Correction to:Cellular&Molecular Immunology https://doi.org/10.1038/cmi.2010.11,published online 22 March 2010 In Figure 4A(panel 3)of this article,the panel labeled“Tumor+Curcumin”was inadvertently placed in th...Correction to:Cellular&Molecular Immunology https://doi.org/10.1038/cmi.2010.11,published online 22 March 2010 In Figure 4A(panel 3)of this article,the panel labeled“Tumor+Curcumin”was inadvertently placed in the“Curcumin”panel instead of the original“Curcumin”panel.The corrected version of Figure 4 is shown below as the revised Figure 4.The figure legend remains the same.展开更多
AIM： To determine the presence of symptomatic accommodative and non-strabismic binocular dysfunctions （A.sBD） in a non-presbyopic population of video display unit （VDU） users with flat-panel displays. METHODS： ...AIM： To determine the presence of symptomatic accommodative and non-strabismic binocular dysfunctions （A.sBD） in a non-presbyopic population of video display unit （VDU） users with flat-panel displays. METHODS： One hundred and one VDU users, aged between 20 to 34y, initially participated in the study. This study excluded contact-lens wearers and subjects who had undergone refractive surgery or had any systemic or ocular disease. First, subjects were asked about the type and nature of eye symptoms they experienced during VDU use. Then, a thorough eye examination excluded those subjects with a significant uncorrected refractive error or other problem, such as ocular motility disorders, vertical deviation, strabismus and eye diseases. Finally, the remaining participants underwent an exhaustive assessment of their accommodative and binocular vision status. RESULTS： Eighty-nine VDU users （46 females and 43 males） were included in this study. They used flat-panel displays for an average of 5±1.9h a day. Twenty subjects presented A.sBD （22.5%）. Convergence excess was the most frequent non-strabismic binocular dysfunction （9 subjects）, followed by fusional vergence dysfunction （3 subjects） and convergence insufficiency （2 subjects）. Within the accommodative dysfunctions, accommodative excess was the most common （4 subjects）, followed by accommodative insufficiency （2 subjects）. Moderate to severe eye symptoms were found in 13 subjects with ANSBD. CONCLUSION： Significant eye symptoms in VDU users with accommodative and/or non-strabismic binocular dysfunctions often occur and should not be underestimated; therefore, an appropriate evaluation of accommodative and binocular vision status is more important for this population,展开更多
BACKGROUND Diabetes has become a widespread metabolic disease affecting multiple organs.Among diabetic complications,cardiovascular complications are the main cause of patient morbidity and mortality.Diabetic cardiomy...BACKGROUND Diabetes has become a widespread metabolic disease affecting multiple organs.Among diabetic complications,cardiovascular complications are the main cause of patient morbidity and mortality.Diabetic cardiomyopathy is a diabetes-specific cardiomyopathy in the absence of other cardiovascular disease and occurs more frequently in type 1 diabetes(T1D)than in type 2 diabetes.Previous studies on diabetic cardiomyopathy have predominantly focused on the effects of diabetes on left ventricular(LV)dysfunction,while studies of right ventricular(RV)dysfunction have been sparse but are gaining attention.Although T1D accounts for only 5%-10%of the total diabetic population,diabetic cardiomyopathy is a major cause of morbidity and mortality in children with life-long,long-term complications.AIM To evaluate longitudinal RV and LV functional changes in female transgenic OVE26,T1D mice and wild-type FVB mice over a 30-week period.METHODS RV and LV structure and function were evaluated by transthoracic echocardiography.RV systolic pressure was measured by a transducer-tipped pressure catheter.Sirius-red staining was used to quantify collagen and fibrosis,wheat germ agglutinin staining was utilized to measure cardiomyocyte size,and quantitative real-time polymerase chain reaction and Western blotting were used to quantify miRNA expression and protein abundance,respectively.RESULTS RV systolic function,measured by tricuspid valve annular plane systolic excursion and RV systolic velocity,was similar between control and T1D mice,but LV systolic function decreased in T1D mice at 30 weeks of age.RV diastolic dysfunction in T1D mice significantly increased by 18 weeks and progressed until 30 weeks,while LV diastolic dysfunction trended towards abnormal at 12 weeks,significantly increased by 18 weeks,and continued to progress by 30 weeks.Furthermore,RV diastolic dysfunction was accompanied by RV cardiac fibrosis and hypertrophy in T1D mice,occurring later than that in the LV.Pulmonary arterial hypertension developed in T1D mice,evidenced by increased pulmonary acceleration time to pulmonary ejection time ratio and increased RV peak systolic pressure at 30 weeks.These results suggest the development of early LV diastolic dysfunction followed by LV systolic dysfunction and RV diastolic dysfunction at 30 weeks in T1D mice.CONCLUSION RV diastolic dysfunction develops later than LV dysfunction in OVE26 T1D mice.Mild pulmonary arterial hypertension appear at later stages of T1D and could contribute to RV systolic impairment and remodeling.展开更多
The superfamily of G protein-coupled receptors (GPCRs) contains immense structural and functional diversity and mediates a myriad of biological processes upon activation by various extracellular signals.Critical roles...The superfamily of G protein-coupled receptors (GPCRs) contains immense structural and functional diversity and mediates a myriad of biological processes upon activation by various extracellular signals.Critical roles of GPCRs have been established in bone development,remodeling,and disease.Multiple human GPCR mutations impair bone development or metabolism,resulting in osteopathologies.Here we summarize the disease phenotypes and dysfunctions caused by GPCR gene mutations in humans as well as by deletion in animals.To date,92 receptors (5 glutamate family,67 rhodopsin family,5 adhesion,4 frizzled/taste2 family,5 secretin family,and 6 other 7TM receptors) have been associated with bone diseases and dysfunctions (36 in humans and 72 in animals).By analyzing data from these 92 GPCRs,we found that mutation or deletion of different individual GPCRs could induce similar bone diseases or dysfunctions,and the same individual GPCR mutation or deletion could induce different bone diseases or dysfunctions in different populations or animal models.Data from human diseases or dysfunctions identified 19 genes whose mutation was associated with human BMD:9 genes each for human height and osteoporosis;4 genes each for human osteoarthritis (OA) and fracture risk;and 2 genes each for adolescent idiopathic scoliosis (AIS),periodontitis,osteosarcoma growth,and tooth development.Reports from gene knockout animals found 40 GPCRs whose deficiency reduced bone mass,while deficiency of 22 GPCRs increased bone mass and BMD;deficiency of 8 GPCRs reduced body length,while 5 mice had reduced femur size upon GPCR deletion.Furthermore,deficiency in 6 GPCRs induced osteoporosis;4 induced osteoarthritis;3 delayed fracture healing;3 reduced arthritis severity;and reduced bone strength,increased bone strength,and increased cortical thickness were each observed in 2 GPCR-deficiency models.The ever-expanding number of GPCR mutation-associated diseases warrants accelerated molecular analysis,population studies,and investigation of phenotype correlation with SNPs to elucidate GPCR function in human diseases.展开更多
Arsenic in drinking water is a worldwide health problem that is associated with cardiovascular disease, but the cause is currently unknown. In order to examine whether arsenic affects vasomotor tone in blood vessels, ...Arsenic in drinking water is a worldwide health problem that is associated with cardiovascular disease, but the cause is currently unknown. In order to examine whether arsenic affects vasomotor tone in blood vessels, we investigated the effect of arsenic on agonist-induced vasorelaxation and vasoconstriction using the isolated rat aortic rings in in vitro organ bath system. Treatment with inorganic arsenite (AsⅢ) inhibited acetylcholine-induced relaxation of aortic rings by inhibiting production of nitric oxide in endothelium.展开更多
BACKGROUND: Previous studies reported that frontal-temporal-parietal-occipital pathological changes and diseased range in the right cerebral hemisphere were closely correlated with neglect. But studies on the correlat...BACKGROUND: Previous studies reported that frontal-temporal-parietal-occipital pathological changes and diseased range in the right cerebral hemisphere were closely correlated with neglect. But studies on the correlation of neglect with diseased region and area in patients who suffer from initial attack of single focus of cerebral infarction (CI) in left and right cerebral hemispheres are few. OBJECTIVE: To observe the status of neglect in patients who suffer from single focus of CI in cerebral hemisphere, and analyze the correlation of neglect with diseased region and area of CI. DESIGN: Case analysis. SETTING: Treatment Center for Cardiocerebrovascular Disease, Second Hospital of Xiamen city; Department of Neurology, First Hospital Affiliated to Baotou Medical College. PARTICIPANTS: All the CI patients hospitalized in the Department of Neurology, First Hospital Affiliated to Baotou Medical College from June 1998 to May 2001 were retrieved. Inclusive criteria: ① Patients who suffered from initial attack of CI, which was confirmed by skull CT or MRI within 24 hours after onset and presented single focus in cerebral hemisphere. ② be conscious and could cooperate in the examination. ③ did not receive formal education, but could do accounts and some simple writing and reading. ④Patients with homonymous hemianopia were excluded through the examination of perimeter. ⑤ Informed consents were obtained from all the patients. Among 67 patients who met the inclusive criteria, 33 suffered from CI in the left cerebral hemisphere and 34 in the right cerebral hemisphere. METHODS: ① Patients received neglect supplement examination and Chinese aphasia examination within 2.5 to 3 months after the attack of CI . The diagnostic criteria of neglect in the tests of line cancellation, line bisection and copying the figures were as follows: In the line cancellation test based on the method of Albert, patients who could not cancel one or more lines were regarded as abnormal. In the line bisection test based on the method of Peter, patients who left deviated 1.16% or right deviated 2.51% were regarded as abnormal. In the test of copying the figures, round-shape, square, cruciform and other shapes were asked to be copied, defect appeared in the figure was regarded as abnormal. The diagnostic criteria of aphasia were according to the diagnostic method of Chinese aphasia examination and type identification flow-sheet of aphasia. Infarct area was calculated based on Palisino formula: infarct area=π/6×the longest diameter of infarct area×the widest diameter of infarct area×the number of CT positive layer. ② Chi-square test was used for comparing the difference of measurement data. MAIN OUTCOME MEASURES: Diseased region and area of CI and their correlations with neglect. RESULTS: Sixty-seven patients were involved in result analysis. ① The correlation of the occurrence of neglect with the diseased regions of CI: Neglect was not found in 33 patients with CI in left cerebral hemisphere, but was found in 7 of 34 patients with CI in right cerebral hemisphere. The diseased regions involved right temporoparietal region, temporal-parietal-occipital region, frontal-temporal-parietal region, frontal-temporal-parietal-occipital region, temporoparietal basal nucleus, basal nucleus and dorsal caudate putamen. ②The correlation of the occurrence of neglect with diseased area: infarct area ≤ 30 cm3 was found in 2 patients with neglect (12.5%), infarct area at 31 to 60 cm3 in 1 patient with neglect (14.3%),infarct area ≥ 61 cm3 in 4 patients with neglect (36.4%). There was no significant difference in infarct area among groups (P > 0.05). CONCLUSION: ① Right cerebral hemisphere takes advantage in spatial attention. ② Neglect is more possibly caused by the combined pathological changes in temporal and parietal lobe. Temporal and parietal lobes may not cause neglect independently, but the occurrence of neglect is not directly correlated with infarct area.展开更多
Disclosure of sexual dysfunctions is difficult due to shame and social stigma.The instruments to measure sexual dysfunctions so far were quite backdated and lengthy.Moreover,there was no specific instrument available ...Disclosure of sexual dysfunctions is difficult due to shame and social stigma.The instruments to measure sexual dysfunctions so far were quite backdated and lengthy.Moreover,there was no specific instrument available that could evaluate all the sexual dysfunctions on the Diagnostic and Statistical Manual of Mental Disorders’criteria in a single scale;separate for men and women.The objective to develop the scale was to provide the non-clinical population with a short and straight-forward measure in English which could help them in deciding about seeking professional help.The constructed scale comprised of 7 items for males and 7 for females and employed 6-points Likert scale for responses.The study involved 79 men and 105 women(N=184;Kaiser-Meyer-Olkin Measure of Sample Adequacy=0.682 for males and 0.618 for females).The inclusion criteria were the practical involvement of the participants in sexual practices and ability to respond to a questionnaire in English.Exploratory Factor Analysis was conducted to measure the reliability and validity of the scale.While employing Principal Component Analysis for extraction and Oblimin with Kaiser Normalization as Rotation,Exploratory Factor Analysis was conducted on 7 items for males and 7 items for females separately.Sampling adequacy was found good and the adequacy of correlations between items and was found highly significant.The Cronbach’s Alpha reliability was satisfactory.4 factors were extracted for males with 78.65%variance explained.3 factors were extracted for females with 66.57%variance explained.The communalities for all the 14 items ranged between 0.554 to 0.937.The study established that Sexual Dysfunctions Tendencies Measure is a valid and reliable tool to measure sexual dysfunctions with the criteria of the Diagnostic and Statistical Manual of Mental Disorders.展开更多
Fundamental organelles that occur in every cell type with the exception of mammal erythrocytes,the mitochondria are required for multiple pivotal processes that include the production of biological energy,the biosynth...Fundamental organelles that occur in every cell type with the exception of mammal erythrocytes,the mitochondria are required for multiple pivotal processes that include the production of biological energy,the biosynthesis of reactive oxygen species,the control of calcium homeostasis,and the triggering of cell death.The disruption of anyone of these processes has been shown to impact strongly the function of all cells,but especially of neurons.In this review,we discuss the role of the mitochondria impairment in the development of the neurodegenerative diseases Amyotrophic Lateral Sclerosis,Parkinson's disease and Alzheimer's disease.We highlight how mitochondria disruption revolves around the processes that underlie the mitochondria's life cycle:fusion,fission,production of reactive oxygen species and energy failure.Both genetic and sporadic forms of neurodegenerative diseases are unavoidably accompanied with and often caused by the dysfunction in one or more of the key mitochondrial processes.Therefore,in order to get in depth insights into their health status in neurodegenerative diseases,we need to focus into innovative strategies aimed at characterizing the various mitochondrial processes.Current techniques include Mitostress,Mitotracker,transmission electron microscopy,oxidative stress assays along with expression measurement of the proteins that maintain the mitochondrial health.We will also discuss a panel of approaches aimed at mitigating the mitochondrial dysfunction.These include canonical drugs,natural compounds,supplements,lifestyle interventions and innovative approaches as mitochondria transplantation and gene therapy.In conclusion,because mitochondria are fundamental organelles necessary for virtually all the cell functions and are severely impaired in neurodegenerative diseases,it is critical to develop novel methods to measure the mitochondrial state,and novel therapeutic strategies aimed at improving their health.展开更多
Sexual dysfunction(SD)is a prevalent but very commonly ignored aspect in the treatment of liver diseases and cirrhosis.The etiology of SD is multifactorial and therefore treatment strategies are complex,especially in ...Sexual dysfunction(SD)is a prevalent but very commonly ignored aspect in the treatment of liver diseases and cirrhosis.The etiology of SD is multifactorial and therefore treatment strategies are complex,especially in females.Phosphodiesterase inhibitors are useful and effective in erectile dysfunction in males but in females,no single drug is available for SD,therefore multimodal treatment is required depending upon the cause.The foremost and fundamental requirement in both genders is to be stress-free and have adequate control of liver diseases.Improved quality of life is helpful in improving SD and vice versa is also true.Therefore,patients suffering from liver diseases should come forward and ask for treatment for SD,and physicians should actively enquire about SD while history taking and evaluating these patients.SD results in deterioration of quality of life,and both are modifiable and treatable aspects of liver diseases,which are never addressed actively,due to social taboos and fears of SD treatment in the presence of liver diseases.The diagnosis of SD does not require costly investigations,as the diagnosis can be established based on validated questionnaires available for both genders,therefore detailed targeted history taking using questionnaires is essential.Data are emerging in this area but is still at an early stage.More studies should be dedicated to SD in liver diseases.展开更多
Background: Maternal death is a major public health problem worldwide, particularly in sub-Saharan Africa. Objective: This study sought to investigate dysfunctions in the management of patients whose outcome was class...Background: Maternal death is a major public health problem worldwide, particularly in sub-Saharan Africa. Objective: This study sought to investigate dysfunctions in the management of patients whose outcome was classified as “maternal death” in the Gynaecology-Obstetrics section of the Departmental University Teaching Hospital of Borgou Alibori (CHUD-BA) from 2017 to 2021. Method: This was a retrospective cross-sectional study with descriptive and analytical purposes. The study population consisted of pregnant women, parturients and puerperas admitted into the CHUD-BA maternity ward from 2017 to 2021. Result: A total of 2011 patients were included in this study. The in-hospital maternal mortality ratio was 1526 per 100,000 live births. The dysfunctions identified were the amount of time spent in the referring center (more than 48 hours) (p = 0.001), delay of more than 2 hours between referral and admission into the referral center (p < 0.001), means of transport (motorcycle or public transport) (p compliance to the protocol for emergency obstetric and neonatal care (SONU) (p < 0.001) and delay of more than 2 hours in the etiological management of pregnant women (p Conclusion: Particular attention should be paid to the management of pregnant women in our healthcare system if we are looking forward to reducing maternal mortality.展开更多
INTRODUCTION: Sexuality is one of the parameters of quality of life, and it is essential to include care for sexual dysfunctions in primary health care.<span style="font-size:10.0pt;font-family:;" "=...INTRODUCTION: Sexuality is one of the parameters of quality of life, and it is essential to include care for sexual dysfunctions in primary health care.<span style="font-size:10.0pt;font-family:;" "=""> </span><span style="font-size:10.0pt;font-family:;" "="">OBJECTIVE: To evaluate the therapeutic approach in female sexual dysfunction in a public health outpatient clinic. DESIGN: A prospective cohort of women with sexual dysfunctions in an outpatient clinic of sexology in the Public Health System. The Female Sexual Function Index (FSFI) and scored 0</span><span style="font-size:10.0pt;font-family:;" "=""> </span><span style="font-size:10.0pt;font-family:;" "="">-</span><span style="font-size:10.0pt;font-family:;" "=""> </span><span style="font-size:10.0pt;font-family:;" "="">10 their sexual satisfaction were applied at the beginning and end of the follow-up. RESULTS: Eighty</span><span style="font-size:10.0pt;font-family:;" "="">-</span><span style="font-size:10.0pt;font-family:;" "="">nine women were included with a median age of 45 years, 69 (77</span><span style="font-size:10.0pt;font-family:;" "="">.</span><span style="font-size:10.0pt;font-family:;" "="">5%) had less than 11 years of schooling and 95</span><span style="font-size:10.0pt;font-family:;" "="">.</span><span style="font-size:10.0pt;font-family:;" "="">5% live</span><span style="font-size:10.0pt;font-family:;" "="">d</span><span style="font-size:10.0pt;font-family:;" "=""> with a partner. The main reasons for referral for follow-up at the outpatient clinic of sexuality were dysfunction of hypoactive sexual desire disorder in 67.4% and pain related to sexual function in 46%. The average number of consultations <span>was five and the main therapeutic interventions were guidance and clarification </span>on sexuality (86.5%), use of topical estrogen (56.2%), and relaxation techniques (37.1%). All FSFI-19 domains had better post-intervention rates (p</span><span style="font-size:10.0pt;font-family:;" "=""> </span><span style="font-size:10.0pt;font-family:;" "="">≤</span><span style="font-size:10.0pt;font-family:;" "=""> </span><span style="font-size:10.0pt;font-family:;" "="">0.005). Considering the domains of the FSFI-19, the medians of desire, arousal,</span><span style="font-size:10.0pt;font-family:;" "=""> lubrication, orgasm, pleasure and pain were higher in the post-intervention period in relation to the pre-intervention period (p</span><span style="font-size:10.0pt;font-family:;" "=""> </span><span style="font-size:10.0pt;font-family:;" "="">≤</span><span style="font-size:10.0pt;font-family:;" "=""> </span><span style="font-size:10.0pt;font-family:;" "="">0.0001 for all analysis). In addition, the score given by the participant on their sexual satisfaction was higher at the post-intervention time compared to the pre-intervention period (p</span><span style="font-size:10.0pt;font-family:;" "=""> </span><span style="font-size:10.0pt;font-family:;" "="">≤</span><span style="font-size:10.0pt;font-family:;" "=""> </span><span style="font-size:10.0pt;font-family:;" "="">0</span><span style="font-size:10.0pt;font-family:;" "="">.</span><span style="font-size:10.0pt;font-family:;" "="">0001). CONCLUSION: In public health, even with the care being performed by different professionals in each consultation, we conclude that through simple interventions</span><span style="font-size:10.0pt;font-family:;" "="">,</span><span style="font-size:10.0pt;font-family:;" "=""> it is possible to improve the sexualities of the women attended. Still, offering care in sexuality is fundamental as part of primary health care and the training of medical professionals.</span>展开更多
Background:Examine the degree of disability in adult ADHD patients in relation to the core symptoms attention deficits and hyperactivity and concomitant minimal cerebral dysfunctions.Methods:Patients from a psychosoma...Background:Examine the degree of disability in adult ADHD patients in relation to the core symptoms attention deficits and hyperactivity and concomitant minimal cerebral dysfunctions.Methods:Patients from a psychosomatic rehabilitation hospital(N=1,453)had answered the“ADHS-SB(attention deficit hyperactivity scale)”,the“MCD-scale(minimal cerebral dysfunction self rating scale)”,the“SCL-90R(Symptom Checklist)”,and reported about impairment at work.Results:Psychological distress and the ability to work are primarily related to problems of orientation,cognitive impairment,vegetative lability,emotional problems,disorders of motor function,but only to a lesser degree to hyperactivity and attention deficit.Conclusion:When dealing with ADHD patients,clinicians should take into account the full variety of MCD symptoms as these are decisive in regard to participation and problems in life.展开更多
The aging process is an inexorable fact throughout our lives and is considered a major factor in develo ping neurological dysfunctions associated with cognitive,emotional,and motor impairments.Aging-associated neurode...The aging process is an inexorable fact throughout our lives and is considered a major factor in develo ping neurological dysfunctions associated with cognitive,emotional,and motor impairments.Aging-associated neurodegenerative diseases are characterized by the progressive loss of neuronal structure and function.展开更多
The cure rate for chronic neurodegenerative diseases remains low,creating an urgent need for improved intervention methods.Recent studies have shown that enhancing mitochondrial function can mitigate the effects of th...The cure rate for chronic neurodegenerative diseases remains low,creating an urgent need for improved intervention methods.Recent studies have shown that enhancing mitochondrial function can mitigate the effects of these diseases.This paper comprehensively reviews the relationship between mitochondrial dysfunction and chronic neurodegenerative diseases,aiming to uncover the potential use of targeted mitochondrial interventions as viable therapeutic options.We detail five targeted mitochondrial intervention strategies for chronic neurodegenerative diseases that act by promoting mitophagy,inhibiting mitochondrial fission,enhancing mitochondrial biogenesis,applying mitochondria-targeting antioxidants,and transplanting mitochondria.Each method has unique advantages and potential limitations,making them suitable for various therapeutic situations.Therapies that promote mitophagy or inhibit mitochondrial fission could be particularly effective in slowing disease progression,especially in the early stages.In contrast,those that enhance mitochondrial biogenesis and apply mitochondria-targeting antioxidants may offer great benefits during the middle stages of the disease by improving cellular antioxidant capacity and energy metabolism.Mitochondrial transplantation,while still experimental,holds great promise for restoring the function of damaged cells.Future research should focus on exploring the mechanisms and effects of these intervention strategies,particularly regarding their safety and efficacy in clinical settings.Additionally,the development of innovative mitochondria-targeting approaches,such as gene editing and nanotechnology,may provide new solutions for treating chronic neurodegenerative diseases.Implementing combined therapeutic strategies that integrate multiple intervention methods could also enhance treatment outcomes.展开更多
Global brain ischemia and neurological deficit are consequences of cardiac arrest that lead to high mortality.Despite advancements in resuscitation science,our limited understanding of the cellular and molecular mecha...Global brain ischemia and neurological deficit are consequences of cardiac arrest that lead to high mortality.Despite advancements in resuscitation science,our limited understanding of the cellular and molecular mechanisms underlying post-cardiac arrest brain injury have hindered the development of effective neuroprotective strategies.Previous studies primarily focused on neuronal death,potentially overlooking the contributions of non-neuronal cells and intercellular communication to the pathophysiology of cardiac arrest-induced brain injury.To address these gaps,we hypothesized that single-cell transcriptomic analysis could uncover previously unidentified cellular subpopulations,altered cell communication networks,and novel molecular mechanisms involved in post-cardiac arrest brain injury.In this study,we performed a single-cell transcriptomic analysis of the hippocampus from pigs with ventricular fibrillation-induced cardiac arrest at 6 and 24 hours following the return of spontaneous circulation,and from sham control pigs.Sequencing results revealed changes in the proportions of different cell types,suggesting post-arrest disruption in the blood-brain barrier and infiltration of neutrophils.These results were validated through western blotting,quantitative reverse transcription-polymerase chain reaction,and immunofluorescence staining.We also identified and validated a unique subcluster of activated microglia with high expression of S100A8,which increased over time following cardiac arrest.This subcluster simultaneously exhibited significant M1/M2 polarization and expressed key functional genes related to chemokines and interleukins.Additionally,we revealed the post-cardiac arrest dysfunction of oligodendrocytes and the differentiation of oligodendrocyte precursor cells into oligodendrocytes.Cell communication analysis identified enhanced post-cardiac arrest communication between neutrophils and microglia that was mediated by neutrophil-derived resistin,driving pro-inflammatory microglial polarization.Our findings provide a comprehensive single-cell map of the post-cardiac arrest hippocampus,offering potential novel targets for neuroprotection and repair following cardiac arrest.展开更多
Ischemia–reperfusion injury is a common pathophysiological mechanism in retinal degeneration.PANoptosis is a newly defined integral form of regulated cell death that combines the key features of pyroptosis,apoptosis,...Ischemia–reperfusion injury is a common pathophysiological mechanism in retinal degeneration.PANoptosis is a newly defined integral form of regulated cell death that combines the key features of pyroptosis,apoptosis,and necroptosis.Oligomerization of mitochondrial voltage-dependent anion channel 1 is an important pathological event in regulating cell death in retinal ischemia–reperfusion injury.However,its role in PANoptosis remains largely unknown.In this study,we demonstrated that voltage-dependent anion channel 1 oligomerization-mediated mitochondrial dysfunction was associated with PANoptosis in retinal ischemia–reperfusion injury.Inhibition of voltage-dependent anion channel 1 oligomerization suppressed mitochondrial dysfunction and PANoptosis in retinal cells subjected to ischemia–reperfusion injury.Mechanistically,mitochondria-derived reactive oxygen species played a central role in the voltagedependent anion channel 1-mediated regulation of PANoptosis by promoting PANoptosome assembly.Moreover,inhibiting voltage-dependent anion channel 1 oligomerization protected against PANoptosis in the retinas of rats subjected to ischemia–reperfusion injury.Overall,our findings reveal the critical role of voltage-dependent anion channel 1 oligomerization in regulating PANoptosis in retinal ischemia–reperfusion injury,highlighting voltage-dependent anion channel 1 as a promising therapeutic target.展开更多
Neurological and psychiatric complications continue to be a public health concern in long coronavirus disease 2019(COVID-19).This varies from olfactory dysfunctions such as parosmia to cognitive and emotional challeng...Neurological and psychiatric complications continue to be a public health concern in long coronavirus disease 2019(COVID-19).This varies from olfactory dysfunctions such as parosmia to cognitive and emotional challenges.Historically,the surge of neurological disorders followed the viral pandemics,for example,the emergence of Encephalitis Lethargica after the outbreak of Spanish Influenza.During and after COVID-19 infection,the problems associated with the sense of smell and the reports of affected olfactory and limbic brain areas are leading to a growing concern about the similarity with the symptoms and the pattern of degeneration observed at the onset of Parkinson's disease and Alzheimer's disease.These reports reveal the essentiality of long-term studies of olfactory and cognitive functions in the post-COVID era and the experiments using animal models to dissect the neural basis of these complications.In this manuscript,we summarize the research reporting the potential correlation between neurological disorders and viral pandemic outbreaks with a historical perspective.Further,we discuss the studies providing evidence of neurodegeneration due to severe acute respiratory syndrome coronavirus 2 infection by focusing on viral Parkinsonism.展开更多
Alzheimer’s disease(AD)is the most common cause of dementia,characterized by progressive cognitive decline,and affects over 55 million people worldwide.AD is pathological featured by the aberrant accumulation of amyl...Alzheimer’s disease(AD)is the most common cause of dementia,characterized by progressive cognitive decline,and affects over 55 million people worldwide.AD is pathological featured by the aberrant accumulation of amyloid-βplaques,neurofibrillary tangles formed by hyperphosphorylated tau,synaptic loss,and dysfunction of neurotransmitter systems.Evidence from in vivo and autopsy studies has consistently shown that synaptic dysfunction and loss are strongly correlated with cognitive decline in AD,particularly in brain regions such as the hippocampus and cortex,which are critical for memory formation and processing.This perspective highlights recent histopathological findings related to synaptic dysfunction in AD,advancements in the development of imaging and fluid-based biomarkers for synaptic loss,and future studies.展开更多
Mitochondrial dysfunction and oxidative stress are widely regarded as primary drivers of aging and are associated with several neurodegenerative diseases.The degeneration of motor neurons during aging is a critical pa...Mitochondrial dysfunction and oxidative stress are widely regarded as primary drivers of aging and are associated with several neurodegenerative diseases.The degeneration of motor neurons during aging is a critical pathological factor contributing to the progression of sarcopenia.However,the morphological and functional changes in mitochondria and their interplay in the degeneration of the neuromuscular junction during aging remain poorly understood.A defined systematic search of the Pub Med,Web of Science and Embase databases(last accessed on October 30,2024)was conducted with search terms including'mitochondria','aging'and'NMJ'.Clinical and preclinical studies of mitochondrial dysfunction and neuromuscular junction degeneration during aging.Twentyseven studies were included in this systematic review.This systematic review provides a summary of morphological,functional and biological changes in neuromuscular junction,mitochondrial morphology,biosynthesis,respiratory chain function,and mitophagy during aging.We focus on the interactions and mechanisms underlying the relationship between mitochondria and neuromuscular junctions during aging.Aging is characterized by significant reductions in mitochondrial fusion/fission cycles,biosynthesis,and mitochondrial quality control,which may lead to neuromuscular junction dysfunction,denervation and poor physical performance.Motor nerve terminals that exhibit redox sensitivity are among the first to exhibit abnormalities,ultimately leading to an early decline in muscle strength through impaired neuromuscular junction transmission function.Parg coactivator 1 alpha is a crucial molecule that regulates mitochondrial biogenesis and modulates various pathways,including the mitochondrial respiratory chain,energy deficiency,oxidative stress,and inflammation.Mitochondrial dysfunction is correlated with neuromuscular junction denervation and acetylcholine receptor fragmentation,resulting in muscle atrophy and a decrease in strength during aging.Physical therapy,pharmacotherapy,and gene therapy can alleviate the structural degeneration and functional deterioration of neuromuscular junction by restoring mitochondrial function.Therefore,mitochondria are considered potential targets for preserving neuromuscular junction morphology and function during aging to treat sarcopenia.展开更多
Alzheimer’s disease,a devastating neurodegenerative disorder,is characterized by progressive cognitive decline,primarily due to amyloid-beta protein deposition and tau protein phosphorylation.Effectively reducing the...Alzheimer’s disease,a devastating neurodegenerative disorder,is characterized by progressive cognitive decline,primarily due to amyloid-beta protein deposition and tau protein phosphorylation.Effectively reducing the cytotoxicity of amyloid-beta42 aggregates and tau oligomers may help slow the progression of Alzheimer’s disease.Conventional drugs,such as donepezil,can only alleviate symptoms and are not able to prevent the underlying pathological processes or cognitive decline.Currently,active and passive immunotherapies targeting amyloid-beta and tau have shown some efficacy in mice with asymptomatic Alzheimer’s disease and other transgenic animal models,attracting considerable attention.However,the clinical application of these immunotherapies demonstrated only limited efficacy before the discovery of lecanemab and donanemab.This review first discusses the advancements in the pathogenesis of Alzheimer’s disease and active and passive immunotherapies targeting amyloid-beta and tau proteins.Furthermore,it reviews the advantages and disadvantages of various immunotherapies and considers their future prospects.Although some antibodies have shown promise in patients with mild Alzheimer’s disease,substantial clinical data are still lacking to validate their effectiveness in individuals with moderate Alzheimer’s disease.展开更多
文摘Correction to:Cellular&Molecular Immunology https://doi.org/10.1038/cmi.2010.11,published online 22 March 2010 In Figure 4A(panel 3)of this article,the panel labeled“Tumor+Curcumin”was inadvertently placed in the“Curcumin”panel instead of the original“Curcumin”panel.The corrected version of Figure 4 is shown below as the revised Figure 4.The figure legend remains the same.
文摘AIM： To determine the presence of symptomatic accommodative and non-strabismic binocular dysfunctions （A.sBD） in a non-presbyopic population of video display unit （VDU） users with flat-panel displays. METHODS： One hundred and one VDU users, aged between 20 to 34y, initially participated in the study. This study excluded contact-lens wearers and subjects who had undergone refractive surgery or had any systemic or ocular disease. First, subjects were asked about the type and nature of eye symptoms they experienced during VDU use. Then, a thorough eye examination excluded those subjects with a significant uncorrected refractive error or other problem, such as ocular motility disorders, vertical deviation, strabismus and eye diseases. Finally, the remaining participants underwent an exhaustive assessment of their accommodative and binocular vision status. RESULTS： Eighty-nine VDU users （46 females and 43 males） were included in this study. They used flat-panel displays for an average of 5±1.9h a day. Twenty subjects presented A.sBD （22.5%）. Convergence excess was the most frequent non-strabismic binocular dysfunction （9 subjects）, followed by fusional vergence dysfunction （3 subjects） and convergence insufficiency （2 subjects）. Within the accommodative dysfunctions, accommodative excess was the most common （4 subjects）, followed by accommodative insufficiency （2 subjects）. Moderate to severe eye symptoms were found in 13 subjects with ANSBD. CONCLUSION： Significant eye symptoms in VDU users with accommodative and/or non-strabismic binocular dysfunctions often occur and should not be underestimated; therefore, an appropriate evaluation of accommodative and binocular vision status is more important for this population,
基金Supported by the University of Louisville-China Pediatric Research Exchange Program(Cai L,Tan Y,Huang J,and Keller B,no salary support)University of Louisville Executive Vice President for Research and Innovation Internal Grant(Huang J and Cai L)University of Louisville School of Medicine Basic Grant(Huang J and Cai L).
文摘BACKGROUND Diabetes has become a widespread metabolic disease affecting multiple organs.Among diabetic complications,cardiovascular complications are the main cause of patient morbidity and mortality.Diabetic cardiomyopathy is a diabetes-specific cardiomyopathy in the absence of other cardiovascular disease and occurs more frequently in type 1 diabetes(T1D)than in type 2 diabetes.Previous studies on diabetic cardiomyopathy have predominantly focused on the effects of diabetes on left ventricular(LV)dysfunction,while studies of right ventricular(RV)dysfunction have been sparse but are gaining attention.Although T1D accounts for only 5%-10%of the total diabetic population,diabetic cardiomyopathy is a major cause of morbidity and mortality in children with life-long,long-term complications.AIM To evaluate longitudinal RV and LV functional changes in female transgenic OVE26,T1D mice and wild-type FVB mice over a 30-week period.METHODS RV and LV structure and function were evaluated by transthoracic echocardiography.RV systolic pressure was measured by a transducer-tipped pressure catheter.Sirius-red staining was used to quantify collagen and fibrosis,wheat germ agglutinin staining was utilized to measure cardiomyocyte size,and quantitative real-time polymerase chain reaction and Western blotting were used to quantify miRNA expression and protein abundance,respectively.RESULTS RV systolic function,measured by tricuspid valve annular plane systolic excursion and RV systolic velocity,was similar between control and T1D mice,but LV systolic function decreased in T1D mice at 30 weeks of age.RV diastolic dysfunction in T1D mice significantly increased by 18 weeks and progressed until 30 weeks,while LV diastolic dysfunction trended towards abnormal at 12 weeks,significantly increased by 18 weeks,and continued to progress by 30 weeks.Furthermore,RV diastolic dysfunction was accompanied by RV cardiac fibrosis and hypertrophy in T1D mice,occurring later than that in the LV.Pulmonary arterial hypertension developed in T1D mice,evidenced by increased pulmonary acceleration time to pulmonary ejection time ratio and increased RV peak systolic pressure at 30 weeks.These results suggest the development of early LV diastolic dysfunction followed by LV systolic dysfunction and RV diastolic dysfunction at 30 weeks in T1D mice.CONCLUSION RV diastolic dysfunction develops later than LV dysfunction in OVE26 T1D mice.Mild pulmonary arterial hypertension appear at later stages of T1D and could contribute to RV systolic impairment and remodeling.
基金supported by grants from the National Key Research and Development Program of China(2018YFC1105102 to J.L.,2016YFC0902102 to J.L.and J.X.)the National Natural Science Foundation of China(81722020,91749204,81472048 to J.L.,81330049 to M.L.,81330059 and 81572640 to J.X.)+2 种基金the Innovation Program of Shanghai Municipal Education Commission(14ZZ051 to J.L.,2017ZZ01017 to J.X.)the Science and Technology Commission of Shanghai Municipality(12ZR1447900 to J.L.,17JC1400903 and 17411950300 to J.X.)the Fundamental Research Funds for the Central Universities(to J.L.)
文摘The superfamily of G protein-coupled receptors (GPCRs) contains immense structural and functional diversity and mediates a myriad of biological processes upon activation by various extracellular signals.Critical roles of GPCRs have been established in bone development,remodeling,and disease.Multiple human GPCR mutations impair bone development or metabolism,resulting in osteopathologies.Here we summarize the disease phenotypes and dysfunctions caused by GPCR gene mutations in humans as well as by deletion in animals.To date,92 receptors (5 glutamate family,67 rhodopsin family,5 adhesion,4 frizzled/taste2 family,5 secretin family,and 6 other 7TM receptors) have been associated with bone diseases and dysfunctions (36 in humans and 72 in animals).By analyzing data from these 92 GPCRs,we found that mutation or deletion of different individual GPCRs could induce similar bone diseases or dysfunctions,and the same individual GPCR mutation or deletion could induce different bone diseases or dysfunctions in different populations or animal models.Data from human diseases or dysfunctions identified 19 genes whose mutation was associated with human BMD:9 genes each for human height and osteoporosis;4 genes each for human osteoarthritis (OA) and fracture risk;and 2 genes each for adolescent idiopathic scoliosis (AIS),periodontitis,osteosarcoma growth,and tooth development.Reports from gene knockout animals found 40 GPCRs whose deficiency reduced bone mass,while deficiency of 22 GPCRs increased bone mass and BMD;deficiency of 8 GPCRs reduced body length,while 5 mice had reduced femur size upon GPCR deletion.Furthermore,deficiency in 6 GPCRs induced osteoporosis;4 induced osteoarthritis;3 delayed fracture healing;3 reduced arthritis severity;and reduced bone strength,increased bone strength,and increased cortical thickness were each observed in 2 GPCR-deficiency models.The ever-expanding number of GPCR mutation-associated diseases warrants accelerated molecular analysis,population studies,and investigation of phenotype correlation with SNPs to elucidate GPCR function in human diseases.
文摘Arsenic in drinking water is a worldwide health problem that is associated with cardiovascular disease, but the cause is currently unknown. In order to examine whether arsenic affects vasomotor tone in blood vessels, we investigated the effect of arsenic on agonist-induced vasorelaxation and vasoconstriction using the isolated rat aortic rings in in vitro organ bath system. Treatment with inorganic arsenite (AsⅢ) inhibited acetylcholine-induced relaxation of aortic rings by inhibiting production of nitric oxide in endothelium.
基金the Natural Science Foundation of Nei Monggol Autonomous Region, No. 980204
文摘BACKGROUND: Previous studies reported that frontal-temporal-parietal-occipital pathological changes and diseased range in the right cerebral hemisphere were closely correlated with neglect. But studies on the correlation of neglect with diseased region and area in patients who suffer from initial attack of single focus of cerebral infarction (CI) in left and right cerebral hemispheres are few. OBJECTIVE: To observe the status of neglect in patients who suffer from single focus of CI in cerebral hemisphere, and analyze the correlation of neglect with diseased region and area of CI. DESIGN: Case analysis. SETTING: Treatment Center for Cardiocerebrovascular Disease, Second Hospital of Xiamen city; Department of Neurology, First Hospital Affiliated to Baotou Medical College. PARTICIPANTS: All the CI patients hospitalized in the Department of Neurology, First Hospital Affiliated to Baotou Medical College from June 1998 to May 2001 were retrieved. Inclusive criteria: ① Patients who suffered from initial attack of CI, which was confirmed by skull CT or MRI within 24 hours after onset and presented single focus in cerebral hemisphere. ② be conscious and could cooperate in the examination. ③ did not receive formal education, but could do accounts and some simple writing and reading. ④Patients with homonymous hemianopia were excluded through the examination of perimeter. ⑤ Informed consents were obtained from all the patients. Among 67 patients who met the inclusive criteria, 33 suffered from CI in the left cerebral hemisphere and 34 in the right cerebral hemisphere. METHODS: ① Patients received neglect supplement examination and Chinese aphasia examination within 2.5 to 3 months after the attack of CI . The diagnostic criteria of neglect in the tests of line cancellation, line bisection and copying the figures were as follows: In the line cancellation test based on the method of Albert, patients who could not cancel one or more lines were regarded as abnormal. In the line bisection test based on the method of Peter, patients who left deviated 1.16% or right deviated 2.51% were regarded as abnormal. In the test of copying the figures, round-shape, square, cruciform and other shapes were asked to be copied, defect appeared in the figure was regarded as abnormal. The diagnostic criteria of aphasia were according to the diagnostic method of Chinese aphasia examination and type identification flow-sheet of aphasia. Infarct area was calculated based on Palisino formula: infarct area=π/6×the longest diameter of infarct area×the widest diameter of infarct area×the number of CT positive layer. ② Chi-square test was used for comparing the difference of measurement data. MAIN OUTCOME MEASURES: Diseased region and area of CI and their correlations with neglect. RESULTS: Sixty-seven patients were involved in result analysis. ① The correlation of the occurrence of neglect with the diseased regions of CI: Neglect was not found in 33 patients with CI in left cerebral hemisphere, but was found in 7 of 34 patients with CI in right cerebral hemisphere. The diseased regions involved right temporoparietal region, temporal-parietal-occipital region, frontal-temporal-parietal region, frontal-temporal-parietal-occipital region, temporoparietal basal nucleus, basal nucleus and dorsal caudate putamen. ②The correlation of the occurrence of neglect with diseased area: infarct area ≤ 30 cm3 was found in 2 patients with neglect (12.5%), infarct area at 31 to 60 cm3 in 1 patient with neglect (14.3%),infarct area ≥ 61 cm3 in 4 patients with neglect (36.4%). There was no significant difference in infarct area among groups (P > 0.05). CONCLUSION: ① Right cerebral hemisphere takes advantage in spatial attention. ② Neglect is more possibly caused by the combined pathological changes in temporal and parietal lobe. Temporal and parietal lobes may not cause neglect independently, but the occurrence of neglect is not directly correlated with infarct area.
文摘Disclosure of sexual dysfunctions is difficult due to shame and social stigma.The instruments to measure sexual dysfunctions so far were quite backdated and lengthy.Moreover,there was no specific instrument available that could evaluate all the sexual dysfunctions on the Diagnostic and Statistical Manual of Mental Disorders’criteria in a single scale;separate for men and women.The objective to develop the scale was to provide the non-clinical population with a short and straight-forward measure in English which could help them in deciding about seeking professional help.The constructed scale comprised of 7 items for males and 7 for females and employed 6-points Likert scale for responses.The study involved 79 men and 105 women(N=184;Kaiser-Meyer-Olkin Measure of Sample Adequacy=0.682 for males and 0.618 for females).The inclusion criteria were the practical involvement of the participants in sexual practices and ability to respond to a questionnaire in English.Exploratory Factor Analysis was conducted to measure the reliability and validity of the scale.While employing Principal Component Analysis for extraction and Oblimin with Kaiser Normalization as Rotation,Exploratory Factor Analysis was conducted on 7 items for males and 7 items for females separately.Sampling adequacy was found good and the adequacy of correlations between items and was found highly significant.The Cronbach’s Alpha reliability was satisfactory.4 factors were extracted for males with 78.65%variance explained.3 factors were extracted for females with 66.57%variance explained.The communalities for all the 14 items ranged between 0.554 to 0.937.The study established that Sexual Dysfunctions Tendencies Measure is a valid and reliable tool to measure sexual dysfunctions with the criteria of the Diagnostic and Statistical Manual of Mental Disorders.
文摘Fundamental organelles that occur in every cell type with the exception of mammal erythrocytes,the mitochondria are required for multiple pivotal processes that include the production of biological energy,the biosynthesis of reactive oxygen species,the control of calcium homeostasis,and the triggering of cell death.The disruption of anyone of these processes has been shown to impact strongly the function of all cells,but especially of neurons.In this review,we discuss the role of the mitochondria impairment in the development of the neurodegenerative diseases Amyotrophic Lateral Sclerosis,Parkinson's disease and Alzheimer's disease.We highlight how mitochondria disruption revolves around the processes that underlie the mitochondria's life cycle:fusion,fission,production of reactive oxygen species and energy failure.Both genetic and sporadic forms of neurodegenerative diseases are unavoidably accompanied with and often caused by the dysfunction in one or more of the key mitochondrial processes.Therefore,in order to get in depth insights into their health status in neurodegenerative diseases,we need to focus into innovative strategies aimed at characterizing the various mitochondrial processes.Current techniques include Mitostress,Mitotracker,transmission electron microscopy,oxidative stress assays along with expression measurement of the proteins that maintain the mitochondrial health.We will also discuss a panel of approaches aimed at mitigating the mitochondrial dysfunction.These include canonical drugs,natural compounds,supplements,lifestyle interventions and innovative approaches as mitochondria transplantation and gene therapy.In conclusion,because mitochondria are fundamental organelles necessary for virtually all the cell functions and are severely impaired in neurodegenerative diseases,it is critical to develop novel methods to measure the mitochondrial state,and novel therapeutic strategies aimed at improving their health.
文摘Sexual dysfunction(SD)is a prevalent but very commonly ignored aspect in the treatment of liver diseases and cirrhosis.The etiology of SD is multifactorial and therefore treatment strategies are complex,especially in females.Phosphodiesterase inhibitors are useful and effective in erectile dysfunction in males but in females,no single drug is available for SD,therefore multimodal treatment is required depending upon the cause.The foremost and fundamental requirement in both genders is to be stress-free and have adequate control of liver diseases.Improved quality of life is helpful in improving SD and vice versa is also true.Therefore,patients suffering from liver diseases should come forward and ask for treatment for SD,and physicians should actively enquire about SD while history taking and evaluating these patients.SD results in deterioration of quality of life,and both are modifiable and treatable aspects of liver diseases,which are never addressed actively,due to social taboos and fears of SD treatment in the presence of liver diseases.The diagnosis of SD does not require costly investigations,as the diagnosis can be established based on validated questionnaires available for both genders,therefore detailed targeted history taking using questionnaires is essential.Data are emerging in this area but is still at an early stage.More studies should be dedicated to SD in liver diseases.
文摘Background: Maternal death is a major public health problem worldwide, particularly in sub-Saharan Africa. Objective: This study sought to investigate dysfunctions in the management of patients whose outcome was classified as “maternal death” in the Gynaecology-Obstetrics section of the Departmental University Teaching Hospital of Borgou Alibori (CHUD-BA) from 2017 to 2021. Method: This was a retrospective cross-sectional study with descriptive and analytical purposes. The study population consisted of pregnant women, parturients and puerperas admitted into the CHUD-BA maternity ward from 2017 to 2021. Result: A total of 2011 patients were included in this study. The in-hospital maternal mortality ratio was 1526 per 100,000 live births. The dysfunctions identified were the amount of time spent in the referring center (more than 48 hours) (p = 0.001), delay of more than 2 hours between referral and admission into the referral center (p < 0.001), means of transport (motorcycle or public transport) (p compliance to the protocol for emergency obstetric and neonatal care (SONU) (p < 0.001) and delay of more than 2 hours in the etiological management of pregnant women (p Conclusion: Particular attention should be paid to the management of pregnant women in our healthcare system if we are looking forward to reducing maternal mortality.
文摘INTRODUCTION: Sexuality is one of the parameters of quality of life, and it is essential to include care for sexual dysfunctions in primary health care.<span style="font-size:10.0pt;font-family:;" "=""> </span><span style="font-size:10.0pt;font-family:;" "="">OBJECTIVE: To evaluate the therapeutic approach in female sexual dysfunction in a public health outpatient clinic. DESIGN: A prospective cohort of women with sexual dysfunctions in an outpatient clinic of sexology in the Public Health System. The Female Sexual Function Index (FSFI) and scored 0</span><span style="font-size:10.0pt;font-family:;" "=""> </span><span style="font-size:10.0pt;font-family:;" "="">-</span><span style="font-size:10.0pt;font-family:;" "=""> </span><span style="font-size:10.0pt;font-family:;" "="">10 their sexual satisfaction were applied at the beginning and end of the follow-up. RESULTS: Eighty</span><span style="font-size:10.0pt;font-family:;" "="">-</span><span style="font-size:10.0pt;font-family:;" "="">nine women were included with a median age of 45 years, 69 (77</span><span style="font-size:10.0pt;font-family:;" "="">.</span><span style="font-size:10.0pt;font-family:;" "="">5%) had less than 11 years of schooling and 95</span><span style="font-size:10.0pt;font-family:;" "="">.</span><span style="font-size:10.0pt;font-family:;" "="">5% live</span><span style="font-size:10.0pt;font-family:;" "="">d</span><span style="font-size:10.0pt;font-family:;" "=""> with a partner. The main reasons for referral for follow-up at the outpatient clinic of sexuality were dysfunction of hypoactive sexual desire disorder in 67.4% and pain related to sexual function in 46%. The average number of consultations <span>was five and the main therapeutic interventions were guidance and clarification </span>on sexuality (86.5%), use of topical estrogen (56.2%), and relaxation techniques (37.1%). All FSFI-19 domains had better post-intervention rates (p</span><span style="font-size:10.0pt;font-family:;" "=""> </span><span style="font-size:10.0pt;font-family:;" "="">≤</span><span style="font-size:10.0pt;font-family:;" "=""> </span><span style="font-size:10.0pt;font-family:;" "="">0.005). Considering the domains of the FSFI-19, the medians of desire, arousal,</span><span style="font-size:10.0pt;font-family:;" "=""> lubrication, orgasm, pleasure and pain were higher in the post-intervention period in relation to the pre-intervention period (p</span><span style="font-size:10.0pt;font-family:;" "=""> </span><span style="font-size:10.0pt;font-family:;" "="">≤</span><span style="font-size:10.0pt;font-family:;" "=""> </span><span style="font-size:10.0pt;font-family:;" "="">0.0001 for all analysis). In addition, the score given by the participant on their sexual satisfaction was higher at the post-intervention time compared to the pre-intervention period (p</span><span style="font-size:10.0pt;font-family:;" "=""> </span><span style="font-size:10.0pt;font-family:;" "="">≤</span><span style="font-size:10.0pt;font-family:;" "=""> </span><span style="font-size:10.0pt;font-family:;" "="">0</span><span style="font-size:10.0pt;font-family:;" "="">.</span><span style="font-size:10.0pt;font-family:;" "="">0001). CONCLUSION: In public health, even with the care being performed by different professionals in each consultation, we conclude that through simple interventions</span><span style="font-size:10.0pt;font-family:;" "="">,</span><span style="font-size:10.0pt;font-family:;" "=""> it is possible to improve the sexualities of the women attended. Still, offering care in sexuality is fundamental as part of primary health care and the training of medical professionals.</span>
文摘Background:Examine the degree of disability in adult ADHD patients in relation to the core symptoms attention deficits and hyperactivity and concomitant minimal cerebral dysfunctions.Methods:Patients from a psychosomatic rehabilitation hospital(N=1,453)had answered the“ADHS-SB(attention deficit hyperactivity scale)”,the“MCD-scale(minimal cerebral dysfunction self rating scale)”,the“SCL-90R(Symptom Checklist)”,and reported about impairment at work.Results:Psychological distress and the ability to work are primarily related to problems of orientation,cognitive impairment,vegetative lability,emotional problems,disorders of motor function,but only to a lesser degree to hyperactivity and attention deficit.Conclusion:When dealing with ADHD patients,clinicians should take into account the full variety of MCD symptoms as these are decisive in regard to participation and problems in life.
文摘The aging process is an inexorable fact throughout our lives and is considered a major factor in develo ping neurological dysfunctions associated with cognitive,emotional,and motor impairments.Aging-associated neurodegenerative diseases are characterized by the progressive loss of neuronal structure and function.
基金partly supported by the Yan’an University Qin Chuanyuan“Scientist+Engineer”Team Special Fund,No.2023KXJ-012(to YL)Yan’an University Transformation of Scientific and Technological Achievements Fund,No.2023CGZH-001(to YL)+2 种基金College Students Innovation and Entrepreneurship Training Program,Nos.D2023158,202410719056(to XS,JM)Yan’an University Production and Cultivation Project,No.CXY202001(to YL)Kweichow Moutai Hospital Research and Talent Development Fund Project,No.MTyk2022-25(to XO)。
文摘The cure rate for chronic neurodegenerative diseases remains low,creating an urgent need for improved intervention methods.Recent studies have shown that enhancing mitochondrial function can mitigate the effects of these diseases.This paper comprehensively reviews the relationship between mitochondrial dysfunction and chronic neurodegenerative diseases,aiming to uncover the potential use of targeted mitochondrial interventions as viable therapeutic options.We detail five targeted mitochondrial intervention strategies for chronic neurodegenerative diseases that act by promoting mitophagy,inhibiting mitochondrial fission,enhancing mitochondrial biogenesis,applying mitochondria-targeting antioxidants,and transplanting mitochondria.Each method has unique advantages and potential limitations,making them suitable for various therapeutic situations.Therapies that promote mitophagy or inhibit mitochondrial fission could be particularly effective in slowing disease progression,especially in the early stages.In contrast,those that enhance mitochondrial biogenesis and apply mitochondria-targeting antioxidants may offer great benefits during the middle stages of the disease by improving cellular antioxidant capacity and energy metabolism.Mitochondrial transplantation,while still experimental,holds great promise for restoring the function of damaged cells.Future research should focus on exploring the mechanisms and effects of these intervention strategies,particularly regarding their safety and efficacy in clinical settings.Additionally,the development of innovative mitochondria-targeting approaches,such as gene editing and nanotechnology,may provide new solutions for treating chronic neurodegenerative diseases.Implementing combined therapeutic strategies that integrate multiple intervention methods could also enhance treatment outcomes.
基金supported by the National Science Foundation of China,Nos.82325031(to FX),82030059(to YC),82102290(to YG),U23A20485(to YC)Noncommunicable Chronic Diseases-National Science and Technology Major Project,No.2023ZD0505504(to FX),2023ZD0505500(to YC)the Key R&D Program of Shandong Province,No.2022ZLGX03(to YC).
文摘Global brain ischemia and neurological deficit are consequences of cardiac arrest that lead to high mortality.Despite advancements in resuscitation science,our limited understanding of the cellular and molecular mechanisms underlying post-cardiac arrest brain injury have hindered the development of effective neuroprotective strategies.Previous studies primarily focused on neuronal death,potentially overlooking the contributions of non-neuronal cells and intercellular communication to the pathophysiology of cardiac arrest-induced brain injury.To address these gaps,we hypothesized that single-cell transcriptomic analysis could uncover previously unidentified cellular subpopulations,altered cell communication networks,and novel molecular mechanisms involved in post-cardiac arrest brain injury.In this study,we performed a single-cell transcriptomic analysis of the hippocampus from pigs with ventricular fibrillation-induced cardiac arrest at 6 and 24 hours following the return of spontaneous circulation,and from sham control pigs.Sequencing results revealed changes in the proportions of different cell types,suggesting post-arrest disruption in the blood-brain barrier and infiltration of neutrophils.These results were validated through western blotting,quantitative reverse transcription-polymerase chain reaction,and immunofluorescence staining.We also identified and validated a unique subcluster of activated microglia with high expression of S100A8,which increased over time following cardiac arrest.This subcluster simultaneously exhibited significant M1/M2 polarization and expressed key functional genes related to chemokines and interleukins.Additionally,we revealed the post-cardiac arrest dysfunction of oligodendrocytes and the differentiation of oligodendrocyte precursor cells into oligodendrocytes.Cell communication analysis identified enhanced post-cardiac arrest communication between neutrophils and microglia that was mediated by neutrophil-derived resistin,driving pro-inflammatory microglial polarization.Our findings provide a comprehensive single-cell map of the post-cardiac arrest hippocampus,offering potential novel targets for neuroprotection and repair following cardiac arrest.
基金supported by the National Natural Science Foundation of China,Nos.82172196(to KX),82372507(to KX)the Natural Science Foundation of Hunan Province,China,No.2023JJ40804(to QZ)the Key Laboratory of Emergency and Trauma(Hainan Medical University)of the Ministry of Education,China,No.KLET-202210(to QZ)。
文摘Ischemia–reperfusion injury is a common pathophysiological mechanism in retinal degeneration.PANoptosis is a newly defined integral form of regulated cell death that combines the key features of pyroptosis,apoptosis,and necroptosis.Oligomerization of mitochondrial voltage-dependent anion channel 1 is an important pathological event in regulating cell death in retinal ischemia–reperfusion injury.However,its role in PANoptosis remains largely unknown.In this study,we demonstrated that voltage-dependent anion channel 1 oligomerization-mediated mitochondrial dysfunction was associated with PANoptosis in retinal ischemia–reperfusion injury.Inhibition of voltage-dependent anion channel 1 oligomerization suppressed mitochondrial dysfunction and PANoptosis in retinal cells subjected to ischemia–reperfusion injury.Mechanistically,mitochondria-derived reactive oxygen species played a central role in the voltagedependent anion channel 1-mediated regulation of PANoptosis by promoting PANoptosome assembly.Moreover,inhibiting voltage-dependent anion channel 1 oligomerization protected against PANoptosis in the retinas of rats subjected to ischemia–reperfusion injury.Overall,our findings reveal the critical role of voltage-dependent anion channel 1 oligomerization in regulating PANoptosis in retinal ischemia–reperfusion injury,highlighting voltage-dependent anion channel 1 as a promising therapeutic target.
基金DBT/Wellcome Trust India Alliance senior,Grant/Award Number:IA/S/22/2/506517Ramalingaswami Fellowship,Department of Biotechnology,Govt.of India,Grant/Award Number:BT/RLF/Re-entry/45/2014Council of Scientific and Industrial Research,India。
文摘Neurological and psychiatric complications continue to be a public health concern in long coronavirus disease 2019(COVID-19).This varies from olfactory dysfunctions such as parosmia to cognitive and emotional challenges.Historically,the surge of neurological disorders followed the viral pandemics,for example,the emergence of Encephalitis Lethargica after the outbreak of Spanish Influenza.During and after COVID-19 infection,the problems associated with the sense of smell and the reports of affected olfactory and limbic brain areas are leading to a growing concern about the similarity with the symptoms and the pattern of degeneration observed at the onset of Parkinson's disease and Alzheimer's disease.These reports reveal the essentiality of long-term studies of olfactory and cognitive functions in the post-COVID era and the experiments using animal models to dissect the neural basis of these complications.In this manuscript,we summarize the research reporting the potential correlation between neurological disorders and viral pandemic outbreaks with a historical perspective.Further,we discuss the studies providing evidence of neurodegeneration due to severe acute respiratory syndrome coronavirus 2 infection by focusing on viral Parkinsonism.
基金supported by Swiss Center for Applied Human Toxicology(SCAHT AP22-01)(to RN).
文摘Alzheimer’s disease(AD)is the most common cause of dementia,characterized by progressive cognitive decline,and affects over 55 million people worldwide.AD is pathological featured by the aberrant accumulation of amyloid-βplaques,neurofibrillary tangles formed by hyperphosphorylated tau,synaptic loss,and dysfunction of neurotransmitter systems.Evidence from in vivo and autopsy studies has consistently shown that synaptic dysfunction and loss are strongly correlated with cognitive decline in AD,particularly in brain regions such as the hippocampus and cortex,which are critical for memory formation and processing.This perspective highlights recent histopathological findings related to synaptic dysfunction in AD,advancements in the development of imaging and fluid-based biomarkers for synaptic loss,and future studies.
基金supported by grants from Collaborative Research Fund(Ref:C4032-21GF)General Research Grant(Ref:14114822)+1 种基金Group Research Scheme(Ref:3110146)Area of Excellence(Ref:Ao E/M-402/20)。
文摘Mitochondrial dysfunction and oxidative stress are widely regarded as primary drivers of aging and are associated with several neurodegenerative diseases.The degeneration of motor neurons during aging is a critical pathological factor contributing to the progression of sarcopenia.However,the morphological and functional changes in mitochondria and their interplay in the degeneration of the neuromuscular junction during aging remain poorly understood.A defined systematic search of the Pub Med,Web of Science and Embase databases(last accessed on October 30,2024)was conducted with search terms including'mitochondria','aging'and'NMJ'.Clinical and preclinical studies of mitochondrial dysfunction and neuromuscular junction degeneration during aging.Twentyseven studies were included in this systematic review.This systematic review provides a summary of morphological,functional and biological changes in neuromuscular junction,mitochondrial morphology,biosynthesis,respiratory chain function,and mitophagy during aging.We focus on the interactions and mechanisms underlying the relationship between mitochondria and neuromuscular junctions during aging.Aging is characterized by significant reductions in mitochondrial fusion/fission cycles,biosynthesis,and mitochondrial quality control,which may lead to neuromuscular junction dysfunction,denervation and poor physical performance.Motor nerve terminals that exhibit redox sensitivity are among the first to exhibit abnormalities,ultimately leading to an early decline in muscle strength through impaired neuromuscular junction transmission function.Parg coactivator 1 alpha is a crucial molecule that regulates mitochondrial biogenesis and modulates various pathways,including the mitochondrial respiratory chain,energy deficiency,oxidative stress,and inflammation.Mitochondrial dysfunction is correlated with neuromuscular junction denervation and acetylcholine receptor fragmentation,resulting in muscle atrophy and a decrease in strength during aging.Physical therapy,pharmacotherapy,and gene therapy can alleviate the structural degeneration and functional deterioration of neuromuscular junction by restoring mitochondrial function.Therefore,mitochondria are considered potential targets for preserving neuromuscular junction morphology and function during aging to treat sarcopenia.
基金supported by the Nature Science Foundation of Liaoning Province,Nos.2022-MS-211,2021-MS-064,and 2024-MS-048(all to YC).
文摘Alzheimer’s disease,a devastating neurodegenerative disorder,is characterized by progressive cognitive decline,primarily due to amyloid-beta protein deposition and tau protein phosphorylation.Effectively reducing the cytotoxicity of amyloid-beta42 aggregates and tau oligomers may help slow the progression of Alzheimer’s disease.Conventional drugs,such as donepezil,can only alleviate symptoms and are not able to prevent the underlying pathological processes or cognitive decline.Currently,active and passive immunotherapies targeting amyloid-beta and tau have shown some efficacy in mice with asymptomatic Alzheimer’s disease and other transgenic animal models,attracting considerable attention.However,the clinical application of these immunotherapies demonstrated only limited efficacy before the discovery of lecanemab and donanemab.This review first discusses the advancements in the pathogenesis of Alzheimer’s disease and active and passive immunotherapies targeting amyloid-beta and tau proteins.Furthermore,it reviews the advantages and disadvantages of various immunotherapies and considers their future prospects.Although some antibodies have shown promise in patients with mild Alzheimer’s disease,substantial clinical data are still lacking to validate their effectiveness in individuals with moderate Alzheimer’s disease.
