Retraction Notice to: ALDH2 Glu504Lys Polymorphism and Susceptibility to Coronary Artery Disease and Myocardial Infarction in East Asians: A Meta-analysis.

This article has been retracted: please see Elsevier Policy on Article Withdrawal (https://www.elsevier.com/locate/withdrawalpolicy). This article has been retracted at the request of the Editorial Board of the Archives of Medical Research after receiving a complaint reporting that the article was based on an unreliable or non-existent statistical method. After analyzing the complaint and carefully reviewing the article, the Editorial Board contacted the corresponding author following due process and received no response. The Editorial Board no longer has confidence in the article and therefore decided to retract the article. Apologies are offered to readers of the journal that this was not detected during the review process.

Development and validation of a simple model to predict functionally significant coronary artery disease in Chinese populations: A two-center retrospective study.

Objectives: This study sought to derive and validate a simple model combining traditional clinical risk factors with biomarkers and imaging indicators easily obtained from routine preoperative examinations to predict functionally significant coronary artery disease (CAD) in Chinese populations. Methods: We developed five models from a derivation cohort of 320 patients retrospective collected. In the derivation cohort, we assessed each model discrimination using the area under the receiver operating characteristic curve (AUC), reclassification using the integrated discrimination improvement (IDI) and net reclassification improvement (NRI), calibration using the Hosmer-Lemeshow test, and clinical benefit using decision curve analysis (DCA) to derive the optimal model. The optimal model was internally validated by bootstrapping, and external validation was performed in another cohort including 96 patients. Results: The optimal model including 5 predictors (age, sex, hyperlipidemia, hs-cTnI and LVEF) achieved an AUC of 0.807 with positive NRI and IDI in the derivation cohort. Moreover, the Hosmer-Lemeshow test showed a good fit, and the DCA demonstrated good clinical net benefit. The C-statistic calculated by bootstrapping internal validation was 0.798, and the calibration curve showed adequate calibration (Brier score = 0.179). In the external validation cohort, the optimal model performance was acceptable (AUC = 0.704; Brier score = 0.20). Finally, a nomogram based on this model was constructed to facilitate its use in clinical practice. Conclusions: A simple model combined clinical risk factors with hs-cTnI and LVEF improving the prediction of functionally significant CAD in Chinese populations. This attractive model may be a choice for clinicians to risk stratification for CAD.

Risk factors of systemic lupus erythematosus: an overview of systematic reviews and Mendelian randomization studies.

BACKGROUND: The etiology of systemic lupus erythematosus is complex and incurable. A large number of systematic reviews have studied the risk factors of it. Mendelian randomization is an analytical method that uses genetic data as tool variables to evaluate the causal relationship between exposure and outcome. OBJECTIVE: To review the systematic reviews and Mendelian randomization studies that focused on the risk factors of systemic lupus erythematosus and shed light on the development of treatments for its prevention and intervention. METHODS: From inception to January 2022, we systematically searched MEDLINE (via PubMed) and Embase for related systematic reviews and Mendelian randomization studies. Extract relevant main data for studies that meet inclusion criteria. The quality of systematic reviews was assessed by using Assessment of Multiple Systematic Reviews 2 (AMSTAR-2). Finally, the risk factors are scored comprehensively according to the results' quantity, quality, and consistency. RESULTS: Our study involved 64 systematic reviews and 12 Mendelian randomization studies. The results of systematic reviews showed that diseases (endometriosis, atopic dermatitis, allergic rhinitis), lifestyle (smoking, drinking, vaccination), and gene polymorphism influenced the incidence of systemic lupus erythematosus. The results of Mendelian randomization studies identified the role of disease (periodontitis, celiac disease), trace elements (selenium, iron), cytokines (growth differentiation factor 15), and gut microbiome in the pathogenesis of systemic lupus erythematosus. CONCLUSION: We should pay attention to preventing and treating systemic lupus erythematosus in patients with endometriosis, celiac disease, and periodontitis. Take appropriate dietary supplements to increase serum iron and selenium levels to reduce the risk of systemic lupus erythematosus. There should be no excessive intervention in lifestyles such as smoking and drinking.

A histidine-rich fusion tag enables real-time monitoring of recombinant protein expression by Pauly reaction-based colorimetric assay.

Commercially available recombinant expression systems always use fusion tags to facilitate target protein purification and SDS-PAGE analysis followed by Coomassie Brilliant Blue (CBB) staining is the classical method to validate the expression level of target protein, which is time-consuming, although not very laborious. Previously, we found that a histidine-rich elastin-like polypeptide (HRELP) tag could make its fusion proteins being quickly and specifically stained with Pauly's reagent. In this study, we designed a Pauly reaction-based colorimetric assay to real-time monitoring of the expression level of recombinant protein tagged HRELP and found that the absorption value of post-induction E. coli cells stained with Pauly's reagent correlated well with both the band intensity of the target protein from Pauly's reagent-stained and CBB-stained gels. Moreover, we found the colorimetric assay could also be helpful to roughly estimate the expression efficiency by using a poly-histidine-tagged protein, which has only 1.17% histidine residue. In our opinion, Pauly reaction-based colorimetric assay could significantly shorten the time to validate the over-expression of recombinant protein tagged with either HRELP or poly-histidine. And HRELP seemed to be an ideal fusion tag for it can not only facilitate protein purification but also simplify protein detection.

Non-invasive brain stimulation treatments for migraine prophylaxis: a network meta-analysis of randomized controlled trials.

BACKGROUND AND OBJECTIVES: Migraine is a major public health problem owing to its long disease duration and disease relapse. Non-invasive brain stimulation treatments were reported effective for the management of migraine, but the comparative effectiveness of three main NIBSs, rTMS, nVNS, and tDCS, has not been studied. We aimed to explore the relative efficacy of rTMS, tDCS, and nVNS in migraine prophylaxis by using network meta-analysis (NMA). METHODS: We searched OVID Medline, Embase, Cochrane Controlled Register of Trials, and Web of Science from inception to 1 January 2022. Randomized controlled trials that reported the efficacy of rTMS, tDCS or nVNS in the prophylactic treatment of migraine were included. The primary outcome was monthly migraine frequency, and secondary outcomes were headache intensity and the impact of headaches on daily life. The relative effects of the treatments in contrast to the others were measured by using standard mean difference (SMD). RESULTS: We included 31 trials with 1659 participants. Fourteen trials were rated as low risk of bias. The results showed that tDCS (SMD - 1.58; 95%CI, - 2.38 to - 0.79; P-score = 0.92) had the largest effect on migraine frequency when compared with sham interventions in reducing monthly migraine frequency, and tDCS had a larger effect than rTMS (SMD - 0.62; 95%CI, - 1.81 to 0.57) and nVNS (SMD - 1.39; 95%CI, - 3.27 to 0.49). tDCS had also the largest effect in reducing pain intensity when compared with sham intervention (SMD - 1.49; 95%CI, - 2.46 to - 0.52) and rTMS (SMD - 0.48; 95%CI, - 2.06 to 1.09). CONCLUSIONS: For the prophylactic treatment of migraine, tDCS was relatively more effective than rTMS and nVNS. Head-to-head comparison trials are needed to confirm the findings.

Dietary interventions for pediatric patients with functional abdominal pain disorders: a systematic review and network meta-analysis.

Dietary therapies are recommended for the treatment of pediatrics with functional abdominal pain disorders (FAPDs), but the comparative effectiveness among them is unclear. Therefore, the main aim of this systematic review and meta-analysis was to compare the effectiveness of differential dietary therapies in pediatrics with functional abdominal pain disorders. We searched PubMed, Embase, and the Cochrane Central Register of Controlled Trials databases from inception to February 28, 2023. Randomized clinical trials of dietary treatments for pediatric patients with functional abdominal pain disorders were included. The primary outcome was the improvement in abdominal pain. The secondary outcomes were changes in pain intensity and pain frequency. Thirty-one studies after screening 8695 retrieved articles were included, and 29 studies were available for network meta-analysis. Compared with placebo, fiber (RR, 4.86; 95%CI, 1.77 to 13.32; P-score = 0.84), synbiotics (RR, 3.92; 95%CI, 1.65 to 9.28; P-score = 0.75), and probiotics (RR, 2.18; 95%CI, 1.46 to 3.26; P-score = 0.46) had significantly larger effect on the improvement in abdominal pain, the three treatments had larger effect than placebo but statistically insignificant in difference in improving pain frequency and intensity. Similarly, there were no significant differences between the dietary treatments after indirect comparisons of the three outcomes.  Conclusion: Fiber supplements, synbiotics, and probiotics were efficacious in improving abdominal pain of FAPDs in children, suggested by very low or low evidence. The evidence of the efficacy of probiotics is more convincing than fiber and synbiotics when sample size and statistical power were considered. No difference in the efficacy of the three treatments. High-quality trials are needed to further investigate the efficacy of dietary interventions. What is Known: • Multiple dietary treatment options are available for functional abdominal pain disorders in the pediatric population, of which the most beneficial one is currently unknown. What is New: • This NMA found very low to low certainty of the evidence suggesting that fiber, synbiotics, and probiotics might be more efficacious in improving abdominal pain of FAPDs in children than the other dietary treatments. • There were no significant differences between active dietary treatments for changes in abdominal pain intensity.

Risk factors of systemic lupus erythematosus: an overview of systematic reviews and Mendelian randomization studies

Abstract Background The etiology of systemic lupus erythematosus is complex and incurable. A large number of systematic reviews have studied the risk factors of it. Mendelian randomization is an analytical method that uses genetic data as tool variables to evaluate the causal relationship between exposure and outcome. Objective To review the systematic reviews and Mendelian randomization studies that focused on the risk factors of systemic lupus erythematosus and shed light on the development of treatments for its prevention and intervention. Methods From inception to January 2022, we systematically searched MEDLINE (via PubMed) and Embase for related systematic reviews and Mendelian randomization studies. Extract relevant main data for studies that meet inclusion criteria. The quality of systematic reviews was assessed by using Assessment of Multiple Systematic Reviews 2 (AMSTAR-2). Finally, the risk factors are scored comprehensively according to the results' quantity, quality, and consistency. Results Our study involved 64 systematic reviews and 12 Mendelian randomization studies. The results of systematic reviews showed that diseases (endometriosis, atopic dermatitis, allergic rhinitis), lifestyle (smoking, drinking, vaccination), and gene polymorphism influenced the incidence of systemic lupus erythematosus. The results of Mendelian randomization studies identified the role of disease (periodontitis, celiac disease), trace elements (selenium, iron), cytokines (growth differentiation factor 15), and gut microbiome in the pathogenesis of systemic lupus erythematosus. Conclusion We should pay attention to preventing and treating systemic lupus erythematosus in patients with endometriosis, celiac disease, and periodontitis. Take appropriate dietary supplements to increase serum iron and selenium levels to reduce the risk of systemic lupus erythematosus. There should be no excessive intervention in lifestyles such as smoking and drinking.

Prognosis of Oligodendroglioma Patients Stratified by Age: A SEER Population-Based Analysis.

PURPOSE: Glioma may affect patients of any age. So far, only a limited number of big data studies have been conducted concerning oligodendroglioma (OG) in diverse age groups. This study evaluated the risk factors for OG in different age groups using the Surveillance, Epidemiology, and End Results (SEER) database built by the National Cancer Institute, which is part of the National Institutes of Health. PATIENTS AND METHODS: A total of 5437 cases within the SEER database were included. These patients were divided into seven age groups. The Kaplan-Meier method was employed for survival analysis. The independent risk factors for the survival of OG patients were identified using the Cox regression model. A nomogram was drawn with R software based on the independent risk factors. The X-tile software was adopted to find the optimal age group at diagnosis. RESULTS: The all-cause mortality and the tumor-specific mortality increased with age. The univariate analysis showed that the patients' age, gender, primary lesion location, side affected by the primary lesion (left or right), surgery for the primary lesion, and tumor size were correlated with survival (P<0.05). Multivariate Cox regression analysis showed that age was an independent risk factor for the survival of OG patients (P<0.05). The optimal cutoff value of age in terms of overall survival (OS) and cause-specific survival (CSS) were identified as 48 and 61 years and 48 and 59 years, respectively. CONCLUSION: The older the age, the worse the survival would be. That's, the mortality increased with age. In the clinic, healthcare professionals should be fully aware of the variability in the prognosis of OG patients in different age groups. Therefore, individualized treatments are recommended to OG patients in different age groups to optimize the prognosis.

Free Triiodothyronine Connected With Metabolic Changes in Patients With Coronary Artery Disease by Interacting With Other Functional Indicators.

This study aims to evaluate the association between free triiodothyronine (FT3) and outcomes of coronary artery disease (CAD) patients, as well as to assess the predictive power of FT3 and related functional markers from the perspective of potential mechanism. A total of 5104 CAD patients with an average follow-up of three years were enrolled into our study. Multivariate Cox regression was used to evaluate the associations between FT3, FT4 (free thyroxin), FT3/FT4 and death, MACE. We developed and validated an age, biomarker, and clinical history (ABC) model based on FT3 indicators to predict the prognosis of patients with CAD. In the multivariable Cox proportional hazards model, FT3 and FT3/FT4 were independent predictors of mortality (Adjusted HR = 0.624, 95% CI = 0.486-0.801; adjusted HR = 0.011, 95% CI = 0.002-0.07, respectively). Meanwhile, emerging markers pre-brain natriuretic peptide, fibrinogen, and albumin levels are significantly associated with low FT3 (p < 0.001). The new risk death score based on biomarkers can be used to well predict the outcomes of CAD patients (C index of 0.764, 95% CI = 0.731-0.797). Overall, our findings suggest that low levels of FT3 and FT3/FT4 are independent predictors of death and MACE risk in CAD patients. Besides, the prognostic model based on FT3 provides a useful tool for the death risk stratification of CAD patients.

Blockage of glioma cell survival by truncated TEAD-binding domain of YAP.

BACKGROUND: Gliomas are highly aggressive and lack of efficient targeted therapy. YAP, as a Hippo pathway downstream effector, plays a key role in promoting tumor development through the interaction with transcription factor TEAD on the NH3-terminal proline-rich domain. Therefore, targeting TEAD-interacting domain of YAP may provide a novel approach for the treatment of gliomas. MATERIALS AND METHODS: We generated a truncated YAP protein which includes the TEAD-binding domain (YAPBD), and supposed YAPBD can interact with endogenous TEAD but lost the function to activate YAP target gene expressions. The association of YAP expression with the malignant characters of glioma tissues were determined by immunohistochemistry. TEAD-binding capacity of YAPBD was determined by co-immunoprecipitation. The cell proliferation and migration were determined by MTT assay, xenograft assay, wound healing assay and transwell assay, respectively. YAP target genes were detected by Western blot. RESULTS: YAP was highly expressed in glioma tissues and associated with tumor malignancy. YAPBD could block the TEAD-YAP complex formation by competing with YAP binding to TEAD. YAPBD could inhibit glioma cell growth both in vitro and in vivo, through the induction of cell cycle arrest and apoptosis. The cell cycle-related gene cyclin D1 and c-myc, and anti-apoptotic gene Bcl-2, Bcl-xL and survivin were inhibited after YAPBD overexpression. Furthermore, YAPBD also decreased cell migration and invasion, and repressed epithelial-mesenchymal transition. CONCLUSION: YAPBD can block glioma cell survival and repress YAP-dependent gene expressions, indicating gene therapy which targets TEAD-YAP complex would be a potential and significant novel approach for human malignant gliomas.

Truncated TEAD-binding protein of TAZ inhibits glioma survival through the induction of apoptosis and repression of epithelial-mesenchymal transition.

Transcriptional coactivator with PDZ-binding motif (TAZ), a Hippo pathway downstream effector, promotes tumor progression by serving as a transcriptional coactivator with TEAD. Here, we introduced a new construct which can express the TEAD-binding domain of TAZ protein (TAZBD), and determined its antitumor effect in malignant glioma both in vitro and in vivo. We first observed that TAZ was upregulated in glioma tissues and related to malignant clinicopathologic characteristic, indicating the crucial role of TAZ during glioma progression. In U87 and U251 cells, TAZBD expression increased the proportion of apoptotic cells, and suppressed the colony formation and tumorigenicity. Further, TAZBD also decreased cell metastasis through the repression of epithelial-mesenchymal transition. The mechanistic study showed that TAZBD suppression of glioma cells was predominantly through blocking the TAZ-TEAD complex formation by competing with endogenous TAZ. Thus, the gene therapy of malignant glioma through blocking TAZ-TEAD complex by TAZBD may provide a new way for the targeted therapy of glioma.

A histidine-rich elastin-like polypeptide functions as a quickly detectable and easily purifiable protein fusion tag.

Although many protein fusion tags have been developed for recombinant protein production to improve protein yields or facilitate purification, determining the expression and purification of the fusion protein still remain to be a time-consuming and laborious procedure. In this work, we designed a histidine-rich elastin-like polypeptide (HRELP) fusion tag and found that it could be efficiently expressed in E. coli cells and specifically stained with Pauly's reagent in a couple of minutes post SDS-PAGE analysis. Moreover, in Pauly's reagent-stained polyacrylamide gels, only the bands of HRELP fusion proteins were yellow and could be clearly visualized with little background. Furthermore, both HRELPs and HRELP20-BMP2 fusion protein could be purified by a method of pH shift-mediated inverse transition cycling (ITC). In our opinion, the HRELP established in this study may be considered as a multifunctional protein tag which could make its fusion proteins being quickly detected by Pauly staining and simply purified by pH-triggered ITC in addition to having the potential to sustained release its fusion proteins.

Optimal hydration volume among high-risk patients with advanced congestive heart failure undergoing coronary angiography.

We investigated the relationship between weight-adjusted hydration volumes and the risk of developing contrast-induced acute kidney injury (CI-AKI) and worsening heart failure (WHF) and explored the relative safety of optimal hydration volumes in patients with advanced congestive heart failure (CHF) undergoing coronary angiography (CAG) or percutaneous coronary intervention. We included 551 patients with advanced CHF (New York Heart Association class > 2 or history of pulmonary edema) undergoing CAG (follow-up period 2.62 ± 0.9 years). There was a significant association between hydration volume-to-weight ratio (HV/W) (quintile Q1, Q2, Q3, Q4, and Q5) and the incidence of CI-AKI (3.7%, 14.6%, 14.3%, 21.1%, and 31.5%, respectively) and WHF (3.6%, 5.4%, 8.3%, 13.6%, and 19.1%, respectively) (all P-trend < 0.001). Receiver operating curve analysis indicated that HV/W = 15 mL/kg and the mean HV/W (60.87% sensitivity and 64.96% specificity) were fair discriminators for CI-AKI (C-statistic 0.696). HV/W >15 mL/kg independently predicted CI-AKI (adjusted odds ratio [OR] 2.33; P = 0.016) and WHF (adjusted OR 2.13; P = 0.018). Moreover, both CI-AKI and WHF were independently associated with increased long-term mortality. Thus, for high-risk patients with advanced CHF undergoing CAG, HV/W > 15 mL/kg might be associated with an increased risk of developing CI-AKI and WHF. The potential benefits of a personalized limitation of hydration volume need further evaluation.

Growth Factor-Reinforced ECM Fabricated from Chemically Hypoxic MSC Sheet with Improved In Vivo Wound Repair Activity.

MSC treatment can promote cutaneous wound repair through multiple mechanisms, and paracrine mediators secreted by MSC are responsible for most of its therapeutic benefits. Recently, MSC sheet composed of live MSCs and their secreted ECMs was reported to promote wound healing; however, whether its ECM alone could accelerate wound closure remained unknown. In this study, Nc-ECM and Cc-ECM were prepared from nonconditioned and CoCl2-conditioned MSC sheets, respectively, and their wound healing properties were evaluated in a mouse model of full-thickness skin defect. Our results showed that Nc-ECM can significantly promote wound repair through early adipocyte recruitment, rapid reepithelialization, enhanced granulation tissue growth, and augmented angiogenesis. Moreover, conditioning of MSC sheet with CoCl2 dramatically enriched its ECM with collagen I, collagen III, TGF-ß1, VEGF, and bFGF via activation of HIF-1α and hence remarkably improved its ECM's in vivo wound healing potency. All the Cc-ECM-treated wounds completely healed on day 7, while Nc-ECM-treated wounds healed about 85.0% ± 8.6%, and no-treatment wounds only healed 69.8% ± 9.6% (p < 0.05). Therefore, we believe that such growth factor-reinforced ECM fabricated from chemically hypoxic MSC sheet has the potential for clinical translation and will lead to a MSC-derived, cost-effective, bankable biomaterial for wound management.

Evaluation of xenogeneic extracellular matrix fabricated from CuCl2-conditioned mesenchymal stem cell sheets as a bioactive wound dressing material.

The extracellular matrix has drawn considerable interest in tissue engineering not only acts as a bioactive three-dimensional scaffold but also regulates cell behaviors through providing biochemical signals. Extracellular matrix-based biomaterials, mainly derived from xenogeneic tissues, have shown positive outcomes in promoting cutaneous wound healing. However, such extracellular matrices only contain low doses of growth factors, which limit their therapeutic efficiency. Recent reports demonstrated that cell sheets made from mesenchymal stem cell can accelerate wound repair through enhanced re-epithelialization and angiogenesis, but its clinical translation is hindered by several limitations, such as the risk of aberrant immune responses and cost implications. In this study, acellular extracellular matrices were prepared from CuCl2-conditioned mesenchymal stem cell sheets and their in vivo wound healing properties were evaluated in a mouse model of full-thickness skin defect. We found that extracellular matrices derived from CuCl2-conditioned mesenchymal stem cell sheets have a compact surface with thick solid-like cross-sectional structure. Moreover, CuCl2 dramatically enriched the extracellular matrices with collagen I, collagen III, transforming growth factor-ß1, vascular endothelial growth factor, and basic fibroblast growth factor via hypoxia-inducible factor-1α activation. And as a consequence, the resulting extracellular matrices showed markedly improved in vivo wound healing potency through early adipocyte mobilization, enhanced granulation tissues formation, rapid re-epithelialization, and augmented angiogenesis. Therefore, we consider that the extracellular matrix derived from CuCl2-conditioned mesenchymal stem cell sheets has the potential for clinical translation and may lead to a novel strategy for wound management.

Intensity of hydration changes the role of renin-angiotensin-aldosterone system blockers in contrast-induced nephropathy risk after coronary catheterisation in patients with chronic kidney disease.

OBJECTIVE: This study evaluated the potential effect of hydration intensity on the role of angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs) on contrast-induced nephropathy in patients with renal insufficiency. METHODS: All eligible patients were included and stratified according to hydration intensity defined as saline hydration volume to body weight tertiles: <10.21 mL/kg, 10.21 to <17.86 mL/kg, and ⩾17.86 mL/kg. RESULTS: In total, 84 (6.7%) of 1254 patients developed contrast-induced nephropathy: 6.2% in the ACEI/ARB group versus 10.8% in the non-ACEI/ARB group ( P=0.029), with an adjusted odds ratio (OR) of 0.89 (95% confidence interval (CI) 0.46-1.73, P=0.735). The incidence of contrast-induced nephropathy was lower in the ACEI/ARB group than in the non-ACEI/ARB group in the second tertile ( P=0.031), while not significantly different in the first ( P=0.701) and third ( P=0.254) tertiles. ACEIs/ARBs were independently associated with a lower contrast-induced nephropathy risk (OR 0.26, 95% CI 0.09-0.74, P=0.012) and long-term all-cause death (hazard ratio 0.461, 95% CI 0.282-0.755, P=0.002) only in the second hydration volume to body weight tertile. CONCLUSION: The effects of ACEIs/ARBs on contrast-induced nephropathy risk vary according to saline hydration intensity in chronic kidney disease patients, and may further reduce contrast-induced nephropathy risk in patients administered moderate saline hydration.

Comparison of Different Risk Scores for Predicting Contrast Induced Nephropathy and Outcomes After Primary Percutaneous Coronary Intervention in Patients With ST Elevation Myocardial Infarction.

Accurate risk stratification for contrast-induced nephropathy (CIN) is important for patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PPCI). We aimed to compare the prognostic value of validated risk scores for CIN. We prospectively enrolled 422 consecutive patients with STEMI undergoing PPCI. Mehran; Gao; Chen; age, serum creatinine (SCr), or glomerular filtration rate, and ejection fraction (ACEF or AGEF); and Global Registry for Acute Coronary Events risk scores were calculated for each patient. The prognostic accuracy of the 6 scores for CIN, and in-hospital and 3-year all-cause mortality and major adverse clinical events (MACEs), was assessed using the c-statistic for discrimination and the Hosmer-Lemeshow test for calibration. CIN was defined as either CIN-narrow (increase in SCr ≥0.5 mg/dl) or CIN broad (≥0.5 mg/dl and/or a ≥25% increase in baseline SCr). All risk scores had relatively high predictive values for CIN-narrow (c-statistic: 0.746 to 0.873) and performed well for prediction of in-hospital death (0.784 to 0.936), MACEs (0.685 to 0.763), and 3-year all-cause mortality (0.655 to 0.871). The ACEF and AGEF risk scores had better discrimination and calibration for CIN-narrow and in-hospital outcomes. However, all risk score exhibited low predictive accuracy for CIN-broad (0.555 to 0.643) and 3-year MACEs (0.541 to 0.619). In conclusion, risk scores for predicting CIN perform well in stratifying the risk of CIN-narrow, in-hospital death or MACEs, and 3-year all-cause mortality in patients with STEMI undergoing PPCI. The ACEF and AGEF risk scores appear to have greater prognostic value.

The cap-translation inhibitor 4EGI-1 induces mitochondrial dysfunction via regulation of mitochondrial dynamic proteins in human glioma U251 cells.

Translation initiation factors (eIFs) are over-activated in many human cancers and may contribute to their progression. The small molecule 4EGI-1, a potent inhibitor of translation initiation through disrupting eIF4E/eIF4G interaction, has been shown to exert anti-cancer effects in human cancer cells. The goal of the present study was to evaluate the anti-cancer effects of 4EGI-1 in human glioma U251 cells. We found that 4EGI-1 impaired the assembly of the eIF4F complex, and inhibited proliferation of U251 cells via inducing apoptosis. 4EGI-1 treatment induced collapse of mitochondrial membrane potential (MMP) and production of intracellular reactive oxygen species (ROS), which were prevented by the ROS scavenger N-acetyl-cysteine (NAC). In addition, 4EGI-1 inhibited mitochondrial ATP synthesis via suppressing complex I activity, but had no effects on mitochondrial biogenesis. The results of fluorescence staining showed that 4EGI-1 indeed fragmented the mitochondrial network of U251 cells. We found a significant decrease in optic atrophy type 1 (Opa-1) and mitofusin 1 (Mfn-1) related to fusion proteins as well as an increase in fission protein dynamin-related protein 1 (Drp-1). Furthermore, the anti-cancer effects of 4GI-1 were partially nullified by knock down of Drp-1 using siRNA. These data indicate that the use of inhibitors that directly target the translation initiation complex eIF4F could represent a potential novel approach for human glioma therapy.

Contrast-induced nephropathy following chronic total occlusion percutaneous coronary intervention in patients with chronic kidney disease.

OBJECTIVES: Contrast-induced nephropathy (CIN) has not been systematically studied in high-risk patients with chronic kidney disease (CKD) undergoing percutaneous coronary intervention (PCI) for chronic total occlusion (CTO). METHODS: We prospectively observed 515 consecutive patients with CKD undergoing PCI. Patients were divided into three groups: patients who underwent attempted PCI for CTO (group A, n = 85), patients who did not receive PCI for CTO (group B, n = 45) and patients without CTO (group C, n = 385). RESULTS: CIN developed in 55 patients (10.68 %). Group A patients received a larger CM dose than group B or group C (p = 0.024). The intravenous hydration volume, age and CIN Mehran score were not significantly different between the three groups. The incidence of CIN was 9.4 % for group A, 6.7 % for group B and 11.4 % for group C (p = 0.344). In-hospital mortality and required renal replacement therapy (p = 0.325) were not significantly different between the groups. Multivariate analysis showed that after adjusting for potential confounding factors, the odds ratio for CIN was 1.03 (p = 0.944) for group A and 0.64 for group B (p = 0.489) compared to group C. CONCLUSIONS: Attempts to achieve recanalization of CTO in patients with CKD might not increase the risk of CIN if appropriate preventative measures are taken. KEY POINTS: • Contrast-induced nephropathy can increase morbidity and mortality • Chronic kidney disease patients are at the greatest risk of CIN • Patients with CKD undergoing CTO-PCI are common • Incidence of CIN has not been reported in CKD patients • CTO-PCI in CKD patients might not increase the risk of CIN.

Statins for the Prevention of Contrast-Induced Nephropathy After Coronary Angiography/Percutaneous Interventions: A Meta-analysis of Randomized Controlled Trials.

BACKGROUND: Statins have been demonstrated to prevent the development of contrast-induced nephropathy (CIN). Nevertheless, clinical research has indicated conflicting results. We performed a meta-analysis of randomized controlled trials (RCTs) to evaluate the protective effects of statins on CIN and the requirement of renal replacement therapy (RRT) in patients undergoing coronary angiography/percutaneous interventions. METHODS: PubMed, MEDLINE, Web of Science, EMBASE, ClinicalTrials.gov, and the Cochrane Central RCTs were searched for RCTs from inception to February 2014 to compare statins with placebo treatment for preventing CIN in patients undergoing coronary angiography/percutaneous interventions. RESULTS: Nine RCTs were identified and analyzed in a total of 5143 patients involving 2560 patients with statin pretreatment and 2583 patients as control. Patients who received statin therapy had a 53% lower risk of CIN with different definitions (within 48 or 72 hours) compared to the control group based on a fixed effect model (risk ratio = 0.47, 95% confidence interval = 0.37-0.60, P < .0001) and were less likely to require RRT based on Peto fixed effect. Subgroup analysis showed that statin pretreatment could decrease the incidence of CIN in patients with preexisting renal dysfunction or diabetes mellitus. In addition, patients on rosuvastatin had a similar reduced incidence of CIN compared to patients on atorvastatin. CONCLUSION: This updated meta-analysis demonstrated that preprocedural statin treatment could reduce the risk of CIN and the need for RRT in patients undergoing coronary angiography/percutaneous interventions. Moreover, statin therapy would be helpful in reducing the incidence of CIN in high-risk patients with preexisting renal dysfunction or diabetes mellitus. Additionally, rosuvastatin and atorvastatin had similar efficacies in preventing CIN development.