Aneurysms in Takayasu's arteritis: a retrospective study of Chinese patients.

OBJECTIVES: Aneurysm formation can cause life-threatening complications in Takayasu's arteritis (TAK). The objective of this study was to evaluate the demographic, clinical and angiographic features, and outcomes of aneurysm secondary to TAK in Chinese patients. METHODS: The medical charts of patients diagnosed with TAK in Changhai Hospital between 2001 and 2017 were retrospectively reviewed. RESULTS: Aneurysms were identified in 66 (16.6%) of 397 patients with TAK. The mean age at onset was 30.4±11.5 years, with a male:female ratio of 1:2.7. Patients with aneurysm had a higher proportion of male (p<0.01), higher incidences of bruit, chest tightness and aortic regurgitation (all p<0.001), and a lower incidence of visual disturbances (p<0.01) as compared with patients without aneurysm. The prevalence of elevated ESR and CRP and ITAS2010 score were higher in patients with than without aneurysm (all p<0.01). Angiographic classification showed that type V (30.3%) was the most frequent pattern in patients with aneurysm though Type I was dominant in patients without aneurysm. Multiple aneurysms were found in 30.3% of patients and the most common site of aneurysms was abdominal aorta (22.1%). Glucocorticoids were prescribed in 86.4% of patients with aneurysm, and surgical procedures were performed in 80.3%. Five of 52 patients died during the median 3-year follow-up period. CONCLUSIONS: These findings could provide useful information on the demographical, clinical and angiographic features of TAK patients with aneurysm. Aneurysm formation in TAK may be associated with male gender and active vascular inflammation.

The effectiveness of propranolol in treating infantile haemangiomas: a meta-analysis including 35 studies.

AIMS: Propranolol may have shown excellent results as a first line therapy in infantile haemangiomas (IHs) at all sites in the body, but this conclusion remains controversial. In an attempt to resolve this issue, we performed a meta-analysis. METHODS: A search of the literature using PubMed, MEDLINE, Cochrane Library databases and China National Knowledge Infrastructure (CNKI) was performed to identify studies which estimated the efficacy of propranolol therapy in infants with haemangiomas all sites of the body. The pooled odds ratio (OR) along with the corresponding 95% confidence intervals (CI) were assessed using a fixed effects model. RESULTS: Thirty-five studies involving 324 infantile haemangioma(IH) patients and 248 controls were retrieved and analyzed. The efficacy of propranolol was greater than other therapies in treating IHs (OR = 9.67, 95% CI 6.62, 14.12, P < 0.001). In a stratified analysis by sites of tumour, propranolol was a more effective therapy when compared with steroids (OR = 9.67, 95% CI 6.61, 14.15, P < 0.001), vincristine (OR = 9.00, 95% CI 2.15, 37.66, P = 0.003) and laser treatment (OR = 9.00, 95% CI 1.42, 57.12, P = 0.020) in treating cutaneous IHs (OR = 24.95, 95% CI 9.48, 65.64, P < 0.001), peri-ocular IHs (OR = 9.39, 95% CI 3.88, 22.71, P < 0.001), infantile airway haemangiomas (OR = 20.91, 95% CI 7.81, 55.96, P < 0.001) and infantile hepatic haemangiomas (OR = 9.89, 95% CI 1.20, 81.54, P = 0.033). CONCLUSION: The current meta-analysis provided strong evidence for propranolol as a first line therapy for IHs.

Micronutrients, their potential effect on patients with systemic sclerosis.

Over the past years, several evidences have supported an important role of specific micronutrients, including vitamin A, vitamin D and vitamin E in immune dysfunction, vascular involvement and fibrotic changes involved in systemic sclerosis (SSc) development. In PubMed, eight clinical trials about the therapy of micronutrients on SSc patients were searched out using medical subject headings terms (SSc: "scleroderma, localized", "scleroderma, systemic", "scleroderma, diffuse" and "scleroderma, limited"; vitamins "vitamin A", "thiamin", "riboflavin", "niacin", "pantothenic acid", "vitamin B 6", "biotin", "folic acid", "vitamin B 12", "inositol", "choline", "ascorbic acid", "vitamin D", "vitamin E", "tocopherols", "vitamin K" and "vitamin P"; and minerals: "calcium", "magnesium", "potassium", "sodium", "phosphorus", "sulfur", "chlorine", "iron", "copper", "iodine", "zinc", "selenium", "manganese", "molybdenum", "cobalt", "chromium", "tin", "vanadium", "silicon", "nickel" and "fluorine"). This brief review will summarize current understanding on that for the further prospect of future studies. Though the clinical trials for the treatment of SSc with micronutrients are still in their infancy, more researches are needed to substantiate the current results and accelerate the knowledge in this field.

Association of TGF-ß1 +869C/T promoter polymorphism with susceptibility to autoimmune diseases: a meta-analysis.

Many case-control studies have investigated the role of TGF-ß1 gene +869C/T promoter polymorphism in autoimmune diseases, but the results are inconsistent. To clarify this point, we performed a meta-analysis based on all available studies in Pubmed, Elsevier Science Direct, Google Searching, Chinese Biomedical Literature Database, Chinese National Knowledge Infrastructure. Crude odds ratios (ORs) with 95% confidence intervals were calculated to estimate the strength of the association. A fixed or random effects model was used on the basis of heterogeneity. A total of 21 papers including 2,693 cases and 3,036 controls were considered in the current meta-analysis. These studies encompass two ankylosing spondylitis (AS), eight rheumatoid arthritis (RA), four systemic lupus erythematosus (SLE), and seven systemic sclerosis (SSc). The results showed that TGF-ß1 +869C/T promoter polymorphism were associated with susceptibility to RA (CC vs. TT: OR=0.65, 95% CI=0.48-0.88, P=0.005; CC vs. CT+TT: OR=0.56, 95% CI=0.45-0.69, P=0.000; C vs. T: OR=0.81, 95% CI=0.71-0.93, P=0.003). When stratified by race, significant association was observed only in Asian population. However, we failed to reveal the association between this gene promoter polymorphism and AS, SLE, and SSc. Therefore, this meta-analysis suggests a possible association between TGF-ß1 +869C/T promoter polymorphism and RA, especially in Asian population.

The effect of TGF-ß1 polymorphism on systemic sclerosis: a systematic review and pooled analysis of available literature.

Transforming growth factor-ß1 (TGF-ß1) plays an important role in the pathogenesis of systemic sclerosis (SSc). To investigate whether TGF-ß1 gene promoter polymorphisms were associated with the susceptibility of SSc, we performed a meta-analysis based on all available studies through PubMed, Elsevier Science Direct, Embase, and Chinese Biomedical, China National Knowledge Infrastructure and Google Scholar with the last report up to March 15, 2013. Crude odds ratios with 95% confidence intervals were used to estimate the strength of the association. A fixed or random effects model was adopted according to heterogeneity test. Heterogeneity among studies was evaluated using I (2) . Meta-regression was used to explore potential sources of between-study heterogeneity. Publication bias was estimated using Begg's and Egger's test. Totally, seven papers with 663 SSc patients and 908 healthy controls were subjected to the final analysis. These studies encompass seven for TGF-ß1 codon 10, three for codon 25 and three for -509C/T. We failed to detect any association of these promoter polymorphism with SSc susceptibility. For TGF-ß1 codon 10 polymorphism, subgroup analyses by race, genotype testing method and classification of SSc were further performed. Similarly, no association was observed. Significant heterogeneity was detected among the studies in all genetic models of TGF-ß1 codon 10 polymorphism. Publication bias was absent. Taken together, our meta-analysis did not provided an evidence of confirming association between TGF-ß1 (codon 10, codon 25, -509C/T) gene polymorphism and SSc. Nevertheless, due to smaller sample sizes, larger sample studies including different ethnic groups should be considered in future to confirm our results.

PADI4 polymorphisms and susceptibility to rheumatoid arthritis: a meta-analysis.

The objective of the study was to investigate the association between peptidylarginine deiminase 4 (PADI4) polymorphism and susceptibility to rheumatoid arthritis (RA). An electronic searching strategy was employed to collect relevant studies on the association between PADI4 polymorphism and susceptibility to RA. The odds ratio (OR) with the 95 % confidence interval (95 % CI) was used to evaluate the RA risk presented by PADI4 polymorphism. Fixed or random effects models were selected based on heterogeneity. Publication bias was assessed using funnel plots, Begg's test, and Egger's test. A total of 27 studies from 21 articles were included. Six gene loci (padi4_94, 104, 92, 90, 89, and 100) were chosen for the meta-analysis. The pooled ORs (95 % CI) for allele 2 versus 1 were 1.08 (1.05-1.12), 1.17 (1.12-1.23), 1.26 (1.18-1.36), 1.17 (1.10-1.24), 1.30 (1.17-1.44), and 1.25 (1.11-1.40), respectively. All six SNPs were significantly associated with RA in Asian populations. Three SNPs (PADI4_104, 90, 89) showed significant associations, while the other three SNPs (PADI4_94, 92, 100) exhibited no associations in the European population. A dose-response relationship between allele 2 of PADI4 and the risk of RA was also identified. In conclusion, this meta-analysis suggests that PADI4 polymorphisms represent a significant risk factor for RA, especially in Asians.

Characteristics of culprit intracranial plaque without substantial stenosis in ischemic stroke using three-dimensional high-resolution vessel wall magnetic resonance imaging.

Background and aims: We aim to analyze the difference in quantitative features between culprit and non-culprit intracranial plaque without substantial stenosis using three-dimensional high-resolution vessel wall MRI (3D hr-vw-MRI). Methods: The patients with cerebral ischemic symptoms of the unilateral anterior circulation were recruited who had non-stenotic intracranial atherosclerosis (<50%) confirmed by computed tomographic angiographic (CTA) or magnetic resonance angiography (MRA). All patients underwent 3D hr-vw MRI within 1 month after symptom onset. 3D hr-vw-MRI characteristics, including wall thickness, plaque burden, enhancement ratio, plaque volume and intraplaque hemorrhage, and histogram features were analyzed based on T2-, precontrast T1-, and post-contrast T1-weighted images. Univariate and multivariate logistic regression analysis were used to identify key determinates differentiating culprit and non-culprit plaques and to calculate the odds ratios (ORs) with 95% confidence intervals (CIs). Results: A total of 150 plaques were identified, of which 133 plaques (97 culprit and 36 non-culprit) were in the middle cerebral artery, three plaques (all culprit) were in the anterior cerebral artery (ACA) and 14 (11 culprit and three non-culprit) were in the internal carotid artery (ICA). Of all the quantitative parameters analyzed, plaque volume, maximum wall thickness, minimum wall thickness, plaque burden, enhancement ratio, coefficient of variation of the most stenotic site, enhancement ratio of whole culprit plaque in culprit plaques were significantly higher than those in non-culprit plaques. Multivariate logistic regression analysis found that plaque volume [OR, 1.527 (95% CI, 1.231-1.894); P < 0.001] and enhancement ratio of whole plaque [OR, 1.095 (95% CI, 1.021-1.175); P = 0.011] were significantly associated with culprit plaque. The combination of the two features obtained a better diagnostic efficacy for culprit plaque with sensitivity and specificity (0.910 and 0.897, respectively) than each of the two parameters alone. Conclusion: 3D hr-vw MRI features of intracranial atherosclerotic plaques provided potential values over prediction of ischemic stroke patients with non-stenotic arteries. The plaque volume and enhancement ratio of whole plaque of stenosis site were found to be effective predictive parameters.

Matrix metalloproteinases: a review of their structure and role in systemic sclerosis.

Matrix metalloproteinases (MMPs) are the main enzymes involved in arterial wall extracellular matrix (ECM) degradation and remodeling, whose activity has been involved in various normal and pathologic processes, such as inflammation, fibrosis. As a result, the MMPs have come to consider as both therapeutic targets and diagnostic tools for the treatment and diagnosis of autoimmune diseases, including systemic lupus erythematosus and rheumatoid arthritis. Systemic sclerosis (SSc) is a rare autoimmune disease of unknown etiology characterized by an excessive over-production of collagen and other ECM, resulting in skin thickening and fibrosis of internal organs. In recent years, abnormal expression of MMPs has been demonstrated with the pathogenesis of SSc, and the association of different polymorphisms on MMPs genes with SSc has been extensively studied. This review describes the structure, function and regulation of MMPs and shortly summarizes current understanding on experimental findings, genetic associations of MMPs in SSc.

Prevalence of unprotected anal intercourse and unprotected vaginal intercourse among HIV-positive men who have sex with men in China: a meta-analysis.

This study aims at deriving a general description of the prevalence of unprotected anal intercourse among HIV-positive MSM in China using published epidemiological research. Comprehensively searching Wanfang, Weipu, China Biological Medicine (CBM), Chinese National Knowledge Infrastructure (CNKI) and Pubmed databases in the systematic review. Meta-analysis were conducted over a final set of nineteen studies (n=1603). The pooled prevalence of unprotected anal intercourse among HIV-positive MSM was 75.4% (95% CI: 67.5%∼82.5%) and unprotected vaginal intercourse was 68.0% (95% CI: 46.0%∼86.4%). The prevalence of unprotected anal intercourse differed significantly in sampling method, data collection method, sample size, location, recruitment setting and data collection period. Studies with the following features had a higher prevalence of unprotected anal intercourse: recruiting participants from 2005 to 2007, sample size being below 50, recruiting participants from MSM venues/internet, using convenience sampling, study location being Chongqing city, and using interviewer administered questionnaire. Findings from this meta-analysis indicate that a majority percentage of HIV-positive MSM engage in unprotected sexual behavior. So that place their sex partners at risk for infecting HIV and also place themselves at risk for other sexually transmitted diseases. An effective strategy for prevention and control is required for this specific population in China.

Polymorphism M55V in gene encoding small ubiquitin-like modifier 4 (SUMO4) protein associates with susceptibility to type 1 (and type 2) diabetes.

BACKGROUND: The association between small ubiquitin-like modifier 4 (SUMO4) gene polymorphism and type 1 diabetes mellitus (T1DM) or type 2 diabetes mellitus (T2DM) has been investigated in several studies. We conducted a meta-analysis to evaluate the association of SUMO4 gene polymorphism with T1DM and T2DM susceptibility. METHODS: A meta-analysis was performed on the published studies before August 2011. The association of SUMO4 M55V polymorphism with T1DM and T2DM was evaluated. Meta-analysis was performed for genotypes AA versus GG, AA versus AG, AA versus AG + GG and A allele versus G allele in a fixed/random effect model. The combined odds ratio (OR) with 95% confidence interval (95% CI) was calculated to estimate the strength of the association. RESULTS: Sixteen case-control studies including 9190 cases and 10 456 healthy controls were included. T1DM patients were divided into Asian and Caucasian subgroup. We detected a significant association of SUMO4 M55V polymorphism with T1DM in Asian population (A versus G: OR = 0.79, 95%CI = 0.72-0.86, p = 0.000) and a significant association of SUMO4 M55V polymorphism with T1DM in Caucasian population (A versus G: OR = 0.84, 95%CI = 0.73-0.97, p = 0.007). Included T2DM patients were all Asian. Meanwhile, a significant association of SUMO4 M55V polymorphism with T2DM was also found (A versus G: OR = 0.86, 95%CI = 0.79-0.94, p = 0.001). CONCLUSIONS: Our study demonstrates significant associations of SUMO4 M55V polymorphism with T1DM in Asian and Caucasian population and with T2DM in Asian population.

Association of the interleukin-10 1082G/A, 819C/T and 3575T/A gene polymorphisms with systemic sclerosis: a meta-analysis.

Many environmental and genetic factors have been contributed to the development of systemic sclerosis (SSc). To determine whether IL-10 gene polymorphisms are associated with SSc, we conducted a meta-analysis approach. A total of eight studies involving 1,034 SSc cases and 1,815 controls were obtained by electronic database, i.e. Embase, Blackwell, Scopus, China National Knowledge Infrastructure database, Chinese Biomedical database, Google searching. We analyzed three gene polymorphisms, including IL-10 -1082G/A (rs1800896), IL-10 -819C/T (rs1800871), IL-10 -3575T/A (rs1800890). The combined odds ratio (OR) with its 95% confidence interval (95% CI) was calculated using fixed or random effect models. We found that IL-10 819C allele might contribute to SSc susceptibility by fixed effect model and IL-10 3575A allele could be an important risk factor for SSc, especially in European descent. No significant heterogeneity were observed. Under random effect model, there was no evidence of statistically significant association between IL-10 1082G/A polymorphism and SSc. Publication bias was absent in all analyses. However, larger scale primary studies are required to further evaluate the IL-10 polymorphism and SSc.

Meta-analysis of association between cytokine gene polymorphisms and lung cancer risk.

The aim of this study was to evaluate the association between various cytokine gene polymorphisms and lung cancer (LC) susceptibility. We searched Pubmed, Elsevier Science Direct, China National Knowledge Infrastructure database, Chinese Biomedical database, Google scholar. Totally, 20 studies involving 6,467 cases and 8,320 controls were included in the meta-analysis. The effects of eight polymorphisms, i.e. TNF-α 308G/A, IL-6 174G/C, IL-1ß 31T/C, IL-1ß 511C/T, COX-2 8473T/C, IL-10 1082G/A, IL-10 819C/T, and IL-10 592C/A were evaluated. The combined odds ratio (OR) with 95% confidence interval (95% CI) was calculated to estimate the strength of the association in a fixed or random effect model. Heterogeneity and publication bias were also assessed. We found a significant association between IL-10 polymorphism and LC. For IL-10 1082G/A, the overall ORs (95% CI) of the G versus A, GG versus AA, and GG/GA versus AA were 2.35 (1.16-4.76), 2.07 (1.16-3.70) and 3.17 (1.31-7.68), respectively. For IL-10 819C/T, the pooled ORs (95% CI) of the C versus T and CC versus TT were 1.27 (1.01-1.58) and 2.27 (1.32-3.89). For IL-10 592C/A, the comparison of subjects in the CC or CC/CA genotype versus AA homozygotes showed significant results (OR = 2.00, 95% CI: 1.24-3.23; OR = 1.80, 95% CI: 1.28-2.54). But, other gene polymorphisms did not reach statistical associations. IL-10 1082G/A, 819C/T and 592C/A polymorphisms might be risk factors for LC. TNF-α 308G/A, IL-6 174G/C, IL-1ß 31T/C, IL-1ß 511C/T, COX-2 8473T/C polymorphisms were not detected to be related to the risk for LC. Due to the limitation of the number of the studies, we should take the conclusion with caution. While, further studies are necessary for more precise association.

Association of Pro12Ala polymorphism in peroxisome proliferator-activated receptor gamma with polycystic ovary syndrome: a meta-analysis.

The association between Pro12Ala polymorphism in peroxisome proliferator-activated receptor gamma (PPAR) and polycystic ovary syndrome (PCOS) has been investigated in several studies, whereas results were often incompatible. We conducted a meta-analysis to evaluate the association of Pro12Ala polymorphism in PPAR with PCOS susceptibility. A meta-analysis was performed on the published studies before November, 2011. Meta-analysis was performed for genotypes CG versus CC, CG+GG versus CC and G allele versus C allele in a fixed effect model. The combined odds ratio (OR) with 95 % confidence interval (95 % CI) was calculated to estimate the strength of the association. A total of 13 studies including 1,598 cases and 1,881 controls were enrolled. Ultimately, sensitivity analysis demonstrated that, in total, there was no significant association between Pro12Ala polymorphism and PCOS in the contrast of G allele versus C allele OR = 0.84 (95 % CI 0.69-1.04) and in Europeans, no significant association in the comparison of G allele versus C allele (OR = 0.84, 95 % CI 0.67-1.06) was also indicated. In summary, according to the results of our meta-analysis, strictly, the Pro12Ala polymorphism did not significantly associate with PCOS, though the protective trend of G allele existed.

A meta-analysis of the association between cytokine gene polymorphisms and systemic sclerosis.

We conducted a comprehensive meta-analysis to quantitatively evaluate the association of cytokine gene polymorphisms with systemic sclerosis (SSc) susceptibility. Electronic databases were used to identify published studies before July 2011. In total, 23 case-control studies including 3524 SSc cases and 6086 healthy controls were included in the meta-analysis. We examined the relationship between five gene polymorphisms [cytotoxic T lymphocyte associated antigen 4 (CTLA-4) -1722T/C, CTLA-4 -318C/T, CTLA-4 +49A/G, angiotensin-converting enzyme I/D, STAT-4 rs7574865] and susceptibility to SSc. The combined odds ratio (OR) with 95% confidence interval (95% CI) was calculated to estimate the strength of the association in a fixed or random effect model. Heterogeneity and publication bias were also assessed. We found a significant association between SSc and STAT rs7574865 (TT vs. GG: OR 0.44, 95% CI 0.36-0.54; TT vs. TG + GG: OR 0.48, 95% CI 0.39-0.59; TT + TG vs. GG: OR 0.74, 95% CI 0.66-0.83; T vs. G: OR 0.72, 95% CI 0.66-0.79), but there were no other statistically significant associations with other gene polymorphisms. Our study suggested that SSc is associated with STAT gene rs7574865 polymorphism.

Regional differences and the driving mechanism of relationships between rural household livelihood and ecosystem services:A case study in upstream watershed of Miyun Reservoir, China.

It is of great significance to link ecosystem and rural household welfare, with the aim to develop different strategies of rural household livelihood management and regional sustainable deve-lopment. Based on 1754 questionnaires of rural households in Beijing and Hebei within the upstream watershed of Miyun Reservoir, we analyzed the relationships between rural household welfare (defined by total income per rural household) and ecosystem reliance (expressed by an index of dependence on ecosystem services) by statistical and econometric methods. The relationships between rural household welfare and ecosystem reliance could be classified into four types, but with significant differences between Beijing and Hebei within the watershed. The rural household type of high welfare and low dependence had the highest proportion (33.9%) in Beijing. The average annual income and livelihood capitals of rural households in Beijing was significantly higher than that of Hebei Province. In Hebei Province, the dominant type was low welfare and high dependency (39.1%) that was the least popular one. The quality of human capital quality, social capital, and financial capital, which were crucial to human well-being, were significantly lower than that of Beijing households. The income of rural households in Hebei mainly depended on agricultural production (41.2%), which led to higher land utilization intensity. The natural resource and human capital quality significantly influenced rural household livelihood in Hebei. Maintaining suitable family size and age structure, improving education and skill levels, and strengthening payment for ecosystem services within low welfare households would be the key to form a good relationship between ecosystems and household welfare (the type of high welfare and low dependency).

Dynamic gadoteridol-enhanced MR imaging in the end of growing long bone of piglets.

BACKGROUND: It is of value to identify the non-invasive means that can accurately reflect the blood supply of epiphysis and is more sensitive in detection of early ischemia of epiphysis than the conventional gadoteridol (Gd)-enhanced SE T1WI. The aim of this study was to evaluate the blood supply of various anatomic regions at the end of normal growing long bone using dynamic Gd-enhanced MR imaging and compare the sensitivities between dynamic Gd-enhanced MR imaging and conventional Gd-enhanced SE T1WI in the detection of decreased blood perfusion of early epiphyseal ischemia. METHODS: Twenty-seven two-week-old piglets were used in this study. For the study of the end of normal growing long bone, unilateral MR imaging of the distal femur and proximal tibia was performed on eleven piglets. The comparison was made among various anatomic regions (physeal and epiphyseal cartilage, metaphyseal spongiosa, the secondary ossification center and metaphysis) using MRI in terms of the enhancement ratio and speed. Their relationships with the histological findings, including RBC/mm(2) and vessel distribution, were evaluated. To examine ischemic femoral head, 16 piglets were divided into two groups, with the control group having 8 piglets (involving 16 normal hips) and an ischemic group having 8 piglets (involving 16 hips with hyperabduction). In the ischemic group, MR imaging was performed on the hips in the hyperabduction immobilized persistently for 30 minutes. After MRI, the piglets were allowed to ambulate freely for 1 day and the same MR scanning was then repeated in a neutral position. The difference in enhancement ratio and speed of the femoral head between the control and ischemic group were evaluated. RESULTS: With regard to the end of normal growing long bone, the enhancement ratio of the metaphyseal spongiosa was greatest among all the anatomic regions (P < 0.001). The enhancement ratio of physeal cartilage was greater than that of epiphyseal cartilage (P < 0. 001), which was the lowest in all tissues (P < 0.001). The enhancement speed of the spongiosa was greater than that of physis but the difference was not significant (P > 0.05). The enhancement speed of physis was greater than that of epiphyseal cartilage (P < 0.05), which was the lowest among all the tissues (P < 0.05). The enhancement ratio and speed were found to be related to the histological findings, including RBC/mm(2) (R > 0.75) and distribution of vessels in the tissues. With ischemic femoral head, the enhancement ratios of physis, anterior part and posterior part of capital femoral epiphysis were significantly lower (P < 0.05) and enhanced more slowly (P < 0.05) than those of normal femoral head on dynamic Gd-enhanced MR imaging. On conventional Gd-enhanced SE T1WI, however, no apparent decrease in enhancement ratio and speed in ischemic hips was found (P < 0.05), when they were compared with those in the normal hips. CONCLUSIONS: Dynamic gadoteridol-enhanced MR imaging can reveal the blood supply in various anatomic regions of the end of normal growing long bone. It is more sensitive than conventional Gd-enhanced SE T1WI in the detection of early epiphyseal ischemia.

HIST1H3D: A promising therapeutic target for lung cancer.

HIST1H3D gene encodes histone H3.1 and is involved in gene-silencing and heterochromatin formation. HIST1H3D expression is upregulated in primary gastric cancer tissue. In this study, we explored the effects of HIST1H3D expression on lung cancer, and its mechanisms. HIST1H3D expression was measured by immunohistochemistry and RT-PCR in lung cancer tissues and human lung cancer cell lines. Cell proliferation was assessed by MTT assay. Flow cytometric analysis was used to determine cell cycle distribution and apoptosis. Levels of related proteins were detected by western blotting. Bioinformatics analysis was performed to investigate related signaling pathways. cDNA microarray analysis was performed to identify differentially expressed genes following HIST1H3D knockdown. HIST1H3D expression was upregulated in lung cancer tissue samples and the H1299 human lung cancer cell line (P<0.01). Regulation of HIST1H3D expression in nucleus of cells in lung cancer tissues was significant associated with tumor stage (P=0.02) and lymph node metastases (P=0.04). Downregulation of HIST1H3D expression led to suppression of proliferation and colony forming ability, cell cycle arrest at the G0/G1 phase, and promotion of cell apoptosis. The microarray data revealed 522 genes that were differentially expressed after HIST1H3D knockdown in H1299 cells. These genes were shown to be linked to numerous pathways, including the cell cycle, p53 signaling, and MCM. Western blot analysis confirmed upregulated expression of the THBS1 and TP53I3 genes, and downregulated expression of the CDK6, CDKN1 and CCNE2 genes. In conclusion, our results suggest that HIST1H3D is highly expressed in lung cancer cell lines and tissues. Furthermore, HIST1H3D may be important in cell proliferation, apoptosis and cell cycle progression, and is implicated as a potential therapeutic target for lung cancer.

Testin is a tumor suppressor in non-small cell lung cancer.

The Testin gene was previously identified in the fragile chromosomal region FRA7G at 7q31.2. It has been implicated in several types of cancers including prostate, ovarian, breast and gastric cancer. In the present study, we investigated the function of the candidate tumor-suppressor Testin gene in non-small cell lung cancer (NSCLC). In NSCLC cell lines, we observed lower expression of Testin compared to that noted in normal human bronchial epithelial cells. MTT assays, flow cytometry, clonogenic assay and invasion assay showed that the overexpression of the Testin gene inhibited cancer cell proliferation, invasion and colony formation. In tumor xenograft models, Testin markedly inhibited lung cancer cell xenograft formation and growth in athymic nude mice. Taken together, these data suggest that Testin plays an important role in the development and progression of NSCLC. Testin may be an effective novel target in NSCLC prevention and treatment.

Asbestos exposure and laryngeal cancer mortality.

OBJECTIVES/HYPOTHESIS: Occupational exposure to asbestos occurs in many workplaces and is well known to cause asbestosis, lung cancer, and mesothelioma. However, the link between asbestos exposure and other malignancies was not confirmed. The aim of the current meta-analysis was to provide a summary measure of risk for laryngeal cancer associated with occupational asbestos exposure. STUDY DESIGN: Systematic review and meta-analysis. METHODS: Electronic databases were searched for studies characterizing the association between asbestos and laryngeal cancer. Standardized mortality rate (SMR) with its 95% confidence interval (CI) of each study was combined using a fixed or random effect model. RESULTS: Significantly increased SMR for laryngeal cancer was observed when subjects were exposed to asbestos (SMR = 1.69, 95% CI = 1.45-1.97, P < .001), with little evidence of heterogeneity among studies (Q = 15.39, P = .803, I(2) = 0.0%). Effect estimates were larger for cohorts controlling for male subjects, Europe and Oceania, mining and textile industries, exposure to crocidolite, long study follow-up (>25 years), and SMR for lung cancer > 2.0. Publication bias was not detect by Begg test (P = .910) and Egger test (P = .340). CONCLUSIONS: Our study supports the association of exposure to asbestos with an increased risk of laryngeal cancer mortality among male workers. LEVEL OF EVIDENCE: NA Laryngoscope, 126:1169-1174, 2016.