Enhancing and Adapting in the Clinic: Source-Free Unsupervised Domain Adaptation for Medical Image Enhancement.

Medical imaging provides many valuable clues involving anatomical structure and pathological characteristics. However, image degradation is a common issue in clinical practice, which can adversely impact the observation and diagnosis by physicians and algorithms. Although extensive enhancement models have been developed, these models require a well pre-training before deployment, while failing to take advantage of the potential value of inference data after deployment. In this paper, we raise an algorithm for source-free unsupervised domain adaptive medical image enhancement (SAME), which adapts and optimizes enhancement models using test data in the inference phase. A structure-preserving enhancement network is first constructed to learn a robust source model from synthesized training data. Then a teacher-student model is initialized with the source model and conducts source-free unsupervised domain adaptation (SFUDA) by knowledge distillation with the test data. Additionally, a pseudo-label picker is developed to boost the knowledge distillation of enhancement tasks. Experiments were implemented on ten datasets from three medical image modalities to validate the advantage of the proposed algorithm, and setting analysis and ablation studies were also carried out to interpret the effectiveness of SAME. The remarkable enhancement performance and benefits for downstream tasks demonstrate the potential and generalizability of SAME. The code is available at https://github.com/liamheng/Annotation-free-Medical-Image-Enhancement.

Efficacy and safety of tirzepatide, dual GLP-1/GIP receptor agonists, in the management of type 2 diabetes: a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Glucose-dependent insulinotropic polypeptide (GIP) and GLP-1 are the main incretin hormones, and be responsible for the insulinotropic incretin effect. The addition of a GIP agonist to a GLP-1agonist has been hypothesized to significantly potentiate the weight-losing and glycemia control effect, which might offer a new therapeutic option in the treatment of type 2 diabetes. The current meta-analysis aims to synthesize evidence of primary efficacy and safety outcomes through clinically randomized controlled trials to evaluate integrated potency and signaling properties. METHOD: We conducted comprehensive literature searches in Cochrane Library, Web of Science, Embase and PubMed for relevant literatures investigating the efficacy and/or safety of Tirzepatide published in the English as of May 30, 2023 was retrieved. We synthesized results using standardized mean differences (SMDs) and 95% confidence intervals (95 CIs) for continuous outcomes, and odds ratios (ORs) along with 95 Cis for dichotomous outcomes. All analyses were done using Revman version 5.3, STATA version 15.1 and the statistical package 'meta'. RESULTS: Participants treated with weekly Tirzepatide achieved HbA1c and body weight target values significantly lower than any other comparator without clinically significant increase in the incidence of hypoglycemic events, serious and all-cause fatal adverse events. However, gastrointestinal adverse events and decreased appetite events were reported more frequently with Tirzepatide treatment than with placebo/controls. CONCLUSION: The Tirzepatide, a dual GIP/GLP-1 receptor co-agonist, for diabetes therapy has opened a new era on personalized glycemia control and weight loss in a safe manner with broad and promising clinical implications.

Serum and supplemental vitamin D levels and insulin resistance in T2DM populations: a meta-analysis and systematic review.

Observational studies have shown a negative correlation between Vitamin D level and the likelihood of developing insulin resistance (IR) and/or diabetes over time, yet evidence remains inconsistent. In this meta-analysis and systematic review, we strive to define the potential association between serum or supplemental Vitamin D Levels and insulin resistance respectively, as well as the contribution of Vitamin D to type 2 diabetes, and to summarize the biologic plausibility of Vitamin D. Four databases (PubMed, Embase, Cochrane Library, and Web of Science) were searched for this Systematic Literature Review (SLR) to find appropriate observational studies and clinical trials published in English through to July 2022. EndNote (version X9) is used to manage the literature search results. We calculated Standard Mean Differences (SMDs) and Risk Ratios (RRs) with their 95% Confidence Intervals (CIs), separately, for continuous and dichotomous outcomes. The correlation coefficients were normalized to z values through Fisher's z-transformation to calculate the relevant statistics. Meta-analyses were carried out for all comparisons, based on a random-effects pooling model. Data analysis was performed using RevMan (version 5.3) and STATA (version 15.1). All statistical tests were two-sided, with P < 0.05 were regarded as significant. In our current meta-analysis, there are 18 RCTs and 20 observational studies including 1243 and 11,063 participants respectively. In the overall analysis, the diabetic with Vitamin D supplement treatment group showed significantly improve serum insulin (SMD = - 0.265, 95% CI - 0.394 to - 0.136, P < 0.05), glucose (SMD = - 0.17, 95% CI - 0.301to - 0.039, P < 0.05) and HOMA-IR (SMD = - 0.441, 95% CI - 0.582 to - 0.3, P < 0.05) compared with the routine treatment group. Correlation analysis results showed that all three outcomes were significantly correlated in a negative manner with raised Vitamin D (insulin: r = - 0.08 95% = - 0.12 to - 0.04; glucose: r = - 0.06 95% = - 0.11 to - 0.01; HOMA-IR: r = - 0.08 95% = - 0.09 to - 0.06). Results of overall analysis proved that vitamin D has shown significant effect on regulates insulin resistance, and there is a significant inverse association between serum Vitamin D level and IR. Vitamin D supplementation is expected to be integrated into conventional medical approaches to prevent type 2 diabetes and to mitigate the burden of diabetes for individuals and society.PROSPERO registration number: CRD42022348295.

Effect of cold atmospheric plasma therapy on wound healing in patients with diabetic foot ulcers: protocol for a systematic review and meta-analysis.

INTRODUCTION: Diabetic foot ulcer (DFU), one of the most common and serious consequences of diabetes, affects many individuals and often leads to amputation, death and other disastrous outcomes. Diabetic foot ulcers have a relatively poor response to therapy, which increases the likelihood of recurrence. Cold atmospheric plasma (CAP) therapy is an emerging treatment method for DFU that can reduce bacterial loads and speed up the healing of chronic wounds. Although some studies have reported that CAP could improve the wound healing speed compared with conventional traditional therapy, the samples in these studies are small and not sufficiently representative. The purpose of the current systematic review and meta-analysis is to evaluate the effectiveness and safety of CAP in DFU treatment and provide a scientific basis for its clinical application. METHODS AND ANALYSIS: The following databases will be searched: Wanfang, China Biology and Medicine CD, Embase, PubMed and The Cochrane Library. We will retrieve publications, conference documents, current trials and internal reports written in English or Chinese related to the effect of CAP therapy on wound healing in patients with diabetic foot ulcers up to 30 June 2022. The selected articles will be read independently by two reviewers, and valid information such as first author, publication date and outcome indicators will be extracted. Researchers will also assess the quality of the literature using the Cochrane risk-of-bias tool 2. RevMan 5.3.5, EndNote X7 and STATA V.13.0 will be used for data analysis. ETHICS AND DISSEMINATION: No ethical review is necessary for this systematic review because it is based on previously published data and does not include patient intervention. A peer-reviewed publication will publish the findings of this investigation.

PM2.5 induce lifespan reduction, insulin/IGF-1 signaling pathway disruption and lipid metabolism disorder in Caenorhabditis elegans.

Introduction: Exposure to fine particulate matter (PM), especially PM2.5, can induce various adverse health effects in populations, including diseases and premature death, but the mechanism of its toxicity is largely unknown. Methods: Water-soluble components of PM2.5 (WS-PM2.5) were collected in the north of China in winter, and combined in two groups with the final concentrations of 94 µg/mL (CL group, AQI ≤ 100) and 119 µg/mL (CH group, 100 < AQI ≤ 200), respectively. The acute and long-term toxic effects of WS-PM2.5 samples were evaluated in several aspects such as development, lifespan, healthspan (locomotion behavior, heat stress tolerance, lipofucin). DAF mutants and genes were applied to verify the action of IIS pathway in WS-PM2.5 induced-effects. RNA-Sequencing was performed to elucidate the molecular mechanisms, as well as ROS production and Oil red O staining were also served as means of mechanism exploration. Results: Body length and lifespan were shortened by exposure to WS-PM2.5. Healthspan of nematodes revealed adverse effects evaluated by head thrash, body bend, pharyngeal pump, as well as intestinal lipofuscin accumulation and survival time under heat stress. The abbreviated lifespan of daf-2(e1370) strain and reduced expression level of daf-16 and hsp-16.2 indicated that IIS pathway might be involved in the mechanism. Thirty-five abnormally expressed genes screened out by RNA-Sequencing techniques, were functionally enriched in lipid/lipid metabolism and transport, and may contribute substantially to the regulation of PM2.5 induced adverse effects in nematodes. Conclusion: WS-PM2.5 exposure induce varying degrees of toxic effects, such as body development, shorten lifespan and healthspan. The IIS pathway and lipid metabolism/transport were disturbed by WS-PM2.5 during WS-PM2.5 exposure, suggesting their regulatory role in lifespan determination.

HSP90 inhibitors and cancer: Prospects for use in targeted therapies (Review).

Heat shock protein 90 (HSP90) is a vital chaperone protein, regulating signaling pathways and correcting misfolded proteins in cancer cells by interacting with oncogenic client proteins and co­chaperones. The inhibition of HSP90 chaperone machinery has been demonstrated as a potential approach with which to inhibit tumor survival, proliferation, invasion and migration. Numerous HSP90 inhibitors have been reported and have exhibited value as cancer­targeted therapies by interrupting the ATPase activity of HSP90, thus suppressing the oncogenic pathways in cancer cells. These inhibitors have been classified into three categories: i) N­terminal domain (NTD) inhibitors; ii) C­terminal domain (CTD) inhibitors; and iii) isoform­selective inhibitors. However, none of these HSP90 inhibitors are used as clinical treatments. The major limiting factors can be summarized into drug resistance, dose­limiting toxicity and poor pharmacokinetic profiles. Novel HSP90­targeted compounds are constantly being discovered and tested for their antitumor efficacy in preclinical and clinical trials, highlighting the prospect of the use of HSP90 inhibitors as cancer­targeted therapies. Additionally, improved antitumor effects have been observed when HSP90 inhibitors are used in combination with chemotherapy, targeted agents, or immunotherapy. In the present review, the effects of HSP90 inhibitors on the management of the cancer process are discussed and previous and novel HSP90­based therapeutic strategies in cancer treatment are summarized. Furthermore, prospective HSP90­targeting candidates are proposed for their future evaluation as cancer treatments.

Sevoflurane-induced POCD-associated exosomes delivered miR-584-5p regulates the growth of human microglia HMC3 cells through targeting BDNF.

BACKGROUND: Inhalation of sevoflurane can cause neuronal apoptosis, and cognitive disorders, inducing to the occurrence and progression of post operative cognitive dysfunction (POCD). This study aimed to explore the roles of sevoflurane-induced POCD-associated exosomes on HMC3 cells and its related mechanisms. METHODS: Exosomes were isolated from the plasma of sevoflurane-induced POCD or non-POCD patients, and were then sent for small RNA sequencing. Real-time quantitative PCR (RT-qPCR) was used to verify the sequencing results, and miR-584-5p was chosen for subsequent study. HMC3 cells were respectively transfected with POCD-derived exosomes and miR-584-5p mimics, and cell viability and apoptosis were measured. Dual-luciferase reporter gene assay was applied to confirm the target of miR-584-5p. RESULTS: After sequencing, 301 differentially expressed miRNAs were identified, including 184 up-regulated miRNAs and 117 down-regulated miRNAs, and were significantly enriched in 3577 GO terms and 121 KEGG pathways. Due to the high level of miR-584-5p in sevoflurane-treated POCD-derived exosomes, HMC3 cells with miR-584-5p enrichment were successfully established. Compared with the control group, POCD-derived exosomes and miR-584-5p significantly inhibited viability and promoted apoptosis of HMC3 cells (P < 0.05). The IL-1ß and TNF-α levels were significantly increased after POCD-derived exosomes and miR-584-5p mimics treatment compared to the control group (P < 0.05). Besides, POCD-derived exosomes and miR-584-5p mimics significantly down-regulated the expression levels of BDNF and p-TrkB, and up-regulated Caspase 3 and IL-1ß. Finally, BDNF was confirmed to be the target of miR-584-5p. CONCLUSIONS: Sevoflurane-induced POCD-associated exosomes delivered miR-584-5p may regulate the growth of HMC3 cells via targeting BDNF.

The links between adipose tissue DNA methylation, obesity, and insulin resistance: A protocol for systematic review.

BACKGROUND AND RATIONALE: Obesity is a metabolic condition brought on by the interplay of hereditary and environmental factors, making it one of the most common diseases in the world. Insulin resistance (IR) and obesity have a close connection and can both be advantageous. One of the main methods of epigenetic regulation is DNA methylation modification. Studies have demonstrated over the past few years that DNA methylation is crucial to the emergence of obesity and DNA methylation can lead to IR. Adipose tissue participates in the physiopathological processes of obesity and IR and functions as an endocrine organ controlling the body's balanced metabolism, thus, adipose tissue-associated gene DNA methylation affects the development of obesity and IR by influencing the function of adipose tissue. Hence, an explanation of current research on DNA methylation, IR, and obesity, following the most recent developments, exploring changes in DNA methylation in different types of adipose tissue in insulin-resistant patients and obese patients may enable the identification of novel targets in clinical obesity prevention and treatment. METHOD AND ANALYSIS: The following electronic bibliographic databases will be searched from inception for peer-reviewed original research published: MEDLINE (through PubMed), Scopus, and EMBASE. Cochrane Library, Cochrane Clinical Trials Registry, the National Institutes for Health Clinical Trials Registry, and the WHO International Clinical Trials Registry Platform from inception to December 31, 2021 will be conducted. Systematic reviews will adhere to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses reporting guidelines. The development of search strategies will make use of medical issue phrases and keywords associated with DNA methylation, Adipose tissue DNA methylation, obesity, and IR. Identified citations will be independently reviewed by two authors to determine eligibility at the title and abstract level, and then at the full text and data extraction phases. Disagreements and conflicts will be resolved through discussion with a third author. Two authors will extract the necessary data from the included studies independently, and The Cochrane Risk of Bias Assessment Tool will be used to assess the bias of randomized controlled studies, and the Newcastle-Ottawa scale for nonrandomized controlled studies. If the interventions and outcomes evaluated are sufficiently homogeneous, results from subgroups of studies will be pooled together in a meta-analysis.

Efficacy of cinnamon supplementation on glycolipid metabolism in T2DM diabetes: A meta-analysis and systematic review.

Background: Cinnamon is a spice used in cooking and in large quantities as a medical complement with hypoglycemic and lipid-lowering properties. The potential pharmacological mechanisms underlying cinnamon's anti-diabetic properties and its active ingredients have not been adequately determined. The current meta-analysis aims to systematically review the potential pharmacological mechanisms underlying the hypoglycemic and hypolipidemic efficacy of cinnamon administration and summarize clinical recommendations of cinnamon and its active ingredients. Method: Relevant randomized clinical trials (RCTs) were identified through a literature search that spanned the years January 2005 to April 2022. Retrieve electronic databases including Web of Science, PubMed, Embase, Medline, and the Cochrane Library. To obtain standardized mean differences (SMDs), continuous outcomes were pooled and 95 percent confidence intervals (CIs) were provided. Categorical outcomes were aggregated to calculate relative risks (RRs) and were accompanied by 95% CIs. Heterogeneity was measured using the Cochrane Q-test and I2 statistics, with a p < 0.05 considered as substantial heterogeneity. If I2 was less than 50%, a fixed effect model was employed; otherwise, a random effect model was used. Subgroup analyses and sensitivity analyses were performed to identify the origins of heterogeneity. Publication bias was retrieved by means of a funnel-plot analysis and Egger's test. The data were analyzed using revman (V.5.3) and stata (V.15) software packages. Results: These 16 RCTs included a total of 1,020 patients who were followed for a duration ranging from 40 days to 4 months. According to the current meta-analysis results, glycolipid levels in diabetic individuals who received cinnamon were significantly improved as compared to those who got placebo (All p < 0.05). An adverse effect was only detected in one patient. Conclusion: These findings imply that cinnamon has a significant influence on lipid and glucose metabolism regulation. An even more pronounced effect was observed in patients with HbA1c of 8%. The results of this study suggested that cinnamon may be utilized as hypoglycemic and lipid-lowering supplement in clinical settings with a guaranteed safety profile.Systematic Review Registration: [PROSPERO], identifier [CRD42022322735].

Effects of glucose availability on αS1-casein synthesis in bovine mammary epithelial cells.

Glucose has been demonstrated to affect milk protein synthesis in dairy cows. However, its potential mechanisms has not been thoroughly studied. The objective of this study was to investigate the effects of glucose availability on αS1-casein synthesis, glucose uptake, metabolism, and the expression of proteins involved in AMP-activated protein kinase (AMPK)/mammalian target of rapamycin (mTOR) signaling pathway in bovine mammary epithelial cells (BMEC). BMEC were treated for 24 h with different concentrations of glucose (0, 7, 10.5, 14, 17.5, and 21 mM). The results showed that 10.5 and 14 mM glucose supply increased the expression of αS1-casein, glucose uptake, cellular ATP content, and the phosphorylation of mTOR and P70S6K, but repressed AMPK phosphorylation in BMEC. Compared with 10.5 and 14 mM glucose supply, 17.5 and 21 mM glucose decreased the expression of αS1-casein, P70S6K phosphorylation as well as the activity of hexokinase (HK) and pyruvate kinase (PK), but increased the activity of glucose-6-phosphate dehydrogenase (G6PD). These results indicate that 10.5 to 14 mM glucose supply is the proper range for αS1-casein synthesis, and the promotion effects may be related to the increase of glucose uptake, ATP content and the changes of key proteins' phosphorylation in AMPK/mTOR signaling pathway. However, the inhibition of the expression of αS1-casein by 17.5 and 21 mM glucose may be associated with the changes of key enzymes' activity involved in glucose metabolism.

Glucose play an important role in milk protein synthesis in dairy cows. But the effects of glucose availability on casein synthesis and its underlying mechanisms has not been thoroughly studied. To elucidate the underlying mechanisms of glucose availability affecting casein synthesis, the effects of glucose availability on αS1-casein synthesis, glucose uptake, metabolism, and the expression of proteins involved in AMP-activated protein kinase (AMPK)/mammalian target of rapamycin (mTOR) signaling pathway in bovine mammary epithelial cells were measured. We found that the expression of αS1-casein increased with 10.5 and 14 mM glucose supplementation, which may be associated with the increase of glucose uptake, ATP content and the changes of key proteins' phosphorylation in AMPK/mTOR signaling pathway. The inhibition of αS1-casein expression with 17.5 and 21 mM glucose supplementation may be related to the changes of key enzymes' activity involved in glucose metabolism. This study provided an insight into the potential mechanisms of glucose availability affecting milk protein synthesis.

Effect of Traditional Chinese Medicine on Treating Antibiotic-Associated Diarrhea in Children: A Systematic Review and Meta-Analysis.

Background: Due to the limited treatment options in antibiotic-associated diarrhea (AAD) in children, more effective treatments should be explored. Traditional Chinese medicine (TCM) has a long history in China, which has produced a pretty effect in clinical practice. Many randomized clinical trials (RCTs) have explored the effect of traditional Chinese medicine on treating AAD in children. However, there has been no systematic review or meta-analysis on the impact of TCM on AAD in children. The aim of this study was to systematically review RCTs on the effect of TCM in children with AAD. Methods: RCTs in the past ten years on TCM for AAD in children were included. We searched Electronic databases as much as possible. This paper was registered in PROSPERO (CRD42022301034). Results: 26 studies were included in this systematic review. 25 studies reported the effects of TCM interventions on the total effective rate (RR = 1.20, CI 1.16 to 1.24; p < 0.001). 7 studies reported the effects of TCM interventions on the time to change the shape of feces (MD = -1.37, CI -1.67 to -1.07; p < 0.001). 17 studies reported the effects of TCM interventions (MD = -1.43, CI -1.71 to -1.15; p < 0.001). The pooled results showed that there were no significant differences between the two groups in CD3+, CD4+, CD8+, CD4 : CD8, time for bowel sounds to return to normal, hs-CRP, and IgM. There was a significant difference between the two groups in frequency of diarrhea on the third day after TCM intervention, vomiting improvement time, diamine oxidase, IL-8, TNF, IgA, IgG, and average hospital stay. Conclusions: TCM interventions combined with conventional therapy can improve the therapeutic effect of AAD in children. However, future studies are still needed for the low methodological quality.

Antioxidant and Anti-Inflammatory Properties of Hydroxyl Safflower Yellow a in Diabetic Nephropathy: A Meta-Analysis of Randomized Controlled Trials.

Background: Diabetic kidney disease (DKD) is a chronic progressive disorder which is a leading cause of chronic kidney disease (CKD). As an important pathogenesis of DKD, the overproduction of reactive oxygen species (ROS) and the inflammatory response have been considered central mediators in the progression of DKD. Herbal products are increasingly being applied as antioxidants and anti-inflammatory agents. Of those, the effect of hydroxyl safflower yellow A (HSYA) on oxidative stress and inflammatory reactions has gradually been investigated for DKD treatment, which may provide therapies for DKD with new insights and promote its application in clinical practice. Methods: We searched CNKI, the Chinese Biomedical Literature Database, the Wanfang Database, PubMed, and Embase from the establishment date of the database to 22 April 2022. The included literature in our study was randomized controlled trials (RCTs) using HSYA to treat DKD. We performed a meta-analysis by calculating the standard mean difference (SMD) with a 95% confidence interval (CI). The inverse-variance method with a random effect was used in our meta-analysis using Stata software and RevMan software. Results: A total of 31 articles with 31 groups containing a total of 2487 participants were included in this meta-analysis. The pooled results showed a statistical improvement in the following measurements: fasting blood glucose (FBG), postprandial blood glucose (PBG), blood urea nitrogen (BUN), urinary albumin excretion rates (UAER), serum creatinine (SCR), hypersensitive C-reactive protein (hsCRP), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), fasting insulin (FINS), total cholesterol (TC), triglycerides (TGs), hemoglobin A1c (HbA1C), homeostasis model assessment insulin resistance (HOMA-IR), and malondialdehyde (MDA). Conclusion: HSYA can effectively treat DKD by inhibiting inflammatory reactions and oxidative stress, decreasing blood glucose and blood lipids, and improving renal function indices. However, more RCTs are still needed in the future to further demonstrate the effect of HSYA on biomarkers of oxidative stress and inflammatory reactions in patients with DKD due to the low quality and small sample size of the literature included in this study. Systematic Review Registration: PROSPERO: CRD 42021235689.

Self-Assembly Catalase Nanocomplex Conveyed by Bacterial Vesicles for Oxygenated Photodynamic Therapy and Tumor Immunotherapy.

Background: Photodynamic therapy (PDT) is an effective therapeutic modality that has been extensively studied in treatment of various cancers. However, issues with inadequate oxygen (O2) concentration in tumor tissue and inadequate immune response generation have hindered its successful application in tumor therapy. Methods: Firstly, the self-assembly nanocomplex (CAT-Ce6), which is composed of hydrophilic catalase and hydrophobic photosensitizer Chlorin e6 (Ce6), was fabricated to support oxygenated PDT. Secondly, for supplying PDT with enhanced antitumoral immunity, CAT-Ce6 was coated with PD-L1 antibody modified-attenuated Salmonella outer membrane vesicles (OMV-aPDL1). Finally, the catalytic activity, tumor targeting, hypoxia ameliorating, immune effect initiating and anti-tumor capacities of the integral nanosystem CAT-Ce6@OMV-aPDL1 were evaluated systematically. Results: The self-assembly nanocomplex (CAT-Ce6) generated sufficient O2 and promoted the solubility of Ce6 simultaneously, which enhanced PDT significantly. OMV-aPDL1 inherited most of the immunogenic membrane-associated components from the parent bacteria, possessing immunomodulation ability for immunosuppressive tumor microenvironment reprogramming and reducing immune escape. The obtained nanosystem CAT-Ce6@OMV-aPDL1 durably relieved hypoxia, resulting in amplifying PDT-mediated cytotoxicity to generate a pool of tumor-associated antigens, stimulating anti-tumor immune responses and even inducing an immune memory effect, which inhibited tumor development efficiently. Conclusion: The resultant CAT-Ce6@OMV-aPDL1 displays excellent efficacy of PDT and immunotherapy to achieve antitumor effects, which provides a new avenue for combinatorial therapy against various cancers.

Effects of diet on obesity-related anthropometric characteristics in adults: a protocol for an umbrella review of meta-analyses of randomised controlled trials.

INTRODUCTION: There have been many meta-analyses of randomised controlled trials on the influence of different diets on obesity-related anthropometric characteristics in adults. However, whether diet interventions can effectively decrease obesity-related anthropometric characteristics remains unclear. The objective of this study is to summarise and synthesise the evidence on the effects of diet on obesity-related anthropometric characteristics in adults by an umbrella review of meta-analyses of randomised controlled trials. METHODS AND ANALYSIS: We will first retrieve English articles only published before 15 December 2021 by searching PubMed, Embase and Web of Science. Only articles that are meta-analyses of randomised controlled trials will be included. Three researchers will independently screen the titles and abstracts of retrieved articles and check the data extracted from each eligible meta-analysis. In each meta-analysis, we will consider calculating the effect size of the mean difference of the effect of each diet on obesity-related anthropometric characteristics in adults using a random-effect model or a fixed-effect model according to heterogeneity. Study heterogeneity (Cochrane's Q and I2 statistics) and small-study effects (Egger's test or Begg's test) will be considered. Evidence of each effect size will be graded according to the NutriGrade scoring system. We will use AMSTAR-2 (A Measurement Tool to Assess Systematic Reviews V.2) to assess the methodological quality of each meta-analysis. ETHICS AND DISSEMINATION: This umbrella review will provide information on the effects of different diets on obesity-related anthropometric characteristics in adults. Ethical approval is not necessary for this study. We will publish the completed umbrella review and related data online. PROSPERO REGISTRATION NUMBER: CRD42021232826.

Effects of lanthanum nitrate on behavioral disorder, neuronal damage and gene expression in different developmental stages of Caenorhabditis elegans.

Rare earth elements (REEs) are widely used in the industry, agriculture, biomedicine, aerospace, etc, and have been shown to pose toxic effects on animals, as such, studies focusing on their biomedical properties are gaining wide attention. However, environmental and population health risks of REEs are still not very clear. Also, the REEs damage to the nervous system and related molecular mechanisms needs further research. In this study, the L1 and L4 stages of the model organism Caenorhabditis elegans were used to evaluate the effects and possible neurotoxic mechanism of lanthanum(III) nitrate hexahydrate (La(NO3)3·6H2O). For the L1 and L4 stage worms, the 48-h median lethal concentrations (LC50s) of La(NO3)3·6H2O were 93.163 and 648.0 mg/L respectively. Our results show that La(NO3)3·6H2O induces growth inhibition and defects in behavior such as body length, body width, body bending frequency, head thrashing frequency and pharyngeal pumping frequency at the L1 and L4 stages in C. elegans. The L1 stage is more sensitive to the toxicity of lanthanum than the L4 stage worms. Using transgenic strains (BZ555, EG1285 and NL5901), we found that La(NO3)3·6H2O caused the loss or break of soma and dendrite neurons in L1 and L4 stages; and α-synuclein aggregation in L1 stage, indicating that Lanthanum can cause toxic damage to dopaminergic and GABAergic neurons. Mechanistically, La(NO3)3·6H2O exposure inhibited or activated the neurotransmitter transporters and receptors (glutamate, serotonin and dopamine) in C. elegans, which regulate behavior and movement functions. Furthermore, significant increase in the production of reactive oxygen species (ROS) was found in the L4 stage C. elegans exposed to La(NO3)3·6H2O. Altogether, our data show that exposure to lanthanum can cause neuronal toxic damage and behavioral defects in C. elegans, and provide basic information for understanding the neurotoxic effect mechanism and environmental health risks of rare earth elements.

An atrial fibrillation detection system based on machine learning algorithm with mix-domain features and hardware acceleration.

This paper presents a real-time electrocardiogram (ECG) analysis system that can detect atrial fibrillation (AF) using machine learning algorithms without a cloud server. The system takes advantage of the heterogeneous structure of the Zynq system-on-chip (SoC) to optimize the tasks of local implementation of AF detection. The features extraction is based on multi-domain features including entropy features and RR interval features, which is conducted using the embedded micro controller to generate significant features for AF detection. An AF classifier based on artificial neural network (ANN) algorithm is then implemented in the programmable logic of the SoC for acceleration. The validation of the proposed system is performed by using the real-world ECG data from MIT-BIH database and CPSC 2018 database. The experimental results show an accuracy 93.60% and 97.78% when tested on these two databases respectively. The AF detection performance of the embedded algorithm is majorly identical to that of the PC-based algorithm, indicating a robust performance of hardware implementation of the AF detection.

Enzyme-Loaded Catalytic Macrophage Vesicles with Cascade Amplification of Tumor-Targeting for Oxygenated Photodynamic Therapy.

BACKGROUND: Realizing that the potential of photodynamic therapy (PDT) is hindered by hypoxic microenvironment of tumor section, it is desirable to provide a cascade oxygenation strategy to enhance PDT. METHODS: The hydrophilic catalase protein was covalently linked to the hydrophobic photosensitizer Ce6 to form the nanocomplex Catalase-Ce6 with self-assembly. And the Catalase-Ce6 was loaded in the M1 macrophage vesicles (EVs) with GOX-modified to construct the nanosystem Catalase-Ce6@MEVs. The synergistic effects of PDT induced by Catalase-Ce6@MEVs were evaluated on the subcutaneous MFC tumor model. RESULTS: The construction of Catalase-Ce6 not only solved the insoluble problem of Ce6, but also induced a cascade effects for hydrolyzing glucose and increasing the hydrogen peroxide content, achieving the purpose of oxygenated PDT. Cascade tumor targeting was also realized through the binding between vascular cell adhesion molecule 1 (VCAM-1) of tumor tissue and α4 integrin of EVs and enhanced vascular permeability, triggering by PDT. Besides, in vivo experiments found that the Catalase-Ce6@MEVs presented M2 macrophage polarization effect. CONCLUSION: Catalase-Ce6@MEVs exhibit the cascade targeting ability after laser irradiation and prominent tumor treatment effect in vivo, which may provide new ideas and methods for targeted PDT in clinical practice.

A Immune-Related Signature Associated with TME Can Serve as a Potential Biomarker for Survival and Sorafenib Resistance in Liver Cancer.

OBJECTIVE: Although many curative treatments are being applied in the clinic, a significant number of patients with liver hepatocellular carcinoma (LIHC) suffer from drug resistance. The tumour microenvironment (TME) has been found to be closely associated with resistance, suggesting that identification of predictive biomarkers related to the TME for resistance in LIHC will be very rewarding. However, there has been no study dedicated to identifying a TME-related biomarker that has the potential to predict resistance in LIHC. METHODS: An integrated analysis was conducted based on data of patients with LIHC suffering from drug resistance from the TCGA database and four GEO datasets. Subsequently, we also validated the expression levels of the identified genes in paraffin-embedded LIHC samples by immunohistochemistry. RESULTS: In this study, we developed a robust and acute TME-related signature consisted of five immune-related genes (FABP6, CD4, PRF1, EREG and COLEC10) that could independently predict both the RFS and OS of LIHC patients. Moreover, the TME-related signature was significantly associated with the immune score, immune cytolytic activity (CYT), HLA, interferon (IFN) response and tumour-infiltrating lymphocytes (TILs), and it might influence tumour immunity mainly by affecting B cells, CD8+ T cells and dendritic cells. Furthermore, our analysis also indicated that the TME-related signature was correlated with the immunotherapy response and had an enormous potential to predict sorafenib resistance in LIHC. CONCLUSION: Our findings demonstrated a TME-related signature which can independently predict both the RFS and OS of LIHC patients, highlighting the predictive potential of the signature for immunotherapy response and sorafenib resistance, potentially enabling more precise and personalized sorafenib treatment in LIHC in the future.