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Objective: To understand the vaccination status of enterovirus type 71 (EV71) inactivated vaccines in China from 2017 to 2021 and provide evidence for making policy on immunization strategy against hand, foot and mouth disease (HFMD). Methods: Using the reported dose number of EV71 vaccination and birth cohort population data collected by the China immunizaiton program information system to estimate the cumulative coverage of EV71 vaccine by the end of 2021 among the birth cohorts since 2012 at national, provincial, and prefecture levels, and analyze the correlation between the vaccination coverage and the potential influencing factors. Results: As of 2021, the estimated cumulative vaccination coverage of the EV71 vaccine was 24.96% in birth cohorts since 2012. The cumulative vaccination coverage was between 3.09% and 56.59% in different provinces, between 0 and 88.17% in different prefectures. There was a statistically significant correlation between vaccination coverage in different regions and the region's previous HFMD prevalence and disposable income per capita. Conclusions: Since 2017, the EV71 vaccines have been widely used nationwide, but the coverage of EV71 vaccination varies greatly among regions. Vaccination coverage is higher in relatively developed regions, and the intensity of previous epidemic of HFMD may have a certain impact on the acceptance of the vaccine and the pattern of immunization service. The impact of EV71 vaccination on the epidemic of HFMD requires further studies.
Subject(s)
Humans , Enterovirus A, Human , Hand, Foot and Mouth Disease/prevention & control , Vaccines, Inactivated , Viral Vaccines , Enterovirus , Vaccination , China/epidemiologyABSTRACT
Objective@#To explore the associations of family structure with adolescent mental health and health associated behaviors, to support interventions to decrease the occurrence of psychological problems and adverse health associated behaviors among adolescents in families without two parents.@*Methods@#The multi stage stratified random cluster sampling method was used to select 18 700 adolescents of the 13 districts and cities from Jiangsu Province for a questionnaire survey on mental health and health associated behaviors, to compare differences in mental health and health associated behaviors among adolescents with different family structures.@*Results@#Among the adolescents, 82.1% had two parent families, 8.6% had single mother families, 4.0% had single father families, and 5.3 % had families with both parents absent. After controlling for age, urban/rural areas, gender, academic period and region, Logistic multivariate regression analysis showed that compared with adolescents from two parent families, the incidence of depression, social anxiety and bullying on campus of adolescents with single mother families increased significantly( OR=1.31, 1.15, 1.36，P ＜0.05). Compared with adolescents in two parent families, adolescents in families without two parents had significantly more types of health risk behaviors, and those in single mother families had significantly less frequent intake of a healthful diet( OR =0.81), significantly more smoking( OR =1.20), drinking behaviors( OR =1.22), and significantly less moderate intensity physical activity ( OR =0.84) and shorter duration of sleep( OR =0.87)( P <0.05).@*Conclusion@#Psychological and health associated problems were significantly higher among adolescents in families without two parents than in those with two parent families. Psychological problems and adverse health associated behaviors were particularly prominent among adolescents in single mother families.
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Objective:To prepare nanoprobes by using polydopamine (PDA) as a carrier which is modified with the sonosensitizer protoporphyrin Ⅸ (PpⅨ) and labeled with 131I, 99Tc m or 177Lu, and to explore the value of these new nanoprobes in diagnosis and combination therapy of breast cancer. Methods:PDA particles were synthesized by aqueous oxidation, and a layer of polyethylene glycol (PEG) and PpⅨ were modified on the surface to product PDA-PEG-PpⅨ. Then the nuclides 131I, 99Tc m and 177Lu were labeled on PDA, respectively, and the labeling yield and stability were determined. The cytotoxicity test was conducted by comparing the viabilities of 4T1 tumor cells in free 131I group and 131I-PDA-PEG-PpⅨ group. The 4T1 cells were divided into 7 groups according to different treatment methods: PDA-PEG-PpⅨ group, PDA-PEG-PpⅨ+ photothermal therapy (PTT) group, PDA-PEG-PpⅨ+ sonodynamic therapy (SDT) group, 131I-PDA-PEG-PpⅨ+ PTT group, 131I-PDA-PEG-PpⅨ+ SDT group, 131I-PDA-PEG-PpⅨ+ PTT+ SDT group (100 μg/ml PDA-PEG-PpⅨ, 925 kBq/ml 131I), and the control group (DMEM culture medium). The cell viabilities of those groups were compared to evaluate the therapeutic effect. 4T1 tumor bearing mouse models were established, then 99Tc m-PDA-PEG-PpⅨ was injected through the tail vein (29.6 MBq) or intratumorally (14.8 MBq) to perform gamma imaging. The independent-sample t test and one-way analysis of variance were used for data analysis. Results:The PDA particles were uniform in size, with a particle size of (160.0±1.5) nm. They had a good photothermal conversion effect. A characteristic peak consistent with PpⅨ (400 nm) appeared in the UV-Vis absorption spectrum of PDA-PEG-PpIX. In the cytotoxicity test, when the radioactivity was 1.850 or 3.700 or 7.400 MBq/ml, the cell viabilities of free 131I group and 131I-PDA-PEG-PpⅨ group were significantly different ((72.18±6.57)% vs (86.07±5.17)%, (59.31±9.06)% vs (80.85±4.21)%, (42.90±1.30)% vs (72.99±5.73)%; t values: 3.71, 4.82, 11.46, P values: 0.006, 0.001, <0.001). The 131I-PDA-PEG-PpⅨ+ PTT+ SDT combination therapy had a better killing effect on 4T1 tumor cells than the combination of 131I-PDA-PEG-PpⅨ+ PTT and 131I-PDA-PEG-PpⅨ+ SDT (cell viabilities: (10.09±2.50)% vs (16.04±2.63)%, (28.65±4.72)%; F=351.66, P<0.001). In vivo imaging showed that 99Tc m-PDA-PEG-PpⅨ was stable in mouse models and could be effectively enriched in tumors. Conclusions:A multifunctional nanoprobe based on PDA is successfully prepared. The radionuclide labeling method is simple and effective, with a good stability. 131I-PDA-PEG-PpⅨ can kill 4T1 cells efficiently. 99Tc m-PDA-PEG-PpⅨ has an obvious tumor concentration effect in mouse models.
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Objective@#To systematically evaluate the diagnostic value of optical imaging combined with indocyanine green (ICG)-guided sentinel lymph node (SLN) biopsy in gastric cancer, and to identify potential factors that would influence diagnostic accuracy.@*Methods@#Study was carried out by searching the electronic database of PubMed, Embase, Medline, Web of Science, and the Cochrane Library with keywords as "gastric/stomach" and "cancer/carcinoma/tumor/tumour/adenocarcinoma/neoplasm" and "sentinel lymph node" and "near-infrared/NIR or fluorescent imaging" and "indocyanine green/ICG" . Literature inclusion criteria: (1) gastric cancer clinical stage was cT0-3; (2) clinical stage determined by at least 2 kinds of imaging modalities; (3) optical imaging (near-infrared or fluorescence imaging) combined with ICG-guided SLN biopsy; (4) prospective study to predict lymph node metastasis; (5) intraoperative or postoperative pathology for all lymph nodes removed; (6) patients number in the literature >10 cases. Exclusion criteria: (1) patients with a history of ICG allergy or chemoradiotherapy; (2) previous history of endoscopic mucosal resection or endoscopic submucosal dissection; (3) patients with a variety of gastrointestinal tumor; (4) case reports, conference abstracts, clinical guidelines, editorials, reviews, meta-analysis and correspondence letters; (5) in vitro or animal experiments; (6) insufficient diagnostic efficacy data. The meta-analysis was performed in the Stata12.0 software using the "bivariate mixed-effects model" combined with the "midas" command to pool the data. Information such as true positive value, false positive value, false negative value, and true negative value of each included articles were extracted. The literature quality assessment map was drawn to describe the overall quality of the articles; the heterogeneity analysis was performed with the forest map, with P<0.01 considered as statistical significance; the funnel plot was used to describe publication bias, with P<0.1 considered as statistically significant. Area under curve (AUC) of summary receiver operator characteristic (SROC) was used to describe the diagnostic accuracy and the AUC closer to 1 indicated higher diagnostic accuracy. If there was heterogeneity (I2>50%) among studies, regression analysis and subgroup analysis were performed. P<0.05 was considered as statistically significant.@*Results@#A total of 15 studies (1020 patients) were included. The optical imaging contained near-infrared (NIR) and fluorescent imaging (FI). The diagnostic value of optical imaging combined with ICG-guided SLN biopsy in gastric cancer was as follows: the pooled sensitivity (Sen) was 0.95 (95% CI: 0.82 to 0.99), specificity (Spe) was 1.00 (95% CI: 0.92 to 1.00), positive likelihood ratio (PLR) was 30.39 (95% CI: 9.14 to 101.06), negative likelihood ratio (NLR) was 0.05 (95% CI:0.01 to 0.20), diagnostic odds ratio (DOR) was 225.54 (95% CI: 88.81 to 572.77), AUC was 1.00 (95% CI: 0.99 to 1.00), threshold value was sensitivity=0.95 (95% CI: 0.82 to 0.99) and specificity=1.00 (95% CI: 0.92 to 1.00). Deeks method revealed DOR funnel plot of SLN biopsy was not asymmetrical obviously with significant difference (P=0.01), which indicated remarkable publishing bias. Meta-subgroup analysis showed that compared to FI, NIR imaging had higher sensitivity (0.98 vs. 0.73); compared to 0 minutes, optical imaging performed 20 minutes after ICG injection had higher sensitivity (0.98 vs. 0.70); compared to mean detected number of SLN of 4, mean detected number≥4 had higher sensitivity (0.96 vs. 0.68); compared to HE stain, immunohistochemistry + HE had higher sensitivity (0.99 vs. 0.84); compared to subserous injection of ICG, submucosa injection of ICG had higher sensitivity (0.98 vs. 0.40); compared to injection of 5 g/L ICG, 0.5 g/L and 0.05 g/L had higher sensitivity (0.98 vs. 0.83); compared to cT2-3 tumor, early stage (cT1) tumor had higher sensitivity (0.96 vs. 0.72); compared to ≤ enrolled 26 cases in the study, > 26 cases had higher sensitivity (0.96 vs. 0.65); compared to papers before 2010, papers after 2010 had higher sensitivity (0.97 vs. 0.81); whose differences were all significant. Sensitivity differences between mean tumor diameter of ≤30 cm and >30 cm, open surgery and laparoscopic surgery, lymph node regional dissection and retrieved dissection were not significant (all P>0.05).@*Conclusions@#Optical imaging combined with ICG-guided SLN biopsy is clinically feasible, and especially suitable for early gastric cancer. However, the ICG being used in current studies may be overdosed. Higher sensitivity may be achieved from NIR imaging when compared with FI method.
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Objective To explore the clinical value of double-balloon enterocopy (DBE) in diagnosis of small intestinal diseases. Methods The clinical and endoscope image data of 231 patients with suspected small bowel disease who underwent DBE from January 2008 to May 2016 were analyzed. Result 231 patients received 257 times of DBE examination, 112 of them were performed by oral and 93 by anal route, 26 patients were underwent by both approaches. The detection rate of intestine diseases was 64.9% (150/231), include 33 cases (14.3%) of nonspecific enteritis, 27 cases (11.7%) of crohn's disease, 19 cases (8.2%) of ulcer, 13 cases (5.6%) of intestinal vascular malformation, 12 cases (5.2%) of small intestinal stromal tumor. The lesion detection rate in obscure abdominal pain and obscure gastrointestinal bleeding were 59.6% (62/104) and 67.0% (63/94). In all patients, there were 1 case of small bowel perforation, the remaining patients had no serious complications such as bleeding and perforation. Conclusion The positive detection rate of double-balloon enteroscopy examination is high, and the double-balloon enteroscopy examination is relatively safe. So, double-balloon enterscopy examination has high diagnostic value for detecting small intestine diseases.
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Objective To explore the clinical value of double-balloon enterocopy (DBE) in diagnosis of small intestinal diseases. Methods The clinical and endoscope image data of 231 patients with suspected small bowel disease who underwent DBE from January 2008 to May 2016 were analyzed. Result 231 patients received 257 times of DBE examination, 112 of them were performed by oral and 93 by anal route, 26 patients were underwent by both approaches. The detection rate of intestine diseases was 64.9% (150/231), include 33 cases (14.3%) of nonspecific enteritis, 27 cases (11.7%) of crohn's disease, 19 cases (8.2%) of ulcer, 13 cases (5.6%) of intestinal vascular malformation, 12 cases (5.2%) of small intestinal stromal tumor. The lesion detection rate in obscure abdominal pain and obscure gastrointestinal bleeding were 59.6% (62/104) and 67.0% (63/94). In all patients, there were 1 case of small bowel perforation, the remaining patients had no serious complications such as bleeding and perforation. Conclusion The positive detection rate of double-balloon enteroscopy examination is high, and the double-balloon enteroscopy examination is relatively safe. So, double-balloon enterscopy examination has high diagnostic value for detecting small intestine diseases.
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Objective:Study on proliferation of gastric cancer cells (GCCs) and expressions of VEGF under the CO2 pneumoperitoneum environment,and effect of Bcl-2 specific inhibitor on the expression of VEGF in GCCs/TAMs co-culture system.Methods:TAMs induced by PMA and IL-4 in vitro.TAMs and MKN-45 cells were co-cultured in Transwell chamber,in pseudo CO2 pneumoperitoneum environment.Proliferation activity of GCCs was detected by MTT assay,and ELISA method was used to detect VEGF concentration in the cell culture supernatant.Results:Co-culture system was divided into CO2 pneumoperitoneum group and control group.Proliferation activity of MKN-45 cell and expression of VEGF of 5mmHg,10mmHg and 15mmHg groups are no difference with the control group;25 mmHg group is opposite to the former.The cells in co-culture group and CO2 pneumoperitoneum group (15 mmHg) were added to ABT-737,VEGF expression of co-culture + ABT-737 group was significantly lower than that of in the control group(P=0.001).Co-cultured cells VEGF expression in pneumoperitoneum group was significantly lower than the control group without inhibitor (P=0.000).Conclusion:Normal laparoscopic pneumoperitoneum is no stimulation of tumor cell proliferation defects,And higher pneumoperitoneum pressure might increase the hypoxia status of tumor microenvironment,promote tumor malignant progression.The interaction between tumor cells and TAMs may be achieved by paracrine Bcl-2-VEGF loop.
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Objective:To explore the effect of VEGF overexpression on the Bcl-2 of TAMs /MCF-7 cell co-culture system.Methods:Application of PMA and IL-4 cells induced THP-1 cell differentiation into TAMs in vitro;TAMs and MCF-7 cell were co-cultured in non-contact Transwell system.MCF-7 cells' proliferation status after co-culture were detected by MTT method;Effect of VEGF over-expression in co-cultured system on Bcl-2 level s in the two cell lines by Western blot assay.Results:PMA and IL-4 induced THP-1 cell become TAMs in vitro.After co-cultured with TAMs 24 h,48 h,MCF-7 cell's proliferation activity increased by 16.16 ％ and 33.99％ vs the control group respectively.TAMs,MCF-7 cells were added VEGF and the supematant of co-culture system respectively,then Bcl-2 levels in both cells were significantly higher,the difference was statistically significant (P＜0.05).Conclusions Tumors secrete VEGF and other chemokines to recruit and activate TAMs.Proliferation,apoptosis and progression of tumor was affected by VEGF/Bcl-2 paracrine loop in tumor microenvironment.
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Objective To stimulate the expansion of natural killer cells (NK) in vivo, to achieve high expression of Flt-3 ligand ( FL) in the mouse liver by hydrodynamic injection technology , to obtain high purity of NK for cell therapy and then to purify the spleen lymphocytes by MicroBeads sorting ( MACS ) technique.Methods C57BL/6 mice were repeatedly treated with hydrodynamic injection of FL expression plasmid .Then, surface markers of splenic NK were analyzed by flow cytometry and purified by MACS technique .Results Compared with mice treated with one hydrodynamic injection, the spleen of mice treated with two hydrodynamic injections showed significant variation, with the absolute num-ber of lymphocytes increased (6.02 ±1.15) times, the proportion of NK subsets increased (2.07 ±0.39) times, and the absolute number of NK subsets increased (12.49 ±2.39) times.Cell surface marker detection confirmed that NK activity and surface markers did not change significantly .NK with a purity of about (83.81 ±0.92)％ was obtained by the combination of two magnetic beads sorted with CD 5 ( Ly-1) MicroBeads Positive selection and EasySep TM Mouse NK Cell Isolation Kit negative selection .Conclusion NK can be expanded in the spleen of mice by hydrodynamic injection of FL plasmid without influence on the NK activity and surface markers.The combined use of CD5 (Ly-1) MicroBeads positive selection with EasySep TM Mouse NK Cell Isolation Kit negative selection can effectively remove T , B and other miscellaneous cells, thereby contributing to obtaining high-purity NK. This study provides good reference for the immunotherapy of tumor cells.
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Objective To evaluate the surgical effect of laparoscopic anterior resection of rectal carcinoma with or without the left colic artery.Methods Through computer searching PubMed,Cochrane Library,Embase,WanFang Date and CNIK Date.Handsearching the Gray literature simultaneously.The randomized controlled trails and clinical controlled trials comparing low ligation with high ligation the inferior mesenteric artery in laparoscopic anterior resection of rectal carcinoma were colected.Data were screened,extracted and evaluated by two reviewers independently.Meta-analyses were conducted using the sofeware STATE12.0.The standardized mean difference were calculated for continuous data and odds ratio for dichotomous and the point estimates of each effect quantity and 95％ confidence interval were calculated.TheI2 test was used to test the heterogeneity of the inchuded literature:if the heterogeneity was small,the fixed effects model was adopted.otherwise,the random effects models was adopted and explored the heterogeneity by sensitivity analysis or subgroup analysis.Results Forteen articles including 15 researches were met the selection criteria.The Meta-analyses showed that the grope of low ligation had lower rate of anastomotic fistula (OR =0.394,95 ％ CI:0.251-0.616,P =0.000) and longer opration time (SMD =0.361,95％CI:0.242-0.480,P =0.000).There is no statistical differences in the number of lymph node dissection besides the root of IMA (SMD =-0.017,95％ CI:-0.130-0.097,P =0.772) intraoperative biood loss (SMD =0.083,95 ％ CI:-0.048-0.214,P =0.213).Conclusions In spite of reserved the left colic artery had longer operation time it can reducedrate of anastomotic fistula effectively and there is no statistical differences in the number of lymph node dissection besides the root of IMA,intraoperative blood loss.It is possible to promote the use of reserved the left colic artery in laparoscopic anterior resection of rectal carcinoma.
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Objective To refine the technique and improve the efficacy of seminal vesiculoscopy in the diagnosis and treatment of seminal vesicle disease.Methods The refined techniques of seminal vesculoscopy,using a patent catheter into the slit-like ejaculatory duct orifice through the verumontanum and another patent catheter introduced into seminal vesicle lumen,were performed in 58 cases,including intractable hematospermia in 42 cases and azoospermia in 16 cases.Results Seminal vesiculoscopy was successfully entered into the seminal vesicular lumen in 46 patients (79％) within 2-3 min.There was no obvious ejaculatory duct orifice in 12 of 16 azoopermia cases,and transurethral resection of verumontanum was performed,then seminal vesiculoscope was directly entered into seminal vesicle lumen.Symptoms of hematospermia were disappeared in 25 cases (60％),improved in 11 cases (26％),and azoospermia were cured in 6 cases (37％),improved in 5 (31％),unchanged in 5 (31％) during the follow-up period of 6-36 months (average 18 months).There were no major or minor complications in this series,and no urine reflux into ejaculatory duct in 19 cases demonstrated by contrast medium.Conclusion Refined seminal vesiculoscopy was technically safe,efficient,simple,and potentially widely used in the cases of hematospermia and ejaculatory duct obstructions.
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<p><b>OBJECTIVE</b>To search for an optimum method for testicular prothesis implantation in the treatment of testis loss.</p><p><b>METHODS</b>We retrospectively analyzed the surgical methods and outcomes of 53 cases of terminal prostate cancer and 4 cases of unilateral testicular torsion treated by implantation of testicular prothesis with the polypropylene mesh.</p><p><b>RESULTS</b>The 57 male patients all received testicular prothesis with the polypropylene mesh. All the patients were satisfied with the appearance and size of the scrotum after surgery. No scrotal hematoma, prosthesis infection, or autoimmune disease occurred postoperatively.</p><p><b>CONCLUSION</b>Testis loss is not a rare condition clinically, for the treatment of which surgical implantation of testicular prothesis with the polypropylene mesh can achieve both a fine tissue compatibility and a desirable scrotal appearance.</p>
Subject(s)
Humans , Male , Polypropylenes , Prostatic Neoplasms , General Surgery , Prostheses and Implants , Retrospective Studies , Scrotum , Spermatic Cord Torsion , General Surgery , Surgical Mesh , TestisABSTRACT
Objective To study the relationship among the angiotensinogen (AGT)gene T174M,M235T polymorphisma,blood glucose level and atherosclerotic cerebral infarction.Methods The polymerase chain reaction-restriction fragment length polymor-phism (PCR-RFLP)method was adopted to detecte the gene polymorphisms of AGT gene 174,235 sites and the fully automatic bi-ochemical analyzer was used to detect the biochemical indexes of GLU,etc.in 396 patients with atherosclerotic cerebral infarction and 360 normal controls.Results The GLU level in the patients of the ACI group carrying genotype TT and TM at AGT gene T174M site was higher than that in the normal control group with statistical differences(P 0.05);the glucose level in the patients carrying genotypes MM,MT and TT at M235T site in the ACI group was higher than that in the normal group,and the difference was statistically significant(P0.05 ).Conclusion No correlation is found among AGT gene T174M,M235T polymorphism,blood glucose level and atherosclerotic cerebral infarction;hyperglycemia is one of the risk factors of atherosclerotic cerebral infarction occurrence.
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Endothelin-3 (ET-3) is aberrantly expressed in both metastatic melanoma tissues and cultured melanoma cells. Our previous work showed that ET-3 could promote survival of metastatic melanoma cells via its altered expression. In this study, we investigated the mechanisms responsible for these gene-induced phenotypes in melanoma cells. An ET-3 gene sequence-specific shRNA vector pLVTHM-ET3-RNAi was constructed and transfected into human malignant melanoma cells A375 and MMRU, and the resultant molecular events and cellular changes were examined. As compared with the empty-vector group, cell proliferation was slowed down, and the growth inhibition rates were 38.9% in A375 cells and 38.4% in MMRU cells after transfection. In addition, cell invasion capability was also inhibited, with a reduction of 62.2% in A375 cells and 54.3% in MMRU cells. The percentage of apoptotic cells was found to increase. Meanwhile, in both cell lines, secreted protein acidic and rich in cysteine (SPARC) levels were down-regulated together with inhibition of its upstream signaling molecule, NF-κB. Thus, the current results suggested that down-regulated expression of ET3 attenuates the malignant behaviors of human melanoma cells partially by decreasing the expression of SPARC and NF-κB.
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The rs10954213 polymorphism and the haplotype diversity in interferon regulatory factor 5 (IRF5) play a special role in systemic lupus erythematosus (SLE) but with inconclusive results. We conducted a meta-analysis integrating case-control and haplotype variant studies in multiple ethnic populations to clearly discern the effect of these two variants on SLE. Eleven studies on the relation between rs10954213 polymorpisms in IRF5 and SLE were included and we selected a random effect model to calculate the pooled odds ratios (ORs) and the corresponding 95% confidence interval (95% CI). A total of 6982 cases and 8077 controls were involved in the meta-analysis. The pooled results indicated that A allele was significantly associated with increased risk of SLE as compared with the IRF5 rs10954213 G allele (A vs. G, P<0.00001) in all subjects. The same pattern of the results was also obtained in the European, African American, and Latin American. Asian population had a much lower prevalence of the A allele (49.1%) than any other population studied, and Europeans had the highest frequency of the IRF5 rs10954213 A allele (62.1%). The significant association of increased SLE risk and TCA haplotype was indicated in the contrast of TCA vs. TTA as the pooled OR was 2.14 (P=0.002). The same result was also found in the contrast of TCA vs. TTG as the pooled OR was 1.45 (P=0.004). This meta-analysis suggests that the A allele of rs10954213 and TCA haplotype (rs2004640-rs2070197-rs10954213) in IRF5 is associated with the increased risk of SLE in different ethnic groups, and its prevalence is ethnicity dependent.
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The rs10954213 polymorphism and the haplotype diversity in interferon regulatory factor 5 (IRF5) play a special role in systemic lupus erythematosus (SLE) but with inconclusive results. We conducted a meta-analysis integrating case-control and haplotype variant studies in multiple ethnic populations to clearly discern the effect of these two variants on SLE. Eleven studies on the relation between rs10954213 polymorpisms in IRF5 and SLE were included and we selected a random effect model to calculate the pooled odds ratios (ORs) and the corresponding 95% confidence interval (95% CI). A total of 6982 cases and 8077 controls were involved in the meta-analysis. The pooled results indicated that A allele was significantly associated with increased risk of SLE as compared with the IRF5 rs10954213 G allele (A vs. G, P<0.00001) in all subjects. The same pattern of the results was also obtained in the European, African American, and Latin American. Asian population had a much lower prevalence of the A allele (49.1%) than any other population studied, and Europeans had the highest frequency of the IRF5 rs10954213 A allele (62.1%). The significant association of increased SLE risk and TCA haplotype was indicated in the contrast of TCA vs. TTA as the pooled OR was 2.14 (P=0.002). The same result was also found in the contrast of TCA vs. TTG as the pooled OR was 1.45 (P=0.004). This meta-analysis suggests that the A allele of rs10954213 and TCA haplotype (rs2004640-rs2070197-rs10954213) in IRF5 is associated with the increased risk of SLE in different ethnic groups, and its prevalence is ethnicity dependent.
Subject(s)
Female , Humans , Male , Genetic Association Studies , Genetic Markers , Genetics , Genetic Predisposition to Disease , Epidemiology , Genetics , Genetic Variation , Genetics , Haplotypes , Genetics , Interferon Regulatory Factors , Genetics , Lupus Erythematosus, Systemic , Epidemiology , Genetics , Polymorphism, Single Nucleotide , Genetics , PrevalenceABSTRACT
Endothelin-3 (ET-3) is aberrantly expressed in both metastatic melanoma tissues and cultured melanoma cells. Our previous work showed that ET-3 could promote survival of metastatic melanoma cells via its altered expression. In this study, we investigated the mechanisms responsible for these gene-induced phenotypes in melanoma cells. An ET-3 gene sequence-specific shRNA vector pLVTHM-ET3-RNAi was constructed and transfected into human malignant melanoma cells A375 and MMRU, and the resultant molecular events and cellular changes were examined. As compared with the empty-vector group, cell proliferation was slowed down, and the growth inhibition rates were 38.9% in A375 cells and 38.4% in MMRU cells after transfection. In addition, cell invasion capability was also inhibited, with a reduction of 62.2% in A375 cells and 54.3% in MMRU cells. The percentage of apoptotic cells was found to increase. Meanwhile, in both cell lines, secreted protein acidic and rich in cysteine (SPARC) levels were down-regulated together with inhibition of its upstream signaling molecule, NF-κB. Thus, the current results suggested that down-regulated expression of ET3 attenuates the malignant behaviors of human melanoma cells partially by decreasing the expression of SPARC and NF-κB.
Subject(s)
Humans , Cell Line, Tumor , Endothelin-3 , Genetics , Gene Silencing , Melanoma , Genetics , Pathology , Osteonectin , GeneticsABSTRACT
<p><b>OBJECTIVE</b>To investigate the effects of sphingosine kinase 1 (SphK1) on the proliferation, migration and invasion of human colon cancer LoVo cells, and to explore the related mechanisms.</p><p><b>METHODS</b>Human colon cancer LoVo cells were divided into three groups: phorbol 12-myristate 13-acetate (PMA) was used to induce the activation of SphK1 in the PMA group, N,N-dimethylsphingosine (DMS) used to suppress the activity of SphK1 in DMS group, and the cells treated with equal amount of 0.9 % NaCl instead of drugs served as the control group. The activity of SphK1 was assayed by autoradiography, the cell proliferation was assessed by MTT assay, cell migration and invasion were examined by Boyden chamber assay, concentrations of sICAM-1 and sVCAM-1 were assayed by ELISA, and RT-PCR and Western blot were used to evaluate the mRNA and protein expression in the cells.</p><p><b>RESULTS</b>The activity of SphK1 was efficiently induced by PMA and significantly suppressed by DMS. PMA induced cell proliferation in a time- and dose-dependent manner. On the contrast, DMS suppressed cell proliferation in a time- and dose-dependent manner. After treating with PMA, the number of migrating and invasing cells were increased to 143.36 ± 8.73 and 118.46 ± 6.25, significantly higher than those of the control group (75.48 ± 6.12 and 64.19 ± 5.36). After treating with DMS, the number of migrating and invasing cells were decreased to 38.57 ± 3.24 and 32.48 ± 4.27, significantly lower than those of the control group (P < 0.01). The relative expression levels of FAK, ICAM-1 and VCAM-1 mRNA in the PMA group were 0.82 ± 0.06, 0.74 ± 0.05 and 0.89 ± 0.09, and those in the DMS group were 0.23 ± 0.02, 0.26 ± 0.03 and 0.37 ± 0.04, with significant differences between the PMA, DMS and control groups (P < 0.01). Compared with the control group, the relative expression levels of FAK and p-FAK proteins in the PMA group (0.52 ± 0.06 and 0.51 ± 0.06) were significantly elevated, and those of the DMS group (0.20 ± 0.03 and 0.09 ± 0.02) were significantly decreased. In addition, the concentrations of sICAM-1 and sVCAM-1 were significantly elevated with the activation of SphK1. On the contrary, those of the DMS group were significantly reduced with the suppression of SphK1 (Both P < 0.01).</p><p><b>CONCLUSIONS</b>SphK1 may enhance the proliferation, migration and invasion of colon cancer LoVo cells through activating FAK pathway and up-regulating the expression of ICAM-1 and VCAM-1.</p>
Subject(s)
Humans , Cell Line, Tumor , Cell Movement , Cell Proliferation , Colonic Neoplasms , Metabolism , Pathology , Dose-Response Relationship, Drug , Enzyme Inhibitors , Pharmacology , Focal Adhesion Kinase 1 , Genetics , Metabolism , Intercellular Adhesion Molecule-1 , Genetics , Metabolism , Neoplasm Invasiveness , Phosphorylation , Phosphotransferases (Alcohol Group Acceptor) , Metabolism , RNA, Messenger , Metabolism , Signal Transduction , Sphingosine , Pharmacology , Tetradecanoylphorbol Acetate , Pharmacology , Vascular Cell Adhesion Molecule-1 , Genetics , MetabolismABSTRACT
<p><b>OBJECTIVE</b>To explore the association between blood pressure level and incidence of carotid arterial plaque in middle-aged and elderly people.</p><p><b>METHODS</b>A total of 5852 individuals were randomly stratified from the 101 510 health examination survey participants in Tangshan Kailuan Company community during 2006-2007. A total of 5440 people (age above 40 years old, free of stroke, TIA and myocardial infarction) were enrolled in the final analysis. A questionnaire survey, blood biochemical analysis and carotid artery ultrasound examination were finished by trained medical staff. Sixteen individuals without carotid artery plaques information and 35 individuals without blood pressure information were excluded. Finally, a total of 5389 participants [3235 male, mean age: (54.7 ± 11.8) years] were analyzed. According to 2010 Chinese guideline to prevention and treatment of hypertension and blood pressure level classification, participants were divided into normotensive group (n = 1377), high normal blood pressure group (n = 1971) and hypertensive group (n = 2041). Multivariate logistic regression analysis was used to determine the risk factors of the carotid artery plaques.</p><p><b>RESULTS</b>Age, male gender, BMI, IMT, TG, FBG, smoking and alcohol drinking rate were significantly higher in high normal blood pressure group than in normotensive group (all P < 0.05), LDL-C, HDL-C, hs-CRP and TC were similar between these two groups. Incidence of carotid artery plaques in normotensive, high normal blood pressure and hypertensive groups was 24.8%, 37.4%, 60.2% respectively. The risk of carotid artery plaques was increased to 38% and 163% in high normal and hypertensive groups compared to normotensive group, the OR ratio was 1.38 (95%CI: 1.15-1.66) and 2.63 (95%CI: 2.18-3.18), respectively. After adjusting gender, age, smoking, alcohol consumption, TG, TC, HDL-C, FBG, hs-CRP and BMI, the risk of developing carotid artery plague was increased in proportion to increasing blood pressure and the OR value was 1.24 (95%CI:1.01-1.52) , 1.69 (95%CI:1.34-2.15) and 2.66 (95%CI:2.20-3.21) in high normal group I [SBP/DBP 121-129/80-84 mm Hg(1 mm Hg = 0.133 kPa)] and high normal group II (SBP/DBP 130-139/85-89 mm Hg) and hypertensive group, respectively.</p><p><b>CONCLUSIONS</b>The cardiovascular risk factors and prevalence of carotid artery plague increase in proportion to blood pressure level in this cohort. The detection rate of carotid artery plague is already significantly increased in individuals with high normal blood pressure.</p>
Subject(s)
Adult , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Blood Pressure , Physiology , Carotid Stenosis , Epidemiology , Risk FactorsABSTRACT
<p><b>OBJECTIVE</b>To investigate the effect of sphingosine kinase 1 (SphK1) on the proliferation, apoptosis, migration and invasion of colon cancer TH-29 cells and to explore its molecular mechanisms.</p><p><b>METHODS</b>Phorbol 12-myristate 13-acetate (PMA) was used to induce the activity of SphK1 and N, N-dimethylsphingosine (DMS) was used to suppress the activity of SphK1. Cell prolieration and apoptosis were detected by MTT assay and flow cytometry, respectively. The migration and invasion capabilities of the cells were assessed in Transwell chambers. The activity of SphK1 was assayed by autoradiography. Western blot was used to evaluate the protein expression of SphK1, p38, phosphorylated p38 (p-p38) and SAPK/JNK.</p><p><b>RESULTS</b>PMA and DMS were able to induce and suppress the activity and protein expression of SphK1 in a time-dependent manner, respectively. PMA enhanced and DMS suppressed the cell viability in a time- and dose-dependent manner. Being treated with 100 nmol/L PMA or 50 µmol/L DMS for 0, 6, 12, 24 h, the cell apoptosis rates of PMA group were (9.35 ± 0.84)%, (7.61 ± 0.48)%, (5.53 ± 0.76)% and (0.56 ± 0.33)%, contrastly, that of DMS group were (9.18 ± 0.94)%, (12.06 ± 1.41)%, (19.80 ± 2.36)% and (31.85 ± 3.60)%, respectively. Compared with the control group, the cell migration and invasion capabilities of the PMA group were significantly enhanced, and that of the DMS group were significantly suppressed. The migration cell number of control, PMA and DMS groups were 68.75 ± 6.15, 109.33 ± 11.63 and 10.83 ± 2.48, the invasion cell number of control, PMA and DMS groups were 55.42 ± 4.50, 90.58 ± 7.06 and 9.58 ± 2.39, respectively. With the elevating activity and expression of SphK1, the protein expressions of p38, p-p38 and SAPK/JNK were strikingly suppressed. On the contrary, after treating with DMS the protein expressions of p38, p-p38 and SAPK/JNK were enhanced.</p><p><b>CONCLUSIONS</b>SphK1 potently enhances the prolieration, migration and invasion of colon cancer HT-29 cells, meanwhile suppresses the cell apoptosis. The suppressing of the p38 and SAPK/JNK signalling pathways may be one of its molecular mechanisms.</p>