Community engagement is increasingly promoted to strengthen the ethics of medical research in low-income countries. One strategy is to use community advisory boards (CABs): semi-independent groups that can potentially...Community engagement is increasingly promoted to strengthen the ethics of medical research in low-income countries. One strategy is to use community advisory boards (CABs): semi-independent groups that can potentially safeguard the rights of study participants and help improve research. However, there is little published on the experience of operating and sustaining CABs. The Shoklo Malaria Research Unit (SMRU) has been conducting research and providing healthcare in a population of refugees, migrant workers, and displaced people on the Thai-Myanmar border for over 25 years. In 2009 SMRU facilitated the establishment of the Tak Province Community Ethics Advisory Board (T-CAB) in an effort to formally engage with the local communities both to obtain advice and to establish a participatory framework within which studies and the provision of health care can take place. In this paper, we draw on our experience of community engagement in this unique setting, and on our interactions with the past and present CAB members to critically reflect upon the CAB’s goals, structure and operations with a focus on the practicalities, what worked, what did not, and on its future directions.展开更多
Machine learning(ML)is a type of artificial intelligence that assists computers in the acquisition of knowledge through data analysis,thus creating machines that can complete tasks otherwise requiring human intelligen...Machine learning(ML)is a type of artificial intelligence that assists computers in the acquisition of knowledge through data analysis,thus creating machines that can complete tasks otherwise requiring human intelligence.Among its various applications,it has proven groundbreaking in healthcare as well,both in clinical practice and research.In this editorial,we succinctly introduce ML applications and present a study,featured in the latest issue of the World Journal of Clinical Cases.The authors of this study conducted an analysis using both multiple linear regression(MLR)and ML methods to investigate the significant factors that may impact the estimated glomerular filtration rate in healthy women with and without non-alcoholic fatty liver disease(NAFLD).Their results implicated age as the most important determining factor in both groups,followed by lactic dehydrogenase,uric acid,forced expiratory volume in one second,and albumin.In addition,for the NAFLD-group,the 5th and 6th most important impact factors were thyroid-stimulating hormone and systolic blood pressure,as compared to plasma calcium and body fat for the NAFLD+group.However,the study's distinctive contribution lies in its adoption of ML methodologies,showcasing their superiority over traditional statistical approaches(herein MLR),thereby highlighting the potential of ML to represent an invaluable advanced adjunct tool in clinical practice and research.展开更多
The present study, carried out in the forest (Daloa) and pre-forest (M’Bahiakro) zones of Cote d’Ivoire, aims to determine soil landscape units using the coding method. Geological maps and satellite images (SRTM and...The present study, carried out in the forest (Daloa) and pre-forest (M’Bahiakro) zones of Cote d’Ivoire, aims to determine soil landscape units using the coding method. Geological maps and satellite images (SRTM and Landsat) were used for this purpose. The methodological approach adopted consisted in producing maps of slope, geology, land use and topography using the codification method. These various maps, integrated into a GIS using the coding aggregation method, were used to generate soil landscape maps. Twenty-seven (27) soil landscapes have been identified for the pre-forest zone (M’Bahiakro), with a strong dominance of acid rock over a moderate relief under savannah, forest/degraded forest and crops/fallow. However, the forest zone (Daloa), with forty-one (41) soil landscapes identified over the entire zone, is characterized by a majority of mafic rocks on a medium altitude under forest/degraded forest, water and crops/fallow. The criteria used from the codification method (sum of aggregations) made it possible to predict the spatial distribution of soil map units according to agro-ecological environments in the humid intertropical zone. This is essential for the orientation and reinforcement of soil survey tools. However, a comparative evaluation of the different multicriteria analysis methods for coding and weighting soil landscape unit mapping would enable us to identify the most suitable and efficient method for drawing up base maps for soil surveys.展开更多
Introduction: Cardiovascular disease represents a major public health burden worldwide. Research and management of risk factors contribute to the prevention of these diseases. The aim of this study was to assess the p...Introduction: Cardiovascular disease represents a major public health burden worldwide. Research and management of risk factors contribute to the prevention of these diseases. The aim of this study was to assess the prevalence of dyslipidemia in the biochemistry unit of the Charles De Gaulle Pediatric University Hospital (CHUP-CDG) in Ouagadougou. Material and Methods: This was a descriptive and analytical cross-sectional study, with retrospective data collection from January 1, 2020 to December 31, 2022. Patients of all ages who performed a lipid panel in the CHUP-CDG biochemistry unit during the study period have been included. Results: A total of 2872 patients have been included. The mean age of the study population was 27.72 ± 19.51 years and the M/F sex ratio was 0.81. Among the patients, 22.84% had at least one dyslipidemia. The prevalences of hypercholesterolemia, hypo-HDL cholesterolemia and hyper-LDL cholesterolemia were 11.57%, 49.19% and 57.50% respectively. Hypertriglyceridemia and mixed hyperlipidemia were present in 9.04% and 2.08% of patients. Hypercholesterolemia was significantly more frequent in the female sex (p = 0.0077);hyper-LDL cholesterolemia (p = 0.0255) and mixed hyperlipidemia (p Conclusion: The relatively high prevalence of dyslipidemia in the study indicates a worrying situation. It would therefore appear essential to extend the search for risk factors nationwide, particularly those that can be modified, in order to reduce morbidity and mortality linked to cardiovascular disease.展开更多
Introduction: Low birth weight (LBW) is defined by the World Health Organization (WHO) as a birth weight strictly below 2500 g, whatever the term of pregnancy. It constitutes a major public health problem, both in dev...Introduction: Low birth weight (LBW) is defined by the World Health Organization (WHO) as a birth weight strictly below 2500 g, whatever the term of pregnancy. It constitutes a major public health problem, both in developed and developing countries, due to its magnitude and its strong association with infant morbidity and mortality. Main objective was to study the factors associated with the occurrence of small-for-gestational-age newborns in Douala. Methodology: We carried out a cross-sectional analytical study with prospective data collection using a technical pretested sheet in the maternity wards of the Douala General Hospital, the Laquintinie Hospital, and the District hospitals of Deido, Nylon and Bonassama over a period of 4 months (January to April 2020). We were interested in any newborn, born alive, vaginally or by cesarean section, of low weight, seen in the first 24 hours from a full-term single-fetal pregnancy whose mother had given her consent. Our sampling was consecutive and non-exhaustive. We excluded newborns whose term was unclear and those with congenital malformations or signs of embryo-foetopathy. Data collection was done using survey sheets. Statistical analyzes were carried out with CS Pro 7.3 and SPSS version 25.0 software. The Student, Chi-square and Fischer tests were used to compare the means of the variables, the percentages with a significance threshold P value Results: During the study period, 305 full-term newborns were included, divided into 172 boys and 133 girls. The percentage of small-for-gestational-age newborns was 9.8%;after multivariate analysis by logistic regression to eliminate confounding factors, we found maternal factors associated with small for gestational age newborns;maternal age less than 20 years, primiparity, gestational age (37 - 38), a delay in prenatal visits greater than 14 weeks, anemia in pregnancy, positive toxoplasmosis serology in pregnancy, a body mass index of Conclusion: Our study revealed the potential determinants of low birth weight at term in the Cameroonian urban context and specifically in Douala.展开更多
Introduction: Spontaneous abortion of the second trimester is an interruption of pregnancy with complete expulsion or not of the product of conception between 15 and 28 weeks of pregnancy without any maneuvers. The ob...Introduction: Spontaneous abortion of the second trimester is an interruption of pregnancy with complete expulsion or not of the product of conception between 15 and 28 weeks of pregnancy without any maneuvers. The objective of our study was to determine the factors associated with second trimester spontaneous abortions at Laquintinie Hospital in Douala. Methodology for this purpose: We conducted a case-control study from January to May 2019 on pregnant women who may or may not have had spontaneous second trimester abortions. Results: In total we recorded 1609 pregnancies and recruited 184 patients, including 46 cases and 138 controls;which gave a frequency of spontaneous abortion in the second trimester of pregnancy of 2.85%. A correlative analysis showed that spontaneous abortions in the second trimester were associated with housewife status (OR = 2.89;CI = 1.21 - 6.79;p = 0.010), gestation > 5 (OR = 4.09;CI = 1.02 - 17.66;p = 0.040), multiparity (OR = 3.81;CI = 1.59 - 9.16;p = 0.002), history of endouterine maneuvers (OR = 5.64;CI = 2.43 - 13 .03;p = 0.000), malaria in pregnancy (OR = 3.99;CI = 1.1 - 14.76;p = 0.030), incompleteness on the second trimester ultrasound (OR = 2.37;CI = 1.18 - 4.70;p = 0.010), jolts when traveling (OR = 46.04;CI = 17.29 - 123.66;p = 0.000), long car journeys (OR = 7.05;CI = 1.99 - 27.77;p = 0.000). After logistic regression eliminating the confounding factors, only the following were associated with abortions: Multiparity (OR = 13.90;CI = 2.96 - 65.18;p = 0.000), endo uterine maneuvers (OR = 3.69;CI = 1. 01 - 13.44;p = 0.047), jolts when traveling (OR = 72.63;CI = 19.47 - 270.96;p = 0.000), long car journeys (OR = 15.41;CI = 2.7 - 85, 95;p = 0.000). Conclusion: Our study reveals that a set of factors contribute to the occurrence of spontaneous abortions in the second trimester of pregnancy in our context.展开更多
Brain-computer interface(BCI)technology is rapidly advancing in medical research and application.As an emerging biomedical engineering technology,it has garnered significant attention in the clinical research of brain...Brain-computer interface(BCI)technology is rapidly advancing in medical research and application.As an emerging biomedical engineering technology,it has garnered significant attention in the clinical research of brain disease diagnosis and treatment,neurological rehabilitation,and mental health.However,BCI also raises several challenges and ethical concerns in clinical research.In this article,the authors investigate and discuss three aspects of BCI in medicine and healthcare:the state of international ethical governance,multidimensional ethical challenges pertaining to BCI in clinical research,and suggestive concerns for ethical review.Despite the great potential of frontier BCI research and development in the field of medical care,the ethical challenges induced by itself and the complexities of clinical research and brain function have put forward new special fields for ethics in BCI.To ensure"responsible innovation"in BCI research in healthcare and medicine,the creation of an ethical global governance framework and system,along with special guidelines for cutting-edge BCI research in medicine,is suggested.展开更多
BACKGROUND The rising prevalence of carbapenem-resistant Acinetobacter baumannii(CRAB)in neonatal intensive care units(NICUs)represents an escalating challenge in healthcare settings,particularly in managing hospital-...BACKGROUND The rising prevalence of carbapenem-resistant Acinetobacter baumannii(CRAB)in neonatal intensive care units(NICUs)represents an escalating challenge in healthcare settings,particularly in managing hospital-acquired infections(HAIs).Studies across various World Health Organization regions have documented a significant incidence of CRAB-related HAIs,with rates as high as 41.7 cases per 1000 patients in ICUs,accounting for 13.6%of all HAIs.These infections pose a doubled mortality risk compared to infections with carbapenem-susceptible Acinetobacter baumannii.A particularly concerning aspect of CRAB colonization is its asymptomatic nature,enabling its transmission through healthcare workers(HCWs)or the NICU environment to vulnerable neonates with developing immune systems.AIM To explore the prevalence of CRAB colonization in NICUs,focusing on neonates,healthcare workers,and the environmental samples,to enhance epidemiological understanding and inform targeted interventions.METHODS We conducted according to PRISMA 2020 checklist guidelines,a comprehensive literature search across multiple databases including MEDLINE(Ovid),EMBASE(Ovid),Global Health(Ovid),Web of Science,and Global Index Me-dicus.Studies were selected based on predetermined criteria,primarily involving neonates,HCWs,and environmental swabs,using culture or molecular methods to detect CRAB colonization.We excluded studies that did not specifically focus on NICUs,were duplicates,or lacked necessary data.The study selection and quality assessment were conducted independently by two reviewers.Data extraction involved collecting comprehensive details about each study.Our statistical analysis used a random-effects model to calculate the pooled prevalence and confidence intervals,stratifying results by regional location.We assessed study heterogeneity using Cochran's Q statistic and I²statistic,with regression tests employed to evaluate potential publication bias.RESULTS We analyzed 737 records from five databases,ultimately including 13 studies from ten countries.For neonates,the pooled prevalence was 4.8%(95%CI:1.1%to 10.5%)with the highest rates observed in South-East Asia(10.5%;95%CI:2.4%to 23.3%).Among HCWs,a single Indian study reported a 3.3%prevalence.Environmental samples showed a prevalence of 2.3%(95%CI:0%to 9.3%),with the highest rates in South-East Asia(10%;95%CI:4.2%to 17.7%).Significant heterogeneity was found across studies,and no publication bias was detected.CONCLUSION This systematic review highlights a significant prevalence of CRAB colonization in neonates across various regions,particularly in South-East Asia,contrasting with lower rates in high-income countries.The study reveals a gap in research on HCWs colonization,with only a single study from India reporting moderate prevalence.Environmental samples indicate moderate levels of CRAB contamination,again higher in South-East Asia.These findings underscore the need for more extensive and focused research on CRAB colonization in NICUs,including exploring the roles of HCWs and the environment in transmission,understanding antimicrobial resistance patterns,and developing effective prevention measures.展开更多
Ischemic stroke is a leading cause of death and disability worldwide,with an increasing trend and tendency for onset at a younger age.China,in particular,bears a high burden of stroke cases.In recent years,the inflamm...Ischemic stroke is a leading cause of death and disability worldwide,with an increasing trend and tendency for onset at a younger age.China,in particular,bears a high burden of stroke cases.In recent years,the inflammatory response after stroke has become a research hotspot:understanding the role of inflammatory response in tissue damage and repair following ischemic stroke is an important direction for its treatment.This review summarizes several major cells involved in the inflammatory response following ischemic stroke,including microglia,neutrophils,monocytes,lymphocytes,and astrocytes.Additionally,we have also highlighted the recent progress in various treatments for ischemic stroke,particularly in the field of stem cell therapy.Overall,understanding the complex interactions between inflammation and ischemic stroke can provide valuable insights for developing treatment strategies and improving patient outcomes.Stem cell therapy may potentially become an important component of ischemic stroke treatment.展开更多
背景:非编码RNA作为一类不编码蛋白质的RNA分子,在细胞调控中发挥关键作用。同时,间充质干细胞具有多向分化潜能,对组织修复和再生至关重要。近年来,研究者们对非编码RNA在调控间充质干细胞功能中的作用展开了深入探讨。目的:通过文献...背景:非编码RNA作为一类不编码蛋白质的RNA分子,在细胞调控中发挥关键作用。同时,间充质干细胞具有多向分化潜能,对组织修复和再生至关重要。近年来,研究者们对非编码RNA在调控间充质干细胞功能中的作用展开了深入探讨。目的:通过文献计量学分析方法系统地了解非编码RNA与间充质干细胞相关研究的发展趋势与关键领域。方法:从Web of Science核心合集1990年至今的科学引文索引扩展获取非编码RNA与间充质干细胞相关研究的文献数据,运用VOSviewer和Cite Space计量学软件对年份、国家或地区、研究机构、被引文献和关键词进行发文量、聚类、被引频次、突增性和中介中心性进行分析,揭示该研究领域的知识基础及前沿热点。结果与结论:(1)最终纳入5348篇文献,发表在1997-2021年,相关文献呈现明显的增长趋势,尽管在2022年略有减少,其发文量仍保持较高水平,中国在该领域的研究中占据主导地位,其中上海交通大学为最活跃的机构。(2)对被引文献分析发现,高突增性、高中介中心性、高被引的文献主要与微小RNA、细胞外囊泡和骨代谢等内容相关,这些文献构成了非编码RNA与间充质干细胞研究领域的重要知识基础。(3)对关键词进行突增性分析发现,至今保持高突增性的关键词包括外泌体、环状RNA、细胞外囊泡和损伤。(4)对关键词进行聚类演变分析,发文量仍保持增长趋势的关键词聚类包括:肿瘤微环境、骨关节炎、氧化应激和细胞外囊泡,这些关键词反映了目前以及未来该领域的研究热点。(5)文章结果不仅展示了非编码RNA与间充质干细胞研究领域的研究态势,更重要的是有望为研究人员提供潜在的方向和启示。展开更多
Irisin is a myokine that is generated by cleavage of the membrane protein fibronectin type Ⅲ domain-containing protein 5(FNDC5) in response to physical exercise. Studies reveal that irisin/FNDC5 has neuroprotective f...Irisin is a myokine that is generated by cleavage of the membrane protein fibronectin type Ⅲ domain-containing protein 5(FNDC5) in response to physical exercise. Studies reveal that irisin/FNDC5 has neuroprotective functions against Alzheimer's disease, the most common form of dementia in the elderly, by improving cognitive function and reducing amyloid-β and tau pathologies as well as neuroinflammation in cell culture or animal models of Alzheimer's disease. Although current and ongoing studies on irisin/FNDC5 show promising results, further mechanistic studies are required to clarify its potential as a meaningful therapeutic target for alleviating Alzheimer's disease. We recently found that irisin treatment reduces amyloid-β pathology by increasing the activity/levels of amyloid-β-degrading enzyme neprilysin secreted from astrocytes. Herein, we present an overview of irisin/FNDC5's protective roles and mechanisms against Alzheimer's disease.展开更多
Spinal cord injury results in paralysis, sensory disturbances, sphincter dysfunction, and multiple systemic secondary conditions, most arising from autonomic dysregulation. All this produces profound negative psychoso...Spinal cord injury results in paralysis, sensory disturbances, sphincter dysfunction, and multiple systemic secondary conditions, most arising from autonomic dysregulation. All this produces profound negative psychosocial implications for affected people, their families, and their communities;the financial costs can be challenging for their families and health institutions. Treatments aimed at restoring the spinal cord after spinal cord injury, which have been tested in animal models or clinical trials, generally seek to counteract one or more of the secondary mechanisms of injury to limit the extent of the initial damage. Most published works on structural/functional restoration in acute and chronic spinal cord injury stages use a single type of treatment: a drug or trophic factor, transplant of a cell type, and implantation of a biomaterial. Despite the significant benefits reported in animal models, when translating these successful therapeutic strategies to humans, the result in clinical trials has been considered of little relevance because the improvement, when present, is usually insufficient. Until now, most studies designed to promote neuroprotection or regeneration at different stages after spinal cord injury have used single treatments. Considering the occurrence of various secondary mechanisms of injury in the acute and sub-acute phases of spinal cord injury, it is reasonable to speculate that more than one therapeutic agent could be required to promote structural and functional restoration of the damaged spinal cord. Treatments that combine several therapeutic agents, targeting different mechanisms of injury, which, when used as a single therapy, have shown some benefits, allow us to assume that they will have synergistic beneficial effects. Thus, this narrative review article aims to summarize current trends in the use of strategies that combine therapeutic agents administered simultaneously or sequentially, seeking structural and functional restoration of the injured spinal cord.展开更多
Objective Ulcerative colitis is a prevalent immunoinflammatory disease.Th17/Treg cell imbalance and gut microbiota dysregulation are key factors in ulcerative colitis pathogenesis.The actin cytoskeleton contributes to...Objective Ulcerative colitis is a prevalent immunoinflammatory disease.Th17/Treg cell imbalance and gut microbiota dysregulation are key factors in ulcerative colitis pathogenesis.The actin cytoskeleton contributes to regulating the proliferation,differentiation,and migration of Th17 and Treg cells.Wdr63,a gene containing the WD repeat domain,participates in the structure and functional modulation of actin cytoskeleton.Recent research indicates that WDR63 may serve as a regulator of cell migration and metastasis via actin polymerization inhibition.This article aims to explore the effect of Wdr63 deletion on Th17/Treg cells and ulcerative colitis.Methods We constructed Wdr63-/-mice,induced colitis in mice using dextran sulfate sodium salt,collected colon tissue for histopathological staining,collected mesenteric lymph nodes for flow cytometry analysis,and collected healthy mouse feces for microbial diversity detection.Results Compared with wild-type colitis mice,Wdr63-/-colitis mice had a more pronounced shortening of colonic tissue,higher scores on disease activity index and histological damage index,Treg cells decreased and Th17 cells increased in colonic tissue and mesenteric lymph nodes,a lower level of anti-inflammatory cytokine IL-10,and a higher level of pro-inflammatory cytokine IL-17A.In addition,WDR63 has shown positive effects on maintaining intestinal microbiota homeostasis.It maintains the balance of Bacteroidota and Firmicutes,promoting the formation of beneficial intestinal bacteria linked to immune inflammation.Conclusion Wdr63 deletion aggravates ulcerative colitis in mice,WDR63 inhibits colonic inflammation likely by regulating Th17/Treg balance and maintains intestinal microbiota homeostasis.展开更多
Alzheimer’s disease is a debilitating,progressive neurodegenerative disorder characterized by the progressive accumulation of abnormal proteins,including amyloid plaques and intracellular tau tangles,primarily within...Alzheimer’s disease is a debilitating,progressive neurodegenerative disorder characterized by the progressive accumulation of abnormal proteins,including amyloid plaques and intracellular tau tangles,primarily within the brain.Lysosomes,crucial intracellular organelles responsible for protein degradation,play a key role in maintaining cellular homeostasis.Some studies have suggested a link between the dysregulation of the lysosomal system and pathogenesis of neurodegenerative diseases,including Alzheimer’s disease.Restoring the normal physiological function of lysosomes hold the potential to reduce the pathological burden and improve the symptoms of Alzheimer’s disease.Currently,the efficacy of drugs in treating Alzheimer’s disease is limited,with major challenges in drug delivery efficiency and targeting.Recently,nanomaterials have gained widespread use in Alzheimer’s disease drug research owing to their favorable physical and chemical properties.This review aims to provide a comprehensive overview of recent advances in using nanomaterials(polymeric nanomaterials,nanoemulsions,and carbon-based nanomaterials)to enhance lysosomal function in treating Alzheimer’s disease.This review also explores new concepts and potential therapeutic strategies for Alzheimer’s disease through the integration of nanomaterials and modulation of lysosomal function.In conclusion,this review emphasizes the potential of nanomaterials in modulating lysosomal function to improve the pathological features of Alzheimer’s disease.The application of nanotechnology to the development of Alzheimer’s disease drugs brings new ideas and approaches for future treatment of this disease.展开更多
Introduction:Alzheimer 's disease(AD) is a common neurodegenerative disorder and the primary cause of dementia. Considerable evidence supports the “amyloid hypothesis,” stating that the pathogenesis of AD is pri...Introduction:Alzheimer 's disease(AD) is a common neurodegenerative disorder and the primary cause of dementia. Considerable evidence supports the “amyloid hypothesis,” stating that the pathogenesis of AD is primarily caused by the deposition of amyloid-β(Aβ), which drives tau phosphorylation, neuroinflammation, and neurodegeneration in the brain. The amyloid hypothesis is strengthened by the significant and moderate benefit of lecanemab, a humanized antibody through an anti-amyloid mechanism,showing slowed clinical decline(van Dyck et al.,2023). The recent positive results of anti-amyloid trials have brought back focus on the amyloid hypothesis through biochemical, genetic, and pharmacological approaches(Zhang, 2023).展开更多
Clay deposits typically exhibit significant degrees of heterogeneity and anisotropy in their strength and stiffness properties.Such non-monotonic responses can significantly impact the stability analysis and design of...Clay deposits typically exhibit significant degrees of heterogeneity and anisotropy in their strength and stiffness properties.Such non-monotonic responses can significantly impact the stability analysis and design of overlying shallow foundations.In this study,the undrained bearing capacity of shallow foundations resting on inhomogeneous and anisotropic clay layers subjected to oblique-eccentric combined loading is investigated through a comprehensive series of finite element limit analysis(FELA)based on the well-established lower-bound theorem and second-order cone programming(SOCP).The heterogeneity of normally consolidated(NC)clays is simulated by adopting a well-known general model of undrained shear strength increasing linearly with depth.In contrast,for overconsolidated(OC)clays,the variation of undrained shear strength with depth is considered to follow a bilinear trend.Furthermore,the inherent anisotropy is accounted for by adopting different values of undrained shear strength along different directions within the soil medium,employing an iterative-based algorithm.The results of numerical simulations are utilized to investigate the influences of natural soil heterogeneity and inherent anisotropy on the ultimate bearing capacity,failure envelope,and failure mechanism of shallow foundations subjected to the various combinations of vertical-horizontal(V-H)and vertical-moment(V-M)loads.展开更多
BACKGROUND Coronavirus disease 2019(COVID-19)is strongly associated with an increased risk of thrombotic events,including severe outcomes such as pulmonary embolism.Elevated D-dimer levels are a critical biomarker for...BACKGROUND Coronavirus disease 2019(COVID-19)is strongly associated with an increased risk of thrombotic events,including severe outcomes such as pulmonary embolism.Elevated D-dimer levels are a critical biomarker for assessing this risk.In Gabon,early implementation of anticoagulation therapy and D-dimer testing has been crucial in managing COVID-19.This study hypothesizes that elevated Ddimer levels are linked to increased COVID-19 severity.AIM To determine the impact of D-dimer levels on COVID-19 severity and their role in guiding clinical decisions.METHODS This retrospective study analyzed COVID-19 patients admitted to two hospitals in Gabon between March 2020 and December 2023.The study included patients with confirmed COVID-19 diagnoses and available D-dimer measurements at admission.Data on demographics,clinical outcomes,D-dimer levels,and healthcare costs were collected.COVID-19 severity was classified as non-severe(outpatients)or severe(inpatients).A multivariable logistic regression model was used to assess the relationship between D-dimer levels and disease severity,with adjusted odds ratios(OR)and 95%CI.RESULTS A total of 3004 patients were included,with a mean age of 50.17 years,and the majority were female(53.43%).Elevated D-dimer levels were found in 65.81%of patients,and 57.21%of these experienced severe COVID-19.Univariate analysis showed that patients with elevated D-dimer levels had 3.33 times higher odds of severe COVID-19(OR=3.33,95%CI:2.84-3.92,P<0.001),and this association remained significant in the multivariable analysis,adjusted for age,sex,and year of collection.The financial analysis revealed a substantial burden,particularly for uninsured patients.CONCLUSION D-dimer predicts COVID-19 severity and guides treatment,but the high cost of anticoagulant therapy highlights the need for policies ensuring affordable access in resource-limited settings like Gabon.展开更多
Stroke is classified as ischemic or hemorrhagic,and there are few effective treatments for either type.Immunologic mechanisms play a critical role in secondary brain injury following a stroke,which manifests as cytoki...Stroke is classified as ischemic or hemorrhagic,and there are few effective treatments for either type.Immunologic mechanisms play a critical role in secondary brain injury following a stroke,which manifests as cytokine release,blood–brain barrier disruption,neuronal cell death,and ultimately behavioral impairment.Suppressing the inflammatory response has been shown to mitigate this cascade of events in experimental stroke models.However,in clinical trials of anti-inflammatory agents,longterm immunosuppression has not demonstrated significant clinical benefits for patients.This may be attributable to the dichotomous roles of inflammation in both tissue injury and repair,as well as the complex pathophysiologic inflammatory processes in stroke.Inhibiting acute harmful inflammatory responses or inducing a phenotypic shift from a pro-inflammatory to an anti-inflammatory state at specific time points after a stroke are alternative and promising therapeutic strategies.Identifying agents that can modulate inflammation requires a detailed understanding of the inflammatory processes of stroke.Furthermore,epigenetic reprogramming plays a crucial role in modulating post-stroke inflammation and can potentially be exploited for stroke management.In this review,we summarize current findings on the epigenetic regulation of the inflammatory response in stroke,focusing on key signaling pathways including nuclear factor-kappa B,Janus kinase/signal transducer and activator of transcription,and mitogen-activated protein kinase as well as inflammasome activation.We also discuss promising molecular targets for stroke treatment.The evidence to date indicates that therapeutic targeting of the epigenetic regulation of inflammation can shift the balance from inflammation-induced tissue injury to repair following stroke,leading to improved post-stroke outcomes.展开更多
Fresh-cut lettuce is widely used in ready-to-eat salads sold in modified atmosphere packages (MAP).Even in MAP,fresh-cut lettuce has short shelf life that results in loss of nutrients.Lettuce cultivars exhibit genetic...Fresh-cut lettuce is widely used in ready-to-eat salads sold in modified atmosphere packages (MAP).Even in MAP,fresh-cut lettuce has short shelf life that results in loss of nutrients.Lettuce cultivars exhibit genetic variation for shelf life in MAP,but their variation for nutrient retention is not known.Fifty accessions were evaluated for initial content of ascorbic acid (AsA),carotenoids,and sugars and their retention in storage.Accessions with high content and/or good retention of one or more nutrients were identified.The romaine accession ‘Floricos’ had high levels of all the three nutrients.Accessions with relatively high retention of all the three nutrients were ‘Salinas 88’,‘Siskiyou’,‘Solar’,SM09A,‘Romance’,and ‘Green Towers’.Romaine cultivars,‘Balady Barrage’,‘Green Towers’,and ‘Darkland’ had relatively high initial levels of all tested nutrients and good rate of their retention.There was no clear correlation between initial AsA/carotene concentrations and their retention rates,suggesting that besides content,retention of nutrients should also be a breeding target in a lettuce nutritional improvement program.Statistical analyses with the Pearson's correlation coefficient determined a negative relationship between tissue deterioration(AUDePS) and retention of all tested nutrients[r of-0.52 (P<0.0001) for AsA,-0.27 (P<0.01) for total carotene,and-0.59 (P<0.0001) for total sugars],suggesting that an increase in tissue deterioration intensifies nutrient decay.Broad-sense heritability (H~2) across the experiments was0.15 for AsA,0.23 for total carotene,and 0.50 for total sugars.Identification of germplasm with high nutrient content,extended shelf life and good nutrient retention provides valuable information for the lettuce industry and associated breeding programs.展开更多
文摘Community engagement is increasingly promoted to strengthen the ethics of medical research in low-income countries. One strategy is to use community advisory boards (CABs): semi-independent groups that can potentially safeguard the rights of study participants and help improve research. However, there is little published on the experience of operating and sustaining CABs. The Shoklo Malaria Research Unit (SMRU) has been conducting research and providing healthcare in a population of refugees, migrant workers, and displaced people on the Thai-Myanmar border for over 25 years. In 2009 SMRU facilitated the establishment of the Tak Province Community Ethics Advisory Board (T-CAB) in an effort to formally engage with the local communities both to obtain advice and to establish a participatory framework within which studies and the provision of health care can take place. In this paper, we draw on our experience of community engagement in this unique setting, and on our interactions with the past and present CAB members to critically reflect upon the CAB’s goals, structure and operations with a focus on the practicalities, what worked, what did not, and on its future directions.
文摘Machine learning(ML)is a type of artificial intelligence that assists computers in the acquisition of knowledge through data analysis,thus creating machines that can complete tasks otherwise requiring human intelligence.Among its various applications,it has proven groundbreaking in healthcare as well,both in clinical practice and research.In this editorial,we succinctly introduce ML applications and present a study,featured in the latest issue of the World Journal of Clinical Cases.The authors of this study conducted an analysis using both multiple linear regression(MLR)and ML methods to investigate the significant factors that may impact the estimated glomerular filtration rate in healthy women with and without non-alcoholic fatty liver disease(NAFLD).Their results implicated age as the most important determining factor in both groups,followed by lactic dehydrogenase,uric acid,forced expiratory volume in one second,and albumin.In addition,for the NAFLD-group,the 5th and 6th most important impact factors were thyroid-stimulating hormone and systolic blood pressure,as compared to plasma calcium and body fat for the NAFLD+group.However,the study's distinctive contribution lies in its adoption of ML methodologies,showcasing their superiority over traditional statistical approaches(herein MLR),thereby highlighting the potential of ML to represent an invaluable advanced adjunct tool in clinical practice and research.
文摘The present study, carried out in the forest (Daloa) and pre-forest (M’Bahiakro) zones of Cote d’Ivoire, aims to determine soil landscape units using the coding method. Geological maps and satellite images (SRTM and Landsat) were used for this purpose. The methodological approach adopted consisted in producing maps of slope, geology, land use and topography using the codification method. These various maps, integrated into a GIS using the coding aggregation method, were used to generate soil landscape maps. Twenty-seven (27) soil landscapes have been identified for the pre-forest zone (M’Bahiakro), with a strong dominance of acid rock over a moderate relief under savannah, forest/degraded forest and crops/fallow. However, the forest zone (Daloa), with forty-one (41) soil landscapes identified over the entire zone, is characterized by a majority of mafic rocks on a medium altitude under forest/degraded forest, water and crops/fallow. The criteria used from the codification method (sum of aggregations) made it possible to predict the spatial distribution of soil map units according to agro-ecological environments in the humid intertropical zone. This is essential for the orientation and reinforcement of soil survey tools. However, a comparative evaluation of the different multicriteria analysis methods for coding and weighting soil landscape unit mapping would enable us to identify the most suitable and efficient method for drawing up base maps for soil surveys.
文摘Introduction: Cardiovascular disease represents a major public health burden worldwide. Research and management of risk factors contribute to the prevention of these diseases. The aim of this study was to assess the prevalence of dyslipidemia in the biochemistry unit of the Charles De Gaulle Pediatric University Hospital (CHUP-CDG) in Ouagadougou. Material and Methods: This was a descriptive and analytical cross-sectional study, with retrospective data collection from January 1, 2020 to December 31, 2022. Patients of all ages who performed a lipid panel in the CHUP-CDG biochemistry unit during the study period have been included. Results: A total of 2872 patients have been included. The mean age of the study population was 27.72 ± 19.51 years and the M/F sex ratio was 0.81. Among the patients, 22.84% had at least one dyslipidemia. The prevalences of hypercholesterolemia, hypo-HDL cholesterolemia and hyper-LDL cholesterolemia were 11.57%, 49.19% and 57.50% respectively. Hypertriglyceridemia and mixed hyperlipidemia were present in 9.04% and 2.08% of patients. Hypercholesterolemia was significantly more frequent in the female sex (p = 0.0077);hyper-LDL cholesterolemia (p = 0.0255) and mixed hyperlipidemia (p Conclusion: The relatively high prevalence of dyslipidemia in the study indicates a worrying situation. It would therefore appear essential to extend the search for risk factors nationwide, particularly those that can be modified, in order to reduce morbidity and mortality linked to cardiovascular disease.
文摘Introduction: Low birth weight (LBW) is defined by the World Health Organization (WHO) as a birth weight strictly below 2500 g, whatever the term of pregnancy. It constitutes a major public health problem, both in developed and developing countries, due to its magnitude and its strong association with infant morbidity and mortality. Main objective was to study the factors associated with the occurrence of small-for-gestational-age newborns in Douala. Methodology: We carried out a cross-sectional analytical study with prospective data collection using a technical pretested sheet in the maternity wards of the Douala General Hospital, the Laquintinie Hospital, and the District hospitals of Deido, Nylon and Bonassama over a period of 4 months (January to April 2020). We were interested in any newborn, born alive, vaginally or by cesarean section, of low weight, seen in the first 24 hours from a full-term single-fetal pregnancy whose mother had given her consent. Our sampling was consecutive and non-exhaustive. We excluded newborns whose term was unclear and those with congenital malformations or signs of embryo-foetopathy. Data collection was done using survey sheets. Statistical analyzes were carried out with CS Pro 7.3 and SPSS version 25.0 software. The Student, Chi-square and Fischer tests were used to compare the means of the variables, the percentages with a significance threshold P value Results: During the study period, 305 full-term newborns were included, divided into 172 boys and 133 girls. The percentage of small-for-gestational-age newborns was 9.8%;after multivariate analysis by logistic regression to eliminate confounding factors, we found maternal factors associated with small for gestational age newborns;maternal age less than 20 years, primiparity, gestational age (37 - 38), a delay in prenatal visits greater than 14 weeks, anemia in pregnancy, positive toxoplasmosis serology in pregnancy, a body mass index of Conclusion: Our study revealed the potential determinants of low birth weight at term in the Cameroonian urban context and specifically in Douala.
文摘Introduction: Spontaneous abortion of the second trimester is an interruption of pregnancy with complete expulsion or not of the product of conception between 15 and 28 weeks of pregnancy without any maneuvers. The objective of our study was to determine the factors associated with second trimester spontaneous abortions at Laquintinie Hospital in Douala. Methodology for this purpose: We conducted a case-control study from January to May 2019 on pregnant women who may or may not have had spontaneous second trimester abortions. Results: In total we recorded 1609 pregnancies and recruited 184 patients, including 46 cases and 138 controls;which gave a frequency of spontaneous abortion in the second trimester of pregnancy of 2.85%. A correlative analysis showed that spontaneous abortions in the second trimester were associated with housewife status (OR = 2.89;CI = 1.21 - 6.79;p = 0.010), gestation > 5 (OR = 4.09;CI = 1.02 - 17.66;p = 0.040), multiparity (OR = 3.81;CI = 1.59 - 9.16;p = 0.002), history of endouterine maneuvers (OR = 5.64;CI = 2.43 - 13 .03;p = 0.000), malaria in pregnancy (OR = 3.99;CI = 1.1 - 14.76;p = 0.030), incompleteness on the second trimester ultrasound (OR = 2.37;CI = 1.18 - 4.70;p = 0.010), jolts when traveling (OR = 46.04;CI = 17.29 - 123.66;p = 0.000), long car journeys (OR = 7.05;CI = 1.99 - 27.77;p = 0.000). After logistic regression eliminating the confounding factors, only the following were associated with abortions: Multiparity (OR = 13.90;CI = 2.96 - 65.18;p = 0.000), endo uterine maneuvers (OR = 3.69;CI = 1. 01 - 13.44;p = 0.047), jolts when traveling (OR = 72.63;CI = 19.47 - 270.96;p = 0.000), long car journeys (OR = 15.41;CI = 2.7 - 85, 95;p = 0.000). Conclusion: Our study reveals that a set of factors contribute to the occurrence of spontaneous abortions in the second trimester of pregnancy in our context.
基金supported by the Ministry of Science and Tech-nology of the People's Republic of China(2021ZD0201900),Project 5(2021ZD0201905).
文摘Brain-computer interface(BCI)technology is rapidly advancing in medical research and application.As an emerging biomedical engineering technology,it has garnered significant attention in the clinical research of brain disease diagnosis and treatment,neurological rehabilitation,and mental health.However,BCI also raises several challenges and ethical concerns in clinical research.In this article,the authors investigate and discuss three aspects of BCI in medicine and healthcare:the state of international ethical governance,multidimensional ethical challenges pertaining to BCI in clinical research,and suggestive concerns for ethical review.Despite the great potential of frontier BCI research and development in the field of medical care,the ethical challenges induced by itself and the complexities of clinical research and brain function have put forward new special fields for ethics in BCI.To ensure"responsible innovation"in BCI research in healthcare and medicine,the creation of an ethical global governance framework and system,along with special guidelines for cutting-edge BCI research in medicine,is suggested.
文摘BACKGROUND The rising prevalence of carbapenem-resistant Acinetobacter baumannii(CRAB)in neonatal intensive care units(NICUs)represents an escalating challenge in healthcare settings,particularly in managing hospital-acquired infections(HAIs).Studies across various World Health Organization regions have documented a significant incidence of CRAB-related HAIs,with rates as high as 41.7 cases per 1000 patients in ICUs,accounting for 13.6%of all HAIs.These infections pose a doubled mortality risk compared to infections with carbapenem-susceptible Acinetobacter baumannii.A particularly concerning aspect of CRAB colonization is its asymptomatic nature,enabling its transmission through healthcare workers(HCWs)or the NICU environment to vulnerable neonates with developing immune systems.AIM To explore the prevalence of CRAB colonization in NICUs,focusing on neonates,healthcare workers,and the environmental samples,to enhance epidemiological understanding and inform targeted interventions.METHODS We conducted according to PRISMA 2020 checklist guidelines,a comprehensive literature search across multiple databases including MEDLINE(Ovid),EMBASE(Ovid),Global Health(Ovid),Web of Science,and Global Index Me-dicus.Studies were selected based on predetermined criteria,primarily involving neonates,HCWs,and environmental swabs,using culture or molecular methods to detect CRAB colonization.We excluded studies that did not specifically focus on NICUs,were duplicates,or lacked necessary data.The study selection and quality assessment were conducted independently by two reviewers.Data extraction involved collecting comprehensive details about each study.Our statistical analysis used a random-effects model to calculate the pooled prevalence and confidence intervals,stratifying results by regional location.We assessed study heterogeneity using Cochran's Q statistic and I²statistic,with regression tests employed to evaluate potential publication bias.RESULTS We analyzed 737 records from five databases,ultimately including 13 studies from ten countries.For neonates,the pooled prevalence was 4.8%(95%CI:1.1%to 10.5%)with the highest rates observed in South-East Asia(10.5%;95%CI:2.4%to 23.3%).Among HCWs,a single Indian study reported a 3.3%prevalence.Environmental samples showed a prevalence of 2.3%(95%CI:0%to 9.3%),with the highest rates in South-East Asia(10%;95%CI:4.2%to 17.7%).Significant heterogeneity was found across studies,and no publication bias was detected.CONCLUSION This systematic review highlights a significant prevalence of CRAB colonization in neonates across various regions,particularly in South-East Asia,contrasting with lower rates in high-income countries.The study reveals a gap in research on HCWs colonization,with only a single study from India reporting moderate prevalence.Environmental samples indicate moderate levels of CRAB contamination,again higher in South-East Asia.These findings underscore the need for more extensive and focused research on CRAB colonization in NICUs,including exploring the roles of HCWs and the environment in transmission,understanding antimicrobial resistance patterns,and developing effective prevention measures.
基金supported by grants from the Major Program of National Key Research and Development Project,Nos.2020YFA0112600(to ZH)the National Natural Science Foundation of China,No.82171270(to ZL)+5 种基金Public Service Platform for Artificial Intelligence Screening and Auxiliary Diagnosis for the Medical and Health Industry,Ministry of Industry and Information Technology of the People’s Republic of China,No.2020-0103-3-1(to ZL)the Natural Science Foundation of Beijing,No.Z200016(to ZL)Beijing Talents Project,No.2018000021223ZK03(to ZL)Beijing Municipal Committee of Science and Technology,No.Z201100005620010(to ZL)CAMS Innovation Fund for Medical Sciences,No.2019-I2M-5-029(to YW)Shanghai Engineering Research Center of Stem Cells Translational Medicine,No.20DZ2255100(to ZH).
文摘Ischemic stroke is a leading cause of death and disability worldwide,with an increasing trend and tendency for onset at a younger age.China,in particular,bears a high burden of stroke cases.In recent years,the inflammatory response after stroke has become a research hotspot:understanding the role of inflammatory response in tissue damage and repair following ischemic stroke is an important direction for its treatment.This review summarizes several major cells involved in the inflammatory response following ischemic stroke,including microglia,neutrophils,monocytes,lymphocytes,and astrocytes.Additionally,we have also highlighted the recent progress in various treatments for ischemic stroke,particularly in the field of stem cell therapy.Overall,understanding the complex interactions between inflammation and ischemic stroke can provide valuable insights for developing treatment strategies and improving patient outcomes.Stem cell therapy may potentially become an important component of ischemic stroke treatment.
文摘背景:非编码RNA作为一类不编码蛋白质的RNA分子,在细胞调控中发挥关键作用。同时,间充质干细胞具有多向分化潜能,对组织修复和再生至关重要。近年来,研究者们对非编码RNA在调控间充质干细胞功能中的作用展开了深入探讨。目的:通过文献计量学分析方法系统地了解非编码RNA与间充质干细胞相关研究的发展趋势与关键领域。方法:从Web of Science核心合集1990年至今的科学引文索引扩展获取非编码RNA与间充质干细胞相关研究的文献数据,运用VOSviewer和Cite Space计量学软件对年份、国家或地区、研究机构、被引文献和关键词进行发文量、聚类、被引频次、突增性和中介中心性进行分析,揭示该研究领域的知识基础及前沿热点。结果与结论:(1)最终纳入5348篇文献,发表在1997-2021年,相关文献呈现明显的增长趋势,尽管在2022年略有减少,其发文量仍保持较高水平,中国在该领域的研究中占据主导地位,其中上海交通大学为最活跃的机构。(2)对被引文献分析发现,高突增性、高中介中心性、高被引的文献主要与微小RNA、细胞外囊泡和骨代谢等内容相关,这些文献构成了非编码RNA与间充质干细胞研究领域的重要知识基础。(3)对关键词进行突增性分析发现,至今保持高突增性的关键词包括外泌体、环状RNA、细胞外囊泡和损伤。(4)对关键词进行聚类演变分析,发文量仍保持增长趋势的关键词聚类包括:肿瘤微环境、骨关节炎、氧化应激和细胞外囊泡,这些关键词反映了目前以及未来该领域的研究热点。(5)文章结果不仅展示了非编码RNA与间充质干细胞研究领域的研究态势,更重要的是有望为研究人员提供潜在的方向和启示。
基金supported by Cure Alzheimer’s Fund (to RET and SHC)JPB Foundation (to RET),and R56AG072054 (to SHC)。
文摘Irisin is a myokine that is generated by cleavage of the membrane protein fibronectin type Ⅲ domain-containing protein 5(FNDC5) in response to physical exercise. Studies reveal that irisin/FNDC5 has neuroprotective functions against Alzheimer's disease, the most common form of dementia in the elderly, by improving cognitive function and reducing amyloid-β and tau pathologies as well as neuroinflammation in cell culture or animal models of Alzheimer's disease. Although current and ongoing studies on irisin/FNDC5 show promising results, further mechanistic studies are required to clarify its potential as a meaningful therapeutic target for alleviating Alzheimer's disease. We recently found that irisin treatment reduces amyloid-β pathology by increasing the activity/levels of amyloid-β-degrading enzyme neprilysin secreted from astrocytes. Herein, we present an overview of irisin/FNDC5's protective roles and mechanisms against Alzheimer's disease.
文摘Spinal cord injury results in paralysis, sensory disturbances, sphincter dysfunction, and multiple systemic secondary conditions, most arising from autonomic dysregulation. All this produces profound negative psychosocial implications for affected people, their families, and their communities;the financial costs can be challenging for their families and health institutions. Treatments aimed at restoring the spinal cord after spinal cord injury, which have been tested in animal models or clinical trials, generally seek to counteract one or more of the secondary mechanisms of injury to limit the extent of the initial damage. Most published works on structural/functional restoration in acute and chronic spinal cord injury stages use a single type of treatment: a drug or trophic factor, transplant of a cell type, and implantation of a biomaterial. Despite the significant benefits reported in animal models, when translating these successful therapeutic strategies to humans, the result in clinical trials has been considered of little relevance because the improvement, when present, is usually insufficient. Until now, most studies designed to promote neuroprotection or regeneration at different stages after spinal cord injury have used single treatments. Considering the occurrence of various secondary mechanisms of injury in the acute and sub-acute phases of spinal cord injury, it is reasonable to speculate that more than one therapeutic agent could be required to promote structural and functional restoration of the damaged spinal cord. Treatments that combine several therapeutic agents, targeting different mechanisms of injury, which, when used as a single therapy, have shown some benefits, allow us to assume that they will have synergistic beneficial effects. Thus, this narrative review article aims to summarize current trends in the use of strategies that combine therapeutic agents administered simultaneously or sequentially, seeking structural and functional restoration of the injured spinal cord.
文摘Objective Ulcerative colitis is a prevalent immunoinflammatory disease.Th17/Treg cell imbalance and gut microbiota dysregulation are key factors in ulcerative colitis pathogenesis.The actin cytoskeleton contributes to regulating the proliferation,differentiation,and migration of Th17 and Treg cells.Wdr63,a gene containing the WD repeat domain,participates in the structure and functional modulation of actin cytoskeleton.Recent research indicates that WDR63 may serve as a regulator of cell migration and metastasis via actin polymerization inhibition.This article aims to explore the effect of Wdr63 deletion on Th17/Treg cells and ulcerative colitis.Methods We constructed Wdr63-/-mice,induced colitis in mice using dextran sulfate sodium salt,collected colon tissue for histopathological staining,collected mesenteric lymph nodes for flow cytometry analysis,and collected healthy mouse feces for microbial diversity detection.Results Compared with wild-type colitis mice,Wdr63-/-colitis mice had a more pronounced shortening of colonic tissue,higher scores on disease activity index and histological damage index,Treg cells decreased and Th17 cells increased in colonic tissue and mesenteric lymph nodes,a lower level of anti-inflammatory cytokine IL-10,and a higher level of pro-inflammatory cytokine IL-17A.In addition,WDR63 has shown positive effects on maintaining intestinal microbiota homeostasis.It maintains the balance of Bacteroidota and Firmicutes,promoting the formation of beneficial intestinal bacteria linked to immune inflammation.Conclusion Wdr63 deletion aggravates ulcerative colitis in mice,WDR63 inhibits colonic inflammation likely by regulating Th17/Treg balance and maintains intestinal microbiota homeostasis.
基金supported by the Natural Science Foundation of Shanghai,No.22ZR147750Science and Technology Innovation Action Plan of Shanghai Science and Technology Commission,No.23Y11906600Shanghai Changzheng Hospital Innovative Clinical Research Project,No.2020YLCYJ-Y02(all to YY).
文摘Alzheimer’s disease is a debilitating,progressive neurodegenerative disorder characterized by the progressive accumulation of abnormal proteins,including amyloid plaques and intracellular tau tangles,primarily within the brain.Lysosomes,crucial intracellular organelles responsible for protein degradation,play a key role in maintaining cellular homeostasis.Some studies have suggested a link between the dysregulation of the lysosomal system and pathogenesis of neurodegenerative diseases,including Alzheimer’s disease.Restoring the normal physiological function of lysosomes hold the potential to reduce the pathological burden and improve the symptoms of Alzheimer’s disease.Currently,the efficacy of drugs in treating Alzheimer’s disease is limited,with major challenges in drug delivery efficiency and targeting.Recently,nanomaterials have gained widespread use in Alzheimer’s disease drug research owing to their favorable physical and chemical properties.This review aims to provide a comprehensive overview of recent advances in using nanomaterials(polymeric nanomaterials,nanoemulsions,and carbon-based nanomaterials)to enhance lysosomal function in treating Alzheimer’s disease.This review also explores new concepts and potential therapeutic strategies for Alzheimer’s disease through the integration of nanomaterials and modulation of lysosomal function.In conclusion,this review emphasizes the potential of nanomaterials in modulating lysosomal function to improve the pathological features of Alzheimer’s disease.The application of nanotechnology to the development of Alzheimer’s disease drugs brings new ideas and approaches for future treatment of this disease.
基金supported by the Massachusetts General Hospital Scientific Projects to Accelerate Research and Collaboration (SPARC) awardCure Alzheimer’s Fund (to CZ)the National Institutes of Health (NIH),including R01NS102190,RF1NS120947,and R01HL161253 (to MBW),RF1NS120947 (to RJT)。
文摘Introduction:Alzheimer 's disease(AD) is a common neurodegenerative disorder and the primary cause of dementia. Considerable evidence supports the “amyloid hypothesis,” stating that the pathogenesis of AD is primarily caused by the deposition of amyloid-β(Aβ), which drives tau phosphorylation, neuroinflammation, and neurodegeneration in the brain. The amyloid hypothesis is strengthened by the significant and moderate benefit of lecanemab, a humanized antibody through an anti-amyloid mechanism,showing slowed clinical decline(van Dyck et al.,2023). The recent positive results of anti-amyloid trials have brought back focus on the amyloid hypothesis through biochemical, genetic, and pharmacological approaches(Zhang, 2023).
文摘Clay deposits typically exhibit significant degrees of heterogeneity and anisotropy in their strength and stiffness properties.Such non-monotonic responses can significantly impact the stability analysis and design of overlying shallow foundations.In this study,the undrained bearing capacity of shallow foundations resting on inhomogeneous and anisotropic clay layers subjected to oblique-eccentric combined loading is investigated through a comprehensive series of finite element limit analysis(FELA)based on the well-established lower-bound theorem and second-order cone programming(SOCP).The heterogeneity of normally consolidated(NC)clays is simulated by adopting a well-known general model of undrained shear strength increasing linearly with depth.In contrast,for overconsolidated(OC)clays,the variation of undrained shear strength with depth is considered to follow a bilinear trend.Furthermore,the inherent anisotropy is accounted for by adopting different values of undrained shear strength along different directions within the soil medium,employing an iterative-based algorithm.The results of numerical simulations are utilized to investigate the influences of natural soil heterogeneity and inherent anisotropy on the ultimate bearing capacity,failure envelope,and failure mechanism of shallow foundations subjected to the various combinations of vertical-horizontal(V-H)and vertical-moment(V-M)loads.
文摘BACKGROUND Coronavirus disease 2019(COVID-19)is strongly associated with an increased risk of thrombotic events,including severe outcomes such as pulmonary embolism.Elevated D-dimer levels are a critical biomarker for assessing this risk.In Gabon,early implementation of anticoagulation therapy and D-dimer testing has been crucial in managing COVID-19.This study hypothesizes that elevated Ddimer levels are linked to increased COVID-19 severity.AIM To determine the impact of D-dimer levels on COVID-19 severity and their role in guiding clinical decisions.METHODS This retrospective study analyzed COVID-19 patients admitted to two hospitals in Gabon between March 2020 and December 2023.The study included patients with confirmed COVID-19 diagnoses and available D-dimer measurements at admission.Data on demographics,clinical outcomes,D-dimer levels,and healthcare costs were collected.COVID-19 severity was classified as non-severe(outpatients)or severe(inpatients).A multivariable logistic regression model was used to assess the relationship between D-dimer levels and disease severity,with adjusted odds ratios(OR)and 95%CI.RESULTS A total of 3004 patients were included,with a mean age of 50.17 years,and the majority were female(53.43%).Elevated D-dimer levels were found in 65.81%of patients,and 57.21%of these experienced severe COVID-19.Univariate analysis showed that patients with elevated D-dimer levels had 3.33 times higher odds of severe COVID-19(OR=3.33,95%CI:2.84-3.92,P<0.001),and this association remained significant in the multivariable analysis,adjusted for age,sex,and year of collection.The financial analysis revealed a substantial burden,particularly for uninsured patients.CONCLUSION D-dimer predicts COVID-19 severity and guides treatment,but the high cost of anticoagulant therapy highlights the need for policies ensuring affordable access in resource-limited settings like Gabon.
基金supported by the National Natural Science Foundation of China,Nos.32070735(to QL),82371321(to QL),82171270(to ZL)Public Service Platform for Artificial Intelligence Screening and Auxiliary Diagnosis for the Medical and Health Industry,Ministry of Industry and Information Technology of the People's Republic of China,No.2020-0103-3-1(to ZL)+2 种基金the Natural Science Foundation of Beijing,No.Z200016(to ZL)Beijing Talents Project,No.2018000021223ZK03(to ZL)Beijing Municipal Committee of Science and Technology,No.Z201100005620010(to ZL)。
文摘Stroke is classified as ischemic or hemorrhagic,and there are few effective treatments for either type.Immunologic mechanisms play a critical role in secondary brain injury following a stroke,which manifests as cytokine release,blood–brain barrier disruption,neuronal cell death,and ultimately behavioral impairment.Suppressing the inflammatory response has been shown to mitigate this cascade of events in experimental stroke models.However,in clinical trials of anti-inflammatory agents,longterm immunosuppression has not demonstrated significant clinical benefits for patients.This may be attributable to the dichotomous roles of inflammation in both tissue injury and repair,as well as the complex pathophysiologic inflammatory processes in stroke.Inhibiting acute harmful inflammatory responses or inducing a phenotypic shift from a pro-inflammatory to an anti-inflammatory state at specific time points after a stroke are alternative and promising therapeutic strategies.Identifying agents that can modulate inflammation requires a detailed understanding of the inflammatory processes of stroke.Furthermore,epigenetic reprogramming plays a crucial role in modulating post-stroke inflammation and can potentially be exploited for stroke management.In this review,we summarize current findings on the epigenetic regulation of the inflammatory response in stroke,focusing on key signaling pathways including nuclear factor-kappa B,Janus kinase/signal transducer and activator of transcription,and mitogen-activated protein kinase as well as inflammasome activation.We also discuss promising molecular targets for stroke treatment.The evidence to date indicates that therapeutic targeting of the epigenetic regulation of inflammation can shift the balance from inflammation-induced tissue injury to repair following stroke,leading to improved post-stroke outcomes.
基金supported by the Specialty Crop Block Grant Program of the U.S. Department of Agriculture's (USDA), Agricultural Marketing Service (AMS) through the California Department of Food and Agriculture (SCB15015)partly also by funding from the California Leafy Greens Research Board and by Oak Ridge Institute for Science and Education (ORISE) Research Participation Program。
文摘Fresh-cut lettuce is widely used in ready-to-eat salads sold in modified atmosphere packages (MAP).Even in MAP,fresh-cut lettuce has short shelf life that results in loss of nutrients.Lettuce cultivars exhibit genetic variation for shelf life in MAP,but their variation for nutrient retention is not known.Fifty accessions were evaluated for initial content of ascorbic acid (AsA),carotenoids,and sugars and their retention in storage.Accessions with high content and/or good retention of one or more nutrients were identified.The romaine accession ‘Floricos’ had high levels of all the three nutrients.Accessions with relatively high retention of all the three nutrients were ‘Salinas 88’,‘Siskiyou’,‘Solar’,SM09A,‘Romance’,and ‘Green Towers’.Romaine cultivars,‘Balady Barrage’,‘Green Towers’,and ‘Darkland’ had relatively high initial levels of all tested nutrients and good rate of their retention.There was no clear correlation between initial AsA/carotene concentrations and their retention rates,suggesting that besides content,retention of nutrients should also be a breeding target in a lettuce nutritional improvement program.Statistical analyses with the Pearson's correlation coefficient determined a negative relationship between tissue deterioration(AUDePS) and retention of all tested nutrients[r of-0.52 (P<0.0001) for AsA,-0.27 (P<0.01) for total carotene,and-0.59 (P<0.0001) for total sugars],suggesting that an increase in tissue deterioration intensifies nutrient decay.Broad-sense heritability (H~2) across the experiments was0.15 for AsA,0.23 for total carotene,and 0.50 for total sugars.Identification of germplasm with high nutrient content,extended shelf life and good nutrient retention provides valuable information for the lettuce industry and associated breeding programs.