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Abstract Background Huanshaodan (HSD) is a Chinese Herbal Compound which has a definite clinical effect on Alzheimer’s disease (AD), however, the underlying mechanism remains unclear. The aim of this study is to preliminarily reveal the mechanism of HSD in the treatment of AD model of SAMP8 mice. Methods Chemical composition of HSD and its drug-containing serum were identified by Q-Orbitrap high resolution liquid mass spectrometry. Six-month-old SAMP8 mice were treated with HSD and Donepezil hydrochloride by gavage for 2 months, and Wogonin for 28 days. Behavioral test was performed to test the learning and memory ability of mice. Immunofluorescence (IF) or Western-blot methods were used to detect the levels of pSer404-tau and β-amyloid (Aβ) in the brain of mice. Hematoxylin–eosin (H&E) staining and Transmission electron microscopy (TEM) assay was applied to observe the pathological changes of neurons. Proteomic technology was carried out to analyze and identify the protein network of HSD interventions in AD. Then the pathological process of the revealed AD-related differential proteins was investigated by IF, Q-PCR, Western-blot, Fluorescence in situ hybridization (FISH) and 16S rRNA sequencing methods. Results The results showed that HSD and Wogonin, one of the components in its drug-containing serum, can effectively improve the cognitive impairments of SAMP8 mice, protect hippocampal neurons and synapses, and reduce the expression of pSer404-tau and Aβ. HSD and Wogonin reduced the levels of fibrinogen β chain (FGB) and γ chain (FGG), the potential therapeutic targets revealed by proteomics analysis, reduced the colocalization of FGB and FGG with Aβ, ionized calcium binding adaptor molecule 1 (Iba-1), glial fibrillary acidic protein (GFAP), increased level of and myelin basic protein (MBP). Meanwhile, HSD and Wogonin increased ZO-1 and Occludin levels, improved brain microvascular injury, and reduced levels of bacteria/bacterial DNA and lipopolysaccharide (LPS) in the brain of mice. In addition, 16S rRNA sequencing indicated that HSD regulated the structure of intestinal microbiota of mice. Conclusion The effects of HSD on AD may be achieved by inhibiting the levels of fibrinogen and the interactions on glia cells in the brain, and by modulating the structure of intestinal microbiota and improving the blood–brain barrier function.

Abnormal glucose metabolism in microglial is closely associated with Alzheimer’s disease (AD). Reprogramming of microglial glucose metabolism is centered on regulating the way in which microglial metabolize glucose to alter microglial function. Therefore, reprogramming microglial glucose metabolism is considered as a therapeutic strategy for AD. Huanshaodan (HSD) is a Chinese herbal compound which shows significant efficacy in treating AD, however, the precise mechanism by which HSD treats AD remains unclear. This study is aim to investigate whether HSD exerts anti-AD effects by regulating the metabolic reprogramming of microglial through the mTOR/HIF-1α signaling pathway. SAMP8 mice and BV2 cells were used to explore the alleviative effect of HSD on AD and the molecular mechanism in vivo and in vitro. The pharmacodynamic effects of HSD was evaluated by behavioral tests. The pathological deposition of Aβ in brain of mice was detected by immunohistochemistry. ELISA method was used to measure the activity of HK2 and the expression of PKM2, IL-6 and TNF-α in hippocampus and cortex tissues of mice. Meanwhile, proteins levels of p-mTOR, mTOR, HIF-1α, CD86, Arg1 and IL-1β were detected by Western-blot. LPS-induced BV2 cells were treated with HSD-containing serum. The analysis of the expression profiles of the CD86 and CD206 markers by flow cytometry allows us to distinguish the BV2 polarization. Glucose, lactic acid, ATP, IL-6 and TNF-α levels, as well as lactate dehydrogenase and pyruvate dehydrogenase activities were evaluated in the BV2. Western-blot analysis was employed to detect mTOR, p-mTOR, HIF-1α and IL-1β levels in BV2. And the mTOR agonist MHY1485 (MHY) was chosen to reverse validate. In this study, it is found that HSD improved cognitive impairment in SAMP8 mice and reduced Aβ deposition, suppressed the levels of glycolysis and neuroinflammation in mice. In LPS-induced BV2 cells, HSD also regulated glycolysis and neuroinflammation, and suppressed the mTOR/HIF-1α signaling pathway. More importantly, these effects were reversed by MHY. It is demonstrated that HSD regulated microglial glucose metabolism reprogramming by inhibiting the mTOR/HIF-1α signaling pathway, alleviated neuroinflammation, and exerted anti-AD effects. This study provided scientific evidence for the clinical application of HSD for treating AD.

BackgroundsIn the petrochemical industry, employees are exposed to various health hazards, which pose serious challenges to their health and hinder the sustainable development of the petrochemical industry. Investing in health has proved a potential strategy to enhance general health. However, global health investment is notably insufficient, mainly due to the public’s limited intention to invest in their health. While past research has identified various determinants of health investment intentions, the relationship between health literacy and health investment intention remains somewhat controversial and needs more empirical validation.ObjectivesThis study aims to assess the level of health literacy and health investment intention among employees in one of China’s largest petrochemical companies and to explore the effect of health literacy on health investment intention.MethodsA cross-sectional study was conducted in a petrochemical company. The valid sample size for this study was 39,911 respondents. Data were collected using a designed questionnaire, including socio-demographic information, questions about health investment intention, and the “2020 National Health Literacy Monitoring Questionnaire.” Several statistical analysis methods were employed, including descriptive analysis, Chi-square test, logistic regression, and multiple linear regression.ResultsThe study disclosed an average health literacy score of 56.11 (SD = 10.34) among employees, with 52.1% surpassing the qualification threshold. The “Chronic Disease” dimension exhibited the lowest qualification rate at 33.0%. Furthermore, 71.5% of the employees expressed an intention to invest in health, yet a significant portion (34.5%) opted for the minimal investment choice, less than 2,000 RMB. Logistic regression analysis indicated a positive correlation between health literacy and health investment intention (OR = 1.474; p

Alzheimer's disease (AD) is characterized by a complex pathogenesis, limited diagnostic methods, and a lack of effective therapeutic drugs in clinical settings, posing significant challenges in modern medical research. Bioinformatics offers new perspectives for identifying key pathological biomarkers of AD, analyzing differentially expressed genes in AD, screening for effective drug targets against AD, studying the mechanisms of AD pathogenesis, and discovering novel anti-AD drugs. However, data preprocessing and statistical analysis methods in bioinformatics research can significantly impact results, and there is a lack of consistency and coordination in analysis methods across platforms and laboratories in practical studies, making it difficult to compare data between studies. Therefore, it is crucial to establish standardized operating procedures and quality control protocols, improve the reproducibility of methods across platforms, and promote data comparison between studies.

Radix Rehmanniae Praeparata (RRP, Shu Dihuang in Cinese) is widely used as primal medicine in Chinese herbal formula for the treatment of Alzheimer’s disease (AD). However, the underlying mechanism of RRP for AD remains unclear. The aim of this study was to investigate the therapeutic effect of RRP on intracerebroventricular injection of streptozotocin (ICV-STZ)-induced AD model mice and its potential mechanism. ICV-STZ mice were continuously gavaged with RRP for 21 days. The pharmacological effects of RRP were evaluated by behavioral tests, brain tissue H&E staining and hippocampal tau protein phosphorylation levels. The expression levels of insulin receptor (INSR), IRS-1, pSer473-AKT/AKT and pSer9-GSK-3β/GSK-3β proteins in hippocampal and cortical tissues were detected by Western-blot method. The 16S rRNA gene sequencing was used to analyze the changes of intestinal microbiota in mice. The compounds in RRP were analyzed by mass spectrometry and their binding ability to INSR proteins was detected by molecular docking. The results showed that RRP ameliorated cognitive dysfunction and neuronal pathological changes of brain tissue in ICV-STZ mice, reduced tau protein hyperphosphorylation, INSR, IRS-1, pSer473-AKT/AKT, and pSer9-GSK-3β/GSK-3β levels in hippocampal and cortical tissues. Meanwhile, RRP reversed ICV-STZ-induced dysregulation of intestinal microbiota in AD mice. Mass spectrometry analysis showed that the RRP consisted mainly of seven compounds, namely Acteoside (Verbascoside), 5-Hydroxymethyl-2-furaldehyde (5-HMF), Apigenin7-O-glucuronide, Icariin, Gallic acid, Quercetin-3β-D-glucoside, and Geniposide. Molecular docking results further indicated that the compounds in RRP have binding ability to INSR protein and potential multiple synergistic effects. RRP ameliorates cognitive dysfunction and brain histopathological changes in AD mice. The mechanism of RRP ameliorating AD may be related to the regulation of INSR/IRS-1/AKT/GSK-3β signaling pathway and intestinal microbiota. This study supports the potential anti-AD efficacy of RRP and initially reveals the pharmacological mechanism of RRP, providing a theoretical basis for further clinical application of RRP.

Blood-brain barrier (BBB) damage is a critical event in ischemic stroke, contributing to aggravated brain damage. Endothelial cell form a major component of the BBB, but its regulation in stroke has yet to be clarified. We investigated the function of Yes-associated protein 1 (YAP) in the endothelium on BBB breakdown during cerebral ischemia/reperfusion (I/R) injury. The effects of YAP on BBB dysfunction were explored in middle cerebral artery occlusion/reperfusion (MCAO/R)-injury model mice and using brain microvascular endothelial cells (BMEC) exposed to oxygen-glucose deprivation/reoxygenation (OGD/R) injury. The degree of brain injury was estimated using staining (2,3,5-Triphenyltetrazolium chloride, hematoxylin and eosin) and the detection of cerebral blood flow. BBB breakdown was investigated by examining the leakage of Evans Blue dye and evaluating the expression of tight junction (TJ)-associated proteins and matrix metallopeptidase (MMP) 2 and 9. YAP expression was up-regulated in the nucleus of BMEC after cerebral I/R injury. Verteporfin (YAP inhibitor) down-regulated YAP expression in the nucleus and improved BBB hyperpermeability and TJ integrity disruption stimulated by cerebral I/R. YAP-targeted small interfering RNA (siRNA) exerted the same effects in BMEC cells exposed to OGD/R injury. Our findings provide new insights into the contributions made by YAP to the maintenance of BBB integrity and highlight the potential for YAP to serve as a therapeutic target to modulate BBB integrity following ischemic stroke and related cerebrovascular diseases.

Background: We aimed to evaluate the predictive value of the 'Timed Up and Go' test (TUGT) for identifying fall risk in community-dwelling elderly. Methods: From Aug 2016 to Feb 2017, cluster sampling was conducted among residents aged over 60 from 15 communities in Songjiang district, Shanghai. Face-to-face questionnaire interviews and TUGT measures were conducted to collect data. Results: 6,014 participants were enrolled, with an average age 72.7±7.0 years. 637 (10.6%) elderly people had a fall experience in the past year. TUGT for the non-fall group, one-fall group and recurrent-fall group was 9.02±4.39, 10.00±5.26 and 10.78±4.51 seconds respectively (P

Michelia champaca var. champaca is an ornamentally important tree in Magnoliaceae. The paper reported the complete chloroplast genome (cpDNA) of M. champaca var. champaca and its basic annotated information. The size of cpDNA is 160,008 bp, with a typical quadripartite structure of a large single-copy (LSC) region of 88,037 bp and a small single-copy (SSC) region of 18,809 bp separated by a pair identical inverted repeat regions (IRs) of 26,581 bp each. The genome contained 131 genes (113 unique), including 86 protein-coding genes (80 unique), 37 tRNA genes (29 unique), and eight rRNA genes (four unique). Phylogenetic analysis showed that M. champaca var. champaca is affinal to M. baillonii and they form a nomophyletic group with other eight Michelia species. This Michelia clade is sister to the Aromadendron cathcartii clade with high support. All genera mentioned in this analysis are nomophyletic under the system of Magnoliaceae by Sima and Lu.

An efficient microwave-assisted extraction (MAE) combined with in-capillary [Fe(ferrozine)3]2+-capillary electrophoresis-Diode Array Detector (in-capillary [Fe(ferrozine)3]2+-CE-DAD) was developed to screen active components with the ability to chelate ferrous ions and determine the total antioxidant activity. The MAE conditions, including methanol concentration, extraction power, extraction time, and the ratio of material to liquid, were optimized by an L9(34) orthogonal experiment. Background buffer, voltage, and cartridge temperature that affect the separation of six compounds were optimized. It was found that rutin and quercetin were the main components chelating ferrous ions in Flos Sophorae Immaturus (Flos Sophorae) by the in-capillary [Fe(ferrozine)3]2+-CE-DAD. The recoveries were ranged from 95.2% to 104%. It was concluded that the MAE combined with in-capillary [Fe(ferrozine)3]2+-CE-DAD method was a simple, reliable, and efficient tool for screening active components from the complex traditional Chinese medicine samples and evaluating their ability to chelate ferrous ions.

Introduction: Facing the challenges of aging populations, increasing chronic diseases prevalence and health system fragmentation, there have been several pilots of integrated health systems in China. But little is known about their structure, mechanism and effectiveness. The aim of this paper is to analyze health system integration and develop recommendations for achieving integration. Method: Huangzhong and Hualong counties in Qinghai province were studied as study sites, with only Huangzhong having implemented health system integration. Questionnaires, interviews, and health ­insurance records were sources of data. Social network analysis was employed to analyze integration, through structure measurement and effectiveness evaluation. Results: Health system integration in Huangzhong is higher than in Hualong, so is system ­effectiveness. The patient referral network in Hualong has more “leapfrog” referrals. The information sharing ­networks in both counties are larger than the other types of networks. The average distance in the joint ­training network of Huangzhong is less than in Hualong. Meanwhile, there are deficiencies common to both systems. Conclusion: Both county health systems have strengths and limitations regarding system integration. The use of medical consortia in Huangzhong has contributed to system effectiveness. Future research might consider alternative more context specific models of health system integration.

With the consideration of the dynamic role of microRNAs (miRNAs) in breast cancer, miRNAs may serve as therapeutic targets, helping to prevent development of therapy resistance, maintain stable disease, and prohibit metastatic spread. We identified the differentially expressed breast cancer-related gene ribonucleotide reductase subunit M2 (RRM2) as the study focus through microarray expression profiles. Next, the upstream regulatory microRNA (miR)-4500 of RRM2 was predicted using bioinformatics website analysis, and their binding was verified by a dual luciferase reporter gene assay. The regulatory effects of miR-4500 on breast cancer cell proliferation, apoptosis, migration, invasion, and capillary-like tube formation of endothelial cells were assessed by gain- and loss-of-function experiments. The experimental data revealed that miR-4500 was downregulated, whereas RRM2 was upregulated in breast cancer cells. Mechanistic analysis revealed that miR-4500 downregulated the RRM2 expression to inactivate the mitogen-activated protein kinase (MAPK) signaling pathway. Furthermore, miR-4500 exerted anti-tumor effects by targeting RRM2 through suppression of the MAPK signaling pathway in vitro, evidenced by attenuated cancer cell migration and invasion and capillary-like tube formation of endothelial cells. The in vivo experiments further corroborated in vitro results. Collectively, overexpressed miR-4500 could downregulate RRM2 and inhibit activation of the MAPK signaling pathway, thus attenuating breast cancer cell proliferation, invasion, migration, and angiogenesis and promoting breast cancer cell apoptosis.

Background: Increases in health care utilization and costs, resulting from the rising prevalence of chronic conditions related to the aging population, is exacerbated by a high level of fragmentation that characterizes health care systems in China. There have been several pilot studies in China, aimed at system-level care coordination and its impact on the full integration of health care system, but little is known about their practical effects. Huangzhong County is one of the pilot study sites that introduced organizational integration (a dimension of integrated care) among health care institutions as a means to improve system-level care coordination. The purposes of this study are to examine the effect of organizational integration on system-level care coordination and to identify factors influencing care coordination and hence full integration of county health care systems in rural China. Methods: We chose Huangzhong and Hualong counties in Qinghai province as study sites, with only Huangzhong having implemented organizational integration. A mixed methods approach was used based on (1) document analysis and expert consultation to develop Best Practice intervention packages; (2) doctor questionnaires, identifying care coordination from the perspective of service provision. We measured service provision with gap index, overlap index and over-provision index, by comparing observed performance with Best Practice; (3) semi-structured interviews with Chiefs of Medicine in each institution to identify barriers to system-level care coordination. Results: Twenty-nine institutions (11 at county-level, 6 at township-level and 12 at village-level) were selected producing surveys with a total of 19 schizophrenia doctors, 23 diabetes doctors and 29 Chiefs of Medicine. There were more care discontinuities for both diabetes and schizophrenia in Huangzhong than in Hualong. Overall, all three index scores (measuring service gaps, overlaps and over-provision) showed similar tendencies for the two conditions. The gap indices of schizophrenia (> 5.10) were bigger for diabetes (< 2.60) in both counties. The over-provision indices of schizophrenia (> 3.25) were bigger than diabetes (< 1.80) in both counties. Overlap indices for the two conditions exceeded justified overlaps, especially for diabetes. Gap index scores for schizophrenia interventions at the township-level and over-provision index scores for diabetes interventions at both village- and township-level showed big differences between the two counties. Insufficient medical staff with appropriate competencies, lack of motivation for care coordination and related supportive policies as well as unconnected information system were identified as barriers to system-level care coordination in both counties. Conclusion: Findings demonstrate that organizational integration in Huangzhong has not achieved a higher level of care coordination at this stage. System-level care coordination is most problematic at village-level institutions in Hualong, but at county-level institutions in Huangzhong. These findings suggest that attention be given to other aspects of integration (e.g., clinical and service integration) to promote system-level care coordination and contribute to the full integration of health care system in the pilot county. [ABSTRACT FROM AUTHOR]