Development and validation of a nomogram for predicting specific mortality risk: A study of competing risk model based on real endometrial cancer patients.

OBJECTIVE: This study aimed to construct a competing risk prediction model for predicting specific mortality risks in endometrial cancer patients from the SEER database based on their demographic characteristics and tumor information. METHODS: We collected relevant clinical data on patients with histologically confirmed endometrial cancer in the SEER database between 2010 and 2015. Univariate and multivariate competing risk models were used to analyze the risk factors for endometrial cancer-specific death, and a predictive nomogram was constructed. C-index and receiver operating characteristic curve (ROC) at different time points were used to verify the accuracy of the constructed nomogram. RESULTS: There were 26 109 eligible endometrial cancer patients in the training cohort and 11 189 in the validation cohort. Univariate and multivariate analyses revealed that Age, Marriage, Grade, Behav, FIGO, Size, Surgery, SurgOth, Radiation, ParaAortic_Nodes, Peritonea, N positive, DX_liver, and DX_lung were independent prognostic factors for specific mortality in endometrial cancer patients. Based on these factors, a nomogram was constructed. Internal validation showed that the nomogram had a good discriminative ability (C-index = 0.883 [95% confidence interval [CI]: 0.881-0.884]), and the 1-, 3-, and 5-year AUC values were 0.901, 0.886 and 0.874, respectively. External validation indicated similar results (C-index = 0.883 [95%CI: 0.882-0.883]), and the 1-, 3-, and 5- AUC values were 0.908, 0.885 and 0.870, respectively. CONCLUSION: We constructed a competing risk model to predict the specific mortality risk among endometrial cancer patients. This model has favorable accuracy and reliability and can provide a reference for the development and update of endometrial cancer prognostic risk assessment tools.

Mitochondrial transplantation as a novel therapeutic strategy for cardiovascular diseases.

Cardiovascular disease (CVD) is the leading cause of noncommunicable disease-related death worldwide, and effective therapeutic strategies against CVD are urgently needed. Mitochondria dysfunction involves in the onset and development of CVD. Nowadays, mitochondrial transplantation, an alternative treatment aimed at increasing mitochondrial number and improving mitochondrial function, has been emerged with great therapeutic potential. Substantial evidence indicates that mitochondrial transplantation improves cardiac function and outcomes in patients with CVD. Therefore, mitochondrial transplantation has profound implications in the prevention and treatment of CVD. Here, we review the mitochondrial abnormalities that occur in CVD and summarize the therapeutic strategies of mitochondrial transplantation for CVD.

Shikonin exerts an anti-leukemia effect against FLT3-ITD mutated acute myeloid leukemia cells via targeting FLT3 tyrosine kinase and its downstream pathways.

INTRODUCTION: Acute myeloid leukemia (AML) with internal tandem duplication (ITD) mutations in Fms-like tyrosine kinase 3 (FLT3) has an unfavorable prognosis. Recently, using newly emerging inhibitors of FLT3 has led to improved outcomes of patients with FLT3-ITD mutations. However, drug resistance and relapse continue to be significant challenges in the treatment of patients with FLT3-ITD mutations. This study aimed to evaluate the anti-leukemic effects of shikonin (SHK) and its mechanisms of action against AML cells with FLT3-ITD mutations in vitro and in vivo. METHODS: The CCK-8 assay was used to analyze cell viability, and flow cytometry was used to detect cell apoptosis and differentiation. Western blotting and real-time polymerase chain reaction (RT-PCR) were used to examine the expression of certain proteins and genes. Leukemia mouse model was created to evaluate the anti-leukemia effect of SHK against FLT3-ITD mutated leukemia in vivo. RESULTS: After screening a series of leukemia cell lines, those with FLT3-ITD mutations were found to be more sensitive to SHK in terms of proliferation inhibition and apoptosis induction than those without FLT3-ITD mutations. SHK suppresses the expression and phosphorylation of FLT3 receptors and their downstream molecules. Inhibition of the NF-κB/miR-155 pathway is an important mechanism through which SHK kills FLT3-AML cells. Moreover, a low concentration of SHK promotes the differentiation of AML cells with FLT3-ITD mutations. Finally, SHK could significantly inhibit the growth of MV4-11 cells in leukemia bearing mice. CONCLUSION: The findings of this study indicate that SHK is a promising drug for the treatment of FLT3-ITD mutated AML.

Application of case-based learning in psychology teaching: a meta-analysis.

BACKGROUND: Case-based learning (CBL) has been found to be effective for many subjects, but there is currently a lack of evidence regarding its utility in psychology education. The present study investigated whether CBL pedagogy can improve students' academic performance in psychology courses compared to the traditional teaching methods. METHODS: A systematic review and meta-analysis were conducted to investigate the effectiveness of CBL in psychology teaching. Databases including PubMed, Embase, Web of Science, China National Knowledge Infrastructure (CNKI), the VIP database, and Wanfang data were searched to find eligible randomized controlled trials. Pooled effect estimates were calculated using Hedges' g under the random effects model, and a subgroup analysis was carried to investigate the heterogeneity among studies. RESULTS: Fifteen studies with 2172 participants, 1086 in the CBL group and 1086 in the traditional lecture-based teaching group, were included in the meta-analysis. Students in the CBL group scored significantly higher on exams than those in the lecture-based group [Hedges' g = 0.68, 95%CI (0.49, 0.88), p < 0.00]. Relatively high heterogeneity was noted among the included studies. Publication bias was examined by the funnel plot and Egger's test, but did not significantly influence the stability of the results. A subsequent evaluation using the trim-and-fill method confirmed that no single study was skewing the overall results. A qualitative review of the included studies suggested that most students in the CBL group were satisfied with the CBL teaching mode. CONCLUSIONS: This meta-analysis indicated that the CBL pedagogy could be effective in psychology education, and might help increase students' academic scores, while encouraging a more engaging and cooperative learning environment. At present, the application of CBL in psychology education is in its initial stage. Problems related to the curriculum itself, research methodology, and challenges faced by both teachers and learners have confined its practice. Fully tapping into the strengths of CBL in psychology teaching will require additional work and advancing research.

Association of metformin monotherapy or combined therapy with cardiovascular risks in patients with type 2 diabetes mellitus.

BACKGROUND: Metformin is a first-line drug in type 2 diabetes mellitus (T2DM) treatment, yet whether metformin may increase all-cause or cardiovascular mortality of T2DM patients remains inconclusive. METHODS: We searched PubMed and Embase for data extracted from inception to July 14, 2020, with a registration in PROSPERO (CRD42020177283). This study included randomized controlled trials (RCT) assessing the cardiovascular effects of metformin for T2DM. This study is followed by PRISMA and Cochrane guideline. Risk ratio (RR) with 95% CI was pooled across trials by a random-effects model. Primary outcomes include all-cause mortality and cardiovascular mortality. RESULTS: We identified 29 studies that randomly assigned patients with 371 all-cause and 227 cardiovascular death events. Compared with untreated T2DM patients, metformin-treated patients was not associated with lower risk of all-cause mortality (RR: 0.98; 95%CI: 0.69-1.38; P = 0.90), cardiovascular mortality (RR: 1.13; 95% CI: 0.60, 2.15; P = 0.70), macrovascular events (RR: 0.87; 95%CI: 0.70-1.07; P = 0.19), heart failure (RR: 1.02; 95% CI:0.61-1.71; P = 0.95), and microvascular events (RR: 0.78; 95% CI:0.54-1.13; P = 0.19). Combination of metformin with another hypoglycemic drug was associated with higher risk of all-cause mortality (RR: 1.49; 95% CI: 1.02, 2.16) and cardiovascular mortality (RR: 2.21; 95% CI: 1.22, 4.00) compared with hypoglycemic drug regimens with no metformin. CONCLUSION: The combination of metformin treatment may impose higher risk in all-cause and cardiovascular mortality. This finding, at least in part, shows no evidence for benefits of metformin in combination in terms of all-cause/cardiovascular mortality and cardiovascular events for T2DM. However, the conclusion shall be explained cautiously considering the limitations from UK Prospective Diabetes Study (UKPDS).

Progressive global perception and local polishing network for lung infection segmentation of COVID-19 CT images.

In this paper, a progressive global perception and local polishing (PCPLP) network is proposed to automatically segment the COVID-19-caused pneumonia infections in computed tomography (CT) images. The proposed PCPLP follows an encoder-decoder architecture. Particularly, the encoder is implemented as a computationally efficient fully convolutional network (FCN). In this study, a multi-scale multi-level feature recursive aggregation (mmFRA) network is used to integrate multi-scale features (viz. global guidance features and local refinement features) with multi-level features (viz. high-level semantic features, middle-level comprehensive features, and low-level detailed features). Because of this innovative aggregation of features, an edge-preserving segmentation map can be produced in a boundary-aware multiple supervision (BMS) way. Furthermore, both global perception and local perception are devised. On the one hand, a global perception module (GPM) providing a holistic estimation of potential lung infection regions is employed to capture more complementary coarse-structure information from different pyramid levels by enlarging the receptive fields without substantially increasing the computational burden. On the other hand, a local polishing module (LPM), which provides a fine prediction of the segmentation regions, is applied to explicitly heighten the fine-detail information and reduce the dilution effect of boundary knowledge. Comprehensive experimental evaluations demonstrate the effectiveness of the proposed PCPLP in boosting the learning ability to identify the lung infected regions with clear contours accurately. Our model is superior remarkably to the state-of-the-art segmentation models both quantitatively and qualitatively on a real CT dataset of COVID-19.

MiR-7-5p suppresses stemness and enhances temozolomide sensitivity of drug-resistant glioblastoma cells by targeting Yin Yang 1.

Glioblastoma multiforme (GBM) is the most malignant tumor of the central nervous system, and chemoresistance blunts the effect of temozolomide (TMZ) in the treatment of GBM. Clarifying the underlying mechanism of chemoresistance might yield novel strategies to improve the patients' response to chemotherapeutics. Mounting evidence indicates that microRNAs (miRNAs) are involved in chemoresistance and tumorigenesis. At present, miR-7-5p has been recognized as a tumor suppressor involved in multiple cancers. However, the biological effects of miR-7-5p in TMZ resistance have not been illuminated. In this study, we used RNA sequencing and high-throughput screening techniques, which revealed that miR-7-5p is significantly downregulated in TMZ resistant LN229 cells (LN229/TMZ-R) compared to control cells (LN229), and low miR-7-5p expression was correlated with recurrence in GBM patients. Ectopic overexpression of miR-7-5p sensitized LN229/TMZ-R cells to TMZ and suppressed the stemness of glioblastoma stem cells (GSCs). Further experiments demonstrated that miR-7-5p exerts its role by directly targeting the 3'-untranslated region of Yin Yang 1 (YY1). Our findings suggest that combinational use of miR-7-5p and TMZ might be a promising therapeutic strategy to increase the long-term drug response in GBM patients.

Saliency Detection Based on the Combination of High-Level Knowledge and Low-Level Cues in Foggy Images.

A key issue in saliency detection of the foggy images in the wild for human tracking is how to effectively define the less obvious salient objects, and the leading cause is that the contrast and resolution is reduced by the light scattering through fog particles. In this paper, to suppress the interference of the fog and acquire boundaries of salient objects more precisely, we present a novel saliency detection method for human tracking in the wild. In our method, a combination of object contour detection and salient object detection is introduced. The proposed model can not only maintain the object edge more precisely via object contour detection, but also ensure the integrity of salient objects, and finally obtain accurate saliency maps of objects. Firstly, the input image is transformed into HSV color space, and the amplitude spectrum (AS) of each color channel is adjusted to obtain the frequency domain (FD) saliency map. Then, the contrast of the local-global superpixel is calculated, and the saliency map of the spatial domain (SD) is obtained. We use Discrete Stationary Wavelet Transform (DSWT) to fuse the cues of the FD and SD. Finally, a fully convolutional encoder-decoder model is utilized to refine the contour of the salient objects. Experimental results demonstrate that the presented model can remove the influence of fog efficiently, and the performance is better than 16 state-of-the-art saliency models.

Melatonin attenuates chronic pain related myocardial ischemic susceptibility through inhibiting RIP3-MLKL/CaMKII dependent necroptosis.

Chronic pain aggravates cardiovascular injury via incompletely understood mechanisms. While melatonin may participate in the pathophysiological process of chronic pain, its cardiovascular effects under chronic pain states remains unknown. In this study, chronic pain was induced by spared nerve injury model (SNI) for 4 weeks. We showed decreased the ipsilateral hind paw withdrawal mechanical threshold (PWMT) in SNI mice. High dose melatonin treatment (60 mg/kg, i.p.) could reversed nociceptive threshold in SNI mice. To verify the effect of chronic pain on the cardiac tolerance to ischemic stress, mice were subjected to myocardial ischemia-reperfusion (MI/R) in vivo. SNI mice showed exaggerated MI/R-induced detrimental effects and myocardial necroptosis compared with control group (P < .05). Mechanically, an increased level of tumor necrosis factor-α (TNF-α) was found in SNI group following by a robust interaction of RIP1/RIP3. RIP3-induced phosphor-MLKL and CaMKII more significantly in SNI mice (P < .05). We found that RIP3 deficiency provided a comparable protection against MI/R-induced necroptosis under chronic pain conditions. More importantly, low dose melatonin (20 mg/kg, i.p.) treatment 10 min before reperfusion decreased the level of TNF-α following with a negatively regulating the RIP3 induced phosphor-MLKL/CaMKII signaling, thus significantly reduced ROS production and cardiomyocyte necroptosis and ameliorated cardiac function. In summarize, our results demonstrated that chronic pain sensitizes heart to MI/R injury and myocardial necrosis plays an important role in this pathophysiological process. We also define melatonin acted as triple cardioprotective effects: ameliorating TNF-α level, suppressing RIP3-MLKL/CaMKII signaling induced necroptosis and exerting analgesia effect.

Synergistic tumoricidal effect of combined hPD-L1 vaccine and HER2 gene vaccine.

Immunotherapy is gathering momentum as a kind of important therapy for cancer patients. However, monotherapies have limited efficacy in improving outcomes and benefit only in a small subset of patients. Combination therapies targeting multiple pathways often can augment an immune response to improve survival further. Here, the tumoricidal effects of the dual hPD-L1(human programmed cell death ligand 1) vaccination/HER2(human epidermal growth factor receptor 2) gene vaccination immunotherapy against the established HER2-expressed cancers were observed. Animals treated with combination therapy using hPD-L1 vaccine and HER2 gene vaccine had significantly improved survival in a mammary carcinoma model. We observed an increase in tumor growth inhibition following treatment. The percentage of the tumor-free mice (%) was much higher in the combined PD-L1/HER2 group. Furthermore, under the tumor-burden condition, hPD-L1 vaccine enhanced humoral immunity of HER2 gene vaccine. And the combination treatment increased the IFN-γ-producing effector T cells. Additionally, splenocytes from the combined PD-L1/HER2 group immunized mice possessed higher CTL activity. Notably, vaccination with combination therapy induced a significant decrease in the percentage of CD4+CD25+ Treg cells. Collectively, these data demonstrate that PD-L1/HER2 gene vaccine combination therapy synergistically generates marked tumoricidal effects against established HER2-expressing cancers.

Identification of genes and pathways potentially related to PHF20 by gene expression profile analysis of glioblastoma U87 cell line.

BACKGROUND: Glioblastoma is the most common and aggressive brain tumor associated with a poor prognosis. Plant homeodomain finger protein 20 (PHF20) is highly expressed in primary human gliomas and its expression is associated with tumor grade. However, the molecular mechanism by which PHF20 regulates glioblastoma remains poorly understood. METHODS: Genome wide gene expression analysis was performed to identify differentially expressed genes (DEGs) in U87 cells with PHF20 gene knockdown. Gene ontology (GO) and pathway enrichment analyses were performed to investigate the functions and pathways of DEGs. Pathway-net and signal-net analyses were conducted to identify the key genes and pathways related to PHF20. RESULTS: Expression of 540 genes, including FEN1 and CCL3, were significantly altered upon PHF20 gene silencing. GO analysis results showed that DEGs were significantly enriched in small molecule metabolic and apoptotic processes. Pathway analysis indicated that DEGs were mainly involved in cancer and metabolic pathways. The MAPK, apoptosis and p53 signaling pathways were identified as the hub pathways in the pathway network, while PLCB1, NRAS and PIK3 s were hub genes in the signaling network. CONCLUSIONS: Our findings indicated that PHF20 is a pivotal upstream regulator. It affects the occurrence and development of glioma by regulating a series of tumor-related genes, such as FEN1, CCL3, PLCB1, NRAS and PIK3s, and activation of apoptosis signaling pathways. Therefore, PHF20 might be a novel biomarker for early diagnosis, and a potential target for glioblastoma therapies.

Chemical sintering of direct-written silver nanowire flexible electrodes under room temperature.

Transparent and flexible electrodes on cost effective plastic substrates for wearable electronics have attract great attention recently. Due to the conductivity and flexibility in network form, metal nanowire is regarded as one of the most promising candidates for flexible electrode fabrication. Prior to application, low temperature joining of nanowire processes are required to reduce the resistance of electrodes and simultaneously maintain the dimensionality and uniformity of those nanowires. In the present work, we presented an innovative, robust and cost effective method to minimize the heat effect to plastic substrate and silver nanowires which allows silver nanowire electrodes been directly written on polycarbonate substrate and sintered by different electrolyte solutions at room temperature or near. It has been rigorously demonstrated that the resistance of silver nanowire electrodes has been reduced by 90% after chemical sintering at room temperature due to the joining of silver nanowires at junction areas. After ∼1000 bending cycles, the measured resistance of silver nanowire electrode was stable during both up-bending and down-bending states. The changes of silver nanowires after sintering were characterized using x-ray photoelectron spectroscopy and transmission electron microscopy and a sintering mechanism was proposed and validated. This direct-written silver nanowire electrode with good performance has broad applications in flexible electronics fabrication and packaging.

Reliability and validity of the international dementia alliance schedule for the assessment and staging of care in China.

BACKGROUND: Clinical and social services both are important for dementia care. The International Dementia Alliance (IDEAL) Schedule for the Assessment and Staging of Care was developed to guide clinical and social care for dementia. Our study aimed to assess the validity and reliability of the IDEAL schedule in China. METHODS: Two hundred eighty-two dementia patients and their caregivers were recruited from 15 hospitals in China. Each patient-caregiver dyad was assessed with the IDEAL schedule by a rater and an observer simultaneously. The Clinical Dementia Rating (CDR), Mini-Mental Status Examination (MMSE), and Caregiver Burden Inventory (CBI) were assessed for criterion validity. IDEAL repeated assessment was conducted 7-10 days after the initial interview for 62 dyads. RESULTS: Two hundred seventy-seven patient-caregiver dyads completed the IDEAL assessment. Inter-rater reliability for the total score of the IDEAL schedule was 0.93 (95%CI = 0.92-0.95). The inter-class coefficient for the total score of IDEAL was 0.95 for the interviewers and 0.93 for the silent raters. The IDEAL total score correlated with the global CDR score (ρ = 0.72, p < 0.001), the CDR-sum of box (CDR-SOB, ρ = 0.74, p < 0.001), the total score of MMSE (ρ = -0.65, p < 0.001) and CBI (ρ = 0.70, p < 0.001). All item scores of the IDEAL schedule were associated with the CDR-SOB (ρ = 0.17 ~ 0.79, all p < 0.05). CONCLUSION: The IDEAL schedule is a valid and reliable tool for the staging of care for dementia in the Chinese population.

Insulin is an important risk factor of endometrial cancer among premenopausal women: a case-control study in China.

The aim of the article was to evaluate the important role played by insulin in the development of endometrial cancer (EC) among Chinese premenopausal women. In this study, 128 endometrial cancer patients and 294 controls who were all premenopausal were included. Baseline characteristics data were collected and serum insulin, C-peptide, sex hormone-binding globulin, C-reaction protein, interleukin-6, and tumor necrosis factor-α levels were measured. Paired t test, χ(2) test, Spearman correlation coefficients, and univariate and multivariate logistic regression models were used in data analysis. Furthermore, insulin levels were categorized into quartiles, and likelihood ratio was calculated for the four categories. Blood insulin levels of the patients were significantly higher than those of the controls (P < 0.001). Factor analysis identified insulin (OR = 2.46; 95 % confidence interval (CI) = 1.55-3.91; P < 0.001) as the independent risk factor of EC. When insulin levels were categorized into quartiles, we found that insulin was positively associated with endometrial cancer risk [HR comparing extreme quartiles (HR q4-q1) = 4.44; 95 % CI = 2.59-7.62; P trend = 0.025]. After adjustment for body mass index (BMI) or waist-hip ratio (WHR), this association was attenuated, but still significant. In conclusion, insulin plays an important role in the carcinogenesis of EC among premenopausal women. Treatment targeting down-regulation of blood insulin levels seems effective in the prevention of this malignancy.

[The Research of Vegetation Water Content Based on Spectrum Analysis and Angle Slope Index].

Vegetation water content is an important indicator of vegetal state, and a vital parameter of studying agriculture, ecological and hydrological. The diagnosis of vegetation water content has great significance for forest fire forecast and natural vegetation drought condition monitoring. The correlation analysis of the vegetation spectral reflectance and vegetation water content shows that the relativity between the spectral reflectance of different wavelengths and the vegetation water content varies considerably. The spectral reflectance of red band of visible light (620～700 nm) and the near-infrared band(800～1 350, 1 600～1 950, 2 200～2 400 nm) had a higher correlation with the vegetation water content. The slope angle indexes were used as parameters for estimating the vegetation water content based on analyzing the relation between the slope angle indexes and vegetation water content. An evaluation model of vegetation water content was set up by utilizing statistical linear regression model method. The band of 660, 850, 1 630, 2 200 nm were selected as RED, NIR, SWIR1 and SWIR2 band value of the slope angle index based on the analysis of the correlation between spectral reflectance and vegetation water content. A large amount of vegetation spectral information and vegetation water content were collected in the study area(the upstream of Minjiang River), and the linear regression model of the slope angle index (SANI, SASI, ANIR) and vegetation water content (FMC) was build. The linear regression model of ANIR and FMC has the highest of linear fitting and the linearity is up to 0.791. The near infrared angle index(ANIR)was improved on the basis of the analysis the linear regression results of angle slope vegetation index and water content. Near infrared angle normalized index (NANI) and near infrared angle slope index (NASI) were defined, and the linear regression model was established. Compared with the slope angle index (SANI, SASI, ANIR) which were proposed by Palacios-Orueta, NANI had more advantages in the vegetation water content inversion in the study area. The determination coefficient (R2) of the inversion model increased from 0.791 to 0.853, and root-mean-square error (RMSE) reduced from 0.047 to 0.039. Angle slope index had higher linear fitting and estimation accuracy by improving the angle of slope index. NANI and FMC linear regression model was established to estimate the vegetation water content in the study area. In this paper, the main innovation point is that the slope angle index NANI and NASI has been proposed on the basis of predecessors' research results, and the improved angle slope index has higher linear fitting and estimation accuracy compared with SANI, SASI, ANIR.

Molecular regulation of cervical cancer growth and invasion by VEGFa.

Although antivascular endothelial growth factor a (VEGFa) treatment has been well applied in cervical cancer therapy, the underlying molecular basis has not been precisely identified. Here, we examined the levels of VEGFa on the tumor growth and invasion in four commonly used human cervical cancer cell lines. We found that overexpression of VEGFa in these lines increased the tumor growth and invasiveness, while inhibition of VEGFa decreased the tumor growth and invasiveness. To figure out the involved signaling pathways, we applied specific inhibitors for ERK/MAPK, JNK, and PI3K/Akt signaling pathways, respectively, to VEGFa-overexpressing cervical cancer lines and found that only inhibition of PI3K/Akt signal transduction abolished VEGFa-induced increases in cell growth and invasiveness. Inhibition of Akt downstream mTor signaling similarly inhibited cell growth and invasion in VEGFa-overexpressing cervical cancer cells, suggesting that VEGFa may activate PI3K/Akt, and subsequently its downstream mTor signaling pathway, to promote cervical cancer cell growth and invasion. Furthermore, the effects of VEGFa-induced activation of mTor signaling cascades appeared to promote cancer cell growth through cyclinD1 and CDK4 activation and promote cancer cell invasion through MMP2 and MMP3. Taken together, our data suggest that anti-VEGFa treatment in cervical cancer may inhibit both tumor cell growth and invasion through PI3k/Akt/mTor signaling pathway.

Expression, purification and characterization of galectin-1 in Escherichia coli.

As a member of beta-galactoside-binding proteins family, Galectin-1 (Gal-1) contains a single carbohydrate recognition domain, by means of which it can bind glycans both as a monomer and as a homodimer. Gal-1 is implicated in modulating cell-cell and cell-matrix interactions and may act as an autocrine negative growth factor that regulates cell proliferation. Besides, it can also suppress TH1 and TH17 cells by regulating dendritic cell differentiation or suppress inflammation via IL-10 and IL-27. In the present study, Gal-1 monomer and concatemer (Gal-1②), which can resemble Gal-1 homodimer, were expressed in Escherichia coli and their bioactivities were analyzed. The results of this indicate that both Gal-1 and Gal-1② were expressed in E. coli in soluble forms with a purity of over 95% after purifying with ion-exchange chromatography. Clearly, both Gal-1 and Gal-1② can effectively promote erythrocyte agglutination in hemagglutinating activity assays and inhibit Jurkat cell proliferation in MTT assays. All these data demonstrate that bacterially-expressed Gal-1 and Gal-1② have activities similar to those of wild type human Gal-1 whereas the bioactivity of concatemer Gal-1② was stronger than those of the bacterially-expressed and wild type human Gal.

Prospective study of effects of endogenous estrogens on myocardial no-reflow risk in postmenopausal women with acute myocardial infarction.

The relationship between endogenous estrogens and cardiovascular disease in menopausal women remains poorly understood. Studies examining the relationship have yielded conflicting results. Therefore, we performed this study to prospectively assess the effects of endogenous estrogen on the risk of myocardial no-reflow in postmenopausal women with ST-elevation myocardial infarction (STEMI). Consecutive 100 postmenopausal women diagnosed with STEMI and who had undergone emergence percutaneous coronary intervention (PCI) were included in this study. Blood samples were obtained before PCI and assayed for endogenous sex hormones. Logistic regression models were developed with adjustment for confounders. Compared with normal-reflow group, the circulating levels of estrone, estradiol, sex hormone binding globulin (SHBG), and hypersensitive C-reaction protein (Hs-CRP) were significantly higher in the no-reflow group (P < 0.05). In univariable logistic regression models, lesion length, reference luminal diameter, thrombus score ≥ 4, and the levels of estrone, estradiol, and SHBG were all found to be positively associated with the risk of no-reflow (P < 0.05). After adjusting for these factors, thrombus score ≥ 4 (OR = 4.994, CI 1.987-10.518; P = 0.035), SHBG (OR = 0.800, CI 0.341-0.983; P = 0.047), and estradiol levels (OR 4.091, CI 1.105-8.582; P = 0.046) continued to demonstrate strong positive associations with the risk of no-reflow. Our data showed that high circulating levels of endogenous estrogens have a positive and statistically significant relationship with no-reflow in postmenopausal women with STEMI. It has been suggested that estrogens may have a potential detrimental effect on myocardial no-reflow. However, our results need to be confirmed in a larger population.

The beneficial effects of postconditioning on no-reflow phenomenon after percutaneous coronary intervention in patients with ST-elevation acute myocardial infarction.

No-reflow phenomenon is a serious complication of percutaneous coronary intervention (PCI) which is closely related to the incidence of major adverse cardiovascular events. It has been demonstrated that Postconditioning (PostC) during primary PCI confers protection against ischemia-reperfusion injury and thus might reduce infarct size. However, whether PostC may exert its beneficial effects on acute myocardial infarction (AMI) patients by reducing no-reflow phenomenon is still unknown. Sixty two patients diagnosed with ST-elevation AMI were randomly assigned to study group (n = 32) or control group (n = 30). Blood samples were obtained and assayed for creatine kinase MB (CK-MB) and high-sensitive C-reactive protein (hs-CRP). Determinants of reflow, including final thrombolysis in myocardial infarction (TIMI) grade-3 flow, ST-segment resolution (STR), myocardial blush grades-3 (MBG-3) and corrected thrombolysis in myocardial infarction frame count (cTFC), were comparative between the two groups. Compared with control group, more patients in study group were identified as the final TIMI grade-3 flow (81.3 vs. 56.7%, P = 0.036), MBG-3 (23 vs. 14%, P = 0.043) and STR ≥50% (93.8 vs. 73.3%, P = 0.029), while patients in study group had less cTFC (28.5 ± 9.1 vs. 37.4 ± 12.4, P = 0.002) After PCI, study group was associated with lower levels of CK-MB (2,397.6 ± 470.2 vs. 2,159.9 ± 485.5, P = 0.028), Troponin-I (197.5 ± 32.5 vs. 154 ± 43.1, P = 0.041) and hs-CRP (5.5 ± 4.5 vs. 9.5 ± 5.2 mg/L, P = 0.019) in comparison with control group. Left ventricle ejection fraction was better in the study group than in the control group (55.1 ± 9.8 vs. 42.9 ± 10.7, P = 0.042). PostC could improve myocardial reperfusion in patients with ST-elevation AMI undergoing PCI by reducing no-reflow. However, due to the limited sample size, the results of our study should not be considered conclusive.

Aberrant DNA methylation of G-protein-coupled bile acid receptor Gpbar1 (TGR5) is a potential biomarker for hepatitis B Virus associated hepatocellular carcinoma.

BACKGROUND: G-protein-coupled bile acid receptor Gpbar1 (TGR5) is a newly identified liver tumor suppressor in carcinogenesis. This present study was therefore to determine the potential value of serum TGR5 promoter methylation in identifying hepatocellular carcinoma (HCC) from chronic hepatitis B (CHB) patients. METHODS: The circulating cell-free DNA (cfDNA) was extracted from a retrospective dataset including 160 HCC, 88 CHB and 45 healthy controls (HCs). Methylation status of TGR5 promoter was examined by methylation-specific polymerase chain reaction (MSP). RESULTS: Hypermethylation of the TGR5 promoter occurred significantly more frequent in HCC (77/160, 48.13%) than CHB (12/88, 13.64%; p<0.01) and HCs (2/45, 4.44%; p<0.01). The methylation rate of TGR5 in HCC patients ≥60 years old was significantly higher than those <60 years old (p<0.05). Alpha fetoprotein (AFP) had sensitivity of 58.13%, 30.63% and 24.38% at cut-off points of 20, 200 and 400ng/ml respectively; while TGR5 methylation combined AFP had sensitivity of 81.25%, 68.13% and 65%. AFP had specificity of 47.73%, 92.05% and 98.86% at cut-off points of 20, 200 and 400ng/ml respectively; while TGR5 methylation combined AFP had specificity of 38.64%, 78.41% and 85.23%. AFP had Youden index of 0.06, 0.23 and 0.23 at cut-off points of 20, 200 and 400ng/ml respectively; while TGR5 methylation combined AFP had Youden index of 0.20, 0.47 and 0.50. CONCLUSIONS: Our findings strongly suggested the combination of serum TGR5 promoter methylation and AFP enhanced the diagnostic value of AFP alone in discriminating HCC from CHB patients.