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1.
Int J Nurs Stud ; 157: 104816, 2024 Sep.
Article in English | MEDLINE | ID: mdl-38824719

ABSTRACT

BACKGROUND: In 2009, China launched a new round of healthcare reform to provide households with secure, efficient, convenient, equitable and affordable healthcare services. Healthcare reform is underpinned by three critical pillars: the health workforce, funding, and infrastructure, with reform of the health workforce being particularly significant. OBJECTIVE: This study analyses the disparities in regional distribution and the inequity of healthcare workforce allocation across hospitals and primary health centers in China over twelve years. DESIGN: Retrospective longitudinal data from the National Health Statistics Yearbook 2011-2022 and National Statistical Yearbook in China from 2011 to 2022 were collected for analysis. PARTICIPANTS: The focus was on hospitals and primary health centers, explicitly examining their health technician and nursing workforce. METHODS: The research utilized four key indicators of the healthcare workforce to evaluate the distribution of health resources between hospitals and primary health centers. Furthermore, the Gini coefficient and Theil index were employed to assess the inequality in allocating the health workforce. RESULTS: Between 2010 and 2021, there was a nationwide increase in the ratio of health workers per 1000 population in hospitals and primary health centers. It is noted that rural districts had higher ratios than urban districts in terms of the number of health technicians and nurses per 1000 population, whether in hospitals or primary health centers; western districts had higher ratios than eastern and central districts did. In the same year, at different levels of medical institutions, the Theil indices of health technicians and nurses in hospitals were lower than those in primary health centers in terms of both demographic and geographical dimensions. Regarding the allocation of the health workforce by population, the Gini coefficient remained below 0.3, while for geographical allocation, it exceeded 0.4. CONCLUSIONS: This study analyzed the temporal trends and inequality of health-resource allocation at the hospital and primary health center levels in China, noting trends of improvements in the quantity and inequality in health workforce allocation from 2010 to 2021, suggesting the success of the government's efforts to advance healthcare reform since 2009. The allocation of health workforce based on population exhibits greater fairness compared to geographical distribution.


Subject(s)
Health Workforce , Primary Health Care , China , Longitudinal Studies , Primary Health Care/statistics & numerical data , Health Workforce/statistics & numerical data , Humans , Hospitals/statistics & numerical data , Healthcare Disparities/statistics & numerical data , Retrospective Studies
2.
J Ethnopharmacol ; 331: 118293, 2024 Sep 15.
Article in English | MEDLINE | ID: mdl-38705430

ABSTRACT

ETHNOPHARMACOLOGICAL RELEVANCE: Da-Chai-Hu-Tang (DCHT), a Chinese traditional herbal compound, has been utilized for the treatment of Hepatic diseases in China for over 1800 years. The DCHT formula contains eight herbals: Bupleurum chinense DC. (chaihu), Scutellaria baicalensis Georgi (huangqin), Paeonia lactiflora Pall. (baishao), Pinellia ternata (Thunb.) Makino (banxia), Rheum officinale Baill. (dahuang), Citrus × aurantium L. (zhishi), Zingiber officinale Roscoe (shengjiang), Ziziphus jujuba Mill. (dazao). Clinical studies have demonstrated the effectiveness of DCHT in hepatocellular carcinoma (HCC) and its ability to enhance the immunity of patients with hepatocellular carcinoma. A total of 20 Chinese articles have been published on the use of DCHT in treating HCC. AIM OF THE STUDY: The study aimed to validate the effect of DCHT in HCC cells and to identify related targets (TP53, AKT1, BCL2, STAT3) in treating HCC by DCHT in vitro experiments. MATERIALS AND METHODS: Cell proliferation and migration were investigated in vitro. Flow cytometry analysis was used to evaluate the cell cycle and apoptosis. Apoptotic bodies in HepG2 cells were observed using a confocal microscope. Biochemical detection was employed to analyze LDH release, MDA levels, and SOD levels. Bioinformatics analysis was used to predict core targets between DCHT and HCC, as well as potential signaling pathways. The protein levels of metastasis-associated, apoptosis, and PI3K, AKT, p-AKT, and STAT3 were further determined through Western blotting. RESULTS: Following treatment with DCHT, the inhibition of viability, migration, and G2/M arrest was observed in HepG2 cells. Flow cytometry analysis and Morphological apoptosis studies provided evidence that DCHT could induce apoptosis in HepG2 cells. Biochemical detection revealed that DCHT could increase LDH release and the level of MDA, and inhibit the viability of the SOD. Bioinformatics analysis identified key targets such as TP53, AKT1, BCL2, STAT3. The PI3K/AKT/STAT3 signaling pathway emerged as a critical pathway in the KEGG enrichment analysis. Western blotting results indicated that DCHT could enhance the expression of E-cadherin, p53, and Bax, while reducing the content of N-cadherin, Bcl-2, PI3K, p-AKT, AKT1, and STAT3. CONCLUSIONS: The results proved that DCHT could inhibit the progression and metastasis of HCC by regulating the expression of E-cadherin, N-cadherin, p53, Bax, Bcl-2, PI3K, p-AKT, AKT, and STAT3 through the PI3K/AKT/STAT3 signaling pathway.


Subject(s)
Apoptosis , Cell Cycle Checkpoints , Drugs, Chinese Herbal , Liver Neoplasms , Proto-Oncogene Proteins c-akt , STAT3 Transcription Factor , Humans , STAT3 Transcription Factor/metabolism , Apoptosis/drug effects , Proto-Oncogene Proteins c-akt/metabolism , Hep G2 Cells , Drugs, Chinese Herbal/pharmacology , Cell Cycle Checkpoints/drug effects , Liver Neoplasms/drug therapy , Liver Neoplasms/pathology , Carcinoma, Hepatocellular/drug therapy , Carcinoma, Hepatocellular/pathology , Carcinoma, Hepatocellular/metabolism , Signal Transduction/drug effects , Phosphatidylinositol 3-Kinases/metabolism , Antineoplastic Agents, Phytogenic/pharmacology , Cell Movement/drug effects , Cell Proliferation/drug effects
3.
Org Lett ; 26(17): 3661-3666, 2024 May 03.
Article in English | MEDLINE | ID: mdl-38656155

ABSTRACT

Considering the ubiquitous presence of pyridine moieties in pharmaceutical compounds, it holds immense value to develop practical and straightforward methodologies for accessing heterocyclic aromatic hydrocarbons. In recent years, N-alkoxypyridinium salts have emerged as convenient radical precursors, enabling the generation of the corresponding alkoxy radicals and pyridine through single-electron transfer. Herein, we present the first report on visible-light-mediated intermolecular alkoxypyridylation of alkenes employing N-alkoxylpyridinium salts as bifunctional reagents with an exceptionally low catalyst loading (0.5 mol %).

4.
Sci Rep ; 14(1): 3504, 2024 02 12.
Article in English | MEDLINE | ID: mdl-38347070

ABSTRACT

This study aims to assess the prevalence of geriatric syndromes and identify factors associated with multiple geriatric syndromes in community-dwelling older adults in China. We utilized a convenience sampling method to recruit older adults and from one rural and one urban community in Chengdu, China, from October 2022 to March 2023. A total of 706 older adults aged 60 years or older were included. Ten geriatric syndromes were investigated including two mental disorders: depressive symptoms, cognitive impairment; and eight somatic disorders: pain, falls, sleep disturbance, constipation, polypharmacy, multimorbidity, malnutrition and frailty. Multiple geriatric syndromes were defined as an individual having two or more geriatric syndromes. The data obtained were analysed using descriptive statistics. The independent risk factors for multiple geriatric syndromes were assessed using a logistic regression model. This study found that 90.5% of the participants had at least one geriatric syndrome, with 72.8% experiencing multiple geriatric syndromes. The top four geriatric syndromes in our study were polypharmacy (58.5%), malnutrition/at risk of malnutrition (43.1%), multimorbidity (42.1%), and frailty/prefrailty (34.3%). Of the older adults, 368(52.1%) had only somatic disorders, 18(2.5%) had only mental disorders and 253 (35.8%) had somatic-mental disorders. According to the logistic regression analysis, residence, age, marriage, BMI, and self-related health were significantly associated with multiple geriatric syndromes among older adults. This study highlights that multiple geriatric syndromes are prevalent among community-dwelling older adults in China, and underscores the significance of certain demographic factors in their occurrence. Future longitudinal studies are needed to establish the temporal relationship between multiple geriatric syndromes and these demographic factors, as well as to explore causal relationships and effective prevention strategies for geriatric syndrome.


Subject(s)
Cognitive Dysfunction , Frailty , Malnutrition , Humans , Aged , Frailty/epidemiology , Frailty/diagnosis , Independent Living , Cognitive Dysfunction/epidemiology , Risk Factors , Malnutrition/epidemiology , Syndrome , Geriatric Assessment/methods
5.
Huan Jing Ke Xue ; 45(1): 439-449, 2024 Jan 08.
Article in Chinese | MEDLINE | ID: mdl-38216493

ABSTRACT

Organic materials containing humic acids (HAs) play important roles in regulating the bioavailability of cadmium (Cd) in soils and thus its accumulation in crops. The effects of the two active components of HAs, humic acid (HA) and fulvic acid (FA), in organic materials and their different ratios (HA/FA) on Cd uptake and accumulation in rice were investigated using a field plot experiment, and their relationships with the Cd fractions and availability in paddy soil as influenced by the use of these organic materials were analyzed in combination with the fractionation method of chemical continuous extraction. The results showed that the effects of HAs on Cd availability in soil and Cd accumulation in rice grains were controlled by the ratios of the active components in the organic materials. The treatments with an HA/FA ratio ≥ 4/6 had a passivating effect on soil Cd, resulting in a significant reduction in Cd availability. Compared with that in the control without the application of HAs (CK), rice grain Cd concentration was reduced by 15.2%-33.3%, whereas those with an HA/FA ratio ≤ 2/8 activated Cd in soil, and the available Cd content was significantly increased. Compared with that in CK, rice grain Cd concentration was increased by 24.2%-42.4%. The ratios of HA/FA in HAs affected the morphological transformation of soil Cd. Compared with the CK treatment, the treatments with ratios of HA/FA ≥ 4/6 promoted the transformation of soil Cd from the exchangeable form (EX-Cd) with high activity to the carbonate bound form (CA-Cd) and Fe and Mn oxide-bound forms (FM-Cd) with low activity, whereas those with ratios of HA/FA ≤ 2/8 showed the opposite effects. The effects of HA and FA on soil pH and available sulfur concentration differed. Soil pH had a significant positive correlation with HA addition but a negative correlation with FA addition, and soil available sulfur content had a significant positive correlation with FA addition at the rice tillering stage. Therefore, to ensure the quality and safety of rice, organic materials with an HA/FA ratio ≥ 4/6 should be selected. The results provided a scientific basis for the directed utilization of organic materials containing HAs.


Subject(s)
Oryza , Soil Pollutants , Soil/chemistry , Cadmium/analysis , Oryza/chemistry , Soil Pollutants/analysis , Humic Substances , Edible Grain/chemistry , Sulfur/metabolism
6.
Org Lett ; 26(1): 315-320, 2024 Jan 12.
Article in English | MEDLINE | ID: mdl-38175121

ABSTRACT

A protocol was developed to achieve stereodivergent synthesis of stereoisomers of δ-lactam bearing vicinal chiral centers. Organocatalytic cascade reactions were employed to produce the target products as the kinetic products, which exhibited remarkable enantioselectivities. In the presence of DBU, the kinetic product underwent epimerization to form a thermodynamically more stable diastereomer without loss in enantioselectivity. By simply switching the chiral organocatalyst and its enantiomer, we can efficiently obtain four stereoisomers with high enantioselectivities.

7.
Skin Res Technol ; 29(12): e13415, 2023 Dec.
Article in English | MEDLINE | ID: mdl-38062667

ABSTRACT

INTRODUCTION: Chronic wounds are wounds that are not healed or have no healing tendency for more than 1 month due to various factors. In clinical nursing, chronic wounds are often not properly treated, and the treatment efficiency is low. Therefore, it is very important to explore effective methods to deal with chronic wounds. OBJECTIVE: To explore the effect of a self-made negative pressure suction device (NPSD) in the nursing of chronic wounds in the elderly. METHODS: A total of 50 elderly patients with chronic wounds who were hospitalised in our hospital from January 2020 to December 2022 were selected as participants by convenient sampling. According to the random number table method, they were divided into a control group and an observation group, with 25 people in each group. The control group was treated with chloroplast foam dressing, debridement gel and alginate dressing. The observation group was treated with a self-made NPSD on the basis of the control group. The wound healing of the two groups was observed. RESULTS: After the intervention of the self-made NPSD, the granulation tissue coverage rate and wound volume reduction rate of the observation group were significantly increased (p < 0.05), and the positive rate of bacterial infection was significantly decreased (p < 0.05). After 3 months of intervention, the total effective rate of the observation group was significantly higher than that of the control group (χ2  = 3.869, p = 0.0492). CONCLUSION: The self-made NPSD can effectively promote the healing of a chronic wound.


Subject(s)
Skin Transplantation , Wound Healing , Humans , Aged , Suction , Treatment Outcome , Debridement , Skin Transplantation/methods
8.
Nat Commun ; 14(1): 8073, 2023 Dec 06.
Article in English | MEDLINE | ID: mdl-38057349

ABSTRACT

How long-term changes in surface topography relate to coseismic uplift is key to understanding the creation of high elevations along active mountain fronts, and remains hotly debated. Here we investigate this link by modeling the development of growth strata and the folding of river terraces above the Pishan duplex system in the southern Tarim Basin. We show that synchronous duplex thrusting of two neighboring faults with varying slip rates, associated with in-sequence propagation of the Pishan thrust system, is required to explain the presence of opposite-dipping panels of growth strata on the duplex front, and basinward migration of terrace fold crests. Importantly, this process of synchronous thrusting within the duplex reconciles the discrepancy between the deformation of terrace folds at the 10-1-100 million-year timescale and the maximum coseismic uplift of the 2015 Mw 6.4 Pishan earthquake on the frontal thrust. These results suggest that topography mismatch at different time scales can reflect the long-term kinematic evolution of fault systems. Thus, our study highlights the importance of characterizing complex subsurface fault kinematics for studying topographic growth, and motivates rethinking of the mountain building process in worldwide active fold-and-thrust belts, from short-term to long-term timescales.

9.
Sci Rep ; 13(1): 19484, 2023 11 09.
Article in English | MEDLINE | ID: mdl-37945611

ABSTRACT

This study aims to describe the activity of daily living (ADL) situation and determine the relationship between health behavior and ADL among older adults in China. A cross-sectional, observational study was conducted in one urban community and one rural community in Chengdu (a city located in Southwest China), China, from October 2022 to March 2023. A total of 706 older adults were included in this study. The associations between health behaviour and ADL were assessed by logistic regression model. Of the 706 older adults, 169 (23.9%) were disabled in ADL. According to the logistic regression analysis, age (60-69 years old: OR = 0.015, 95% CI 0.007 to 0.035, P < 0.001; 70-79 years old: OR = 0.116, 95% CI 0.060 to 0.227, P < 0.001), resident(OR = 0.568, 95% CI 0.330 to 0.976, P = 0.041), chronic disease (0 type: OR = 0.023, 95% CI 0.001 to 0.379, P = 0.008; 1-4 types: OR = 0.357, 95% CI 0.219 to 0.582, P < 0.001), no exercise (OR = 4.562, 95% CI 2.263 to 8.026, P < 0.001), and physical examination (OR = 2.217, 95% CI 1.294 to 3.496, P = 0.003) were significantly associated with ADL among older adults in Southwest China. This study showed that older adults had a higher ADL disability ratio. Age, resident, chronic disease, exercise and physical examination were associated with ADL among older adults. The study indicates that medium/high exercise maybe a protective factor for older adults, and nursing staff can encourage older adults to exercise when carrying out primary prevention measures. The government and public health institutions should give special attention to older adults and help them to acquire the habit of having an annual physical examination.


Subject(s)
Activities of Daily Living , Disabled Persons , Humans , Aged , Middle Aged , Cross-Sectional Studies , China/epidemiology , Health Behavior , Chronic Disease
11.
Eur J Radiol ; 168: 111133, 2023 Nov.
Article in English | MEDLINE | ID: mdl-37827088

ABSTRACT

OBJECTIVES: To evaluate the performance of coronary computed tomography angiography (CCTA) derived characteristics including CT derived fractional flow reserve (CT-FFR) with FFR as a reference standard in identifying the lesion-specific ischemia by machine learning (ML) algorithms. METHODS: The retrospective analysis enrolled 596 vessels in 462 patients (mean age, 61 years ± 11 [SD]; 71.4 % men) with suspected coronary artery disease who underwent CCTA and invasive FFR. The data were divided into training cohort, internal validation cohort, external validation cohorts 1 and 2 according to participating centers. All CCTA-derived parameters, which contained 10 qualitative and 33 quantitative plaque parameters, were collected to establish ML model. The Boruta and unsupervised clustering algorithm were implemented to select important and non-redundant parameters. Finally, the eight features with the highest mean importance were included for further ML model establishment and decision tree building. Five models were built to predict lesion-specific ischemia: stenosis degree from CCTA, CT-FFR, ΔCT-FFR, ML model and nested model. RESULTS: Low-attenuation plaque, bend and lesion length were the main predictors of ischemia-specific lesions. Of 5 models, the ML model showed favorable discrimination for ischemia-specific lesions in the training and three validation sets (area under the curve [95 % confidence interval], 0.93 [0.90-0.96], 0.86 [0.79-0.94], 0.88 [0.83-0.94], and 0.90 [0.84-0.96], respectively). The nested model which combined the ML model and CT-FFR showed better diagnostic efficacy (AUC [95 %CI], 0.96 [0.94-0.99], 0.92 [0.86-0.99], 0.92 [0.86-0.99] and 0.94 [0.91-0.98], respectively; all P < 0.05), and net reclassification improvement (NRI) and integrated discrimination improvement (IDI) were significantly higher than CT-FFR alone. CONCLUSIONS: Comprehensive CCTA-derived multiparameter model could better predict the ischemia-specific lesions by ML algorithms compared to stenosis degree from CTA, CT-FFR and ΔCT-FFR. Decision tree can be used to predict myocardial ischemia effectively.


Subject(s)
Coronary Artery Disease , Coronary Stenosis , Fractional Flow Reserve, Myocardial , Plaque, Atherosclerotic , Female , Humans , Male , Middle Aged , Computed Tomography Angiography/methods , Constriction, Pathologic , Coronary Angiography/methods , Coronary Artery Disease/diagnostic imaging , Coronary Stenosis/diagnostic imaging , East Asian People , Ischemia , Machine Learning , Predictive Value of Tests , Retrospective Studies , Tomography, X-Ray Computed , Aged
12.
Inorg Chem ; 62(38): 15711-15718, 2023 Sep 25.
Article in English | MEDLINE | ID: mdl-37695723

ABSTRACT

Exploring highly efficient blue-emissive lead-free halide materials is a significant and challenging objective in the study of luminescent materials. This study reports the synthesis of a new zero-dimensional (0D) hybrid zinc halide of [CYP]ZnBr4 (CYP = 1-cyclohexylpiperazine) containing an isolated [ZnBr4]2- tetrahedron. [CYP]ZnBr4 exhibits strong blue light emission with a high photoluminescence quantum yield (PLQY) of 79.22%, surpassing all previously reported 0D zinc halide counterparts. According to the theoretical and experimental studies, the blue light emission is attributed to intrinsic self-trapped excitons resulting from strong electron-phonon coupling and structural deformation. Importantly, [CYP]ZnBr4 demonstrates excellent structural and luminescence stability toward high temperatures (180 °C) over at least half a month. High luminescence efficiency and stability enable [CYP]ZnBr4 to be an efficient blue phosphor to fabricate white light-emitting diodes (LEDs), which produces high-quality white light with a color rendering index (CRI) of 93.1 and a correlated color temperature (CCT) of 5304 K, closely resembling natural sunlight. This white LED also exhibits consistent performance and stability across different drive currents, suggesting the potential for high-power optoelectronic applications. Overall, this study paves the way for the utilization of 0D hybrid halides in advanced solid-state lighting applications.

13.
Zhongguo Zhen Jiu ; 43(9): 1028-32, 2023 Sep 12.
Article in Chinese | MEDLINE | ID: mdl-37697878

ABSTRACT

OBJECTIVE: To compare the therapeutic effect between Hunyuan moxibustion and oral western medication on diarrhea-predominant irritable bowel syndrome(IBS-D)of spleen and kidney yang deficiency. METHODS: Sixty patients with IBS-D of spleen and kidney yang deficiency were randomly divided into a Hunyuan moxibustion group and a western medication group, 30 cases each group. The Hunyuan moxibustion group was treated with Hunyuan moxibustion at Guanyuan(CV 4),40 min each time, once a day; in the western medication group,loperamide hydrochloride capsules (2 mg each time, 3 times a day) and bacillus licheniformis live capsules (0.5 g each time, 3 times a day) were given orally.Both groups were treated for 20 days. The scores of irritable bowel syndrome(IBS)symptom severity scale(IBS-SSS), IBS quality of life scale (IBS-QOL) and TCM symptom grading quantitative were observed before and after treatment, and the clinical efficacy and safety were evaluated in the two groups. RESULTS: After treatment,each item scores and total scores of IBS-SSS in the two groups were lower than those before treatment(P<0.05), and the total scores of IBS-QOL were higher than those before treatment (P<0.05);each item score and total score of IBS-SSS in the Hunyuan moxibustion group were lower than those in the western medication group (P<0.05), and the total score of IBS-QOL in the Hunyuan moxibustion group was higher than that in the western medication group (P<0.05).After treatment, each item score and total score of TCM symptom grading quantitative in the Hunyuan moxibustion group were lower than those before treatment (P<0.05), the abdominal pain, diarrhea, lack of appetite scores and total score in the western medication group were lower than those before treatment (P<0.05);and the abdominal pain, soreness and weakness of waist and knees, fear to cold and cold limbs scores and total score in the Hunyuan moxibustion group were lower than those in the western medication group (P<0.05).The total effective rate was 90.0%(27/30)in the Hunyuan moxibustion group, which was higher than 73.3%(22/30)in the western medication group (P<0.05). No adverse reactions occurred in both groups during treatment. CONCLUSION: Hunyuan moxibustion can effectively improve the symptom severity and quality of life in patients with IBS-D of spleen and kidney yang deficiency, especially in improving the symptoms of abdominal pain, soreness and weakness of waist and knees, fear to cold and cold limbs.Its therapeutic effect is superior to western medication.


Subject(s)
Irritable Bowel Syndrome , Moxibustion , Humans , Spleen , Irritable Bowel Syndrome/therapy , Quality of Life , Capsules , Yang Deficiency/therapy , Kidney , Abdominal Pain/etiology , Abdominal Pain/therapy , Diarrhea/therapy
14.
Anticancer Res ; 43(8): 3479-3486, 2023 Aug.
Article in English | MEDLINE | ID: mdl-37500134

ABSTRACT

BACKGROUND/AIM: Hepatocellular carcinoma (HCC) currently represents the third most prevalent cause of cancer-related deaths globally. HCC is typically diagnosed at advanced stages with metastasis, and has a poor outcome. In order to identify useful biomarkers for early diagnosis and develop novel therapeutic targets, it is necessary to better understand the cellular mechanisms driving HCC progression. MATERIALS AND METHODS: Public datasets were used to detect Sjögren's syndrome nuclear autoantigen-1 (SSNA1) expression in HCC. Scratch assay and transwell invasion assays were used to evaluate the migration and invasion ability of HCC cells. We explored the molecular mechanism by western blotting, viability and transfection assays. RESULTS: SSNA1 was found up-regulated in human HCC tissues. SSNA1 expression increased along with HCC progression. In addition, elevated SSNA1 expression in HCC patients was closely correlated to a poor prognosis. The proliferation and apoptosis of HCC cells were unaffected by reducing SSNA1 expression. Meanwhile, STAT3/EMT axis inhibition mediated by SSNA1 depletion prevented HCC cells from migrating and invading in vitro. CONCLUSION: SSNA1 could be used as a biomarker for HCC diagnosis and prognosis, and point the direction for the future investigation of innovative approaches to target and treat HCC.


Subject(s)
Carcinoma, Hepatocellular , Liver Neoplasms , Humans , Carcinoma, Hepatocellular/pathology , Liver Neoplasms/pathology , Cell Movement , Cell Line, Tumor , Prognosis , Epithelial-Mesenchymal Transition , Gene Expression Regulation, Neoplastic , Cell Proliferation/genetics , Neoplasm Metastasis , STAT3 Transcription Factor/genetics , STAT3 Transcription Factor/metabolism
15.
Front Pharmacol ; 14: 1194869, 2023.
Article in English | MEDLINE | ID: mdl-37465526

ABSTRACT

The normal function of the medial prefrontal cortex (mPFC) is essential for regulating neurocognition, but it is disrupted in the early stages of Alzheimer's disease (AD) before the accumulation of Aß and the appearance of symptoms. Despite this, little is known about how the functional activity of medial prefrontal cortex pyramidal neurons changes as Alzheimer's disease progresses during aging. We used electrophysiological techniques (patch-clamping) to assess the functional activity of medial prefrontal cortex pyramidal neurons in the brain of 3xTg-Alzheimer's disease mice modeling early-stage Alzheimer's disease without Aß accumulation. Our results indicate that firing rate and the frequency of spontaneous excitatory postsynaptic currents (sEPSCs) were significantly increased in medial prefrontal cortex neurons from young Alzheimer's disease mice (4-5-month, equivalent of <30-year-old humans) compared to age-matched control mice. Blocking ionotropic glutamatergic NMDA receptors, which regulate neuronal excitability and Ca2+ homeostasis, abolished this neuronal hyperactivity. There were no changes in Ca2+ influx through the voltage-gated Ca2+ channels (VGCCs) or inhibitory postsynaptic activity in medial prefrontal cortex neurons from young Alzheimer's disease mice compared to controls. Additionally, acute exposure to Aß42 potentiated medial prefrontal cortex neuronal hyperactivity in young Alzheimer's disease mice but had no effects on controls. These findings indicate that the hyperactivity of medial prefrontal cortex pyramidal neurons at early-stage Alzheimer's disease is induced by an abnormal increase in presynaptic glutamate release and postsynaptic NMDA receptor activity, which initiates neuronal Ca2+ dyshomeostasis. Additionally, because accumulated Aß forms unconventional but functional Ca2+ channels in medial prefrontal cortex neurons in the late stage of Alzheimer's disease, our study also suggests an exacerbated Ca2+ dyshomeostasis in medial prefrontal cortex pyramidal neurons following overactivation of such VGCCs.

16.
Front Pharmacol ; 14: 1152667, 2023.
Article in English | MEDLINE | ID: mdl-37063258

ABSTRACT

Single-nucleotide polymorphisms are connected with the risk of epilepsy on occurrence, progress, and the individual response to drugs. Progress in genomic technology is exposing the complex genetic architecture of epilepsy. Compelling evidence has demonstrated that purines and adenosine are key mediators in the epileptic process. Our previous study found the interconnection of P2Y12 receptor single-nucleotide polymorphisms and epilepsy. However, little is known about the interaction between the purine nucleoside A2A receptor and rate-limiting enzyme ecto-5'-nucleotidase/CD73 and epilepsy from the genetic polymorphism aspect. The aim of the study is to evaluate the impact of A2AR and CD73 polymorphisms on epilepsy cases. The study group encompassed 181 patients with epilepsy and 55 healthy volunteers. A significant correlation was confirmed between CD73 rs4431401 and epilepsy (p < 0.001), with TT genotype frequency being higher and C allele being lower among epilepsy patients in comparison with healthy individuals, indicating that the presence of the TT genotype is related to an increased risk of epilepsy (OR = 2.742, p = 0.006) while carriers of the C allele demonstrated a decreased risk of epilepsy (OR = 0.304, p < 0.001). According to analysis based on gender, the allele and genotype of rs4431401 in CD73 were associated with both male and female cases (p < 0.0001, p = 0.026, respectively). Of note, we found that A2AR genetic variants rs2267076 T>C (p = 0.031), rs2298383 C>T (p = 0.045), rs4822492 T>G (p = 0.034), and rs4822489 T>G (p = 0.029) were only associated with epilepsy in female subjects instead of male. It is evident that the TT genotype and T allele of rs4431401 in CD73 were genetic risk factors for epilepsy, whereas rs2267076, rs2298383, rs4822492, and rs4822489 polymorphisms of the A2AR were mainly associated with female subjects.

18.
Front Cardiovasc Med ; 10: 1120543, 2023.
Article in English | MEDLINE | ID: mdl-37077741

ABSTRACT

Aims: To assess longitudinal changes in blood pressure (BP) and fasting plasma glucose (FPG) in primary care patients with concomitant hypertension and type 2 diabetes mellitus (T2DM), and to explore factors associated with patients' inability to improve BP and FPG at follow-up. Methods: We constructed a closed cohort in the context of the national basic public health (BPH) service provision in an urbanised township in southern China. Primary care patients who had concomitant hypertension and T2DM were retrospectively followed up from 2016 to 2019. Data were retrieved electronically from the computerised BPH platform. Patient-level risk factors were explored using multivariable logistic regression analysis. Results: We included 5,398 patients (mean age 66 years; range 28.9 to 96.1 years). At baseline, almost half [48.3% (2,608/5,398)] of patients had uncontrolled BP or FPG. During follow-up, more than one-fourth [27.2% (1,467/5,398)] of patients had no improvement in both BP and FPG. Among all patients, we observed significant increases in systolic BP [2.31 mmHg, 95% confidence interval (CI): 2.04 to 2.59, p < 0.001], diastolic BP (0.73 mmHg, 0.54 to 0.92, p < 0.001), and FPG (0.12 mmol/l, 0.09 to 0.15, p < 0.001) at follow-up compared to baseline. In addition to changes in body mass index [adjusted odds ratio (aOR)=1.045, 1.003 to 1.089, p = 0.037], poor adherence to lifestyle advice (aOR = 1.548, 1.356 to 1.766, p < 0.001), and unwillingness to actively enrol in health-care plans managed by the family doctor team (aOR = 1.379, 1.128 to 1.685, p = 0.001) were factors associated with no improvement in BP and FPG at follow-up. Conclusion: A suboptimal control of BP and FPG remains an ongoing challenge to primary care patients with concomitant hypertension and T2DM in real-world community settings. Tailored actions aiming to improve patients' adherence to healthy lifestyles, expand the delivery of team-based care, and encourage weight control should be incorporated into routine healthcare planning for community-based cardiovascular prevention.

19.
J Ethnopharmacol ; 312: 116523, 2023 Aug 10.
Article in English | MEDLINE | ID: mdl-37080364

ABSTRACT

ETHNOPHARMACOLOGICAL RELEVANCE: The capitulum of Coreopsis tinctoria Nutt. (CT, Xue-Ju in Chinese) is a precious medicine in Xinjiang Uygur Autonomous region of China. The Coreopsis tinctoria Nutt. is used to prevent and treat dyslipidemia, coronary heart disease, etc. Recent studies have shown that its extract has a pharmacological effect on hyperlipidemia and hyperglycemia. AIM OF THE STUDY: The study aimed to systematically evaluate the lipid-lowering activity of CT through a mice model of hyperlipidemia and a human hepatoma G2 (HepG2) cells model of lipid accumulation, and to investigate its main active components and mechanism. MATERIALS AND METHODS: Biochemical analysis of blood/liver lipids and liver histopathology were used to evaluate the effect of the aqueous extract of Coreopsis tinctoria Nutt. (AECT) on hyperlipidemia mice. High-performance liquid chromatography (HPLC) analysis was used to identify the main components in the AECT. Oil red O staining, immunofluorescence, western blotting, and determination of the total cholesterol (TC), total triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C) were used to further study the effect and potential mechanism of the AECT main components on sodium oleate-induced lipid accumulation in HepG2 cells. RESULTS: We confirmed the lipid-lowering activity of the aqueous extract and further identified flavonoids as its main components. Among them, five Coreopsis tinctoria Nutt. flavonoids mixture (FM) significantly reduced lipid droplet area, lipid content, TC, TG, and LDL-C levels, and elevated HDL-C levels in HepG2 cells induced by sodium oleate. Furthermore, they increased lipophagy in HepG2 lipid-accumulating cells, while decreasing the ratio of p-PI3K/PI3K, p-AKT/AKT, and p-mTOR/mTOR. Most importantly, marein may be a key component. CONCLUSIONS: Our study demonstrated that AECT, with flavonoids as the main component, can improve diet-induced hyperlipidemia in obese mice. Among the main five flavonoids, marein plays a key role in promoting lipophagy by regulating the PI3K/AKT/mTOR pathway, resulting in a lipid-lowering effect.


Subject(s)
Hyperlipidemias , Phosphatidylinositol 3-Kinases , Mice , Humans , Animals , Proto-Oncogene Proteins c-akt , Cholesterol, LDL , Flavonoids/pharmacology , Flavonoids/therapeutic use , Hyperlipidemias/metabolism , Lipids/therapeutic use , Triglycerides , TOR Serine-Threonine Kinases
20.
Zhongguo Zhong Yao Za Zhi ; 48(3): 681-688, 2023 Feb.
Article in Chinese | MEDLINE | ID: mdl-36872231

ABSTRACT

To maintain the precision and stability of the efficacy of classical formulas, this study compared the origins and specifications of Bupleuri Radix and revealed the precise application regularity of Bupleurum chinense(Beichaihu) and Bupleurum scorzonerifolium(Nanchaihu) in classical formulas. The efficacy and indications of formulas with Bupleuri Radix as the sovereign drug in the Treatise on Cold Damage and Miscellaneous Diseases(Shang Han Za Bing Lun) were investigated. The difference in the efficacy of Bupleuri Radix as well as the differences in the chemical composition, and liver-protecting and lipid-lowering effects of the decoctions of Beichaihu and Nanchaihu were analyzed with LC-MS technology based on the CCl_4-induced liver injury model in mice and sodium oleate-induced HepG2 hyperlipidemia cell model. The results showed that seven classical formulas with Bupleuri Radix as the sovereign drug in the Treatise on Cold Damage and Miscellaneous Diseases were mainly used in the treatment of digestive, metabolic, immune, circulatory, and other diseases. Bupleuri Radix mainly played the functions of protecting the liver, benefiting the gallbladder, and lowering the lipid, and had different focuses in different formulas. There were 14 differential components in the decoctions of Beichaihu and Nanchaihu, and the chemical structures of 11 components were identified, including 10 saponins and one flavonoid. The results of the liver-protecting efficacy experiment showed that compared with the Nanchaihu decoction, Beichaihu decoction could reduce the serum aspartate aminotransferase(AST) activity in liver injury model mice(P<0.01). The results of the lipid-lowering efficacy experiment proved that Beichaihu and Nanchaihu decoctions both showed highly significant differences in lowering the total cholesterol(TC) and triglyceride(TG) content in HepG2 cells(P<0.01), and Nanchaihu decoction was superior to Beichaihu decoction in lowering the lipid. The results of this study preliminarily proved that there were differences in chemical composition, and liver-protecting and lipid-lowering effects of Beichaihu and Nanchaihu decoctions, indicating that it was necessary to determine the precise origin of Bupleuri Radix in the clinical formulation of traditional Chinese medicine. The study provides a scientific basis for both precise clinical medication and purpose-based accurate quality evaluation of traditional Chinese medicine in clinical application.


Subject(s)
Bupleurum , Liver , Animals , Mice , Aspartate Aminotransferases
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