Artificial intelligence-enabled 8-lead ECG detection of atrial septal defect among adults: a novel diagnostic tool.

Background: Patients with atrial septal defect (ASD) exhibit distinctive electrocardiogram (ECG) patterns. However, ASD cannot be diagnosed solely based on these differences. Artificial intelligence (AI) has been widely used for specifically diagnosing cardiovascular diseases other than arrhythmia. Our study aimed to develop an artificial intelligence-enabled 8-lead ECG to detect ASD among adults. Method: In this study, our AI model was trained and validated using 526 ECGs from patients with ASD and 2,124 ECGs from a control group with a normal cardiac structure in our hospital. External testing was conducted at Wuhan Central Hospital, involving 50 ECGs from the ASD group and 46 ECGs from the normal group. The model was based on a convolutional neural network (CNN) with a residual network to classify 8-lead ECG data into either the ASD or normal group. We employed a 10-fold cross-validation approach. Results: Statistically significant differences (p < 0.05) were observed in the cited ECG features between the ASD and normal groups. Our AI model performed well in identifying ECGs in both the ASD group [accuracy of 0.97, precision of 0.90, recall of 0.97, specificity of 0.97, F1 score of 0.93, and area under the curve (AUC) of 0.99] and the normal group within the training and validation datasets from our hospital. Furthermore, these corresponding indices performed impressively in the external test data set with the accuracy of 0.82, precision of 0.90, recall of 0.74, specificity of 0.91, F1 score of 0.81 and the AUC of 0.87. And the series of experiments of subgroups to discuss specific clinic situations associated to this issue was remarkable as well. Conclusion: An ECG-based detection of ASD using an artificial intelligence algorithm can be achieved with high diagnostic performance, and it shows great clinical promise. Our research on AI-enabled 8-lead ECG detection of ASD in adults is expected to provide robust references for early detection of ASD, healthy pregnancies, and related decision-making. A lower number of leads is also more favorable for the application of portable devices, which it is expected that this technology will bring significant economic and societal benefits.

Comparative efficacy and safety of sodium-glucose cotransporter 2 inhibitors for renal outcomes in patients with type 2 diabetes mellitus: a systematic review and network meta-analysis.

In this study, the summarized WMDs and RRs were calculated using a pairwise analysis and a network meta-analysis with a random effects model, to compare and rank the efficacy and safety of SGLT-2i for renal outcomes in patients with T2DM. Among 1894 identified articles, 30 trials including 50,244 patients with T2DM were evaluated. Network analysis revealed that the administration of canagliflozin was associated with a reduced risk of renal impairment (surface under the cumulative ranking: 90.8%). Further, although the administration of SGLT-2i was not associated with the risk of renal impairment (RR = 0.88, 95%CI = 0.68-1.15, p = 0.354), the administration of empagliflozin was associated with a reduced risk of renal impairment compared to that with the administration of placebo (RR = 0.74, 95%CI = 0.62-0.90, p = 0.002). Moreover, compared with the administration of a placebo, the administration of 50, 100, and 200 mg of canagliflozin was associated with lower serum creatinine levels. Furthermore, compared with the administration of a placebo, the administration of 100 mg canagliflozin, 2.5 mg dapagliflozin, and 25 mg empagliflozin was associated with a lower reduction in the estimated glomerular filtration rate. Except for 300 mg canagliflozin, all SGLT-2i were associated with greater increases in blood urea nitrogen levels (WMD = 1.39, 95%CI = 1.20-1.59, p < 0.001). Finally, the administration of all SGLT-2i significantly increased the ratio of urinary glucose to creatinine compared with the ratio upon administration of placebo (WMD = 36.21, 95%CI = 31.50-40.92, p < 0.001). Briefly, canagliflozin exerts the greatest therapeutic effect in terms of reducing the risk of renal impairment. Empagliflozin and canagliflozin may be more effective than other SGLT-2i in preventing renal impairment.

Preparation of Multifunctional Nano-Molybdenum Disulfide and Its Tribological Properties in Water-Based Cutting Fluids.

In order to meet the advanced requirements of the manufacturing industry, the use of water-based cutting fluids (WCFs) in metal processing is gradually increasing. However, their lubrication performance still needs to be improved considerably. Therefore, new multifunctional molybdenum disulfide nanoparticles (m-MoS2 NPs) were developed to improve the lubricating properties of WCFs. M-MoS2 NPs modified with silver nanoparticles were prepared by an in situ surface modification. The morphology and chemical composition of the m-MoS2 NPs were characterized by scanning electron microscopy (SEM), high-resolution transmission electron microscopy (HR-TEM), X-ray diffraction (XRD), and X-ray photoelectron spectroscopy (XPS). Furthermore, the dispersion and bactericidal properties of m-MoS2 NPs with different weight percents in WCFs were also studied experimentally. The effect of m-MoS2 NPs concentration on friction properties and their friction mechanism were investigated in this research. The results revealed that the prepared m-MoS2 NPs were all nanoscale particles with a layered structure. The dispersion and bactericidal properties of m-MoS2 NPs in WCFs were better than those of MoS2 NPs. The best dispersion and bactericidal properties were observed with 1 wt % MoS2 NPs, as well as friction reduction and antiwear properties. During friction, the two friction surfaces were in the boundary lubrication state,and the prepared m-MoS2 NPs entered the friction contact zone along with the WCFs. A friction chemical reaction film rich in MoS2 and Ag NPs was formed on the friction surface to fill and repair the worn surface, exerting a good lubrication effect.

Application and risk prediction of thrombolytic therapy in cardio-cerebrovascular diseases: a review.

Cardiocerebrovascular diseases (CVDs) are the leading cause of death worldwide, consuming huge healthcare budget. For CVD patients, the prompt assessment and appropriate administration is the crux to save life and improve prognosis. Thrombolytic therapy, as a non-invasive approach to achieve recanalization, is the basic component of CVD treatment. Still, there are risks that limits its application. The objective of this review is to give an introduction on the utilization of thrombolytic therapy in cardiocerebrovascular blockage diseases, including coronary heart disease and ischemic stroke, and to review the development in risk assessment of thrombolytic therapy, comparing the performance of traditional scales and novel artificial intelligence-based risk assessment models.

FMO1 Promotes Nonalcoholic Fatty Liver Disease Progression by Regulating PPARα Activation and Inducing Ferroptosis.

BACKGROUND: The function of flavin containing dimethylaniline monooxygenase 1 (FMO1), which is known to play a part in lipid metabolism, remains unclear in the development of nonalcoholic fatty liver disease (NAFLD). This research has the objective of examining the contributions of FMO1 in the progression of NAFLD and the associated mechanisms, particularly the peroxisome proliferator activated receptor alpha (PPARα) and ferroptosis pathways. METHODS: An in vitro NAFLD model was established by treating L02 cells with free fatty acids (FFAs). The FMO1 and ferroptosis levels were examined in the cellular NAFLD model. FMO1 was knocked down using short-interfering RNA transfection. The effects of FMO1 knockdown on lipid accumulation, PPARα expression, and ferroptosis were examined in the cellular NAFLD model. Additionally, the effects of FMO1 and/or PPARα overexpression on lipid metabolism and ferroptosis were analyzed. Furthermore, L02 cells were pre-treated with GW7647 (PPARα agonist) or RSL3 (ferroptosis activator) and stimulated with FFAs. RESULTS: The levels of FMO1 and ferroptosis were upregulated in the in vitro NAFLD model. FMO1 knockdown suppressed the FFA-induced accumulation of lipids in hepatocytes, downregulation of PPARα expression, and upregulation of ferroptosis. In contrast, FMO1 overexpression dysregulated lipid metabolism and downregulated PPARα levels. Meanwhile, PPARα overexpression mitigated the FMO1 overexpression-induced upregulation of ferroptosis and lipid accumulation. Treatment with RSL3 suppressed the effects of PPARα overexpression on lipid accumulation and FMO1 expression. CONCLUSIONS: FMO1 upregulates ferroptosis by suppressing PPARα in NAFLD, which leads to the dysregulation of lipid metabolism.

Identification of GPD1L as a Potential Prognosis Biomarker and Associated with Immune Infiltrates in Lung Adenocarcinoma.

Lung adenocarcinoma (LUAD) is one of the most prevalent pathological kinds of lung cancer, which is a common form of cancer that has a high death rate. Over the past several years, growing studies have indicated that GPD1L was involved in the advancement of a number of different cancers. However, its clinical significance in LUAD has not been investigated. In this study, following an examination of the TGCA datasets, we found that GPD1L displayed a dysregulated state in a wide variety of cancers; this led us to believe that GPD1L is an essential regulator in the progression of malignancies. In addition, we found that the expression of GPD1L was much lower in LUAD tissues when compared with nontumor specimens. According to the findings of ROC tests, GPD1L was able to effectively identify LUAD specimens from nontumor samples with an AUC value of 0.828 (95% confidence interval: 0.793 to 0.863). On the basis of the clinical study, a low expression of GPD1L was clearly related with both the N stage and the clinical stage. Moreover, based on the findings of a Kaplan-Meier survival study, elevated GPD1L expression was a strong indicator of considerably improved overall survival (OS) and disease-specific survival (DSS). GPD1L expression and clinical stages were found to be independent prognostic indicators for overall survival and disease-free survival in LUAD patients, according to multivariate analyses. Based on multivariate analysis, the C-indexes and calibration plots of the nomogram demonstrated an effective prediction performance for LUAD patients. Besides, the expression of GPD1L was positively related to mast cells, eosinophils, Tcm, TFH, iDC, DC, and macrophages, while negatively associated with Th2 cells, NK CD56dim cells, Tgd, Treg, and neutrophils. Finally, qRT-PCR was able to demonstrate that GPD1L had a significant amount of expression in LUAD. Additionally, according to the results of functional tests, overexpression of GPD1L had a significant inhibiting effect on the proliferation of LUAD cells. In general, the results of our study suggested that GPD1L had the potential to serve as a diagnostic and prognostic marker for LUAD.

SARS-CoV-2 ORF3a expression in brain disrupts the autophagy-lysosomal pathway, impairs sphingolipid homeostasis, and drives neuropathogenesis.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection causes injury to multiple organ systems, including the brain. SARS-CoV-2's neuropathological mechanisms may include systemic inflammation and hypoxia, as well as direct cell damage resulting from viral infections of neurons and glia. How the virus directly causes injury to brain cells, acutely and over the long term, is not well understood. In order to gain insight into this process, we studied the neuropathological effects of open reading frame 3a (ORF3a), a SARS-CoV-2 accessory protein that is a key pathological factor of the virus. Forced ORF3a brain expression in mice caused the rapid onset of neurological impairment, neurodegeneration, and neuroinflammation-key neuropathological features found in coronavirus disease (COVID-19, which is caused by SARS-CoV-2 infection). Furthermore, ORF3a expression blocked autophagy progression in the brain and caused the neuronal accumulation of α-synuclein and glycosphingolipids, all of which are linked to neurodegenerative disease. Studies with ORF3-expressing HeLa cells confirmed that ORF3a disrupted the autophagy-lysosomal pathway and blocked glycosphingolipid degradation, resulting in their accumulation. These findings indicate that, in the event of neuroinvasion by SARS-CoV-2, ORF3a expression in brain cells may drive neuropathogenesis and be an important mediator of both short- and long-term neurological manifestations of COVID-19.

[Corrigendum] Leonurine protects cardiac function following acute myocardial infarction through anti­apoptosis by the PI3K/AKT/GSK3ß signaling pathway.

Subsequently to the publication of the above article, the authors have realized that Fig. 3 was published with an error: Essentially, the image selected for Masson's staining of the Leonurine group in Fig. 3A (the right-hand panel) was inadvertently selected from Fig. 4 in an article published previously by the same group [Zhu H, Jiang X, Li X, Hu M, Wan W, Wen Y, He Y and Zheng X: Intramyocardial delivery of VEGF165 via a novel biodegradable hydrogel induces angiogenesis and improves cardiac function after rat myocardial infarction. Heart Vessels 31: 963­975, 2016]. However, owing to the time that has elapsed since this article was published, the authors no longer had access to their original data; therefore, they were granted permission by the Editor to repeat the experiments shown in Fig. 3, and the revised version of Fig. 3 is shown below. Note that this error did not significantly affect the results or the conclusions reported in this paper. All the authors agree to the publication of this Corrigendum, are grateful to the Editor of Molecular Medicine Reports for allowing them the opportunity to correct this error, and apologize to the readership for any inconvenience caused. [Molecular Medicine Reports 18: 1582­1590, 2018; DOI: 10.3892/mmr.2018.9084].

Pseudomonas xiamenensis in the cutting fluids on corrosion behavior of aluminum alloy 2219.

Aluminum alloy workpieces are prone to black spots and other corrosion problems in the cutting process, which greatly puzzles the machining industry and brings serious losses. However, the cause and mechanism of workpiece corrosion are still unclear. In this study, the effect of P. xiamenensis breeding in the cutting fluid on the corrosion of aluminum alloy 2219 (AA 2219) was studied by corrosion product characterization, biofilm evaluation, corrosion profile, quantitative pit analysis, and electrochemical characterization. The results showed that P. xiamenensis adhered to the surface of AA 2219, forming uneven corrosion product film and biofilm. The state of the film on the surface of the aluminum alloy changed, and pitting corrosion intensified after being immersed in cutting fluid containing P. xiamenensis. The maximum corrosion depths of the coupons were found to be 2.7 µm and 15.8 µm in sterile and inoculated cutting fluids, respectively. The corrosion rate of the aluminum alloy was as high as 9.16 × 10-3 mm/y, which was about 9 times higher than the corrosion rate in the microbial-free cutting fluid. The presence of a P. xiamenensis biofilm accelerated the formation of the water-soluble corrosion product Al(OH)4-, which destroyed the passive film and accelerated pitting corrosion.

A rare left ventricular cardiac myxoma mimicking fibroma.

BACKGROUND: In most cases, it is not difficult to differentiate common left ventricular (LV) cardiac myxomas from fibromas because they are different disease entities and have different imaging findings. Herein, we present a case of a tumor with histological characteristics of a LV cardiac myxoma even though its imaging and macroscopical views were similar to that of fibroma. CASE PRESENTATION: A 65-year-old woman was admitted to the hospital with chest tightness and palpitations which persisted for 2 years. Transthoracic echocardiogram and transesophageal echocardiography revealed a 23 mm × 8 mm, polyp-like-shaped, homogeneous, firm, solitary, mobile and solitary LV mass, which protruded into the left atrium during systole, resulting in mild mitral regurgitation. LV contrast-enhanced echocardiography revealed that there was little contrast agent filling in the LV mass. To further clarify the nature of the mass, non-enhanced and contrast-enhanced coronary computed tomography (CT) angiograms showed a 19 mm × 8 mm relatively homogeneous low density with punctate calcifications mass and no significant enhancement. Thus, we preoperatively diagnosed her condition as a LV fibroma and performed excision of the tumor under cardiopulmonary by-pass by using port-access approach through right mini-thoracotomy. The postoperative pathological diagnosis of the tumor was in fact a LV myxoma. CONCLUSIONS: LV cardiac myxomas mimicking fibroma makes diagnosis difficult, and sonographers should be aware of this imaging changes.

Crocin protects the renal tubular epithelial cells against high glucose-induced injury and oxidative stress via regulation of the SIRT1/Nrf2 pathway.

Objectives: Renal tubular damage is critical pathological feathers of diabetic nephropathy (DN). This study aimed to explore the protective activity and related mechanisms of crocin in renal epithelial cell injury induced by high glucose. Materials and Methods: Renal tubular epithelial HK-2 cells were cultured with D-glucose to establish an in vitro DN model. Cell viability was evaluated by CCK-8 assay. Apoptosis was detected by Annexin V-FITC kit. Oxidative stress was evaluated by colorimetry. RT-qPCR was carried out to determine the mRNA expressions of NF-E2-related factor 2 (Nrf2) and its pathway genes. Western blot was applied to determine the protein expressions of Nrf2 and related proteins. Results: High glucose (5.5, 30, and 50 mM D-glucose) decreased cell viability at 72 hr, which was attenuated by crocin (25 and 50 µM). Crocin also attenuated the high glucose (30 mM D-glucose) induced apoptosis of HK-2 cells, decreased MDA content, and increased SOD activity in culture media. Crocin increased mRNA levels of Nrf2, HO-1, and NQO1. Moreover, crocin increased protein expressions of Nrf2, Sirtuin 1 (SIRT1), and p-Akt (Ser473). Inhibition of Nrf2 using siRNA, and inhibitors of SIRT1 (nicotinamide, NAM, 20 µM) and PI3K/Akt (LY294002, 50 µM) all attenuated the protective effect of crocin. Nrf2 siRNA and NAM also partially attenuated the inhibitory effect on oxidative stress and increase in the Nrf2 protein by crocin treatment. Conclusion: Crocin protects renal epithelial cells against injury induced by high glucose, and the mechanism is associated with partial activation of the SIRT1-Nrf2 pathway.

Identification of two lipid phosphatases that regulate sphingosine-1-phosphate cellular uptake and recycling.

Sphingosine-1-phosphate (S1P) is a sphingolipid metabolite that serves as a potent extracellular signaling molecule. Metabolic regulation of extracellular S1P levels impacts key cellular activities through altered S1P receptor signaling. Although the pathway through which S1P is degraded within the cell and thereby eliminated from reuse has been previously described, the mechanism used for S1P cellular uptake and the subsequent recycling of its sphingoid base into the sphingolipid synthesis pathway is not completely understood. To identify the genes within this S1P uptake and recycling pathway, we performed a genome-wide CRISPR/Cas9 KO screen using a positive-selection scheme with Shiga toxin, which binds a cell-surface glycosphingolipid receptor, globotriaosylceramide (Gb3), and causes lethality upon internalization. The screen was performed in HeLa cells with their sphingolipid de novo pathway disabled so that Gb3 cell-surface expression was dependent on salvage of the sphingoid base of S1P taken up from the medium. The screen identified a suite of genes necessary for S1P uptake and the recycling of its sphingoid base to synthesize Gb3, including two lipid phosphatases, PLPP3 (phospholipid phosphatase 3) and SGPP1 (S1P phosphatase 1). The results delineate a pathway in which plasma membrane-bound PLPP3 dephosphorylates extracellular S1P to sphingosine, which then enters cells and is rephosphorylated to S1P by the sphingosine kinases. This rephosphorylation step is important to regenerate intracellular S1P as a branch-point substrate that can be routed either for dephosphorylation to salvage sphingosine for recycling into complex sphingolipid synthesis or for degradation to remove it from the sphingolipid synthesis pathway.

Th1 immune maturation effects of Nocardia rubra cell-wall skeleton via PI3K/Akt/PAX8 regulatory axis.

Nocardia rubra cell-wall skeleton (Nr-CWS) is reported as an external immunotherapeutic enhancer with the advantage of antitumor effect on human cancers. However, the immune regulatory role of Nr-CWS is not fully illustrated. We studied mouse CD4+ T lymphocytes isolated from mice spleen were induced by Nr-CWS and observed that the differentiation of Th1 CD4+ T cells and the cytokines of IL-2, TNF-α, IFN-γ were all enhanced by Nr-CWS. Furthermore, RNA sequencing was conducted to investigate the different mRNA profiling induced by Nr-CWS. We observed that paired box 8 (PAX8) was significantly up-regulated in Nr-CWS-treated Th1 cells compared to control. As a transcription factor, chromatin immunoprecipitation sequencing was carried out to study the genome-wide distribution of PAX8. Interestingly, we found that the binding domain of PAX8 was elevated by Nr-CWS, and the target genes associated with these binding sites showed a positive correlation between their transcription and PAX8 binding strength. Finally, we determined that Nr-CWS could enhance the activity of the PI3 K/Akt signaling pathway. Akt agonist could mimic the effect of Nr-CWS for PAX8 up-regulation, while Akt inhibitor compromised the expression of PAX8. Taken together, we determined a novel role of Nr-CWS in boosting the activity of Th1 maturation via the PI3 K/Akt/PAX8 axis.

Automatic pulmonary auscultation grading diagnosis of Coronavirus Disease 2019 in China with artificial intelligence algorithms: A cohort study.

BACKGROUND AND OBJECTIVE: Research on automatic auscultation diagnosis of COVID-19 has not yet been developed. We therefore aimed to engineer a deep learning approach for the automated grading diagnosis of COVID-19 by pulmonary auscultation analysis. METHODS: 172 confirmed cases of COVID-19 in Tongji Hospital were divided into moderate, severe and critical group. Pulmonary auscultation were recorded in 6-10 sites per patient through 3M littmann stethoscope and the data were transferred to computer to construct the dataset. Convolutional neural network (CNN) were designed to generate classifications of the auscultation. F1 score, the area under the curve (AUC) of the receiver operating characteristic curve, sensitivity and specificity were quantified. Another 45 normal patients were served as control group. RESULTS: There are about 56.52%, 59.46% and 78.85% abnormal auscultation in the moderate, severe and critical groups respectively. The model showed promising performance with an averaged F1 scores (0.9938 95% CI 0.9923-0.9952), AUC ROC score (0.9999 95% CI 0.9998-1.0000), sensitivity (0.9938 95% CI 0.9910-0.9965) and specificity (0.9979 95% CI 0.9970-0.9988) in identifying the COVID-19 patients among normal, moderate, severe and critical group. It is capable in identifying crackles, wheezes, phlegm sounds with an averaged F1 scores (0.9475 95% CI 0.9440-0.9508), AUC ROC score (0.9762 95% CI 0.9848-0.9865), sensitivity (0.9482 95% CI 0.9393-0.9578) and specificity (0.9835 95% CI 0.9806-0.9863). CONCLUSIONS: Our model is accurate and efficient in automatically diagnosing COVID-19 according to different categories, laying a promising foundation for AI-enabled auscultation diagnosing systems for lung diseases in clinical applications.

Development and Validation of a Prognostic Risk Score System for COVID-19 Inpatients: A Multi-Center Retrospective Study in China.

Coronavirus disease 2019 (COVID-19) has become a worldwide pandemic. Hospitalized patients of COVID-19 suffer from a high mortality rate, motivating the development of convenient and practical methods that allow clinicians to promptly identify high-risk patients. Here, we have developed a risk score using clinical data from 1479 inpatients admitted to Tongji Hospital, Wuhan, China (development cohort) and externally validated with data from two other centers: 141 inpatients from Jinyintan Hospital, Wuhan, China (validation cohort 1) and 432 inpatients from The Third People's Hospital of Shenzhen, Shenzhen, China (validation cohort 2). The risk score is based on three biomarkers that are readily available in routine blood samples and can easily be translated into a probability of death. The risk score can predict the mortality of individual patients more than 12 d in advance with more than 90% accuracy across all cohorts. Moreover, the Kaplan-Meier score shows that patients can be clearly differentiated upon admission as low, intermediate, or high risk, with an area under the curve (AUC) score of 0.9551. In summary, a simple risk score has been validated to predict death in patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2); it has also been validated in independent cohorts.

A Novel Cluster-Based Method for Single-channel Fetal Electrocardiogram Detection.

Fetal electrocardiography (FECG) is a promising technology for non-invasive fetal monitoring. However, due to the low amplitude and non-stationary characteristics of the FECG signal, it is difficult to extract it from maternal abdominal signals. Moreover, most FECG extraction methods are based on multiple channels, which make it difficult to achieve fetal monitoring outside the clinic. This paper proposes an efficient cluster-based method for accurate FECG extraction and fetal QRS detection only using one channel signal. We designed min-max-min group as the basis for feature extraction. The extracted features are used to distinguish the different components of the abdominal signal, and finally extract the FECG signal. To verify the effectiveness of our algorithm, we conducted experiments on a public dataset and a dataset record from the Tongji Hospital. Experimental results show that our method can achieve an accuracy rate of more than 96% which is better than other algorithms.

SMG9 Serves as an Oncogene to Promote the Tumor Progression via EMT and Wnt/ß-Catenin Signaling Pathway in Hepatocellular Carcinoma.

Background/Aims: SMG9 participates in the nonsense-mediated mRNA decay process that degrades mRNA harboring nonsense mutations introduced either at the level of transcription or RNA processing. However, little is known about the role of SMG9 in hepatocellular carcinoma (HCC). The objective of this research was to clarify the effects of SMG9 expression on HCC progression. Methods: Microarray data were acquired from NCBI Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) database to bioinformatically analyze the differential expression of SMG9 between HCC patients and normal controls. SMG9 mRNA level was measured in sixteen sets of fresh tumor tissues and adjacent non-cancerous liver tissues (ANLTs) via reverse transcription-quantitative polymerase chain reaction (RT-qPCR). SMG9 protein expression was analyzed in ninety-five sets of paired formalin-fixed and paraffin-embedded tissue specimens by immunohistochemistry (IHC). In addition, clinicopathological features of SMG9 in HCC were checked. For in vitro studies, small interfering RNA (siRNA) was used to silence SMG9 expression for exploring biological functions and underlying mechanisms of SMG9 in SMMC-7721 and HepG2. Results: We found that SMG9 was upregulated in HCC tissues and SMG9 levels were closely related to TNM stage, tumor number and tumor size. Cox regression and Kaplan-Meier proportional hazards analyses showed that high expression of SMG9 was associated with poor patient survival. Furthermore, proliferation, apoptosis resistance, migration and invasion of both SMMC-7721 and HepG2 cells were suppressed by SMG9 inhibition. In addition, EMT and the Wnt/ß-catenin signaling pathway were involved in SMG9-mediated HCC progression. Conclusions: SMG9 may serve as a potential novel prognostic biomarker and therapeutic target in HCC patients.

Osteoclasts May Affect Glucose Uptake-Related Insulin Resistance by Secreting Resistin.

OBJECTIVES: Bone may play a role in the modulation of insulin sensitivity. Insulin resistance can be caused by increased resistin. However, whether osteoclasts affect the insulin resistance via resistin remains unclear. In the present study, we show the expression of resistin in osteoclasts and the possible underlying role of resistin on glucose uptake-related insulin resistance in vitro. METHODS: Conditioned mediums (CM) were collected from Raw264.7 cells treated without (CCM) or with RANKL (CM3, treated with RANKL for 3 days; CM5, treated with RANKL for 5 days) and transfected with control or resistin siRNA (CMsiRNA). The osteoclast formation was examined by tartrate resistant acid phosphatase (TRAP) staining. C2C12 myoblasts were cultured with the CM or CMsiRNA. Glucose uptake was evaluated by 2-NBDG fluorescence intensity. Resistin expression was evaluated by quantitative real-time polymerase chain reaction (qRT-PCR) and enzyme-linked immunosorbent assay. Statistical analysis was performed by an independent two sample t-test or one-way ANOVA. RESULTS: The 2-NBDG fluorescence intensity was higher in C2C12 cells treated with CCM compared to those that received CM3 and CM5 (p < 0.05). Resistin mRNA and protein expressions were both increased in RAW264.7 cells treated with RANKL for 3 days and 5 days compared with those cells without RANKL administration. The 2-NBDG fluorescence intensities in C2C12 cells treated with CMsiRNA and CM5+Anti-resistin antibody were significantly higher than those cultured with CM5 (p < 0.05). CONCLUSION: Osteoclasts may promote glucose uptake-related insulin resistance by secreting resistin.

Association of Serum Melatonin Level with Mild Cognitive Impairment in Type 2 Diabetic Patients: A Cross-Sectional Study.

OBJECTIVES: Melatonin is an essential neuroendocrine hormone that participates in the regulation of sleep rhythm and cognitive function. This study aimed to determine serum melatonin levels with mild cognitive impairment (MCI) in patients with type 2 diabetes (T2DM). METHODS: A total of 247 T2DM patients were recruited in this retrospective study and divided into 75 subjects with MCI and 172 with normal cognition. Cognitive function was evaluated by the Montreal Cognitive Assessment (MoCA). Their blood sample was examined for the level of melatonin and other biochemical parameters. RESULTS: Melatonin concentration was decreased in MCI patients to non-MCI patients (P < 0.001). Melatonin level was negatively correlated with age (r = -0.202; P = 0.001), diabetes duration (r = -0.282; P < 0.001), serum HbA1c (r = -0.195; P = 0.002), hs-CRP (r = -0.324; P < 0.001), and TSH (r = -0.184; P = 0.004) levels and positively correlated with MoCA score, serum HDL-C (r = 0.145; P < 0.001), FT3 (r = 0.241; P < 0.001), and FT4 (r = 0.169; P = 0.008) levels. The multivariable analysis indicated that fewer years of formal education, longer diabetes duration, higher serum HbA1c, higher serum hs-CRP, and lower serum melatonin are the predisposing factors for MCI. CONCLUSION: Lower melatonin level was associated with cognitive impairment in patients with T2DM. Melatonin might serve as a potential protective molecule against cognitive dysfunction in T2DM.