Microglia,the resident immune cells of the central nervous system,exhibit a wide array of functional states,even in their so-called“homeostatic”condition,when they are not actively responding to overt pathological s...Microglia,the resident immune cells of the central nervous system,exhibit a wide array of functional states,even in their so-called“homeostatic”condition,when they are not actively responding to overt pathological stimuli.These functional states can be visualized using a combination of multi-omics techniques(e.g.,gene and protein expression,posttranslational modifications,mRNA profiling,and metabolomics),and,in the case of homeostatic microglia,are largely defined by the global(e.g.,genetic variations,organism’s age,sex,circadian rhythms,and gut microbiota)as well as local(specific area of the brain,immediate microglial surrounding,neuron-glia interactions and synaptic density/activity)signals(Paolicelli et al.,2022).While phenomics(i.e.,ultrastructural microglial morphology and motility)is also one of the key microglial state-defining parameters,it is known that cells with similar morphology can belong to different functional states.展开更多
Background:Excessive use of inorganic trace minerals(ITMs)in swine production leads to high fecal mineral excretion and environmental risks,while most studies on organic trace minerals(OTMs)focus on single elements,wi...Background:Excessive use of inorganic trace minerals(ITMs)in swine production leads to high fecal mineral excretion and environmental risks,while most studies on organic trace minerals(OTMs)focus on single elements,with limited data on the synergistic effects and molecular mechanisms of combined OTMs(Fe,Cu,Mn,Zn)in growing-finishing pigs.Methods:This study aimed to investigate the effects of graded levels of micromineral proteinates(combined OTMs)on growth performance,mineral metabolism,and mRNA expression of mineral regulatory proteins.A total of 360 crossbred Duroc×Landrace×Large White pigs(initial body weight 47.1±4.8 kg)were randomly assigned to 6 dietary treatments:basal diet without microminerals(CON),basal diet with ITMs at commercially recommended levels(IT),and basal diets with 15%(OT 15%),25%(OT 25%),35%(OT 35%)commercially recommended levels(CRL)of combined micromineral proteinates.After a 70-day feeding trial,samples were analyzed using ICP-OES,ELISA,and RT-qPCR.Results:Results showed that reduced levels(15-35%CRL)of micromineral proteinates did not significantly affect average daily gain,average daily feed intake,or feed conversion ratio(gain-to-feed ratio)compared to IT(P>0.05),but significantly increased plasma Cu(1.73-1.83μg/mL)and Zn(1.72-1.97μg/mL)concentrations(P<0.05)and elevated activities of Cu/Zn-superoxide dismutase(32.9-35.9 U/L)and manganese superoxide dismutase(20.5-24.1 U/L)compared to CON(P<0.05),with no significant differences from IT(P>0.05).Fecal excretion of Fe,Cu,Mn,and Zn was significantly reduced by 35-50%in OT 15%-OT 35%groups compared to IT(P<0.05).OT 25%group exhibited the highest apparent absorptivity of Fe(38.5%),Cu(27.8%),and Zn(42.4%)(P<0.05),which was associated with significantly regulated mRNA expression of mineral regulatory proteins:upregulated DMT1,FPN1,ZIP4,and MT1A in the duodenum,and modulated HAMP,ATP7B,ZIP14,and ZnT1 in the liver(P<0.05).Conclusion:In conclusion,dietary supplementation with 25%CRL or less of combined micromineral proteinates can fully meet the nutritional needs of growing-finishing pigs,improve mineral absorptivity,and reduce fecal mineral excretion by regulating intestinal and hepatic mineral transport and homeostatic proteins,providing a sustainable alternative to high-dose ITMs.展开更多
Hyperexcitability of neural network is a key neurophysiological mechanism in several neurological disorders including epilepsy, neuropathic pain, and tinnitus. Although standard paradigm of pharmacological management ...Hyperexcitability of neural network is a key neurophysiological mechanism in several neurological disorders including epilepsy, neuropathic pain, and tinnitus. Although standard paradigm of pharmacological management of them is to suppress this hyperexcitability, such as having been exemplified by the use of certain antiepileptic drugs, their frequent refractoriness to drug treatment suggests likely different pathophysiological mechanism. Because the pathogenesis in these disorders exhibits a transition from an initial activity loss after injury or sensory deprivation to subsequent hyperexcitability and paroxysmal discharges, this process can be regarded as a process of functional compensation similar to homeostatic plasticity regulation, in which a set level of activity in neural network is maintained after injury-induced activity loss through enhanced network excitability. Enhancing brain activity, such as cortical stimulation that is found to be effective in relieving symptoms of these disorders, may reduce such hyperexcitability through homeostatic plasticity mechanism. Here we review current evidence of homeostatic plasticity in the mechanism of acquired epilepsy, neuropathic pain, and tinnitus and the effects and mechanism of cortical stimulation. Establishing a role of homeostatic plasticity in these disorders may provide a theoretical basis on their pathogenesis as well as guide the development and application of therapeutic approaches through electrically or pharmacologically stimulating brain activity for treating these disorders.展开更多
Membrane depolarization induces the release of the serine proteinase tissue-type plasminogen activator(t PA) from the presynaptic terminal of cerebral cortical neurons.Once in the synaptic cleft this t PA promotes t...Membrane depolarization induces the release of the serine proteinase tissue-type plasminogen activator(t PA) from the presynaptic terminal of cerebral cortical neurons.Once in the synaptic cleft this t PA promotes the exocytosis and subsequent endocytic retrieval of glutamate-containing synaptic vesicles,and regulates the postsynaptic response to the presynaptic release of glutamate.Indeed,t PA has a bidirectional effect on the composition of the postsynaptic density(PSD) that does not require plasmin generation or the presynaptic release of glutamate,but varies according to the baseline level of neuronal activity.Hence,in inactive neurons t PA induces phosphorylation and accumulation in the PSD of the Ca^(2+)/calmodulin-dependent protein kinase IIα(pCa MKIIα),followed by pCa MKIIα-induced phosphorylation and synaptic recruitment of Glu R1-containing α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid(AMPA) receptors.In contrast,in active neurons with increased levels of pCa MKIIα in the PSD t PA induces pCa MKIIα and p Glu R1 dephosphorylation and their subsequent removal from the PSD.These effects require active synaptic N-methyl-D-aspartate(NMDA) receptors and cyclin-dependent kinase 5(Cdk5)-induced phosphorylation of the protein phosphatase 1(PP1) at T320.These data indicate that t PA is a homeostatic regulator of the postsynaptic response of cerebral cortical neurons to the presynaptic release of glutamate via bidirectional regulation of the pCa MKIIα/PP1 switch in the PSD.展开更多
<strong>Background: </strong>Progressive insulin resistance (IR) is an important pathophysiologic mechanism of gestational diabetes mellitus (GDM). Homeostatic model assessment (HOMA) is commonly used as a...<strong>Background: </strong>Progressive insulin resistance (IR) is an important pathophysiologic mechanism of gestational diabetes mellitus (GDM). Homeostatic model assessment (HOMA) is commonly used as a parameter of the severity of insulin resistance. <strong>Aims:</strong> To determine indices of insulin resistance (IR) and <em>β</em>-cell function in gestational diabetes mellitus (GDM). <strong>Methods:</strong> This cross sectional study was conducted from March 2017 to September 2018 at Department of Endocrinology, Bangabandhu Sheikh Mujib Medical University (B中央人民政府), Dhaka, Bangladesh. The study was performed with 41 GDM and equal number of pregnant women with normal glucose tolerance (NGT) diagnosed on basis of WHO criterion-2013 during 24 - 40 weeks of gestation. Serum glucose was measured by glucose oxidase method and fasting serum insulin was measured by chemiluminescent immunoassay. Equations of homeostatic model assessment (HOMA) were used to calculate insulin indices like-insulin resistance (HOMA-IR), <em>β</em>-cell function (HOMA-B) and insulin sensitivity (HOMA-%S). Data were analyzed and compared by statistical tests. <strong>Results: </strong>A total of eighty-two (82) subjects [41 women with GDM (age: 28.29 ± 3.79 years, BMI: 27.16 ± 4.13 kg/m2) and 41 women with NGT (age: 26.22 ± 5.13 years, BMI: 25.27 ± 3.01 kg/m2)] were included in this study. It was observed that GDM women were significantly older (p = 0.041) and had significantly higher BMI (p = 0.020) than pregnant women with NGT. The GDM group had significantly higher IR as indicated by higher fasting insulin value [GDM vs. NGT;10.19 (7.71 - 13.34) vs. 6.88 (5.88 - 8.47) μIU/ml, median (IQR);p = 0.001] and HOMA-IR [GDM vs. NGT;2.31 (1.73 - 3.15) vs. 1.42 (1.15 - 1.76), median (IQR);p < 0.001], poor <em>β</em>-cell secretory capacity [GDM vs. NGT;HOMA-B: 112.63 (83.52 - 143.93) vs. 128.60 (108.77 - 157.58), median (IQR);p = 0.04] and low insulin sensitivity [GDM vs. NGT;HOMA-%S: 43.29 (31.77 - 57.98) vs. 70.42 (56.86 - 86.59), median (IQR);p < 0.001]. Conclusions: GDM is associated with both insulin resistance and inadequate insulin secretion.展开更多
Humans have been using Cannabis and its extracts for a few thousand years as a medicinal and recreational drug. How- ever, the chemical component in Cannabis sativa, △9-tet- rahydrocannabinol (△9-THC), an exogenou...Humans have been using Cannabis and its extracts for a few thousand years as a medicinal and recreational drug. How- ever, the chemical component in Cannabis sativa, △9-tet- rahydrocannabinol (△9-THC), an exogenous cannabinoid, remained unknown until it was isolated and identified as the main psychoactive ingredient (Gaoni and Mechoulam, 1964).展开更多
The paper considers new approaches to system analysis of natural phenomena in physics, chemistry and bi- ology. It lays the foundation of the homeostatic determinate systems theory that allows revealing the mecha- nis...The paper considers new approaches to system analysis of natural phenomena in physics, chemistry and bi- ology. It lays the foundation of the homeostatic determinate systems theory that allows revealing the mecha- nism by which the basic principle of natural science, determinism, is being realized. Evolution of the mate- rial world is represented as inevitable and continuous growth of orderliness (negentropy) based on transition from one type of determinate systems to another. Increasing negentropy is shown to be closely associated with continuous accumulation of information, which determines the natural diversity in physics, chemistry and biology.展开更多
Mechanisms of homeostatic plasticity promote compensatory changes of cellular excitability in response to chronic changes in the network activity.This type of plasticity is essential for the maintenance of brain circu...Mechanisms of homeostatic plasticity promote compensatory changes of cellular excitability in response to chronic changes in the network activity.This type of plasticity is essential for the maintenance of brain circuits and is involved in the regulation of neural regeneration and the progress of neurodegenerative disorders.One of the most studied homeostatic processes is synaptic scaling,where global synaptic adjustments take place to restore the neuronal firing rate to a physiological range by the modulation of synaptic receptors,neurotransmitters,and morphology.However,despite the comprehensive literature on the electrophysiological properties of homeostatic scaling,less is known about the structural adjustments that occur in the synapses and dendritic tree.In this study,we performed a meta-analysis of articles investigating the effects of chronic network excitation(synaptic downscaling)or inhibition(synaptic upscaling)on the dendritic spine density of neurons.Our results indicate that spine density is consistently reduced after protocols that induce synaptic scaling,independent of the intervention type.Then,we discuss the implication of our findings to the current knowledge on the morphological changes induced by homeostatic plasticity.展开更多
The autophagosomes were identified in the viable cycloheximide (CHX)-treated cells which had an incapacitated translational process and thus disabled synthesis of endoplasmic reticulum (ER)-derived vesicular transport...The autophagosomes were identified in the viable cycloheximide (CHX)-treated cells which had an incapacitated translational process and thus disabled synthesis of endoplasmic reticulum (ER)-derived vesicular transporters. They were found devoid of the proteins transported from ER to cell organelles, were unable to fuse with ER, Golgi or mitochondria, and displayed affinity with lysosomes. The analysis of autophagosomes, derived from the CHX cell organelles, revealed that their lipid composition resemble that of the maternal organelle. Thus, the ER-derived autophagosomes were marked with the presence of phosphatidylinositol (PI), Golgi-derived vesicles contained sphingomyelin (SM) and glycosphingolipids (GLL), and the mitochondria-derived autophagosomes contained phosphatidylglycerol (PG) and cardiolipin (CL). The incubation of the vesicles with intact lysosomes afforded their and the lysosome membrane lipids degradation. The analysis of the products derived from incubation of lysosomes and autophagosomes with radiolabeled SM, in the presence and the absence of TritonX100, allowed us to conclude that during autophagosome degradation the lysosomal enzymes are not released to cytosol, and that only lysosomes contain the enzymes degrading membrane lipids. In summary, our findings allowed us to authenticate the vesicles generated in the CHX-treated cells as organelle-specific autophagosomes and to determine that complete cycle of cell restitution and debridement includes intralysosomal degradation of the lysosomal membrane engulfing the autophagosomes vesicles.展开更多
In this paper the making of homeostatic models of the bioenergetic informational acupunctural human’s system of the “Pentacube” and the “Hexagon” according to the Wu Xing rules and energy shifts dynamics is consi...In this paper the making of homeostatic models of the bioenergetic informational acupunctural human’s system of the “Pentacube” and the “Hexagon” according to the Wu Xing rules and energy shifts dynamics is considering. The making of the meridional homeostatic model of the bioenergetic informational acupunctural human’s system based on the existing knowledges about the human body meridians is considering. Preference to choice of the homeostatic functional models of the human body organs energies interaction is substantiated. The meridional control submodel of homeostatic system is defined and constructed. The description of control submodel, perspectives of application and development are represented.展开更多
Sleep is a fundamental biological process essential for maintaining brain function,cognitive performance,and overall health.Despite over a century of research,the mechanisms underlying sleep homeostasis-the process by...Sleep is a fundamental biological process essential for maintaining brain function,cognitive performance,and overall health.Despite over a century of research,the mechanisms underlying sleep homeostasis-the process by which the need for sleep accumulates during wakefulness and dissipates during sleep-remain incompletely understood.This article explores the latest advancements in sleep research,focusing on the role of synaptic plasticity in sleep homeostasis,as illuminated by Sawada et al.(2024).展开更多
In this work,we propose and investigate a human immunodeficiency virus(HIV)infection model that considers CD4^(+)T cell homeostasis and the cytotoxic T lymphocyte(CTL)response.The local stability of the disease-free a...In this work,we propose and investigate a human immunodeficiency virus(HIV)infection model that considers CD4^(+)T cell homeostasis and the cytotoxic T lymphocyte(CTL)response.The local stability of the disease-free and endemic equilibrium point is established.Further,the global stability of the disease-free and endemic equilibrium points is investigated.Under specific parametric conditions,it is shown that the model exhibits backward,forward(transcritical)bifurcation,Hopf and Hopf-Hopf bifurcation.We have further considered a time lag in the model to represent the time delay between CD4^(+)T cell infection and the viral particle production and performed the stability and bifurcation analysis for the delay model.We conduct comprehensive numerical experiments to visualize the dynamical behavior of the HIV model and validate our findings.展开更多
Cell function has a tight relationship with cell architecture.Distribution of proteins to the correct compartment is one of the functions of the traffic pathway through the Golgi apparatus.The others are to ensure pro...Cell function has a tight relationship with cell architecture.Distribution of proteins to the correct compartment is one of the functions of the traffic pathway through the Golgi apparatus.The others are to ensure proper protein folding,the addition of post-translational modifications,and delivering to intracellular and extracellular destinations.Astrocytes are fundamental homeostatic cells,controlling multiple aspects of the central nervous system physiology,such as ion balance,nutrients,blood flow,neurotransmitters,and responses to insults.Astrocytes are polarized cells,and,such as neurons,extensively use the secretory pathway for secreting factors and exposing functional receptors,channels,and transporters on the plasma membrane.In this review,we will underline the importance of studying the Golgi apparatus and the secretory pathway in astrocytes,based on the possible tight connection between the Golgi apparatus and astrocytes’homeostatic function.Given the topic of this review,we will provide examples mostly about the Golgi apparatus structure,function,localization,and its involvement in astrocytes’homeostatic response,with an insight into congenital glycosylation disorders,as an example of a potential future field in the study of astrocyte homeostatic failure and Golgi apparatus alteration.展开更多
Adaptation is an eternal theme of biological evolution. The paper aims at exploring the conception of positive correlation between traditional Chinese medicine (TCM) and human homeostatic evolution based on medical ...Adaptation is an eternal theme of biological evolution. The paper aims at exploring the conception of positive correlation between traditional Chinese medicine (TCM) and human homeostatic evolution based on medical perspective. Discussions mainly involve TCM conforming to natural laws and natural evolution of life, spontaneous harmonization of yin and yang and operating system of human self-healing, modern human immunology and human endogenous immune function in TCM, self-homeostasis of human micro-ecological state and balance mechanism on regulating base in TCM, as well as adaptation--eternal theme of biological evolution and safeguarding adaptability--value of TCM. In perspective of medicine, theory and practice of TCM are in positive correlation with human homeostatic evolution, and what TCM tries to maintain is human intrinsic adaptive capability to disease and nature. Therefore, it is the core value of TCM, which is to be further studied, explored, realized and known to the world.展开更多
In this paper,we investigate a delayed HIV infection model that considers the homeostatic prolif-eration of CD4^(+)T cells.The existence and stability of uninfected equilibrium and infected equilibria(smaller and larg...In this paper,we investigate a delayed HIV infection model that considers the homeostatic prolif-eration of CD4^(+)T cells.The existence and stability of uninfected equilibrium and infected equilibria(smaller and larger ones)are studied by analyzing the characteristic equation of the system.The intracellular delay does not affect the stability of uninfected equilibrium,but it can change the stability of larger positive equilibrium and Hopf bifurcation appears inducing stable limit cycles.Furthermore,direction and stability of Hopf bifur-cation are well investigated by using the central manifold theorem and the normal form theory.The numerical simulation results show that the stability region of larger positive equilibrium becomes smaller as the increase of time delay.Moreover,when the maximum homeostatic growth rate is very small,the larger positive equilibrium is always stable.On the contrary,when the rate of supply of T cells is very small,the larger positive equilibrium is always unstable.展开更多
Antimicrobial resistance(AMR)is a growing public health crisis that requires innovative solutions.Emerging multidrug resistant(MDR)Salmonella typhimurium has raised concern for its effect on pathogenic infection and m...Antimicrobial resistance(AMR)is a growing public health crisis that requires innovative solutions.Emerging multidrug resistant(MDR)Salmonella typhimurium has raised concern for its effect on pathogenic infection and mortality in humans caused by enteric diseases.To combat these MDR Salmonella typhimurium pathogens,highly effective and broad-spectrum antibiotics such as flufenicol(FFC)need to be evaluated for their potent antibacterial activity against Salmonella typhimurium.However,the low solubility and low oral bioavailability of flufenicol need to be addressed to better combat AMR.In this work,we develop a novel nano-formulation,flufenicol nano-micelles(FTPPM),which are based on d-α-tocopherol polyethylene glycol 1,000 succinate(TPGS)/poloxamer 188(P188),for the targeted treatment of biofilms formed by drug-resistant Salmonella typhimurium in the intestine.Herein,FTPPM were prepared via a thin film hydration method.The preparation process for the mixed micelles is simple and convenient compared with other existing nanodrug delivery systems,which can further decrease production costs.The optimized FTPPM demonstrated outstanding stability and sustained release.An evaluation of the in vivo anti-drug-resistant Salmonella typhimurium efficacy demonstrated that FTPPM showed a stronger efficacy(68.17%)than did florfenicol-loaded TPGS polymer micelles(FTPM),flufenicol active pharmaceutical ingredients(FFC-API),and flufenicol commercially available medicine(FFC-CAM),and also exhibited outstanding biocompatibility.Notably,FTPPM also inhibited drug-resistant Salmonella typhimurium from forming biofilms.More importantly,FTPPM effectively restored intestinal flora disorders induced by drug-resistant Salmonella typhimurium in mice.In summary,FTPPM significantly improved the solubility and oral bioavailability of florfenicol,enhancing its efficacy against drug-resistant Salmonella typhimurium both in vitro and in vivo.FTPPM represent a promising drug-resistant Salmonella typhimurium treatment for curbing bacterial resistance via oral administration.展开更多
Osteoarthritis(OA)is one of the most common degenerative and age-related diseases in joints,which affects 654 million people worldwide.Current therapies could not fundamentally reverse the pathologic process of OA due...Osteoarthritis(OA)is one of the most common degenerative and age-related diseases in joints,which affects 654 million people worldwide.Current therapies could not fundamentally reverse the pathologic process of OA due to the complex pathogenesis.Although OA mechanisms have been investigated on a large scale over the past decade,the OA pathology correlated with aging-associated changes is still largely unrevealed.Therefore,in-depth analysis of the aging microenvironment and aging-related molecular mechanisms in OA may offer additional strategies for clinical prevention and treatment.In this review,we discuss the potential pathogenesis of OA in light of aging-associated changes and summarize three main components of the aging microenvironment of the OA joint:immune homeostatic imbalance,cellular senescence,and stem cell exhaustion,which could be induced by aging and further exacerbate OA progression.Additionally,it is emphasized that immune homeostatic imbalance appears before established OA,which occurs in the early stage and is the therapeutic window of opportunity for better clinical outcomes.Importantly,we evaluate recent therapeutic targets and promising interventions against these components,as well as the challenges and prospects for precise and individualized therapies of OA patients,which we believe would guide the construction of novel combined strategies targeting aging-related factors against OA for better treatments in the future.展开更多
AIM: This study was undertaken to evaluate the hepatic effects of silybum marianum on non alcoholic fatty liver disease (NAFLD). METHODS: In 72 patients affected by NAFLD, main metabolic, hepatic and anti-inflammatory...AIM: This study was undertaken to evaluate the hepatic effects of silybum marianum on non alcoholic fatty liver disease (NAFLD). METHODS: In 72 patients affected by NAFLD, main metabolic, hepatic and anti-inflammatory parameters were assayed after 3 mo of a restricted diet and before silymarin treatment (twice a day orally). The brightness of liver echography texture (hepatorenal ratio brightness) was also defined at same time. These evaluations were repeated after 6 mo of treatment. RESULTS: Serum levels of some metabolic and anti-inflammatory data nonsignificantly lowered after 6 mo of silymarin. On the contrary, Steato test, alanine aminotransferase (ALT), aspartate aminotransferase (AST) and gamma-glutamyl transpeptidase were significantly (P < 0.001) reduced. Instead, the AST/ALT ratio unchanged. Finally, the hepatorenal brightness ratio, as an index of hepatic steatosis, significantly (P < 0.05) dropped. CONCLUSION: The obtained results indicate that silymarin appears to be effective to reduce the biochemical, inflammatory and ultrasonic indices of hepatic steatosis. Some parameters indicative of early stage of atherosclerosis were also lowered.展开更多
The growing worldwide burden of insulin resistance(IR) emphasizes the importance of early identification for improved management.Obesity,particularly visceral obesity,has been a key contributing factor in the developm...The growing worldwide burden of insulin resistance(IR) emphasizes the importance of early identification for improved management.Obesity,particularly visceral obesity,has been a key contributing factor in the development of IR.The obesity-associated chronic inflammatory state contributes to the development of obesity-related comorbidities,including IR.Adipocytokines,which are released by adipose tissue,have been investigated as possible indicators of IR.Visfatin was one of the adipocytokines that attracted attention due to its insulinmimetic activity.It is released from a variety of sources,including visceral fat and macrophages,and it influences glucose metabolism and increases inflammation.The relationship between visfatin and IR in obesity is debatable.As a result,the purpose of this review was to better understand the role of visfatin in glucose homeostasis and to review the literature on the association between visfatin levels and IR,cardiovascular diseases,and renal diseases in obesity.展开更多
BACKGROUND Acute non-variceal upper gastrointestinal bleeding(ANVUGIB)constitutes a prevalent emergency within Gastroenterology,encompassing 80%-90%of all gastrointestinal hemorrhage incidents.This condition is distin...BACKGROUND Acute non-variceal upper gastrointestinal bleeding(ANVUGIB)constitutes a prevalent emergency within Gastroenterology,encompassing 80%-90%of all gastrointestinal hemorrhage incidents.This condition is distinguished by its abrupt onset,swift progression,and notably elevated mortality rate.AIM To gather clinical data from patients with ANVUGIB at our hospital in order to elucidate the clinical characteristics specific to our institution and analyze the therapeutic effectiveness of endoscopic hemostasis.METHODS We retrospectively retrieved the records of 532 patients diagnosed with ANVUGIB by endoscopy at our hospital between March 2021 and March 2023,utilizing our medical record system.Data pertaining to general patient information,etiological factors,disease outcomes,and other relevant variables were meticulously collected and analyzed.RESULTS Among the 532 patients diagnosed with ANVUGIB,the male-to-female ratio was 2.91:1,with a higher prevalence among males.Notably,43.6%of patients presented with black stool as their primary complaint,while 27.4%had hematemesis as their initial symptom.Upon admission,17%of patients exhibited both hematemesis and black stool,while most ANVUGIB patients primarily complained of overt gastrointestinal bleeding.Urgent routine blood examinations at admission revealed that 75.8%of patients had anemia,with 63.4%experiencing moderate to severe anemia,and 1.5%having extremely severe anemia(hemoglobin<30 g/L).With regard to etiology,53.2%of patients experienced bleeding without a definitive trigger,24.2%had a history of using gastric mucosa-irritating medications,24.2%developed bleeding after alcohol consumption,2.8%attributed it to improper diet,1.7%to emotional excitement,and 2.3%to fatigue preceding the bleeding episode.Drug-induced ANVUGIB was more prevalent in the elderly than middle-aged and young individuals,while bleeding due to alcohol consumption showed the opposite trend.Additionally,diet-related bleeding was more common among the young age group compared to the middle-aged group.Gastrointestinal endoscopy identified peptic ulcers as the most frequent cause of ANVUGIB(73.3%),followed by gastrointestinal malignancies(10.9%),acute gastric mucous lesions(9.8%),and androgenic upper gastrointestinal bleeding(1.5%)among inpatients with ANVUGIB.Of the 532 patients with gastrointestinal bleeding,68 underwent endoscopic hemostasis,resulting in an endoscopic treatment rate of 12.8%,with a high immediate hemostasis success rate of 94.1%.展开更多
基金supported by Deutsche Forschungsgemeinschaft,German Research Foundation grant GA 654/13-2 to OG.
文摘Microglia,the resident immune cells of the central nervous system,exhibit a wide array of functional states,even in their so-called“homeostatic”condition,when they are not actively responding to overt pathological stimuli.These functional states can be visualized using a combination of multi-omics techniques(e.g.,gene and protein expression,posttranslational modifications,mRNA profiling,and metabolomics),and,in the case of homeostatic microglia,are largely defined by the global(e.g.,genetic variations,organism’s age,sex,circadian rhythms,and gut microbiota)as well as local(specific area of the brain,immediate microglial surrounding,neuron-glia interactions and synaptic density/activity)signals(Paolicelli et al.,2022).While phenomics(i.e.,ultrastructural microglial morphology and motility)is also one of the key microglial state-defining parameters,it is known that cells with similar morphology can belong to different functional states.
基金financially supported by the Hainan Province Science and Technology Special Fund(Grant no:ZDYF2024XDNY187).
文摘Background:Excessive use of inorganic trace minerals(ITMs)in swine production leads to high fecal mineral excretion and environmental risks,while most studies on organic trace minerals(OTMs)focus on single elements,with limited data on the synergistic effects and molecular mechanisms of combined OTMs(Fe,Cu,Mn,Zn)in growing-finishing pigs.Methods:This study aimed to investigate the effects of graded levels of micromineral proteinates(combined OTMs)on growth performance,mineral metabolism,and mRNA expression of mineral regulatory proteins.A total of 360 crossbred Duroc×Landrace×Large White pigs(initial body weight 47.1±4.8 kg)were randomly assigned to 6 dietary treatments:basal diet without microminerals(CON),basal diet with ITMs at commercially recommended levels(IT),and basal diets with 15%(OT 15%),25%(OT 25%),35%(OT 35%)commercially recommended levels(CRL)of combined micromineral proteinates.After a 70-day feeding trial,samples were analyzed using ICP-OES,ELISA,and RT-qPCR.Results:Results showed that reduced levels(15-35%CRL)of micromineral proteinates did not significantly affect average daily gain,average daily feed intake,or feed conversion ratio(gain-to-feed ratio)compared to IT(P>0.05),but significantly increased plasma Cu(1.73-1.83μg/mL)and Zn(1.72-1.97μg/mL)concentrations(P<0.05)and elevated activities of Cu/Zn-superoxide dismutase(32.9-35.9 U/L)and manganese superoxide dismutase(20.5-24.1 U/L)compared to CON(P<0.05),with no significant differences from IT(P>0.05).Fecal excretion of Fe,Cu,Mn,and Zn was significantly reduced by 35-50%in OT 15%-OT 35%groups compared to IT(P<0.05).OT 25%group exhibited the highest apparent absorptivity of Fe(38.5%),Cu(27.8%),and Zn(42.4%)(P<0.05),which was associated with significantly regulated mRNA expression of mineral regulatory proteins:upregulated DMT1,FPN1,ZIP4,and MT1A in the duodenum,and modulated HAMP,ATP7B,ZIP14,and ZnT1 in the liver(P<0.05).Conclusion:In conclusion,dietary supplementation with 25%CRL or less of combined micromineral proteinates can fully meet the nutritional needs of growing-finishing pigs,improve mineral absorptivity,and reduce fecal mineral excretion by regulating intestinal and hepatic mineral transport and homeostatic proteins,providing a sustainable alternative to high-dose ITMs.
基金supported in part by the NIH DA039530(to XJ)a grant from the CURE Epilepsy Foundation(to XJ)
文摘Hyperexcitability of neural network is a key neurophysiological mechanism in several neurological disorders including epilepsy, neuropathic pain, and tinnitus. Although standard paradigm of pharmacological management of them is to suppress this hyperexcitability, such as having been exemplified by the use of certain antiepileptic drugs, their frequent refractoriness to drug treatment suggests likely different pathophysiological mechanism. Because the pathogenesis in these disorders exhibits a transition from an initial activity loss after injury or sensory deprivation to subsequent hyperexcitability and paroxysmal discharges, this process can be regarded as a process of functional compensation similar to homeostatic plasticity regulation, in which a set level of activity in neural network is maintained after injury-induced activity loss through enhanced network excitability. Enhancing brain activity, such as cortical stimulation that is found to be effective in relieving symptoms of these disorders, may reduce such hyperexcitability through homeostatic plasticity mechanism. Here we review current evidence of homeostatic plasticity in the mechanism of acquired epilepsy, neuropathic pain, and tinnitus and the effects and mechanism of cortical stimulation. Establishing a role of homeostatic plasticity in these disorders may provide a theoretical basis on their pathogenesis as well as guide the development and application of therapeutic approaches through electrically or pharmacologically stimulating brain activity for treating these disorders.
基金supported in part by National Institutes of Health Grants NS-079331(to MY)and NS-091201(to MY)
文摘Membrane depolarization induces the release of the serine proteinase tissue-type plasminogen activator(t PA) from the presynaptic terminal of cerebral cortical neurons.Once in the synaptic cleft this t PA promotes the exocytosis and subsequent endocytic retrieval of glutamate-containing synaptic vesicles,and regulates the postsynaptic response to the presynaptic release of glutamate.Indeed,t PA has a bidirectional effect on the composition of the postsynaptic density(PSD) that does not require plasmin generation or the presynaptic release of glutamate,but varies according to the baseline level of neuronal activity.Hence,in inactive neurons t PA induces phosphorylation and accumulation in the PSD of the Ca^(2+)/calmodulin-dependent protein kinase IIα(pCa MKIIα),followed by pCa MKIIα-induced phosphorylation and synaptic recruitment of Glu R1-containing α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid(AMPA) receptors.In contrast,in active neurons with increased levels of pCa MKIIα in the PSD t PA induces pCa MKIIα and p Glu R1 dephosphorylation and their subsequent removal from the PSD.These effects require active synaptic N-methyl-D-aspartate(NMDA) receptors and cyclin-dependent kinase 5(Cdk5)-induced phosphorylation of the protein phosphatase 1(PP1) at T320.These data indicate that t PA is a homeostatic regulator of the postsynaptic response of cerebral cortical neurons to the presynaptic release of glutamate via bidirectional regulation of the pCa MKIIα/PP1 switch in the PSD.
文摘<strong>Background: </strong>Progressive insulin resistance (IR) is an important pathophysiologic mechanism of gestational diabetes mellitus (GDM). Homeostatic model assessment (HOMA) is commonly used as a parameter of the severity of insulin resistance. <strong>Aims:</strong> To determine indices of insulin resistance (IR) and <em>β</em>-cell function in gestational diabetes mellitus (GDM). <strong>Methods:</strong> This cross sectional study was conducted from March 2017 to September 2018 at Department of Endocrinology, Bangabandhu Sheikh Mujib Medical University (B中央人民政府), Dhaka, Bangladesh. The study was performed with 41 GDM and equal number of pregnant women with normal glucose tolerance (NGT) diagnosed on basis of WHO criterion-2013 during 24 - 40 weeks of gestation. Serum glucose was measured by glucose oxidase method and fasting serum insulin was measured by chemiluminescent immunoassay. Equations of homeostatic model assessment (HOMA) were used to calculate insulin indices like-insulin resistance (HOMA-IR), <em>β</em>-cell function (HOMA-B) and insulin sensitivity (HOMA-%S). Data were analyzed and compared by statistical tests. <strong>Results: </strong>A total of eighty-two (82) subjects [41 women with GDM (age: 28.29 ± 3.79 years, BMI: 27.16 ± 4.13 kg/m2) and 41 women with NGT (age: 26.22 ± 5.13 years, BMI: 25.27 ± 3.01 kg/m2)] were included in this study. It was observed that GDM women were significantly older (p = 0.041) and had significantly higher BMI (p = 0.020) than pregnant women with NGT. The GDM group had significantly higher IR as indicated by higher fasting insulin value [GDM vs. NGT;10.19 (7.71 - 13.34) vs. 6.88 (5.88 - 8.47) μIU/ml, median (IQR);p = 0.001] and HOMA-IR [GDM vs. NGT;2.31 (1.73 - 3.15) vs. 1.42 (1.15 - 1.76), median (IQR);p < 0.001], poor <em>β</em>-cell secretory capacity [GDM vs. NGT;HOMA-B: 112.63 (83.52 - 143.93) vs. 128.60 (108.77 - 157.58), median (IQR);p = 0.04] and low insulin sensitivity [GDM vs. NGT;HOMA-%S: 43.29 (31.77 - 57.98) vs. 70.42 (56.86 - 86.59), median (IQR);p < 0.001]. Conclusions: GDM is associated with both insulin resistance and inadequate insulin secretion.
基金supported by National Institutes of Health grants NS076815
文摘Humans have been using Cannabis and its extracts for a few thousand years as a medicinal and recreational drug. How- ever, the chemical component in Cannabis sativa, △9-tet- rahydrocannabinol (△9-THC), an exogenous cannabinoid, remained unknown until it was isolated and identified as the main psychoactive ingredient (Gaoni and Mechoulam, 1964).
文摘The paper considers new approaches to system analysis of natural phenomena in physics, chemistry and bi- ology. It lays the foundation of the homeostatic determinate systems theory that allows revealing the mecha- nism by which the basic principle of natural science, determinism, is being realized. Evolution of the mate- rial world is represented as inevitable and continuous growth of orderliness (negentropy) based on transition from one type of determinate systems to another. Increasing negentropy is shown to be closely associated with continuous accumulation of information, which determines the natural diversity in physics, chemistry and biology.
基金supported by scholarships from Conselho Nacional de Desenvolvimento Científico e Tecnológico(CNPq)Coordenaao de Aperfeicoamento de Pessoal de Nível Superior(CAPES),Brazil(to TCM and DR)+2 种基金supported by the Kungl Vetenskapssamh Scholarship(Royal Society of Arts and Scientists)provided by Uppsala University,Sweden(to TCM)supported by the Swedish Research Council and the Swedish Brain Research Foundation(to HBS)。
文摘Mechanisms of homeostatic plasticity promote compensatory changes of cellular excitability in response to chronic changes in the network activity.This type of plasticity is essential for the maintenance of brain circuits and is involved in the regulation of neural regeneration and the progress of neurodegenerative disorders.One of the most studied homeostatic processes is synaptic scaling,where global synaptic adjustments take place to restore the neuronal firing rate to a physiological range by the modulation of synaptic receptors,neurotransmitters,and morphology.However,despite the comprehensive literature on the electrophysiological properties of homeostatic scaling,less is known about the structural adjustments that occur in the synapses and dendritic tree.In this study,we performed a meta-analysis of articles investigating the effects of chronic network excitation(synaptic downscaling)or inhibition(synaptic upscaling)on the dendritic spine density of neurons.Our results indicate that spine density is consistently reduced after protocols that induce synaptic scaling,independent of the intervention type.Then,we discuss the implication of our findings to the current knowledge on the morphological changes induced by homeostatic plasticity.
文摘The autophagosomes were identified in the viable cycloheximide (CHX)-treated cells which had an incapacitated translational process and thus disabled synthesis of endoplasmic reticulum (ER)-derived vesicular transporters. They were found devoid of the proteins transported from ER to cell organelles, were unable to fuse with ER, Golgi or mitochondria, and displayed affinity with lysosomes. The analysis of autophagosomes, derived from the CHX cell organelles, revealed that their lipid composition resemble that of the maternal organelle. Thus, the ER-derived autophagosomes were marked with the presence of phosphatidylinositol (PI), Golgi-derived vesicles contained sphingomyelin (SM) and glycosphingolipids (GLL), and the mitochondria-derived autophagosomes contained phosphatidylglycerol (PG) and cardiolipin (CL). The incubation of the vesicles with intact lysosomes afforded their and the lysosome membrane lipids degradation. The analysis of the products derived from incubation of lysosomes and autophagosomes with radiolabeled SM, in the presence and the absence of TritonX100, allowed us to conclude that during autophagosome degradation the lysosomal enzymes are not released to cytosol, and that only lysosomes contain the enzymes degrading membrane lipids. In summary, our findings allowed us to authenticate the vesicles generated in the CHX-treated cells as organelle-specific autophagosomes and to determine that complete cycle of cell restitution and debridement includes intralysosomal degradation of the lysosomal membrane engulfing the autophagosomes vesicles.
文摘In this paper the making of homeostatic models of the bioenergetic informational acupunctural human’s system of the “Pentacube” and the “Hexagon” according to the Wu Xing rules and energy shifts dynamics is considering. The making of the meridional homeostatic model of the bioenergetic informational acupunctural human’s system based on the existing knowledges about the human body meridians is considering. Preference to choice of the homeostatic functional models of the human body organs energies interaction is substantiated. The meridional control submodel of homeostatic system is defined and constructed. The description of control submodel, perspectives of application and development are represented.
基金supported by Japan Society forthe Promotion of Science(JSPS)Grants-in-Aidfor Scientific Research(KAKENHI)(20H05894,20H05903,21K15136,22K21351,23H02518A,23H02663,and 23K18147 to SS),JST-CREST(JPMJCR24T4 to SS),the World PremierInternational Research Center Initiative(WPI)fromthe Ministry of Education,Culture,Sports,Scienceand Technology(MEXT)to SS(WPI-IIIS),the TopRunners in Strategy of Transborder AdvancedResearches(TRiSTAR)by the MEXT to SSJapanAgency for Medical Research and Development(AMED)(JP21zf0127005 to SS),Cell ScienceResearch Foundation Grant to YI,38th Brain ScienceFoundation Research Grant to YI,Research Granton Biogenic Amines and Neurological Diseases(Sumitomo pharma)to YI.
文摘Sleep is a fundamental biological process essential for maintaining brain function,cognitive performance,and overall health.Despite over a century of research,the mechanisms underlying sleep homeostasis-the process by which the need for sleep accumulates during wakefulness and dissipates during sleep-remain incompletely understood.This article explores the latest advancements in sleep research,focusing on the role of synaptic plasticity in sleep homeostasis,as illuminated by Sawada et al.(2024).
基金funded by the University Grant Commission(UGC)with File No.169(June 2018)/2019(NET/CSIR)while Anuj Kumar Umrao acknowledges Council for Scientific and Industrial Research(CSIR)under Grant No.09/1023(0038)/2020-EMR-I。
文摘In this work,we propose and investigate a human immunodeficiency virus(HIV)infection model that considers CD4^(+)T cell homeostasis and the cytotoxic T lymphocyte(CTL)response.The local stability of the disease-free and endemic equilibrium point is established.Further,the global stability of the disease-free and endemic equilibrium points is investigated.Under specific parametric conditions,it is shown that the model exhibits backward,forward(transcritical)bifurcation,Hopf and Hopf-Hopf bifurcation.We have further considered a time lag in the model to represent the time delay between CD4^(+)T cell infection and the viral particle production and performed the stability and bifurcation analysis for the delay model.We conduct comprehensive numerical experiments to visualize the dynamical behavior of the HIV model and validate our findings.
文摘Cell function has a tight relationship with cell architecture.Distribution of proteins to the correct compartment is one of the functions of the traffic pathway through the Golgi apparatus.The others are to ensure proper protein folding,the addition of post-translational modifications,and delivering to intracellular and extracellular destinations.Astrocytes are fundamental homeostatic cells,controlling multiple aspects of the central nervous system physiology,such as ion balance,nutrients,blood flow,neurotransmitters,and responses to insults.Astrocytes are polarized cells,and,such as neurons,extensively use the secretory pathway for secreting factors and exposing functional receptors,channels,and transporters on the plasma membrane.In this review,we will underline the importance of studying the Golgi apparatus and the secretory pathway in astrocytes,based on the possible tight connection between the Golgi apparatus and astrocytes’homeostatic function.Given the topic of this review,we will provide examples mostly about the Golgi apparatus structure,function,localization,and its involvement in astrocytes’homeostatic response,with an insight into congenital glycosylation disorders,as an example of a potential future field in the study of astrocyte homeostatic failure and Golgi apparatus alteration.
基金Supported by the Soft Scientific Project of Henan Province (No.102400440059)the Philosophy and Social Science Program of Henan Province,China(No.2011FYY014)
文摘Adaptation is an eternal theme of biological evolution. The paper aims at exploring the conception of positive correlation between traditional Chinese medicine (TCM) and human homeostatic evolution based on medical perspective. Discussions mainly involve TCM conforming to natural laws and natural evolution of life, spontaneous harmonization of yin and yang and operating system of human self-healing, modern human immunology and human endogenous immune function in TCM, self-homeostasis of human micro-ecological state and balance mechanism on regulating base in TCM, as well as adaptation--eternal theme of biological evolution and safeguarding adaptability--value of TCM. In perspective of medicine, theory and practice of TCM are in positive correlation with human homeostatic evolution, and what TCM tries to maintain is human intrinsic adaptive capability to disease and nature. Therefore, it is the core value of TCM, which is to be further studied, explored, realized and known to the world.
基金supported by the National Natural Science Foundation of China(Nos.11871235,11901225)the Natural Science Foundation of Hubei Province(2019CFB189)+1 种基金the Fundamental Research Funds for the Central Universities(Nos.CCNU19TS030,CCNU18XJ041)by the Japan Society for the Promotion of Science“Grand-in-Aid 20K03755”。
文摘In this paper,we investigate a delayed HIV infection model that considers the homeostatic prolif-eration of CD4^(+)T cells.The existence and stability of uninfected equilibrium and infected equilibria(smaller and larger ones)are studied by analyzing the characteristic equation of the system.The intracellular delay does not affect the stability of uninfected equilibrium,but it can change the stability of larger positive equilibrium and Hopf bifurcation appears inducing stable limit cycles.Furthermore,direction and stability of Hopf bifur-cation are well investigated by using the central manifold theorem and the normal form theory.The numerical simulation results show that the stability region of larger positive equilibrium becomes smaller as the increase of time delay.Moreover,when the maximum homeostatic growth rate is very small,the larger positive equilibrium is always stable.On the contrary,when the rate of supply of T cells is very small,the larger positive equilibrium is always unstable.
基金supported by the grants from the National Key Research and Development Program of China(Grant No.:2024YFE0106300)the Key Projects of Natural Science Foundation of Anhui Provincial Department of Education,China(Grant No.:2023AH051017)+2 种基金the Outstanding Youth Scientific Research Foundation of the Anhui Education Department,China(Grant No.:2024AH030019)the National Natural Science Foundation of China(Grant No.:32302923)Natural Science Foundation of Anhui Province,China(Grant No.:2208085MC79).
文摘Antimicrobial resistance(AMR)is a growing public health crisis that requires innovative solutions.Emerging multidrug resistant(MDR)Salmonella typhimurium has raised concern for its effect on pathogenic infection and mortality in humans caused by enteric diseases.To combat these MDR Salmonella typhimurium pathogens,highly effective and broad-spectrum antibiotics such as flufenicol(FFC)need to be evaluated for their potent antibacterial activity against Salmonella typhimurium.However,the low solubility and low oral bioavailability of flufenicol need to be addressed to better combat AMR.In this work,we develop a novel nano-formulation,flufenicol nano-micelles(FTPPM),which are based on d-α-tocopherol polyethylene glycol 1,000 succinate(TPGS)/poloxamer 188(P188),for the targeted treatment of biofilms formed by drug-resistant Salmonella typhimurium in the intestine.Herein,FTPPM were prepared via a thin film hydration method.The preparation process for the mixed micelles is simple and convenient compared with other existing nanodrug delivery systems,which can further decrease production costs.The optimized FTPPM demonstrated outstanding stability and sustained release.An evaluation of the in vivo anti-drug-resistant Salmonella typhimurium efficacy demonstrated that FTPPM showed a stronger efficacy(68.17%)than did florfenicol-loaded TPGS polymer micelles(FTPM),flufenicol active pharmaceutical ingredients(FFC-API),and flufenicol commercially available medicine(FFC-CAM),and also exhibited outstanding biocompatibility.Notably,FTPPM also inhibited drug-resistant Salmonella typhimurium from forming biofilms.More importantly,FTPPM effectively restored intestinal flora disorders induced by drug-resistant Salmonella typhimurium in mice.In summary,FTPPM significantly improved the solubility and oral bioavailability of florfenicol,enhancing its efficacy against drug-resistant Salmonella typhimurium both in vitro and in vivo.FTPPM represent a promising drug-resistant Salmonella typhimurium treatment for curbing bacterial resistance via oral administration.
基金supported by grants from National Natural Science Foundation of China(32370892)Science and Technology Commission of Shanghai Municipality(23141901200)+3 种基金Shanghai Natural Science Foundation(24ZR1450100)Health Commission of Shanghai Municipality(2022JC029)Biomaterials and Regenerative Medicine Institute Cooperative Research Project,Shanghai Jiaotong University School of Medicine(2022LHA11)Talent-Introduction Program of Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine(2022YJRC05).
文摘Osteoarthritis(OA)is one of the most common degenerative and age-related diseases in joints,which affects 654 million people worldwide.Current therapies could not fundamentally reverse the pathologic process of OA due to the complex pathogenesis.Although OA mechanisms have been investigated on a large scale over the past decade,the OA pathology correlated with aging-associated changes is still largely unrevealed.Therefore,in-depth analysis of the aging microenvironment and aging-related molecular mechanisms in OA may offer additional strategies for clinical prevention and treatment.In this review,we discuss the potential pathogenesis of OA in light of aging-associated changes and summarize three main components of the aging microenvironment of the OA joint:immune homeostatic imbalance,cellular senescence,and stem cell exhaustion,which could be induced by aging and further exacerbate OA progression.Additionally,it is emphasized that immune homeostatic imbalance appears before established OA,which occurs in the early stage and is the therapeutic window of opportunity for better clinical outcomes.Importantly,we evaluate recent therapeutic targets and promising interventions against these components,as well as the challenges and prospects for precise and individualized therapies of OA patients,which we believe would guide the construction of novel combined strategies targeting aging-related factors against OA for better treatments in the future.
文摘AIM: This study was undertaken to evaluate the hepatic effects of silybum marianum on non alcoholic fatty liver disease (NAFLD). METHODS: In 72 patients affected by NAFLD, main metabolic, hepatic and anti-inflammatory parameters were assayed after 3 mo of a restricted diet and before silymarin treatment (twice a day orally). The brightness of liver echography texture (hepatorenal ratio brightness) was also defined at same time. These evaluations were repeated after 6 mo of treatment. RESULTS: Serum levels of some metabolic and anti-inflammatory data nonsignificantly lowered after 6 mo of silymarin. On the contrary, Steato test, alanine aminotransferase (ALT), aspartate aminotransferase (AST) and gamma-glutamyl transpeptidase were significantly (P < 0.001) reduced. Instead, the AST/ALT ratio unchanged. Finally, the hepatorenal brightness ratio, as an index of hepatic steatosis, significantly (P < 0.05) dropped. CONCLUSION: The obtained results indicate that silymarin appears to be effective to reduce the biochemical, inflammatory and ultrasonic indices of hepatic steatosis. Some parameters indicative of early stage of atherosclerosis were also lowered.
文摘The growing worldwide burden of insulin resistance(IR) emphasizes the importance of early identification for improved management.Obesity,particularly visceral obesity,has been a key contributing factor in the development of IR.The obesity-associated chronic inflammatory state contributes to the development of obesity-related comorbidities,including IR.Adipocytokines,which are released by adipose tissue,have been investigated as possible indicators of IR.Visfatin was one of the adipocytokines that attracted attention due to its insulinmimetic activity.It is released from a variety of sources,including visceral fat and macrophages,and it influences glucose metabolism and increases inflammation.The relationship between visfatin and IR in obesity is debatable.As a result,the purpose of this review was to better understand the role of visfatin in glucose homeostasis and to review the literature on the association between visfatin levels and IR,cardiovascular diseases,and renal diseases in obesity.
基金Supported by Xi’an Health Commission Residential Training Base Construction Project,No.2023zp09.
文摘BACKGROUND Acute non-variceal upper gastrointestinal bleeding(ANVUGIB)constitutes a prevalent emergency within Gastroenterology,encompassing 80%-90%of all gastrointestinal hemorrhage incidents.This condition is distinguished by its abrupt onset,swift progression,and notably elevated mortality rate.AIM To gather clinical data from patients with ANVUGIB at our hospital in order to elucidate the clinical characteristics specific to our institution and analyze the therapeutic effectiveness of endoscopic hemostasis.METHODS We retrospectively retrieved the records of 532 patients diagnosed with ANVUGIB by endoscopy at our hospital between March 2021 and March 2023,utilizing our medical record system.Data pertaining to general patient information,etiological factors,disease outcomes,and other relevant variables were meticulously collected and analyzed.RESULTS Among the 532 patients diagnosed with ANVUGIB,the male-to-female ratio was 2.91:1,with a higher prevalence among males.Notably,43.6%of patients presented with black stool as their primary complaint,while 27.4%had hematemesis as their initial symptom.Upon admission,17%of patients exhibited both hematemesis and black stool,while most ANVUGIB patients primarily complained of overt gastrointestinal bleeding.Urgent routine blood examinations at admission revealed that 75.8%of patients had anemia,with 63.4%experiencing moderate to severe anemia,and 1.5%having extremely severe anemia(hemoglobin<30 g/L).With regard to etiology,53.2%of patients experienced bleeding without a definitive trigger,24.2%had a history of using gastric mucosa-irritating medications,24.2%developed bleeding after alcohol consumption,2.8%attributed it to improper diet,1.7%to emotional excitement,and 2.3%to fatigue preceding the bleeding episode.Drug-induced ANVUGIB was more prevalent in the elderly than middle-aged and young individuals,while bleeding due to alcohol consumption showed the opposite trend.Additionally,diet-related bleeding was more common among the young age group compared to the middle-aged group.Gastrointestinal endoscopy identified peptic ulcers as the most frequent cause of ANVUGIB(73.3%),followed by gastrointestinal malignancies(10.9%),acute gastric mucous lesions(9.8%),and androgenic upper gastrointestinal bleeding(1.5%)among inpatients with ANVUGIB.Of the 532 patients with gastrointestinal bleeding,68 underwent endoscopic hemostasis,resulting in an endoscopic treatment rate of 12.8%,with a high immediate hemostasis success rate of 94.1%.