content; the flow cytometry (FCM) was used to detect the expression of CD71 and GPA on K562 cells.

RESULTSK562 cells treated with 4 µg/ml pulsatilla saponin A differentiated into the erythroid lineage. With the treatment of pulsatilla saponin A, the hemoglobin content in K562 cells increased significantly; CD71 and GPA expression on the K562 cell surface were up-regulated.

CONCLUSIONPulsatilla saponin A can induce K562 cells to differentiate into erythroid lineage.

Antineoplastic Agents ; Cell Differentiation ; Cell Lineage ; Erythroid Cells ; Humans ; K562 Cells ; Saponins

PURPOSE: Increased lipoprotein-associated phospholipase A2 (Lp-PLA2) activity and Rho kinase activity may be associated with atherosclerosis. The principal aim of this study was to examine whether darapladib (a selective Lp-PLA2 inhibitor) could reduce the elevated Lp-PLA2 and Rho kinase activity in atherosclerosis. MATERIALS AND METHODS: Studies were performed in male Sprague-Dawley rats. The atherosclerosis rats were prepared by feeding them with a high-cholesterol diet for 10 weeks. Low-dose darapladib (25 mg.kg-1.d-1) and high-dose darapladib (50 mg.kg-1.d-1) interventions were then administered over the course of 2 weeks. RESULTS: The serum levels of triglycerides, total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), high-sensitivity C-reactive protein (hs-CRP), and Lp-PLA2, significantly increased in atherosclerosis model groups, as did Rho kinase activity and cardiomyocyte apoptosis (p<0.05 vs. sham group), whereas nitric oxide (NO) production was reduced. Levels of TC, LDL-C, CRP, Lp-PLA2, and Rho kinase activity were respectively reduced in darapladib groups, whereas NO production was enhanced. When compared to the low-dose darapladib group, the reduction of the levels of TC, LDL-C, CRP, and Lp-PLA2 was more prominent in the high-dose darapladib group (p<0.05), and the increase of NO production was more prominent (p<0.05). Cardiomyocyte apoptosis of the high-dose darapladib group was also significantly reduced compared to the low-dose darapladib group (p<0.05). However, there was no significant difference in Rho kinase activity between the low-dose darapladib group and the high-dose darapladib group (p>0.05). CONCLUSION: Darapladib, a Lp-PLA2 inhibitor, leads to cardiovascular protection that might be mediated by its inhibition of both Rho kinase and Lp-PLA2 in atherosclerosis.
1-Alkyl-2-acetylglycerophosphocholine Esterase/*antagonists & inhibitors/blood/drug effects ; Animals ; Atherosclerosis/blood/*drug therapy/*enzymology ; *Benzaldehydes ; C-Reactive Protein/metabolism ; Cholesterol/blood ; Cholesterol, HDL/blood ; Cholesterol, LDL/blood ; Dose-Response Relationship, Drug ; Male ; *Oximes ; Phospholipase A2 Inhibitors/*administration & dosage/adverse effects ; Rats ; Rats, Sprague-Dawley ; Triglycerides/blood ; rho-Associated Kinases/*metabolism