Vasohibin-2 promotes proliferation and metastasis of cervical cancer cells by regulating epithelial-mesenchymal transition / 南方医科大学学报

OBJECTIVE@#To explore the role of vasohibin-2 (VASH2) in regulation of proliferation and metastasis of cervical cancer cells.@*METHODS@#We analyzed the differentially expressed genes between cervical cancer cells with flotillin-1 overexpression and knockdown by RNA-seq combined with analysis of public databases. The expression levels of VASH2 were examined in normal cervical epithelial cells (HcerEpic), cervical cancer cell lines (HeLa, C-33A, Ca ski, SiHa and MS751) and fresh cervical cancer tissues with different lymph node metastasis status. We further tested the effects of lentivirus-mediated overexpression and interference of VASH2 on proliferation, migration, invasion and lymphatic vessel formation of the cervical cancer cells and detected the expression levels of key epithelial-mesenchymal transition (EMT) markers and TGF-β mRNA.@*RESULTS@#RNA-seq and analysis of public databases showed that VASH2 expression was significantly upregulated in cervical cancer cells exogenously overexpressing flotillin-1 (P < 0.05) and downregulated in cells with flotillin-1 knockdown (P < 0.05), and was significantly higher in cervical cancer tissues with lymph node metastasis than in those without lymph node metastasis (P < 0.01). In cervical cancer cell lines Ca Ski, SiHa, and MS751 and cervical cancer tissue specimens with lymph node metastasis, VASH2 expression was also significantly upregulated as compared with HcerEpic cells and cervical cancer tissues without lymph node metastasis (P < 0.05). Exogenous overexpression of VASH2 significantly promoted proliferation, migration, invasion and lymphatic vessel formation of cervical cancer cells, whereas these abilities were significantly inhibited in cells with VASH2 knockdown (P < 0.05). The cervical cancer cells overexpressing VASH2 showed significant down- regulation of e-cadherin and up- regulation of N-cadherin, Vimentin and VEGF-C, while the reverse changes were detected in cells with VASH2 knockdown (P < 0.05). TGF-β mRNA expression was significantly up-regulated in cervical cancer cells overexpressing VASH2 and down-regulated in cells with VASH2 knockdown (P < 0.001).@*CONCLUSION@#Flotillin-1 may participate in TGF-β signaling pathway-mediated EMT through its down-stream target gene VASH2 to promote the proliferation, migration, invasion and lymphatic vessel formation of cervical cancer cells in vitro.

Physical exercise and associated factors of rural primary and secondary school students in the north of Jiangsu Province / 中国学校卫生

Objective@#To understand the current situation and influencing factors of physical exercise participation of rural primary and secondary school students in Jiangsu Province, and to provide reference for promoting healthy development of rural youth in Northern Jiangsu.@*Methods@#A total of 3 597 rural primary and middle school students in Northern Jiangsu Province were selected to conduct a questionnaire survey on the status quo of physical exercise.@*Results@#Only 37.6% of students in Northern Jiangsu had more than 3 hours of physical education every week, 23.6% of the students participated in extracurricular physical exercise for more than 3 times a week, 14.3% of the students participated in physical exercise for more than 1 hour every day, 77.9% of the students master more than 1 sports skills, 72.0% of students participated in extracurricular activities perceived, and 27.3% of the students participated in extracurricular sports professional counseling; 35.7% of the students reported lack of parental support physical education curriculum lacks of interest, 17.0% of the students didn t like the physical education teachers or their teaching methods, 28.6% of the students reported lack of sports venues or equipment, 8.4% of the students reported that their parents do not support, 38.2% of the students reported lack of extracurricular sports professional guidance, 18.1% of the students think that the performance of physical education didn t affect the evaluation and progress of the school. Univariate Logistic regression analysis showed that gender, academic stage, dislike of physical education teaching methods and lack of physical education professional guidance were the influencing factors of physical exercise participation havior of rural students(P<0.05).@*Conclusion@#The present situation of physical exercise of rural primary and secondary school students in Northern Jiangsu Province is not optimistic. Special attention to the formation of female exercise behavior, improve the teaching quality of rural physical education and support the off campus sports training institutions.

Analysis on the current situation and influencing factors of college students’ participation in physical exercise in Jiangsu / 中国学校卫生

Objective@#To understand the current situation and influencing factors of college students’ participation in physical exercise in Jiangsu Province, and to provide reference for promoting the healthy development of college students’ physique.@*Methods@#A questionnaire survey was conducted among 2 643 college students in 12 universities in Jiangsu Province.@*Results@#Only 2.3%(60/2 643) of college students attended physical education classes more than 3 hours a week, 29.9%(790/2 643) of them participated in physical exercise more than 3 times a week, 14.8%(391/2 643) of them participated in physical exercise more than 1 hour a day, and 23.0%(609/2 643) of them mastered more than 3 sports skills. Among the items, 45.7%(1 208/2 643) of the college students did not participate in sports associations, 17.8%(471/2 643) of the college students participated in sports social organizations such as off-campus sports clubs; 40.1%(1 059/2 643) of the students thought that the content of physical education curriculum lacked interest. About 31.9%(845/2 643) of the students did not like the physical education teachers or their teaching methods; 19.4%(514/2 643) of the students thought that they lacked sports venues or equipment; 21.1%(558/2 643) of the students thought that physical exercise had no effect on learning, and 28.9%(764/2 643) of the students thought that physical exercise had no effect on learning. The students thought that physical education curriculum and related activities had no effect on employment. About 17.1%(451/2 643) of the students thought that the performance of physical education did not affect the evaluation and progress; The present situation of college students’participation in physical exercise and the reasons for their dislike of physical exercise are different in gender, grade and region(P<0.05); single factor Logistic regression analysis showed that gender, grade, place and so on. The lack of interesting contents, dislike of PE teachers’ teaching methods, lack of sports venues or equipment were the influencing factors of college students’ participation in physical exercise in Jiangsu Province(P<0.05).@*Conclusion@#The current situation of college students’ participation in physical exercise in Jiangsu Province is not optimistic. To promote college students’participation in physical exercise needs the co-operation of society, schools and individuals.

Analysis of status of physical exercises among primary and middle school students in Nanjing City / 中国学校卫生

Objective@#To understand the current situation of physical exercise participation of primary and secondary school students in Nanjing, and to provide the reference for promoting the healthy development of physical fitness of primary and secondary school students.@*Methods@#By using stratified cluster sampling method, 4 161 students from 14 primary and secondary schools in Nanjing, Jiangsu Province were selected to conduct a questionnaire survey on their participation in physical exercise.@*Results@#Among the primary and secondary school students in Nanjing, 55.57% had more than three hours of physical education class per week, 81.09% of them participated in large class activities organized by the school every day, 23.19% of them participated in extracurricular sports activities more than three times a week, 13.96% of them participated in physical exercise for one hour every day,there were significant in physical exercise items among students of different stages(χ2=52.76, 29.90, 16.14, 39.34; 624.61, 53.04, 151.25, 189.45, P<0.05). 34.34% of the parents supported and accompanied their classmates in family physical exercise, 46.07% of parents supported students’ physical exercise but do not accompanied them, 14.83% of parents’ attitude was not clear, 4.76% of parents did not support students’ physical exercise, 14.32% of families made physical exercise plans; There were significant differences in family physical exercise items among students of different genders and stages(χ2=42.72; 229.44, 26.43, P<0.01). 49.82% of students had more than three sports skills in personal physical exercise, 17.45% of students participated in physical training classes, only 7.14% of students participated in physical exercise weekly. There were genders and stages differences in the current situation of students’ participation in physical exercise(χ2=12.32, 5.60, 24.06; 167.51, 237.90, 223.15, P<0.05).@*Conclusion@#In Nanjing, the reporting rate of regular participation in physical exercise among primary and secondary school students is low, and family-school interaction is needed to promote the healthy development of students.

Obesity-Associated Metabolic Signatures Correlate to Clinical and Inflammatory Profiles of Asthma: A Pilot Study

PURPOSE: Obesity is associated with metabolic dysregulation, but the underlying metabolic signatures involving clinical and inflammatory profiles of obese asthma are largely unexplored. We aimed at identifying the metabolic signatures of obese asthma. METHODS: Eligible subjects with obese (n = 11) and lean (n = 22) asthma underwent body composition and clinical assessment, sputum induction, and blood sampling. Sputum supernatant was assessed for interleukin (IL)-1β, -4, -5, -6, -13, and tumor necrosis factor (TNF)-α, and serum was detected for leptin, adiponectin and C-reactive protein. Untargeted gas chromatography time-of-flight mass spectrometry (GC-TOF-MS)-based metabolic profiles in sputum, serum and peripheral blood monocular cells (PBMCs) were analyzed by orthogonal projections to latent structures-discriminate analysis (OPLS-DA) and pathway topology enrichment analysis. The differential metabolites were further validated by correlation analysis with body composition, and clinical and inflammatory profiles. RESULTS: Body composition, asthma control, and the levels of IL-1β, -4, -13, leptin and adiponectin in obese asthmatics were significantly different from those in lean asthmatics. OPLS-DA analysis revealed 28 differential metabolites that distinguished obese from lean asthmatic subjects. The validation analysis identified 18 potential metabolic signatures (11 in sputum, 4 in serum and 2 in PBMCs) of obese asthmatics. Pathway topology enrichment analysis revealed that cyanoamino acid metabolism, caffeine metabolism, alanine, aspartate and glutamate metabolism, phenylalanine, tyrosine and tryptophan biosynthesis, pentose phosphate pathway in sputum, and glyoxylate and dicarboxylate metabolism, glycerolipid metabolism and pentose phosphate pathway in serum are suggested to be significant pathways related to obese asthma. CONCLUSIONS: GC-TOF-MS-based metabolomics indicates obese asthma is characterized by a metabolic profile different from lean asthma. The potential metabolic signatures indicated novel immune-metabolic mechanisms in obese asthma with providing more phenotypic and therapeutic implications, which needs further replication and validation.

Is Folate Status a Risk Factor for Asthma or Other Allergic Diseases?

PURPOSE: It is controversial whether folate status is a risk factor for the development of asthma or other allergic diseases. This study was conducted to investigate whether indirect or direct exposure to folate and impaired folate metabolism, reflected as methylene-tetrahydrofolate reductase (MTHFR) C677T polymorphism, would contribute to the development of asthma and other allergic diseases. METHODS: Electronic databases were searched to identify all studies assessing the association between folate status and asthma or other allergic diseases. Two reviewers independently assessed the eligibility of studies and extracted data. The relative risk (RR) or odds ratio (OR) with 95% confidence intervals (CI) was calculated and pooled. RESULTS: Twenty-six studies (16 cohort, 7 case-control, and 3 cross-sectional studies) were identified. Maternal folic acid supplementation was not associated with the development of asthma, atopic dermatitis (AD), eczema, and sensitization in the offspring, whereas exposure during early pregnancy was related to wheeze occurrence in the offspring (RR=1.06, 95% CI=[1.02-1.09]). The TT genotype of MTHFR C677T polymorphism was at high risk of asthma (OR=1.41, 95% CI=[1.07-1.86]). CONCLUSIONS: It is indicated that maternal folic acid supplementation during early pregnancy may increase the risk of wheeze in early childhood and that the TT genotype of MTHFR C677T polymorphism impairing folic acid metabolism would be at high risk of asthma development. These results might provide additional information for recommendations regarding forced folate consumption or folic acid supplements during pregnancy based on its well-established benefits for the prevention of congenital malformations. However, currently available evidence is of low quality which is needed to further elucidate.

Current asthma control predicts future risk of asthma exacerbation: a 12-month prospective cohort study / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>The performance of asthma control test (ACT) at baseline for predicting future risk of asthma exacerbation has not been previously demonstrated. This study was designed to explore the ability of the baseline ACT score to predict future risk of asthma exacerbation during a 12-month follow-up.</p><p><b>METHODS</b>This post hoc analysis included data from a 12-month prospective cohort study in patients with asthma (n = 290). The time to the first asthma exacerbation was analyzed and the association between baseline ACT scores and future risk of asthma exacerbation was calculated as adjusted odds ratio (OR) using Logistic regression models. Further, sensitivity and specificity were estimated at each cut-point of ACT scores for predicting asthma exacerbations.</p><p><b>RESULTS</b>The subjects were divided into three groups, which were uncontrolled (U, n = 128), partly-controlled (PC, n = 111), and well controlled (C, n = 51) asthma. After adjustment, the decreased ACT scores at baseline in the U and PC groups were associated with an increased probability of asthma exacerbations (OR 3.65 and OR 5.75, respectively), unplanned visits (OR 8.03 and OR 8.21, respectively) and emergency visits (OR 20.00 and OR 22.60, respectively) over a 12-month follow-up period. The time to the first asthma exacerbation was shorter in the groups with U and PC asthma (all P < 0.05). The baseline ACT of 20 identified as the cut-point for screening the patients at high risk of asthma exacerbations had an increased sensitivity of over 90.0% but a lower specificity of about 30.0%.</p><p><b>CONCLUSION</b>Our findings indicate that the baseline ACT score with a high sensitivity could rule out patients at low risk of asthma exacerbations and predict future risk of asthma exacerbations in clinical practice.</p>

Analysis on anti-vascular inflammatory mechanism in vitro of total flavones from Artemisia anomala / 中国中药杂志

<p><b>OBJECTIVE</b>To study the impact of total flavones from Artemisia anomala (TFAS) on activation of macrophages, cell oxidative stress, auto-nitration of CuZn-SOD, platelet aggregation and isolated vascular tension.</p><p><b>METHOD</b>LPS and IFN-gamma induced activation of macrophages and oxidative stress in rats; H2O2 and nitrite induced auto-nitration of CuZn-SOD; ADP, AA and collagen induced platelet aggregation in vitro in mice; PE stimulates isolated vascular tension; nitrite content of macrophages was measured by Griess assay; MTT assay and FRAP assay was applied for cell viability and total cell antioxidant capacity; auto-nitration of CuZn-SOD was measured by Western blot and colorimetric methods; platelet aggregation was detected by turbidimetry; and aorta ring relaxation was recorded by isolated vascular function experience devices for rats.</p><p><b>RESULT</b>TFAS demonstrated dose dependence (25, 50, 100, 200 mg x L(-1)) on inhibiting induced macrophages NO production from generating, while increasing cell viability and total anti-oxidant capacity. Auto-nitration of CuZn-SOD was suppressed by TFAS in dose dependence (0.5, 5, 50 mg x L(-1)). TFAS showed an inhibitory effect on collagen-induced platelet aggregation at 50 mg x L(-1) and an endothelium-dependent relaxation effect on PE-induced vasoconstriction at 1 g x L(-1).</p><p><b>CONCLUSION</b>TFAS shows effect on anti-inflammation, anti-oxidation, anti-nitration, anti-platelet aggregation and vasodilatation in experiment in vitro, which may inhibit vascular inflammatory by regulating multiple target points. It is among material bases for promoting blood circulation and removing blood stasis.</p>

Expression of glucocorticoid receptor alpha and beta in chronic rhinosinusitis with nasal polyp / 中华耳鼻咽喉头颈外科杂志

<p><b>OBJECTIVE</b>To detect the expression of glucocorticoid receptor (GR) alpha and beta in nasal polyps, and analyze the possible relationship between over-expression of GR beta and steroid insensitivity.</p><p><b>METHODS</b>The expression of GR alpha and GR beta was examined by immunohistochemical SP method in the specimens from 17 patients with recurring nasal polyp, 18 patients with chronic rhinosinusitis and nasal polyp (CRSwNP), and 12 patients with chronic rhinosinusitis without nasal polyp (CRSsNP) that did not recur during follow-up for 1.5 - 2 years.</p><p><b>RESULTS</b>The difference of numbers of GR alpha-positive cells (x +/- s) between groups with recurrent nasal polyp (20.2 +/- 6.9), CRSwNP (20.7 +/-7.2) , CRSsNP (16.9 +/- 7.2) and normal subjects (16.1 +/- 5.3) was not significant (P > 0.05). The numbers of GR beta-positive cells in recurring group (34.2 +/- 7.4) or CRSwNP (31.5 +/- 5.9) were higher than that in CRSsNP (19.8 +/- 7.8) and normal group (10.1 +/- 6.7) respectively (all P < 0.05). There was a trend toward higher level in recurring polyp compared with that of CRSwNP patients without recurrence in follow-up period, although this was not statistically different (P = 0.558). The difference of GR beta/GR alpha ratios (x +/- s) in recurring specimens (1.80 +/- 0.47) and CRSwNP group (1.65 +/- 0.49) was significant compared with normal group (0.77 +/- 0.66) respectively (P < 0.05), while there was no significance compared with CRSsNP (1.23 +/- 0.27, P > 0.05).</p><p><b>CONCLUSIONS</b>The high expression of GR beta in nasal polyp is related to the development of nasal polyp.</p>

Relationship between Staphylococcal superantigens and the dominant expression of T-cell receptor V beta gene in chronic rhinosinusitis with nasal polyp / 中华耳鼻咽喉头颈外科杂志

<p><b>OBJECTIVE</b>To analyse the relationship between superantigens produced by Staphylococcus aureus and the mRNA expression of T-cell receptor V beta region (TCR Vbeta), and to investigate the possible role of Staphylococcal superantigens in the pathogenesis of nasal polyps.</p><p><b>METHODS</b>Sinonasal mucus and polyp/mucosa tissue were obtained from patients with chronic rhinosinusitis (22 patients with bilateral nasal polyps, 15 without nasal polyps) and 12 normal subjects as comparative negative controls. Mucus specimens were assayed by enzyme-linked immunosorbent assay (ELISA) for Staphylococcal exotoxins,and analyzed for the expression of TCR Vbeta genes using the technique of reverse transcriptase-polymerase chain reaction (RT-PCR).</p><p><b>RESULTS</b>The percentages of Staphylococcus exotoxins in nasal polyps were 54.54% (21/22) for chronic rhinosinusitis with nasal polyp (CRSwNP) subjects. There were no positive results in the CRSsNP or control groups. The expressional intensity of Vbeta3 (10.02), Vbeta14 (3.54), Vbeta15 (2.39), Vbeta17 (3.48), and Vbeta20 (2.94) was increased significantly for Staphylococcal exotoxin B (SEB) positive subjects (P < 0.05). Vbeta2 (13.8) and Vbeta6. 1-3 (6.53) were significantly highly expressed for toxic shock syndrome toxin-1 (TSTf-1) positive subjects in CRSwNP group (P < 0.05). There were no dominantly used Vbeta fragments in ELISA- negative specimens. In the group of chronic rhinosinusitis without nasal polyp (CRSsNP), most of TCR Vbeta gene subfamilies demonstrated a trend toward higher expressional levels compared with those of normal controls, although there was no statistical difference (P > 0.05).</p><p><b>CONCLUSIONS</b>There was relationship between Staphylococcal superantigens and the excursion of TCR Vbeta gene spectra in nasal polyp, and superantigens possibly play an important role in the pathogenesis of CRSwNP.</p>