Association of white matter hyperintensities with long-term EGFR-TKI treatment and prediction of progression risk.

PURPOSE: The purpose of this study was to test the hypothesis that brain white matter hyperintensities (WMH) are more common in patients receiving epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) and identify clinical risk factors associated with WMH. EXPERIMENTAL DESIGN: This multiple-center, prospective cohort study was conducted from March 2017 to July 2020. Two groups of patients with non-small cell lung cancer (NSCLC) who received or did not receive EGFR-TKI were included and followed up for more than 24 months. The progression of WMH was defined as an increase of ≥1 point on the Fazekas visual rating scale between the baseline and at the 2-year follow-up. A modified Poisson regression model was performed to evaluate risk factors on increased WMH load. RESULTS: Among 286 patients with NSCLC, 194 (68%) patients with NSCLC who received EGFR-TKI and 92 (32%) patients with NSCLC without EGFR-TKI treatment were analyzed. Modified Poisson regression analysis showed that EGFR-TKI treatment was independently associated with the WMH progression (EGFR-TKI: aRR 2.72, 95% confidence interval [CI] 1.46-5.06, p = .002). Interleukin (IL)-2, IL-4, and IL-10 were associated with increased WMH in the adjusted model (IL-2: aRR 1.55 [95% CI 1.06-2.25], p = .023; IL-4: aRR 1.66 [95% CI 1.13-2.43], p = .010; IL-10: aRR 1.48 [95% CI 1.06-2.06], p = .020). CONCLUSION: Patients with NSCLC who received EGFR-TKI may be at higher risk of developing WMH or worsening of WMH burden. The impact of increased WMH lesions in these patients is to be further assessed. IL-2, IL-4, and IL-10 may be used as potential biomarkers to monitor the risk of increased WMH burden.

Adaptive Gravity Compensation Framework Based on Human Upper Limb Model for Assistive Robotic Arm Extender.

The Assistive Robotic Arm Extender (ARAE) is an upper limb assistive and rehabilitation robot that belongs to the end-effector type, enabling it to assist patients with upper limb movement disorders in three-dimensional space. However, the problem of gravity compensation for the human upper limb with this type of robot is crucial, which directly affects the deployment of the robot in the assistive or rehabilitation field. This paper presents an adaptive gravity compensation framework that calculates the compensated force based on the estimated human posture in 3D space. First, we estimated the human arm joint angles in real-time without any wearable sensors, such as inertial measurement unit (IMU) or magnetic sensors, only through the kinematic data of the robot and established human model. The performance of the estimation method was evaluated through a motion capture system, which validated the accuracy of joint angle estimation. Second, the estimated human joint angles were input to the rigid link model to demonstrate the support force profile generated by the robot. The force profile showed that the support force provided by the developed ARAE robot could adaptively change with human arm postures in 3D space. The adaptive gravity compensation framework can improve the usability and feasibility of the 3D end-effector rehabilitation or assistive robot.

The Safety, Pharmacokinetics, and Pharmacodynamics of SHR2285, an Oral Small Molecule Factor XIa Inhibitor, in Healthy Chinese Volunteers.

BACKGROUND AND OBJECTIVE: There is an unmet need for a safer anticoagulant since bleeding remains a concern with currently approved anticoagulants. Coagulation factor XI (FXI) is an attractive anticoagulant drug target with limited a role in physiological hemostasis. The objective of this study was to evaluate the safety, pharmacokinetics, and pharmacodynamics of SHR2285, a novel small molecule FXIa inhibitor, in healthy Chinese volunteers. METHODS: The study consisted of single ascending doses part (part 1: 25-600 mg) and multiple ascending doses part (part 2: 100, 200, 300, and 400 mg). In both parts, subjects were randomized in a 3:1 ratio to receive SHR2285 or placebo orally. Blood, urine and feces samples were collected to describe its pharmacokinetic and pharmacodynamic profile. RESULTS: In total, 103 healthy volunteers completed the study. SHR2285 was well tolerated. SHR2285 was absorbed rapidly with median time to maximum plasma concentration (Tmax) of 1.50 to 3.00 h. The geometric median half-life (t1/2) of SHR2285 varied from 8.74 to 12.1 h across 25-600 mg single dose. Total systemic exposure of metabolite SHR164471 was approximately 1.77- to 3.61-fold that of the parent drug. The plasma concentration of SHR2285 and SHR164471 reached steady state by the morning of Day 7, with low accumulation ratio (0.956-1.20 and 1.18-1.56, respectively). The increase in pharmacokinetic exposure of SHR2285 and SHR164471 was less than dose proportional. Food has minimal effect on the pharmacokinetics of SHR2285 and SHR164471. SHR2285 produced an exposure-dependent prolongation of activated partial thromboplastin time (APTT) and a decrease in FXI activity. The maximum FXI activity inhibition rate (geometric mean) at steady state was 73.27%, 85.58%, 87.77% and 86.27% for 100-400 mg, respectively. CONCLUSIONS: SHR2285 was generally safe and well tolerated in healthy subjects across a wide range of doses. SHR2285 exhibited a predictable pharmacokinetic profile and an exposure-related pharmacodynamic profile. CLINICALTRIALS: gov Identifier NCT04472819; registered on July 15, 2020.

TM4SF1 upregulates MYH9 to activate the NOTCH pathway to promote cancer stemness and lenvatinib resistance in HCC.

TM4SF1, a member of the transmembrane 4 superfamily, is crucial for both healthy and malignant human tissues. The significant function of TM4SF1 in the incidence and progression of cancer has been widely recognized in recent years. Although some achievements have been made in the study of TM4SF1, the effect of TM4SF1 on cancer stemness in hepatocellular carcinoma (HCC) and its molecular basis are yet to be reported. We found through abundant in vitro and in vivo experiments which the expression of TM4SF1 was positively correlated with the progression and cancer stemness of HCC. We identified the downstream protein MYH9 of TM4SF1 and its final regulatory target NOTCH pathway using bioinformatics analysis and protein mass spectrometry. We cultivated a Lenvatinib-resistant strain from HCC cells to examine the relationship between cancer stemness and tumor drug resistance. The study confirmed that TM4SF1 could regulate the NOTCH pathway by upregulating MYH9, thus promoting cancer stemness and Lenvatinib resistance in HCC. This study not only provided a new idea for the pathogenesis of HCC but also confirmed that TM4SF1 might become a new intervention point to improve the clinical efficacy of Lenvatinib in treating HCC.

Learning-Based Motion-Intention Prediction for End-Point Control of Upper-Limb-Assistive Robots.

The lack of intuitive and active human-robot interaction makes it difficult to use upper-limb-assistive devices. In this paper, we propose a novel learning-based controller that intuitively uses onset motion to predict the desired end-point position for an assistive robot. A multi-modal sensing system comprising inertial measurement units (IMUs), electromyographic (EMG) sensors, and mechanomyography (MMG) sensors was implemented. This system was used to acquire kinematic and physiological signals during reaching and placing tasks performed by five healthy subjects. The onset motion data of each motion trial were extracted to input into traditional regression models and deep learning models for training and testing. The models can predict the position of the hand in planar space, which is the reference position for low-level position controllers. The results show that using IMU sensor with the proposed prediction model is sufficient for motion intention detection, which can provide almost the same prediction performance compared with adding EMG or MMG. Additionally, recurrent neural network (RNN)-based models can predict target positions over a short onset time window for reaching motions and are suitable for predicting targets over a longer horizon for placing tasks. This study's detailed analysis can improve the usability of the assistive/rehabilitation robots.

Efficacy and Safety of Tyrosine Kinase Inhibitors Alone or Combination with Programmed Death-1 Inhibitors in Treating of Hepatitis C-Related Hepatocellular Carcinoma.

Background: Tyrosine kinase inhibitors (TKI) combined with programmed cell death-1 (PD-1) inhibitor is a potential treatment modality for patients with HCV-related unresectable hepatocellular carcinoma (uHCC). Methods: The participants of the present work included the patients having HCV-related uHCC who were treated with TKI monotherapy (TKI group) or TKI combined with PD-1 inhibitors therapy (combination group) in our center between June 2018 and June 2021. In addition, the patients were classified into RNA-positive and RNA-negative groups based on whether or not the baseline HCV RNA was detectable. The overall survival (OS) was used as the primary efficacy endpoint, while progression-free survival (PFS), objective response rate (ORR), and disease control rate (DCR) were used as secondary endpoints. The adverse events were recorded and evaluated. Results: Among the 67 patients contained this work, 43 patients were classified into the TKI group, while 24 patients formed the combination group. In relative to the TKI group, the combination group presented notably better median OS (21 months vs 13 months, p = 0.043) and median PFS (8 months vs 5 months, p = 0.005). No evident differences were observed between the two groups in terms of the DCR (58.1% vs 79.2%, p = 0.080), ORR (13.9% vs 25.0%, p = 0.425) and the incidence of grade 3-4 adverse events (34.8% vs 33.3%, p = 1.000). In addition, there existed no obvious difference between the RNA-positive group and RNA-negative group in terms of median OS (14 months vs 19 months, p = 0.578) and median PFS (4 months vs 6 months, p = 0.238). Conclusion: The patients having HCV-related uHCC after being treated with the TKI and PD-1 inhibitor combination therapy exhibited a better prognosis and manageable toxicity compared to the patients who underwent TKI monotherapy.

Identification of risk factors for iatrogenic hypophosphatemia: A retrospective case-control study.

BACKGROUND AND OBJECTIVES: To investigate the iatrogenic risk factors for hypophosphatemia in intensive care unit (ICU) patients. METHODS AND STUDY DESIGN: A total of 120 patients were enrolled and further divided into 4 groups, namely normal, mild, moderate or severe, according to the degree of hypophosphatemia. A number of related factors were analyzed and compared among the 4 groups, including the treatment method and outcomes. Univariate and multivariate regression analyses were employed to identify and confirm the risk factors associated with the occurrence of hypophosphatemia. RESULTS: The results revealed that the acute physiology and chronic health evaluation II (APACHEII), Sequential Organ Failure Assessment (SOFA), modified NUTrition Risk in Critically ill (NUTRIC) scores as well as the length of patient stays in ICUs exhibited a gradually increasing trend of aggravation of hypophosphatemia. Univariate regression analysis identified the use of dehydrating drugs to be closely associated with the occurrence of hypophosphatemia, which was further confirmed by a multivariate regression analysis. CONCLUSIONS: The use of dehydrating drugs led to hypophosphatemia; therefore blood phosphorus concentrations should be closely monitored during treatment of ICU patients.

Internet Use and Job Satisfaction: Evidence from China.

We explore the causal effects of Internet use on job satisfaction using a sample of 83,012 Chinese labor force members aged 16-64 years from the China Family Panel Studies (CFPS) from 2010 to 2018. We use ordered logistic estimation and find that Internet use significantly increases job satisfaction by 3.2%. Heterogeneity analysis shows that the Internet has a more positive impact on those who are in urban areas and have higher incomes and higher education. Our results are robust after eliminating endogeneity using instrumental variables and solving the self-selection problem using the PSM method. Our mechanistic analysis leads to similar conclusions to mainstream research, where Internet use induces job satisfaction by increasing time efficiency and enhancing job autonomy. Specifically, shorter working hours boosted job satisfaction by approximately 0.3%, while working in informal places boosted job satisfaction by 5.4%. Thus, employers may consider encouraging employees to access the Internet.

miR-3682-3p directly targets FOXO3 and stimulates tumor stemness in hepatocellular carcinoma via a positive feedback loop involving FOXO3/PI3K/AKT/c-Myc.

BACKGROUND: Cancer stem cells (CSCs) have been implicated in tumorigenesis and tumor recurrence and metastasis are key therapeutic targets in cancer treatment. MicroRNAs display therapeutic potential by controlling the properties of CSCs; however, whether an association exists between miR-3682-3p and CSCs is unknown. AIM: To investigate the mechanism by which miR-3682-3p promotes stemness maintenance in hepatocellular carcinoma (HCC). METHODS: MiR-3682-3p expression in HCC cell lines and 34 pairs of normal and HCC specimens was assayed by quantitative polymerase chain reaction. The functional role of miR-3682-3p was investigated in vitro and in vivo. Dual-luciferase reporter and chromatin immunoprecipitation assays were performed for target asse ssment, and western blotting was utilized to confirm miR-3682-3p/target relationships. RESULTS: We found that miR-3682-3p plays a key role in HCC pathogenesis by promoting HCC cell stemness. The upregulation of miR-3682-3p enhanced CSC spheroid-forming ability, side population cell fractions, and the expression of CSC factors in HCC cells in vitro and the tumorigenicity of transplanted HCC cells in vivo. Furthermore, silencing miR-3682-3p prolonged the survival of HCC-bearing mice. Mechanistically, we found that miR-3682-3p targets FOXO3 and enables FOXO3/ß-catenin interaction, which promotes c-Myc expression through PI3K/AKT; c-Myc, in turn, activates miR-3682-3p, forming a positive feedback loop. Intriguingly, miR-3682-3p expression was induced by hepatitis B virus X protein (HBx) and was involved in HBx-induced tumor stemness-related pathogenesis. CONCLUSION: Our findings reveal a novel mechanism by which miR-3682-3p promotes stemness in HCC stem cells. Silencing miR-3682-3p may represent a novel therapeutic strategy for HCC.

Adjustment Method of College Students' Mental Health Based on Data Analysis Under the Background of Positive Psychology.

Colleges and universities are in an important position to train builders and successors of the socialist cause whilst promoting quality education. Mental health education is an important foundation and condition for comprehensively improving students' overall quality. This research explores adjustment methods for college students' mental health based on virtual reality under the background of positive psychology. It discusses the importance of system requirements analysis in the software development process, analyzes the system's functional requirements, safety requirements, and software and hardware requirements, and uses the Apriori algorithm to explore the influencing factors of college students' mental health. Based on the system engineering method and using the data mining clustering method undertake detailed analysis and research on the mental health of college students, it then designs an anomaly mining algorithm based on clustering to quickly find anomalous data health problems. The interface design of the system is concise and the operation is simple. Users can conveniently input, query, and count information according to the various controls on the interface, which fully embodies human-oriented characteristics. Exploration of the characteristics of students' frequent Internet access ensures the efficiency, accuracy, and comprehensiveness of the evaluation and consultation work, facilitating psychological counseling for teachers and students, and saving paper. By establishing a data mining model, mining the database, and learning about different student groups and their respective characteristics, we discuss our research on student psychology and summarize the mental health status and gender, adaptation and anxiety, introversion, emotionality, and calmness of college students. We also consider the relationship between sex, negative, and courage. Using positive psychology theory, we examine the positive experiences of students and interconnected qualities, to build a mental health practice system. In the experiment, the happiness index evaluation of the virtual reality treatment system group was significant, P = 0.002 < 0.05. Mental health education plays an important role in cultivating the healthy psychology of college students, developing their psychological potential, enhancing their adaptability, and improving their personality. This analysis based on actual data provides a reliable basis for psychological educators to improve the efficiency and effectiveness of school psychological counseling and to facilitate schools in establishing new methods of early prevention and intervention for psychological disorders, enabling institutions to create a healthy atmosphere for college students.

Endothelial ETS1 inhibition exacerbate blood-brain barrier dysfunction in multiple sclerosis through inducing endothelial-to-mesenchymal transition.

Blood-brain barrier (BBB) dysfunction has been recognized as an early pathological feature and contributing factor in multiple sclerosis. Endothelial-to-mesenchymal transition is a process associated with endothelial dysfunction leading to the disruption of vessel stability and barrier function, yet its functional consequence in multiple sclerosis remains unclear. Here, we demonstrated that endothelial-to-mesenchymal transition accompanied the blood-brain barrier dysfunction in several neurological disorders, especially in multiple sclerosis. The activity of transcription factor ETS1, which is highly expressed in endothelial cells (ECs) and responded to an inflammatory condition, is suppressed in the central nervous system (CNS) ECs in MS and its animal model experimental autoimmune encephalomyelitis. We identify ETS1 as a central regulator of endothelial-to-mesenchymal transition (EndMT) associated with the compromise of barrier integrity. These phenotypical and functional alterations can further induce high permeability, immune infiltration, and organ fibrosis in multiple sclerosis, thus promoting disease progression. Together, these results demonstrate a functional role of EndMT in blood-brain barrier dysfunction and propose ETS1 as a potential transcriptional switch of EndMT to target the development of multiple sclerosis.

Identification of MAD2L1 as a Potential Biomarker in Hepatocellular Carcinoma via Comprehensive Bioinformatics Analysis.

BACKGROUND: Hepatocellular carcinoma (HCC) is widely acknowledged as a malignant tumor with rapid progression, high recurrence rate, and poor prognosis. At present, there is a paucity of reliable biomarkers at the clinical level to guide the management of HCC and improve patient outcomes. Our research is aimed at assessing the prognostic value of MAD2L1 in HCC. METHODS: Four datasets, GSE121248, GSE101685, GSE85598, and GSE62232, were selected from the GEO database to analyze differentially expressed genes (DEGs) between HCC and normal liver tissues. After functional analysis, we constructed a protein-protein interaction network (PPI) for DEGs and identified core genes in this network with high connectivity with other genes. We assessed the relationship between core genes and the pathogenesis and prognosis of HCC. Finally, we explored the gene regulatory signaling mechanisms involved in HCC pathogenesis. RESULTS: 145 DEGs were screened from the intersection of the four GEO datasets. MAD2L1 was associated with most genes according to the PPI network and was selected as a candidate gene for further study. Survival analysis suggested that high MAD2L1 expression in HCC correlated with a worse prognosis. In addition, real-time quantitative PCR (RT-qPCR), western blot (WB), and immunohistochemistry (IHC) findings suggested that the expression of MAD2L1 was abnormally increased in HCC tissues and cells compared to paraneoplastic tissues and normal hepatocytes. CONCLUSION: We found that high MAD2L1 expression in HCC was significantly associated with overall patient survival and clinical features. We also explored the potential biological properties of this gene.

A Microfabricated Dual Slip-Pressure Sensor with Compliant Polymer-Liquid Metal Nanocomposite for Robotic Manipulation.

Conventional grippers fall behind their human counterparts as they do not have integrated sensing capabilities. Piezoresistive and capacitive sensors are popular choices because of their design and sensitivity, but they cannot measure pressure and slip simultaneously. It is imperative to measure slip and pressure concurrently. We demonstrate a dual slip-pressure sensor based on a thermal approach. The sensor comprises two concentric microfabricated heaters maintained at constant temperature. An elastic dome, with embedded liquid metal droplets, is placed on top of concentric heaters. Heat transfer between sensor and the object in contact occurs through the elastic dome. This heat transfer causes changes in the power absorbed by the sensor to maintain its temperature and allows for measurement of pressure while identifying slip events. Liquid metal droplets contribute to enhanced thermal conductivity (0.37 W/m-K) and reduced specific heat (0.86 kJ/kg-K) of the polymer without compromising on mechanical properties (Young's modulus-0.5 MPa). For pressure monitoring, sensor measures change in power ratio against increase in applied force, demonstrating a highly linear performance, with a high sensitivity of 0.0356 N-1 (pressure only) and 0.0189 N-1 (slip with simultaneous pressure applied). The sensor discriminates between different contact types with a 96% accuracy. Response time of the sensor (60-75 ms) matches the measured response time in human skin. The sensor does not get affected by mechanical vibrations paving way for easy integration with robotic manipulators and prosthetics.

Long non-coding RNAs in neurodegenerative diseases.

Neurodegenerative diseases are gradually becoming the main burden of society. The morbidity and mortality caused by neurodegenerative diseases remain significant health-care concerns. For most neurodegenerative diseases, there are no effective treatments. Over the past few decades, in a quest to exploit efficacious disease-modifying therapies for the treatment of neurodegenerative diseases, disease mechanisms, reliable biomarkers and therapeutic targets have become a research priority. At present, lncRNA is an area with potential research value. In this article, we first summarize some of the existing results of research into lncRNAs, including origin, molecular characteristics, location types, and functional types. We then introduce the possible functions of lncRNAs in different neurodegenerative diseases. Furthermore, some lncRNAs which show promise as biomarkers or potential therapeutic targets are systematically summarized.

Risk factors and predictors of QTc prolongation in critically ill Chinese patients.

BACKGROUND: To recognize and validate the predictor of risk factors for ICU patients with QTc intervals ≥500 ms. METHODS: We retrospectively reviewed 160 ICU patients with their medical electronic records including all demographic data, diagnosis measurements, ECGs and medication from March 1, 2018 to December 1, 2018. All information of patients' baseline, comorbidities, electrolytes and Long QT syndrome (LQTS)-inducing medications of patients with QT interval corrected (QTc) ≥ 500 ms (n = 80) and <500 ms (n = 80) were collected and analyzed using univariate and multivariate analyses to find predictors. RESULTS: Comparing to patients with QTc < 500 ms, patients with QTc ≥ 500 ms had increased SOFA (P = 0.010) and APACHE II scores (P = 0.002), longer lengths of ICU stays (P < 0.001), greater incidence of congestive heart failure (P = 0.005) and more preset risk factors (P < 0.001). The frequency of administration of mosapride (P = 0.015), amiodarone (P = 0.027) and number of combined LQTS-inducing medications (P = 0.012) were greater in patients with QTc ≥ 500 ms than in those with QTc < 500 ms. But after multivariate analysis, we found that risk factors related to a QTc ≥ 500 ms were only congestive heart failure (OR: 5.28), number of combined LQTS-inducing medications (OR: 1.60) and APACHE II score (OR: 1.08). CONCLUSIONS: For critically ill patients, congestive heart failure, number of combined LQTS-inducing medications and APACHE II score are proved as risk factors associated with QTc > 500 ms.

pH-Sensitive, Cerebral Vasculature-Targeting Hydroxyethyl Starch Functionalized Nanoparticles for Improved Angiogenesis and Neurological Function Recovery in Ischemic Stroke.

Angiogenesis, an essential restorative process following ischemia, is a promising therapeutic approach to improve neurological deficits. However, overcoming the blood-brain barrier (BBB) and effective drug enrichment are challenges for conventional drug delivery methods, which has limited the development of treatment strategies. Herein, a dual-targeted therapeutic strategy is reported to enable pH-sensitive drug release and allow cerebral ischemia targeting to improve stroke therapeutic efficacy. Targeted delivery is achieved by surface conjugation of Pro-His-Ser-Arg-Asn (PHSRN) peptides, which binds to integrin α5 ß1 enriched in the cerebral vasculature of ischemic tissue. Subsequently, smoothened agonist (SAG), an activator of sonic hedgehog (Shh) signaling, is coupled to PHSRN-HES by pH-dependent electrostatic adsorption. SAG@PHSRN-HES nanoparticles can sensitively release more SAG in the acidic environment of ischemic brain tissue. More importantly, SAG@PHSRN-HES exerts the synergistic mechanisms of PHSRN and SAG to promote angiogenesis and BBB integrity, thus improving neuroplasticity and neurological function recovery. This study proposes a new approach to improve the delivery of medications in the ischemic brain. Dual-targeted therapeutic strategies have excellent potential to treat patients suffering from cerebral infarction.

Elbow Motion Trajectory Prediction Using a Multi-Modal Wearable System: A Comparative Analysis of Machine Learning Techniques.

Motion intention detection is fundamental in the implementation of human-machine interfaces applied to assistive robots. In this paper, multiple machine learning techniques have been explored for creating upper limb motion prediction models, which generally depend on three factors: the signals collected from the user (such as kinematic or physiological), the extracted features and the selected algorithm. We explore the use of different features extracted from various signals when used to train multiple algorithms for the prediction of elbow flexion angle trajectories. The accuracy of the prediction was evaluated based on the mean velocity and peak amplitude of the trajectory, which are sufficient to fully define it. Results show that prediction accuracy when using solely physiological signals is low, however, when kinematic signals are included, it is largely improved. This suggests kinematic signals provide a reliable source of information for predicting elbow trajectories. Different models were trained using 10 algorithms. Regularization algorithms performed well in all conditions, whereas neural networks performed better when the most important features are selected. The extensive analysis provided in this study can be consulted to aid in the development of accurate upper limb motion intention detection models.

Effects of nurse-led sedation protocols on mechanically ventilated intensive care adults: A systematic review and meta-analysis.

OBJECTIVES: The objective of the study was to compare nurse-led sedation protocols with physician-led usual care in intensive care units (ICUs) in treating mechanically ventilated adult patients. REVIEW METHOD USED: This is a systematic review and meta-analysis. DATA SOURCES: PubMed, Cochrane Library, EMBASE, CINAHL, China National Knowledge Infrastructure, and China Wanfang databases were interrogated for articles published before May 2020. REVIEW METHOD: As per Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, eight randomised controlled trials (RCTs) and six preintervention and postintervention studies published in English and Chinese met the inclusion criteria for the meta-analysis. Two reviewers independently extracted data into a tabular format using predefined data fields. Disagreements were resolved by consensus. The quality of the included RCTs and preintervention and postintervention studies was assessed using the Cochrane Quality Assessment Tool and Risk Of Bias In Non-randomised Studies of Interventions assessment tool. RESULTS: Eight RCTs were of intermediate methodological quality, and six preintervention and postintervention studies exhibited a low to moderate risk of bias. Compared with usual care, nurse-led sedation protocols resulted in significantly decreased durations of mechanical ventilation (days) (standardised mean difference = -1.765; 95% confidence interval [CI] = -2.461, -1.068); P < 0.001; I2 = 97.7%); decreased length of ICU stay (days) (standardised mean difference = -1.463; 95% CI = -2.181, -0.745; P < 0.001; I2 = 97.3%); reduced ICU mortality (relative risk [RR] = 0.854; 95% CI = 0.747, 0.983; P = 0.027), I2 = 0%); and decreased incidence of ventilator-associated pneumonia (RR = 0.438; 95% CI = 0.292, 0.657; P < 0.001; I2 = 41.4%), delirium (RR = 0.522; 95% CI = 0.338, 0.807; P = 0.003; I2 = 26.6%), and extubation failure (RR = 0.498; 95% CI = 0.266, 0.932; P = 0.029; I2 = 45.1%). CONCLUSIONS: Although pre-post intervention study design cannot establish causality, the present findings raise the considerable possibility that a sedation protocol can be safely implemented by nurses to reduce mortality in ICUs and sedation-related adverse events in patients on mechanical ventilation compared with physician-led usual care.

Effects of Taurine on Broiler Aortic Endothelial Apoptosis Induced by Heat Stress.

Heat stress is an environmental factor that causes severe economic loss to the current intensive breeding industry and induces huge impact on the long-term growth in livestock and poultry industry. Many animal experiments confirmed that heat stress is a major cause of heat stroke death, which is due to severe damage to endothelial cells. In order to provide a theoretical basis for the treatment or mitigation of heat stress related diseases in broilers, the effect of taurine on injury and apoptosis of aortic endothelial cells in broilers under heat stress was investigated in the present study. Ten days healthy broilers were sacrificed, then aortic tissue was used to isolate and cultivate primary broiler aortic endothelial cells. The third to the fifth generations of cells were used in the experiment. The cells were randomly divided into five groups, including control group (C), heat stress group (HS), low taurine (HS+LTau) group, mild taurine (HS+MTau) group and high taurine (HS+HTau) group. Cells in all groups were cultivated for 24 h in cell incubator (37 °C, 5% CO2). Then the heat stress group cells were cultivated in a 43 °C thermostatic water bath for 6 h under heat stress, and then re-incubated under 37 °C for 1 h. The results showed that compared with the control group, expression levels of Bax, Caspase-9, Caspase-3, Cyt-c, P53 and other pro-apoptosis factors in HS groups were significantly increased (P < 0.05), while expression levels of anti-apoptosis factor Bcl-2 showed a significant decrease (P < 0.05). Compared with HS group, expression levels of Bcl-2 in endothelial cells were significantly increased by taurine administration (P < 0.05), while expression of Bax, Caspase-9, Caspase-3, Cyt-c and P53 were significantly increased by taurine (P < 0.05). In summary, the present data indicated that taurine could protect against injury and apoptosis of aortic endothelial cells under heat stress by inhibiting the activation of mitochondria-mediated apoptotic pathways.

Discrimination of lymphoma using laser-induced breakdown spectroscopy conducted on whole blood samples.

Lymphoma is a significant cancer that affects the human lymphatic and hematopoietic systems. In this work, discrimination of lymphoma using laser-induced breakdown spectroscopy (LIBS) conducted on whole blood samples is presented. The whole blood samples collected from lymphoma patients and healthy controls are deposited onto standard quantitative filter papers and ablated with a 1064 nm Q-switched Nd:YAG laser. 16 atomic and ionic emission lines of calcium (Ca), iron (Fe), magnesium (Mg), potassium (K) and sodium (Na) are selected to discriminate the cancer disease. Chemometric methods, including principal component analysis (PCA), linear discriminant analysis (LDA) classification, and k nearest neighbor (kNN) classification are used to build the discrimination models. Both LDA and kNN models have achieved very good discrimination performances for lymphoma, with an accuracy of over 99.7%, a sensitivity of over 0.996, and a specificity of over 0.997. These results demonstrate that the whole-blood-based LIBS technique in combination with chemometric methods can serve as a fast, less invasive, and accurate method for detection and discrimination of human malignancies.