Machine Learning-Based Prediction of In-Hospital Complications in Elderly Patients Using GLIM-, SGA-, and ESPEN 2015-Diagnosed Malnutrition as a Factor

Background: Malnutrition is prevalent in elderly inpatients and is associated with various adverse outcomes during their hospital stay, but the diagnosis of malnutrition still lacks widely applicable criteria. This study aimed to investigate the association of malnutrition diagnosed with the SGA, ESPEN 2015, and GLIM criteria, respectively, with in-hospital complications in elderly patients. Method: Hospitalized patients over 65 years old who had been assessed with the SGA guideline for malnutrition at admission were retrospectively recruited from a large observational cohort study conducted in 34 level-A tertiary hospitals in 18 cities in China from June to September 2014. Malnutrition was then retrospectively diagnosed using the GLIM and ESPEN 2015 criteria, respectively, for comparison with the results of the SGA scale. The risk factors for malnutrition were analyzed using logistic regression, and the value of the three diagnostic criteria in predicting the in-hospital complications was subsequently explored using multivariate regression and the random forest machine learning algorithm. Results: A total of 2526 subjects who met the inclusion and exclusion criteria of the study were selected from the 7122 patients in the dataset, with an average age of 74.63 ± 7.12 years, 59.2% male, and 94.2% married. According to the GLIM, SGA, and ESPEN 2015 criteria, the detection rates of malnutrition were 37.8% (956 subjects), 32.8% (829 subjects), and 17.0% (429 subjects), respectively. The diagnostic consistency between the GLIM and the SGA criteria is better than that between the ESPEN 2015 and the SGA criteria (Kappa statistics, 0.890 vs. 0.590). Logistic regression showed that the risk of developing complications in the GLIM-defined malnutrition patients is 2.414 times higher than that of normal patients, higher than those of the ESPEN 2015 and SGA criteria (1.786 and 1.745 times, respectively). The random forest classifications show that the GLIM criteria have a higher ability to predict complications in these elderly patients than the SGA and ESPEN 2015 criteria with a mean decrease in accuracy of 12.929, 10.251, and 5.819, respectively, and a mean decrease in Gini of 2.055, 1.817, and 1.614, respectively. Conclusion: The prevalence of malnutrition diagnosed with the GLIM criteria is higher than that of the SGA and the ESPEN 2015 criteria. The GLIM criteria are better than the SGA and the ESPEN 2015 criteria for predicting in-hospital complications in elderly patients.     

High-Throughput Screening of FDA-Approved Drug Library Reveals Ixazomib Is a Broad-Spectrum Antiviral Agent against Arboviruses

The emergence of significant arboviruses and their spillover transmission to humans represent a major threat to global public health. No approved drugs are available for the treatment of significant arboviruses in circulation today. The repurposing of clinically approved drugs is one of the most rapid and promising strategies in the identification of effective treatments for diseases caused by arboviruses. Here, we screened small-molecule compounds with anti-tick-borne encephalitis virus, West Nile virus, yellow fever virus and chikungunya virus activity from 2580 FDA-approved drugs. In total, 60 compounds showed antiviral efficacy against all four of the arboviruses in Huh7 cells. Among these compounds, ixazomib and ixazomib citrate (inhibitors of 20S proteasome β5) exerted antiviral effects at a low-micromolar concentration. The time-of-drug-addition assay suggested that ixazomib and ixazomib citrate disturbed multiple processes in viruses’ life cycles. Furthermore, ixazomib and ixazomib citrate potently inhibited chikungunya virus replication and relieved virus-induced footpad swelling in a mouse model. These results offer critical information which supports the role of ixazomib as a broad-spectrum agent against arboviruses.     

银杏叶中单体活性成分抑制Aβ1-42聚集和纤维的形成

目的:研究银杏叶提取物中单体活性成分银杏黄酮及银杏内酯对Aβ聚集和纤维形成的影响。方法:运用硫磺素-T荧光分析和透射电镜,通过体外孵育方式观察银杏黄酮、银杏内酯干预Aβ1-42聚集和纤维形成作用。结果:银杏黄酮能明显抑制Aβ1-42的聚集和纤维形成;对老化Aβ纤维亦有明显抑制作用。在电镜下银杏黄酮可使Aβ1-42聚集少,无明显Aβ纤维形成。结论:提示银杏黄酮比银杏内酯具有更强抑制Aβ的聚集和纤维形成的作用,可能是银杏叶提取物中抑制Aβ的聚集的主要活性成分。     

蝶枕角与颅底诸结构至耳眼平面垂直距离的纵向比较

目的:为人颅底的生长发育研究提供正常的颅底结构测量数据和参照标准;初步分析颅底生长发育趋势和特点。方法:对人不同生长发育阶段颅底标本诸结构进行观察和测量,并对其进行相互比较和纵向分析。结果:颅底在不同发育阶段各有其趋势和特点,蝶枕角随着年龄的增长逐渐变小,但性别之间无差异,颅前窝诸结构变化幅度最大,颅中窝的变化相对最小,11项测量指标在不同生长发育阶段的变化各异。结论:观察测量数据可为人颅底生长发育进一步研究提供依据,蝶枕角、耳眼(FH)平面可作为颅底生长发育的观察测量指标和参照平面。     

Quantitative chemical sensing of drugs in scattering media with Bessel beam Raman spectroscopy

Scattering can seriously affect the highly sensitive detection and quantitative analysis of chemical substances in scattering media and becomes a significant challenge for in vivo application of Raman spectroscopy. In this study, we demonstrated a proof of concept for using the self-reconstructing Bessel beam for Raman spectroscopic sensing of the chemicals in the handmade scattering media and biological tissue slices. The homebuilt Bessel beam Raman spectroscopy (BRS) was capable of accurately detecting the Raman spectra of the chemicals buried in the scattering media, and had a superiority in quantitative analysis. The feasibility of the developed technique was verified by detecting the Raman spectra of pure samples in air. Compared with the spectra acquired by the Gaussian beam Raman spectroscope, the performance of the BRS system in terms of Raman spectrum detection and Raman peak recognition was confirmed. Subsequently, by employing the technique for the detection of acetaminophen buried in the scattering media, the application of the new technology in detecting and quantitating the chemicals in the scattering media were underlined, offering greater detection depth and better linear quantification capability than the conventional Gaussian beam Raman spectroscopy. Finally, we explored the potential of the BRS system for chemical sensing of acetaminophen in biological tissue slices, indicating a significant development towards the evaluation of drug in vivo.     

Ulinastatin attenuates lung ischemia-reperfusion injury in rats by inhibiting tumor necrosis factor alpha

Ischemia-reperfusion (I/R) injury may influence graft function following transplantation. Ulinastatin, a urinary trypsin inhibitor has been shown to attenuate I/R injury in various organs such as intestine, heart, and kidney in animals. The present experiment was designed to evaluate the effect of pretreatment with ulinastatin on I/R-induced lung injury. METHODS: After establishing a constant left lung warm ischemia-reperfusion model in rats, 45 animals were randomly divided into three experimental groups: sham group (n = 15), IR group (n = 15), and ulinastatin (5000 U/kg pre-ischemia) + IR group (n = 15). The lung injury was evaluated by tissue myeloperoxidase activity, with simultaneous estimation of the serum concentration of TNFalpha. RESULTS: The ulinastatin-pretreated animals exhibited markedly decreased lung tissue myeloperoxidase activity (P < .05). Blood gas analysis demonstrated, that the treated animals had significantly ameliorated pulmonary oxygenation (P < .05). The serum concentration of TNF-alpha in the ulinastatin-pretreated group was markedly decreased compared with that of the I/R group (P < .05). CONCLUSIONS: Ulinastatin attenuated I/R-induced lung injury. This function is partly related to the capacity of the agent to inhibit myeloperoxidase activity in lung tissue and decrease systemic expression to TNF-alpha.     

心肌梗死后心力衰竭大鼠上胸段硬膜外阻滞治疗后心功能和β_3肾上腺素能受体表达变化

目的:探讨上胸段硬膜外阻滞治疗对心肌梗死(MI)后心力衰竭大鼠心功能和β3肾上腺素能受体基因表达的影响.方法:48只大鼠随机分为假手术组(S组,n=12)和左冠状动脉结扎组(LAD组,n=36),LAD组大鼠再随机分为心衰组(CHF组,n=14)和硬膜外阻滞治疗组(HTEA组,n=14).4 wk后各组均经寰枕关节置入PE-10导管至胸段硬膜外腔,置管术后24 h S组和CHF组于硬膜外腔注入9 g/L生理盐水(100 μL/kg,2次/d,4 wk).HTEA组于硬膜外腔注入125 g/L布比卡因(100 μL/kg,2次/d,4 wk).4 wk后行超声多普勒测定心功能的参数;测量和计算心脏与体质量(HW/BW)、左心室与体质量(LVW/BW)的比值;逆转录-聚合酶链反应(RT-PCR)半定量测定心肌组织β3AR和eNOS mRNA.结果:与CHF组相比较,HTEA组的LVEDd和LVEDs减小,EF和FS有所增加;HW/BW和LVW/BW有所降低;β3AR和eNOS mRNA表达明显减少.结论:上胸段硬膜外阻滞治疗可以改善MI后心衰大鼠的心功能,减缓心室重构,降低或延缓β3AB和eNOS mBNA的表达.     

Identification of novel biomarkers differentially expressed between African-American and Caucasian-American prostate cancer patients

Prostate cancer (PCa) incidence and mortality rate vary among racial and ethnic groups with the highest occurrence in African American (AA) men who have mortality rates twice that of Caucasians (CA). In this study, we focused on differential expression of proteins in AA prostate cancer compared to CA using Protein Pathway Array Analysis (PPAA), in order to identify protein biomarkers associated with PCa racial disparity. Fresh frozen prostate samples (n=90) obtained from radical prostatectomy specimens with PCa, including 25 AA tumor, 21 AA benign, 23 CA tumor, 21 CA benign samples were analyzed. A total of 286 proteins and phosphoproteins were assessed using PPAA. By PPAA analysis, 33 proteins were found to be significantly differentially expressed in tumor tissue (n=48, including both CA and AA) in comparison to benign tissue (n=42). We further compared protein expression levels between AA and CA tumor groups and found that 3 proteins were differentially expressed (P<0.05 and q<5%). Aurora was found to be significantly increased in AA tumors, while Cyclin D1 and HNF-3a proteins were downregulated in AA tumors. Predicted risk score was significantly different between AA and CA ethnic groups using logistic regression analysis. In conclusion, we identified Aurora, Cyclin D1 and HNF-3a proteins as being differentially expressed between AA and CA in PCa tissue. Our study suggests that these proteins might be involved in different pathways that lead to aggressive PCa behavior in AA patients, potentially serving as biomarkers for the PCa racial disparity.