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To investigate radiotherapy (RT)-related brain network changes in patients with nasopharyngeal carcinoma (NPC) over time and develop least absolute shrinkage and selection operator (LASSO)-based multivariable normal tissue complication probability (NTCP) models to predict RT-related brain network changes.36 NPC patients were followed up at four timepoints: baseline, within 3 months (acute), 6 months (subacute), and 12 months (delayed) post-RT. 15 comparable healthy controls (HCs) were finally included and followed up in parallel. Functional neuroimaging data, dose-volume parameters of bilateral temporal lobes and Montreal Cognitive Assessment (MoCA) were acquired. Graph theoretical analysis and mixed-design analysis of variance were performed to investigate how the brain global and nodal changes were affected by RT. Multivariate logistic regression NTCP models were developed. LASSO with nested cross-validation strategy was used to select features. The relationships between network changes and MoCA changes were also examined.Significant changes were detected in nodal efficiency (NE) in NPC patients but not in HCs over time. Altered NE was distributed in the bilateral frontal, temporal lobes and the right insula, which showed a "decrease-increase/recovery" pattern over time. Among all models, the model for predicting NE changes of STG.R showed a relatively good performance (area under the receiver operating curve: 0.68), and DOur findings indicate that RT-induced brain injury begin at the acute period and follow a recovery over time. Furthermore, our study presents prediction models for brain dysfunction based on the dosimetric and clinical parameters.

Most critically ill patients experience malnutrition, resulting in a poor prognosis. This study aimed to evaluate the association of prealbumin (PAB) with the prognosis for severely and critically ill coronavirus disease 2019 (COVID-19) patients and explore factors related to this association. Patients with laboratory-confirmed COVID-19 from West Campus of Union Hospital in Wuhan from January 29, 2020 to March 31, 2020 were enrolled in this study. Patients were classified into the PAB1 (150–400 mg/L; N = 183) and PAB2 (< 150 mg/L; N = 225) groups. Data collection was performed using the hospital’s electronic medical records system. The predictive value of PAB was evaluated by measuring the area under the receiver-operating characteristic (AUROC) curve. Patients were defined as severely or critically ill based on the Guidance for COVID-19 (7th edition) by the National Health Commission of China. During this analysis, 316 patients had severe cases and 65 had critical cases. A reduced PAB level was associated with a higher risk of mortality and a longer hospital stay. The AUROC curve for the prognosis based on the PAB level was 0.93, with sensitivity of 97.2% and specificity of 77.6%. For severe cases, a lower level of PAB was associated with a higher risk of malnutrition, higher NK cell counts, and lower B lymphocyte counts; these factors were not significant in critical cases. C-reactive protein and nutritional status mediated the association between PAB and prognosis. This retrospective analysis suggests that the PAB level on admission is an indicator of the prognosis for COVID-19.

To analyze the difference in clinical efficacy of minimally invasive transforaminal lumbar interbody fusion (MIS-TLIF) under Quadrant channel system combined with microscope and percutaneous pedicle screw in the treatment of degenerative lumbar spondylolisthesis.A total of 114 patients with single-segment degenerative lumbar spondylolisthesis from June 2015 to February 2019, were divided into three groups according to the surgical methods, such as the MIS-TLIF under the microscope surgery group ( microscope group), MIS-TLIF combined with percutaneous pedicle screw technique surgery group(percutaneous group) and posterior lumbar interbody fusion surgery group (open group). In the microscope group, there were 12 males and 26 females, aged from 42 to 83 years with an average of (63.29±9.09) years. In the percutaneous group, there were 16 males and 22 females, aged from 45 to 82 years with an average of (63.37±7.50) years. In the open group, there were 12 males and 26 females, aged from 51 to 82 years with an average of (63.76±8.21) years. The general conditions of operation, such as operation time, intraoperative blood loss, postoperative drainage, length of surgical incision, frequency of intraoperative fluoroscopy and postoperative time of lying in bed were recorded to analyze the differences in surgical related indicators. Visual analogue scale (VAS) of waist and leg pain in preoperative and postoperative period (3 days, 3 months, 6 months and 12 months) were recorded to evaluate pain remission;Oswestry Disability Index(ODI), Japanese Orthopaedic Association (JOA) score were recorded to evaluate the recovery of waist and leg function on preoperative and postoperative 12 months. The lumbar spondylolisthesis rate and intervertebral height at 12 months after operation were recorded to evaluate the reduction of spondylolisthesis. The Siepe intervertebral fusion standard was used to analyze the intervertebral fusion rate at 12 months after operation.①All 114 patients were followed up more than 1 year, and no complications related to incision infection occurred. In the microscope group, there was 1 case of subcutaneous effusion 8 days after operation. After percutaneous puncture and drainage, waist compression, and then the healing was delayed. In the percutaneous group, 2 cases of paravertebral muscle necrosis occurred on the side of decompression, and the healing was delayed after debridement. In open group, there was 1 case of intraoperative dural tear, which was packed with free adipose tissue during the operation. There was no postoperative cerebrospinal fluid leakage and other related complications.① Compared with microscope group, percutaneous group increased in operation time, intraoperative blood loss, postoperative wound drainage, surgical incision length, intraoperative fluoroscopy times, and postoperative bed rest time. In open group, intraoperative blood loss, postoperative wound drainage, surgical incision length, and postoperative bed rest time increased, but the intraoperative fluoroscopy time decreased. Compared with percutaneous group, the intraoperative blood loss, wound drainage, surgical incision length, and postoperative bed rest time in open group increased, but operative time and the intraoperative fluoroscopy time decreased(The MIS-TLIF assisted by microscope and the MIS-TLIF combined with percutaneous pedicle screw are safe and effective to treat the degenerative lumbar spondylolisthesis with single-segment, and the MIS-TLIF assisted by microscope may be more invasive, cause less blood loss and achieve better clinical efficacy.

The emphasis of our study was to determine the physiological function of miR-1224-5p in rectal cancer (RC) and its in-depth mechanism. First, the expression of miR-1224-5p in RC tissues was analyzed using public data from the TCGA database. Then, miR-1224-5p expression in RC cell lines SW480 and SW837 was measured using the qRT-PCR assay. The subsequent CCK-8 assay was executed to assess the function of miR-1224-5p in the viability of the RC cell. Bioinformatics prediction prompted that SLC29A3 may be a potential target gene for miR-1224-5p. Western blotting and dual-luciferase reporter assays were performed to affirm the above forecasting. Kaplan-Meier analysis and Cox multivariate analysis were carried out to assess the relationship between SLC29A3 and prognosis. Finally, CCK-8, colony formation assay, and transwell assay were used for functional analysis of miR-1224-5p/ SLC29A3 axis in vitro. MiR-1224-5p was expressed at low levels in RC tissues and cell lines. Up-regulation of miR-1224-5p inhibited SW480 cell viability, while inhibition of miR-1224-5p enhanced the viability of SW837 cells. What is more, we affirmed that miR-1224-5p could direct target SLC29A3, which was expressed at high levels in RC tissues. In addition, SLC29A3 could be used as an independent predictive factor of prognosis in patients with RC, and the higher SLC29A3 expression, the lower survival rate. Finally, cellular functional experiments evidenced that miR-1224-5p mimic can reduce the cell viability, invasion, and migration, while overexpression of SLC29A3 presented an opposite effect. Importantly, co-transfection experiments indicated that SLC29A3 can reverse miR-1224-5p-mediated inhibition in the malignant progression of RC cells. Our work raised the possibility that miR-1224-5p functioned as a tumor suppressor in RC, which achieved its function via targeting SLC29A3.

To observe the genotypes and composition ratio of thalassemia in couples of reproductive age, and provide a reference for the prevention and control of thalassemia in Haikou.Gene diagnosis was performed in 2 494 subjects who were screened for thalassemia before marriage or prenatal by cross-breakpoint PCR, PCR-reverse dot hybridization, and PCR-electrophoresis.A total of 1 037 thalassemia gene carriers were detected in 2 494 samples, with a detection rate of 41.57%, of which 75.02% was α-thalassemia, 18.61% was β-thalassemia, and 6.36% was α-β complex thalassemia. There were 778 cases of α-thalassemia, mainly of deletion type, accounting for 76.99% (599/778). Twenty genotypes were detected, the highest three was --In Haikou city, the gene carrying rate of thalassemia is very high, and the genotype distribution is different from other cities in Hainan Province, attention should be paid to the impact of population inflow on the frequency spectrum change of local thalassemia gene.海口地区2 494例育龄夫妇地中海贫血基因检测结果分析.分析海口地区育龄夫妇地中海贫血（简称地贫）基因型和构成比，为本地区的地贫防控工作提供参考。.采用跨越断裂点PCR、PCR-反向点杂交及PCR-电泳法，对婚前或产前地贫筛查的2 494例被检者进行基因检测。.2 494例样本中共检出1 037例地贫基因携带者，检出率为41.57%，其中α-地贫、β-地贫及α-β复合型地贫 分别占75.02%、18.61%及6.36%。α-地贫778例，以缺失型为主，占76.99%（599/778），共检出20种基因型，占比最高的依次是--海口市育龄人群的地贫基因携带率较高，基因型分布与本省其他市县有一定差异，需注意人口流入对本地区地贫基因频谱改变的影响。.

Background Recent studies have suggested that pregnancy-associated plasma protein-A (PAPP-A) is involved in the pathogenesis of atherosclerosis. This study aim is to investigate the role and mechanisms of PAPP-A in reverse cholesterol transport (RCT) and inflammation during the development of atherosclerosis. Methods and Results: PAPP-A was silenced in apolipoprotein E (apoE-/-) mice with administration of PAPP-A shRNA. Oil Red O staining of the whole aorta root revealed that PAPP-A knockdown reduced lipid accumulation in aortas. Oil Red O, hematoxylin and eosin (HE) and Masson staining of aortic sinus further showed that PAPP-A knockdown alleviated the formation of atherosclerotic lesions. It was found that PAPP-A knockdown reduced the insulin-like growth factor 1 (IGF-1) levels and repressed the PI3K/Akt pathway in both aorta and peritoneal macrophages. The expression levels of LXRα, ABCA1, ABCG1, and SR-B1 were increased in the aorta and peritoneal macrophages from apoE-/-mice administered with PAPP-A shRNA. Furthermore, PAPP-A knockdown promoted RCT from macrophages to plasma, the liver, and feces in apoE-/-mice. In addition, PAPP-A knockdown elevated the expression and secretion of monocyte chemoattractant protein-1 (MCP-1), interleukin-6 (IL-6), tumor necrosis factor-α, and interleukin-1β through the nuclear factor kappa-B (NF-κB) pathway. Conclusions The present study results suggest that PAPP-A promotes the development of atherosclerosis in apoE-/-mice through reducing RCT capacity and activating an inflammatory response.

The study aims to investigate whether there is difference in pre-treatment white matter parameters in treatment-resistant and treatment-responsive schizophrenia. Diffusion tensor imaging (DTI) was acquired from 60 first-episode drug-naïve schizophrenia (39 treatment-responsive and 21 treatment-resistant schizophrenia patients) and 69 age- and gender-matched healthy controls. Imaging data was preprocessed via FSL software, then diffusion parameters including fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD) and radial diffusivity (RD) were extracted. Besides, structural network matrix was constructed based on deterministic fiber tracking. The differences of diffusion parameters and topology attributes between three groups were analyzed using analysis of variance (ANOVA). Compared with healthy controls, treatment-responsive schizophrenia showed altered white matter mainly in anterior thalamus radiation, splenium of corpus callosum, cingulum bundle as well as superior longitudinal fasciculus. While treatment-resistant schizophrenia patients showed white matter abnormalities in anterior thalamus radiation, cingulum bundle, fornix and pontine crossing tract relative to healthy controls. Treatment-resistant schizophrenia showed more severe white matter abnormalities in anterior thalamus radiation compared with treatment-responsive patients. There was no significant difference in white matter network topological attributes among the three groups. The performance of support vector machine (SVM) showed accuracy of 63.37% in separating the two patient subgroups (本文旨在探索首发未用药状态下，抗精神病药物治疗不同反应的精神分裂症患者白质参数是否存在不同模式的改变。采集 60 例首发未用药精神分裂症患者（药物治疗有效者 39 例，难治者 21 例）与 69 例年龄、性别匹配的健康对照的磁共振弥散张量成像（DTI）数据，运用 FSL 软件进行数据处理，提取反映白质微结构完整性的参数并进行确定性的纤维追踪，并基于纤维追踪的结果构建网络矩阵，通过方差分析比较三组间白质参数及白质连接网络拓扑属性的差异。结果发现相比于健康对照，药物治疗有效组白质异常主要表现在丘脑前辐射、胼胝体压部、扣带束和上纵束，而药物难治组白质异常主要分布在丘脑前辐射、扣带束、穹隆和脑桥交叉纤维束。药物难治组在丘脑前辐射表现出比药物治疗有效组更严重的白质异常。此外，三组被试之间白质连接网络拓扑属性差异无统计学意义。支持向量机（SVM）的结果显示两个患者亚组之间分类的准确度为 63.37%（

Objective. This study aimed to research the impact that a coal mine lighting environment has on human safety behavior in an underground coal mine. Methods. We built a coal mine lighting simulation ...

Schizophrenia is a serious mental illness for which the mainstay of treatment is antipsychotics. Up to 30% of schizophrenia patients show limited response to antipsychotics. Identifying these patients before treatment could guide individualized treatment for improving outcomes in those not likely to show robust benefit from antipsychotics. Diffusion tensor imaging was performed with 56 drug-naïve first-episode schizophrenia patients and 69 matched healthy controls. Patients were followed clinically after one-year of antipsychotic treatment and classified at that point into groups of 17 poor outcome and 39 good outcome patients based on whether they showed at least a 50% reduction of Positive and Negative Syndrome Scale (PANSS) scores from baseline. Tract-based spatial statistics were applied to assess white matter microstructure in the two patient subgroups and healthy controls. Poor outcome patients showed reduced pretreatment fractional anisotropy (FA) in left cingulum and anterior thalamic radiation and increased FA in right superior and inferior longitudinal fasciculus compared with good outcome patients. FA in each of these four tracts was decreased in both patient subgroups relative to healthy controls. Considered together, the four altered tracts showed promising ability to differentiate poor from good outcome patients (sensitivity = 74.4%, specificity = 95.2%, AUC = 0.90, p 0.001), and superior prediction of clinical outcome to baseline PANSS scores (p 0.015). Prediction of outcomes using DTI features was not related to duration of untreated psychosis. Baseline alterations in white matter integrity may identify schizophrenia patients less likely to respond to treatment, which could be useful information for stratification in clinical trials and for individualized treatment planning.

Introduction. This study aimed to perform an in-depth analysis of a catastrophic coach crash that occurred on the Chinese expressway, and thus draw useful lessons to avoid similar mistakes. Methods. Various causes were identified from the investigation report based on a proposed accident causation model, which provides a universal pathway for accident analysis from the individual level to the organizational level. Results. Driver error in an emergency affected by fatigue and speeding led directly to the crash. Accordingly, drivers in coaches should be monitored effectively and their unsafe acts must be corrected in a timely manner to avoid the formation of unsafe habits. Based on individual flaws, weaknesses in the construction of the organizational safety management system and safety culture were further deduced and discussed. Conclusion. The work and rest system, as well as the dynamic monitoring system for drivers, should be perfected strictly according to the regulations. Additionally, external factors regarding deficiencies in the design and management of the expressway and the supervision of the transportation company also had great impact on this crash. In summary, more efforts should be taken regarding root causes at the organizational level, regardless of internal or external factors.

Esophageal cancer (EC) ranks the eighth in morbidity and the sixth in mortality around the whole world, which is an aggressive malignancy. To authenticate potential therapeutic targets for EC is therefore imperative. Although miR-301b might display changed expression in esophageal adenocarcinoma by utilizing Taqman miRNA profiling analysis, much less is known about the impact of miR-301b in EC.By analyzing the data of 187 cancer tissues and 13 normal samples from TCGA database, we discovered that miR-301b was highly expressed in EC tissues. Then, RT-qPCR determined that miR-301b was up-regulated in EC cell lines (ECA109, JAR, TE-1 and OE33). Besides, miR-301b expression level was higher in ESCC cell line-TE-1 cells and lower in ESCC cell line-ECA109 cells compared to other EC cell lines. Hence, ECA109 cell line was used to up-regulate miR-301b expression while TE-1 cell line was applied to down-regulate miR-301b expression in the subsequent experiments. Additionally, OE33, as an ECA cell line, was applied to upregulate miR-301b expression to reflect the influence of miR-301b overexpression on EC progression. More interestingly, miR-301b appeared to act as a promoting effect on the proliferation of EC cells, which was tested by CCK8. Dystrobrevin alpha (DTNA) was a targeting gene of miR-301b, which was predicted by the websites of miRanda, miRWalk and TargetScan. Additionally, DTNA was low expressed in EC tissues and was an independent predictor of EC. Meanwhile, the low expression of DTNA was related to worse overall survival in EC patients. The Pearson correlation coefficient analyzed that DTNA expression was negatively correlated with miR-301b. Furthermore, RT-qPCR and western blotting assays ulteriorly indicated that DTNA was negatively modulated by miR-301b. The facilitating impact of miR-301b re-expression on ECA109 and OE33 cell growth, invasion and migration was receded by DTNA over-expression, whilst the repressive effect of miR-301b ablation on TE-1 cell growth, invasion and migration was inversed by DTNA silencing. Overexpression of miR-301b accelerated EC cell growth, migration and invasion through targeting DTNA.Above all, we concluded that miR-301b was concerned with the progression of EC via regulating DTNA, suggesting that miR-301b and its target gene, DTNA, might serve as predictive biomarkers for EC therapy.

Hippocampal volume deficits have been reported in chronically-treated schizophrenia patients, however, the longer-term effects of antipsychotic medications on hippocampal anatomy are unclear. This case-control study investigated volume differences in hippocampal subfields of never-treated and antipsychotic-treated patients with long-term schizophrenia. High spatial-resolution T1-weighted magnetic resonance images were collected from 29 never-treated and 40 antipsychotic-treated patients with long-term schizophrenia matched for illness duration (all ≥ 5 years), and 40 demographically-matched healthy controls. Hippocampal subfield volumes were measured using FreeSurfer v6.0, compared across groups and between hemispheres, and correlated with clinical features. Volume reductions were found in both patient groups compared to healthy controls in 8 of 26 hippocampal subfields (Cohen's d = 0.46 - 1.17, P = .001 - .03), and more diffusely and obviously in never-treated than treated patients (Cohen's d = 0.50 - 0.90, P = .001 - .04). Greater right-than-left volumes were seen in treated patients and healthy controls in 11 of 13 subfields (T = 2.30 - 7.29, P = .001 - .03), but not in never-treated patients, in whom the volumes were reduced more on the right than on the left. Subfield volumes were negatively correlated with symptom severity and illness duration, and declined with age in never-treated patients. Findings indicate clinically-relevant and age-related volume reductions in hippocampal subfields of never-treated patients with long-term schizophrenia. Broader and greater subfield deficits in never-treated than treated patients, especially in the right hippocampus, suggest that long-term antipsychotic treatment may benefit hippocampal structures over the longer-term course of illness.

In this paper, we propose a novel hyper-Laplacian regularized multiview subspace clustering with low-rank tensor constraint method, which is referred as HLR-MSCLRT. In the HLR-MSCLRT model, the subspace representation matrices of different views are stacked as a tensor, and then the high order correlations among data can be captured. To reduce the redundancy information of the learned subspace representations, a low-rank constraint is adopted to the constructed tensor. Since data in the real world often reside in multiple nonlinear subspaces, the HLR-MSCLRT model utilizes the hyper-Laplacian graph regularization to preserve the local geometry structure embedded in a high-dimensional ambient space. An efficient algorithm is also presented to solve the optimization problem of the HLR-MSCLRT model. The experimental results on some data sets show that the proposed HLR-MSCLRT model outperforms many state-of-the-art multi-view clustering approaches.

Gram-positive bacteria are responsible for a broad range of infectious diseases, and the emergency and wide spread of drug-resistant Gram-positive pathogens including MRSA and MRSE has caused great concern throughout the world. 4-Quinolones which are exemplified by fluoroquinolones are mainstays of chemotherapy against various bacterial infections including Gram-positive pathogen infections, and their value and role in the treatment of bacterial infections continues to expand. However, the resistance of Gram-positive organisms to 4-quinolones develops rapidly and spreads widely, making them more and more ineffective. To overcome the resistance and reduce the toxicity, numerous of 4-quinolone derivatives were synthesized and screened for their in vitro and in vivo activities against Gram-positive pathogens, and some of them exhibited excellent potency. This review aims to outlines the recent advances made towards the discovery of 4-quinolone-based derivatives as anti-Gram-positive pathogens agents and the critical aspects of design as well as the structure-activity relationship of these derivatives. The enriched SAR paves the way to the further rational development of 4-quinolones with a unique mechanism of action different from that of the currently used drugs to overcome the resistance, well-tolerated and low toxic profiles.

It is well known that liver cancer is a highly aggressive malignancy with poor prognosis. Andrographolide (AD), a major bioactive component of Andrographis paniculata (Burm. F.), is a potential anti-cancer pharmacophore and the synthesis of AD derivatives with better cytotoxicity to cancer cells has attracted considerable attentions. In the present study, we evaluated the in vivo inhibitory effects of ADN-9, a 15-benzylidene substituted derivative of AD, on the growth and metastasis of murine hepatoma H22 using an orthotopic xenograft model and a subcutaneous xenograft model, and we further studied the anti-angiogenic action and the related mechanisms of ADN-9 in vivo and in vitro. Importantly, ADN-9 remarkably suppressed the growth and metastasis of both orthotopic and subcutaneous xenograft tumors, and the serum AFP level in orthotopic hepatoma-bearing mice treated with 100mg/kg ADN-9 (ig.) was decreased to the normal level. We also found that ADN-9 showed stronger abilities than AD in shrinking tumors, suppressing the invasion and metastasis of H22 cells, decreasing the MVD and promoting tumor cell apoptosis in subcutaneous xenograft of mice. Additionally, ADN-9 exhibited stronger inhibitory activity than AD against the migration and VEGF-induced capillary-like tube formation in HUVECs, which was further proved to be associated with attenuating VEGF/VEGFR2/AKT signaling pathway. The present research provides the first evidence that a 15-substituted AD derivative is more promising than the parent compound in therapeutic treatment of liver cancer.

Parental migration has caused millions of children left behind, especially in China and India. Left-behind children (LBC) have a high risk of mental disorders and may present negative life outcomes in the future. However, little is known whether there are cerebral structural alterations in LBC in relative to those with parents. This study is to explore the effect of parental migration on brain maturation by comparing gray matter volume (GMV) and fractional anisotropy (FA) of LBC with well-matched non-LBC. Thirty-eight LBC (21 boys, age = 9.60 ± 1.8 years) and 30 non-LBC (19 boys, age = 10.00 ± 1.95 years) were recruited and underwent brain scans in 3.0 T MR. Intelligence quotient and other factors including family income, guardians’ educational level and separation time were also acquired. GMV and FA were measured for each participant and compared between groups using 2-sample t-tests with atlas-based analysis. Compared to non-LBC, LBC exhibited greater GMV in emotional and cortico-striato-thalamo-cortical circuits, and altered FA in bilateral superior occipitofrontal fasciculi and right medial lemniscus (p < 0.05, Cohen’s d > 0.89, corrected for false-discovery rate). Other factors including family income, guardians’ educational level and separation time were not associated with these brain changes. Our study provides empirical evidence of altered brain structure in LBC compared to non-LBC, responsible for emotion regulation and processing, which may account for mental disorders and negative life outcome of LBC. Our study suggests that absence of direct biological parental care may impact children’s brain development. Therefore, public health efforts may be needed to provide additional academic and social/emotional supports to LBC when their parents migrate to seeking better economic circumstances, which has become increasingly common in developing countries.

Laryngeal cancer is one of the most malignant cancers among the head and neck malignant tumors. Abnormal expression of microRNAs (miRNAs) contributes to cancer development through regulating proliferation and apoptosis of cancer cells. In this study, we aim to explore the roles of microRNA-141 (miR-141), Homeobox C6 (HOXC6) and TGF-β signaling pathway in epithelial-mesenchymal transition (EMT) and lymph node metastasis in laryngeal cancer. Initially, we identified differentially expressed genes in laryngeal cancer, among which HOXC6 was identified. Then the target miRNA of HOXC6 was predicted and verified. Next, expression of miR-141, HOXC6, TGF-β1, Smad3, Vimentin and Snail in cancer tissues was detected. Then, AMC-HN-8 cells were transfected with miR-141 mimic, miR-141 inhibitor and HOXC6-siRNA to investigate specific role of miR-141, HOXC6 and TGF-β signaling pathway in laryngeal cancer in vivo and in vitro. Our results showed that HOXC6 was a target gene of miR-141, which was downregulated in laryngeal cancer. Besides, overexpression of miR-141 could downregulate HOXC6 and inhibit the TGF-β signaling pathway. Upregulation of miR-141 or silencing of HOXC6 can repress EMT, viability, migration and invasion abilities of laryngeal cancer cells. In addition, upregulation of miR-141 inhibited the tumor growth and lymph node metastasis in vivo. In summary, our findings demonstrated that upregulated miR-141 decreased HOXC6 expression, and inhibited the TGF-β signaling pathway, EMT and lymph node metastasis in laryngeal cancer, which is of clinical significance in the treatment of laryngeal cancer.

A large body of evidence indicates that both the altered cytokines that mediate the immune-inflammatory process and abnormal gray matter are associated with schizophrenia. Whether peripheral cytokines are related to cerebral structural abnormality remains unclear. Therefore, we aimed to investigate the association of peripheral cytokine levels with gray matter abnormalities at the whole brain level in schizophrenia. Forty-four outpatients with schizophrenia and 44 controls were recruited. The serum levels of interleukin-1 beta (IL-1β), IL-2, IL-6, IL-8, interferon-gamma (IFN-γ), transforming growth factor-beta (TGF-β), and IL-10 were measured using a quantitative chemiluminescence assay. High-resolution T1 weighted images were acquired from all subjects and processed using FreeSurfer software to obtain the cortical thickness, surface area, and cortical and subcortical gray matter volumes. The cytokines and cerebral structures were compared between patients and controls using analysis of covariance (ANCOVA). The association between the cytokines and whole cerebral structures was performed using stepwise linear regression. Patients had higher levels of IL-2, IL-6, IL-8, and IL-10 than controls. In patients, the IL-6 level was significantly associated with the cortical thickness in the left pars opercularis, right pars triangularis, left superior temporal gyrus, and right middle temporal gyrus, which showed structural differences between the two groups. Altered cytokine levels may be associated with particular but not all cortical abnormalities in schizophrenia, especially IL-6, which was significantly associated with the abnormal cortical thickness of the bilateral Broca's area and temporal gyrus, which provided neuroimaging evidence to support the relationship between peripheral cytokines and the cerebral cortex in schizophrenia.

Introduction Currently, there is a lack of specific analytical tools for general aviation accidents (GAAs). This has led to loopholes in the prevention of GAAs. Methods A Swiss Cheese model for general aviation (SCM-GA) is proposed to identify the human and organizational factors involved in GAAs. In the proposed SCM-GA, 5 categories, 45 subcategories, a general aviation safety management system (GA-SMS) and safety culture were developed based on the classic accident causation models combined with the laws and regulations and safety management practices in the general aviation industry. Results One GAA was analyzed using SCM-GA. The human and organizational causes revealed by SCM-GA were more complete than the causes revealed through the accident report. The identification results of the deficiencies in the subcategories of GA-SMS and the safety culture were more consistent with the requirements in the general aviation laws and regulations than the organizational factors in the accident report. Based on the subcategories of SCM-GA, 41 GAAs that occurred between 1996 and 2010 in China were statistically analyzed and χ2 test analyses were performed to estimate the statistical strength of the association between two adjacent subcategories of SCM-GA. The results showed that two adjacent subcategories of SCM-GA were significantly associated. They helped to determine the hidden problems in the accident report based on the path of accident. Conclusions SCM-GA is an accident analysis tool that can comprehensively analyze the human and organizational deficiencies involved in GAAs. The accident causes revealed by SCM-GA were more consistent with the general aviation safety management practices. Practical applications General aviation companies should establish their own GA-SMS and safety culture based on the subcategories developed herein. Using SCM-GA for routine safety inspection and accident investigation will help the management and the staff make effective safety decisions to effectively prevent GAAs.

Human and organizational factors have been proven to be the prime causes of Chinese hazardous chemical accidents (HCAs). A modified version of the Human Factors Analysis and Classification System (HFACS), namely the HFACS-Hazardous Chemicals (HC), was developed to identify the human factors involved in Chinese HCAs. The '8.12' Tianjin Port fire and explosion, the costliest HCA in recent years, was reanalyzed using this framework, and the results were compared with the official accident inquiry report to determine their differences related to the identification of human and organizational factors. The study revealed that interacting human factors from different levels in Ruihai Company led to this catastrophe, and the inquiry report had limitations in the identification of human factors and the guidance for similar accident prevention. This study showed the applicability of the HFACS-HC in HCA analyses as well as the necessity to recommend this approach for future HCA investigations.

Serum Epstein-Barr virus DNA has been approved for diagnosing nasopharyngeal carcinoma (NPC). The goal of this meta-analysis was to evaluate the clinical value of the serum Epstein-Barr virus DNA in the diagnosis of NPC. The PubMed, Embase, Web of Knowledge, Chinese Wanfang Med Online, and National Knowledge Infrastructure (CNKI) databases were searched to identify suitable studies. The pooled sensitivity, specificity, positive likelihood ratio (LR+), negative likelihood ratio (LR-), and diagnostic odds ratio (DOR) of the serum Epstein-Barr virus DNA for the diagnosis of NPC were calculated. Summary receiver operating characteristic curves were used to summarize overall test performances. Meta-Disc 1.4 and Stata 12.0 softwares were used to analyze the data. A total of 2,520 patients from ten trials were subjected to meta-analysis. The summary estimates of the serum Epstein-Barr virus DNA for NPC diagnosis were as follows: sensitivity 0.69 (95 % confidence interval (CI) 0.65-0.72), specificity 0.84 (95 % CI = 0.82-0.86), LR + 4.81 (95 % CI = 2.94-7.88), LR - 0.25 (95 % CI = 0.13-0.48), DOR 24.65 (95 % CI = 12.64-48.07), and area under the summary receiver operator characteristic (SROC) curve (AUC) was 0.8979. Our study demonstrates that the serum Epstein-Barr virus DNA could be a useful tumor marker for NPC diagnosis.

Introduction: Senior managers’ attitudes towards safety are very important regarding the safety practices in an organization. The study is to describe the current situation of senior managers′ attitudes towards safety in the Chinese coal industry. Method: We evaluated the changing trends as well as the reasons for these changes in the Chinese coal industry in 2009 and in 2014 with 168 senior manager samples from large Chinese state-owned coal enterprises. Evaluations of 15 safety concepts were performed by means of a questionnaire. Results and Conclusions: Results indicate that, in 2014, three concepts were at a very high level (mean > 4.5), and six were at a relatively high level (4.5 > mean > 4.0). Analyses of changing trends revealed that nine concepts improved significantly, while four greatly declined in 2014 compared to those in 2009. The data reported here suggest that the reasons for the significant improvement with respect to the nine concepts include the improvement in social and legal environments, the improvement of the culture of social safety, workers′ safety demands being met, and scientific and technical advances in the coal industry. The decline of the four concepts seemed to be caused by a poor awareness of managers in the coal industry that safety creates economic benefits, insufficient information on safety, inadequate attention to the development of a safety culture and safety management methods, and safety organizations and workers′ unions not playing their role effectively. Practical Applications: We therefore recommend strengthening the evidence that safety creates economic benefits, providing incentives for employees to encourage their participation in safety management, and paying more attention to the prevention of accidents in coal mines via safety organizations and unions. These results can provide guidelines for workers, industrialists, and government regarding occupational safety in the whole coal industry.

In the present study, andrographolide (Andro, 1) derivatives were screened to identify potent inhibitors against tumor-cell migration and invasion, and associated structure–activity relationships were studied. Compared to 1 , compounds 8a – 8d exhibited more potent activities against migration in SGC-7901, PC-3, A549, HT-29 and Ec109 cell lines. Improved activities against tumor-cell migration and invasion were proved to be associated with the down-regulation of MMPs.

Introduction This study develops an integrative model of safety management based on social cognitive theory and the total safety culture triadic framework. The purpose of the model is to reveal the causal linkages between a hazardous environment, safety climate, and individual safety behaviors. Method Based on primary survey data from 209 front-line workers in one of the largest state-owned coal mining corporations in China, the model is tested using structural equation modeling techniques. Results An employee's perception of a hazardous environment is found to have a statistically significant impact on employee safety behaviors through a psychological process mediated by the perception of management commitment to safety and individual beliefs about safety. Impact on industry The integrative model developed here leads to a comprehensive solution that takes into consideration the environmental, organizational and employees' psychological and behavioral aspects of safety management.

Objective To explore Notch3 mutation sites of Chinese patients with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). Methods Direct sequencing of all exons in Notch3 gene was performed on 12 unrelated suspected CADASIL cases from mainland China. Result A missense p.Arg587Cys (1759C>T) mutation in exon 11 was identified in 2 patients through genetic analysis. Conclusion Chinese patients with CADASIL of R587C mutation in exon 11 was firstly reported.

Background: Although enhanced external counterpulsation (EECP) showed short-term effects in improving coronary flow in patients with coronary slow flow (CSF), whether such improvement is durable remains uncertain, and the relationships between such improvement and changes in endothelial function as well as inflammatory markers have not been elucidated. Objectives: The aim of the present study was to investigate the effects of EECP on transthoracic coronary flow, flow-mediated dilatation (FMD), and high-sensitivity C-reactive protein (hsCRP) in patients with CSF. Methods: Forty-five patients with documented CSF underwent transthoracic Doppler echocardiography (TTDE) for the assessment of coronary diastolic peak flow velocity (DPFV) and coronary flow reserve (CFR), and measurements of FMD and hsCRP; they were then nonrandomly assigned to two groups. Subjects in the control group (n = 24) received only medical therapy, and those in the EECP group (n = 21) were additionally treated with the 36 one-hour sessions of EECP. After 8 weeks of medical/EECP therapy, TTDE, FMD, and hsCRP examinations were repeated, and TTDE was additionally repeated after the 6-month clinical follow-up. Results: In the EECP group, resting DPFV, hyperemic DPFV, and CFR were significantly increased shortly after therapy (p < 0.001) and the improvement was maintained up to the 6-month follow-up, whereas in the control group those variables were not statistically increased. Meanwhile, hsCRP significantly decreased and FMD increased after therapy in the EECP group (p < 0.001). In all subjects, CFR improvement was negatively correlated with hsCRP change and positively correlated with FMD increase (p < 0.001). Conclusions: EECP may have a durable effect in improving coronary flow in patients with CSF. Such improvement is related to the favorable effects of EECP on vascular inflammation and endothelial function.

1. Cell transplantation has promise as a therapeutic option for restoring impaired heart function after acute myocardial infarction (AMI). However, the optimal cell type to use remains controversial. We investigated the therapeutic efficacy and feasibility of intramyocardial transplantation of human umbilical cord blood-derived endothelial progenitor cells (hUCB-EPC) in rats with AMI. 2. The Wistar rats myocardial infarction model was established by ligating the left anterior descending artery. The labelled hUCB-EPC were transplanted through intramyocardial injection. Left ventricular function was assessed using a pressure-volume catheter and echocardiogram. Anti-VIII immunohistochemistry staining was used to reflect the degree of angiogenesis in peri-infarcted areas by calculating the average capillary density. The fibrosis degree of infarcted myocardium was analysed by Masson staining and the collagen volume fraction was calculated. 3. The labelled donor endothelial progenitor cells were detected in the new microvessels in host myocardium by double-positive staining with CM-Dil and FITC-UEA-l. An increase in left ventricular ejection fraction, left ventricular fractional shortening, left ventricular end-systolic pressure, first derivative of left ventricular pressure (+dP/dtmax and -dP/dtmax), as well as a decrease in the left ventricular end-diastolic pressure in rats with cell therapy indicated a significant improvement in global heart function. The cell therapy group had increased microvessel formation and a decreased degree of myocardial fibrosis compared to the control group. Moreover, the degree of myocardial fibrosis was less than that of the control group. 4. The improved global heart function and decreased cardiac fibrosis in rats with AMI implies the potential benefit of hUCB-EPC transplantation.

The behavior of fibroblasts on patterned substrates was examined in order to elucidate the role of dermal structure in wound healing. Dermal fibroblasts were cultured on micro-patterned silicone elastomer substrates designed to enforce cell adhesion only to fibronectin microdots. The morphology, expression of α-smooth muscle actin (α-SMA), proliferation, apoptotic cells, and soluble collagen production of cells were measured. Cells grown on patterned substrates showed some signs of a scar-fibroblast phenotype such as: elongated pseudopodia, enhanced expression of alpha smooth muscle actin (α-SMA), and increased collagen/pre-collagen, in comparison to unpatterned controls. Cells also showed low proliferation rates and high apoptotic index. The results showed that the microdot arrays, acting as a grid of limited focal adhesion sites, could force cells to adopt constrained morphologies and limited adhesion areas, which affect the cytoskeleton, ultimately leading to expression of a scar-tissue fibroblast phenotype. This study provides insight into the regulatory mechanisms of micro-topology on cell behavior in wound healing.

Background Interleukin-16 (IL-16), a pleiotropic cytokine, plays a fundamental role in inflammatory diseases. This study investigates the association between IL-16 polymorphisms and the risk of knee osteoarthritis (OA) in a Chinese population. Methods The IL-16 rs11556218, rs4072111, and rs4778889 polymorphisms were determined in 150 knee OA cases and 147 healthy controls through polymerase chain reaction-restriction fragment length polymorphism. Results The results suggested that the variants in IL-16 gene rs11556218 site were associated with a decreased knee OA risk after adjusting for age, sex, BMI, and smoking and drinking status (TG vs. TT: OR, 0.69; 95% CI, 0.53–0.89; P = 0.006; GG vs. TT: OR, 0.64; 95% CI, 0.45–0.90; P = 0.042; dominant model: OR, 0.68; 95% CI, 0.29–0.87; P = 0.002; G vs. T allele: OR, 0.77; 95% CI, 0.66–0.90; P = 0.003). Similarly, subjects bearing the rs4072111 variant genotypes and alleles also had a lower susceptibility to knee OA compared with those bearing the wild-type (CT vs. CC: OR, 0.66; 95% CI, 0.53–0.83; P = 0.002; TT vs. CC: OR, 0.57; 95% CI, 0.40–0.82; P = 0.027; dominant model: OR, 0.65; 95%, CI 0.52–0.80; P

To assess the quality of life (QOL) of advanced schistosomiasis patients, and understand its influencing factors.A questionnaire survey was carried out by using WHOQOL-BREF, and the information of demography, family, illness, health status, and health service was collected.Among the 217 advanced patients, the average age was (75.33 ± 6.94) years, the ratio of male to female was 2:5, 89.86% of them were farmers, 75.58% were illiterate or semi-illiterate, and 88.94% belonged to the splenomegaly type. Totally 61.29% of the cases had the scores over average for the overall QOL, but the scores for the health and well-being were lower. There were a significant difference among the average scores of different domains of QOL (χ2 = 23.46, P0.01). Both the year of being diagnosed and clinical classification was not associated with the scores of QOL. Regularly taking physical activities was significantly associated with each of all the 4 domains. The factors such as onset of acute disease in 2 weeks, taking therapeutic pills daily, marital status, age, etc. impacted the specific domains of QOL. The overall QOL and the 4 domains of the patients were at medium level; meanwhile, the score of physiological domain was lower than the scores of the other 3 domains.The QOL(s) of advanced schistosomiasis patients in Qingpu District are relatively good. It is important to provide effective community health services and encourage the patients to take part in tempered sports or physical activities in order to keep their normal activities of daily living.

We report on methodologies for use in the design of a biodegradable Mg alloy appropriate for load-bearing but temporary orthopedic implant applications. Comparative studies of Mg-5Ca and Mg-5Ca-1Zn were conducted to explore the effects of a combination of minor alloying and hot extrusion, on the alloy's mechanical properties and corrosion resistance. The extruded Mg-5Ca-1Zn exhibited high ultimate compressive strength of 385 MPa and suffered no significant structural degradation even after immersion in simulated body fluid for 30 days. Mg-5Ca-1Zn alloy showed the mechanical strength and controlled corrosion rate to be considered as an ideal candidate for biodegradable orthopedic implant material.

Increasing evidences have illuminated the fundamental role of inflammation in mediating all stages of atherosclerosis. miR-155, a typical multi-functional miRNA, has recently emerged as a novel component of inflammatory signal transduction in the pathogenesis of atherosclerosis. However, little is known about whether endothelial highly expressed miR-155 can regulate endothelial inflammation-related transcription factors and the predicted role of miR-155 as a negative feedback regulator in endothelial inflammation involved in atherosclerosis. Bioinformatics analysis showed that RELA (nuclear factor-κB p65) is a potential target gene of miR-155 and this was confirmed by a luciferase reporter assay. Our results show that microRNA-155 mediate endothelial inflammation and decrease NFкB p65 and adhesion molecule expression in TNFα-stimulated endothelial cells. Transfection with miR-155 significantly inhibited TNFα-induced monocyte adhesion to endothelium. Inhibition of miR-155 enhanced p65 level and endothelial inflammatory response which was counteracted through the depletion of P65 by Si-P65. On the other hand, knockdown of eNOS, another target of miR-155, while transfecting with miR-155 inhibitor resulted in more significant inflammatory response. miR-155 is highly expressed in TNFα treated HUVECs, deprived of endogenous p65 could reverse TNFα-induced upregulation of miR-155. Thus, TNFα induced miR-155 may serve as a negative feedback regulator in endothelial inflammation involved in atherosclerosis by targeting nuclear transcription factor P65. These results provide a rationale for intervention of intracellular microRNA as possible anti-atherosclerotic targets.

A series of novel 3beta, 7alpha, 11alpha-trihydroxy-pregn-21-benzylidene-5-en-20-one derivatives were synthesized and characterized by NMR, HRMS. The pregnenolone (1) was first biotransformed by Mucor circinelloides var lusitanicus to 3beta, 7alpha, 11alpha-trihydroxy-pregn-5-en-20-one (3), then 3 was treated with various benzaldehydes to produce 3beta, 7alpha, 11alpha-trihydroxy-pregn-21-benzylidene-5-en-20-one derivatives. These derivatives showed remarkable activity against EC109 cells. The absolute configuration of 3 was also confirmed by signal-crystal X-ray analysis.

To discuss clinical effects of complex acetabular fracture.From January 2005 to December 2010, totally 31 patients with complex acetabular fracture received surgery. There were 21 males and 10 females with an average age of 38.6 years old (ranged, 31 to 57). X-ray, CT, operation scheme and clinical efficiacy were retrospectively analyzed. American Academy of Orthopaedic Surgery standard was used to evaluate hip joint function.All patients were followed up from 12 to 36 months with an average of 17.6 months. No complications and neurovascular injury occurred. One case received total hip replacement arthroplasty. There were 17 cases obtained anatomical reduction, 12 cases got satisfied reduction and 2 cases not satisfied. According to American Academy of Orthopaedic Surgery standard, 18 cases got excellent result, good in 9 cases, fair in 3 cases and poor in 1 case.Complex acetabular fracture combine with lots of complications and easily had occurre postoperative complications. It can improve curative effect by accurate reduction and reliable fixation and maximize restoring function of hip joint.

To evaluate the efficacy of Kirschner wires and tension-band fixation through posterolateral minimal incision for the treatment of displaced supracondylar humeral fractures in children.From January 2005 to December 2010, there were 62 children (38 males and 24 females, ranging in age from 2 to 14 years, averaged 6.8 years) with Gartland type III supracondylar humeral fractures. All the injuries were caused by falling, and all the fractures were fresh injuries. The duration from injury to surgery ranged from 5 to 20 hours. All the children were treated with open reduction through a posterolateral minimal approach, Kirschnere wires and tension-band fixation were fixed with plaster at 90 degrees of elbow flexion, forearm supination, and palms facing upwards. The kirschner pins and wires were removed after fractures healing. The Flynn's criterion was used to evaluate therapeutic effects.The operation time ranged from 30 to 50 min (averaged 45 min). All the patients achieved solid union. Sixty patients were followed up, and the mean follow-up time was 15 months (ranged from 6 to 24 months). At the 6th month after operation, 48 patients got an excellent result, 9 good, 3 bad (light cubitus varus with varus angle about 6 degree, without infection on function) according to Flynn's criteria. There were no complications such as procedure-related pin tract infection, iatrogenic nerve and vascular injuries and myositis ossificans.The Kirschner wires and tension-band fixation through posterolateral minimal incision approach can obtain clearer surgical field, simple in operation, and few wound complications. Therefore, this modified treatment is an effective and reliable method for pediatric displaced Gartland type III supracondylar humeral fractures.

Cell transplantation has great potential for promoting endothelial repair and reducing the complications of percutaneous coronary intervention (PCI). The aim of this study was to investigate the effect of transplantation of human umbilical cord blood endothelial progenitor cells (EPCs) on injured arteries.Umbilical cord blood mononuclear cells were obtained from post-partum lying-in women, and EPCs were isolated, cultured, expanded and identified by immunofluorescence. The carotid arterial endothelium of New Zealand white rabbits was injured by dilatation with a 3F balloon, and the EPCs were injected into the lumen of the injured artery in the transplanted group (n = 16), while an equal volume of phosphated buffered saline (PBS) was injected into the control group after balloon injury (n = 16). The animals were sacrificed after either 2 or 4 weeks, and the grafted cells were identified by double immunofluorescence staining with human nuclear antigen (HNA) and CD31 antibodies. Arterial cross sections were analyzed by pathology, immunohistochemistry and morphometry to evaluate the reparative effects of EPCs. Proliferating cell nuclear antigen (PCNA) and transforming growth factor (TGF)-β1 mRNA expression were detected by reverse transcription-polymerase chain reaction (RT-PCR).Fluorescence-labeled EPCs were found in the neointima. The neointimal area and the neointimal/medial area ratio were significantly lower in the transplanted group than in the control group (P0.05). von Willebrand factor (vWF) immunohistostaining showed more VWF-positive cells in the transplanted animals than in the controls (8.75 ± 2.92 vs. 4.50 ± 1.77, P0.05). Compared with the control group, the transplanted group had lower expression of PCNA mRNA (0.67 ± 0.11 vs. 1.25 ± 0.40, P0.01) and higher expression of TGF-β1 mRNA (1.10 ± 0.21 vs. 0.82 ± 0.07, P0.05).EPCs derived from human umbilical cord blood were successfully transplanted into injured vessels. The transplanted EPCs inhibited neointimal hyperplasia and promoted vascular re-endothelialization.

To investigate the efficacy and safety of the comprehensive protocol of integrative medicine in preventing and treating perioperative delayed cerebrovasospasm (DCVS) in patients with aneurysmal subarachnoid hemorrhage (aSAH).Using a prospective randomized controlled trial design, 63 aSAH inpatients were assigned to the treatment group (31 cases, 24 treated by intervention treatment and 7 by craniotomy) and the control group (32 cases, 26 treated by intervention treatment and 6 by craniotomy). All patients were treated with basic therapy and nimodipine. Those in the treatment group additionally took naomai jiejing decoction No. 1 and No. 2. The incidence and the mortality of DCVS, re-bleeding, hydrocephalus were compared on the 180th day. The middle cerebral artery mean flow velocity (Vm), PI value, linde-gard index on day 1, 3, 7, and 14 were compared. The Chinese medicine syndrome score, NIHSS, and revised Rankin questionnaire on day 1, 14, and 180 were compared.The DCVS occurred in 9 cases (29. 0%) of the treatment group and 17 patients (53.1%) of the control group, showing statistical difference (P0.05). The occurrence of re-hemorrhage was obviously lower in the treatment than in the control group (3.2% vs. 6.2%), showing statistical difference (P0. 05). There was no statistical difference in the mortality (6.4% vs. 9.4%) or the occurrence of hydrocephalus (29.0% vs 25.0%, P0.05). The Vm, PI, and linde-gard index on day 7, the Vm and linde-gard index on day 14 were obviously lower in the treatment group than in the control group (P0.05). The Chinese medicine syndrome score and NIHSS on day 14 and 180 were lower in the treatment group than in the control group, showing statistical difference (P0.05).The comprehensive protocol of integrative medicine could reduce the incidence of aSAH patients' DCVS, the Chinese medicine syndrome score and NIHSS, and improve their clinical symptoms.

To investigate the association of polymorphisms of arylhydrocarbon receptor (AhR)-1661G/A with glutathione S-transferase pi (GSTP1) -313A/G and the susceptibility to endometriosis in southern Han Chinese.Total of 432 endometriosis patients undergoing laparoscopic or laparotomy surgery matched with 493 patients with fallopian tube ligation, tubal recanalization, laparoscopic hydrotubation, benign ovarian tumor and teratoma surgeries without endometriosis as control group were enrolled in this study. The single nucleotide polymorphism (SNP) of AhR -1661G/A and GSTP1 -313A/G were detected by using a fluorescent quantitative PCR-based high resolution melting (HRM).The numbers of combined genotypes AhR -1661G/A and GSTP1 -313A/G were 120 patients with AG + AA, 64 patients with AG + AG, 8 patients with AG + GG, 109 patients with GG + AA, 84 patients with GG + AG, 4 patients with GG + GG, 31 patients with AA + AA, 10 patients with AA + AG, 1 patient with AA + GG at endometriosis group and 131 patients with AG + AA, 68 patients with AG + AG, 6 patients with AG + GG, 157 patients with GG + AA, 66 patients with GG + AG, 4 patients with GG + GG, 35 patients with AA + AA, 20 patients with AA + AG, 3 patients with AA + GG at endometriosis group. There was no statistically different frequencies of genotypes between endometriosis group and control group (χ(2) = 12.558, P = 0.128). Compared with genotype GG + AA, the risk of endometriosis with genotype GG + AG was increased 1.833 time (95%CI: 1.233 - 2.274).The combined genotype GG + AG [from AhR -1661G/A (GG) and GSTP1 -313A/G (AG)] might be related with susceptibility to endometriosis.

To investigate the association of tumor necrosis factor-alpha (TNF-α) gene promoter region -1031T/C and its combination with interleukin-6 (IL-6) gene promoter region -634C/G single nucleotide polymorphisms (SNP) with the genetic susceptibility to endometriosis.Total of 432 endometriosis patients and 499 non-endometriosis women who had received an operation due to tubal ligation, tubal recanalization, laparoscopic hydrotubation, ovarian simple cyst and teratoma were collected and separated into endometriosis group and control group, that all cases were confirmed by operation and pathology. A case-control study was performed in endometriosis and control group to evaluate the association of these SNP with the susceptibility to endometriosis by using a fluorescent quantitative PCR-based high resolution melting (HRM) method.(1) TNF-α -1031T/C genotype:the T and C of TNF-α -1031T/C allele frequencies in the endometriosis group and control group were 79.2% (684/864), 20.8% (180/864) and 81.8% (816/998), 18.2% (182/998), respectively. The TT, TC and CC of TNF-α -1031T/C genotype frequencies in the two groups were 63.7% (275/432), 31.0% (134/432), 5.3% (23/432) and 66.5% (332/499), 30.5% (152/499), 3.0% (15/499), respectively. There were no statistical significances in the TNF-α -1031T/C alleles and genotypes distributions between the two groups (P = 0.158, P = 0.186). (2) TNF-α -1031T/C and IL-6 -634C/G conjoint genotypes: to research on the TNF-α -1031T/C and IL-6 -634C/G genotypes for conjoint analysis, the TT+CC, TC+CC, CC+CC, TT+CG, TC+CG, CC+CG, TT+GG, TC+GG and CC+GG combination genotype frequencies in the two groups were 39.4% (170/432), 19.4% (84/432), 4.6% (20/432), 20.6% (89/432), 8.8% (38/432), 0.9% (4/432), 3.5% (15/432), 2.3% (10/432), 0.5% (2/432) and 36.7% (183/499), 17.4% (87/499), 1.4% (7/499), 26.1% (130/499), 10.4% (52/499), 1.2% (6/499), 3.8% (19/499), 2.6% (13/499), 0.4% (2/499), respectively. There were no statistical significances in the combination genotypes distributions between the two groups (P = 0.107). As compared with carriers of TT+CC combination genotype, the endometriosis risk of carriers of CC+CC combination genotype enhanced 3.076 times (95%CI: 1.268 - 7.457, P = 0.009), and the endometriosis risk of carriers of other combination genotypes were no statistical significances (all P0.05).The study demonstrates that there are no significant association between the SNP of TNF-α -1031T/C and genetic susceptibility to endometriosis. However the results indicate that there are significant association between genetic susceptibility to endometriosis and the combination polymorphisms of TNF-α -1031T/C and IL-6 -634C/G.

Incomplete right bundle branch block (ICRBBB) is commonly associated with atrial septal defect (ASD), but lacks sufficient diagnostic test characteristics. An abnormal T wave is also often observed in ASD, with horizontal or inverted displacement of the proximal T wave limb in the right precordial leads, termed "defective T wave" (DTW).We examined the diagnostic test characteristics of combining ICRBBB with DTW as a new index to diagnose ASD. A total of 132 consecutive patients with ASD and 132 cases of age/gender-matched controls without ASD were enrolled.Sensitivities of DTW, ICRBBB, and both were 87.1% - 87.9%. Specificities were 97.0%, 96.2%, and 100%, respectively. Positive predictive values were 1.3%, 1.1%, and 100.0% respectively, while negative predictive values were 99.9% for each.Combining ICRBBB with DTW in electrocardiogram (ECG) as a new index significantly increased the specificity and positive predictive values while maintaining a high sensitivity in diagnosing ASD.

To investigate the association of interleukin 6 gene (IL-6) promoter region 634C/G (rs1800796) single nucleotide polymorphism (SNP) with the genetic susceptibility to endometriosis (Ems) in south Han Chinese women.A case-control study was performed in 432 Ems patients and 499 control women to evaluate the SNP of IL-6 634C/G by using a fluorescent quantitative PCR-based high resolution melting (HRM) method.There were statistical significances in the IL-6 634C/G alleles, whether or not to carry allele G and genotype distributions between Ems patients and control women (P=0.032, 0.014 and 0.045, respectively). Allele C enhanced the risk of Ems 1.057 times while allele G reduced the risk of Ems 0.835 time. Carrying allele G reduced the risk of Ems 0.822 time, whereas not carrying allele G enhanced the risk of Ems 1.143 times. Compared with genotype CC, the risk of Ems with genotype CG reduced 0.704 time (95% CI: 0.533-0.931). There was no significant difference in whether or not carrying allele G distribution between Ems patients and control women (P=0.729).The present study demonstrated significant association between the SNP of IL-6 634C/G and genetic susceptibility to Ems in south Han Chinese women.

To investigate the association of single nucleotide polymorphisms in cytochrome P450 17 (CYP17) and estrogen receptor alpha (ERα ) genes with the risk of endometriosis among southern Chinese women.Two SNPs rs743572 (CYP17 gene 34T/C) and rs9322331 (ERα gene -397T/C) were genotyped by high resolution melting curve in 432 endometriosis patients and 499 matched controls.There was no significant difference in the genotype frequencies of the two loci between endometriosis patients and the control subjects (P0.05). And there was no significant interaction effect of these two genes on the disease either.CYP17 gene and ERα gene may not be genetic risk factors for endometriosis among southern women in China.

Purpose The arguments about whether posterior-substituting prostheses or cruciate-retaining prostheses are superior to the other after total knee arthroplasty never stop. This meta-analysis was conducted to evaluate the clinical effects of these two different designs. Methods The study was performed according to the guidelines described in the Cochrane handbook for systematic reviews of interventions. Methodological features were collected and extracted by two reviewers independently. Results Nine randomized controlled trials with 1261 knees were eligible for pooled analysis. The meta-analysis demonstrated there were no statistical differences in the Knee Society Score, Hospital for Special Surgery, Western Ontario and McMaster Universities index, tibial component alignment, femoral component alignment, tibial posterior slope, joint line, and incidence of complications with short-to medium-term follow-up ( p >0.01). Statistically difference in postoperative range of motion (WMD: 4.34°, 95% CI: 3.18° to 5.50°) in favor of PS prostheses was found between groups ( p Conclusion The findings indicate there were no significant statistical differences in knee scores, radiological outcomes, and complications between the two types of implants. Statistically significant difference in postoperative ROM was found between the two groups, but no clinical difference.

To explore the association between the arylhydrocarbon receptor gene (AhR) 1661G/A or arylhydrocarbon nuclear translocatorgene (ARNT) 567G/C polymorphism and endometriosis in southern Han Chinese women.The polymorphisms of AhR gene 1661G/Aand ARNT gene 567G/C in 431 cases of endometriosis and 499 healthy women were genotyped by fluorescence quantitative PCR-based high resolution melting.The frequencies of genotypes AA, AG, GG and alleles A and G in controls were 12.0%, 41.9%, 46.1%, 33.0% and 67.0%, respectively, which were not significantly different from those in patients with endometriosis (9.7%, 44.6%, 45.7%, 32.0% and 68.0%, respectively). The genotype frequencies of GG, GC, CC and alleles C and G in controls (15.6 %, 51.7%, 32.7%, 58.5%, 41.5%) were not significantly different from those in patients with endometriosis (13.5%, 47.8%, 38.7%, 62.6%, 37.4%), either. And no interaction of AhR 1661G/A and ARNT 567G/C on endometriosis was found.No association between AhR 1661G/A and ARNT 567G/C genetic polymorphisms and endometriosis was found in the southern Han Chinese women in this study.

Enhanced external counterpulsation (EECP) improves ischemia in patients with refractory angina pectoris, but the mechanism remains unclear. To explore the mechanisms of EECP action, we detected progenitor cells presenting any of the following markers CD34(+), CD29(+), and CD106(+).Growth cytokines-mediated progenitor cell mobilization and associated angiogenesis potential were assessed in a porcine model of hypercholesterolemia. Twenty-four male domestic swines were randomly assigned to 4 groups: normal diet (control, n = 6), hypercholesterolemic diet (CHOL, n = 6), hypercholesterolemic diet with administration of recombinant human granulocyte colony-stimulating factor (rhG-CSF) (rhG-CSF, n = 6), and hypercholesterolemic diet with EECP treatment (EECP, n = 6). EECP was applied 2 hours every other day for a total of 36 hours. Serum levels of vascular endothelial growth factor (VEGF) and granulocyte colony-stimulating factor (G-CSF), peripheral blood progenitor cell counts, level of regional angiogenesis, and expression of VEGF and stromal cell derived factor 1alpha (SDF-1alpha) in porcine myocardium were assessed, respectively.A porcine model of hypercholesterolemia-induced arteriosclerosis was successfully established. There was no significant difference in serum levels of VEGF among the four groups. The serum levels of G-CSF in the EECP group increased significantly at week 15 and week 18 ((38.3 +/- 5.6) pg/ml at week 15 vs (26.2 +/- 3.7) pg/ml at week 12, P0.05, and (46.9 +/- 6.1) pg/ml at week 18 vs (26.2 +/- 3.7) pg/ml at week 12, P0.01). The serum levels of G-CSF in group 3 increased also significantly after receiving rhG-CSF injection for five days ((150 +/- 13.9) pg/ml at week 18 vs (24.8 +/- 5.4) pg/ml at week 12, P0.01). Compared to other groups and other time points, progenitor cell counts increased significantly after 2-hour EECP treatment (108 +/- 13 vs 26 +/- 6 per 10(5) leukocytes, P0.01), but not at week 18. The progenitor cell counts also increased significantly after subcutaneous injection of rhG-CSF for five days compared to the week 12 (baseline) (180 +/- 21 vs 25 +/- 7 per 10(5) leukocytes, P0.01). There was no significant difference among the four groups at other time points. Moreover, the expression of VEGF and SDF-1alpha and the level of regional angiogenesis in myocardium increased significantly in both EECP and rhG-CSF groups.The results demonstrated that EECP could facilitate angiogenesis in the myocardium of atherosclerotic swines by increasing endogenous G-CSF, inducing an enhanced mobilization of progenitor cells and augmenting myocardial expression of VEGF and SDF-1alpha.

Cell-based vascular therapies of endothelial progenitor cells (EPCs) mediated neovascularization is still a novel but promising approach for the treatment of ischemic disease. The present study was designed to investigate the therapeutic potentials of human umbilical cord blood-derived EPCs (hUCB-EPCs) in rat with acute myocardial infarction.Human umbilical cord blood (hUCB) mononuclear cells were isolated using density gradient centrifugation from the fresh human umbilical cord in healthy delivery woman, and cultured in M199 medium for 7 days. The EPCs were identified by double-positive staining with 1, 1'-dioctadecyl-3, 3, 3', 3'-tetramethylindocarbocyanine percholorate-labeled acetylated low-density lipoprotein (Dil-Ac-LDL) and fluorescein isothiocyanate-conjugated Ulex europaeus lectin (FITC-UEA-l). The rat acute myocardial infarction model was established by the ligation of the left anterior descending artery. The hUCB-EPCs were intramyocardially injected into the peri-infarct area. Four weeks later, left ventricular function was assessed by a pressure-volume catheter. The average capillary density (CAD) was evaluated by anti-VIII immunohistochemistry staining to reflect the development of neovascularization at the peri-infarct area. The graft cells were identified by double immunofluorescence staining with human nuclear antigen (HNA) and CD31 antibody, representing human origin of EPCs and vascular endothelium, respectively. Expressions of cytokines, proliferating cell nuclear angigen (PCNA), platelet endothelial cell adhesion molecule (PECAM) and vascular endothelial growth factor (VEGF) were detected to investigate the underlying mechanisms of cell differentiation and revascularization.The donor EPCs were detectable and integrated into the host myocardium as confirmed by double-positive immunofluorescence staining with HNA and CD31. And the anti-VIII staining demonstrated a higher degree of microvessel formation in EPCs transplanted rats, associated with a significant improvement of global heart function in terms of the increase of left ventricular end-systolic pressure (LVESP), +dp/dtmax and -dp/dtmax as well as the decrease of LVEDP in rats with EPCs therapy comparing to the control rats (P0.05). Moreover, the expression of the rat PCNA mRNA and PECAM were both enhanced in the EPCs group compared with that of the control group.The human umbilical cord blood-derived EPCs could incorporate into new-born capillaries in rat myocardium, induce revascularization and improve the proliferation activity in the peri-infarct area, resulting in the improvement of global heart function. This may indicate a promising stem cell resource in cell-based therapy for ischaemic diseases.

An ideal gene carrier is required both in safety and efficiency for transfection. Polyethylenimine (PEI), a well-studied cationic polymer, has been proved with high transfection efficiency, but is reported as toxicity in many cell lines. In this study, PEI was coupled with polyethylene glycol (PEG) to reduce its cytotoxicity. PEG-PEI copolymers were synthesized with isoporon diisocyanate (IPDI) in two steps. A set of PEG-PEI with different PEG molecular weights (MWs) and amounts of PEG were synthesized. The molecular structure of the resulting copolymers was evaluated by nuclear magnetic resonance spectroscopy ((1)H NMR), infrared spectroscopy (IR), and gel permeation chromatography (GPC), all of which had successfully verified formation of the copolymers. The particle size and zeta potential of polymer/DNA complexes were measured, and their cytotoxicity and transfection efficiency in Hela cells were evaluated. We found that the copolymer block structure significantly influenced not only the physicochemical properties of complexes, but also their cytotoxicity and transfection efficiency. PEG (5 kDa) significantly reduced the diameter of the spherical complexes. The zeta potential of complexes was reduced with increasing amount of PEG grafting. Cytotoxicity was dependent not on PEG MW but on the amount of PEG grafting. Copolymer PEG-PEI (2-25-1) with 1.89 PEG (2 kDa) was proved to be more efficient for in vitro gene transfer. In conclusion, PEG MW and the degree of PEGylation were found to significantly influence the biological activity of PEG-PEI/DNA complexes. These results provide new sights into the studies using block copolymer as gene delivery systems.

Human umbilical cord blood contains abundant immature stem/progenitor cells, which may contribute to the repair of infarcted myocardium. Present study aimed to explore the feasibility and effects of human umbilical cord blood mononuclear cells (HUCBC) transplantation for the treatment of myocardial infarction.Forty-five male Wistar rats were randomly divided into three groups: (1) Myocardial infarction (MI plus vehicle, n = 15), (2) MI plus cell transplantation (HUCBC were implanted into the peri-infarct area immediately after MI, n = 15), (3) Normal control group (n = 15). After echocardiography and hemodynamic measurements, the rats were sacrificed for histological and immunochemical examinations one month post MI.The transplanted HUCBC survived and participated the repair process in host heart. Significantly improved left ventricular function was evidenced by echocardiography in cell transplantation group compared to the MI control group. Left ventricular end-diastolic pressure was significantly reduced LVEDP (21.08 +/- 8.10) vs (30.82 +/- 9.59) mm Hg, P0.05], +dp/dt(max) [(4.29 +/- 1.27) vs (3.24 +/- 0.75) mm Hg/ms, P0.05] and -dp/dt(max) increased [(3.71 +/- 0.79) vs (3.00 +/- 0.49) mm Hg/ms, P0.05] in cell transplantation rats compared with MI control rats. vWF immunostaining examination showed significantly increased microvessels within the boundary of infarcted myocardium in cell transplantation group compared to the MI control group (P0.01).HUCBC transplantation may improve cardiac function in MI rats by promoting microvessel formation.

N(3)-Hydroxyethyltegafur (3) was synthesized in 91.0% yield under a new condition. A series of novel fatty acid esters of 3 were synthesized. These fatty acid-nucleoside conjugates have shown cytotoxicities against Ec9706 cells and A549 cells, and the structure activity relationship was discussed.

Human umbilical cord blood contains an abundance of immature stem/progenitor cells, which may participate in the repair of hearts that have been damaged by myocardial infarction (MI). This study aimed to evaluate the effects of human umbilical cord blood mononuclear cells (hUCBC) transplantation on cardiac function and left ventricular remodeling in rat model of MI.Forty-five male Wistar rats were randomized into three groups: MI or control group (n = 15), MI plus cell transplantation (n = 15), and sham group (n = 15). Acute myocardial infarction (AMI) was established by ligating the left anterior descending artery, thereafter, hUCBC were implanted into the marginal area of infarcted myocardium. In MI/control group, DMEM was injected instead of hUCBC following the same protocol. Left ventricular function assessment was carried out by echocardiography and invasive hemodynamic measurements one month post MI. All rats were sacrificed for histological and immunochemical examinations.The transplanted hUCBC survived and engaged in the process of myocardial repair in the host heart. Echocardiography demonstrated that left ventricular function improved significantly in the rats that underwent cell transplantation. Hemodynamic studies found a significantly decreased left ventricular end-diastolic pressure (LVEDP) [(21.08 +/- 8.10) mmHg vs (30.82 +/- 9.59) mmHg, P0.05], increase in +dp/dt(max) [(4.29 +/- 1.27) mmHg/ms vs (3.24 +/- 0.75) mmHg/ms, P0.05), and increase in -dp/dt(max) [(3.71 +/- 0.79) mmHg/ms vs (3.00 +/- 0.49) mmHg/ms, P0.05] among MI group with hUCBC transplantation when compared with MI/control group. Masson's trichrome staining revealed that the collagen density in the left ventricle was significantly lower in rats of transplantation group than that in the MI control groups [(6.33 +/- 2.69)% vs (11.10 +/- 3.75)%, P0.01]. Based on immunostaining of alpha-actin, the numbers of microvessels were significantly (P0.01) increased at the boundary of infarction site. Similarly higher mRNA expression of vascular endothelial growth factor (VEGF) 164 and VEGF188 were found at 7- and 28-day post cell transplantation in MI group with hUCBC transplantation when compared with MI/control group.Transplanted hUCBC can survive in host myocardium without immunorejection, significantly improve left ventricular remodeling after AMI and promote a higher level of angiogenesis in the infarct zones. All these factors beneficially affect cardiac repair in the setting of MI. Therefore human umbilical cord blood may be potential source for cell-based therapy for AMI.