1,002 results on '"Zhao, Yinan"'
Search Results
602. The Mutual Regulatory Role of Ferroptosis and Immunotherapy in Anti-tumor Therapy.
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Mao Z, Hu Y, Zhao Y, Zhang X, Guo L, Wang X, Zhang J, and Miao M
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- Humans, Animals, Lipid Peroxidation drug effects, Ferroptosis drug effects, Ferroptosis genetics, Neoplasms immunology, Neoplasms therapy, Neoplasms pathology, Neoplasms drug therapy, Immunotherapy, Tumor Microenvironment immunology, Tumor Microenvironment drug effects
- Abstract
Ferroptosis is a form of cell death that is triggered by the presence of ferrous ions and is characterized by lipid peroxidation induced by these ions. The mechanism exhibits distinct morphological characteristics compared to apoptosis, autophagy, and necrosis. A notable aspect of ferroptosis is its ability to inhibit uncontrolled tumor replication and immortalization, especially in malignant, drug-resistant, and metastatic tumors. Additionally, immunotherapy, a novel therapeutic approach for tumors, has been found to have a reciprocal regulatory relationship with ferroptosis in the context of anti-tumor therapy. A comprehensive analysis of ferroptosis and immunotherapy in tumor therapy is presented in this paper, highlighting the potential for mutual adjuvant effects. Specifically, we discuss the mechanisms underlying ferroptosis and immunotherapy, emphasizing their ability to improve the tumor immune microenvironment and enhance immunotherapeutic effects. Furthermore, we investigate how immunotherapeutic factors may increase the sensitivity of tumor cells to ferroptosis. We aim to provide a prospective view of the promising value of combined ferroptosis and immunotherapy in anticancer therapy by elucidating the mutual regulatory network between each., (© 2024. The Author(s).)
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- 2024
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603. Network pharmacology and experimental validation reveal the mechanisms of sniffing essential oil of Acori Tatarinowii rhizoma in treating olfactory dysfunction.
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Zhao Y, Hu Y, Yang J, Qi Y, Miao J, and Miao M
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Ethnopharmacological Relevance: Acorus tatarinowii Rhizoma, a traditional Chinese medicine known for open the orifices and transform phlegm, is used in the treatment of brain disorders. The essential oil of Acorus tatarinowii Rhizoma (EOAT) has demonstrated neuroprotective properties clinically. However, research into its effect on Olfactory Dysfunction (OD) remains limited., Aim of the Study: This study aimed to investigate the effects and mechanisms of sniffing EOAT on improving olfactory function in a 3-Methylindole (3-MI)-induced OD mouse model., Materials and Methods: The research involved intraperitoneal injection of 3-MI to induce OD in mice. The effects of EOAT treatment were assessed on olfactory function, olfactory bulb (OB) pathology, inflammatory factors, olfactory marker protein (OMP), microglial activation, and related pathway proteins and mRNA., Results: Based on the GC-MS analysis results of EOAT and network pharmacology studies, we predicted 18 targets associated with the treatment of OD. SLC6A3, MAOB, DRD1, and PTGS2 were identified as the core targets of EOAT against OD. Molecular docking and KEGG enrichment results indicated that EOAT may exert anti-inflammatory effects by acting on the core target PTGS2, with its anti-inflammatory mechanism possibly related to the PI3K/Akt signaling pathway. Subsequent animal experiments confirmed that inhalation of EOAT significantly increased the body weight of OD model mice, shortened the foraging time, enhanced the expression of OMP in OB, reduced damage to the OB cells, and improved olfactory function. Meanwhile, EOAT significantly alleviated the inflammatory response in OB of OD model mice, inhibited the activation of microglial cells, and suppressed the expression of PI3K/Akt signaling pathway proteins and mRNA., Conclusion: EOAT inhalation could improve olfactory function in 3-MI-induced OD model. The underlying mechanism may be related to the modulation of the PI3K/Akt signaling pathway., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)
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- 2024
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604. Developing deprotectase biocatalysts for synthesis.
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Kennedy L, Sajjad M, Herrera MA, Szieber P, Rybacka N, Zhao Y, Steven C, Alghamdi Z, Zlatkov I, Hagen J, Lauder C, Rudolfova N, Abramiuk M, Bolimowska K, Joynt D, Lucero A, Ortiz GP, Lilienkampf A, Hulme AN, and Campopiano DJ
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- Amino Acids chemistry, Amino Acids metabolism, Esterases chemistry, Esterases metabolism, Sphingomonas enzymology, Sphingomonas metabolism, Bacillus enzymology, Bacillus metabolism, Biocatalysis
- Abstract
Organic synthesis often requires multiple steps where a functional group (FG) is concealed from reaction by a protecting group (PG). Common PGs include N -carbobenzyloxy (Cbz or Z) of amines and tert -butyloxycarbonyl (O
t Bu) of acids. An essential step is the removal of the PG, but this often requires excess reagents, extensive time and can have low % yield. An overarching goal of biocatalysis is to use "green" or "enzymatic" methods to catalyse chemical transformations. One under-utilised approach is the use of "deprotectase" biocatalysts to selectively remove PGs from various organic substrates. The advantage of this methodology is the exquisite selectivity of the biocatalyst to only act on its target, leaving other FGs and PGs untouched. A number of deprotectase biocatalysts have been reported but they are not commonly used in mainstream synthetic routes. This study describes the construction of a cascade to deprotect doubly-protected amino acids. The well known Bacillus BS2 esterase was used to remove the Ot Bu PG from various amino acid substrates. The more obscure Sphingomonas Cbz-ase (amidohydrolase) was screened with a range of N -Cbz-modified amino acid substrates. We then combined both the BS2 and Cbz-ase together for a 1 pot, 2 step deprotection of the model substrate CBz-L-Phe Ot Bu to produce the free L-Phe. We also provide some insight into the residues involved in substrate recognition and catalysis using docked ligands in the crystal structure of BS2. Similarly, a structural model of the Cbz-ase identifies a potential di-metal binding site and reveals conserved active site residues. This new biocatalytic cascade should be further explored for its application in chemical synthesis.- Published
- 2024
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605. Preparation and exploration of anti-tumor activity of Poria cocos polysaccharide gold nanorods.
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Zhao Y, Nie F, Liu W, He W, and Guo Y
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With the continuous advancement of nanotechnology, the application of gold nanorods (AuNRs) functionalized with polysaccharides in the realm of cancer photothermal therapy is garnering increasing attention. To harness photothermal therapy for cancer treatment, FLP-MPBA-AuNRs were successfully synthesized in this study for the first time, utilizing Poria cocos polysaccharides (FLP), mercaptophenylboronic acid (MPBA), and gold nanorods (AuNRs). FLP-MPBA-AuNRs are a nanomaterial characterized by a unique rod-shaped structure, featuring a long diameter of 29.3 nm and a short diameter of 6.5 nm, which conferred exceptional photothermal stability and remarkable photothermal conversion efficiency. Under near-infrared light irradiation, FLP-MPBA-AuNRs elicited significant photothermal effects, effectively curtailing the proliferation of various cancer cells. Additionally, FLP-MPBA-AuNRs impeded cancer progression by inducing cell apoptosis and releasing reactive oxygen species (ROS). Furthermore, FLP-MPBA-AuNRs suppressed the metastasis and growth of cancer cells in zebrafish models. In summary, FLP-MPBA-AuNRs showcased immense potential in cancer therapy by inhibiting tumor cell growth through photothermal and photodynamic mechanisms., Competing Interests: Declaration of competing interest The authors have no conflicts of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)
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- 2024
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606. The effects of different interruption conditions on mental workload: an experimental study based on multimodal measurements.
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Jin H, Liu L, Luo Z, Meng S, and Zhao Y
- Abstract
Interruptions in the working environment cause extra mental workload for the operators, and this phenomenon has garnered significant research attention. This study designed four interruption conditions based on the perceptual and cognitive perspectives of human information processing, using a 2(perceptual primary task and cognitive primary task)*2(perceptual interruption task and cognitive interruption task) factorial design. Multimodal measurement methods were used to evaluate mental workload in different interruption conditions. The results show that when the primary task and the interruption task are different load types, they generate a higher mental workload than the same load type. It can be attributed to the fact that perceptual tasks and cognitive tasks increase mental workload during switching. In addition, based on the multimodal index data, the prediction model of interruption recovery delay time and the classification model of interruption conditions are established, which provides a basis for rational scheduling of work and preventing mental overload.
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- 2024
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607. Older adults' perceptions and experiences of engaging in web- and mobile-based physical activity interventions: A systematic review and qualitative meta-synthesis.
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Peng R, Chang J, Du Y, Zhang C, Li X, Guo Y, Zhao Y, and Feng H
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- Aged, Humans, Internet, Mobile Applications, Motivation, Qualitative Research, Exercise psychology, Health Promotion methods, Perception
- Abstract
Background: Web- and mobile-based physical activity interventions effectively promote physical and mental health among older adults, but participation and adherence are suboptimal., Methods: This qualitative review used the mega-aggregation approach. Searches were conducted in five databases from the earliest to November 2023. Quality assessment and data extraction used JBI tools. Data synthesis used the COM-B model as a guide., Results: Sixteen sub-themes were identified from the eight studies and categorized into the COM-B model. Sub‑themes were physical and psychological changes, digital skills and knowledge, older adult-friendly design, integration into daily routines, social influence, family engagement and support, health benefits and impairments, accessibility and flexibility, low cost, visibility and interaction, instructions and feedback, personalization and progression, incentives, self-efficacy, visual cues, self-monitoring., Discussion: Web- and mobile-based interventions motivate older adults to engage in physical activity, but modifications are necessary. This includes age-appropriate interfaces and contents, tailored behavioral change techniques, and family engagement., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)
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- 2024
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608. The effect of self-rated health on depressive symptoms in Chinese older adults: The mediating role of social participation and spouse health.
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Zhang C, Zhao Y, Li X, Guo Y, Peng R, Wan X, Zhou Q, Yang J, Wu S, and Feng H
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- Humans, Female, Male, Aged, China, Middle Aged, Surveys and Questionnaires, Aged, 80 and over, East Asian People, Depression psychology, Spouses psychology, Social Participation psychology, Quality of Life psychology, Health Status
- Abstract
This study investigates the relationship between self-rated health, social participation, spouse health, and depressive symptoms in older adults. It also analyzed the moderating effects of gender, drinking, visual function, diet, quality of life, and economic level on the model. We analyzed data from 5119 participants aged 60 and above, from the CLHLS. We used a partial least squares structural equation model to explore the correlation between self-rated health, spouse health, social participation, and depressive symptoms. Self-rated health was significantly correlated with spouse health, social participation, and depressive symptoms (P < 0.001). Social participation (β=-0.034) and spouse health (β=-0.029) were mediators of self-rated health to depressive symptoms. In addition, gender, drinking, visual function, diet, quality of life, and economic level were mediated factors. This study provides evidence that self-rated health has direct or indirect associations with depressive symptoms in older people, with social participation and spouse health playing a crucial mediating role., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)
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- 2024
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609. Molecular mechanism of Chang Shen Hua volatile oil modulating brain cAMP-PKA-CREB pathway to improve depression-like behavior in rats.
- Author
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Zhang S, Hu Y, Zhao Y, Feng Y, Wang X, Miao M, and Miao J
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- Animals, Male, Rats, Acorus chemistry, Antidepressive Agents pharmacology, Behavior, Animal drug effects, Cyclic AMP metabolism, Cyclic AMP Response Element-Binding Protein metabolism, Disease Models, Animal, Molecular Docking Simulation, Rats, Sprague-Dawley, Signal Transduction drug effects, Brain drug effects, Brain metabolism, Depression drug therapy, Drugs, Chinese Herbal pharmacology, Drugs, Chinese Herbal chemistry, Oils, Volatile pharmacology, Oils, Volatile chemistry
- Abstract
Background: Depression is a common and complex mental illness that manifests as persistent episodes of sadness, loss of interest, and decreased energy, which might lead to self-harm and suicide in severe cases. Reportedly, depression affects 3.8 % of the world's population and has been listed as one of the major global public health concerns. In recent years, aromatherapy has been widely used as an alternative and complementary therapy in the prevention and treatment of depression; people can relieve anxiety and depression by sniffing plant aromatic essential oils. Acorus tatarinowii and Panax ginseng essential oils in Chang Shen Hua volatile oil (CSHVO) are derived from Acorus tatarinowii and Panax ginseng, respectively, the main medicines in the famous Chinese medicine prescription Kai Xin San (KXS), Then, these oils are combined with the essential oil of Albizia julibrissin flower to form a new Chinese medicine inhalation preparation, CSHVO. KXS has been widely used in the treatment of depression; however, whether CSHVO can ameliorate depression-like behavior, its pharmacological effects, and the underlying mechanisms of action are yet to be elucidated., Study Design and Methods: A rat model of chronic and unpredictable mild stimulation (CUMS) combined with orphan rearing was treated with CSHVO for 4 weeks. Using behavioral tests (sucrose preference, force swimming, tail suspension, and open field), the depression-like degree was evaluated. Concurrently, brain homogenate and serum biochemistry were analyzed to assess the changes in the neurotransmitters and inflammatory and neurotrophic factors. Furthermore, tissue samples were collected for histological and protein analyses. In addition, network pharmacology and molecular docking analyses of the major active compounds, potential therapeutic targets, and intervention pathways predicted a role of CSHVO in depression relief. Subsequently, these predictions were confirmed by in vitro experiments using a corticosterone (CORT)-induced PC12 cell damage model., Results: CSHVO inhalation can effectively improve the weight and depression-like behavior of depressed rats and regulate the expression of inflammatory factors and neurotransmitters. Hematoxylin-eosin, Nissl, and immunofluorescence staining indicated that compared to the model group, the pathological damage to the brain tissues of rats in the CSHVO groups was improved. The network pharmacological analysis revealed that 144 CSHVO active compounds mediate 71 targets relevant to depression treatment, most of which are rich in the cAMP signaling and inflammatory cytokine pathways. Protein-protein interaction analysis showed that TNF, IL6, and AKT are the core anti-depressive targets of CSHVO. Molecular docking analysis showed an adequate binding between the active ingredients and the key targets. In vitro experiments showed that compared to the model group, the survival rate of PC12 cells induced by CSHVO intervention was increased, the apoptosis rate was decreased, and the expression of inflammatory cytokines in the cell supernatant was improved. Western blot analysis and immunofluorescence staining confirmed that CSHVO regulates PC12 cells in the CORT model through the cAMP-PKA-CREB signaling pathway, and pretreatment with PKA blocker H89 eliminates the protective effect of CSHVO on CORT-induced PC12 cells., Conclusions: CSHVO improves CORT-induced injury in the PC12 cell model and CUMS combined with orphan rearing-induced depression model in rats. The antidepressant mechanism of CSHVO is associated with the modulation of the cAMP-PKA-CREB signaling pathway., Competing Interests: Declaration of competing interest The authors declare no competing interests associated with this study., (Copyright © 2024. Published by Elsevier GmbH.)
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- 2024
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610. Prevalence and Burden of Multiple Sclerosis in China, 1990-2019: Findings From the Global Burden of Disease Study 2019.
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Zhang C, Liu W, Wang L, Wang F, Li J, Liu Z, Zhao Y, Zhou M, Yin P, and Hao J
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- Humans, China epidemiology, Prevalence, Male, Adult, Female, Middle Aged, Young Adult, Disability-Adjusted Life Years, Aged, Adolescent, Quality-Adjusted Life Years, Cost of Illness, Multiple Sclerosis epidemiology, Global Burden of Disease
- Abstract
Background and Objectives: Multiple sclerosis (MS) is the leading cause of neurologic disability in young adults, but the burden caused by MS in China is lacking. We aimed to comprehensively describe the prevalence and health loss due to MS by demographic and geographical variables from 1990 to 2019 across China., Methods: Data were obtained from the Global Burden of Diseases, Injuries, and Risk Factors Study 2019 (GBD 2019). We used GBD methodology to systematically analyze the prevalence, disability-adjusted life-years (DALYs), years of life lost (YLLs), and years lived with disability (YLDs) due to MS by age, sex, and location from 1990 to 2019 in mainland China and its provinces. We also compared the MS burden in China with the world and other Group of 20 (G20) countries., Results: In 2019, 42,571 (95% uncertainty interval [UI] 33,001-53,329) individuals in China had MS, which doubled from 1990. The age-standardized prevalence rate of MS was 2.32 per 100,000 (95% UI 1.78-2.91), which increased by 23.31% (95% UI 20.50-25.89) from 1990, with most of the growth occurring after 2010. There was a positive latitudinal gradient with the increasing prevalence from south to north across China. The total DALYs caused by MS were 71,439 (95% UI 58,360-92,254) in 2019, ranking China third among G20 countries. Most of the MS burden in China derived from premature mortality, with the higher fraction of YLLs than that at the global level and most other G20 countries. From 1990 to 2019, the age-standardized DALY and YLL rate had nonsignificant changes; however, the age-standardized YLD rate substantially increased by 23.33% (95% UI 20.50-25.89). The geographic distribution of MS burden varied at the provincial level in China, with a slight downward trend in the age-standardized DALY rates along with increasing Socio-Demographic Index over the study period., Discussion: Although China has a low risk of MS, the substantial and increasing prevalent cases should not be underestimated. The high burden due to premature death and geographic disparity of MS burden reveals insufficient management of MS in China, highlighting the needs for increased awareness and effective intervention.
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- 2024
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611. The Inhibition Mechanisms of Three Structurally Different Salvianolic Acids on the Non-Enzymatic Glycation of Bovine Serum Albumin.
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Feng G, Yan Y, Wang M, Gao Z, Zhao Y, and Peng X
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- Glycosylation drug effects, Alkenes pharmacology, Alkenes chemistry, Animals, Glycation End Products, Advanced chemistry, Glycation End Products, Advanced metabolism, Cattle, Molecular Docking Simulation, Depsides, Serum Albumin, Bovine chemistry, Caffeic Acids pharmacology, Caffeic Acids chemistry, Polyphenols pharmacology, Polyphenols chemistry, Benzofurans pharmacology, Benzofurans chemistry, Lactates pharmacology, Lactates chemistry
- Abstract
The antiglycation mechanisms of three structurally different salvianolic acids (Sals) including salvianolic acid A (Sal-A), salvianolic acid B (Sal-B) and salvianolic acid C (Sal-C) were investigated using the bovine serum albumin (BSA)-fructose model. The results showed that the three compounds could inhibit the formation of glycation products, maintain protein structural stability, mitigate the development of amyloid fibrils and scavenge radicals. Notably, Sal-A possessed the highest anti-glycated activity compared with Sal-B and Sal-C. This may be related to the fact that Sal-A contained the most molecules of caffeic acid (Sal-A, Sal-B, and Sal-C possessing two, one, and zero caffeic acid units, respectively), and caffeic acid played a leading role in the antiglycation properties relative to Danshensu. Moreover, these compounds quenched the intrinsic fluorescence intensity of BSA in a static mode, with the binding constants in the order of Sal-A > Sal-B > Sal-C. Obviously, Sal-A possessed the strongest binding affinity among these compounds, which may be one of the reasons why it exhibited the optimal antiglycation capability. Furthermore, molecular docking demonstrated that the three Sals exerted protective effects on BSA by preventing glycation modification of lysine and arginine residues. These findings would provide valuable insights into the potential application of Sals for alleviating non-enzymatic glycation of protein., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)
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- 2024
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612. Effects of Momordica charantia L. supplementation on glycemic control and lipid profile in type 2 diabetes mellitus patients: A systematic review and meta-analysis of randomized controlled trials.
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Zhang X, Zhao Y, Song Y, and Miao M
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Background and Aims: Momordica charantia L. ( M. charantia ) has been traditionally utilized as a medicinal intervention for managing type 2 diabetes mellitus (T2DM). The current study was designed to offer a GRADE-assessed systematic review and meta-analysis of randomized controlled trials (RCTs) examining the impact of M. Charantia intake on glycemic indexes and the lipid profile of patients with T2DM., Methods: A comprehensive search was conducted across several databases, including PubMed, EMBASE, Web of Science, and Cochrane Library, from the inception of each database until April 22, 2023. The Hartung-Knapp adjustment was applied to ensure conservative summary estimates with broad confidence intervals., Results: A total of eight trials involving 423 patients with T2DM were included in this study. Compared to the control group, the intake of M. charantia supplementation resulted in significant reductions in fasting blood glucose (FBG) (WMD: -0.85 mmol/L; 95%CI: -1.44, -0.26; p = 0.005; I
2 = 73.4 %), postprandial glucose (PPG) (WMD: -2.28 mmol/L; 95%CI: -3.35, -1.21; p = 0.000; I2 = 66.9 %), glycosylated hemoglobin A1c (HbA1c) (WMD: -0.38 %; 95%CI: -0.53, -0.23; p = 0.000; I2 = 37.6 %), and total cholesterol (TC) (WMD: -0.38 mmol/L; 95%CI: -0.70, -0.07; p = 0.017; I2 = 63.6 %). These results remained statistically significant even after applying the Hartung-Knapp adjustment. However, no significant differences were observed in terms of triglyceride (TG), high-density lipoprotein (HDL), and low-density lipoprotein (LDL)., Conclusions: The findings of this study suggest that M. charantia could serve as a potential alternative for individuals with T2DM, particularly those with elevated total cholesterol levels. However, further high-quality studies are necessary to validate these results., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)- Published
- 2024
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613. An arabinose-rich heteropolysaccharide isolated from Belamcanda chinensis (L.) DC treats liver cancer by targeting FAK and activating CD40.
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Zhao Y, Hou J, Liu Y, Xu J, and Guo Y
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- Animals, Carbohydrate Sequence, Zebrafish, Polysaccharides pharmacology, Polysaccharides therapeutic use, Polysaccharides chemistry, Arabinose, Liver Neoplasms drug therapy
- Abstract
An undisclosed polysaccharide, BCP80-2, was isolated from Belamcanda chinensis (L.) DC. Structural investigation revealed that BCP80-2 consists of ten monosaccharide residues including t-α-Araf-(1→, →3,5)-α-Araf-(1→, →5)-α-Araf-(1→, →4)-β-Xylp-(1→, →3)-α-Rhap-(1→, →4)-β-Manp-(1→, t-β-Glcp-(1→, →6)-α-Glcp-(1→, t-β-Galp-(1→, and→3)-α-Galp-(1→. In vivo activity assays showed that BCP80-2 significantly suppressed neoplasmic growth, metastasis, and angiogenesis in zebrafish. Mechanistic studies have shown that BCP80-2 inhibited cell migration of HepG2 cells by suppressing the FAK signaling pathway. Moreover, BCP80-2 also activated immunomodulation and upregulated the secretion of co-stimulatory molecules CD40, CD86, CD80, and MHC-II. In conclusion, BCP80-2 inhibited tumor progression by targeting the FAK signaling pathway and activating CD40-induced adaptive immunity., Competing Interests: Declaration of competing interest Each author has completed the corresponding work, and there is no conflict of interest between the authors., (Copyright © 2024 Elsevier Ltd. All rights reserved.)
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- 2024
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614. Sucrose ester embedded lipid carrier for DNA delivery.
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Zhao Y, Ma W, Tian K, Wang Z, Fu X, Zuo Q, Qi Y, and Zhang S
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- DNA metabolism, Sucrose chemistry, Lipids chemistry, Liposomes chemistry, Esters chemistry
- Abstract
Sucrose esters (SEs) have great potential in the field of nucleic acid delivery due to their unique physical and chemical properties and good biosafety. However, the mechanism of the effect of SEs structure on delivery efficiency has not been studied. The liposomes containing peptide lipids and SEs were constructed, and the effects of SEs on the interaction between the liposomes and DNA were studied. The addition of SEs affects the binding rate of liposomes to DNA, and the binding rate gradually decreases with the increase of SEs' carbon chain length. SEs also affect the binding site and affinity of liposomes to DNA, promoting the aggregation of lipids to form liposomes, where DNA wraps around or compresses inside the liposomes, allowing it to compress DNA without damaging the DNA structure. COL-6, which is composed of sucrose laurate, exhibits the optimal affinity for DNA, and SE promotes the formation of ordered membrane structure and enhances membrane stability, so that COL-6 exhibits a balance between rigidity and flexibility, and thus exhibits the highest delivery efficiency of DNA among these formulations. This work provides theoretical foundations for the application of SE in gene delivery and guides for the rational design of delivery systems., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)
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- 2024
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615. Treatment algorithms of relapsing multiple sclerosis: an exploration based on the available disease-modifying therapies in China.
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Guo J, Wu J, Wang L, Liu H, Wu X, Yang H, Li W, Wang H, Bu B, Yang C, Zhou H, Guo S, Zhao Y, Wang Z, Li C, Tian DC, Chen S, Xue H, Zhang Y, Xu Y, Liang H, Wu Z, Zhang Y, Dong Q, Wang J, and Quan C
- Abstract
Multiple sclerosis (MS) was defined as a rare disease in China due to its low prevalence. For a long time, interferon β was the only approved disease-modifying therapy (DMT). Since the first oral DMT was approved in 2018, DMT approval accelerated, and seven DMTs were approved within 5 years. With an increasing number of DMTs being prescribed in clinical practice, it is necessary to discuss the standardized MS treatment algorithms depending on the disease activity and DMT availability. In this review paper, more than 20 Chinese experts in MS have reviewed the therapeutic progress of MS in China and worldwide and discussed algorithms for treating relapsing MS (RMS) based on the available DMTs in China, providing insights for establishing the standardized RMS treatment algorithms in this country., (© The Author(s), 2024.)
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- 2024
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616. Enhancing OFDM with index modulation using heuristic geometric constellation shaping and generalized interleaving for underwater VLC.
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Zhao Y, Chen C, Zhong X, Cao H, Liu M, Lin B, and Savović S
- Abstract
In this paper, we propose and demonstrate enhanced orthogonal frequency division multiplexing with index modulation (OFDM-IM) schemes for bandlimited underwater visible light communication (UVLC) systems via geometric constellation shaping (GCS) and subblock interleaving. Specifically, two heuristic GCS approaches based on particle swarm optimization (PSO) and hybrid genetic algorithm-PSO (GA-PSO) algorithms are proposed to generate IM-preferable constellations. Moreover, a generalized interleaving technique is further proposed to overcome the low-pass effect of bandlimited UVLC systems, where an optimal step size can be obtained to perform subblock interleaving. Simulation and experiments are conducted to evaluate the performance of the proposed enhanced OFDM-IM schemes in bandlimited UVLC systems, where both OFDM with single-mode index modulation (OFDM-SM) and OFDM with dual-mode index modulation (OFDM-DM) schemes are considered. The experimental results demonstrate remarkable signal-to-noise ratio (SNR) gains of 1.3 and 1.9 dB for OFDM-SM and OFDM-DM in comparison to the benchmark schemes, respectively.
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- 2024
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617. Trajectories of depressive symptom and its association with air pollution: evidence from the Mr. OS and Ms. OS Hong Kong cohort study.
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Zhao Y, Liu Q, Chen Y, Kwok TCY, Leung JCS, Feng H, and Wong SYS
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- Aged, Female, Humans, Cohort Studies, Hong Kong epidemiology, Longitudinal Studies, Quality of Life, Male, Air Pollution adverse effects, Depression diagnosis, Depression epidemiology, Depression psychology, East Asian People
- Abstract
Background: Depression is a global health priority. Maintaining and delaying depressive symptoms in older adults is a key to healthy aging. This study aimed to identify depressive symptom trajectories, predictors and mortality, while also exploring the relationship between air quality and depressive symptoms in older adults in the Hong Kong community over 14 years., Methods: This study is a longitudinal study in Hong Kong. The target population was community-dwelling older adults over age 65. Depressive symptoms were measured by the Geriatric Depression Scale (GDS-15). Group-based trajectory model was used to identify heterogeneity in longitudinal changes over 14 years and examine the associations between baseline variables and trajectories for different cohort members using multinomial logistic regression. The Kaplan-Meier method was employed to conduct survival analysis and explore the variations in survival probabilities over time among different trajectory group. Linear mixed model was used to explore the relationship between air quality and depressive symptoms., Results: A total of 2828 older adults were included. Three different trajectories of depressive symptoms in older people were identified: relatively stable (15.4%), late increase (67.1%) and increase (17.5%). Female, more number of chronic diseases, poor cognitive function, and poor health-related quality of life (HRQOL) were significantly associated with other less favorable trajectories compared with participants with stable levels of depressive symptoms. The late increase group had a lower mortality rate than the relatively stable and increased groups. Lower baseline ambient air pollutant exposure to NO
2 over 14 years was significantly associated with fewer depressive symptoms., Conclusions: In this study, we found that a late increase in depressive symptoms was the predominant trend in older Chinese people in Hong Kong. Poorer HRQOL was predictive of less favorable trajectories of depressive symptoms. Ambient air pollution was associated with depressive symptoms. This novel observation strengthens the epidemiological evidence of longitudinal changes in depressive symptoms and associations with late-life exposure to air pollution., (© 2024. The Author(s).)- Published
- 2024
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618. Evaluation of the Correlation Between Distribution Location and Vulnerability of Carotid Plaque in Patients with Transient Ischemic Attack.
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Zhao Y, Gu Y, Liu Y, and Guo Z
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- Humans, Retrospective Studies, Carotid Arteries diagnostic imaging, Plaque, Atherosclerotic complications, Ischemic Attack, Transient diagnostic imaging, Ischemic Attack, Transient epidemiology, Ischemic Attack, Transient etiology, Carotid Artery Diseases diagnostic imaging, Carotid Stenosis complications, Carotid Stenosis diagnostic imaging
- Abstract
Purpose: To analyze the relationship among distribution location, characteristics, and vulnerability of carotid plaque using CTA and provide more information on the risk factors of carotid atherosclerotic plaque., Patients and Methods: We retrospectively analyzed the CTA images of the head and neck of 93 patients with carotid atherosclerosis. Atherosclerosis was developed in 148 carotid arteries. The plaques were divided into a high-risk plaque group and a low-risk plaque group according to whether the plaques had high-risk characteristics. The maximum cross-sectional area of carotid artery bifurcation plaque on the axial image was selected, and the cross-sectional lumen was equally divided into four 90-degree sectors, ventral side wall, dorsal side wall, inner side wall, and outer side wall. The differences in the characteristics and distribution locations of the plaques in the two groups were analyzed. The characteristic parameters of the cross-sectional plaques at the bifurcation of the carotid artery. The logistic regression analysis was used to further analyze the risk factors associated with plaque vulnerability., Results: Among 148 carotid arteries,80 were classified as high-risk and 68 as low-risk groups. There were significant differences between the two groups concerning the thickness, length, maximum cross-sectional area, burden, and cross-sectional distribution of the plaques (P < 0.05). The plaque distribution on the dorsal side wall of the carotid bifurcation was higher in the high-risk group than that in the low-risk group (P < 0.05), dorsal side wall plaque-independent risk factors for the development of vulnerability of plaques in transient ischemic attack (TIA) patients (95% CI:1.522~6.991, P<0.05)., Conclusion: High-risk plaques tend to occur on the dorsal side wall of the carotid bifurcation, whereas low-risk plaques tend to occur on the outer side wall of the carotid bifurcation., Competing Interests: The authors report no conflicts of interest in this work., (© 2024 Zhao et al.)
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- 2024
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619. Pericarotid Fat Stranding at Computed Tomography Angiography: A Marker of the Short-Term Prognosis of Acute Ischemic Stroke.
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Liu Y, Zhao Y, Guo Z, Li M, Shan H, Zhang Y, Miao C, and Gu Y
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- Male, Humans, Middle Aged, Aged, Aged, 80 and over, Computed Tomography Angiography methods, Retrospective Studies, Tomography, X-Ray Computed methods, Prognosis, Angiography, Infarction, Adipose Tissue diagnostic imaging, Adipose Tissue pathology, Cerebral Angiography, Ischemic Stroke, Stroke complications
- Abstract
Purpose: Perivascular epicardial fat stranding detected in the coronary computed tomography (CT) angiography is associated with culprit lesions and provides helpful information on the risk of acute coronary syndrome. This study aimed to evaluate the potential clinical significance of pericarotid fat stranding (PCFS) and investigate the association between PCFS and short-term prognosis in acute stroke using head and neck CT angiography (CTA)., Methods: This study included 80 patients (mean age, 69.69 ± 11.03; 58 men) who underwent both head and neck CTA and magnetic resonance imaging within a 1-week period. Baseline characteristics, pericarotid adipose tissue attenuation, plaque characteristics, ischemic penumbra, infarct core volume, infarct core growth rate (CGR), and the grade of collateral status were recorded and compared between a PCFS group and a non-PCFS group. Data were compared using the 2-sample t test, Mann-Whitney U test, Fisher exact test, and Spearman rank correlation analysis., Results: We found that patients with PCFS had a significantly higher pericarotid adipose tissue density than patients without PCFS (-55.75 ± 5.53 vs -65.82 ± 9.65, P < 0.001). Patients with PCFS showed a larger infarct core volume (166.43 ± 73.07 vs 91.43 ± 55.03, P = 0.001) and faster CGR (39.57 ± 12.01 vs 19.83 ± 32.77; P < 0.001), and the frequency of adverse prognosis was more significant than in control participants (83.33% vs 19.11%)., Conclusions: Individuals with PCFS showed higher CGR, which was substantially related to worse outcomes in patients with acute stroke with ipsilateral carotid atherosclerosis. Recognition of PCFS may help predict stroke prognosis and allow doctors to take early action to improve patient prognosis., Competing Interests: The authors declare no conflict of interest., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.)
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- 2024
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620. A novel predictive model based on pericarotid adipose tissue and lumen stenosis for stroke risk in patients with asymptomatic carotid stenosis.
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Liu Y, Zhao Y, Guo Z, Zhang Y, Miao C, and Gu Y
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- Humans, Constriction, Pathologic, Retrospective Studies, Adipose Tissue diagnostic imaging, Carotid Stenosis complications, Carotid Stenosis diagnostic imaging, Ischemic Stroke, Stroke diagnostic imaging, Plaque, Atherosclerotic
- Abstract
The study aimed to investigate the predictive value of clinical characteristics, major computed tomography angiography (CTA) indexes of carotid AS (carotid lumen stenosis and plaque burden), and inflammatory pericarotid adipose tissue for acute stroke risk in patients with a moderate or higher degree of carotid stenosis. In all, 119 patients with unilateral carotid stenosis who underwent head and neck computed tomography angiography were included and assigned to the stroke group or non-stroke group according to magnetic resonance imaging. Pericarotid adipose tissue attenuation value, net enhancement value in the base phase and the enhancement phase, and atherosclerotic features (plaque burden and lumen stenosis) were recorded. Multivariate logistic regression analysis and the operating characteristic curve (ROC) were performed to establish a predictive model for the presence of acute ischemic stroke. ROC analysis showed that pericarotid adipose tissue attenuation value and lumen stenosis were predictive factors for stroke. The AUC of pericarotid adipose tissue attenuation (PCAT) attenuation, lumen stenosis, the novel prediction model independently constructed based on PCAT attenuation, and lumen stenosis resulted in 0.838 (95% CI 0.759-0.899), 0.700 (95% CI 0.826-0.944), and 0.942 (95% CI 0.884-0.977), respectively. The model had a sensitivity and specificity of 0.909 and 0.893, respectively, when the cutoff value was 0.388. We found that the risk model combining pericarotid adipose tissue attenuation value and lumen stenosis has significant predictive values for the presence of symptomatic stroke among patients with a moderate or higher degree of carotid stenosis., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
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- 2024
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621. Intrinsic capacity trajectories, predictors and associations with care dependence in community-dwelling older adults: A social determinant of health perspective.
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Zhao Y, Chen Y, Xiao LD, Liu Q, Nan J, Li X, and Feng H
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- Humans, Aged, Cohort Studies, Longitudinal Studies, Retrospective Studies, Independent Living, Social Determinants of Health
- Abstract
Aims: To identify intrinsic capacity trajectories, predictors of intrinsic capacity trajectories and associations between intrinsic capacity trajectories and care dependence in community-dwelling older adults in China., Methods: A retrospective longitudinal study was conducted, and the data were obtained from a five-year national longitudinal cohort study of older adults in China between 2011 and 2015. The social determinants of health framework informed the data analysis and interpretation., Results: A total of 3893 older adults met the selection criteria and were included in the study. Three intrinsic capacity trajectories were identified: high trajectory (15.7 %), stable trajectory (52.7 %) and declining trajectory (31.6 %). Social determinants contribute to intrinsic capacity decline in older adults. Decreased cognitive function, psychological status, and locomotion at baseline were associated with care dependence., Conclusion: Approximately thirty percent of the older adults in this cohort study experienced a decline in intrinsic capacity within a 5-year period. Social determinants contributed to this decline in older adults., Competing Interests: Declaration of competing interest On behalf of all the authors, I declare that all authors have contributed to the work, we all agree with the findings presented, and that the work has not been published before nor is being considered for publication in another journal. There is no interest conflict in this study., (Copyright © 2023. Published by Elsevier Inc.)
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- 2024
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622. Effect of ticagrelor versus clopidogrel after implantation of drug-eluting stents guided by either intravascular ultrasound or angiography in patients with acute coronary syndrome-propensity score matching analysis.
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Zhao Y, Yang Y, Guo L, Shen D, Dong Z, Lin Y, Liu H, Wei Y, and Zhang B
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- Humans, Clopidogrel adverse effects, Coronary Angiography adverse effects, Platelet Aggregation Inhibitors adverse effects, Propensity Score, Ticagrelor adverse effects, Treatment Outcome, Ultrasonography, Interventional adverse effects, Acute Coronary Syndrome diagnostic imaging, Acute Coronary Syndrome therapy, Acute Coronary Syndrome etiology, Drug-Eluting Stents adverse effects, Percutaneous Coronary Intervention adverse effects, Percutaneous Coronary Intervention methods, Thrombosis etiology
- Abstract
Background: The effect of different dual antiplatelet therapies on thrombotic events on the background of intravascular ultrasound (IVUS) guidance is unclear. We investigated whether ticagrelor can provide any additional benefit to clopidogrel in reducing thrombotic events in acute coronary syndrome (ACS) treated with drug- eluting stent (DES), when guided by IVUS or not., Methods: A total of 5,666 ACS patients who underwent DES implantation and who were discharged on dual antiplatelet therapy were enrolled and grouped according to the use of IVUS or not. Each group was subdivided into two subgroups according to the type of P2Y12 inhibitor used after discharge. Propensity score matching (PSM) was used between the IVUS and no-IVUS groups. Covariate adjustment of Cox proportional hazards model was used between the ticagrelor and clopidogrel groups. Thrombotic event at 12 months was compared in groups separately., Results: After PSM, 12-month follow-up data were available for 1,174 patients. Major adverse cardiac events (MACE) were less frequent in the IVUS-guided group (2.2% vs. 4.3%, P = 0.081) with a trend toward statistical significance. Comparison of antiplatelet regimens revealed significantly fewer major adverse cardiac and cerebrovascular events (MACCE) with ticagrelor in the entire PSM cohort and angiography-guided subgroup (2.9% vs. 5.7%, P = 0.035; 3.1% vs. 6.4%, P = 0.020, respectively). Among patients in the IVUS-guided group the outcome was comparable (2.5% vs. 4.4%, P = 0.312). Ticagrelor was associated with increasing bleeding incidence in the entire PSM cohort (1.3% vs. 3.3%, P = 0.030), mainly due to Bleeding Academic Research Consortium type 2 bleeding (0.7% vs. 2.6%, P = 0.010). The results were consistent after covariate adjustment of Cox proportional hazards model., Conclusion: The comparison of ischemic benefit between ticagrelor and clopidogrel was similar in patients receiving IVUS guidance during stent implantation, probably due to the precise implantation of IVUS. Multicenter, randomized studies should be performed to validate this conclusion., (© 2023. The Author(s).)
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- 2024
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623. Dual-mode spatial index modulation for MIMO-OWC.
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Zhong X, Chen C, Zhao Y, Liu M, He C, and Haas H
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In this Letter, we propose and demonstrate a dual-mode spatial index modulation (DM-SIM) scheme for spectral efficiency enhancement of band-limited multiple-input multiple-output optical wireless communication (MIMO-OWC) systems. By performing dual-mode index modulation in the spatial domain, DM-SIM can transmit both spatial and constellation symbols. Since constellation design plays a vital role in the proposed DM-SIM scheme, we further propose three dual-mode constellation design approaches including phase rotation, amplitude scaling and joint phase rotation and amplitude scaling. Moreover, we also designed a differential log-likelihood ratio (LLR) detector for the proposed DM-SIM scheme. Experimental results show that the joint phase rotation and amplitude scaling approach can achieve a remarkable 3.2 dB signal-to-noise ratio (SNR) gain compared with the phase rotation approach in a 2×2 MIMO-OWC system applying DM-SIM.
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- 2024
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624. Bidirectional associations between hearing difficulty and cognitive function in Chinese adults: a longitudinal study.
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Li X, Hu M, Zhao Y, Peng R, Guo Y, Zhang C, Huang J, Feng H, and Sun M
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Background: Middle-aged and older adults frequently experience hearing loss and a decline in cognitive function. Although an association between hearing difficulty and cognitive function has been demonstrated, its temporal sequence remains unclear. Therefore, we investigated whether there are bidirectional relationships between hearing difficulty and cognitive function and explored the mediating role of depressive symptoms in this relationship., Method: We used the cross-lagged panel model and the random-intercept cross-lagged panel model to look for any possible two-way link between self-reported hearing difficulty and cognitive function. To investigate depressive symptoms' role in this association, a mediation analysis was conducted. The sample was made up of 4,363 adults aged 45 and above from the China Health and Retirement Longitudinal Study (CHARLS; 2011-2018; 44.83% were women; mean age was 56.16 years). One question was used to determine whether someone had a hearing impairment. The tests of cognitive function included episodic memory and intelligence. The Center for Epidemiologic Studies Depression Scale, which consists of 10 items, was used to measure depressive symptoms., Results: A bidirectional association between hearing and cognition was observed, with cognition predominating (Wald χ 2 (1) = 7.241, p < 0.01). At the between-person level, after controlling for potential confounders, worse hearing in 2011 predicted worse cognitive function in 2013 ( β = -0.039, p < 0.01) and vice versa ( β = -0.041, p < 0.01) at the between-person level. Additionally, there was no corresponding cross-lagged effect of cognitive function on hearing difficulty; rather, the more hearing difficulty, the greater the cognitive decline at the within-person level. According to the cross-lagged mediation model, depressive symptoms partially mediates the impact of cognitive function on subsequent hearing difficulty (indirect effect: -0.003, bootstrap 95% confidence interval: -0.005, -0.001, p < 0.05), but not the other way around., Conclusion: These results showed that within-person relationships between hearing impairment and cognitive function were unidirectional, while between-person relationships were reciprocal. Setting mental health first may be able to break the vicious cycle that relates hearing loss to cognitive decline. Comprehensive long-term care requires services that address depressive symptoms and cognitive decline to be integrated with the hearing management., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Li, Hu, Zhao, Peng, Guo, Zhang, Huang, Feng and Sun.)
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- 2023
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625. Improved Frequency Domain Turbo Equalization with Expectation Propagation Interference Cancellation in Underwater Acoustic Communications.
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Jiang B, Tang Y, Zhao Y, Bao J, Liu C, and Tang X
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This paper proposes an improved frequency domain turbo equalization (IFDTE) with iterative channel estimation and feedback to achieve both a good performance and low complexity in underwater acoustic communications (UWACs). A selective zero-attracting (SZA) improved proportionate normal least mean square (SZA-IPNLMS) algorithm is adopted by utilizing the sparsity of the UWAC channel to estimate it using a training sequence. Simultaneously, a set-membership (SM) SZA differential IPNLMS (SM SZA-DIPNLMS) with variable step size is adopted to estimate the channel status information (CSI) in the iterative channel estimation with soft feedback. In this way, the computational complexity for iterative channel estimation is reduced effectively with minimal performance loss. Different from traditional schemes in UWACs, an IFDTE with expectation propagation (EP) interference cancellation is adopted to estimate the a posteriori probability of transmitted symbols iteratively. A bidirectional IFDTE with the EP interference cancellation is proposed to further accelerate the convergence. THe simulation results show that the proposed channel estimation obtains 1.9 and 0.5 dB performance gains, when compared with those of the IPNLMS and the l0-IPNLMS at a bit error rate (BER) of 10-3. The proposed channel estimation also effectively reduces the unnecessary updating of the coefficients of the UWAC channel. Compared with traditional time-domain turbo equalization and FDTE in UWACs, the IFDTE obtains 0.5 and 1 dB gains in the environment of SPACE'08 and it obtains 0.5 and 0.4 dB gains in the environment of MACE'04 at a BER of 10-3. Therefore, the proposed scheme obtains a good BER performance and low complexity and it is suitable for efficient use in UWACs.
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- 2023
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626. Dual functionalized hyaluronic acid micelles loading paclitaxel for the therapy of breast cancer.
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Liu Z, Chen X, Jin Q, Li M, Zhu S, Zhang Y, Zhi D, Zhao Y, Li L, and Zhang S
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Although many carriers for the delivery of chemotherapeutic drugs have been investigated, the disadvantages of passive targeting and uncontrolled drug release limit their utility. Herein, hyaluronic acid (HA) was hydrophobically modified to serve as a carrier for binding to cluster determinant 44 (CD44) overexpressed on tumor cell surfaces. Specifically, after deacetylation, HA was grafted to dodecylamine or tetradecylamine to afford amphiphilic zwitterionic polymer micelles, designated dHAD and dHAT, respectively, for the delivery of paclitaxel (PTX). The micelles were negatively charged at pH 7.4 and positively charged at pH 5.6, and this pH sensitivity facilitated PTX release under acidic conditions. The cell uptake efficiencies of the dHAD-PTX and dHAT-PTX micelles by MCF-7 cells after 4 h of incubation were 96.9% and 95.4%, respectively, and their affinities for CD44 were twice that of HA. Furthermore, the micelles markedly inhibited tumor growth both in vitro and in vivo , with IC
50 values of 1.943 μg/mL for dHAD-PTX and 1.874 μg/mL for dHAT-PTX for MCF-7 cells; the tumor inhibition rate of dHAD-PTX (92.96%) was higher than that of dHAT-PTX (78.65%). Importantly, dHAD and dHAT micelles showed negligible systemic toxicity. Our findings suggest that these micelles are promising delivery vehicles for antitumor drugs., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Liu, Chen, Jin, Li, Zhu, Zhang, Zhi, Zhao, Li and Zhang.)- Published
- 2023
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627. Multisectoral drivers of decarbonizing battery electric vehicles in China.
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Wang F, Zhang S, Zhao Y, Ma Y, Zhang Y, Hove A, and Wu Y
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China has made great progress in the electrification of passenger cars, and the sales of battery electric vehicles (BEVs) have exceeded 10%. We applied a life-cycle assessment (LCA) method to estimate the carbon dioxide (CO
2 ) emissions of the past (2015), present (2020), and future (2030) BEVs, incorporating China's carbon peaking and neutrality policies, which would substantially reduce emissions from the electricity, operation efficiency, metallurgy, and battery manufacturing industries. BEVs can reduce cradle-to-grave (C2G) CO2 emissions by ∼40% compared with internal combustion engine vehicles (ICEVs) on the national-average level in 2020, far more significant than the benefit in 2015. Improved BEV operating efficiency was the largest factor driving emission reductions from 2015 to 2020. Looking forward to 2030, China's BEVs equipped with nickel-cobalt-manganese (NCM) batteries can achieve a further 43% of CO2 emissions reductions, among which 51 g km-1 of reduction is from the well-to-wheels (WTW) stage majorly owing to the further cleaner electricity mix, while other vehicle-cycle benefits are mainly from the advancement of battery (12 g km-1 ) and related metal materials (5 g km-1 ). We highlight the importance of better material efficiency and synchronized decarbonization through the automotive industrial chain in promoting climate mitigation from transport activities., (© The Author(s) 2023. Published by Oxford University Press on behalf of National Academy of Sciences.)- Published
- 2023
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628. Clustering and machine learning-based integration identify cancer associated fibroblasts genes' signature in head and neck squamous cell carcinoma.
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Wang Q, Zhao Y, Wang F, and Tan G
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Background: A hallmark signature of the tumor microenvironment in head and neck squamous cell carcinoma (HNSCC) is abundantly infiltration of cancer-associated fibroblasts (CAFs), which facilitate HNSCC progression. However, some clinical trials showed targeted CAFs ended in failure, even accelerated cancer progression. Therefore, comprehensive exploration of CAFs should solve the shortcoming and facilitate the CAFs targeted therapies for HNSCC. Methods: In this study, we identified two CAFs gene expression patterns and performed the single-sample gene set enrichment analysis (ssGSEA) to quantify the expression and construct score system. We used multi-methods to reveal the potential mechanisms of CAFs carcinogenesis progression. Finally, we integrated 10 machine learning algorithms and 107 algorithm combinations to construct most accurate and stable risk model. The machine learning algorithms contained random survival forest (RSF), elastic network (Enet), Lasso, Ridge, stepwise Cox, CoxBoost, partial least squares regression for Cox (plsRcox), supervised principal components (SuperPC), generalised boosted regression modelling (GBM), and survival support vector machine (survival-SVM). Results: There are two clusters present with distinct CAFs genes pattern. Compared to the low CafS group, the high CafS group was associated with significant immunosuppression, poor prognosis, and increased prospect of HPV negative. Patients with high CafS also underwent the abundant enrichment of carcinogenic signaling pathways such as angiogenesis, epithelial mesenchymal transition, and coagulation. The MDK and NAMPT ligand-receptor cellular crosstalk between the cancer associated fibroblasts and other cell clusters may mechanistically cause immune escape. Moreover, the random survival forest prognostic model that was developed from 107 machine learning algorithm combinations could most accurately classify HNSCC patients. Conclusion: We revealed that CAFs would cause the activation of some carcinogenesis pathways such as angiogenesis, epithelial mesenchymal transition, and coagulation and revealed unique possibilities to target glycolysis pathways to enhance CAFs targeted therapy. We developed an unprecedentedly stable and powerful risk score for assessing the prognosis. Our study contributes to the understanding of the CAFs microenvironment complexity in patients with head and neck squamous cell carcinoma and serves as a basis for future in-depth CAFs gene clinical exploration., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Wang, Zhao, Wang and Tan.)
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- 2023
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629. Research progress in the hospitalization-associated disability among elderly patients.
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Wu S, Zhao Y, Ning H, Hu H, and Feng H
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- Humans, Aged, Hospitalization, Hospitals, Risk Factors, Activities of Daily Living, Disabled Persons
- Abstract
Hospitalized patients who lose one or more activities of daily living at the time of discharge compared with 2 weeks before admission (before acute onset) are referred to as hospitalization-associated disability (HAD). The incidence of HAD is high among elderly patients, which leads to the increased readmission rates, long-term care rates, and mortality, bringing a huge burden on patients, families, and society. It is vital for doctors and nurses to identify the risk factors of HAD of the elderly patients and take targeted intervention measures to prevent and improve HAD. At present, the research on HAD in foreign countries is relatively perfect, while the research on HAD in China is still in its infancy, and there is still lack of systematic research and reports on the incidence, influencing factors, and intervention measures of HAD. Domestic clinical nursing practice can learn from foreign mature interventions, carry out cultural adjustment, create a friendly environment in the hospital for elderly patients, pay attention to the assessment of the influencing factors of HAD in elderly patients, and provide personalized and patient-centered nursing measures for hospitalized elderly patients according to the assessment results, maintain their function during hospitalization and prevent the occurrence of HAD.
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- 2023
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630. Trajectories of Social Participation and Its Predictors in Older Adults: Based on the CLHLS Cohorts from 2002 to 2018.
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Zhang C, Zhao Y, Chen X, Li X, Liu Q, Peng R, Chen Y, and Feng H
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- Humans, Aged, Longitudinal Studies, Cohort Studies, Aging psychology, Cognition, China epidemiology, Social Participation psychology, Activities of Daily Living psychology
- Abstract
Social participation is a key factor in achieving active aging. This study aimed to explore the trajectories and predictors of social participation changes among older adults in China. The data used in this study are from the ongoing national longitudinal study CLHLS. A total of 2492 older adults from the cohort study were included. Group-based trajectory models (GBTM) were used to identify potential heterogeneity in longitudinal changes over time and investigate associations between baseline predictors and trajectories for different cohort members using logistic regression. Four different trajectories of social participation were reported in older adults, namely, stable (8.9%), slow decline (15.7%), lower score with decline (42.2%), and higher score with decline (9.5%). On multivariate analyses, age, years of schooling, pension, mental health, cognitive function, instrumental activities of daily living, and initial social participation scores significantly impact the rate of change in social participation over time. Four trajectories of social participation were identified in the Chinese elderly population. Management of mental health, physical function, and cognitive function appear to be important in maintaining the long-term social participation of older people in the community. Early identification of factors influencing the rapid decline in social participation and timely interventions can maintain or improve social participation levels in older adults.
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- 2023
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631. Integration of bulk RNA sequencing and single-cell analysis reveals a global landscape of DNA damage response in the immune environment of Alzheimer's disease.
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Lai Y, Lin H, Chen M, Lin X, Wu L, Zhao Y, Lin F, and Lin C
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- Humans, Prospective Studies, Single-Cell Analysis, DNA Damage, Alzheimer Disease genetics, RNA, Long Noncoding genetics
- Abstract
Background: We developed a novel system for quantifying DNA damage response (DDR) to help diagnose and predict the risk of Alzheimer's disease (AD)., Methods: We thoroughly estimated the DDR patterns in AD patients Using 179 DDR regulators. Single-cell techniques were conducted to validate the DDR levels and intercellular communications in cognitively impaired patients. The consensus clustering algorithm was utilized to group 167 AD patients into diverse subgroups after a WGCNA approach was employed to discover DDR-related lncRNAs. The distinctions between the categories in terms of clinical characteristics, DDR levels, biological behaviors, and immunological characteristics were evaluated. For the purpose of choosing distinctive lncRNAs associated with DDR, four machine learning algorithms, including LASSO, SVM-RFE, RF, and XGBoost, were utilized. A risk model was established based on the characteristic lncRNAs., Results: The progression of AD was highly correlated with DDR levels. Single-cell studies confirmed that DDR activity was lower in cognitively impaired patients and was mainly enriched in T cells and B cells. DDR-related lncRNAs were discovered based on gene expression, and two different heterogeneous subtypes (C1 and C2) were identified. DDR C1 belonged to the non-immune phenotype, while DDR C2 was regarded as the immune phenotype. Based on various machine learning techniques, four distinctive lncRNAs associated with DDR, including FBXO30-DT, TBX2-AS1, ADAMTS9-AS2, and MEG3 were discovered. The 4-lncRNA based riskScore demonstrated acceptable efficacy in the diagnosis of AD and offered significant clinical advantages to AD patients. The riskScore ultimately divided AD patients into low- and high-risk categories. In comparison to the low-risk group, high-risk patients showed lower DDR activity, accompanied by higher levels of immune infiltration and immunological score. The prospective medications for the treatment of AD patients with low and high risk also included arachidonyltrifluoromethane and TTNPB, respectively., Conclusions: In conclusion, immunological microenvironment and disease progression in AD patients were significantly predicted by DDR-associated genes and lncRNAs. A theoretical underpinning for the individualized treatment of AD patients was provided by the suggested genetic subtypes and risk model based on DDR., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Lai, Lin, Chen, Lin, Wu, Zhao, Lin and Lin.)
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- 2023
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632. Nursing assistants' knowledge, attitudes and training needs regarding urinary incontinence in nursing homes: a mixed-methods study.
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Liao L, Feng H, Jiao J, Zhao Y, and Ning H
- Subjects
- Humans, Aged, Health Knowledge, Attitudes, Practice, Nursing Homes, Surveys and Questionnaires, Urinary Incontinence diagnosis, Urinary Incontinence therapy, Nursing Assistants education
- Abstract
Background: Urinary incontinence is an increasingly common problem, especially among older people in nursing homes. Nursing assistants are the leading workforce in nursing homes, and their knowledge and attitudes regarding urinary incontinence have garnered considerable attention in the context of aging in China. However, most previous studies on this issue have focused on registered nurses. This study aimed to explore nursing assistants' knowledge, attitudes and training needs with regard to urinary incontinence., Methods: We conducted a two-part mixed-methods study. After institutional manager approval, we surveyed the knowledge and attitudes of 509 nursing assistants regarding urinary incontinence. We carried out semi-structured interviews with 40 nursing assistants to elicit detailed information on training needs., Results: In general, knowledge about urinary incontinence was poor (14.00 ± 4.18), although attitudes were primarily positive (35.51 ± 3.19). Most nursing assistants were very willing to learn more about urinary incontinence (93.9%, 478/509), but time constraints and low educational background may be barriers to learning motivation. The three preferred training styles among nursing assistants were face-to-face guidance from a mentor, training combining theory with practice, and online video training., Conclusions: Chinese nursing assistants had poor knowledge but positive attitudes toward urinary incontinence. Facility managers should focus on developing training and learning mechanisms regarding urinary incontinence. It is important to adopt diverse training styles according to the actual situation of nursing homes., (© 2023. The Author(s).)
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- 2023
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633. Strain evolution and confinement effect in InAs/AlAs short-period superlattices studied by Raman spectroscopy.
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Zhao Y, Lu K, Yao J, Ning J, Chen B, Lu H, and Zheng C
- Abstract
Raman spectra of two series of InAs/AlAs short-period superlattices were measured at room temperature to investigate the impact of strain on the phonon modes taking into consideration the confinement effect and interface mode. The evolution of strain in the InAs layer and the AlAs layer was studied in (InAs)
2 /(AlAs)2 superlattices grown at various temperatures (400-550 °C). While the strain existed in the AlAs layer remained almost constant, the strain in the InAs layer varied significantly as the growth temperature increased from 500 to 550 °C. The confinement effect on the optical phonons was analyzed based on results from (InAs)n /(AlAs)n grown at 450 °C (n = 2, 3, 4, and 5). Additionally, the confinement effect was found to be stronger in shorter periods with higher interface quality. The interface phonon modes were resolved between the longitudinal optical and transverse optical phonon modes, which assist in the rough estimation of the thickness of the layers. The disorder-activated acoustic phonon modes at the low-frequency side were also addressed., (© 2023. The Author(s).)- Published
- 2023
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634. A novel immune signature predicts immunotherapy responsiveness and reveals the landscape of the tumor immune microenvironment in head and neck squamous cell carcinoma.
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Wang Q, Zhao Y, Wang F, and Tan G
- Abstract
Background: Immune-checkpoint blockade (ICB) has been routinely implemented to treat head and neck squamous cell carcinoma (HNSCC) patients. However, only a few patients benefit from immune checkpoint inhibitor (ICI) therapies. Methods: In this study, we used a combined cohort (including the GSE41613, GSE65858, TCGA, and CELL cohorts) to identify hub genes significantly associated with ICB and activated CD8
+ T-cell gene signatures. We performed single-sample gene set enrichment analysis (ssGSEA) to quantify the expression of hub genes; we then constructed a novel immune signature named "the IMS" that can predict immunotherapy responsiveness, prognosis, immune infiltration, and clinical characteristics. Data from the GSE102349 external cohort and the pembrolizumab cohort obtained from a clinical trial were used to validate the efficiency of the IMS. In addition, we revealed potential mechanisms of the antitumor response by analyzing the HNSCC single-cell database. Finally, we used the LASSO algorithm to build an IMS-related risk model. Results: The high IMS group was associated with significant immune activation, better prognosis, and increased immunotherapy responsiveness; thus, the IMS potentially represents a candidate biomarker for ICB. Moreover, a tumor microenvironment with a higher IMS underwent remarkable metabolic reprogramming characterized by enrichment in the glycolysis/gluconeogenesis, oxidative phosphorylation, and citrate cycle (TCA cycle) pathways. We also revealed key information on cellular crosstalk between the IMS and other immune lineages, which may mechanistically explain immune escape. In addition, we constructed and validated a risk prediction model (CD2, TBC1D10C, and CD3E) that could stratify HNSCC patients based on survival and response to ICB treatment. Conclusion: IMS is a signature closely correlated with the tumor immune microenvironment. The findings of this study contribute to the understanding of the immune landscape in HNSCC patients. IMS may aid in the clinical management of HNSCC patients through the identification of effective immunotherapies for specific patients., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Wang, Zhao, Wang and Tan.)- Published
- 2022
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635. Ablation of sphingosine kinase 2 suppresses fatty liver-associated hepatocellular carcinoma via downregulation of ceramide transfer protein.
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Liu XT, Chung LH, Liu D, Chen J, Huang Y, Teo JD, Han XD, Zhao Y, Guan FHX, Tran C, Lee JY, Couttas TA, Liu K, McCaughan GW, Gorrell MD, Don AS, Zhang S, and Qi Y
- Abstract
Hepatocellular carcinoma (HCC) accounts for 90% of primary liver cancer, the third leading cause of cancer-associated death worldwide. With the increasing prevalence of metabolic conditions, non-alcoholic fatty liver disease (NAFLD) is emerging as the fastest-growing HCC risk factor, and it imposes an additional layer of difficulty in HCC management. Dysregulated hepatic lipids are generally believed to constitute a deleterious environment cultivating the development of NAFLD-associated HCC. However, exactly which lipids or lipid regulators drive this process remains elusive. We report herein that sphingosine kinase 2 (SphK2), a key sphingolipid metabolic enzyme, plays a critical role in NAFLD-associated HCC. Ablation of Sphk2 suppressed HCC development in NAFLD livers via inhibition of hepatocyte proliferation both in vivo and in vitro. Mechanistically, SphK2 deficiency led to downregulation of ceramide transfer protein (CERT) that, in turn, decreased the ratio of pro-cancer sphingomyelin (SM) to anti-cancer ceramide. Overexpression of CERT restored hepatocyte proliferation, colony growth and cell cycle progression. In conclusion, the current study demonstrates that SphK2 is an essential lipid regulator in NAFLD-associated HCC, providing experimental evidence to support clinical trials of SphK2 inhibitors as systemic therapies against HCC., (© 2022. The Author(s).)
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- 2022
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636. The impact of unified discharge standards on the clinical efficacy and prognosis of hemiarthroplasty in elderly patients with hip fractures.
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Zhao Y, Niu Z, Sun Q, Li Z, Liu Y, Wu Y, and Li Y
- Abstract
Objectives: The aim of this study was to investigate the impact of unified discharge standards on the clinical efficacy and prognosis of hemiarthroplasty in elderly patients with hip fractures., Methods: Retrospective study of 158 elderly patients with hip fractures who underwent artificial femoral head replacement in our hospital from March 2016 to July 2019 were enrolled. According to the unified discharge standards, patients were divided into the observation (65 cases who met discharge criteria) and control group (93 cases who failed to meet all discharge criteria). Histopathological feature, operation status, postoperative Harris Hip score, therapeutic outcome, postoperative complications, readmission and mortality rate were compared between the two groups., Results: Surgery duration and intraoperative blood loss exhibited no difference between the two groups, while transfusion volume and length of hospital stay were significantly increased in the observation group. There was no significant difference in the Harris Hip score between the two groups 12 months postoperatively. The incidence of postoperative complications during the follow-up period was notably lower in the observation group. In addition, the three-month readmission rate and one-year mortality rate were significantly lower in the observation group., Conclusions: For elderly patients with hip fractures undergoing artificial femoral head replacement, the incidence of postoperative complications and postoperative readmission/mortality rate could be reduced through the establishment of unified discharge standards, which should be used in future clinical practice., Competing Interests: None., (AJTR Copyright © 2022.)
- Published
- 2022
637. Influence of Different Protection States on the Mental Fatigue of Nurses During the COVID-19 Pandemic.
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Jin H, Xiao M, Gong Z, and Zhao Y
- Abstract
Background: COVID-19 has brought greater workload pressures to the medical field, such as medical staff being required to wear personal protective equipment (PPE). While PPE can protect the safety of staff during the pandemic, it can also accelerate the accumulation of fatigue among operators., Objective: This study explores the influence of different protection states on the mental fatigue of nurses., Methods: In this study, 10 participants (5 males and 5 females) were randomly selected among applicants to monitor mental fatigue during the nurses' daily work in four different PPE states (low temperature and low protection; low temperature and high protection; high temperature and low protection; high temperature and high protection). The NASA subjective mental fatigue scale was used for subjective evaluation. Reaction time, attention concentration, attention distribution, memory, and main task completion time were used for objective evaluation., Results: The results demonstrated a significant difference in the effects of different protection states on mental fatigue. The state of high temperature and high protection had the greatest influence on mental fatigue, the state of low temperature and low protection had the least, and states of high (low) temperature and low (high) protection had intermediate effects on mental fatigue. Furthermore, the correlation between the subjective and objective fatigue indices was analyzed using a multiple regression model., Conclusion: This study clarified the influence of different protection states on the mental fatigue of nurses, and verified that nurses require more time and energy to complete the same work as before under high protection states. It provides a basis for evaluating the mental fatigue of nurses in the unique period of the COVID-19 pandemic and specific ideas for optimizing the nursing process., Competing Interests: The authors declare that they have no conflicts of interest in this work., (© 2022 Jin et al.)
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- 2022
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638. Long-term modification of gut microbiota by broad-spectrum antibiotics improves stroke outcome in rats.
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Liu C, Cheng X, Zhong S, Liu Z, Liu F, Lin X, Zhao Y, Guan M, Xiao T, Jolkkonen J, Wang Y, and Zhao C
- Subjects
- Animals, Rats, Ampicillin pharmacology, Anti-Bacterial Agents, Ciprofloxacin pharmacology, Cytokines, Endothelin-1 pharmacology, Fatty Acids, Volatile, Infarction complications, Meropenem pharmacology, Metronidazole pharmacology, Vancomycin pharmacology, Gastrointestinal Microbiome, Stroke drug therapy, Stroke complications
- Abstract
Background: The brain-gut axis is a major regulator of the central nervous system. We investigated the effects of treatment with broad-spectrum antibiotics on gut and brain inflammation, infarct size and long-term behavioral outcome after cerebral ischemia in rats., Methods: Rats were treated with broad-spectrum antibiotics (ampicillin, vancomycin, ciprofloxacin, meropenem and metronidazole) for 4 weeks before the endothelin-1 induced ischemia. Treatment continued for 2 weeks until the end of behavioral testing, which included tapered ledged beam-walking, adhesive label test and cylinder test. Gut microbiome, short-chain fatty acids and cytokine levels were measured together with an assessment of infarct size, neuroinflammation and neurogenesis., Results: The results revealed that the antibiotics exerted a clear impact on the gut microbiota. This was associated with a decrease in systemic and brain cytokine levels, infarct size and apoptosis in the perilesional cortex and improved behavioral outcome., Conclusion: Our results highlighted the significant relationship between intestinal microbiota and beneficial neuro-recovery after ischemic stroke., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)
- Published
- 2022
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639. Cost-effectiveness analysis of prolonged-release fampridine to treat walking disability of multiple sclerosis in China.
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Zhao X, Yang H, Wei T, Zhao J, Liu J, Huang Z, Zhu L, Zhao Y, and Li W
- Subjects
- 4-Aminopyridine therapeutic use, Adult, Cost-Benefit Analysis, Double-Blind Method, Humans, Quality-Adjusted Life Years, Treatment Outcome, Walking, Multiple Sclerosis complications, Multiple Sclerosis drug therapy
- Abstract
Objectives: This study evaluates the cost-effectiveness of adding prolonged-release (PR)-fampridine to best supportive care (BSC) versus BSC alone in adult multiple sclerosis patients with walking disability in China. Materials & methods: A hybrid decision tree and Markov model from both the societal and healthcare perspectives were constructed. Parameters were derived from clinical trials of PR-fampridine, published sources and clinical expert interviews. Results: Over a 10-year time horizon, adding PR-fampridine to BSC led to 0.15 quality-adjusted life year (QALY) gain and lower costs, with incremental cost-effectiveness ratios of -238,806 Chinese Yuan/QALY and -113,488 Chinese Yuan/QALY from the societal and healthcare perspectives, respectively. Conclusion: Compared with BSC alone, PR-fampridine plus BSC is considered an economically dominant strategy for the treatment of multiple sclerosis-related walking disability in China.
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- 2022
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640. Trajectories of physical functioning and its predictors in older adults: A 12-year longitudinal study in China.
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Zhao Y, Duan Y, Feng H, Nan J, Li X, Zhang H, and Xiao LD
- Subjects
- Aged, China epidemiology, Health Status, Humans, Longitudinal Studies, Male, Activities of Daily Living, Independent Living
- Abstract
Objective: Maintaining and delaying a decline in physical function in older adults is critical for healthy aging. This study aimed to explore trajectories, critical points of the trajectory changes, and predictors among older people in the Chinese community., Design: This study was one with a longitudinal design performed in China., Setting and Participants: The target population was community-dwelling older adults aged over 65 years. A total of 2,503 older adults from the Chinese Longitudinal Healthy Longevity Survey (CLHLS) were included in this study., Methods: Physical functioning was measured by instrumental activities of daily living (IADL). Population-based trajectory models were used to identify potential heterogeneity in longitudinal changes over 12 years and to investigate associations between baseline predictors and different trajectories for different cohort members using LASSO regression and logistic regression., Results: Four trajectories of physical function were identified: slow decline (33.0%), poor function and moderate decline (8.1%), rapid decline (23.5%), and stable function (35.4%). Older age, male sex, worse self-reported health status, worse vision status, more chronic diseases, worse cognitive function, and a decreased frequency of leisure activity influenced changes in the trajectory of physical function. Having fewer teeth, stronger depressive symptoms, a lack of exercise, and reduced hearing may increase the rate of decline., Conclusion and Implications: Four trajectories of physical function were identified in the Chinese elderly population. Early prevention or intervention of the determinants of these trajectories can maintain or delay the rate of decline in physical function and improve healthy aging., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Zhao, Duan, Feng, Nan, Li, Zhang and Xiao.)
- Published
- 2022
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641. Comprehensive Analysis of Molecular Subtypes and Hub Genes of Sepsis by Gene Expression Profiles.
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Lai Y, Lin C, Lin X, Wu L, Zhao Y, Shao T, and Lin F
- Abstract
Background: Sepsis is a systemic inflammatory response syndrome (SIRS) with heterogeneity of clinical symptoms. Studies further exploring the molecular subtypes of sepsis and elucidating its probable mechanisms are urgently needed. Methods: Microarray datasets of peripheral blood in sepsis were downloaded from the Gene Expression Omnibus (GEO) database, and differentially expressed genes (DEGs) were identified. Weighted gene co-expression network analysis (WGCNA) analysis was conducted to screen key module genes. Consensus clustering analysis was carried out to identify distinct sepsis molecular subtypes. Subtype-specific pathways were explored using gene set variation analysis (GSVA). Afterward, we intersected subtype-related, dramatically expressed and module-specific genes to screen consensus DEGs (co-DEGs). Enrichment analysis was carried out to identify key pathways. The least absolute shrinkage and selection operator (LASSO) regression analysis was used for screen potential diagnostic biomarkers. Results: Patients with sepsis were classified into three clusters. GSVA showed these DEGs among different clusters in sepsis were assigned to metabolism, oxidative phosphorylation, autophagy regulation, and VEGF pathways, etc. In addition, we identified 40 co-DEGs and several dysregulated pathways. A diagnostic model with 25-gene signature was proven to be of high value for the diagnosis of sepsis. Genes in the diagnostic model with AUC values more than 0.95 in external datasets were screened as key genes for the diagnosis of sepsis. Finally, ANKRD22, GPR84, GYG1, BLOC1S1, CARD11, NOG, and LRG1 were recognized as critical genes associated with sepsis molecular subtypes. Conclusion: There are remarkable differences in and enriched pathways among different molecular subgroups of sepsis, which may be the key factors leading to heterogeneity of clinical symptoms and prognosis in patients with sepsis. Our current study provides novel diagnostic and therapeutic biomarkers for sepsis molecular subtypes., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Lai, Lin, Lin, Wu, Zhao, Shao and Lin.)
- Published
- 2022
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642. Maternal Ezh1/2 deficiency in oocyte delays H3K27me2/3 restoration and impairs epiblast development responsible for embryonic sub-lethality in mouse.
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Zhao Y, Bai D, Wu Y, Zhang D, Liu M, Tian Y, Lu J, Wang H, Gao S, and Lu Z
- Subjects
- Animals, Enhancer of Zeste Homolog 2 Protein genetics, Enhancer of Zeste Homolog 2 Protein metabolism, Female, Germ Layers metabolism, Mice, Oocytes metabolism, Placenta metabolism, Pregnancy, Histones, Polycomb Repressive Complex 2 metabolism
- Abstract
How maternal Ezh1 and Ezh2 function in H3K27 methylation in vivo in pre-implantation embryos and during embryonic development is not clear. Here, we have deleted Ezh1 and Ezh2 alone or simultaneously from mouse oocytes. H3K27me3 was absent in oocytes without Ezh2 alone, while both H3K27me2 and H3K27me3 were absent in Ezh1/Ezh2 (Ezh1/2) double knockout (KO) oocytes. The effects of Ezh1/2 maternal KO were inherited in zygotes and early embryos, in which restoration of H3K27me3 and H3K27me2 was delayed by the loss of Ezh2 alone or of both Ezh1 and Ezh2. However, the ablation of both Ezh1 and Ezh2, but not Ezh1 or Ezh2 alone, led to significantly decreased litter size due to growth retardation post-implantation. Maternal Ezh1/2 deficiency caused compromised H3K27me3 and pluripotent epiblast cells in late blastocysts, followed by defective embryonic development. By using RNA-seq, we examined crucial developmental genes in maternal Ezh1/2 KO embryos and identified 80 putatively imprinted genes. Maternal Ezh1/2-H3K27 methylation is inherited in offspring embryos and has a critical effect on fetal and placental development. Thus, this work sheds light on maternal epigenetic modifications during embryonic development., Competing Interests: Competing interests The authors declare no competing or financial interests., (© 2022. Published by The Company of Biologists Ltd.)
- Published
- 2022
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643. Identification and immunological characterization of cuproptosis-related molecular clusters in Alzheimer's disease.
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Lai Y, Lin C, Lin X, Wu L, Zhao Y, and Lin F
- Abstract
Introduction: Alzheimer's disease is the most common dementia with clinical and pathological heterogeneity. Cuproptosis is a recently reported form of cell death, which appears to result in the progression of various diseases. Therefore, our study aimed to explore cuproptosis-related molecular clusters in Alzheimer's disease and construct a prediction model., Methods: Based on the GSE33000 dataset, we analyzed the expression profiles of cuproptosis regulators and immune characteristics in Alzheimer's disease. Using 310 Alzheimer's disease samples, we explored the molecular clusters based on cuproptosis-related genes, along with the related immune cell infiltration. Cluster-specific differentially expressed genes were identified using the WGCNA algorithm. Subsequently, the optimal machine model was chosen by comparing the performance of the random forest model, support vector machine model, generalized linear model, and eXtreme Gradient Boosting. Nomogram, calibration curve, decision curve analysis, and three external datasets were applied for validating the predictive efficiency., Results: The dysregulated cuproptosis-related genes and activated immune responses were determined between Alzheimer's disease and non-Alzheimer's disease controls. Two cuproptosis-related molecular clusters were defined in Alzheimer's disease. Analysis of immune infiltration suggested the significant heterogeneity of immunity between distinct clusters. Cluster2 was characterized by elevated immune scores and relatively higher levels of immune infiltration. Functional analysis showed that cluster-specific differentially expressed genes in Cluster2 were closely related to various immune responses. The Random forest machine model presented the best discriminative performance with relatively lower residual and root mean square error, and a higher area under the curve (AUC = 0.9829). A final 5-gene-based random forest model was constructed, exhibiting satisfactory performance in two external validation datasets (AUC = 0.8529 and 0.8333). The nomogram, calibration curve, and decision curve analysis also demonstrated the accuracy to predict Alzheimer's disease subtypes. Further analysis revealed that these five model-related genes were significantly associated with the Aβ-42 levels and β-secretase activity., Conclusion: Our study systematically illustrated the complicated relationship between cuproptosis and Alzheimer's disease, and developed a promising prediction model to evaluate the risk of cuproptosis subtypes and the pathological outcome of Alzheimer's disease patients., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Lai, Lin, Lin, Wu, Zhao and Lin.)
- Published
- 2022
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644. Cationic Nanoparticulate System for Codelivery of MicroRNA-424 and Podophyllotoxin as a Multimodal Anticancer Therapy.
- Author
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Wang R, Xuan Y, Zhao Y, Wang W, Ma P, Ju B, Zhen Y, and Zhang S
- Subjects
- Animals, B7-H1 Antigen metabolism, Cell Line, Tumor, Ecosystem, Mice, Podophyllotoxin pharmacology, Tumor Microenvironment, Lung Neoplasms drug therapy, MicroRNAs genetics
- Abstract
Because of the complexity of cancer ecosystems, the efficacy of single-agent chemotherapy is limited. Herein, we report the use of cationic nanoparticles (designated PPCNs) generated from a chemically modified form of the chemotherapeutic agent podophyllotoxin (PPT) to deliver both microRNA-424 (miR-424) and PPT to tumor cells, thus combining chemotherapy and gene therapy. We evaluated the optimal loading ratio of miR-424─which targets programmed cell death ligand 1 (PD-L1) mRNA and reduces PD-L1 production, thus promoting the attack of tumor cells by T cells─for effective delivery of miR-424 and PPCNs into nonsmall-cell lung cancer cells (H460). Because miR-424 can reverse chemotherapy resistance, treatment of the tumor cells with the combination of miR-424 and PPT enhanced their sensitivity to PPT. Because miR-424 and the PPCNs regulated PD-L1 production in different ways, the miR-424@PPCN complexes were significantly more efficacious than either miR-424 or PPCNs alone. We also demonstrated that treatment of tumor-bearing mice with these complexes significantly inhibited tumor growth and extended survival. Moreover, additional in vitro experiments revealed that the complexes could remodel the tumor immune microenvironment, relieve immunosuppression, and achieve immune normalization. This novel system for delivering a combination of PPT and miR-424 shows great potential for the multimodal treatment of lung cancer.
- Published
- 2022
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645. Perspectives of older adults, caregivers, healthcare providers on frailty screening in primary care: a systematic review and qualitative meta-synthesis.
- Author
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Nan J, Duan Y, Wu S, Liao L, Li X, Zhao Y, Zhang H, Zeng X, and Feng H
- Subjects
- Aged, Health Personnel, Humans, Primary Health Care, Qualitative Research, Caregivers, Frailty diagnosis
- Abstract
Background: Screening is often recommended as a first step in frailty management. Many guidelines call to implicate frailty screening into practice in the primary care setting. However, few countries or organizations implement it. Understanding and clarifying the stakeholders' views and issues faced by the implementation is essential to the successful implementation of frailty screening. However, the systematic review on stakeholders' views of frailty screening in primary care is decidedly limited. Our objective was to explore the perspective of older adults, caregivers, and healthcare providers on frailty screening and determine the enablers and barriers to implementing frailty screening in primary care., Methods: A systematic search of six databases and other resources was conducted following JBI's three-step search strategy. The search resulted in 7362 articles, of which 97 were identified for further assessment according to the inclusion criteria. After the full-text screening, quality assessment and data extraction were carried out using the tools from Joanna Briggs Institute (JBI). Moreover, reviewers used the approach of meta-aggregative of JBI to analyze data and synthesis the findings., Results: Six studies were included. A total of 63 findings were aggregated into 12 categories and then further grouped into three synthesized findings:1) capacity of healthcare providers and older adults; 2) opportunity in the implementation of frailty screening; 3) motivation in the implementation of frailty screening. These themes can help identify what influences the implementation of screening from the perspective of stakeholders., Conclusions: This meta-synthesis provides evidence on the barriers and enablers of frailty screening in primary care, from the aspects of psychological, physical, social, material, etc. However, stakeholder perspectives of frailty screening have not been adequately studied. More research and efforts are needed to explore the influencing factors and address the existing barriers., (© 2022. The Author(s).)
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- 2022
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646. Impact of Pain and Psychosocial Factors on Frailty Among Older Adults With Physical Functional Limitations: A Cross-Sectional Study.
- Author
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Ning H, Zhao Y, Liao L, Chen H, Tao Z, Chen X, and Feng H
- Subjects
- Aged, Cross-Sectional Studies, Frail Elderly psychology, Geriatric Assessment, Humans, Pain epidemiology, Pain psychology, Prevalence, Frailty complications, Frailty epidemiology
- Abstract
Aims: The objective of this study was to determine the prevalence of frailty and pain among older adults with physical functional limitations in China. We also assessed the impact of pain and psychosocial determinants on frailty among this vulnerable population., Design: This study was a cross-sectional study., Setting and Participants: Totally, 2,323 Chinese elders with physical functional limitation were enrolled., Methods: Physical functioning was assessed by the Barthel Index, participants who reported "often troubled with pain" were further asked about the intensity of their pain using a 1-10 numeric rating scale, and frailty was assessed by the Assessment of frailty FRAIL scale. The impact of pain and psychosocial factors on frailty was assessed by multivariable binary logistic regression., Results: The prevalence of frailty and pain were 30.9% and 46.1%, respectively. Compared with subjects who reported no pain, those who reported mild (odds ratio [OR] = 1.70, 95% confidence interval [CI] = 1.21-2.31), moderate (OR = 2.10, 95% CI = 1.53-2.82), or severe pain (OR = 2.31, 95% CI = 1.56-3.40) tended to be more vulnerable to frailty. Furthermore, compared with participants with positive psychosocial determinants, those with negative psychosocial determinants seemed more likely to be frail., Conclusions: These findings suggest that the incidence of pain, negative psychosocial status, and frailty were prevalent, and the presence of pain and negative psychosocial factors increased the risk of frailty among older adults with physical functional limitation., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 American Society for Pain Management Nursing. Published by Elsevier Inc. All rights reserved.)
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- 2022
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647. Necroptosis is Related to Anti-PD-1 Treatment Response and Influences the Tumor Microenvironment in Head and Neck Squamous Cell Carcinoma.
- Author
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Wang Q, Wang F, Zhao Y, and Tan G
- Abstract
The latest research suggesting that necroptosis plays a vital role in immune response. However, the influence of necroptosis on tumor microenvironment (TME) remodeling and immunotherapy is still unclear. We analyzed the variations in the expression of 26 necroptosis-related molecules in HNSCC and the influence of genome changes. We investigated HNSCC samples and determined that there are two necroptosis phenotypes in HNSCC cancer, and there are significant differences in cell infiltration characteristics and survival in different necroptosis phenotypes. We used the single-sample gene set enrichment analysis to measure the level of necroptosis in patients with NecroticScore, we confirmed that the NecroticScore can predict the prognosis of HNSCC patients and the response to immunotherapy. Patients with a high NecroticScore are more sensitive to immunotherapy and have a better prognosis. Our study suggests a significant correlation between the expression imbalance of necroptosis-related molecules and suggests necroptosis plays an important role in modeling the TME. In addition, we construct a risk prediction model which could stratify patients with HNSCC and predict patient prognosis according to this necroptosis-related molecules. In conclusion, evaluating necroptosis modification patterns contributes to enhancing our understanding of TME and can guide more effective immunotherapy strategies., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Wang, Wang, Zhao and Tan.)
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- 2022
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648. Poisoning Associated with Consumption of a Homemade Medicinal Liquor - Chongqing, China, 2018.
- Author
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Zhou C, Luo S, Tang J, Quick L, Liu H, and Zhao Y
- Subjects
- Adult, Alcoholic Beverages, China epidemiology, Humans, Japan, Aconitum, Drugs, Chinese Herbal, Poisoning
- Abstract
On May 3, 2018, Chongqing Center for Disease Control and Prevention (CQCDC) received a report of 15 persons with numbness of the tongue or limbs and vomiting of unknown etiology; all ill persons had attended an adult birthday luncheon in Bishan District, Chongqing municipality, in southwest China. Initial reports indicated that one person had died. Within 2 hours, CQCDC and Western Chinese Field Epidemiology Training Program staff members launched an investigation that included identification of cases, laboratory testing of drinks, and patient interviews to identify the cause of what appeared to be a poisoning. Among the 15 cases, five persons died. The investigation of this apparent mass intoxication implicated a homemade alcoholic beverage produced from a highly toxic flowering plant in the genus Aconitum used in traditional Chinese medicine. Although the risk of aconite toxicity is known, approximately 5,000 cases of aconite poisoning incidents were reported in China, Germany, Japan, and other countries during 1993-2005; most cases of fatal poisoning occurred in China (1). This event highlights the importance of enforcing and complying with existing regulations regarding sale and purchase of Aconitum species (also known as wolfbane), and of dissemination of critical public health messages., Competing Interests: All authors have completed and submitted the International Committee of Medical Journal Editors form for disclosure of potential conflicts of interest. No potential conflicts of interest were disclosed.
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- 2022
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649. Self-Assembly of Podophyllotoxin-Loaded Lipid Bilayer Nanoparticles for Highly Effective Chemotherapy and Immunotherapy via Downregulation of Programmed Cell Death Ligand 1 Production.
- Author
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Wang R, Zhao Y, Huang Z, Zhou Y, Wang W, Xuan Y, Zhen Y, Ju B, Guo S, and Zhang S
- Subjects
- Animals, Apoptosis, Cell Line, Tumor, Down-Regulation, Immunologic Factors pharmacology, Immunotherapy, Ligands, Lipid Bilayers, Mice, Podophyllotoxin pharmacology, Tumor Microenvironment, Lung Neoplasms drug therapy, Nanoparticles
- Abstract
Low drug delivery efficiency elevates the cost of medication, lowers the therapeutic efficacy, and appears as a leading reason for unmet needs in anticancer therapies. Herein, we report the development of self-assembled podophyllotoxin-loaded lipid bilayer nanoparticles that inhibit the production of programmed cell death ligand 1 in lung cancer cells and promote tumor-specific immune responses, thus offering a strategy for regulating the immunosuppressive microenvironment of tumors. In addition, encapsulation of podophyllotoxin in the nanoparticles reduced its systemic toxicity, enhanced its penetration into tumors, and increased its antitumor efficacy. Systemic injection of the nanoparticles into tumor-bearing mice not only prevented tumor immune escape but also significantly inhibited tumor growth and extended survival. In general, the podophyllotoxin-loaded nanoparticles exhibited both immunological effects and antitumor effects in addition to having better targeting activity and fewer side effects than free podophyllotoxin. We expect our findings to facilitate the development of therapies for lung cancer.
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- 2022
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650. Male Patients with Takayasu Arteritis and Coronary Artery Involvement are Prone to Have Serious Coronary Stenosis and High Mortality.
- Author
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Ci W, Zhao Y, and Bi T
- Subjects
- Constriction, Pathologic pathology, Coronary Vessels diagnostic imaging, Coronary Vessels pathology, Female, Humans, Male, Retrospective Studies, Coronary Stenosis diagnostic imaging, Coronary Stenosis therapy, Takayasu Arteritis diagnostic imaging, Takayasu Arteritis epidemiology
- Abstract
Background: Takayasu arteritis (TAK) is a rare autoimmune vasculitis that predominantly affects the aorta and its major branches, including the coronary arteries. Information is limited regarding sex-specific differences in coronary artery involvement among TAK patients., Objective: To assess the differences in coronary angiographic findings and long-term outcomes between male and female TAK patients with coronary artery involvement., Methods: This retrospective cohort study included 87 TAK patients, grouped by sex, who underwent coronary angiography. General characteristics, clinical features, coronary angiographic findings, and therapeutic strategies were obtained from medical records. Major Adverse Cardiac Events (MACE), including death from any cause, myocardial infarction, repeated coronary artery revascularization, and rehospitalization due to unstable or progressive angina or heart failure occurring during follow-up, were also recorded., Results: A total of 207 coronary lesions with stenosis were found in 87 TAK patients. The prevalence of ostial coronary lesions was lower in men than in women (9.1 vs. 23.9%, p=0.031). We observed less moderate stenosis (6.8 vs. 22.7%, p=0.018) and more severe stenosis or occlusion (70.5 vs. 46.0%, p=0.004) in the coronary lesions of male TAK patients. During the up to 7-year follow- up, death from any cause was greater in men than in women (21.4 vs. 1.5%, p=0.003); no other significant differences in MACE occurrence were observed between sexes., Conclusion: Among TAK patients with coronary artery involvement, males tend to have more serious coronary stenosis and a higher risk for long-term mortality than females., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)
- Published
- 2022
- Full Text
- View/download PDF
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