Circular ribonucleic acid circ-FADS2 promotes colorectal cancer cell proliferation and invasion by regulating miR-498/S100A16.

The aim of this study is to examine the role and functional mechanism of circ-FADS2 in colorectal cancer (CRC). The levels of expression of circ-FADS2 were detected in 48 patients with CRC and their paired normal tissue samples and cell lines (SW480, SW620, HCT116, HT29, and NCM460) using quantitative real-time polymerase chain reaction (qRT-PCR). Circ-FADS2 was then silenced in SW480 and HT29 cells using two small interfering ribonucleic acids. Themolecular mechanism of circ-FADS2 in CRC progression and migration was then examined by sponging miR-498 and promoting S100A16 expression. After this, the expression of miR-498 and S100A16 in CRC tissues was analyzed using a qRT-PCR. In results: circ-FADS2 was found to be significantly upregulated in CRC tissues, when compared with paired normal tissues. Higher circ-FADS2 expression was associated with advanced stages, lymphatic metastasis, and reduced overall survival (OS). In addition, silencing circ-FADS2 markedly inhibited the proliferation and invasion of CRC and increased the percentage of cancer cells in the G1 phase in vitro. Reducing circ-FADS2 decreased SW480 cell proliferation in vivo. By inhibiting miR-498 expression, circ-FADS2 promoted S100A16 expression leading to the activation of the AKT pathway, resulting in CRC progression. We conclude that Circ-FADS2 expression was upregulated in CRC tissues and cells and was found to be correlated with advanced cancer, metastasis, and poor OS. A study of the molecular mechanism suggests that a circ-FADS2/miR-498/S100A16/AKT signaling cascade may be a potential therapeutic target for the treatment of CRC.

Effects of IL-1ß and IL-18 induced by NLRP3 inflammasome activation on myocardial reperfusion injury after PCI.

OBJECTIVE: To investigate the effect of nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) inflammasome in the serum levels of interleukin-1ß (IL-1ß) and interleukin-18 (IL-18) in patients with myocardial reperfusion injury after the percutaneous coronary intervention (PCI). PATIENTS AND METHODS: Twenty healthy controls (control group) and forty patients (treatment group) were recruited in this study. The enzyme-linked immunosorbent assay (ELISA) was used to measure the serum levels of IL-1ß and IL-18 at various time points in both the control and treatment groups. Data processing and analysis were performed using the Statistical Product and Service Solution (SPSS) 22.0 software (IBM Corp, Armonk, NY, USA). Pearson's correlation coefficient test was applied in all data analyses. A difference was statistically significant when p<0.05. RESULTS: The levels of IL-1ß and IL-18 in the treatment group were significantly higher than those in the control group (p<0.05). The IL-1ß level in the treatment group peaked at 0.5 h after PCI and then, gradually decreased. The multiple regression analysis showed that IL-1ß level was positively correlated with levels of LDL-C and IL-18 (p<0.05, r=0.527 and 0.955 respectively), and negatively correlated with the HDL-C level (p<0.05, r=-0.34). CONCLUSIONS: The levels of IL-1ß and IL-18 significantly rose in patients with myocardial ischemia-reperfusion injury after PCI.

MiR-92a contributes to the cardiovascular disease development in diabetes mellitus through NF-κB and downstream inflammatory pathways.

OBJECTIVE: To explore the role of microRNA-92a (miR-92a) during the development of cardiovascular disease (CAD) in diabetes mellitus (DM) patients, and to investigate its correlation with NF-κB and downstream inflammatory cytokines in diabetes mellitus-associated cardiovascular disease (DM-CAD). PATIENTS AND METHODS: Expression of miR-92a in DM and DM-CAD patients was estimated by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). Receiver operating characteristic (ROC) analysis was used to estimate the capability of miR-92a to discriminate between DM-CAD and DM patients. Nuclear factor-κB (NF-κB) p65 protein expression and serum concentrations of monocyte chemotactic protein-1 (MCP-1), endothelin-1 (ET-1) and intercellular adhesion molecule-1 (ICAM-1) were investigated. Correlations between miR-92a and NF-κB p65, inflammatory factors were assessed. Risk analysis based on miR-92a was performed for DM-CAD patients. RESULTS: MiR-92a expression was increased in DM-CAD group compared with both DM and healthy groups (all p<0.05). The expression of miR-92a was associated with FIB and HbA1c of DM-CAD patients. MiR-92a could be used to distinguish DM-CAD patients from DM patients with an area under the ROC curve (AUC) of 0.866. Moreover, miR-92a was demonstrated to be a risk factor for DM-CAD onset. Expression levels of NF-κB p65, ET-1, MCP-1, and ICAM-1 were all elevated in DM-CAD patients and shown positive correlations with miR-92a. CONCLUSIONS: Expression of miR-92a in DM-CAD patients is up-regulated, and serves as a potential marker to predict the CAD in DM patients. MiR-92a may contribute to the development of CAD through activation of NF-κB and downstream inflammatory pathways.

High expression of carbonic anhydrase 12 (CA12) is associated with good prognosis in breast cancer.

The purpose of this research was to explore whether the expression of carbonic anhydrase 12 (CA12) and the prognosis had a significant relationship in breast cancer patients. A total of 262 breast cancer specimens and 75 normal breast tissue specimens were recruited in this study. The expression of CA12 was detected by immunohistochemistry (IHC), and its correlation with the clinicopathological characteristics of breast cancer patients and their prognosis were further analyzed through standard statistical algorithms. The result of immunohistochemical staining showed that CA12 was detected in both normal breast tissue and breast cancer tissue. Compared to normal breast tissue, CA12 was significant higher expressing in cancer tissues (P=0.009). Statistical analysis showed that the high expression of CA12 in breast cancer tissue was related to estrogen receptor expression level (P<0.001). The follow-up of 262 cases of breast cancer patients within 5 years showed that patients with high expression of CA12 had significant better outcome in DFS (P=0.020) and OS (P=0.019) than patients with low expression of CA12. Univariate analysis of DFS showed that lymph node metastasis (P=0.034) and CA12 (P=0.024) are prognostic indicators. Multivariate analysis manifested that the expression of CA12 (P=0.025) and lymph node metastasis (P=0.024) are two independent factors affecting the prognosis of breast cancer. Conclusion: In breast cancer patients, CA12 can be seen as a new prognostic indicator and even a new target for treatment.

Study on sildenafil combined with inhalational nitric oxide therapy on the curative effects and serum levels of HIF-1α, ET-1, and calcium in neonatal pulmonary hypertension.

OBJECTIVE: To explore the effect of sildenafil combined with inhalational nitric oxide (NO) therapy on the curative effects and serum levels of hypoxia-inducible factor (HIF)-1α, endothelin-1 (ET-1), and calcium in persistent pulmonary hypertension of the newborn (PPHN). PATIENTS AND METHODS: Eighty-six patients with neonatal pulmonary hypertension treated in Xuzhou Children's Hospital from March 2015 to February 2016 were randomly divided into the observation group and control group, treated with sildenafil and sildenafil combined with inhalational NO, respectively. The clinical efficacy of newborns in the two groups was compared. Fraction of inspiration O2 (FiO2), Oxygen Index (OI), blood oxygen partial pressure (PaO2), blood oxygen saturation (SpO2), and pulmonary arterial pressure of newborns in the two groups were compared before treatment and 2 h, 12 h, and 24 h after treatment. The serum levels of HIF-1α, ET-1, and calcium of patients in the two groups were compared before treatment and 3, 5, 7 days after treatment. RESULTS: The total effective rate of the observation group (95.34%) was significantly higher than that of the control group (74.41%) (p<0.05). After treatment, FiO2, OI, and pulmonary arterial pressure of patients in the two groups decreased, and the decrease in the observation group was significantly lower than in the control group (p<0.05). After treatment, PaO2 and SpO2 of patients in the observation group were higher than those of the control group. The levels of HIF-1α and ET-1 of patients in the two groups decreased and were significantly lower in the observation group compared with the control group. The levels of calcium of patients in the two groups increased and were significantly higher in the observation group than the control group (p<0.05). CONCLUSIONS: Sildenafil combined with inhalational NO therapy for neonatal pulmonary hypertension can quickly improve oxygenation, effectively reduce pulmonary arterial hypertension, and is worthy of clinical application.

Study on the correlation of changes of IGF-1, GH, and NGB levels and NBNA score in neonates with hypoxic ischemic encephalopathy.

OBJECTIVE: The aim of this work was to investigate the correlation between dynamic changes of serum insulin-like growth factor 1 (IGF-1), growth hormone (GH), neuroglobin (NGB), and neonatal behavioral neurological assessment (NBNA) scores in different periods in neonates with hypoxic ischemic encephalopathy (HIE). PATIENTS AND METHODS: Sixty HIE patients in the Neonatal Department of our hospital were selected. They were divided into the mild group (35 cases), moderate group (19 cases), and severe group (six cases) according to the diagnostic criteria. During the same period, 18 neonatal patients born at term in our hospital were chosen as the control group. Data were analyzed by SPSS19.0 statistical software (SPSS Inc., Chicago, IL, USA). The dynamic changes of IGF-1, GH, and NGB in different periods, as well as NBNA scores in HIE patients and in the control group, were analyzed. Furthermore, we analyzed the degree of correlation of IGF-1, GH, and NGB in different periods as well as NBNA scores in HIE patients and in the control group. RESULTS: 1- IGF-1 levels between the three groups of HIE patients and control group had significant differences (p<0.05); 2- Comparing GH levels between the HIE experimental groups and control group, there was no statistical significance; 3-Comparing serum NGB levels between the three HIE experimental groups and control group, there were significant differences (p<0.05); 4- Comparing NBNA scores of the three groups of HIE patients and control group, there was a significant difference between the mild group and control group; 5- Serum IGF-1 and NBNA scores were positively correlated in the acute and recovery phase, while NGB level and NBNA scores were negatively correlated in the acute and recovery phase (p<0.05), which had statistical significance. CONCLUSIONS: In neonatal HIE, serum IGF-1, GH, and NGB levels change. IGF-1 and NGB levels correlate with the prognosis of HIE.

The clinical effects of combined use of inhaled nitric oxide at early stage to cure severe respiratory failure in neonates.

OBJECTIVE: To observe the clinical effects of combined use of inhaled nitric oxide at the early stage to cure severe respiratory failure in neonates. PATIENTS AND METHODS: 45 cases of neonates with severe respiratory failure, who were admitted to the neonatal intensive care unit (NICU) of XuZhou Children's Hospital from November 2014 to February 2016, were selected as objects of study, namely the iNO treatment group. On the basis of conventional treatment and mechanical ventilation, all of them were treated with the combined use of iNO at the early stage. The arterial blood gas index, respiratory function index and other indexes of those children were observed before iNO treatment and 1 h, 6 h, 12 h and 24 h post-treatment. 31 cases of newborns with severe respiratory failure admitted to the NICU of the same hospital from July 2013 to August 2014 were analyzed and selected as the control group. The cases in this group met the same criteria as those administered the iNO treatment. Comparisons were made between both groups in terms of the duration of ventilator support, complications during treatment, oxygen supply time, hospital stay and other data. RESULTS: When treated after 1 h, 6 h, 12 h and 24 h, the pH value, arterial oxygen and carbon dioxide partial pressure of children in the iNO inhalation group significantly improved compared to those before treatment, and the difference was significant (p<0.05). When treated after 6, 12 and 24 h, the inspired oxygen concentration and oxygenation values of children significantly decreased compared to before treatment (p<0.05). When treated after 6, 12, and 24 h, the mean airway pressure of children was less than that before treatment and the difference was statistically significant (p<0.05). When treated after 1 h, 6, 12, 24 h, the arterial alveolar oxygen partial pressure ratio of children was greater than that before treatment and the difference was significant (p<0.05). When treated after 24 h, the pulmonary artery pressure of children significantly decreased compared to before treatment (p<0.05). Compared to the control group, the complications during the treatment, the respirator use time, oxygen supply time, length of stay and the mortality of children in the iNO treatment group were significantly decreased. CONCLUSIONS: Mechanical ventilation, combined with iNO therapy, can effectively improve the respiratory function and arterial blood gas index of neonates with severe respiratory failure, improve the oxygenation, reduce complications and improve the quality of rescue, which is worthy of promotion.

Research on the correlation between the fibrinogen ß and attack of pediatric pneumonia.

OBJECTIVE: To investigate the correlation of the gene polymorphism of ß-148C/T of fibrinogen with the expression of fibrinogen and the attack of pediatric pneumonia. PATIENTS AND METHODS: We employed polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) to detect the gene polymorphism of beta-fibrinogen gene-148C/T (ß-148C/T). The expression level of fibrinogen in plasma was measured using enzyme-linked immunosorbent assay (ELISA), and the expression level of fibrinogen ß protein was determined using Western-blot method. RESULTS: Compared with the healthy control group, the expression level of fibrinogen ß was significantly higher in patients with pneumonia. Additionally, the frequency of CC genotype, as well as the allele of C, in the pneumonia group were significantly higher than that in the control group. Meanwhile, the frequency of TT genotype and the allele of T were remarkably lower in patients with pneumonia compared to those in the control group. No significant difference was found in comparison with the CT genotype frequency between the two groups. Compared with the patients with TT genotypes, expressions of fibrinogen, IL-6 and CRP were significantly higher in the patients with the CC and CT genotypes. However, the odds ratio (OR) of pediatric pneumonia patients with TT genotype was 0.21, OR of pediatric pneumonia patients with CT genotype was 0.77 and OR of pediatric pneumonia patients with CC genotype was 12.73. The OR of patients with T allele was 1.85 and OR of patients with C allele was 5.15. CONCLUSIONS: We concluded that ß-148C/T gene polymorphism of fibrinogen was correlated with the susceptibility of pediatric pneumonia, suggesting that it may be a genetic risk factor, and fibrinogen ß-148C/T gene may be involved in the onset of pediatric pneumonia through affecting the concentration of fibrinogen ß in plasma.

Factors responsible for mother to child transmission (MTCT) of HIV-1 - a review.

Many factors have been identified to influence the risk of mother to child transmission (MTCT) of HIV. Chief amongst these is high maternal VL and advanced disease. High maternal viral load (mVL), measured at delivery, has been described as the strongest risk factor for both in utero (IU) and intrapartum (IP) transmission. Similarly, CD4+ T cell count and clinical stage of infection are also the confirmed significant predictors of transmission. Correspondingly, higher mVL in the genital tract has also been independently associated with a higher risk of MTCT of HIV-1. So, the present review article would put light on various aspects of factors responsible for MTCT of HIV in pediatric patients.

Protein metabolism and exercise in children - a review.

General nutritional strategies to promote whole body protein retention, particularly with relation to exercise, have been largely based on adult research that does not consider the dynamic process of growth and often ignores scenarios commonly experienced by children (e.g., exercise in the heat). Therefore, the aim of the present review is to highlight the importance of post-exercise protein quantity and timing in active children, specifically with respect to the whole body protein turnover.

Hypothermia in neonatal hypoxic-ischemic encephalopathy (HIE).

Neonatal hypoxic-ischemic encephalopathy (HIE) significantly affects neurodevelopment in infants and is also considered as an important cause of neonatal deaths worldwide. Medical research is being focused worldwide for the development of therapeutic avenues but it is still managed by supportive care. The latest studies in the above field have shown the efficacy of prolonged cooling of neonate's head or whole body at the age of 18 months (approx.) in providing relief from the pathological state of HIE. Moreover, hypothermia is the first reported therapeutic modality that proved beneficial for HIE young patients. Further, it acts by decreasing the cerebral metabolism to mitigate neurological outcomes of the pathological state. The present review article would discuss all-important aspects of hyperthermia therapy in the improvement of young patients affected by HIE.

Pediatric protein metabolism techniques - a review.

Some invasive techniques could be safely and ethically applied to estimate protein metabolism in children. Although these methodologies provide valuable information on whole body protein metabolism, a reflection of what is happening to thousands of protein molecules across a variety of different tissues. However, they provide little information regarding the contribution of specific tissues and proteins to the whole-body changes observed (e.g., whether the increase in protein synthesis was a result of the muscle or splanchnic tissues) which might otherwise be determined in more invasive procedures such as those with muscle biopsies. Considering ethical constraints in pediatric research, it is not possible to perform stable isotope methods with concurrent muscle biopsies. The present review article enlightens the techniques in use for measurement of pediatric protein metabolism.

The effects of second messenger cAMP and its relative components on the contraction of uterine smooth muscle of rat.

OBJECTIVE: To investigate the effect of second messenger pathways on the uterine smooth muscle contraction and their associated mechanisms, and compare the evaluation methods. MATERIALS AND METHODS: Preparation of uterine smooth muscle strips from healthy pregnant 18-21 d SD and non-pregnant rats. When the contraction of muscle strips was stable, we conducted gradient administration: PDE4 inhibitors (Z90), prostaglandin PGE2, adenylate cyclase inhibitor (SQ 22,530), cAMP analogs (dbcAMP) and AMPK agonists (AICAR), solvent dimethyl sulfoxide (DMSO) as controlled. Gradient administration of acetylcholine (Ach) and oxytocin (oxytocin) induced the contraction of muscle strips. The tension transducer and biological information collecting system were applied to record the changes, including duration, dilation tension, contraction tension, peak height, and mean tension, before and after different administration. Principal components analysis was adopted to evaluate the five changes. RESULTS: SQ 22,530, DMSO, cAMP alone had no significant effect on the contraction of uterine smooth muscle; Z90 can inhibit the spontaneous contraction of pregnant uterine smooth muscle strips; dbcAMP and AICAR can antagonize acetylcholine and oxytocin-induced the contraction of pregnant uterine smooth muscle strips. Z90, SQ 22,530 + Z90, dbcAMP, AICAR can inhibit the uterine contraction peak, diastolic amplitude, average muscle tone and contraction duration of the pregnant uterine smooth muscle in a concentration-dependent manners. At the same time, we compared the parameters, which reflect the contraction of uterine smooth muscle, and conduct main components analysis to determine the effect of the drugs. CONCLUSIONS: The second messenger cAMP and its related components ATP, 5'- AMP, AC, PDE, PKA, and AMPK can affect the uterine smooth muscle contraction via related signaling pathway in rats, and principal components analysis can be adopted to evaluate the smooth muscle relaxant.

Application of percutaneous epididymal sperm aspiration in azoospermia.

OBJECTIVE: The present study introduces the application of percutaneous epididymal sperm aspiration (PESA) for diagnosis of obstructive azoospermia and non-obstructive azoospermia. PATIENTS AND METHODS: 96 cases diagnosed with azoospermia were selected, standard methods were used to measure testicular volume, chemiluminescence was used to test serum sexual hormone levels, and No. 7 butterfly needles were applied to puncture the head of the epididymis and aspirate epididymal luminal fluid. RESULTS: Among 96 cases of azoospermia, sperm was found in the epididymal luminal fluid of 49 cases, among which there were 41 cases with normal testicular volume and 8 cases with low volume. 39 cases had normal serum FSH levels, and 10 cases had increased serum FSH levels. There were 47 cases with no sperm, among which there were 26 cases with normal testicular volume and 21 cases with low volume. 29 cases had normal serum FSH levels, and 18 cases had increased levels. The success rate of puncture for patients with normal testicular volume was higher than that of patients with low volume, and the difference was statistically significant (p < 0.05). The success rate of puncture for patients with normal serum FSH levels was higher than that of patients with increased levels, and the difference was statistically significant (p < 0.05). CONCLUSIONS: PESA is simple and efficient, and is a feasible method for diagnosis of azoospermia.

Differential diagnosis of IgG4-related sialadenitis, primary Sjögren syndrome, and chronic obstructive submandibular sialadenitis.

Our aim was to differentiate IgG4-related sialadenitis, primary Sjögren syndrome, and chronic obstructive submandibular sialadenitis by analysing clinical, radiographic, and pathological features. Fifty-five patients, 50, and 50 were enrolled, respectively and their baseline characteristics and serological, sialographic, and pathological findings compared. The male:female ratio for IgG4-related sialadenitis was 1:1.2 for primary Sjögren syndrome 1:15.7, and for chronic obstructive submandibular sialadenitis1:0.92. Numbers with enlarged salivary glands were 55, 16, and 50; with xerostomia 26, 48, and 0; with a history of allergy 26, 4, and 6, and with coexisting systemic disease 12, 19, and 0 (p=0.14). Mean (SD) serum IgG4 concentrations were 109.1 (97.9), 4.9. (1.9) g/L, and 5.3 (1.6) g/L, p<0.001 in all cases. Sialography showed enlargement of the gland, dilatation of the duct, and slightly decreased secretory function in IgG4-related disease; obvious sialectasia and decreased secretory function in Sjögren syndrome; and dilatation of Wharton's duct and filling defects in obstructive sialadenitis. Histopathological examination showed lymphoplasmacytic infiltration with storiform fibrosis, lymphoplasmacytic inflammation and lymphoepithelial lesions, and dilatation of the duct with epithelial metaplasia in the three groups, respectively. The number of IgG4-positive plasma cells was 123 (45)/HPF, 8 (3)/HPF, and 5 (4)/HPF, while the IgG4-/IgG-positive cell ratio was 71.7 (13.9)%, 4.6 (2.5)%, 18.9 (19.7)%, respectively (p<0.001). The three conditions have different clinical, radiographic, and pathological features that provide important clues to the differential diagnosis. Serological and histological tests are important, and comprehensive consideration is necessary.

Effect of nitric oxide inhalation for the treatment of neonatal pulmonary hypertension.

OBJECTIVE: To investigate the effect of nitric oxide (NO) inhalation for the treatment of neonatal pulmonary hypertension. PATIENTS AND METHODS: Eighty-six patients with neonatal pulmonary hypertension who were treated for the first time Xuzhou Children's Hospital from January 2013 to January 2016 were selected and randomly divided into the observation group and control group, with 43 cases each. Patients in the control group were treated with high-frequency oscillatory ventilation, while those in the observation group were treated with high-frequency oscillatory ventilation combined with inhalational NO therapy. The therapeutic effects were compared. RESULTS: Over time, fraction of inspired oxygen (FiO2) of patients in both groups decreased, and the FiO2 levels of patients in the observation group at the different time points were lower than those of the control group; oxygen pressure (PaO2) and oxygen saturation (SpO2) showed an upward trend; the PaO2 and SpO2 levels in the observation group were higher than those of the control group at all time points. Oxygenation index (OI) increased, and the OI levels of the observation group at each time point were higher than those of the control group. Pulmonary artery pressure decreased at each time point, and the levels in the observation group were lower than those of the control group. The differences were statistically significant (p < 0.05). The duration of mechanical ventilation, duration of oxygen therapy, and mortality in the observation group were significantly lower than those of the control group, and the differences were statistically significant (p < 0.05). CONCLUSIONS: Using NO inhalation to treat neonatal pulmonary hypertension can significantly improve oxygen supply, reduce pulmonary artery pressure, shorten treatment time, and reduce mortality. It is, therefore, worthy of clinical application.

aEEG monitoring analysis of lesion degree and long-term prognosis in newborns with HIE.

OBJECTIVE: To conduct monitoring analysis of lesion degree and long-term prognosis using ambulatory electroencephalography (aEEG) in newborns with hypoxic-ischemic encephalopathy (HIE). PATIENTS AND METHODS: 48 cases of newborns with HIE (aged 37 to 41 weeks) as the observation group and another 50 cases of full-term infants with non-traumatic brain illness as the control group were chosen from March 2012 to March 2013. The aEEG were observed, and the continuity and sleep-wake cycle (SWC) between the two groups were compared. The relevance of aEEG monitoring results and HIE, as well as the long-term prognosis, were analyzed. RESULTS: 33.33% (16/48) of EEG results appeared to be continuous and 20.83% (10/48) of the SWC results were mature for observation group. These EEG and SWC results are conspicuously lower than the control group 100% (50/50) and differences were statistically significant (p<0.05). The maximum voltage of observation group was 56.54±19.33 LV, notably higher than the control group (37.77±2.79 LV). The minimum voltage of the observation group was 4.26±1.25 LV, markedly lower than the control group (7.75±0.67 LV) and these differences were statistically significant (p<0.05). Correlational analysis based on the Spearman approach showed that the monitoring results are positively correlated with clinical classification of HIE. After six months of follow-up, 11 of the 48 cases (22.92%) were found to be disabled (including mental retardation and cerebral palsy). CONCLUSIONS: aEEG enjoys easy operation, effective diagnosis, supports continuous monitoring and reflects the lesion degree as well as long-term prognosis of newborns with HIE and is, thus, highly recommended in clinical practices.

Association between PADI4 gene polymorphisms and anti-cyclic citrullinated peptide antibody positive rheumatoid arthritis in a large Chinese Han cohort.

OBJECTIVES: The present study was undertaken to investigate the association of peptidyl-arginine-deiminase type IV gene (PADI4) single nucleotide polymorphisms (SNPs) with rheumatoid arthritis (RA) susceptibility, and to determine whether there is any impact of PADI4 polymorphisms on RA subsets or phenotypes in a large Chinese Han cohort. METHODS: Two PADI4 SNPs (rs2240340 and rs1748033) were genotyped in 1216 Chinese Han RA patients and 1040 unaffected controls by TaqMan SNP Assays. Serum anti-CCP antibody and anti-PAD4 antibody levels were measured by ELISA. Bone destruction was scored by Sharp-van der Heijde scores (SHSs) of hands in 463 patients. RESULTS: The two SNPs rs2240340 and rs1748033 of PADI4 showed strong association with RA susceptibility (OR=1.23, 95% CI 1.09-1.38, p=6.66×10⁻4; and OR=1.24, 95% CI 1.10-1.41, p=6.98×10⁻4, respectively). RA risk genotypes of PADI4 were specifically associated with anti-CCP positive RA (rs2240340: p=5.13×10⁻6; rs1748033: p=2.97×10⁻³, respectively). Furthermore, there was a trend association between PADI4 rs2240340 and radiographic severity, though it did not reach the statistic significance (p=0.088). CONCLUSIONS: Our data provide strong evidence that PADI4 polymorphisms are risk factors contributed to RA susceptibility, especially for anti-CCP positive RA, and may confer higher risk of RA radiographic severity in Chinese Han population.

Peptides-staple method development and its application in cancer therapy.

α-Helixes are important structural motifs of protein three dimension structures and are largely involved in protein- protein interactions. This review covers the recent advances of the peptide stabilizing methodologies and introduces their applications in cancer research.

Functional analysis of DNA methylation in lung cancer.

OBJECTIVES: We aimed to explore the DNA methylation difference between lung cancer samples and non-cancer lung samples, and to investigate the role of DNA methylation in the mechanism of lung cancer development. Besides, we analyzed the transcriptional regulation network of DNA methylation and the miRNAs regulated by DNA methylation. This study provides a framework for DNA methylation in other tumors or diseases. MATERIALS AND METHODS: DNA methylation and gene expression profiles used were obtained from Gene Expression Omnibus. Firstly, we identified differentially methylated genes (DMGs) by Student's t-test. Then we detected the biological processes and pathways changed in lung cancer by Gene Ontology (GO) and KEGG pathway enrichment analysis. The transcriptional factors in differential genes were identified and the microRNAs regulated by them were also obtained in TransmiR. RESULTS: We obtained 108 DMGs between lung cancer samples and non-cancer samples. Besides development related biological processes and pathways were dramatically disordered. For the DMGs, we identified 11 transcriptional factors regulating them. Moreover, we screened out 21 relationships between DMGs and their transcriptional targets. Five microRNAs are reported to be regulated by DNA methylation genes. Finally a regulation network of DNA methylation was constructed. CONCLUSIONS: DNA methylation participates in carcinogenesis at the transcriptional and post-transcriptional level. Aberrant DNA methylation will prevent its binding with the upstream regulatory proteins, inhibit the function of downstream target genes and regulate the expression of downstream miRNA, and consequently affect cell development, immunoresponse and apoptosis.