Exosomes in liver fibrosis: The role of modulating hepatic stellate cells and immune cells, and prospects for clinical applications

Liver fibrosis is a global health problem caused by chronic liver injury resulting from various factors. Hepatic stellate cells (HSCs) have been found to play a major role in liver fibrosis, and pathological stimuli lead to their transdifferentiation into myofibroblasts. Complex multidirectional interactions between HSCs, immune cells, and cytokines are also critical for the progression of liver fibrosis. Despite the advances in treatments for liver fibrosis, they do not meet the current medical needs. Exosomes are extracellular vesicles of 30-150 nm in diameter and are capable of intercellular transport of molecules such as lipids, proteins and nucleic acids. As an essential mediator of intercellular communication, exosomes are involved in the physiological and pathological processes of many diseases. In liver fibrosis, exosomes are involved in the pathogenesis mainly by regulating the activation of HSCs and the interaction between HSCs and immune cells. Serum-derived exosomes are promising biomarkers of liver fibrosis. Exosomes also have promising therapeutic potential in liver fibrosis. Exosomes derived from mesenchymal stem cells and other cells exhibit anti-liver fibrosis effects. Moreover, exosomes may serve as potential therapeutic targets for liver fibrosis and hold promise in becoming drug carriers for liver fibrosis treatment

Stakeholder efforts to mitigate antiretroviral therapy interruption among people living with HIV during the COVID-19 pandemic in China: a qualitative study.

INTRODUCTION: The COVID-19 pandemic has affected antiretroviral therapy (ART) continuity among people living with HIV (PLHIV) worldwide. We conducted a qualitative study to explore barriers to ART maintenance and solutions to ART interruption when stringent COVID-19 control measures were implemented in China, from the perspective of PLHIV and relevant key stakeholders. METHODS: Between 11 February and 15 February 2020, we interviewed PLHIV, community-based organization (CBO) workers, staff from centres for disease control and prevention (CDC) at various levels whose work is relevant to HIV care (CDC staff), HIV doctors and nurses and drug vendors from various regions in China. Semi-structured interviews were conducted using a messaging and social media app. Challenges and responses relevant to ART continuity during the COVID-19 pandemic were discussed. Themes were identified by transcript coding and mindmaps. RESULTS: Sixty-four stakeholders were recruited, including 16 PLHIV, 17 CBO workers, 15 CDC staff, 14 HIV doctors and nurses and two drug vendors. Many CDC staff, HIV doctors and nurses responsible for ART delivery and HIV care were shifted to COVID-19 response efforts. Barriers to ART maintenance were (a) travel restrictions, (b) inadequate communication and bureaucratic obstacles, (c) shortage in personnel, (d) privacy concerns, and (e) insufficient ART reserve. CBO helped PLHIV maintain access to ART through five solutions identified from thematic analysis: (a) coordination to refill ART from local CDC clinics or hospitals, (b) delivery of ART by mail, (c) privacy protection measures, (d) mental health counselling, and (e) providing connections to alternative sources of ART. Drug vendors contributed to ART maintenance by selling out-of-pocket ART. CONCLUSIONS: Social and institutional disruption from COVID-19 contributed to increased risk of ART interruption among PLHIV in China. Collaboration among key stakeholders was needed to maintain access to ART, with CBO playing an important role. Other countries facing ART interruption during current or future public health emergencies may learn from the solutions employed in China

Actively implementing an evidence-based feeding guideline for critically ill patients (NEED): a multicenter, cluster-randomized, controlled trial

Background: Previous cluster-randomized controlled trials evaluating the impact of implementing evidence-based guidelines for nutrition therapy in critical illness do not consistently demonstrate patient benefits. A large-scale, sufficiently powered study is therefore warranted to ascertain the effects of guideline implementation on patient-centered outcomes. Methods: We conducted a multicenter, cluster-randomized, parallel-controlled trial in intensive care units (ICUs) across China. We developed an evidence-based feeding guideline. ICUs randomly allocated to the guideline group formed a local "intervention team", which actively implemented the guideline using standardized educational materials, a graphical feeding protocol, and live online education outreach meetings conducted by members of the study management committee. ICUs assigned to the control group remained unaware of the guideline content. All ICUs enrolled patients who were expected to stay in the ICU longer than seven days. The primary outcome was all-cause mortality within 28 days of enrollment. Results: Forty-eight ICUs were randomized to the guideline group and 49 to the control group. From March 2018 to July 2019, the guideline ICUs enrolled 1399 patients, and the control ICUs enrolled 1373 patients. Implementation of the guideline resulted in significantly earlier EN initiation (1.20 vs. 1.55 mean days to initiation of EN; difference − 0.40 [95% CI − 0.71 to − 0.09]; P = 0.01) and delayed PN initiation (1.29 vs. 0.80 mean days to start of PN; difference 1.06 [95% CI 0.44 to 1.67]; P = 0.001). There was no significant difference in 28-day mortality (14.2% vs. 15.2%; difference − 1.6% [95% CI − 4.3% to 1.2%]; P = 0.42) between groups. Conclusions: In this large-scale, multicenter trial, active implementation of an evidence-based feeding guideline reduced the time to commencement of EN and overall PN use but did not translate to a reduction in mortality from critical illness. Trial registration: ISRCTN, ISRCTN12233792. Registered November 20th, 2017

Actively implementing an evidence-based feeding guideline for critically ill patients (NEED): a multicenter, cluster-randomized, controlled trial.

BackgroundPrevious cluster-randomized controlled trials evaluating the impact of implementing evidence-based guidelines for nutrition therapy in critical illness do not consistently demonstrate patient benefits. A large-scale, sufficiently powered study is therefore warranted to ascertain the effects of guideline implementation on patient-centered outcomes.MethodsWe conducted a multicenter, cluster-randomized, parallel-controlled trial in intensive care units (ICUs) across China. We developed an evidence-based feeding guideline. ICUs randomly allocated to the guideline group formed a local "intervention team", which actively implemented the guideline using standardized educational materials, a graphical feeding protocol, and live online education outreach meetings conducted by members of the study management committee. ICUs assigned to the control group remained unaware of the guideline content. All ICUs enrolled patients who were expected to stay in the ICU longer than seven days. The primary outcome was all-cause mortality within 28 days of enrollment.ResultsForty-eight ICUs were randomized to the guideline group and 49 to the control group. From March 2018 to July 2019, the guideline ICUs enrolled 1399 patients, and the control ICUs enrolled 1373 patients. Implementation of the guideline resulted in significantly earlier EN initiation (1.20 vs. 1.55 mean days to initiation of EN; difference - 0.40 [95% CI - 0.71 to - 0.09]; P = 0.01) and delayed PN initiation (1.29 vs. 0.80 mean days to start of PN; difference 1.06 [95% CI 0.44 to 1.67]; P = 0.001). There was no significant difference in 28-day mortality (14.2% vs. 15.2%; difference - 1.6% [95% CI - 4.3% to 1.2%]; P = 0.42) between groups.ConclusionsIn this large-scale, multicenter trial, active implementation of an evidence-based feeding guideline reduced the time to commencement of EN and overall PN use but did not translate to a reduction in mortality from critical illness.Trial registrationISRCTN, ISRCTN12233792 . Registered November 20th, 2017

Actively implementing an evidence-based feeding guideline for critically ill patients (NEED): a multicenter, cluster-randomized, controlled trial (vol 26, 46, 2022)

BackgroundPrevious cluster-randomized controlled trials evaluating the impact of implementing evidence-based guidelines for nutrition therapy in critical illness do not consistently demonstrate patient benefits. A large-scale, sufficiently powered study is therefore warranted to ascertain the effects of guideline implementation on patient-centered outcomes.MethodsWe conducted a multicenter, cluster-randomized, parallel-controlled trial in intensive care units (ICUs) across China. We developed an evidence-based feeding guideline. ICUs randomly allocated to the guideline group formed a local "intervention team", which actively implemented the guideline using standardized educational materials, a graphical feeding protocol, and live online education outreach meetings conducted by members of the study management committee. ICUs assigned to the control group remained unaware of the guideline content. All ICUs enrolled patients who were expected to stay in the ICU longer than seven days. The primary outcome was all-cause mortality within 28 days of enrollment.ResultsForty-eight ICUs were randomized to the guideline group and 49 to the control group. From March 2018 to July 2019, the guideline ICUs enrolled 1399 patients, and the control ICUs enrolled 1373 patients. Implementation of the guideline resulted in significantly earlier EN initiation (1.20 vs. 1.55 mean days to initiation of EN; difference - 0.40 [95% CI - 0.71 to - 0.09]; P = 0.01) and delayed PN initiation (1.29 vs. 0.80 mean days to start of PN; difference 1.06 [95% CI 0.44 to 1.67]; P = 0.001). There was no significant difference in 28-day mortality (14.2% vs. 15.2%; difference - 1.6% [95% CI - 4.3% to 1.2%]; P = 0.42) between groups.ConclusionsIn this large-scale, multicenter trial, active implementation of an evidence-based feeding guideline reduced the time to commencement of EN and overall PN use but did not translate to a reduction in mortality from critical illness.Trial registrationISRCTN, ISRCTN12233792 . Registered November 20th, 2017

Growth, Secondary Metabolites and Enzyme Activity Responses of Two Edible Fern Species to Drought Stress and Rehydration in Northeast China

The drought resistance mechanism of Matteuccia struthiopteris (L.) Todar. and Athyrium multidentatum (Doll.) Ching were measured under natural drought exposure. The results showed that the two edible fern species showed stronger resistance in the early stages of drought, mainly expressed as the decrease of relative leaf water content (RLWC), increase of osmotic substances, secondary metabolites such as flavonoids (FC), total phenols (TPC), proantho cyanidins (PCC) content and enzyme activity (superoxide dismutase (SOD), peroxidase (POD), catalase (CAT) and ascorbate peroxidase (APX)). The higher RLWC, FC, TPC, PCC and abscisic acid (ABA) content and lower H2O2 content indicates the stronger non-enzymatic antioxidant system and drought resistance of A. multidentatum. However, the proline (Pro) content changed slowly, and the synthesis of soluble protein (SP), total phenols, proantho cyanidins and ABA, SOD activity of two fern species were inhibited in the late stages of drought stress. This study can provide a scientific basis for the cultivation and utilization of edible fern species under forest in Northeast China

Enhanced Z-LDA for Small Sample Size Training in Brain-Computer Interface Systems

Background. Usually the training set of online brain-computer interface (BCI) experiment is small. For the small training set, it lacks enough information to deeply train the classifier, resulting in the poor classification performance during online testing. Methods. In this paper, on the basis of Z-LDA, we further calculate the classification probability of Z-LDA and then use it to select the reliable samples from the testing set to enlarge the training set, aiming to mine the additional information from testing set to adjust the biased classification boundary obtained from the small training set. The proposed approach is an extension of previous Z-LDA and is named enhanced Z-LDA (EZ-LDA). Results. We evaluated the classification performance of LDA, Z-LDA, and EZ-LDA on simulation and real BCI datasets with different sizes of training samples, and classification results showed EZ-LDA achieved the best classification performance. Conclusions. EZ-LDA is promising to deal with the small sample size training problem usually existing in online BCI system

Determination of Levamisole and Mebendazole and Its Two Metabolite Residues in Three Poultry Species by HPLC-MS/MS

A high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) method was developed to simultaneously analyze levamisole (LMS) and mebendazole (MBZ) and its two metabolites, 5-hydroxymebendazole (HMBZ) and 2-amino-5-benzoylbenzimidazole (AMBZ), in poultry muscle (chicken, duck and goose). In the sample preparation process, basic ethyl acetate was used as the extraction agent, and the extracted samples were back-extracted with hydrochloric acid, purified by Oasis MCX solid-phase extraction (SPE) cartridges, and reconstituted in the initial mobile phase after being blown dry with nitrogen. Chromatographic separation was performed on an Xbridge C18 column (4.6 mm × 150 mm, 5 μm) with 0.1% formic acid in water and acetonitrile as the mobile phases, and gradient elution was performed at a flow rate of 0.6 mL/min and a column temperature of 35 °C. In blank poultry muscle samples, the spiked concentrations of LMS, MBZ, HMBZ, and AMBZ were within the range of the limit of quantitation (LOQ) to 25 μg/kg. The peak areas of the four target drugs had a good linear relationship with the concentration, and the determination coefficient (R2) values were higher than 0.9990. The average recoveries of LMS, MBZ, HMBZ, and AMBZ were 86.77–96.94%; the intraday relative standard deviations (RSDs) were 1.75–4.99% at LOQ, 0.5 maximum residue limit (MRL), 1.0 MRL, and 2.0 MRL; the interday RSDs were 2.54–5.52%; and the LODs and LOQs were 0.04–0.30 μg/kg and 0.12–0.80 μg/kg, respectively

A novel brain inception neural network model using EEG graphic structure for emotion recognition

Purpose EEG analysis of emotions is greatly significant for the diagnosis of psychological diseases and brain-computer interface (BCI) applications. However, the applications of EEG brain neural network for emotion classification are rarely reported and the accuracy of emotion recognition for cross-subject tasks remains a challenge. Thus, this paper proposes to design a domain invariant model for EEG-network based emotion identification. Methods A novel brain-inception-network based deep learning model is proposed to extract discriminative graph features from EEG brain networks. To verify its efficiency, we compared our proposed method with some commonly used methods and three types of brain networks. In addition, we also compared the performance difference between the EEG brain network and EEG energy distribution for emotion recognition. Result One public EEG-based emotion dataset (SEED) was utilized in this paper, and the classification accuracy of leave-one-subject-out cross-validation was adopted as the comparison index. The classification results show that the performance of the proposed method is superior to those of the other methods mentioned in this paper. Conclusion The proposed method can capture discriminative structural features from the EEG network, which improves the emotion classification performance of brain neural networks