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Drug-drug interactions are one of the main concerns in drug discovery. Accurate prediction of drug-drug interactions plays a key role in increasing the efficiency of drug research and safety when multiple drugs are c o-prescribed. With various data sources that describe the relationships and properties between drugs, the comprehensive approach that integrates multiple data sources would be considerably effective in making high-accuracy prediction. In this paper, we propose a Deep Attention Neural Network based Drug-Drug Interaction prediction framework, abbreviated as DANN-DDI, to predict unobserved drug-drug interactions. First, we construct multiple drug feature networks and learn drug representations from these networks using the graph embedding method; then, we concatenate the learned drug embeddings and design an attention neural network to learn representations of drug-drug pairs; finally, we adopt a deep neural network to accurately predict drug-drug interactions. The experimental results demonstrate that our model DANN-DDI has improved prediction performance compared with state-of-the-art methods. Moreover, the proposed model can predict novel drug-drug interactions and drug-drug interaction-associated events.

Glucagon-like peptide-1(GLP-1) is a multifunctional polypeptide throughout the lifespan via activating Glucagon-like peptide-1 receptor (GLP-1R).GLP-1 can affect food ingestion, enhance the secretion of insulin from pancreatic islets induced by glucose and be utilized to treat type 2 diabetes mellitus(T2DM).But, accumulating evidences from the decades suggest that activation GLP-1R can not only regulate the blood glucose, but also sustain the homeostasis of intracellular environment and protect neuron from various damaged responses such as oxidative stress, inflammation, excitotoxicity, ischemia and so on. And more and more pre-clinical and clinical studies identified that GLP-1 and its analogues may play a significant role in improving multiple central nervous system (CNS) diseases including neurodegenerative diseases, epilepsy, mental disorders, ischemic stroke, hemorrhagic stroke, traumatic brain injury, spinal cord injury, chronic pain, addictive disorders, other diseases neurological complications and so on. In order to better reveal the relationship between GLP-1/GLP-1R axis and the growth, development and survival of neurons, herein, this review is aimed to summarize the multi-function of GLP-1/GLP-1R axis in CNS diseases.

Drug repositioning/repurposing is a very important approach towards identifying novel treatments for diseases in drug discovery. Recently, large-scale biological datasets are increasingly available for pharmaceutical research and promote the development of drug repositioning, but efficiently utilizing these datasets remains challenging. In this paper, we develop a novel multimodal framework, termed GraphPK (Graph-based Prior Knowledge) for improving in silico drug repositioning via using the prior knowledge from a drug knowledge graph. First, we construct a knowledge graph by integrating relevant bio-entities (drugs, diseases, etc.) and associations/interactions among them, and apply the knowledge graph embedding technique to extract prior knowledge of drugs and diseases. Moreover, we make use of the known drug-disease association, and obtain known association-based features from an association bipartite graph through graph embedding, and also take into account biological domain features, i.e., drug chemical structures and disease semantic similarity. Finally, we design a multimodal neural network to combine three types of features from the knowledge graph, the known associations and the biological domain, and build the prediction model for predicting drug-disease associations. Massive experiments show that our method outperforms other state-of-the-art methods in terms of most metrics, and the ablation analysis regarding the three types of features reveals that prior knowledge from knowledge graphs can not only lift the predictive power of in silico drug repositioning, but also enhance the model's robustness to different scenarios. The results of case studies offer support that GraphPK has the potential for actual use.

The Internet and the Internet of Things (IoT) connect the world inside and outside the network through online and offline communication, which forms the original single network virtual platform. The integration of IoT, virtual reality and artificial intelligence can provide intelligent WebVR interaction for various application fields. However, we need to solve the problems of data lightweight, real-time data transmission based on the IoT, and visualization of scene data on the Web. This paper uses the IoT and virtual reality technology to propose a virtual reality scene modeling method based on the IoT platform, as well as the database dynamic loading management method and device of the virtual reality system, which includes building the database, storing the involved data structures for various scenes and functions in the virtual reality system. The time–space IoT engine is connected with the integrated service sharing center. The IoT platform collects data through the IoT sensor system and provides support for the application platform through the integrated service sharing center. The proposed method can meet the needs of large-scale data acquisition and modeling, shorten the loading time, improve the efficiency, and save the wasted computing resources and memory.

Background: Rhabdomyolysis (RM) associated acute kidney injury (AKI) is the most common systemic complication of RM. The present study aimed to assess the clinical characteristics and risk factors for intensive care unit (ICU) transfer for patients with RM-associated AKI.Methods: We included all patients who were age ≥ 18 years old with a diagnosis of RM from September 2012 to October 2018 and divided them into RM-associated AKI group and RM without AKI group. The primary outcome was transferring to ICU treatment. Regression analysis was performed to identify factors associated with ICU treatment and recovery of renal function.Results: Among the 149 patients with RM, 68 (45.6%) developed AKI. The percentage of patients with AKI who transferred to ICU was higher than patients without AKI (33.8% versus 12.3%, P < 0.002). Additionally, patients with AKI had higher percentage of undergoing dialysis (19.1% versus 2.5%, P < 0.01), all-cause mortality (13.2% versus 1.2%, P < 0.01), cost of hospitalization [10.8 1,000 yuan, IQR (5.5, 3.5) versus 5.9 1,000 yuan, IQR 5.9 (3.6, 9.9), P = 0.03], as well as longer length of hospital stay [8.0 (5.0, 14.0)] versus [6.0 (4.0, 11.0)], P = 0.02). Moreover, most patients with AKI achieved complete recovery (77.9%) at discharge. After adjusting for potential risk factors, RM-associated AKI remained an independent risk factor for ICU transfer (OR = 3.0, 95% CI, 1.11–8.3, P = 0.03). However, ICU transfer was not associated with recovery of renal function (OR = 0.88, 95% CI, 0.22–3.57, P = 0.856).Conclusion: RM leaded to AKI in most patients. RM-associated AKI could cause worse clinical outcome and predict ICU transfer for patients with RM.

Tyrosine kinases expressed by BCR-ABL fusion genes can cause changes in cell proliferation, adhesion, and survival properties, which are the main causes of chronic myelogenous leukemia (CML). Inhibiting the activity of BCR-ABL tyrosine kinase has become one of the effective methods for the treatment of chronic myelogenous leukemia. Initially, imatinib was the first small molecule of BCR-ABL tyrosine kinases inhibitors (TKIs) for the effective treatment of chronic myelogenous leukemia. Later, due to the emergence of various BCR-ABL mutations, especially T315I mutation, imatinib developed strong resistance. The second-generation kinase inhibitors dasatinib and nilotinib were able to overcome most of the mutation resistance but not T315I mutations. Therefore, in order to further overcome the problem of drug resistance, new types of KTIs such as flumatinib and radotinib have been developed, providing more options for clinical treatment. Some new drugs have entered clinical trials. In this review, two new BCRABL inhibitors (flumatinib and radotinib) and five new BCR-ABL inhibitors have been introduced into the clinical market in recent years. We reviewed their research status, synthesis methods, and clinical applications.

Existing current sensors suffer from insufficient measurement bandwidth or large insertion area to faithfully capture the continuous switching transient current of wide-bandgap devices. The combinational Rogowski coil concept is proposed here, where the self-integrating region of a shielded Rogowski coil is combined with its differentiating region to extend the overall measurement bandwidth. The coil design methodology including the parasitic element model and practical design boundaries is discussed. The concept is implemented with printed circuit boards and prototypes demonstrated up to 300 MHz bandwidth. The coil can also be easily integrated in a SiC MOSFET module power stage and it is shown that the switching transient current waveform are faithfully captured.

Yongjie Zhou,1– 3,&ast; Wen Zhang,1– 3,&ast; Jingqin Ma,1– 3 Zihan Zhang,1– 3 Minjie Yang,1– 3 Jianjun Luo,1– 4 Zhiping Yan1– 4 1Department of Interventional Radiology, Zhongshan Hospital, Fudan University, Shanghai, People’s Republic of China; 2Shanghai Institution of Medical Imaging, Shanghai, People’s Republic of China; 3National Clinical Research Center for Interventional Medicine, Zhongshan Hospital, Fudan University, Shanghai, People’s Republic of China; 4Center for Tumor Diagnosis and Therapy, Jinshan Hospital, Fudan University, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jianjun Luo; Zhiping Yan, Department of Interventional Radiology, Zhongshan Hospital, Fudan University No. 180 Fenglin Road, Shanghai, 200032, People’s Republic of China, Email luo.jianjun@zs-hospital.sh.cn; yan.zhiping@zs-Hospital.sh.cnPurpose: We conducted this large population-based study to evaluate the impact of socioeconomic status (SES) factors on cancer-specific survival (CSS) of patients with hepatocellular carcinoma (HCC). We further assessed the value of a novel TNM-SES staging system, which incorporated these SES factors with TNM stage on staging and prognosis.Methods: A total of 13,791 patients diagnosed with HCC from 2012 to 2016 were retrieved from one large population database. Cox proportional hazards regression model and Harrell’s concordance index (C-index) were used to identify the SES factors associated with CSS and analyze the prognostic value of TNM-SES stage. Kaplan–Meier curves and Log rank test were performed to evaluate CSS.Results: Four SES factors (marital status, insurance status, education, household income) were identified as the prognostic factors associated with CSS. The SES-2 (lower SES) stage was significantly correlated to unfavorable CSS of the patients with HCC, with a 32.0% increased risk (HR = 1.32, 95% CI (1.26– 1.39), P < 0.001), after adjusting for several confounders. The C-index of the TNM-SES stage was 0.735 (95% CI (0.729– 0.741)) which was higher than that of the TNM stage (0.718, 95% CI (0.712– 0.724)), indicating a high accuracy of prognostic prediction.Conclusion: Our comprehensive study revealed that SES was significantly associated with prognosis of patients with HCC after adjusting several confounders. The novel TNM-SES staging system which combined TNM stage and SES stage had more superior predictive value than the traditional TNM stage. Disparity on SES should receive more attention for patients with HCC in clinical management.Keywords: socioeconomic status, TNM stage, hepatocellular carcinoma SEER database

Problem definition: To improve the poor performance of supply chains caused by misaligned incentives under the wholesale price contract, theory proposes coordinating contracts. However, a common finding of experimental studies testing such contracts is that they tend to yield only a marginal, if any, performance improvement over wholesale pricing. These studies identify several behavioral factors that are at play but none accounted for by the theory proposing coordinating contracts. Among them, identified as the single most detrimental for the supply chain performance, is incomplete information about preferences for fairness causing contract rejections. Can the supply chain performance be improved with a contract designed allowing for this type of information asymmetry? What does this contract (mechanism) look like? Academic/practical relevance: The extant research characterized the optimal contracting mechanisms for such important practical cases as the suppliers’ private information about production cost or the retailers’ private information about the end customer demand. The present study addresses the gap in another important practical case: when the source of information asymmetry is the private information about preferences for fairness. Methodology: The underlying research method is mechanism design. Results: We prove that the optimal mechanism consists of a single contract positioned on the Pareto frontier and characterize the optimal profit split between the supplier and the retailer. We show that, under a wide range of preferences for fairness, the efficiency loss because of private information is strictly positive, but exceptions are possible. We also show that the optimal mechanism can be implemented with a variety of commonly used in practice and widely studied in academic literature contracts, including the minimum order quantity and the two-part tariff ones. Managerial implications: We establish a direct link between a large volume of theoretical and empirical literature on social preferences with the research on supply chain contracts. Because rejections that are because of incomplete information are an important cause of contract inefficiency observed in the laboratory, managers should avoid take it or leave it offers when they negotiate contracts. Instead, the bargaining process should be geared toward discovering the extent of the fairness preferences of the contracting parties.

Simultaneous multi-frequency observations can be of great advantage when line ratios need to be accurately determined. Five meters Dome A Terahertz Explorer (DATE5) telescope is proposed with two observation bands: 0.85 THz band and 1.35 THz band. In this paper, we report on a dual-band receiver based on a single quasi-optical superconducting hot-electron bolometer mixer. This novel concept allows simultaneous observation of the two bands for DATE5 telescope. Our measurement results show that the dual-band HEB receiver can simultaneously resolve the line spectra in both frequency bands. In particular, an RF tone has been observed with in single and dual frequency mode and the heterodyne performance of the HEB mixer has been compared. Although there is a reduction of mixer conversion gain, the available observation time can be improved by decreasing the time for source pointing and double-beam switching. Whats more, compared with conventional broadband receiver system, this novel technique can achieve compact system and provide a system redundancy for unattended observation.

An orbital angular momentum (OAM) antenna based on chiral harmonic diffraction of spoof surface plasmon polaritons (SSPP) is demonstrated in this paper. Due to the diffraction of the helical wire, SSPP is transformed into the high-purity OAM mode. The operation frequency is determined by SSPP, and the topological charge is manipulated by modulating the harmonic order. Additionally, this system achieves a frequency-controlled beam-scanning characteristic in a wide bandwidth from 7.8 GHz to 12.6 GHz, and the measurement data agrees well with the theoretical analysis and the simulation results. Furthermore, the OAM antenna validated in this work is compact, easy-fabricated, and robust. The underlying principle opens up a new train of thought for generating OAM mode and paves the versatile applications involving wireless communication

Titanium possesses excellent mechanical properties, unrivalled corrosion resistance, and biocompatibility. Still, it is restricted to some niche applications due to its high embodied energy consumption and production cost. The Kroll process used for most commercial titanium powder production is energy-intensive, non-eco-friendly, and costly. The increased production cost and environmental issues have resulted in enormous research and development activities to develop new methods to produce high-purity titanium powder economically and eco-friendly. These new methods have been categorised into three primary groups: thermochemical, electrochemical, and solution-phase methods. Recent developments are focused on the electrolysis process, including cathodic and anodic reduction. Recent development in hydrogen-assisted magnesiothermic reduction (HAMR) seems promising to produce high-purity titanium at a low cost and low energy consumption. This article, for the first time, discusses the solution-phase methods to produce titanium powder directly. Particular emphasis on the sustainable production of titanium has also been highlighted.

For enhancing the photoelectric performance of the GaAs photovoltaic cell, the non-dominated sorted genetic algorithm-II (NSGA-II) is employed to solve the multi-objective optimization problem, which consists of the thicknesses of active layer (GaAs) and three anti-reflection (AR) films (TiO2-HfO2-SiO2). Through maximizing (minimizing) the light absorption of photons with energies higher (lower) than the bandgap in the active layer directly and reducing the cost at the same time, the Pareto optimal solution is obtained. An increment in the absorptance, short circuit current and photoelectric conversion efficiency by 50%, 43.4% and 44.9% is achieved by the optimal GaAs solar cell due to excellent AR properties obtained by NSGA-II optimization. We systematically investigate the effects of carrier lifetime, surface recombination velocity, carrier mobility as well as doping concentration on the photovoltaic parameters, and acquire the limitations of these parameters. The strong robustness of the optimal GaAs solar cell enables it to be adapted to wide-angle sunlight incident, and the probability to achieve an absorptance of 0.963 is 97% even if there is a 20% machining error.

Implantation of intraocular lens after combined procedure of vitrectomy and cataract surgery is usually required to reduce the postoperative refraction errors. However, because of the severe fibrosis of the anterior capsule and the adhesion between the anterior and posterior capsules, it is difficult to reopen the capsular bag to complete the secondary IOL implantation. We describe here a surgical approach for reopening the severe adhesion between capsules and removing the significant fibro-proliferative membranous material by injecting viscoelastic agent into the periphery of the capsular bag to separate the anterior and posterior capsules. The IOL was implanted into the capsular bag without any zonular rupture or posterior capsule tear. The position of the intraocular lens was stable during postoperative follow-ups up to 3 months. Our procedure to open a severely fibrosis capsule is safe and effective, and may be used as a preferred method.

In recent years, with the rapid development of the world economy, the environment and resources have been seriously damaged, and the global climate is changing quietly. People began to pay more and more attention to the protection of environment and resources. In the process of building residential buildings, the construction industry also needs to strengthen the application of green building design, so as to achieve the purpose of green environmental protection. The author makes an in-depth research and analysis on the characteristics of green building design, and puts forward the effective strategies for the application of green building design in residential buildings, hoping to help improve the green environmental protection of residential buildings.

The outer dimensions and 3D model of ring forgings in industrial production are the important parameters to ensure the quality of the products. In order to realize the measurement of the outer dimensions and 3D model of the ring forgings, a measuring method for the ring forgings combining with a CCD camera and a 2D laser scanner is proposed in this paper. Firstly, the image information of the ring forgings is obtained by the CCD camera. The radiuses of different sections for ring forgings are acquired by pixel calibration and edge detection. Secondly, the point cloud data of different sections are obtained by laser scanner with the movement of the transmission mechanism. Then, the position discrimination method of straight line fitting is used to reduce the error data. And the radius matching method is used in the further processing of the point cloud data based on image detection, and the point cloud data with high accuracy is further extracted. Finally, the 3D point cloud data and 3D model of the ring forgings are obtained by rotating the 2D point cloud data. The outer dimensions of forgings are derived from the 3D model. The experiments were carried out with two different ring forgings. According to the experimental results, the feasibility of the method proposed in this paper is verified.

Background. Functional constipation (FC) is one of the prevalent gastrointestinal disorders that affect people of all ages. Long-term FC has significant effects on the quality of life of patients. Although commonly used drugs have reliable short-term effects, they are easily addictive and have side effects. Therefore, pursuing a convenient drug-food homogenous program is critical for FC patients. Maxing Xianchang Su is a functional food based on traditional Chinese medicine. To investigate the efficacy and safety of Maxing Xianchang Su in FC treatment, we conducted a randomized controlled trial. Methods. We carried out a prospective multicenter randomized parallel controlled study in three hospitals in Jiangsu Province, China, from January 2020 to March 2021, which included 206 FC patients. All patients were arbitrarily assigned into a treatment group and a control group at a ratio of 1 : 1; 103 cases in each group. The treatment group was given oral Maxing Xianchang Su, whereas the control group was treated with lactulose oral solution. The course of treatment was two weeks. The two groups of patients were evaluated after six weeks for symptom improvement before and after taking the drug. Furthermore, the safety of Maxing Xianchang Su was assessed. Results. Both groups of patients successfully completed the study without shedding cases. The effective rates of the treatment group and control group after two weeks were 90.6% and 67.0%, respectively. The treatment group had a better curative effect than the control group ( P < 0.05 ). The symptom score of the two groups improved compared with that before the treatment. The difference between the two groups was statistically significant ( P < 0.05 ). During the treatment process, neither group experienced abnormal changes in blood lipid, blood glucose, routine hematuria, or liver and kidney functions. There were no adverse reactions in both groups. Conclusion. Maxing Xianchang Su has a positive effect on FC treatment with reliable mid-term effect and a high level of safety.

Background There is a paucity of studies conducted in China on the outcomes of all live-birth extremely premature infants (EPIs) and there is no unified recommendation on the active treatment of the minimum gestational age in the field of perinatal medicine in China. We aimed to investigate the current treatment situation of EPIs and to provide evidence for formulating reasonable treatment recommendations. Methods We established a real-world ambispective cohort study of all live births in delivery rooms with gestational age (GA) between 24+0 and 27+6 weeks from 2010 to 2019. Results Of the 1163 EPIs included in our study, 241 (20.7%) survived, while 849 (73.0%) died in the delivery room and 73 (6.3%) died in the neonatal intensive care unit. Among all included EPIs, 862 (74.1%) died from withholding or withdrawal of care. Regardless of stratification according to GA or birth weight, the proportion of total mortality attributable to withdrawal of care is high. For infants with the GA of 24 weeks, active treatment did not extend their survival time (P = 0.224). The survival time without severe morbidity of the active treatment was significantly longer than that of withdrawing care for infants older than 25 weeks (P P Conclusions The mortality rate of EPIs is still high. Withdrawal of care is common for EPIs with smaller GA, especially in the delivery room. It is necessary to use a multi-center, large sample of real-world data to find the survival limit of active treatment based on our treatment capabilities.

Precast concrete frame structure with nonrectangular columns are becoming attractive to researchers and engineers owing to advantages such as avoiding column protrusion from walls and saving space. This paper presents the experimental investigation of a full-scale precast concrete frame structure with L-shaped columns (PCFS) subjected to reverse cyclic loading. The precast connection adopted grouted anchor connection. As a comparison and benchmark, one full-scale monolithic sample (RCFS) was also tested. The results indicates that the greater steel ratio in the grouted anchor connection region leads to a high local stiffness of the elements, which contributed to delaying occurrence of the first crack at the grouting holes. The failure mode, lateral load capacity, stiffness degradation, load-carrying capacity degradation, energy-dissipating capacity, ductility and interlayer residual deformation were compared between two specimens. PCFS specimen exhibited comparatively better hysteretic behavior, energy-dissipating capacity, residual deformation-resisting capacity and ductility. For RCFS and PCFS specimens, the peak load difference was within 7%. About 15% increases in ductility were observed for PCFS specimen compared with RCFS specimen. The test results would provide reference for the application of the precast concrete structure with nonrectangular columns in the new residential buildings.

Circadian rhythm disorder (CRD) in space flight can lead to memory impairment, performance decrements and adverse health outcomes, the main manifestations of which are circadian desynchronization, sleep loss and insomnia. Sleep deprivation (SD) provide the means to evaluate these effects and the risks associated with CRD on ground. Gastrodia elata Blume (GEB) has beneficial effects on the treatment of sleep disturbances and memory loss. Fresh GEB (FG), an unprocessed raw tuber of GEB, has been used as functional health food in Asian countries for a long time. However, the research report of FG to ameliorate memory impairment caused by insomnia or lack of sleep is meager. In this study, ICR male mice were sleep-deprived continuously and water extract of FG (WFG) was orally administrated (3 and 9 g/kg/d, i.g) during the SD process lasted for 25 days, except control and model groups gavage administration with water, positive control group with modafinil (MOD, 0.1 g/kg/d, i.g). We studied the effect of WFG on CRD-induced learning and memory impairment using a set of behavioral analyses including the object location recognition test (OLRT), novel object recognition test (NORT), and the passive avoidance test (PAT). In addition, oxidative stress parameters were assessed by measuring the malondialdehyde (MDA) and superoxide dismutase (SOD) reactivity in serum and hippocampus. Our results revealed that SD decreased discrimination index (DI) in OLRT and NORT, with shorter latency into the dark chamber in PAT. Both WFG and MOD treatment can reverse these changes (P0.05). We concluded that WFG treatment improve CRD-induced learning and memory impairment and oxidative stress damage which makes FG a promising candidate as herbal health product of memory decline in CRD.

Melatonin has been well documented for its neuroprotective role through inhibiting oxidative stress against traumatic brain injury (TBI). However, the specific role of melatonin and the exact effects on cell responses (neurons, astrocytes, and microglia) in different brain regions are unclear. Here, we subjected mice to closed head injury, to establish a repeated mild TBI model and detect neuronal activity and glial responses in cognition-related brain regions after melatonin administration. Melatonin only showed cognitive enhancement if administered during early pathological stages, but not in late (chronic) stages. Additionally, we observed a significant increase in neuronal activity and inhibition of astrocyte reactivation in medial prefrontal cortex and hippocampus, but not in other cognitive deficit related brain regions. Furthermore, by activating astrocytes in these brain regions, we found neuronal activity upregulation and cognitive improvement following melatonin treatment. Therefore, we concluded that melatonin administration during the early stages of TBI is necessary to inhibit astrocyte reactivation and to promote cognitive function. Our results provide evidence for use of melatonin for cognitive improvement after TBIs.

Objective To assess the safety and efficacy of bronchial artery embolization (BAE) for hemoptysis. Methods and materials Databases with articles published in English, including Pubmed, Embase, Web of science and Chochrane library, were comprehensively searched to get accurate, up-to-date and sufficient literature about BAE for hemoptysis until March 2020. The technical success rates, immediate control rates, recurrence rates, mortality rates, and total complication rates (minor and major complication rates) extracted from the articles were pooled to estimate and assess the efficacy and safety of BAE using random-effects and fixed-effects models. Results 21 articles published between 2008 and 2019, which include a total of 2511 patients, were studied to evaluate safety and efficacy of BAE. The Technical success and immediate control rates are 99.9% (95%CI: 99%–100%) and 99.5% (95%CI: 97.8%–99.2%), respectively. This study showed hemoptysis recurrence in 23.7% (95%CI: 18.5%–28.9%) with a mortality rate of 2% (95%CI: 0–3%). Additionally, the assessment of complications revealed a total complication rate of 13.4% (95% CI: 7.6–19.2%), in which 0.2% (95% CI: 0.2–0.4%) were major complications and 10% (95% CI: 4.7–9.6%) were minor complications. Conclusion BAE is an effective, safe, and feasible procedure with a low complication rate for hemoptysis patients. However, recurrence of hemoptysis is still at high risk after BAE due to different underlying diseases.

OBJECTIVES To explore the diagnostic value of contrast-enhanced ultrasound (CEUS) combined with the Chinese Thyroid Imaging Reporting and Data System (C-TIRADS) for differentiation of benign and malignant thyroid nodules. METHODS A retrospective analysis of the conventional ultrasound and CEUS data of 388 nodules in 355 patients who had undergone thyroid nodule resection was conducted. All nodules had clear pathological results. The CEUS observation indexes included the enhancement degree in the arterial phase (no enhancement, scant punctate-linear enhancement, mild enhancement, moderate enhancement, and high enhancement) and wash-out patterns (rapid wash-out, slow wash-out, and isochronous wash-out). Chi-square test between groups and receiver operating characteristic curves (ROC) were used to determine the malignant (+1 point) and benign (-1 point) observation indexes that were statistically significant for the differentiation between benign and malignant thyroid nodules. The CEUS and C-TIRADS malignant and benign indexes were combined to score and draw the ROC curve, which was compared with the ROC curve scored by C-TIRADS alone to compare the diagnostic efficacy of the two methods for differentiating between benign and malignant thyroid nodules. RESULTS Among the CEUS observation indexes, mild enhancement and rapid wash-out were malignant indexes, while isochronous wash-out was a benign index. The best diagnostic cut-off value for the differentiation of benign and malignant thyroid nodules using the C-TIRADS score and the C-TIRADS and CEUS combined score (C-TIRADS + CEUS score) was 2. The sensitivity, specificity, positive predictive values (PPV), and negative predictive values (NPV) of the two methods were 79.97, 75.48, 82.9, 70.5%, and 89.7, 72.9, 83.3, 82.5%, respectively. The area under the curve values were 0.840 and 0.877 (P

Paper-based fluorescence devices, with smartphone aids, bring considerable operation convenience for tetracycline (TC) sensing. Nevertheless, they must meet the challenge in real determination against complicated backgrounds. Considering that, we present a programmable-printing paper-based device and then apply it to TC determination for various natural samples. MoS2 NPs and Gmp/Eu-Cit are synthetized as composite probes. A static quenching process is found with MoS2 NP fluorescence at 430 nm, while significant magnification of Gmp/Eu-Cit emission is obtained at 617 nm, establishing a valuable ratiometric indicator. Remarkably, two-stage programmable printing maximizes the proposed sensing capability. A transitive device, containing a gradually changing amount of a certain probe, is prepared to sense TC. With a homemade smartphone application and 3D-printed measurement chamber, the corresponding signals are examined to explore optimal setups. These setups are automatically processed to prepare the final-version device, not requiring manual operations. Benefitting from this interesting feature, the proposed device gains many rewards in performances. It effectively senses TC in a wide range from 12.7 nM to 80 μM and simultaneously provides naked eye-legible signals and smartphone-based readouts with confident selectivity and stability. This device is consequently applied for various samples of soil, river water, milk, and serum and meets well with HPLC-MS and recovery tests.

Background The incidence of overweight and obesity in rural-to-urban migrants and rural residents is increasing rapidly. This study aims to explore the perceptions and attitudes toward obesity and its management among rural-urban migrants and rural residents who are left in rural regions, China. Methods We performed a cross-sectional survey investigating migrants and rural residents aged 18-45 in China from October to November 2020. We created a questionnaire. Two hundred five questionnaires were completed. Results Finally, 184 were included, of which 102 were migrants and 82 were non-migrants. More respondents were male (62%). There was no significant difference in BMI between the two groups. The migrants had good knowledge about obesity as a disease (75.5%) and agreed that obesity seriously threatens health (93.1%). It is worth noting that more non-migrant group believed that obesity was due to a lack of willpower (87.3% vs. 54.9%, p = 0.000) than the migrant group. More than half in both groups believed that obesity was caused by a bad lifestyle (69.6%) or addiction to food (58.7%). Half of the participants believed that biological factors caused obesity. Most participants in both groups still believed weight loss modalities were limited to exercise and diet while having extremely poor acceptance of pharmacotherapy and bariatric surgery. Conclusions This study found that the migrants and rural residents had a good understanding of obesity as a disease, and better among migrants than rural residents. However, they showed significant uncertainty and misconceptions about the efficacy and safety of pharmacotherapy and bariatric surgery.

There were approximately 1.93 million new cases and 940 000 deaths from colorectal cancer in 2020. The first‐line chemotherapeutic drugs for colorectal cancer are mainly based on 5‐fluorouracil, although the use of these drugs is limited by the development of drug resistance. Consequently, there is a need for novel chemotherapeutic drugs for the efficient treatment of colorectal cancer patients. In the present study, we screened 160 drugs approved by the Food and Drug Administration and identified that cabazitaxel (CBT), a microtube inhibitor, can suppress colony formation and cell migration of colorectal cancer cells in vitro. CBT also induces G2/M phase arrest and apoptosis of colorectal cancer cells. Most importantly, it inhibits the growth of colorectal cancer cell xenograft tumors in vivo. Transcriptome analysis by RNA‐sequencing revealed that Tub family genes are abnormally expressed in CBT‐treated colorectal cancer cells. The expression of several p53 downstream genes that are associated with cell cycle arrest, apoptosis, and inhibition of angiogenesis and metastasis is induced by CBT in colorectal cancer cells. Overall, our results suggests that CBT suppresses colorectal cancer by upregulating the p53 pathway, and thus CBT may have potential as an alternative chemotherapeutic drug for colorectal cancer., In the present study, we screened 160 drugs approved by the Food and Drug Administration, aiming to identify novel chemotherapeutic agents for colorectal cancer (CRC) treatment. We identified that the microtubule inhibitor cabazitaxel (CBT) has a suppressive effect on CRC cells both in vitro and in vivo. Transcriptome analysis revealed that CBT induced apoptosis in CRC cells by upregulating the p53 pathway, implying that CBT may hold chemotherapeutic potential for the treatment of patients with CRC.

In this paper, we explore how a monopoly manufacturer chooses the market strategies and decides the optimal price to obtain maximum profit. We divide the market into the C-type market and the N-type market, and analyze the profitability of the monopoly manufacturer who takes the pure-selling, pure-leasing and hybrid strategy respectively, considering consumers’ capital constraint and the life span of the durable goods in an indefinite time horizon model. (1) We find that a larger proportion of the consumers with capital constraint has a more significant impact on the prices and it could slow down the development of the rental market. When the scale of the group attains up to a threshold level, it would greatly influence the customers’ demand and their marketing strategy, and encourages more manufacturers to take the leasing strategy. (2) In the Hybrid Strategy, we see explicit growth in the overall profit with both the leasing channel and the selling channel working together, although the former outperforms the latter. The suppressed selling channel, in fact, has to lower the price to keep the market coverage, with an independent market structure. (3) Finally, we find that a leasing agent may help the manufacturer at first and then become a tough competitor. These findings provide new insights for the operation of large construction machinery manufacturing companies. subject classification numbers as needed.

Terahertz (THz) vortex beams carrying orbital angular momentum (OAM) with high purity and tunable topological charge (TC) will undoubtedly bring extraordinary capacities for advanced imaging or communication systems. We propose a convenient and efficient method to generate a tunable and broadband vortex beam that is excited by superradiant Smith Purcell radiation (SSPR) on a helical grating. This scheme fully explores the advantages of natural broadband evanescent wave carried by the electron beam and the Bloch’s theorem regulated helical periodic systems. An explicit relation is established between the index of the spatial harmonic wave on the grating and the topological charge of the vortex beam. The electron energy in the SSPR can be customized to ignite the specific spatial harmonics and manipulate the OAM beam, accordingly. The separated radiation region also promises the high purity of the OAM spectrum. The harmonic excitation reduces the communality between the wavelength and the device size and alleviates the difficulty of device fabrication in the THz band. The proposed vortex scheme can not only be handily scaled to microwave and mid‑infrared regions, but also bring possibilities to applications based on compact tunable vortex beam sources.

In this article, we present a new microwave system with the tunable ability of the heating region and heating effect. The heating region is changed by choosing different antennas above different heating region, which leads to larger heating range. And this system can be utilized in precise temperature control in ammonia synthesis phase. The frequency-space domain modulation technology is ingeniously suggested in our heating system. The different antennas above different heating region is then selected by changing the input working frequency. Based on the frequency-space domain modulation, we further add time domain modulation to increase the tunability of heating effect at different heating regions. By adjusting the frequency distribution of the input microwave source in time domain, where we named as time-frequency-space domain synthesis modulation method, the tunable heating region and effect is finally achieved. A simple microwave system is fabricated, and different heating effects are measured. The proposed heating method and system has benefits as following, simple structure, low cost, uniform heating, and controllable heating effect, which results in great improvement in microwave heating.

Objectives The innate immune system participates in immunoglobulin G4–related disease (IgG4-RD). While the role of innate lymphoid cells (ILCs) in IgG4-RD remains to be elucidated, we aimed to evaluate the phenotype, function and clinical significance of ILCs in IgG4-RD patients. Methods Sixty-seven untreated IgG4-RD patients and 44 age- and sex-matched healthy controls (HCs) were enrolled. Circulating and tissue infiltration of ILCs were detected by flow cytometry. Serum suppression of tumorigenicity 2 (sST2) was detected by ELISA and membrane-bound ST2 (ST2L) was detected by flow cytometry. Tissue infiltration of IL-33 was measured by immunohistochemistry staining. Real-time quantitative PCR was performed to analyse the expression pattern of ILC2-associated genes between HCs and IgG4-RD patients. In addition, correlation analysis was performed in order to evaluate the clinical significance of ILCs in IgG4-RD. Results The frequency of circulating pan ILCs in IgG4-RD patients was lower than in HCs. ILC2s were higher in IgG4-RD compared with HCs, whereas ILC1s were lower in IgG4-RD. sST2 and ST2L were higher in IgG4-RD than in HCs. Infiltration of ILC1s in the submandibular glands of IgG4-RD patients was more prominent than ILC2s. Intracellular secretion of IL-9 was increased in ILC2s of IgG4-RD patients than in HCs. Circulating ILC2s correlated positively with Treg cells and the surface expression of CD154, PD-1 and CXCR5 in ILC2s correlated positively with CD19+ B cells, serum IgG4 levels and serum IgE, respectively. Conclusion ILCs and their subsets were significantly altered in IgG4-RD. We demonstrated the dysfunction of ILC2s in IgG4-RD by phenotype, correlation analysis and function investigation, revealing ILC2s participated in the pathogenesis of IgG4-RD.

BACKGROUND In mainland China, HPV vaccines have been available to the public. However, only a few related studies among health care providers, as the key information providers, were reported although public concerns on HPV vaccines still exist. In this study, we aim to assess the knowledge of HPV, its vaccines, and attitudes toward HPV vaccines among the three most important groups of health care providers in Western China. METHOD This was a cross-sectional questionnaire-based study. Health care providers including obstetrician-gynecologists (OB-GYNs), pediatricians, and immunization service providers in Western China were investigated regarding their knowledge of HPV and its vaccines and their attitudes toward HPV vaccines. RESULTS Of 1079 health care providers completing the survey, 1015 (94.1%) knew HPV infection is the primary cause of cervical cancer. However, lower knowledge levels of other HPV-related diseases were also found (43.2%). About three-quarters (74.1%) of practitioners interviewed would be willing to recommend HPV vaccination, which was found to be lower among the OB-GYNs (69.6%) and the pediatricians (73.2%). "Lack of relevant knowledge," "concerns on safety and efficacy" and price were the three most important concerns surrounding HPV vaccination. CONCLUSION The interviewed practitioners did not have adequate knowledge of HPV and its vaccines in depth. Education interventions are highly recommended to the health care providers, especially for OB-GYNs and pediatricians, to increase the coverage of HPV vaccination among the population. For the currently high price of vaccines, a future co-sharing mechanism between the government, the providers, and the individuals might be a solution.

Acute myelomagakaryocytic leukemia is a diagnostic and therapeutic challenge owing to its heterogeneity and overlapping features with other types of acute leukemia. In order to build a diagnostic profile, we analyzed the biological, clinical and hematologic characteristics of acute myelomagakaryocytic leukemia. We found that, in three patients diagnosed with acute myelomagakaryocytic leukemia, there were two types of leukemia cells. One type was myeloblastic with positive peroxidase (POX) stainig and the expression of antigens CD13 and CD33. The other type was megakaryoblastic with negative POX staining and the expression of antigens CD36, CD41, CD42a and CD61. Three patients displayed the same cytogenetic abnormality, a (9: 22) translocation. Among the three patients with RT-PCR, two patients displayed BCR-ABL fusion gene amplification and one patient showed a previously undescribed OTT-MAL fusion gene amplification.

Background Endometriosis is a chronic disease that affects women in reproductive age, and adenomyosis was known as “endometriosis in the uterus”. Endometriosis is an immune-dysfunction-related disease, contributing to the diversity of microbiota in the lower genital tract. Endometriosis is also an infection-related disease, the number of bacteria may contribute to some unknown mechanisms. Presently, the feature of microbiota between endometriosis patients and normal people is not fully understood. Methods To identify the microbiota differences and features of endometriosis patients, 298 samples from the cervical canal, posterior fornix of the vagina and uterine cavity were analyzed by 16s-rRNA sequencing. Raw data were filtered, analyzed, and visualized. We conducted diversity analysis, statistical data of microbiota abundance, biomarker identification, random forest, and environmental factors analysis. Results Alpha diversity was not distinctive in endometriosis and adenomyosis patients. Posterior fornix near cervix was a better sampling location to analyze the dysmenorrhea-related microbiota feature; few dysmenorrhea-related bacteria were identified. Endometrial bacteria is controversial, and the result of 16s-rRNA sequencing was not good enough to conduct further analysis. Anaerococcus was a possible biomarker of adenomyosis-endometriosis patients. The identified bacteria were representative only in specific periods during the menstrual cycle. GnRH-a treatment impacted microbiota feature the most compared with other environmental factors. Conclusion This study provided us with a new concept of endometriosis and bacteria; different microbiota features may relate to endometriosis. The bacterial involvement should be considered in the future study of endometriosis. New non-invasive diagnosis and therapeutic methods through bacterial medication are prospective.

Knowledge graphs (KGs) express relationships between entity pairs, and many real-life problems can be formulated as knowledge graph reasoning (KGR). Conventional approaches to KGR have achieved promising performance but still have some drawbacks. On the one hand, most KGR methods focus only on one phase of the KG lifecycle, such as KG completion or refinement, while ignoring reasoning over other stages, such as KG extraction. On the other hand, traditional KGR methods, broadly categorized as symbolic and neural, are unable to balance both scalability and interpretability. To resolve these two problems, we take a more comprehensive perspective of KGR with regard to the whole KG lifecycle, including KG extraction, completion, and refinement, which correspond to three subtasks: knowledge extraction, relational reasoning, and inconsistency checking. In addition, we propose the implementation of KGR using a novel neural symbolic framework, with regard to both scalability and interpretability. Experimental results demonstrate that our proposed methods outperform traditional neural symbolic models.

Schizophrenia is a mental illness characterized by episodes of psychosis, apathy, social withdrawal, and cognitive impairment. White matter lesions and glutamatergic hypofunction are reported to be the key pathogeneses underlying the multiple clinical symptoms of schizophrenia. Cuprizone (CPZ) is a copper chelator that selectively injures oligodendrocytes, and MK-801 is an antagonist of the N-methyl d-aspartate (NMDA) receptor. To better mimic the psychosis and complicated pathogenesis of schizophrenia, a novel possible mouse model was established by the combination of CPZ and MK-801. After exposure to CPZ for 5 weeks, the mice received a daily intraperitoneal injection of MK-801 for 2-weeks. Behavioral changes in the mouse model were evaluated using Y-maze, object recognition, and open field tests. Pathological changes were observed by transmission electron microscopy, oil red O staining, immunohistochemistry, and western blotting. The results showed that the novel mouse model induced by CPZ plus MK-801 exhibited severe spatial and recognition memory deficits, hyperactivity, and anxiety disorder. Moreover, the mice showed obvious demyelination and white matter damage and decreased expression levels of myelin basic protein (MBP) and 2',3'-cyclic nucleotide-3'-phosphodiesterase (CNPase) in the corpus callosum. Furthermore, the phosphorylation levels of Fyn and NMDA receptor 2B in the corpus callosum and NMDA receptor 1 in the cerebral cortex were noticeably decreased. Taken together, the novel mouse model induced by the combination of cuprizone and MK-801 showed comprehensive behavioral and neurobiological changes, which might make it a suitable animal model for schizophrenia.

A three-port plasmonic array is proposed to achieve a dual-field superfocusing using the forward-propagation method based on spatial Fourier transform. The algorithm of fast Fourier transform is used to facilitate the design process. Both the electric and magnetic fields can be superfocused on the focal plane of z = 0.1 λ ( λ is the free-space wavelength) based on an effect of radiationless electromagnetic interference. The full widths of the half-maximum of both two fields are 0.060 λ and 0.072 λ , respectively. Besides, the metrics of the dual-field superfocusing are 1.67 and 1.39. The proposed theory can simplify the design process of superfocusing, and the plasmonic array with brief three ports can sufficiently facilitate the construction of the desired source. This letter can be beneficial for the development of beam steering, sophisticated holography, super-resolution imaging, and other applications of near- or far-field devices.

Introduction The standard chemotherapy for squamous NSCLC (sqNSCLC) includes platinum plus gemcitabine. Sintilimab, an anti–programmed cell death protein 1 antibody, plus platinum and gemcitabine (GP) has revealed encouraging efficacy as first-line therapy for sqNSCLC in a phase 1b study. We conducted a randomized, double-blind, phase 3 study to further compare the efficacy and safety of sintilimab with placebo, both in combination with GP. Methods ORIENT-12, a randomized, double-blind, phase 3 study, was conducted at 42 centers in the People’s Republic of China ( ClinicalTrials.gov , number NCT03629925). Patients with locally advanced or metastatic sqNSCLC and without EGFR-sensitive mutations or ALK rearrangements were enrolled in the study. The stratification factors included clinical stage, choice of platinum, and programmed death-ligand 1 tumor proportion score. The patients, investigators, research staff, and sponsor team were masked to treatment assignment. Eligible patients were randomized 1:1, using an integrated web-response system, to receive sintilimab 200 mg or placebo plus GP every 3 weeks for four or six cycles, followed by sintilimab or placebo as maintenance therapy until disease progression or 2 years. The primary end point was progression-free survival (PFS), assessed by an independent radiographic review committee. Results Between September 25, 2018 and July 26, 2019, a total of 543 patients were screened, of whom 357 patients were randomized to the sintilimab-GP group (n = 179) and the placebo-GP group (n = 178). After a median follow-up period of 12.9 months, sintilimab-GP continued to reveal a meaningful improvement in PFS than placebo-GP (hazard ratio = 0.536 [95% confidence interval: 0.422–0.681], p Conclusions Regarding PFS, sintilimab plus GP reveals clinical benefit than GP alone as first-line therapy in patients with locally advanced or metastatic sqNSCLC. The toxicity was acceptable, and no new unexpected safety signals were observed.

Background: Adult chronic idiopathic thrombocytopenic purpura (ITP) is a chronic and usually lifelong hemorrhagic disorder in which enhanced platelet destruction and ­weakened platelet production lead to thrombocytopenia. In this study, the p38 mitogen-activated protein kinase (p38-MAPK), early growth response 1 (EGR-1), p53, Bcl-xL, Bak, Bax, and reactive oxygen species (ROS) in platelets from adult patients with chronic ITP were investigated. Methods: Platelets were isolated from blood samples collected from 20 adult patients with chronic ITP and 20 healthy volunteers. p38-MAPK, EGR-1, p53, Bcl-xL, Bak, Bax, and ROS were determined by flow cytometry, and the results were analyzed by EXPO32 ADC. Results: Flow cytometry showed the expression levels of p38-MAPK (61.66 ± 19.38% vs. 27.52 ± 14.34%), EGR-1 (62.22 ± 20.48% vs. 9.05 ± 5.79%), p53 (56.82 ± 20.07% vs. 4.35 ± 2.04%), Bak (39.86 ± 11.45% vs. 20.82 ± 11.85%), Bax (36.85 ± 15.99% vs. 6.69 ± 5.01%), and ROS (19.98 ± 1.47% vs. 1.29 ± 0.10%) were all elevated (p < 0.05 compared with healthy volunteers). In addition, pro-survival Bcl-xL (5.38 ± 1.52% vs. 21.20 ± 6.04%) was decreased markedly in platelets from adult patients with chronic ITP (p < 0.05 compared with healthy volunteers). Conclusions: Our findings reveal that platelets in adults with chronic ITP display a proapoptotic gene expression phenotype, based on the enhanced expression of p38-MAPK, EGR-1, p53, Bak, Bax, and ROS, and attenuated expression of Bcl-xL, suggesting increased sensitivity toward apoptosis.

Based on the demand for ideal selective solar absorbers to harvest a full solar spectrum, we present an auspicious method, the multi-island genetic algorithm (MIGA), to optimize the configuration of a universal selective solar absorber, which can avoid the premature phenomenon and superior to traditional genetic algorithm. The selective solar absorber equipped with the set of optimal geometric parameters exhibits the solar absorptance greater than 0.932 with 96% probability and mid-infrared emittance lower than 0.058 at the same time considering unavoidable 20% fabrication uncertainties in the design variables. In addition, the absorber is a combination of great characteristics, such as polarization independence and angle insensitivity. The hybrid resonance modes of Wood’s anomaly, surface plasmon polariton and magnetic polariton are responsible for the high absorption performance. The MIGA method presented is proved to be an effective and robust tool in the optimization of micro-nano structures with manufacturability for thermal and energy applications.

Yan Song, Tao Qu, Honggang Zhang, Yongkun Sun, Chengxu Cui, Yihebali Chi, Wen Zhang, Xingyuan Wang, Lin Yang Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, People’s Republic of ChinaCorrespondence: Lin Yang; Tao QuDepartment of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, People’s Republic of ChinaEmail linyang@cicams.ac.cn; thomasqu1972@hotmail.comBackground: In FRESCO trial, a phase III study of fruquintinib demonstrated a significant improvement on the overall survival (OS) of patients with metastatic colorectal cancer (mCRC) who failed to response to available standard treatments. The aim of the current study was to evaluate the safety and effectiveness of fruquintinib in Chinese mCRC patients in the real-world setting.Methods: Patients with mCRC treated with fruquintinib at our hospital were retrospectively reviewed. Patient demographics, treatment, adverse events and survival data were collected. OS and progression-free survival (PFS) were estimated using the Kaplan–Meier method.Results: In total, 76 patients were evaluated from December 2018 to January 2020. The median (range) age was 59.5 (34– 86) years, ECOG PS 0-1/2 was 86.8%/13.2%, and 38 (50%)/30 (39.5%) patients had experienced more than two prior therapies for mCRC. The median treatment duration was 3.6 cycles. Treatment-related adverse events (TRAEs) resulted in dose reduction were 17.1% of the patients without any treatment discontinuation. The most common grade 3 or 4 TRAEs were hypertension (9.2%), hand-foot skin reaction (7.9%), thrombocytopenia (3.9%), anaemia (2.6%), increased ALT (1.3%), oral mucositis (1.3%), proteinuria (1.3%) and neutropenia (1.3%). The median PFS was 5.1 months (95% CI 3.8– 6.4 months), and the median OS was 12.0 months (95% CI 8.0– 16.1 months). In patients with hypertension or hypothyroidism, a survival extension approximate to 6 months was observed, but the difference is not yet statistically significant. CEA decreased after fruquintinib treatment could be considered as a potential predictor for better OS.Conclusion: The outcome of this real-life study was consistent with that of the randomised controlled trial. There were no new safety concerns. Future studies of fruquintinib should be conducted to identify patients who tend to obtain more benefits from fruquintinib alone or in combination with other agents.Keywords: fruquintinib, metastatic colorectal cancer, real-world settings, toxicities

The purpose of the present study was to examine the protective action and mechanisms of quercetin on the blood-brain barrier (BBB) in rats subjected to transient middle cerebral artery occlusion (tMCAO) and reperfusion. Quercetin (10, 30, 50 mg/kg) was intraperitoneally administered at the onset of reperfusion. The results showed that quercetin significantly reduced cerebral infarct volume, neurological deficit, BBB permeability and ROS generation via Sirt1/Nrf2/HO-1 signaling pathway. Moreover, EX527, a selective inhibitor of Sirt1, reversed these neuroprotective effects. Our findings indicate that quercetin has neuroprotective effects against cerebral ischemia-reperfusion injury by protecting BBB through Sirt1 signaling pathway in MCAO rats.

Background Sudden sensorineural hearing loss (SSNHL) is a common disease in otology, and steroids play an important role in its treatment. Steroids can be administered systemically or locally, and the efficacies of different administration routes remain controversial. Methods We searched the Cochrane, EMBASE, PubMed, Web of Science, CNKI, Wanfang and Weipu databases for randomized controlled trials (RCTs) on glucocorticoid treatments for SSNHL to compare the efficacy of topical and systemic steroid administration. The Review Manager 5.4 software was used for synthesis of data: the rate of reported hearing improvement and change in pure-tone audiometry (PTA). Results In all the included studies, when intratympanic administration was compared to systemic therapies, the risk difference (RD) using reported hearing improvement as an outcome measure was 0.08 (95% CI: 0.01–0.14, I2 = 45%). Using PTA changes as an outcome measure in 4 studies, the mean difference (MD) was 10.43 dB (95% CI: 3.68–17.18, I2 = 81%). Hearing improvement RD was also compared among different types of steroid, recovery criteria, follow-up times and diagnostic criteria, and showed no significant differences exception for recovery criteria (>10 dB) (RD -0.06, 95% CI: 0.14-0.2, I2 = 0%). Conclusion As the initial treatment for SSNHL, topical steroids seem to be superior to systemic steroid administration, especially in patients with contraindications to systemic steroids usage. However, further verification based on high-quality research is needed.

Background Currently no study has investigated whether Web-based interactive technology can influence females to adopt healthy behaviors. We investigated how and under what conditions do Web-based interactivity influence vaccination intentions among young females. Methods In this randomized controlled trail, we conduct a 2 (mode of information presentation: narrative vs. data visualization) × 2 (interactivity: interactive information vs. noninteractive information) between-groups design. A total of 180 Chinese female undergraduate students who had never received HPV vaccination were randomly allocated to 4 experimental groups. Each participant was assessed for their information avoidance behavior and vaccination intention. The hypotheses were tested using a moderated mediation model. All analyses were performed using SPSS version 22.0 with probability set at 0.05 alpha level. Results The indirect relationship between interactivity and behavioral intention though information avoidance was moderated by the mode of presentation. Under the narrative condition, interactivity (vs. non-interactivity) decreased information avoidance and increased the intention to receive HPV vaccination (B = -.23, SE = 0.10, P Conclusion The findings suggest that when young females experience difficulties in manipulating or understanding HPV-related information, their information-avoidance behavior is likely to increase. Rather than use interactive statistical or graphical information, young females are more likely to be persuaded by interactive narratives.

We aimed to explore the feasibility of 2D and 3D radiomics signature based on the unenhanced computed tomography (CT) images to predict BRCA1-associated protein 1 (BAP1) gene mutation status for malignant pleural mesothelioma (MPM) patients.74 patients with MPM were retrospectively enrolled (22 mutant BAP1, 52 wild-type BAP1 demonstrated by Sanger sequencing). The radiomic features were extracted respectively from the 2D and 3D segmentation of unenhanced pre-treatment CT images, and the dataset was randomly divided into training (n = 51) and test (n = 23) sets for radiomics model development and internal validation. The synthetic minority over-sampling technique (SMOTE) was used for data balancing in the training set. 2D or 3D features were sequentially selected by ICC 0.8, correlation analysis (cut-value 0.7), univariate analysis or univariate logistic regression (LR), which were involved into multivariate LR for LR model construction. Following the comparison of the 2D and 3D models by the ROC analysis and Delong test for AUC, the calibration and clinical utility of 2D and 3D models were evaluated.3D radiomic features showed better ICCs compared with 2D in both intra- (P0.001) and inter-observer (P 0.001) analysis. 3D radiomic model based on selected features developed from a balanced training dataset presented a favorable predictive performance with AUC of 0.786 and 0.768 in the training and test sets, respectively. The predictive performance of 3D model was superior to 2D model (1 feature) both in the training (AUC 0.786 vs. 0.683, P = 0.036) and the test (AUC 0.768 vs.0.652, P = 0.441) set. The calibration curve and decision curves also indicate a better BAP1 prediction performance and clinical benefit for 3D model than that of 2D model.The developed unenhanced CT-based 3D radiomics signature is potential as a noninvasive marker for predicting BAP1 mutation status.

Wenyu Ni,1,&ast; Zhou Zhang,1,&ast; Bing Zhang,2 Wen Zhang,2 Haiyan Cheng,1 Yingwen Miao,1 Wei Chen,1 Jiani Liu,2 Dalong Zhu,1 Yan Bi1 1Department of Endocrinology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, People’s Republic of China; 2Department of Radiology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yan BiDepartment of Endocrinology, Drum Tower Hospital, Affiliated to Nanjing University Medical School, No. 321, Zhongshan Road, Nanjing, 210008, People’s Republic of ChinaTel +86 25-83304616-61431Fax +86 25-83304616-61431Email biyan@nju.edu.cnAim: Few studies have investigated the associations between diabetic peripheral neuropathy (DPN) and cognitive decline. Olfactory impairment is related to neurodegenerative diseases and type 2 diabetes mellitus (T2DM); however, the cognitive alterations of patients with DPN and the role of olfactory function in DPN are not known. We explored alterations in cognition with DPN and the associations of neuropathy parameters with cognition and olfaction.Methods: Healthy controls (HCs) and patients with T2DM underwent nerve-conduction tests, detailed cognitive assessment, olfactory-behavior tests, and odor-induced functional magnetic resonance imaging (fMRI). T2DM patients were divided into two groups (non-DPN [NDPN] and DPN). Olfactory brain regions showing different activation between the two groups were selected for functional connectivity (FC) analyses. A structural equation model (SEM) was also generated to demonstrate the association among cognition, olfactory, and neuropathy parameters.Results: One hundred individuals (36 HCs, 36 NDPN, and 28 DPN) were matched for age, sex, and educational level. Compared with the NDPN group, the DPN group had significantly lower scores for memory and processing speed, as well as lower olfactory identification and memory scores, decreased activation of the left frontal lobe, and reduced seed-based functional connectivity in the right insula. The nerve conduction velocity in patients with T2DM was associated with cognitive functions. The association between nerve conduction and executive function was mediated by olfactory behavior.Conclusion: Patients with DPN had worse cognition than the NDPN patients in the domains of memory and processing speed. Cognitive dysfunction could be predicted by olfactory-behavior tests and electrophysiological examination.Keywords: type 2 diabetes mellitus, peripheral neuropathy, cognitive dysfunction, olfactory behavior, odor-induced brain activation