Relationships between apolipoprotein E and insulin resistance in patients with obstructive sleep apnoea: a large-scale cross-sectional study.

BACKGROUND: Obstructive sleep apnoea (OSA) is commonly associated with insulin resistance (IR) and dyslipidaemia. Apolipoprotein E (APOE) plays important roles in lipid metabolism. The study aimed to disentangle the multifactorial relationships between IR and APOE based on a large-scale population with OSA. METHODS: A total of 5,591 participants who underwent polysomnography for OSA diagnosis were finally enrolled. We collected anthropometric, fasting biochemical and polysomnographic data for each participant. Linear regression analysis was performed to evaluate the relationships between APOE, IR, and sleep breathing-related parameters. Logistic regression, restricted cubic spline (RCS) and mediation analyses were used to explore relationships between APOE and IR in patients with OSA. RESULTS: Increasing OSA severity was associated with greater obesity, more obvious dyslipidaemia, and higher levels of APOE and IR. APOE was positively correlated with the apnoea-hypopnoea index (AHI), oxygen desaturation index (ODI) and microarousal index (MAI) even after adjusting for age, sex, body mass index, and smoking and drinking levels (ß = 0.107, ß = 0.102, ß = 0.075, respectively, all P < 0.001). The risks of IR increased from the first to fourth quartiles of APOE (odds ratio (OR) = 1.695, 95% CI: 1.425-2.017; OR = 2.371, 95% confidence interval (CI): 2.009-2.816; OR = 3.392, 95% CI: 2.853-4.032, all P < 0.001) after adjustments. RCS analysis indicated non-linear and dose response relationships between APOE, AHI, ODI, MAI and insulin resistance. Mediation analyses showed that HOMA-IR explained 9.1% and 10% of the association between AHI, ODI and APOE. The same trends were observed in men, but not in women. CONCLUSIONS: This study showed that APOE is a risk factor for IR; moreover, IR acts as a mediator between OSA and APOE in men. APOE, IR, and OSA showed non-linear and multistage relationships. Taken together, these observations revealed the complex relationships of metabolic disorders in patients with OSA, which could lead to the development of new treatment modalities and a deeper understanding of the systemic impact of OSA.

Novel progressive deep learning algorithm for uncovering multiple single nucleotide polymorphism interactions to predict paclitaxel clearance in patients with nonsmall cell lung cancer.

Background: The rate at which the anticancer drug paclitaxel is cleared from the body markedly impacts its dosage and chemotherapy effectiveness. Importantly, paclitaxel clearance varies among individuals, primarily because of genetic polymorphisms. This metabolic variability arises from a nonlinear process that is influenced by multiple single nucleotide polymorphisms (SNPs). Conventional bioinformatics methods struggle to accurately analyze this complex process and, currently, there is no established efficient algorithm for investigating SNP interactions. Methods: We developed a novel machine-learning approach called GEP-CSIs data mining algorithm. This algorithm, an advanced version of GEP, uses linear algebra computations to handle discrete variables. The GEP-CSI algorithm calculates a fitness function score based on paclitaxel clearance data and genetic polymorphisms in patients with nonsmall cell lung cancer. The data were divided into a primary set and a validation set for the analysis. Results: We identified and validated 1184 three-SNP combinations that had the highest fitness function values. Notably, SERPINA1, ATF3 and EGF were found to indirectly influence paclitaxel clearance by coordinating the activity of genes previously reported to be significant in paclitaxel clearance. Particularly intriguing was the discovery of a combination of three SNPs in genes FLT1, EGF and MUC16. These SNPs-related proteins were confirmed to interact with each other in the protein-protein interaction network, which formed the basis for further exploration of their functional roles and mechanisms. Conclusion: We successfully developed an effective deep-learning algorithm tailored for the nuanced mining of SNP interactions, leveraging data on paclitaxel clearance and individual genetic polymorphisms.

Serum Prealbumin as a Potential Predictive Factor for Age-Related Hearing Loss: A Retrospective Study.

Objectives: Age-related hearing loss (ARHL) is a complex disease associated with the interaction of multiple factors. Furthermore, indicators of liver function represent the body's metabolic, immune, and repair abilities. This study investigated correlations between liver function and ARHL. Methods: A total of 107 patients with ARHL and 107 age- and sex-matched healthy volunteers were included. Linear correlations, logistic regression, and receiving operator characteristic curves were used to assess the associations between liver function and ARHL. Results: Serum prealbumin (PAB) levels were significantly lower in the ARHL group compared to the control group. Logistic regression analysis indicated that low PAB levels may be an independent risk factor for ARHL. The ARHL was divided into 2 groups according to the degree of hearing loss (moderately severe-to-profound and mild-to-moderate); the median ages in the 2 groups were 70.48 and 66.85 years, respectively, with the difference being significant. Age was an independent risk factor for moderately severe-to-profound ARHL, as shown by the logistic regression analysis. Conclusions: Lower PAB levels in patients with ARHL suggested that PAB may be a risk factor for ARHL. Furthermore, higher age in patients with ARHL was associated with a greater degree of hearing loss.

Comparing the cost-effectiveness of sintilimab + pemetrexed plus platinum and pemetrexed plus platinum alone as a first-line therapy for Chinese patients with nonsquamous non-small cell lung cancer.

Background: Pemetrexed plus platinum alone is the conventional first-line therapy for locally advanced metastatic nonsquamous non-small cell lung cancer (NSCLC) without targetable genetic aberrations. The ORIENT-11 trial revealed that sintilimab + pemetrexed plus platinum could yield more survival benefits for patients with nonsquamous NSCLC. The present study aimed to assess the cost-effectiveness of sintilimab + pemetrexed plus platinum vs. that of pemetrexed plus platinum alone as the first-line therapy for patients with nonsquamous NSCLC to inform clinically rational drug use and provide a basis for medical decision-making. Methods: A partitioned survival model was created to evaluate the cost-effectiveness of two groups from the perspective of the healthcare system in China. The clinical data for adverse event probabilities and extrapolating long-term survival originally collected in a phase III clinical trial (ORIENT-11) were retrieved. Local public databases and literature were used to acquire data on utility and cost. The heemod package in R software was used to calculate the life years (LYs), quality-adjusted LYs (QALYs), and total costs in each group to generate the incremental cost-effectiveness ratio (ICER) in the base case and to conduct deterministic sensitivity analysis (DSA) and probabilistic sensitivity analysis (PSA). Results: Our base case analysis (BCA) revealed that sintilimab combined with pemetrexed plus platinum provided an increase of 0.86 in QALYs with an increasing cost of United State dollar (USD) $4,317.84 relative to pemetrexed plus platinum in Chinese patients with nonsquamous NSCLC who were negative for targetable genetic variations, which induced an ICER of USD $5,020.74/QALY. The ICER value was lower than the set threshold value. The results exhibited strong robustness in the sensitivity analysis. In DSA, the parameter for the overall survival (OS) curve in chemotherapy and the cost of best supportive care were the main factors that impacted the result of the ICER. The PSA indicated that sintilimab and chemotherapy combination therapy was cost-effective. Conclusions: This study suggests that the combination of sintilimab + pemetrexed plus platinum is cost-effective as a first-line therapy in Chinese patients with nonsquamous NSCLC who are negative for targetable genetic variations from the perspective of the healthcare system.

Anthropometric Determinants of Autonomic Control in Obstructive Sleep Apnea: A Large-Scale Study.

OBJECTIVE: Autonomic dysfunction is an independent risk factor for cardiovascular disease (CVD). Both obesity and obstructive sleep apnea (OSA) are associated with heart rate variability (HRV) (a hall marker of sympathetic arousal) and increased risk of CVD. This study aims to investigate whether anthropometric parameters could predict reduced HRV in adult OSA during wakefulness. STUDY DESIGN: Cross-sectional study. SETTING: Sleep center of Shanghai Jiao Tong University Affiliated Sixth Hospital from 2012 to 2017. METHODS: Total of 2134 subjects (503 non-OSA and 1631 OSA) were included. Anthropometric parameters were recorded. HRV was recorded during a 5-minute wakefulness period and analyzed by using time-domain method and frequency-domain method. Multiple step-wise linear regressions were performed to determine significant predictors of HRV with and without adjustments. Multiplicative interactions between gender, OSA, and obesity on HRV were also determined and evaluated. RESULTS: Waist circumference (WC) was significant negative determinant of root mean square of successive NN intervals (ß = -.116, p < .001) and high-frequency power (ß = -.155, p < .001). Age was the strongest determining factor of HRV. Significant multiplicative interactions between obesity and OSA on HRV, gender, and obesity on cardiovascular parameters were observed. CONCLUSION: Anthropometric parameters could predict reduced HRV during wakefulness in patients with OSA, especially WC was the strongest influenceable factor. Obesity and OSA had significant multiplicative interaction on HRV. Gender and obesity had significant multiplicative interaction on cardiovascular parameters. Early intervention for obesity, especially centripetal obesity, may improve reduction of autonomic function and risk of CVD.

Associations between common sleep disturbances and cardiovascular risk in patients with obstructive sleep apnea: A large-scale cross-sectional study.

Objectives: Studies have shown that obstructive sleep apnea (OSA) is inextricably linked with cardiovascular diseases (CVD). However, the roles of certain common sleep disturbances, such as low slow-wave sleep, excessive daytime sleepiness and short sleep duration, in the pathogenesis and progression of CVD in patients with OSA have not been determined. Therefore, we conducted a large cross-sectional study to explore the effect of low slow-wave sleep, excessive daytime sleepiness and short sleep duration on the risk of CVD in patients with OSA. Methods: Subjects were consecutively enrolled to participate in the sleep center of Shanghai Jiao Tong University Affiliated Sixth People's Hospital. All OSA patients were diagnosed by standard polysomnography, while controls were all simple snorers. A total of 4,475 participants were strictly recruited. The Framingham Risk Score were employed to assess the 10-year risk of CVD, and logistic regression was used to measure the association between sleep disturbances and the moderate-to-high CVD risk. Results: In the whole cohort, OSA, excessive daytime sleepiness, and low slow-wave sleep were all risk factors for the moderate-to-high 10-year CVD risk (odds ratio [OR] = 3.012, 95% confidence interval [CI] 2.418-3.751; OR = 1.407, 95% CI: 1.228-1.613, and OR = 0.973,95% CI: 0.967-0.980), but sleep duration did not contribute significantly to that risk. Whether in patients with OSA and controls, low SWS (<12.8%) could increase the risk of CVD. Subjective excessive daytime sleepiness would significantly increase the risk of CVD only in patients with severe OSA. Conclusion: It is important to pay more attention to the impact of sleep on cardiovascular health. Patients with sleep disturbances should adopt a healthy lifestyle and undergo regular follow-up of cardiovascular indicators to prevent cardiovascular complications. Trial registration: [http://www.chictr.org.cn/showproj.aspx?proj=43057], identifier [ChiCTr1900025714].

Metabolomics Combined with Network Pharmacology-Based Strategy to Reveal the Underlying Mechanism of Zhenhuang Submicron Emulsion in Treating Oropharyngeal Mucositis Complications of Radiation Therapy for Head and Neck Cancer.

Introduction: Head and neck tumors account for more than 6% of all cancers. The primary treatment for tumors of the head and neck is radiation therapy, which can induce oropharyngeal mucositis as a side effect. At present, there is no widely available therapeutic for the treatment of oropharyngeal mucositis in clinical practice. Based on the traditional prescription Liushen Wan, the pathogenesis and pathology, we developed a new Chinese medicine prescription and made Zhenhuang submicron emulsion (ZHSE) spray, which has an efficacious therapeutic effect for oropharyngeal mucositis. However, its mechanism is unclear. Methods: This research explored the mechanism behind the modulatory effects of ZHSE by a strategy of metabolomics and network pharmacology. Multivariate data analyses, including unsupervised principal component analysis (PCA) and supervised orthogonal partial least squares discriminant analysis (OPLS-DA), were performed. Potential biomarkers were identified depending on the mass-charge ratio of the selected compound. Statistical and pathway enrichment analysis was performed in the KEGG pathway database. Network pharmacology combining metabolomic analyses was conducted to illustrate the key targets and pathways. Results: Critical metabolic pathways were investigated, 56f biomarkers were enriched and key metabolites such as linoleic acid, 9,10-epoxyoctadecenoic acid, acetoacetic acid and citric acid were identified. A complex network of "compound-target-potential metabolite" interactions was drawn to illuminate the regulation of chemical constituents on key metabolites. These findings manifest that ZHSE regulates endogenous metabolite disorders during the treatment of oropharyngeal mucositis by various constituents, interacting with multiple targets associated with inflammation and pain. Conclusion: In this work, we determined several critical biomarkers and metabolic pathways and identified the possible regulatory mechanism by which ZHSE functions in the treatment of oropharyngeal mucositis. This study provides a new perspective on integrating metabolomics and network pharmacology for exploring improved therapy for head and neck tumors based on the traditional classic prescription of LSW.

Differential weighting of temporal envelope cues from the low-frequency region for Mandarin sentence recognition in noise.

BACKGROUND: Temporal envelope cues are conveyed by cochlear implants (CIs) to hearing loss patients to restore hearing. Although CIs could enable users to communicate in clear listening environments, noisy environments still pose a problem. To improve speech-processing strategies used in Chinese CIs, we explored the relative contributions made by the temporal envelope in various frequency regions, as relevant to Mandarin sentence recognition in noise. METHODS: Original speech material from the Mandarin version of the Hearing in Noise Test (MHINT) was mixed with speech-shaped noise (SSN), sinusoidally amplitude-modulated speech-shaped noise (SAM SSN), and sinusoidally amplitude-modulated (SAM) white noise (4 Hz) at a + 5 dB signal-to-noise ratio, respectively. Envelope information of the noise-corrupted speech material was extracted from 30 contiguous bands that were allocated to five frequency regions. The intelligibility of the noise-corrupted speech material (temporal cues from one or two regions were removed) was measured to estimate the relative weights of temporal envelope cues from the five frequency regions. RESULTS: In SSN, the mean weights of Regions 1-5 were 0.34, 0.19, 0.20, 0.16, and 0.11, respectively; in SAM SSN, the mean weights of Regions 1-5 were 0.34, 0.17, 0.24, 0.14, and 0.11, respectively; and in SAM white noise, the mean weights of Regions 1-5 were 0.46, 0.24, 0.22, 0.06, and 0.02, respectively. CONCLUSIONS: The results suggest that the temporal envelope in the low-frequency region transmits the greatest amount of information in terms of Mandarin sentence recognition for three types of noise, which differed from the perception strategy employed in clear listening environments.

Electroencephalography Microstate Alterations in Otogenic Vertigo: A Potential Disease Marker.

Objectives: A huge population, especially the elderly, suffers from otogenic vertigo. However, the multi-modal vestibular network changes, secondary to periphery vestibular dysfunction, have not been fully elucidated. We aim to identify potential microstate electroencephalography (EEG) signatures for otogenic vertigo in this study. Materials and Methods: Patients with recurrent otogenic vertigo and age-matched healthy adults were recruited. We performed 256-channel EEG recording of all participants at resting state. Neuropsychological questionnaires and vestibular function tests were taken as a measurement of patients' symptoms and severity. We clustered microstates into four classes (A, B, C, and D) and identified their dynamic and syntax alterations of them. These features were further fed into a support vector machine (SVM) classifier to identify microstate signatures for vertigo. Results: We compared 40 patients to 45 healthy adults, finding an increase in the duration of Microstate A, and both the occurrence and time coverage of Microstate D. The coverage and occurrence of Microstate C decreased significantly, and the probabilities of non-random transitions between Microstate A and D, as well as Microstate B and C, also changed. To distinguish the patients, the SVM classifier, which is built based on these features, got a balanced accuracy of 0.79 with a sensitivity of 0.78 and a specificity of 0.8. Conclusion: There are several temporal dynamic alterations of EEG microstates in patients with otogenic vertigo, especially in Microstate D, reflecting the underlying process of visual-vestibular reorganization and attention redistribution. This neurophysiological signature of microstates could be used to identify patients with vertigo in the future.

Relative Weights of Temporal Envelope Cues in Different Frequency Regions for Mandarin Vowel, Consonant, and Lexical Tone Recognition.

Objectives: Mandarin-speaking users of cochlear implants (CI) perform poorer than their English counterpart. This may be because present CI speech coding schemes are largely based on English. This study aims to evaluate the relative contributions of temporal envelope (E) cues to Mandarin phoneme (including vowel, and consonant) and lexical tone recognition to provide information for speech coding schemes specific to Mandarin. Design: Eleven normal hearing subjects were studied using acoustic temporal E cues that were extracted from 30 continuous frequency bands between 80 and 7,562 Hz using the Hilbert transform and divided into five frequency regions. Percent-correct recognition scores were obtained with acoustic E cues presented in three, four, and five frequency regions and their relative weights calculated using the least-square approach. Results: For stimuli with three, four, and five frequency regions, percent-correct scores for vowel recognition using E cues were 50.43-84.82%, 76.27-95.24%, and 96.58%, respectively; for consonant recognition 35.49-63.77%, 67.75-78.87%, and 87.87%; for lexical tone recognition 60.80-97.15%, 73.16-96.87%, and 96.73%. For frequency region 1 to frequency region 5, the mean weights in vowel recognition were 0.17, 0.31, 0.22, 0.18, and 0.12, respectively; in consonant recognition 0.10, 0.16, 0.18, 0.23, and 0.33; in lexical tone recognition 0.38, 0.18, 0.14, 0.16, and 0.14. Conclusion: Regions that contributed most for vowel recognition was Region 2 (502-1,022 Hz) that contains first formant (F1) information; Region 5 (3,856-7,562 Hz) contributed most to consonant recognition; Region 1 (80-502 Hz) that contains fundamental frequency (F0) information contributed most to lexical tone recognition.

Association of Glycosylated Hemoglobin A1c Level With Sudden Sensorineural Hearing Loss: A Prospective Study.

Glycosylated hemoglobin A1c (HbA1c) level has strong relevance to microvascular disorders, which are also thought to be the current main aspect of sudden sensorineural hearing loss (SSNHL), so we aim to elucidate the association of the HbA1c level with the severity, types, and prognosis of SSNHL. In this study, comparative analyses based on propensity score matching of the severity, types, and prognosis of SSNHL with the HbA1c level in 116 patients diagnosed as SSNHL were conducted, where they were divided into diabetes mellitus (DM) group and non-DM group. We finally found that, among patients with SSNHL, diabetic patients had a higher HbA1c level, more severe hearing loss, and poorer prognosis than non-diabetic patients. The HbA1c level was found to be significantly correlated with the severity and types of SSNHL, while no strong relevance was found between the higher HbA1c level and the poorer prognosis of SSNHL.

Association of Prior to Intensive Care Unit Statin Use With Outcomes on Patients With Acute Kidney Injury.

Purpose: To evaluate the association of prior to intensive care unit (ICU) statin use with the clinical outcomes in critically ill patients with acute kidney injury (AKI). Materials and Methods: Patients with AKI were selected from the Medical Information Mart for Intensive Care IV (version 1.0) database for this retrospective observational study. The primary outcome was 30-day intensive care unit (ICU) mortality. A 30-day in-hospital mortality and ICU length of stay (LOS) were considered as secondary outcomes. Comparison of mortality between pre-ICU statin users with non-users was conducted by the multivariate Cox proportional hazards model. Comparison of ICU LOS between two groups was implemented by multivariate linear model. Three propensity score methods were used to verify the results as sensitivity analyses. Stratification analyses were conducted to explore whether the association between pre-ICU statin use and mortality differed across various subgroups classified by sex and different AKI stages. Results: We identified 3,821 pre-ICU statin users and 9,690 non-users. In multivariate model, pre-ICU statin use was associated with reduced 30-day ICU mortality rate [hazard ratio (HR) 0.68 (0.59, 0.79); p < 0.001], 30-day in-hospital mortality rate [HR 0.64 (0.57, 0.72); p < 0.001] and ICU LOS [mean difference -0.51(-0.79, -0.24); p < 0.001]. The results were consistent in three propensity score methods. In subgroup analyses, pre-ICU statin use was associated with decreased 30-day ICU mortality and 30-day in-hospital mortality in both sexes and AKI stages, except for 30-day ICU mortality in AKI stage 1. Conclusion: Patients with AKI who were administered statins prior to ICU admission might have lower mortality during ICU and hospital stay and shorter ICU LOS.

Force transmission characteristics in a multiple-fulcrum supporting platform with heavy loads.

This study aims to investigate the force transmission characteristics of a multiple-fulcrum supporting platform, and the significance of this paper is to creatively put forward the law of uniform force characteristics of multiple-fulcrum supporting platform with heavy loads and layout reconfiguration methods to realize the law. In this paper, firstly, a force transmission model for the multiple-fulcrum supporting platform has been constructed, the relationship between force transmission characteristics and layout parameters for all fulcrums has been discussed in detail, and the layout law for all fulcrums with the same supporting force has been discovered. Then, layout reconfiguration methods have been proposed to realize the uniform force characteristics of all fulcrums under different types of constraint surfaces (rectangular or square constrained surface, circular constrained surface, and unconstrained surface). Finally, layout reconfiguration methods have been applied to some engineering problems by ADAMS simulation. The simulation results show that the supporting force of all fulcrums in the supporting platform is equal when the layout central point (LCP) of all fulcrums is coincident with the force equivalent point (FEP) of external loads. The results provide theoretical guidance and support for the reconfiguration of multiple-fulcrum supporting platforms that can realize uniform forces among all fulcrums.

Roles of CCNB2 and NKX3-1 in Nasopharyngeal Carcinoma.

Background: Nasopharyngeal carcinoma (NPC) is leading form of cancer occurring in a few well-defined regions, including southern China. NPC possess a unique and intricate etiology that remains to be elucidated. Herein, we determine expression patterns of CCNB2 and NKX3-1 and identify their roles in NPC. Materials and Methods: Gene-expression profiles of NPC in the Gene Expression Omnibus (GEO) were analyzed. Cell viability, invasion, apoptosis, cell cycle entry and mitochondrial membrane potential (MMP) were evaluated in the presence of NKX3-1 or in the absence of CCNB2. Results: In all, 187 upregulated genes and 683 downregulated genes were obtained by analyzing GSE13597. NKX3-1, the downregulated gene, and CCNB2, the upregulated one, were further confirmed by in vitro studies. Overexpression of NKX3-1 was shown to inhibit NPC cell viability and invasion. Knockdown of CCNB2 was demonstrated to reduce cell cycle entry and MMP but induce apoptosis in NPC cells. Conclusions: Taken together, the key finding obtained from the study supports CCNB2 and NKX3-1 as two promising therapeutic candidates for NPC. Molecular mechanisms that control CCNB2 or NKX3-1 disturbance require further investigation and clarification.

[Isolation of Heavy Metal Immobilizing and Plant Growth-Promoting Bacteria and Its Effects on Reducing Heavy Metal Accumulation in Wheat].

The effects of heavy metal contamination on farmland continues to worsen progressively with an increase in anthropogenic activities such as industrial pollution and mining. Excess Cd and Pb in agricultural soils enter the food chain and adversely affect all organisms. Therefore, it is important to find an eco-friendly way to reduce heavy metal accumulation in crops. Based on their heavy metal resistance and growth-promoting characteristics, functional bacterial strains were screened and their effects on growth and heavy metal accumulation in wheat were verified via shaking flask adsorption and sand culture tests. Eighteen functional strains were isolated from the rhizospheric soil of Salvia setaria. Among them, Bacillus megaterium N3 and Serratia liquefaciens H12 were most effective at resisting high Cd (650 mg·L-1) and Pb (2700 mg·L-1) concentrations, and at producing indole-3-acetic acid (IAA) (56.6 mg·L-1and 69.1 mg·L-1, respectively), siderophores, and 1-Amino-1-cyclopropanecarboxylic acid (ACC) deaminase. Static incubation experiments showed that strains N3 and H12 significantly increased the NH4+ concentration and pH, and decreased the Cd (63.1%-73.8%) and Pb (69.1%-81.8%) concentration in solution. In sand cultures, strains N3 and H12 not only increased the dry weight of wheat roots (47.2%-97.4%) and shoots (65.3%-153%) significantly, but also significantly reduced the Cd (49.2%-68.3%) and Pb (27.4%-84.5%) content in wheat roots and shoots. Thus, the results provide strain resources and a theoretical basis for the remediation of Cd- and Pb-contaminated farmlands for the safer production of crops.

Myelin-associated glycoprotein associated neuropathies: clinical features and antibody detection / 中华神经科杂志

Objective To investigate the clinical and electrophysiological characteristics of anti-myelin-associated glycoprotein (MAG)-associated peripheral neuropathy, as well as its antibody detection methods, treatment and prognosis. Methods Six cases of IgM paraproteinemia and anti-MAG antibody-associated peripheral neuropathy were summarized. All of the patients came from Peking Union Medical College Hospital and Qilu Hospital since April 2014 to February 2018. The clinical features, electrophysiological characteristics, and auxiliary examinations including anti-MAG antibody results were analyzed, and the treatment and prognosis were followed. Results Of the six patients, five were male and one was female. The age of onset was 50-77 years and the duration was three months to six years. All the six cases suffered from numbness of distal limbs and gradually progressed to the proximal limbs, of which three cases had muscle weakness. Walking instability occurred in five cases. One patient had electricity-like pain in the lower extremities. Reflexes in the four limbs decreased in five cases, and gloves and socks-like deep sensation decreased in six cases. Five patients underwent lumbar puncture and the cerebral spinal fluid protein ranged from 0.75 to 1.33 g/L. Serum monoclonal proteins were found in six patients, of which four were IgM kappa and two were IgG kappa and IgM kappa biclonal. Four cases were diagnosed with monoclonal gammopathy of undetermined significance and two cases were diagnosed with Waldenstr?m's macroglobulinaemia. Abnormal electromyography was detected in all the six cases, suggesting demyelinating peripheral nerve damage with secondary axonal damage, which was sensory predominant and more severe in lower limbs than upper limbs. In all the six cases, anti-MAG-IgM antibodies were all positive by indirect immunofluorescence assay based on transfected cells and peripheral nerve tissues. After the diagnosis, three patients underwent RCD (rituxima + dexamethasone + cyclophosphamide) chemotherapy. One patient improved (the modified Rankin scale (mRS) score was 3 before treatment and 2 three years after treatment), one patient was stable, and one patient was still in follow-up. One patient was treated with rituxima, and the condition improved (the mRS score was 3 before treatment and 1 one year after treatment). Conclusions MAG-associated peripheral neuropathy can present a slow progressed distal symmetric sensomotor peripheral neuropathy with predominant sensory symptoms. Electromyography shows demyelinating change. Monoclonal protein is usually IgM kappa. MAG-IgM antibodies detection by indirect immunofluorescence assay based on transfected cells and peripheral nerve tissues can support the diagnosis. RCD chemotherapy may be effective.

Serum uric acid: a new therapeutic target for nonalcoholic fatty liver disease.

INTRODUCTION: Nonalcoholic fatty liver disease (NAFLD) is a major, worldwide public health problem. NAFLD is recognized as a major cause of liver-related morbidity and mortality. However, physicians are currently limited by available treatment options. Recently, numerous studies have reported a correlation between serum uric acid (SUA) and NAFLD with numerous clinical and experimental studies demonstrating a significant correlation. This review will focus on the role of SUA in the development of NAFLD and its potential role as a new target for therapeutic intervention. AREAS COVERED: This review discusses SUA as a significant independent factor in the development of NAFLD. Moreover, we introduce the causal relationship between SUA, metabolic syndrome, and NAFLD. We discuss two major theories of insulin resistance and inflammasomes as potential explanations of the mechanistic link between SUA and NAFLD. In addition, we review current and emerging therapeutic medications to control appropriate SUA levels. EXPERT OPINION: There is an urgent need to develop novel, safe and effective therapies for the growing NAFLD epidemic. Reduction of SUA may be a promising potential treatment for patients with NAFLD. Clinical studies are required to determine the therapeutic effect of attenuation of hyperuricemia in humans with NAFLD.

Investigation on the Consistency of Five Measurement Systems for Serum Lipids / 现代检验医学杂志

Objective To explore achieving the consistent method of blood lipid examination by comparing the results of 5 dif-ferent blood lipid detection system commonly used in the use of refernce method to assign freach blood serum before and af-ter calibration.Methods Used the indoor quality control total variation (CV%)to evaluate the 5 blood lipid examination system of the imprecision.Referenced the United States Clinical and Laboratory Standardization Institution (CLSI)9A2 EP program,compared with 54 fresh blood serum in 5 commonly used examination system of Total Cholesterol (TC)and Tri-glyceride (TG),and then estimated the bias between the different detection systems and mean value.8 of the samples were determined by the reference method and estimate the bias of different system.The fresh frozen serum samples assigned by reference method were used to evaluate the above examination system,then compare and estimate the bias again with the same 54 fresh serum samples.Compared the variation of 54 samples in different detection system before and after calibra-tion.Results The TG imprecision of 5 examination system were between 3.76%~23.65%,the TC imprecision between 2.19%~23.43%,that mean the results were good,the r value of TG were between 0.996 7~0.999 6 and the TC were 0.956 2~0.996 7.But there were obvious differences between the results of the systems,and the biggest difference were 14.72%~34.21% in TG and 3.11%~14.57% in TC.After use the serum assignment by reference method,the variation of the systems has been significantly decreased.Conclusion Using the reference method to assign the fresh serum of different blood lipid detection system can effectively improve the consistency of the results.

Effects of nano-TiO2 on antibiotic resistance transfer mediated by RP4 plasmid.

The potential risks of nano-materials and the spread of antibiotic resistance genes (ARGs) have become two major global public concerns. Studies have confirmed that nano-alumina can promote the spread of ARGs mediated by plasmids. Nano-titanium dioxide (TiO(2)), an excellent photocatalytic nano-material, has been widely used and is often present in aqueous environments. At various nano-material concentrations, bacterial density, matting time, and matting temperature, nano-TiO(2) can significantly promote the conjugation of RP4 plasmid in Escherichia coli. We developed a mathematical model to quantitatively describe the conjugation process and used this model to evaluate the effects of nano-TiO(2) on the spread of ARGs. We obtained analytical solutions for total and resistant bacteria, which were enumerated by the abundance of genetic loci unique to the plasmid and the chromosome using qPCR. Our results showed that the mathematic model was able to fit the experimental data well and can be used to quantitatively evaluate the effects of nano-TiO(2). According to our model, the presence of nano-TiO(2) decreased the bacterial growth rate from 0.0360 to 0.0323 min(-1) and increased the conjugative transfer rate from 6.69 × 10(-12) to 3.93 × 10(-10 )mL cell(-1) min(-1). These results indicate that nano-TiO(2) inhibited bacterial growth and promoted conjugation simultaneously. The data for morphology and mRNA expression also demonstrated this phenomenon. Our results confirm that environmental nano-TiO(2) may cause the spread of ARGs and thus poses an environmental risk. In addition, we provide a potential method for monitoring changes in ARGs that result from conjugation and evaluating the effects of antimicrobial substances on ARG expression.

An RF dosimeter for independent SAR measurement in MRI scanners.

PURPOSE: The monitoring and management of radio frequency (RF) exposure is critical for ensuring magnetic resonance imaging (MRI) safety. Commercial MRI scanners can overestimate specific absorption rates (SAR) and improperly restrict clinical MRI scans or the application of new MRI sequences, while underestimation of SAR can lead to tissue heating and thermal injury. Accurate scanner-independent RF dosimetry is essential for measuring actual exposure when SAR is critical for ensuring regulatory compliance and MRI safety, for establishing RF exposure while evaluating interventional leads and devices, and for routine MRI quality assessment by medical physicists. However, at present there are no scanner-independent SAR dosimeters. METHODS: An SAR dosimeter with an RF transducer comprises two orthogonal, rectangular copper loops and a spherical MRI phantom. The transducer is placed in the magnet bore and calibrated to approximate the resistive loading of the scanner's whole-body birdcage RF coil for human subjects in Philips, GE and Siemens 3 tesla (3T) MRI scanners. The transducer loop reactances are adjusted to minimize interference with the transmit RF field (B1) at the MRI frequency. Power from the RF transducer is sampled with a high dynamic range power monitor and recorded on a computer. The deposited power is calibrated and tested on eight different MRI scanners. Whole-body absorbed power vs weight and body mass index (BMI) is measured directly on 26 subjects. RESULTS: A single linear calibration curve sufficed for RF dosimetry at 127.8 MHz on three different Philips and three GE 3T MRI scanners. An RF dosimeter operating at 123.2 MHz on two Siemens 3T scanners required a separate transducer and a slightly different calibration curve. Measurement accuracy was ∼3%. With the torso landmarked at the xiphoid, human adult whole-body absorbed power varied approximately linearly with patient weight and BMI. This indicates that whole-body torso SAR is on average independent of the imaging subject, albeit with fluctuations. CONCLUSIONS: Our 3T RF dosimeter and transducers accurately measure RF exposure in body-equivalent loads and provide scanner-independent assessments of whole-body RF power deposition for establishing safety compliance useful for MRI sequence and device testing.