Circular RNA circHIPK3 serves as a prognostic marker to promote chronic myeloid leukemia progression.

Increasing evidence demonstrate that circular RNAs (circRNAs) play critical role in regulation of gene expression, which participate in the pathogenesis of cancer, including chronic myeloid leukemia (CML). In this study, we aimed to investigate the expression profiling of circHIPK3 in CML. We found that circHIPK3 was significantly upregulated in peripheral blood mononuclear cells (PBMC) and serum samples from CML compared with healthy controls. High circHIPK3 expression predicted a poor outcome of CML patients. Further loss-function experiments suggested the oncogenic role of circHIPK3 in CML. Our findings provide insights on the role of circHIPK3 in the development and treatment of CML.

[Correlation analysis about cranial magnetic resonance imaging and electroencephalogram abnormalities and event-related potentials in patients with temporal lobe epilepsy].

Objective: To investigate and evaluate the correlation between event-related potentials, cranial magnetic resonance imaging and electroencephalogram on cognitive function in patients with temporal lobe epilepsy. Methods: According to the exclusion criteria, 60 adult temporal lobe epilepsy patients (24 males and 36 females, 34±13 years old of average age) were enrolled in the First Affiliated Hospital of Kunming Medical University from March 2017 to September 2018. The magnetic resonance imaging (MRI), 24 h video electroencephalogram (EEG) and event-related potentials (ERPs) were detected in all patients, comparing the latency of N1, P2, N2, P3 waves and the amplitude of P3 waves. Results: The mean latency of the waves of N1, P2, N2 and P3 and the mean amplitude of P3 wave were (108±25), (182±30), (256±33), (367±40) ms and (6.4±5.8) µV. There were significant differences in ERPs (latency of N1 wave, N2 wave and P3 wave) between the MRI abnormal group and the normal group (all P<0.05). There was a statistically significant difference in the ERPs (P3 wave latency) between EEG examination found epileptiform or paroxysmal slow waves release group and the patients with EEG normality in the past 1 year (P<0.05) and the EEG test results were positively correlated with the latency of P2, N2 and P3 waves in ERPs, and negatively correlated with the amplitude of P3 waves (P<0.05). Conclusion: Patients with cognitive dysfunction in temporal lobe epilepsy are more likely to have abnormal MRI and EEG in the head. Both of them show different effects on the cognitive process of patients in ERPs.

Effects of short-term step aerobics exercise on bone metabolism and functional fitness in postmenopausal women with low bone mass.

Measurement of bone turnover markers is an alternative way to determine the effects of exercise on bone health. A 10-week group-based step aerobics exercise significantly improved functional fitness in postmenopausal women with low bone mass, and showed a positive trend in reducing resorption activity via bone turnover markers. INTRODUCTION: The major goal of this study was to determine the effects of short-term group-based step aerobics (GBSA) exercise on the bone metabolism, bone mineral density (BMD), and functional fitness of postmenopausal women (PMW) with low bone mass. METHODS: Forty-eight PMW (aged 58.2 ± 3.5 years) with low bone mass (lumbar spine BMD T-score of -2.00 ± 0.67) were recruited and randomly assigned to an exercise group (EG) or to a control group (CG). Participants from the EG attended a progressive 10-week GBSA exercise at an intensity of 75-85 % of heart rate reserve, 90 min per session, and three sessions per week. Serum bone metabolic markers (C-terminal telopeptide of type 1 collagen [CTX] and osteocalcin), BMD, and functional fitness components were measured before and after the training program. Mixed-models repeated measures method was used to compare differences between the groups (α = 0.05). RESULTS: After the 10-week intervention period, there was no significant exercise program by time interaction for CTX; however, the percent change for CTX was significantly different between the groups (EG = -13.1 ± 24.4 % vs. CG = 11.0 ± 51.5 %, P < 0.05). While there was no significant change of osteocalcin in both groups. As expected, there was no significant change of BMD in both groups. In addition, the functional fitness components in the EG were significantly improved, as demonstrated by substantial enhancement in both lower- and upper-limb muscular strength and cardiovascular endurance (P < 0.05). CONCLUSION: The current short-term GBSA exercise benefited to bone metabolism and general health by significantly reduced bone resorption activity and improved functional fitness in PMW with low bone mass. This suggested GBSA could be adopted as a form of group-based exercise for senior community.

Association of interleukin-1ß -511C/T promoter polymorphism with COPD risk: a meta-analysis.

Studies examining the role of interleukin (IL)-1ß -511C/T promoter polymorphism in the pathogenesis of chronic obstructive pulmonary disease (COPD) have shown inconsistent results. This meta-analysis was performed to assess the association between the IL-1ß-511C/T promoter polymorphism and COPD susceptibility. Published case-control, cross-sectional, and cohort studies from Pubmed, Embase, and China National Knowledge Infrastructure databases were retrieved. Data were extracted and pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated. Twelve studies with 1692 cases and 2009 controls were included in this meta-analysis. Pooled effect size showed an overall but not significantly decreased risk of IL-1ß-511 C/T with COPD susceptibility (OR = 0.89, 95%CI = 0.78-1.01) in a complete overdominant genetic model (TT+CC vs CT), indicating that homozygous individuals (CC and TT) have a decreased risk for COPD compared with heterozygotes (CT). In subgroup analysis by ethnicity, IL-1ß-511C/T was significantly correlated with a decreased risk of COPD in Asians (OR = 0.73, 95%CI = 0.60-0.88, P = 0.001), but not in Caucasians (OR = 1.02, 95%CI = 0.83- 1.24, P = 0.46), confirming a protective role of IL-1ß-511C/T in COPD in Asians. Moreover, after excluding studies that included populations not in Hardy-Weinberg equilibrium, the pooled results were robust and no publication bias was observed. This meta-analysis suggests that the IL-1ß-511C/T promoter polymorphism deceases the risk of COPD in Asians.

High expression of CD98 alters epithelial barrier functions to promote induction of airway allergy.

BACKGROUND: Epithelial barrier dysfunction is critical in the induction of allergy; the aetiology is to be further understood. A recent report indicates that CD98 plays a role in the intestinal epithelial barrier dysfunction. OBJECTIVES: This study aimed to investigate the role of overexpression of CD98 in the induction of nasal allergy. METHODS: The nasal epithelium samples were collected from 30 patients with allergic rhinitis and 30 healthy subjects. The contents of CD98 and Staphylococcal enterotoxin B (SEB) in the nasal epithelium samples were evaluated by using Western blotting. The effect of SEB of inducing the expression of CD98 was evaluated with an airway epithelial cell line, the 16HBE14o cells. The epithelial barrier function was assessed with the indicators of transepithelial resistance (TER) and permeability to horseradish peroxidase (HRP). A mouse model was employed to evaluate the role of CD98 in the induction of nasal allergy. RESULTS: High levels of CD98 and SEB were detected in the nasal epithelium of patients with allergic rhinitis. A positive correlation was identified between CD98 and SEB in nasal epithelium samples. Exposure to SEB could induce the overexpression of CD98 in RPMI 2650 and 16HBE14o cells. The overexpression of CD98 down-regulated TER and increased the permeability to HRP in 16HBE14o monolayers. Concurrent exposure to SEB and OVA induced nasal allergies in a mouse model that could be blocked by pre-treatment with anti-CD98 antibody. CONCLUSIONS AND CLINICAL RELEVANCE: CD98 plays a critical role in compromising the airway epithelial barrier function that contributes to the induction of airway allergy.

Staphylococcal enterotoxin B compromises the immune tolerant status in the airway mucosa.

BACKGROUND: The breakdown of immune tolerance plays a critical role in allergic disorders; the mechanism of breaching immune tolerance remains largely unknown. OBJECTIVE: The present study aimed to investigate the role of Staphylococcal enterotoxin B (SEB) in the interference of the immune tolerance in the nasal mucosa. METHODS: The immune tolerant components, tolerogenic dendritic cells (TolDC) and regulatory T cells (Treg), were assessed in the surgically removed nasal mucosa from patients with allergic rhinitis (AR) or non-AR chronic rhinitis. The contents of SEB and integrin alphavbeta6 (avb6) in the nasal epithelium were assessed using enzyme-linked immunoassay. The ability of avb6 on TolDC induction and the effect of SEB on suppression of avb6 in nasal epithelial cells were observed in cell culture. RESULTS: Compared with that in the non-AR nasal mucosa, the frequencies of TolDCs/Tregs were lower, the contents of SEB were higher and the contents of avb6 were lower in the AR nasal mucosa. Avb6 had the ability to induce the development of TolDCs in vitro; the latter had the ability to induce Treg development. The expression of avb6 was detected in nasal epithelial cells in culture that could be suppressed by SEB. CONCLUSIONS AND CLINICAL RELEVANCE: The components of immune tolerance machinery, TolDCs and Tregs were suppressed in the AR nasal mucosa. The increases in SEB and decreases in avb6 in nasal epithelium are associated with the compromises of immune tolerance in the nasal mucosa. SEB has the ability to suppress the expression of avb6 in nasal epithelial cells.

Effects of prolonged intensive training on the resting levels of salivary immunoglobulin A and cortisol in adolescent volleyball players.

AIM: Concerns have been raised regarding the effects of prolonged intensive training on adolescent athletes. This study investigated the differences in mucosal immune functions and stress responses between intensively trained male adolescent volleyball players and age-matched sedentary controls. METHODS: Twelve male volleyball players (16.5 [0.7] years of age) and sixteen healthy sedentary male volunteers (17.1 [0.6] years of age) participated in this study. Volleyball players were engaged in regular and year-round training. Unstimulated saliva samples were collected from volleyball players during the high-intensity training period and from the counterparts at the same timepoints after at least 18 hours of rest. Concentrations of salivary total protein, secretory immunoglobulin A (SIgA), cortisol, and lactoferrin were measured. RESULTS: Results of this study revealed that the SIgA concentrations and the ratio of SIgA/total protein in volleyball players were significantly lower compared with those in sedentary controls. However, the salivary cortisol concentrations and the ratio of cortisol/total protein in volleyball players were markedly higher compared with those in sedentary controls. No significant difference was observed in lactoferrin levels between volleyball players and sedentary controls. CONCLUSION: The findings of this study suggest that the prolonged intensive training may elicit a sustained stress and induce a suppressive effect on mucosal immunity in regularly and intensively trained adolescent athletes.

Specific immunotherapy suppresses Th2 responses via modulating TIM1/TIM4 interaction on dendritic cells.

BACKGROUND: Specific immunotherapy (SIT) is the only curable remedy for allergic disorders currently; however, the underlying mechanism is not fully understood yet. This study aimed to elucidate the mechanism of SIT on suppressing TIM4 (T cell immunoglobulin mucin domain molecule 4) expression in dendritic cells (DCs) and modulating the skewed T helper 2 (Th2) responses in patients with airway allergy. METHODS: Twenty patients with allergic rhinitis (AR) were treated with SIT for 3 months. Before and after SIT, the expression of TIM4 in peripheral DC and TIM1 in Th2 cells was examined. The role of Fc gamma receptor (FcgammaR) I and II in modulating the expression of TIM4 in DCs was investigated. RESULTS: The interaction of TIM1/TIM4 played a critical role in sustaining the polarization status of Th2 cells in AR patients. Cross-linking FcgammaRI by antigen/IgG complexes increased the production of TIM4 by dendritic cells via upregulating tumor necrosis factor-alpha in DCs. Exposure to microbial products promoted the expression of FcgammaRI in DCs that further increased the expression of TIM4. Exposure to specific antigens alone upregulated the expression of FcgammaRII in DCs, that suppressed the expression of TIM4. CONCLUSIONS: We conclude that SIT suppresses the skewed Th2 responses via disrupting the interaction of TIM1/TIM4 in antigen-specific Th2 cells.

Expression and release of IL-29 by mast cells and modulation of mast cell behavior by IL-29.

BACKGROUND: The role of interleukin (IL)-29 in innate immunity has been recognized recently, and it is regarded as a potent bioactive molecule. However, little is known about its role in the pathogenesis of allergy. Because mast cells are recognized as primary effector cells of allergy, we investigated the potential relationship between IL-29 and mast cells in this study. OBJECTIVE: To examine the expression of IL-29 in mast cells and the influence of IL-29 on mast cell mediator release and accumulation. METHODS: Expression of IL-29 in mast cells was determined by double-labeling immunohistochemistry and flow cytometry analysis. Mast cell cell-line was cultured to examine the mediator release, and mouse peritoneal model was employed to observe the mast cell accumulation. RESULTS: Large proportions of mast cells expressing IL-29 were localized in human tissue including the colon, tonsil and lung. Mast cells can release substantial quantity of IL-29 upon challenge with proteolytic allergens. Extrinsic IL-29 provoked IL-4 and IL-13 release from mast cell line P815 cells through PI3K/Akt and (JAK)/STAT3 signaling pathways, but failed to induce mast cell histamine release from human mast cells. Extrinsic IL-29 also induced mast cell infiltration in mouse peritoneum by a CD18- and ICAM1-dependent mechanism. CONCLUSION: Mast cell-derived IL-29 has the potential to be involved in the pathogenesis of allergic inflammation.

[Expression and significance of c-fos in resistant cell line TU177/VCR of larynx squamous cell carcinoma].

Objective: To explore the effect of c-fos on multidrug resistance of laryngeal cancer TU177 cells. Method: Increasing drug concentration gradient is adopted to establish the stability of the laryngeal cancer drug resistance in cell line; RT-PCR and Western blot were used to detect difference of the c-fos between TU177 and TU177/VCR cells; plasmids with human c-fos knockdown or over expression were transfected into TU177/VCR and TU177 cells respectively, and the effects of different treatment on cell proliferation were investigated with MTT. Results: The drug resistance of TU177/VCR cells was 26.25-fold in vincristine (VCR), 7.33-fold in Paclitaxel (TAX), 2.41 in cisplatin (DDP), and 5.50 in 5-fluorouracil (5-FU), comparing with TU177( P<0.05). The TU177/VCR cells had significantly higher c-fos expression compared to TU177 cells( P<0.05). The results showed that the IC(50) values of 5-FU for the NC group and c-fos shRNA group were (306.2±6.3)µmol/L and (81.3±3.9)µmol/L, respectively, which was decreased by 73% in the c-fos shRNA group compared to that in the NC group (P<0.05). Similarly, the results showed that the IC(50) values for 5-FU were (55.3±9.4) µmol/L in NC group and (288.1±7.3)µmol/L in c-fos WT group, which was increased 5.21-fold in c-fos WT cells. Conclusion: C-fos plays important role in multidrug resistance of larynx cancer cell TU177/VCR, and might become a new molecular target for laryngeal cancer treatment.

[The contrast analysis of endoscopic thyroidectomy by complete areola approach and conventional open thyroidectomy].

Objective:To compare the clinical efficacy between the endoscopic thyroidectomy by complete areola approach and the conventional open thyroidectomy.Method:One hundred and twenty-one cases of endoscopic thyroidectomy by complete areola approach or conventional open thyroidectomy patients were reviewed retrospectively, whose operation time, median blood lose, volume of postoperative drainage, incision scar formation rate and patient satisfaction were observed and compared.Result:There were obvious advantages in the median blood lose, volume of postoperative drainage, incision scar formation rate and patient satisfaction in the group of endoscopic thyroidectomy by complete areola approach comparing conventional open thyroidectomy. The difference was statistically significant（P <0.05）.Conclusion:The method of endoscopic thyroidectomy by complete areola approach is obviously better , which has many advantages, such as Less bleeding, less volume of wound drainage and small skin incision scar. The patients were satisfied with the treatment.It is worthy of clinical application.

Biosynthesis of the vancomycin group of antibiotics: characterisation of a type III polyketide synthase in the pathway to (S)-3,5-dihydroxyphenylglycine.

3,5-dihydroxyphenylacetate, a precursor for the non-proteinogenic amino acid 3,5-dihydroxyphenylglycine occurring in glycopeptide antibiotics, is determined to be catalysed by a type III polyketide synthase using malonyl-CoA as a starter unit.

Characterisation of a hydroxymandelate oxidase involved in the biosynthesis of two unusual amino acids occurring in the vancomycin group of antibiotics.

ORF22 from the chloroeremomycin gene cluster has been cloned, expressed and characterised as a hydroxymandelate oxidase (HmO) that is involved in the formation of both (S)-4-hydroxyphenylglycine and (S)-3,5-dihydroxyphenylglycine.

The incidence of insulin-dependent diabetes mellitus in urban districts of Shanghai (1989-1993).

A retrospective study on the incidence of insulin-dependent diabetes mellitus (IDDM) among children aged 0-14 years was carried out from 1989-1993 in urban Shanghai, China. The average annual population at risk (0-14 yr) consisted of 1,401,664 children. All the cases were collected from the hospitals (primary source) and from primary and middle schools and kindergartens (second source) with independent validation of case ascertainment. There were 53 IDDM cases from the primary source, 23 from the secondary source, with a total of 58. The ascertainment corrected total number of IDDM cases was 67 by the capture-recapture method. The average crude annual incidence rate was 0.83 [95% confidence interval (CI) 0.61-1.04] and ascertainment corrected incidence rate 0.96 (95% CI 0.80-1.12) per 100,000. Peak incidence fell in 1992 and in the 9 year-old group. The incidence of childhood IDDM in the urban districts of Shanghai was reconfirmed to be the lowest in the world but by comparing the results of former investigations a trend was found of increasing incidence of IDDM.

Effects of processing steps on the contents of minor compounds and oxidation of soybean oil.

The effects of minor compounds on the oxidative stability of soybean oil were studied by measuring the contents of peroxides, headspace oxygen and volatile compounds. The effects of processing on minor component contents were also studied. Fatty acids, mono- and diacylglycerols, thermal or oxidized triacylglycerols, oxidized tocopherols and peroxides acted as prooxidant in soybean oil during storage at 55 degrees C. The phospholipids acted as prooxidant or antioxidant depending on the presence or absence of metals in the oil. The tocopherols acted as prooxidant or antioxidant depending on their concentration in the oil. The chlorophyll acted as a sensitizer to generate singlet oxygen in the photooxidation of soybean oils.

A nine-year prospective study on the incidence of childhood type 1 diabetes mellitus in China.

To investigate the epidemiological characteristics of childhood type 1 diabetes mellitus in China, newly diagnosed cases of type 1 diabetes with an onset age under 15 years were retrospectively registered by 23 local centers in China following a standardized protocol on the basis of the nationwide registry established by the WHO DiaMond Project China Participating Center, Chinese Academy of Preventive Medicine (CAPM). A population of about 24 million children were covered in the defined areas. A two-sample capture-recapture method was used to estimate case ascertainment. Between 1988 and 1996, 903 diabetic cases were registered in 9 ethnic groups. The overall ascertainment corrected incidence rate (IR) was 0.59 per 100,000 person-year. The IR was 0.52/100,000 (95% CI: 0.50-0.54) for males and 0.66/100,000 (95% CI: 0.64-0.68) for females. The standardized ascertainment corrected IR by the national age-specific population in 1990 was 0.57 per 100,000 person-year. The incidence among various ethnic groups ranged from 0.25/100,000 to 3. 06/100,000. The IRs increased with northern latitude, and the IR of Han population was significantly higher in North China compared with South China (0.67 versus 0.53 per 100,000 respectively, P < 0.01). A correlation model of incidence and calendar time showed that the IR increased significantly between 1988 and 1996 (r = 0.86, P = 0.0027). The relative risk (RR) of type 1 diabetes mellitus for different age-groups estimated by a Poisson regression model showed that taking RR as 1.00 for age-group from 0 to 4 years, the RR for age-group from 5 to 9 year and from 10 to 14 year was 2.30 and 3.60 respectively. The standardized ascertainment corrected IR of childhood type 1 diabetes mellitus in China in much lower than in other countries. The geographic and ethnic variability of the incidence suggests that both genetic and environmental factors play a role in the development of childhood diabetes in China.

Si-jun-zi-tang regulate granulocyte macrophage colony-stimulating factor secretion by human peripheral blood mononuclear cells.

Si-Jun-Zi-Tang is one of the widely used Chinese herbal medicines. In this study, human peripheral blood monocytes were treated in vitro with 50% hot ethanol extract of Si-Jun-Zi-Tang and its four major ingredients (Dangshen, Baizhu, Gancao and Fuling). The concentration of granulocyte-macrophage colony-stimulating factor (GM-CSF) in the culture supernatant at 3 hours and 18 hours were measured using an ELISA. Dangshen and Gancao significantly suppressed GM-CSF secretion in a dose-dependent manner. Baizhu showed no statistically significant effect on GM-CSF secretion 18 hours after in vitro drug-treatment. Fuling, by contrast, significantly augmented GM-CSF secretion in a dose-dependent manner after 18 hours of drug treatment. Si-Jun-Zi-Tang showed a suppressive effect on GM-CSF secretion at 3 hours but significantly augmented GM-CSF secretion when the cells were treated with 8 mg/ml of the drug for 18 hours. The data suggested that Si-Jun-Zi-Tang might modulate hematopoiesis and immune response via regulating GM-CSF secretion, and the presence of Fuling in Si-Jun-Zi-Tang could counteract the suppressive effect of Dangshen and Gancao on GM-CSF secretion.

Na+/Ca2+ exchange current in myocytes isolated from rat hypertrophied heart.

Effects of myocardial hypertrophy on the Na+/Ca2+ exchange current in isolated rat cardiac myocytes were investigated, using whole cell patch techniques. Goldblatt 2-kidney, one-clip technique was used to induce cardiomyocyte hypertrophy. The results demonstrated that the Ni(2+)-sensitive Na+/Ca2+ exchange current density was larger in hypertrophied cells than that in normal cells. At a holding potential of mV, the outward current densities were 1.53 +/- 0.31 pA/pF in normal cells and 2.62 +/- 0.53 pA/pF in hypertrophied cells (P < 0.01). At a holding potential of -100 mV, the inward current densities were 0.42 +/- 0.14 pA/pF in normal cells and 1.12 +/- 0.33 pA/pF in hypertrophied cells (P < 0.001). The results suggest that during myocardial hypertrophy the Na+/Ca2+ exchange current is significantly increased.

[Study of pharmacokinetics of liver targeting antimalarial agent neoglycoalbumin-primaquine conjugate (NGA-PQ) and primaquine phosphate in mouse].

A normal phase high-performance liquid chromatography process was used to separate and detect primaquine in blood and liver after a single intravenous dose of the hepatic targeting agent neoglycoalbumine-primaquine conjugate (NGA-PQ) and primaquine phosphate (PQP) in mice. 6-Methoxy-8-(4-amino-butyrylamino) quinoline synthesized and identified by us was used as an internal standard to be added to biologic samples obtained from mice at different times after given NGA-PQ or PQP. The mixture was extracted with ether after alkalinization in the PQP group. In the NGA-PQ group, the biological samples must be hydrolized by heating under nitrogen and acid condition in a domestic pressure cooker before extraction. The extracts were evaporated to dryness under nitrogen, then dissolved in the mobile phase (chloroform-methanol-amonium hydroxide = 86.8: 12.5: 0.7). The results showed that the hepatic PQ collecting ratio and the retention time of PQ in liver in the NGA-PQ group were higher and longer than those in the PQP group. The results also point out that NGA-PQ has liver targeting property.

[Study on the enzyme dependant colon targeting prodrug--dexamethasone succinate dextran and its tablets].

AIM: To develop an orally administered colon targeting drug delivery system dexamethasone succinate dextran (DSD) tablets. METHODS: Dexamethasone succinate dextran was synthesized in an anhydrous environment. Using 4-dimethyl aminopyridine and 1,1'-carbonyldiimidazole as the catalyzer. The chemical structure was identified by UV, IR, NMR and MS. The contents of dexamethasone in various samples were determined by HPLC. RESULTS: Dexamethasone was distributed mainly in plasma and gastric contents after the oral administration of common tablets. In contrast, after oral administration of DSD tablets, the recovery of dexamethasone in plasma and gastric contents decreased significantly, while the percentage of dexamethasone in cecum and colon increased obviously. CONCLUSION: The experimental results showed the good colon targeting property of DSD prodrug compared with free dexamethasone.