Interfacial engineering in SnO2-embedded graphene anode materials for high performance lithium-ion batteries.

Tin dioxide is regarded as an alternative anode material rather than graphite due to its high theoretical specific capacity. Modification with carbon is a typical strategy to mitigate the volume expansion effect of SnO2 during the charge process. Strengthening the interface bonding is crucial for improving the electrochemical performance of SnO2/C composites. Here, SnO2-embedded reduced graphene oxide (rGO) composite with a low graphene content of approximately 5 wt.% was in situ synthesized via a cetyltrimethylammonium bromide (CTAB)-assisted hydrothermal method. The structural integrity of the SnO2/rGO composite is significantly improved by optimizing the Sn-O-C electronic structure with CTAB, resulting a reversible capacity of 598 mAh g-1 after 200 cycles at a current density of 1 A g-1. CTAB-assisted synthesis enhances the rate performance and cyclic stability of tin dioxide/graphene composites, and boosts their application as the anode materials for the next-generation lithium-ion batteries.

D-glucaro-1,4-lactone improves Diethylnitrosamine induced hepatocellular carcinoma in rats via the uric acid-ROS pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Liuwei dihuang pills is a famous Traditional Chinese Medicine with various anti-cancer properties. Over 50 pharmaceutical manufacturers produce Liuwei dihuang pills in China and an estimated millions of people around the world orally take it every day. D-glucaro-1,4-lactone (1,4-GL) was quantified to be about 12.0 mg/g in Liuwei dihuang pills and a primary bioactive component of it inhibiting the activity of ß-glucuronidase in vivo. 1,4-GL can prevent and effectively inhibit various types of cancer. However, its exact mechanism of action remains unknown. The study would justify the traditional usage of Liuwei dihuang pills against cancers. AIM OF THE STUDY: 1,4-GL, a bioactive ingredient derived from Liuwei dihuang pills, a famous Traditional Chinese Medicine, could delay the progression of diethylnitrosamine (DEN)-induced hepatocellular carcinoma (HCC) in rats. The mechanism underpinning the effect, however, remains poorly understood. MATERIALS AND METHODS: Healthy and HCC rats were treated with or without 1,4-GL (40.0 mg/kg) and 1HNMR-based metabonomic analysis was employed. 10 metabolites in uric acid pathway were quantitatively determined by UPLC-MS/MS. The expression of xanthine dehydrogenase (XDH), SLC2A9 mRNA, and SLC2A9 protein was determined using RT-qPCR and Western Blot. The effect of 1,4-GL on HCC-LM3 cells was verified in vitro. The alterations of ROS activity, SLC2A9 and XDH gene levels were observed in NCTC-1469 cells induced by lipopolysaccharide (LPS) after 1,4-GL treatment. RESULTS: After the intervention of 1,4-GL, improved pathological morphology, liver lesions in HCC rats was observed with restored serum levels of AFP, AST, ALP, γ-GGT and Fisher's ratio. Hepatic metabonomics revealed that puring metabolism were significantly regulated by 1,4-GL in HCC rats. Uric acid, xanthine and hypoxanthine levels were quantified by UPLC-MS/MS and found to be nearly restored to control levels after 1,4-GL treatment in HCC rats. Changes in xanthine oxidase activity, XDH mRNA expression, and SLC2A9 mRNA and protein expression were also reversed. 1,4-GL treatment in LM3 HCC cells were consistent with the results in vivo. Furthermore, oxidative stress indicators such as T-SOD, GSH, CAT and MDA in serum and liver were improved after HCC rats treated with 1,4-GL. In vitro, 1,4-GL was observed to reduce lipopolysaccharide-induced ROS levels in NCTC-1469 cells with enhanced mRNA and protein expression of SLC2A9 and decreased mRNA level of XDH. CONCLUSION: The protective effects of 1,4-GL against DEN-induced HCC by reducing uric acid and ROS levels due to down-regulation of uric acid production and up-regulation of SLC2A9 expressions. 1,4-GL may represent a novel treatment that improves recovery from HCC by targeting uric acid-ROS pathway.

Clinical efficacy of different therapeutic strategies in patients with spontaneous rupture of the esophagus: a multicenter retrospective cohort study.

BACKGROUND: The therapeutic strategy for patients with spontaneous rupture of the esophagus includes surgical repair, endoscopic therapy, supportive care, and others. However, no evidence exists to direct clinical decision-making regarding the choice of operative and nonoperative management. The aim of this study was to determine the clinical efficacy of different therapeutic strategies in both general and stratified patients. METHODS: This study retrospectively analyzed a consecutive cohort of 101 patients at nine tertiary referral hospital centers in China. Patients were divided into operative and nonoperative groups based on the initial treatment. Short-term outcomes, including 90-day mortality, length of hospital stay, and postoperative leakage were compared. Subgroup analysis was performed based on treatment timing and Pittsburgh perforation severity score (PSS). RESULTS: Of 101 patients, 60 (58.4%) underwent operative management. A significant difference of 90-day mortality between operative and nonoperative groups was observed (15.0% vs. 34.1%, P=0.031). Operative management tend to yield similar therapeutic benefits in timely (OR, 0.250; 95% CI, 0.05-1.14, P=0.073) and delayed (OR, 0.42; 95% CI, 0.12-1.47, P=0.175) treatment groups. Based on PSS stratification, operative management significantly decreased the risk of 90-day mortality (OR, 0.211; 95% CI, 0.064-0.701; P=0.011) for patients in low- and moderate-risk groups but may be detrimental for patients in high-risk group (OR, 1.333; 95% CI, 0.233-7.626; P=0.746). CONCLUSIONS: Operative management might be superior to nonoperative management for low- and moderate-risk patients with spontaneous rupture of the esophagus. However, for patients at high risks, operative management might not provide additional benefits compared with nonoperative management. Further research involving larger sample sizes is required for accurate patient stratification and conclusive evidence-based guideline.

Pharmacokinetics and apparent Michaelis constant for metabolite conversion of sorafenib in healthy and hepatocellular carcinoma-bearing rats.

Aim: Investigation of the pharmacokinetics of sorafenib (SRF) in rats with hepatocellular carcinoma (HCC). Methods: A reproducible ultra-HPLC-MS method for simultaneous determination of serum SRF, N-hydroxymethyl sorafenib and N-demethylation sorafenib. Results: Both the maximum serum concentrations (2.5-times) and the area under the serum concentration-time curve from 0 h to infinity (4.5-times) of SRF were observed to be significantly higher, with a greater than 3.0-fold decrease in the clearance rate in the HCC-bearing rats compared with these values in healthy animals. Further study revealed approximately 3.8- and 3.2-times increases in the apparent Michaelis constant for N-hydroxymethyl sorafenib and N-demethylation sorafenib conversions in the HCC-bearing rats. Conclusion: The low efficiency for the SRF conversions was a key contributor to the increased serum concentrations of SRF.

[Box: see text].

The emerging threat of fluroquinolone-, bedaquiline-, and linezolid-resistant Mycobacterium tuberculosis in China: Observations on surveillance data.

BACKGROUND: Drug-resistant tuberculosis (TB), especially multidrug-resistant tuberculosis (MDR-TB), constitutes a major obstacle to fulfill end TB strategy globally. Although fluoroquinolones (FQs), linezolid (LZD) and bedaquiline (BDQ) were classified as Group A drugs for MDR-TB treatment, our knowledge of the prevalence of TB which were resistant to Group A drugs in China is quite limited. METHODS: In this study, we conducted a prospective multicenter surveillance study in China to determine the proportion of TB patients that were resistant to Group A drugs. A total of 1877 TB patients were enrolled from 2022 at four TB specialized hospitals. The drug susceptibility of isolated strains was conducted using the MGIT 960 system and the molecular mechanisms conferring drug resistance were investigated by Sanger sequencing. RESULTS: 12.9% of isolates were resistant to levofloxacin (LFX), 13.2% were resistant to moxifloxacin (MOX), 0.2% were resistant to bedaquiline (BDQ), and 0.8% were resistant to linezolid (LZD). Totally, 14.0% and 0.4% were classified as multidrug resistant- (MDR-) and extensively drug resistant- (XDR-) TB. The drug resistance was more common in retreated TB cases compared to new cases. In addition, 70.0% of fluoroquinolone (FQ)-resistant isolates harbored mutations in the gyrA and gyrB gene. By contrast, the common drug-resistant mutations were only found in 50% BDQ-resistant and 20% LZD-resistant isolates. CONCLUSIONS: Our data demonstrate that approximate half of MDR -TB patients are resistant to fluoroquinolones, with extremely low prevalence of initial BDQ and LZD resistance. Findings from this study provide important implications for the current management of MDR-TB patients.

Microbiota and mycobiota in bronchoalveolar lavage fluid of silicosis patients.

BACKGROUND: The contribution of bronchoalveolar lavage fluid (BALF) microbiota and mycobiota to silicosis has recently been noticed. However, many confounding factors can influence the accuracy of BALF microbiota and mycobiota studies, resulting in inconsistencies in the published results. In this cross-sectional study, we systematically investigated the effects of "sampling in different rounds of BALF" on its microbiota and mycobiota. We further explored the relationship between silicosis fatigue and the microbiota and mycobiota. METHODS: After obtaining approval from the ethics board, we collected 100 BALF samples from 10 patients with silicosis. Demographic data, clinical information, and blood test results were also collected from each patient. The characteristics of the microbiota and mycobiota were defined using next-generation sequencing. However, no non-silicosis referent group was examined, which was a major limitation of this study. RESULTS: Our analysis indicated that subsampling from different rounds of BALF did not affect the alpha- and beta-diversities of microbial and fungal communities when the centrifuged BALF sediment was sufficient for DNA extraction. In contrast, fatigue status significantly influenced the beta-diversity of microbes and fungi (Principal Coordinates Analysis, P = 0.001; P = 0.002). The abundance of Vibrio alone could distinguish silicosis patients with fatigue from those without fatigue (area under the curve = 0.938, 95% confidence interval [CI] 0.870-1.000). Significant correlations were found between Vibrio and haemoglobin levels (P < 0.001, ρ = -0.64). CONCLUSIONS: Sampling in different rounds of BALF showed minimal effect on BALF microbial and fungal diversities; the first round of BALF collection was recommended for microbial and fungal analyses for convenience. In addition, Vibrio may be a potential biomarker for silicosis fatigue screening.

α-Linolenic Acid Inhibits RANKL-Induced Osteoclastogenesis In Vitro and Prevents Inflammation In Vivo.

Inflammation is an important risk factor for bone-destroying diseases. Our preliminary research found that Zanthoxylum bungeanum seed oil (ZBSO) is abundant in unsaturated fatty acids and could inhibit osteoclastogenesis in receptor activator of nuclear factor κB ligand (RANKL)-induced RAW264.7 cells. However, the key constituents in ZBSO in the prevention of osteoclastogenesis and its possible mechanism related to inflammation are still unclear. Therefore, in this study, oleic acid (OA), linoleic acid (LA), palmitoleic acid (PLA), and alpha-linolenic acid (ALA) in ZBSO, havingthe strongest effect on RANKL-induced osteoclastogenesis, were selected by a tartrate-resistant acid phosphatase (TRAP) staining method. Furthermore, the effects of the selected fatty acids on anti-inflammation and anti-osteoclastogenesis in vitro and in vivo were assessed using RT-qPCR. Among the four major unsaturated fatty acids we tested, ALA displayed the strongest inhibitory effect on osteoclastogenesis. The increased expression of free fatty acid receptor 4 (FFAR4) and ß-arrestin2 (ßarr2), as well as the decreased expression of nuclear factor-kappa B (NF-κB), tumor necrosis factor-α (TNF-α), nuclear factor of activated T-cells c1 (NFATc1), and tartrate-resistant acid phosphatase (TRAP) in RAW264.7 cells after ALA treatment were observed. Moreover, in ovariectomized osteoporotic rats with ALA preventive intervention, we found that the expression of TNF-α, interleukin-6 (IL-6), interleukin-1ß (IL-1ß), NFATc1, and TRAP were decreased, while with the ALA therapeutic intervention, downregulated expression of NF-κB, NFATc1, TRAP, and transforming growth factor beta-activated kinase 1 (TAK1) were noticed. These results indicate that ALA, as the major unsaturated fatty acid in ZBSO, could inhibit RANKL-induced osteoclastogenesis via the FFAR4/ßarr2 signaling pathway and could prevent inflammation, suggesting that ZBSO may be a promising potential natural product of unsaturated fatty acids and a dietary supplement for the prevention of osteoclastogenesis and inflammatory diseases.

Oral mycobiota and pancreatic ductal adenocarcinoma.

Early detection of pancreatic ductal adenocarcinoma (PDAC) is essential for survival. Preliminary research demonstrated significant associations between structural alternation of mycobiota and PDAC. In this study, we investigated the associations between oral mycobiota and PDAC. We further explored mycobiota biomarkers for PDAC detection. We enrolled 34 PDAC patients and 35 matched healthy controls from West China hospital in Southwest China. Demographic data, clinical information, and salivary samples were collected. Mycobiota characteristics were defined using Internal Transcribed Spacer (ITS) ribosomal RNA sequencing. We found that the PDAC patients had significant increase in fungal abundance (P < 0.001) and significant decrease in fungal diversity (P < 0.001) in comparison to the healthy controls. A higher abundance of Basidiomycota and Unclassifed_p_Ascomycota was associated with an increased risk of PDAC. With each increase of abundance of g__unclassified_k__Fungi and g__unclassified_p__Ascomycota in PDAC patients, the risk of pancreatic cancer increased by 1.359 odds and 1.260 odds, respectively. Aspergillus (AUC = 0.983, 95% CI 0.951-1.000) and Cladosporium (AUC = 0.969, 95% CI 0.921-1.000) achieved high classification powers to distinguish PDAC patients from the healthy controls. The rapid, inexpensive tests of ITS1 sequencing of mycobiota and PCR detection of potential fungal biomarkers make it promising for the clinical practice to use oral microbes for PDAC early detection and prevention. Results of our study provide evidence that salivary mycobiota may provide insights into cancer risk, prevention, and detection.

Perinatal Outcomes and Related Risk Factors of Single vs Twin Pregnancy Complicated by Gestational Diabetes Mellitus: Meta-Analysis.

Objective: Perinatal outcomes and related risk factors of single vs twin pregnancy complicated with gestational diabetes mellitus (GDM) were clarified, providing evidence for developing preventive measures. Methods: The Chinese National Knowledge Infrastructure (CNKI), China Biology Medicine (CBM), CQVIP, Wanfang, and PubMed databases were searched for published research on the perinatal outcomes and risk factors of single and twin pregnancy complicated by GDM from 2000 to 2021. The quality of the included literature was evaluated according to the Newcastle-Ottawa Scale (NOS). Meta-analysis of the included literature was conducted using RevMan5.3 software. Results: Relative to a single pregnancy group, infertility, gestational weight gain, and family history of diabetes presented statistical significance in the twin pregnancy group (P < 0.05); gestational age at delivery, cesarean section, preterm birth < 37 weeks, and preeclampsia presented statistical significance in the twin pregnancy group (P < 0.05); and neonatal birth weight, small for gestational age (SGA), neonatal asphyxia, neonatal hypoglycemia, neonatal respiratory distress syndrome (NRDS), neonatal hyperbilirubinemia, and neonatal death presented statistical significance in the twin pregnancy group (P < 0.05). Conclusion: Infertility, prenatal weight gain, and diabetes in the family are all risk factors for postpartum impaired glucose metabolism in pregnant women with GDM who are carrying twins. The gestational age at delivery, cesarean section, preterm birth < 37 weeks, and preeclampsia of twin pregnant women with diabetes will affect the perinatal status of twin pregnant women. Neonatal birth weight, SGA, neonatal asphyxia, neonatal hypoglycemia, NRDS, neonatal hyperbilirubinemia, neonatal death, etc. should be paid special attention in the perinatal process.

Predicting Drug-Target Affinity Based on Recurrent Neural Networks and Graph Convolutional Neural Networks.

BACKGROUND: Drug development requires a lot of money and time, and the outcome of the challenge is unknown. So, there is an urgent need for researchers to find a new approach that can reduce costs. Therefore, the identification of drug-target interactions (DTIs) has been a critical step in the early stages of drug discovery. These computational methods aim to narrow the search space for novel DTIs and to elucidate the functional background of drugs. Most of the methods developed so far use binary classification to predict the presence or absence of interactions between the drug and the target. However, it is more informative but also more challenging to predict the strength of the binding between a drug and its target. If the strength is not strong enough, such a DTI may not be useful. Hence, the development of methods to predict drug-target affinity (DTA) is of significant importance Method: We have improved the GraphDTA model from a dual-channel model to a triple-channel model. We interpreted the target/protein sequences as time series and extracted their features using the LSTM network. For the drug, we considered both the molecular structure and the local chemical background, retaining the four variant networks used in GraphDTA to extract the topological features of the drug and capturing the local chemical background of the atoms in the drug by using BiGRU. Thus, we obtained the latent features of the target and two latent features of the drug. The connection of these three feature vectors is then inputted into a 2 layer FC network, and a valuable binding affinity is the output. RESULT: We used the Davis and Kiba datasets, using 80% of the data for training and 20% of the data for validation. Our model showed better performance when compared with the experimental results of GraphDTA Conclusion: In this paper, we altered the GraphDTA model to predict drug-target affinity. It represents the drug as a graph and extracts the two-dimensional drug information using a graph convolutional neural network. Simultaneously, the drug and protein targets are represented as a word vector, and the convolutional neural network is used to extract the time-series information of the drug and the target. We demonstrate that our improved method has better performance than the original method. In particular, our model has better performance in the evaluation of benchmark databases.

Current treatment and outcome of esophageal perforation: A single-center experience and a pooled analysis.

BACKGROUND: Esophageal perforation has been one of the serious clinical emergencies, because of the high mortality and complication rates. However, the current prognosis of esophageal perforation and the outcomes of available treatment methods are not well defined. This study attempted to pool the immediate outcomes of esophageal perforation in the past 2 decades. METHODS: The clinical data of 22 consecutive adult patients with esophageal perforation in our center were analyzed. A pooled analysis was also conducted to summarize results from the literatures published between 1999 and 2020. Studies that met the inclusion criteria were assessed, and their methodological quality was examined. RESULTS: The mortality and complication rates in our center were 4.55% and 31.82%, separately. The pooled analysis included 45 studies published between 1999 and 2019, which highlighted an overall immediate mortality rate of 9.86%. Surgical treatments were associated with a pooled immediate mortality of 10.01%, and for conservative treatments of 6.49%. Besides, in the past decade, the mortality and complication rates decreased by 27.12% and 46.75%, respectively. CONCLUSIONS: In the past 2 decades, the overall immediate mortality rate of esophageal perforation was about 10% in the worldwide, and the outcomes of esophageal perforation treatment are getting better in the last 10 years. ETHICS REGISTRATION INFORMATION: LW2020011.

Quantifying the Effect of Abdominal Body Wall on In Situ Peak Rarefaction Pressure During Diagnostic Ultrasound Imaging.

In this study, 3-D non-linear ultrasound simulations and experimental measurements were used to estimate the range of in situ pressures that can occur during transcutaneous abdominal imaging and to identify the sources of error when estimating in situ peak rarefaction pressures (PRPs) using linear derating, as specified by the mechanical index (MI) guideline. Using simulations, it was found that, for a large transmit aperture (F/1.5), MI consistently over-estimated in situ PRP by 20%-48% primarily owing to phase aberration. For a medium transmit aperture (F/3), the MI accurately estimated the in situ PRP to within 8%. For a small transmit aperture (F/5), MI consistently underestimated the in situ PRP by 32%-50%, with peak locations occurring 1-2 cm before the focal depth, often within the body wall itself. The large variability across body wall samples and focal configurations demonstrates the limitations of the simplified linear derating scheme. The results suggest that patient-specific in situ PRP estimation would allow for increases in transmit pressures, particularly for tightly focused beams, to improve diagnostic image quality while ensuring patient safety.

Radiological Society of North America/Quantitative Imaging Biomarker Alliance Shear Wave Speed Bias Quantification in Elastic and Viscoelastic Phantoms.

OBJECTIVES: To quantify the bias of shear wave speed (SWS) measurements between different commercial ultrasonic shear elasticity systems and a magnetic resonance elastography (MRE) system in elastic and viscoelastic phantoms. METHODS: Two elastic phantoms, representing healthy through fibrotic liver, were measured with 5 different ultrasound platforms, and 3 viscoelastic phantoms, representing healthy through fibrotic liver tissue, were measured with 12 different ultrasound platforms. Measurements were performed with different systems at different sites, at 3 focal depths, and with different appraisers. The SWS bias across the systems was quantified as a function of the system, site, focal depth, and appraiser. A single MRE research system was also used to characterize these phantoms using discrete frequencies from 60 to 500 Hz. RESULTS: The SWS from different systems had mean difference 95% confidence intervals of ±0.145 m/s (±9.6%) across both elastic phantoms and ± 0.340 m/s (±15.3%) across the viscoelastic phantoms. The focal depth and appraiser were less significant sources of SWS variability than the system and site. Magnetic resonance elastography best matched the ultrasonic SWS in the viscoelastic phantoms using a 140 Hz source but had a - 0.27 ± 0.027-m/s (-12.2% ± 1.2%) bias when using the clinically implemented 60-Hz vibration source. CONCLUSIONS: Shear wave speed reconstruction across different manufacturer systems is more consistent in elastic than viscoelastic phantoms, with a mean difference bias of < ±10% in all cases. Magnetic resonance elastographic measurements in the elastic and viscoelastic phantoms best match the ultrasound systems with a 140-Hz excitation but have a significant negative bias operating at 60 Hz. This study establishes a foundation for meaningful comparison of SWS measurements made with different platforms.

Erratum: Effect of type 2 diabetes mellitus caveolin-3 K15N mutation on glycometabolism.

[This corrects the article DOI: 10.3892/etm.2019.7840.].

Deep Network for the Automatic Segmentation and Quantification of Intracranial Hemorrhage on CT.

BACKGROUND: The ABC/2 method is usually applied to evaluate intracerebral hemorrhage (ICH) volume on computed tomography (CT), although it might be inaccurate and not applicable in estimating extradural or subdural hemorrhage (EDH, SDH) volume due to their irregular hematoma shapes. This study aimed to evaluate deep framework optimized for the segmentation and quantification of ICH, EDH, and SDH. METHODS: The training datasets were 3,000 images retrospectively collected from a collaborating hospital (Hospital A) and segmented by the Dense U-Net framework. Three experienced radiologists determined the ground truth by marking the pixels as hemorrhage area. We utilized the Dice and intra-class correlation coefficients (ICC) to test the reliability of the ground truth. Moreover, the testing datasets consisted of 211 images (internal test) from Hospital A, and 86 ICH images (external test) from another hospital (Hospital B). In this study, we chose scatter plots, ICC, and Pearson correlation coefficients (PCC) with ground truth to evaluate the performance of the deep framework. Furthermore, to validate the effectiveness of the deep framework, we did a comparative analysis of the hemorrhage volume estimation between the deep model and the ABC/2 method. RESULTS: The high Dice (0.89-0.95) and ICC (0.985-0.997) showed the consistency of the manual segmentations among the radiologists and the reliability of the ground truth. For the internal test, the Dice coefficients of ICH, EDH, and SDH were 0.90 ± 0.06, 0.88 ± 0.12, and 0.82 ± 0.16, respectively. For the external test, the segmentation Dice was 0.86 ± 0.09. Comparatively, the ICC and PCC of ICH volume estimations were 0.99 performed by Dense U-Net that overmatched the ABC/2 method. CONCLUSION: This study revealed the excellent performance of hematoma segmentation and volume evaluation based on Dense U-Net, which indicated our deep framework might contribute to efficiently developing treatment strategies for intracranial hemorrhage in clinics.

20S proteasome and glyoxalase 1 activities decrease in erythrocytes derived from Alzheimer's disease patients.

As a result of accumulating methylglyoxal and advanced glycation end products in the brains of patients with Alzheimer's disease, it is considered a protein precipitation disease. The ubiquitin proteasome system is one of the most important mechanisms for cells to degrade proteins, and thus is very important for maintaining normal physiological function of the nervous system. This study recruited 48 individuals with Alzheimer's disease (20 males and 28 females aged 75 ± 6 years) and 50 healthy volunteers (21 males and 29 females aged 72 ± 7 years) from the Affiliated Hospital of Youjiang Medical University for Nationalities (Baise, China) between 2014 and 2017. Plasma levels of malondialdehyde and H2O2 were measured by colorimetry, while glyoxalase 1 activity was detected by spectrophotometry. In addition, 20S proteasome activity in erythrocytes was measured with a fluorescent substrate method. Ubiquitin and glyoxalase 1 protein expression in erythrocyte membranes was detected by western blot assay. The results demonstrated that compared with the control group, patients with Alzheimer's disease exhibited increased plasma malondialdehyde and H2O2 levels, and decreased glyoxalase 1 activity; however, expression level of glyoxalase 1 protein remained unchanged. Moreover, activity of the 20S proteasome was decreased and expression of ubiquitin protein was increased in erythrocytes. These findings indicate that proteasomal and glyoxalase activities may be involved in the occurrence of Alzheimer's disease, and erythrocytes may be a suitable tissue for Alzheimer's disease studies. This study was approved by the Ethics Committee of Youjiang Medical University for Nationalities (approval No. YJ12017013) on May 3, 2017.

Effect of type 2 diabetes mellitus caveolin-3 K15N mutation on glycometabolism.

Caveolin-3 (CAV3) is a muscle-specific protein present within the muscle cell membrane that affects signaling pathways, including the insulin signaling pathway. A previous assessment of patients with newly developed type 2 diabetes (T2DM) demonstrated that CAV3 gene mutations may lead to changes in protein secondary structure. A severe CAV3 P104L mutation has previously been indicated to influence the phosphorylation of skeletal muscle cells and result in impaired glucose metabolism. In the present study, the effect of CAV3 K15N gene transfection in C2C12 cells was assessed. Transfection with K15N reduced the expression of total CAV3 and AKT2 proteins in the cells, and the translocation of glucose transporter type 4 to the muscle cell membrane, which resulted in decreased glucose uptake and glycogen synthesis in myocytes. In conclusion, these results indicate that the CAV3 K15N mutation may cause insulin-stimulated impaired glucose metabolism in myocytes, which may contribute to the development of T2DM.

The caveolin-3 P104L mutation in LGMD-1C patients inhibits non-insulin-stimulated glucose metabolism and growth but promotes myocyte proliferation.

The caveolin-3 (CAV3) protein is known to be specifically expressed in various myocytes, and skeletal muscle consumes most of the blood glucose as an energy source to maintain normal cell metabolism and function. The P104L mutation in the coding sequence of the human CAV3 gene leads to autosomal dominant disease limb-girdle muscular dystrophy type 1C (LGMD-1C). We previously reported that C2C12 cells transiently transfected with the P104L CAV3 mutant exhibited decreased glucose uptake and glycogen synthesis after insulin stimulation. The present study aimed to examine whether the P104L mutation affects C2C12 cell glucose metabolism, growth, and proliferation without insulin stimulation. C2C12 cells stably transfected with CAV3-P104L were established, and biochemical assays, western blot analysis and confocal microscopy were used to observe glucose metabolism as well as cell growth and proliferation and to determine the effect of the P104L mutation on the PI3K/Akt signaling pathway. Without insulin stimulation, C2C12 cells stably transfected with the P104L CAV3 mutant exhibited decreased glucose uptake and glycogen synthesis, decreased CAV3 expression and reduced localization of CAV3 and GLUT4 on the cell membrane. The P104L mutant significantly reduced the cell diameters, but accelerated cell proliferation. Akt phosphorylation was inhibited, and protein expression of GLUT4, p-GSK3ß, and p-p70s6K, which are molecules downstream of Akt, was significantly decreased. The CAV3-P104L mutation inhibits glycometabolism and cell growth but accelerates C2C12 cell proliferation by reducing CAV3 protein expression and cell membrane localization, which may contribute to the pathogenesis of LGMD-1C.

Mobile Phone-Based Telemedicine Practice in Older Chinese Patients with Type 2 Diabetes Mellitus: Randomized Controlled Trial.

BACKGROUND: Previous studies on telemedicine interventions have shown that older diabetic patients experience difficulty in using computers, which is a barrier to remote communication between medical teams and older diabetic patients. However, older people in China tend to find it easy to use mobile phones and personal messaging apps that have a user-friendly interface. Therefore, we designed a mobile health (mHealth) system for older people with diabetes that is based on mobile phones, has a streamlined operation interface, and incorporates maximum automation. OBJECTIVE: The goal of the research was to investigate the use of mobile phone-based telemedicine apps for management of older Chinese patients with type 2 diabetes mellitus (T2DM). Variables of interest included efficacy and safety. METHODS: A total of 91 older (aged over 65 years) patients with T2DM who presented to our department were randomly assigned to one of two groups. Patients in the intervention group (n=44) were provided glucometers capable of data transmission and received advice pertaining to medication, diet, and exercise via the mHealth telemedicine system. Patients assigned to the control group (n=47) received routine outpatient care with no additional intervention. Patients in both groups were followed up at regular 3-month intervals. RESULTS: After 3 months, patients in the intervention group showed significant (P<.05) improvement in postprandial plasma glucose level. After 6 months, patients in the intervention group exhibited a decreasing trend in postprandial plasma glucose and glycated hemoglobin levels compared with the baseline and those in the control group (P<.05). CONCLUSIONS: Mobile phone-based telemedicine apps help improve glycemic control in older Chinese patients with T2DM. TRIAL REGISTRATION: China Clinical Trial Registration Center ChiCTR 1800015214; http://www.chictr.org.cn/showprojen.aspx?proj=25949 (Archived by WebCite at http://www.webcitation.org/73wKj1GMq).

Evaluating a Fully Automated Pulmonary Nodule Detection Approach and Its Impact on Radiologist Performance.

PURPOSE: To compare sensitivity in the detection of lung nodules between the deep learning (DL) model and radiologists using various patient population and scanning parameters and to assess whether the radiologists' detection performance could be enhanced when using the DL model for assistance. MATERIALS AND METHODS: A total of 12 754 thin-section chest CT scans from January 2012 to June 2017 were retrospectively collected for DL model training, validation, and testing. Pulmonary nodules from these scans were categorized into four types: solid, subsolid, calcified, and pleural. The testing dataset was divided into three cohorts based on radiation dose, patient age, and CT manufacturer. Detection performance of the DL model was analyzed by using a free-response receiver operating characteristic curve. Sensitivities of the DL model and radiologists were compared by using exploratory data analysis. False-positive detection rates of the DL model were compared within each cohort. Detection performance of the same radiologist with and without the DL model were compared by using nodule-level sensitivity and patient-level localization receiver operating characteristic curves. RESULTS: The DL model showed elevated overall sensitivity compared with manual review of pulmonary nodules. No significant dependence regarding radiation dose, patient age range, or CT manufacturer was observed. The sensitivity of the junior radiologist was significantly dependent on patient age. When radiologists used the DL model for assistance, their performance improved and reading time was reduced. CONCLUSION: DL shows promise to enhance the identification of pulmonary nodules and benefit nodule management.© RSNA, 2019Supplemental material is available for this article.