The oral cavity is a complex physiological community encompassing a wide range of microorganisms.Dysbiosis of oral microbiota can lead to various oral infectious diseases,such as periodontitis and tooth decay,and even...The oral cavity is a complex physiological community encompassing a wide range of microorganisms.Dysbiosis of oral microbiota can lead to various oral infectious diseases,such as periodontitis and tooth decay,and even affect systemic health,including brain aging and neurodegenerative diseases.Recent studies have highlighted how oral microbes might be involved in brain aging and neurodegeneration,indicating potential avenues for intervention strategies.In this review,we summarize clinical evidence demonstrating a link between oral microbes/oral infectious diseases and brain aging/neurodegenerative diseases,and dissect potential mechanisms by which oral microbes contribute to brain aging and neurodegeneration.We also highlight advances in therapeutic development grounded in the realm of oral microbes,with the goal of advancing brain health and promoting healthy aging.展开更多
BACKGROUND Gastric subepithelial lesions(SELs)are elevated lesions originating from the muscularis mucosa,submucosa,or muscularis propria,and may also include extraluminal lesions.For small SELs(less than 5 cm),comple...BACKGROUND Gastric subepithelial lesions(SELs)are elevated lesions originating from the muscularis mucosa,submucosa,or muscularis propria,and may also include extraluminal lesions.For small SELs(less than 5 cm),complete endoscopic excision is the preferred treatment.Endoscopic full-thickness resection(EFTR)has proven to be an effective approach.AIM To evaluate the efficacy of the interrupted closure technique compared to the traditional closure technique in EFTR for gastric SELs.METHODS This single-center,prospective,randomized controlled trial was conducted at a tertiary hospital from September 2023 to September 2024.A total of 90 patients who underwent EFTR for gastric SELs were randomly allocated to either the interrupted closure group(n=44)or the traditional closure group(n=46).RESULTS All patients had complete resection and wound closure without any severe postoperative complications.The incidence of intraoperative gas-related complications was significantly lower in the interrupted closure group than in the traditional closure group(2.27%vs 26.09%,P=0.001),demonstrating interrupted closure technique can reduce the incidence of gas-related issues.Statistical analysis revealed that the incidence of postoperative infection was significantly lower in the experimental group than in the control group(15.91%vs 41.30%,P=0.008).Additionally,the median duration of antibiotic use was lower in the experimental group(3.5 days vs 5 days,P=0.013).Abdominal pain levels on postoperative days 1 and 4 were also lower in the experimental group compared to the control group(P<0.001).CONCLUSION The interrupted closure technique in EFTR for treating gastric SELs is safe and effective,reducing the incidence of intraoperative gas complications and postoperative infections.展开更多
Several promising plasma biomarker proteins,such as amyloid-β(Aβ),tau,neurofilament light chain,and glial fibrillary acidic protein,are widely used for the diagnosis of neurodegenerative diseases.However,little is k...Several promising plasma biomarker proteins,such as amyloid-β(Aβ),tau,neurofilament light chain,and glial fibrillary acidic protein,are widely used for the diagnosis of neurodegenerative diseases.However,little is known about the long-term stability of these biomarker proteins in plasma samples stored at-80°C.We aimed to explore how storage time would affect the diagnostic accuracy of these biomarkers using a large cohort.Plasma samples from 229 cognitively unimpaired individuals,encompassing healthy controls and those experiencing subjective cognitive decline,as well as 99 patients with cognitive impairment,comprising those with mild cognitive impairment and dementia,were acquired from the Sino Longitudinal Study on Cognitive Decline project.These samples were stored at-80°C for up to 6 years before being used in this study.Our results showed that plasma levels of Aβ42,Aβ40,neurofilament light chain,and glial fibrillary acidic protein were not significantly correlated with sample storage time.However,the level of total tau showed a negative correlation with sample storage time.Notably,in individuals without cognitive impairment,plasma levels of total protein and tau phosphorylated protein threonine 181(p-tau181)also showed a negative correlation with sample storage time.This was not observed in individuals with cognitive impairment.Consequently,we speculate that the diagnostic accuracy of plasma p-tau181 and the p-tau181 to total tau ratio may be influenced by sample storage time.Therefore,caution is advised when using these plasma biomarkers for the identification of neurodegenerative diseases,such as Alzheimer's disease.Furthermore,in cohort studies,it is important to consider the impact of storage time on the overall results.展开更多
Background:Poor sleep quality has been associated with changes in brain volume among veterans,particularly those who have experienced mild traumatic brain injury(mTBI)and post-traumatic stress disorder(PTSD).This stud...Background:Poor sleep quality has been associated with changes in brain volume among veterans,particularly those who have experienced mild traumatic brain injury(mTBI)and post-traumatic stress disorder(PTSD).This study sought to investigate:1)whether poor sleep quality is associated with decreased cortical thickness in Iraq and Afghanistan war veterans,and 2)whether these associations differ topographically depending on the presence or absence of mTBI and PTSD.Methods:A sample of 440 post-9/11 era U.S.veterans enrolled in the Translational Research Center for Traumatic Brain Injury and Stress Disorders study at VA Boston,MA from 2010 to 2022 was included in the study.We examined the relationship between sleep quality,as measured by the Pittsburgh Sleep Quality Index(PSQI),and cortical thickness in veterans with mTBI(n=57),PTSD(n=110),comorbid mTBI and PTSD(n=129),and neither PTSD nor mTBI(n=144).To determine the topographical relationship between subjective sleep quality and cortical thickness in each diagnostic group,we employed a General Linear Model(GLM)at each vertex on the cortical mantle.The extent of topographical overlap between the resulting statistical maps was assessed using Dice coefficients.Results:There were no significant associations between PSQI and cortical thickness in the group without PTSD or mTBI(n=144)or in the PTSD-only group(n=110).In the mTBI-only group(n=57),lower sleep quality was significantly associated with reduced thickness bilaterally in frontal,cingulate,and precuneus regions,as well as in the right parietal and temporal regions(β=-0.0137,P<0.0005).In the comorbid mTBI and PTSD group(n=129),significant associations were observed bilaterally in frontal,precentral,and precuneus regions,in the left cingulate and the right parietal regions(β=-0.0094,P<0.0005).Interaction analysis revealed that there was a stronger relationship between poor sleep quality and decreased cortical thickness in individuals with mTBI(n=186)compared with those without mTBI(n=254)specifically in the frontal and cingulate regions(β=-0.0077,P<0.0005).Conclusions:This study demonstrates a significant relationship between poor sleep quality and lower cortical thickness primarily within frontal regions among individuals with both isolated mTBI or comorbid diagnoses of mTBI and PTSD.Thus,if directionality is established in longitudinal and interventional studies,it may be crucial to consider addressing sleep in the treatment of veterans who have sustained mTBI.展开更多
Objectives Diabetes remains a major global health challenge in China.Artificial intelligence(AI)has demonstrated considerable potential in improving diabetes management.This study aimed to assess healthcare providers...Objectives Diabetes remains a major global health challenge in China.Artificial intelligence(AI)has demonstrated considerable potential in improving diabetes management.This study aimed to assess healthcare providers’perceptions regarding AI in diabetes care across China.Methods A cross-sectional survey was conducted using snowball sampling from November 12 to November 24,2024.We selected 514 physicians and nurses by a snowball sampling method from healthcare providers across 30 cities or provinces in China.The self-developed questionnaire comprised five sections with 19 questions assessing medical workers’demographic characteristics,AI-related experience and interest,awareness,attitudes,and concerns regarding AI in diabetes care.Statistical analysis was performed using t-test,analysis of variance(ANOVA),and linear regression.Results Among them,20.0%and 48.1%of respondents had participated in AI-related research and training,while 85.4%expressed moderate to high interest in AI training for diabetes care.Most respondents reported partial awareness of AI in diabetes care,and only 12.6%exhibited a comprehensive or substantial understanding.Attitudes toward AI in diabetes care were generally positive,with a mean score of 24.50±3.38.Nurses demonstrated significantly higher scores than physicians(P<0.05).Greater awareness,prior AI training experience,and higher interest in AI training in diabetes care were strongly associated with more positive attitudes(P<0.05).Key concerns regarding AI included trust issues from AI-clinician inconsistencies(77.2%),increased workload and clinical workflow disruptions(63.4%),and incomplete legal and regulatory frameworks(60.3%).Only 34.2%of respondents expressed concerns about job displacement,indicating general confidence in their professional roles.Conclusions While Chinese healthcare providers show moderate awareness of AI in diabetes care,their attitudes are generally positive,and they are considerably interested in future training.Tailored,role-specific AI training is essential for equitable and effective integration into clinical practice.Additionally,transparent,reliable,ethical AI models must be prioritized to alleviate practitioners’concerns.展开更多
In clinical specialties focusing on neurological disorders,there is a need for comprehensive and integrated non-invasive,sensitive,and specific testing methods.Both Parkinson's disease and multiple system atrophy ...In clinical specialties focusing on neurological disorders,there is a need for comprehensive and integrated non-invasive,sensitive,and specific testing methods.Both Parkinson's disease and multiple system atrophy are classified asα-synucleinopathies,characterized by abnormal accumulation ofα-synuclein protein,which provides a shared pathological background for their comparative study.In addition,both Parkinson's disease and multiple system atrophy involve neuronal death,a process that may release circulating cell–free DNA(cfDNA)into the bloodstream,leading to specific alterations.This premise formed the basis for investigating cell–free DNA as a potential biomarker.Cellfree DNA has garnered attention for its potential pathological significance,yet its characteristics in the context of Parkinson's disease and multiple system atrophy are not fully understood.This study investigated the total concentration,nonapoptotic level,integrity,and cellfree DNA relative telomere length of cell-free DNA in the peripheral blood of 171 participants,comprising 76 normal controls,62 patients with Parkinson's disease,and 33 patients with multiple system atrophy.In our cohort,75.8%of patients with Parkinson's disease(stage 1–2 of Hoehn&Yahr)and 60.6%of patients with multiple system atrophy(disease duration less than 3 years)were in the early stages.The diagnostic potential of the cell-free DNA parameters was evaluated using receiver operating characteristic(ROC)analysis,and their association with disease prevalence was examined through logistic regression models,adjusting for confounders such as age,sex,body mass index,and education level.The results showed that cell-free DNA integrity was significantly elevated in both Parkinson's disease and multiple system atrophy patients compared with normal controls(P<0.001 for both groups),whereas cell-free DNA relative telomere length was markedly shorter(P=0.003 for Parkinson's disease and P=0.010 for multiple system atrophy).Receiver operating characteristic analysis indicated that both cell-free DNA integrity and cell-free DNA relative telomere length possessed good diagnostic accuracy for differentiating Parkinson's disease and multiple system atrophy from normal controls.Specifically,higher cell-free DNA integrity was associated with increased risk of Parkinson's disease(odds ratio[OR]:5.72;95%confidence interval[CI]:1.54–24.19)and multiple system atrophy(OR:10.10;95%CI:1.55–122.98).Conversely,longer cell-free DNA relative telomere length was linked to reduced risk of Parkinson's disease(OR:0.16;95%CI:0.04–0.54)and multiple system atrophy(OR:0.10;95%CI:0.01–0.57).These findings suggest that cell-free DNA integrity and cellfree DNA relative telomere length may serve as promising biomarkers for the early diagnosis of Parkinson's disease and multiple system atrophy,potentially reflecting specific underlying pathophysiological processes of these neurodegenerative disorders.展开更多
Our study introduces scITDG,a tool designed for the analysis of time-dependent gene expression in single-cell transcriptomic sequencing data,effectively filling a gap in current analytical resources.A key advantage of...Our study introduces scITDG,a tool designed for the analysis of time-dependent gene expression in single-cell transcriptomic sequencing data,effectively filling a gap in current analytical resources.A key advantage of scITDG is its ability to identify dynamic gene expression patterns across multiple time points at single-cell resolution,which is pivotal for deciphering com-plex biological processes such as aging and tissue regeneration.The tool is compatible with widely used single-cell analysis platforms such as Seurat and Scanpy.By integrating natural cubic splines regression with bootstrapping resampling,scITDG enhances the functionality of these platforms and broadens their applicability.In this study,based on scITDG,we revealed intricate gene expression modules in mice aging and axolotl limb regeneration,providing valuable insights into cellular function and response mechanisms.The versatility of scITDG makes it applicable to a wide range of biological contexts,including development,circadian rhythms,disease progression,and therapeutic responses.展开更多
Background Postoperative delirium is one of the most common complications in the older surgical population,but its pathogenesis and biomarkers are largely undetermined.Retinal layer thickness has been demonstrated to ...Background Postoperative delirium is one of the most common complications in the older surgical population,but its pathogenesis and biomarkers are largely undetermined.Retinal layer thickness has been demonstrated to be associated with cognitive function in mild cognitive impairment and patients with Alzheimer’s disease.However,relatively little is known about possible retinal layer thickness among patients with postoperative delirium.Aims We aimed to investigate the relationship between retinal layer thickness and postoperative delirium in this cross-sectional study.Methods The participants(≥65 years old)having elective surgery under general anaesthesia were screened via medical records from Shanghai 10th People’s Hospital.Preoperative macular thickness and peripapillary retinal nerve fibre layer(RNFL)thickness were measured using optical coherence tomography(OCT).The Confusion Assessment Method(CAM)algorithm and CAM-Severity(CAM-S)were used to assess the incidence and severity of postoperative delirium on the first,second and third days after surgery.Results Among 169 participants(mean(standard deviation(SD)71.15(4.36)years),40(24%)developed postoperative delirium.Notably,individuals who developed postoperative delirium exhibited thicker preoperative macular thickness in the right eye compared with those who did not(mean(SD)283.35(27.97)µm vs 273.84(20.14)µm,p=0.013).Furthermore,the thicker preoperative macular thickness of the right eye was associated with a higher incidence of postoperative delirium(adjusted odds ratio 1.593,95%confidence interval(CI)1.093 to 2.322,p=0.015)and greater severity(adjusted mean difference(β)=0.256,95%CI 0.037 to 0.476,p=0.022)after adjustment for age,sex and Mini-Mental State Examination(MMSE)scores.However,such a difference or association did not appear in the left macular or bilateral peripapillary RNFL thicknesses.Conclusions Current findings demonstrated that preoperative macular thickness might serve as a potential non-invasive marker for the vulnerability of developing postoperative delirium in older surgical patients.Further large-scale validation studies should be performed to confirm these results.展开更多
Complex circuitry and limited regenerative power make central nervous system(CNS)disorders the most challenging and difficult for functional repair.With elusive disease mechanisms,traditional surgical and medical inte...Complex circuitry and limited regenerative power make central nervous system(CNS)disorders the most challenging and difficult for functional repair.With elusive disease mechanisms,traditional surgical and medical interventions merely slow down the progression of the neurodegenerative diseases.However,the number of neurons still diminishes in many patients.Recently,stem cell therapy has been proposed as a viable option.Mesenchymal stem cells(MSCs),a widely-studied human adult stem cell population,have been discovered for more than 20 years.MSCs have been found all over the body and can be conveniently obtained from different accessible tissues:bone marrow,blood,and adipose and dental tissue.MSCs have high proliferative and differentiation abilities,providing an inexhaustible source of neurons and glia for cell replacement therapy.Moreover,MSCs also show neuroprotective effects without any genetic modification or reprogramming.In addition,the extraordinary immunomodulatory properties of MSCs enable autologous and heterologous transplantation.These qualities heighten the clinical applicability of MSCs when dealing with the pathologies of CNS disorders.Here,we summarize the latest progress of MSC experimental research as well as human clinical trials for neural and retinal diseases.This review article will focus on multiple sclerosis,spinal cord injury,autism,glaucoma,retinitis pigmentosa and age-related macular degeneration.展开更多
Due to safety concerns and side effects of many antidepressant medications, herbal psychopharmacology research has increased, and herbal remedies are becoming increasingly popular as alternatives to prescribed medicat...Due to safety concerns and side effects of many antidepressant medications, herbal psychopharmacology research has increased, and herbal remedies are becoming increasingly popular as alternatives to prescribed medications for the treatment of major depressive disorder （MDD）. Of these, accumulating trials reveal positive effects of the spice saffron （Crocus sativus L.） for the treatment of depression. A comprehensive and statistical review of the clinical trials examining the effects of saffron for treatment of MDD is warranted. OBJECTIVE： The purpose of this study was to conduct a meta-analysis of published randomized controlled trials examining the effects of saffron supplementation on symptoms of depression among participants with MDD. SEARCH STRATEGY： We conducted electronic and non-electronic searches to identify all relevant randomized, double-blind controlled trials. Reference lists of all retrieved articles were searched for relevant studies. INCLUSION CRITERIA： The criteria for study selection included the following： （1） adults （aged 18 and older） with symptoms of depression, （2） randomized controlled trial, （3） effects of saffron supplementation on depressive symptoms examined, and （4） study had either a placebo control or antidepressant comparison group. DATA EXTRACTION AND ANALYSIS： Using random effects modeling procedures, we calculated weighted mean effect sizes separately for the saffron supplementation vs placebo control groups, and for the saffron supplementation vs antidepressant groups. The methodological quality of all studies was assessed using the Jadad score. The computer software Comprehensive Meta- analysis 2 was used to analyze the data. RESULTS： Based on our pre-specified criteria, five randomized controlled trials （n = 2 placebo controlled trials, n = 3 antidepressant controlled trials） were included in our review. A large effect size was found for saffron supplementation vs placebo control in treating depressive symptoms （M ES = 1.62, P 〈 0.001）, revealing that saffron supplementation significantly reduced depression symptoms compared to the placebo control. A null effect size was evidenced between saffron supplementation and the antidepressant groups （M ES = -0.15） indicating that both treatments were similarly effective in reducing depression symptoms. The mean Jadad score was 5 indicating high quality of trials. CONCLUSION： Findings from clinical trials conducted to date indicate that saffron supplementation can improve symptoms of depression in adults with MDD. Larger clinical trials, conducted by research teams outside of Iran, with long-term follow-ups are needed before firm conclusions can be made regarding saffron＇s efficacy and safety for treating depressive symptoms.展开更多
Carboplatin, a second-generation platinum chemotherapeutic drug, is considerably less ototoxic than cisplatin. While common laboratory species such as mice, guinea pigs and rats are highly resistant to carboplatin oto...Carboplatin, a second-generation platinum chemotherapeutic drug, is considerably less ototoxic than cisplatin. While common laboratory species such as mice, guinea pigs and rats are highly resistant to carboplatin ototoxicity, the chinchilla stands out as highly susceptible. Moreover, carboplatin causes an unusual gradient of cell death in chinchillas. Moderate doses selectively damage type I spiral ganglion neurons (SGN) and inner hair cells (IHC) and the lesion tends to be relatively uniform along the length of the cochlea. Higher doses eventually damage outer hair cells (OHC), but the lesion follows the traditional gradient in which damage is more severe in the base than the apex. While carboplatin ototoxicity has been well documented in adult animals in vivo, little is known about its in vitro toxicity. To elucidate the ototoxic effects of carboplatin in vitro, we prepared cochlear and vestibular organotypic cultures from postnatal day 3 rats and adult chinchillas. Chinchilla cochlear and vestibular cultures were treated with carboplatin concentrations ranging from 50 μM to 10 mM for 48 h. Consistent with in vivo data, carboplatin selectively damaged IHC at low concentrations (50-100 μM). Surprisingly, IHC loss decreased at higher doses and IHC were intact at doses exceeding 500 μM. The mechanisms underlying this nonlinear response are unclear but could be related to a decrease in carboplatin uptake via active transport mechanisms (e.g., copper). Unlike the cochlea, the carboplatin dose-response function increased with dose with the highest dose destroying all chinchilla vestibular hair cells. Cochlear hair cells and auditory nerve fibers in rat cochlear organotypic cultures were unaffected by carboplatin concentrations <10 μM; however, the damage in OHC were more severe than IHC once the dose reached 100 μM. A dose at 500 μM destroyed all the cochlear hair cells, but hair cell loss decreased at high concentrations and nearly all the cochlear hair cells were present at the highest dose, 5 mM. Unlike the nonlinear dose-response seen with cochlear hair cells, rat auditory nerve fiber and spiral ganglion losses increased with doses above 50 μM with the highest dose destroying virtually all SGN. The remarkable species differences seen in vitro suggest that chinchilla IHC and type I SGN posse some unique biological mechanism that makes them especially vulnerable to carboplatin toxicity.展开更多
Objective The inhalation anesthetic isoflurane has been shown to induce mitochondrial dysfunction and caspase activation, which may lead to learning and memory impairment. Ginsenoside Rgl is reported to be neuroprotec...Objective The inhalation anesthetic isoflurane has been shown to induce mitochondrial dysfunction and caspase activation, which may lead to learning and memory impairment. Ginsenoside Rgl is reported to be neuroprotective. We therefore set out to determine whether ginsenoside Rgl can attenuate isoflurane-induced caspase activation via inhibiting mitochondrial dysfunction. Methods We investigated the effects of ginsenoside Rgl at concentrations of 12.5, 25, and 50 μmol/L and pretreatment times of 12 h and 24 h on isoflurane-induced caspase-3 activation in H4 naive and stably transfected H4 human neuroglioma cells that express full-length human amyloid precursor protein （APP） （H4-APP cells）. For mitochondrial dysfunction, we assessed mitochondrial permeability transition pore （mPTP） and adenosine-5＇-triphosphate （ATP） levels. We employed Western blot analysis, chemiluminescence, and flowcytometry. Results Here we show that pretreatment with 50 μmol/L ginsenoside Rgl for 12 h attenuated isoflurane-induced caspase-3 activation and mitochondrial dysfunction in H4-APP cells, while pretreatment with 25 and 50 μmol/L ginsenoside Rgl for 24 h attenuated isoflurane-induced caspase-3 activation and mitochondrial dysfunction in both H4 naive and H4-APP cells. Conclusion These data suggest that ginsenoside Rgl may ameliorate isoflurane-induced caspase-3 activation by inhibiting mitochondrial dysfunction. Pending further studies, these findings might recommend the use of ginsenoside Rgl in preventing and treating isoflurane-induced neurotoxicity.展开更多
Hypertension is a primary risk factor for the progression of cognitive impairment caused by cerebral small vessel disease,the most common cerebrovascular disease.Howeve r,the causal relationship between hypertension a...Hypertension is a primary risk factor for the progression of cognitive impairment caused by cerebral small vessel disease,the most common cerebrovascular disease.Howeve r,the causal relationship between hypertension and cerebral small vessel disease remains unclear.Hypertension has substantial negative impacts on brain health and is recognized as a risk factor for cerebrovascular disease.Chronic hypertension and lifestyle factors are associated with risks for stro ke and dementia,and cerebral small vessel disease can cause dementia and stroke.Hypertension is the main driver of cerebral small vessel disease,which changes the structure and function of cerebral vessels via various mechanisms and leads to lacunar infarction,leukoaraiosis,white matter lesions,and intracerebral hemorrhage,ultimately res ulting in cognitive decline and demonstrating that the brain is the to rget organ of hypertension.This review updates our understanding of the pathogenesis of hypertensioninduced cerebral small vessel disease and the res ulting changes in brain structure and function and declines in cognitive ability.We also discuss drugs to treat cerebral small vessel disease and cognitive impairment.展开更多
Osteoporosis represents one major health condition for our growing elderly population. It accounts for severe morbidity and increased mortality in postmenopausal women and it is becoming an emerging health concern eve...Osteoporosis represents one major health condition for our growing elderly population. It accounts for severe morbidity and increased mortality in postmenopausal women and it is becoming an emerging health concern even in aging men. Screening of the population at risk for bone degeneration and treatment assessment of osteoporotic patients to prevent bone fragility fractures represent useful tools to improve quality of life in the elderly and to lighten the related socio-economic impact. Bone mineral density(BMD) estimate by means of dual-energy X-ray absorptiometry is normally used in clinical practice for osteoporosis diagnosis. Nevertheless, BMD alone does not represent a good predictor of fracture risk. From a clinical point of view, bone microarchitecture seems to be an intriguing aspect to characterize bone alteration patterns in aging and pathology. The widening into clinical practice of medical imaging techniques and the impressive advances in information technologies together with enhanced capacity of power calculation have promoted proliferation of new methods to assess changes of trabecular bone architecture(TBA) during aging and osteoporosis. Magnetic resonance imaging(MRI) has recently arisen as a useful tool to measure bone structure in vivo. In particular, high-resolution MRI techniques have introduced new perspectives for TBA characterization by non-invasive non-ionizing methods. However, texture analysis methods have not found favor with clinicians as they produce quite a few parameters whose interpretation is difficult. The introduction in biomedical field of paradigms, such as theory of complexity, chaos, and fractals, suggests new approaches and provides innovative tools to develop computerized methods that, by producing a limited number of parameters sensitive to pathology onset and progression, would speed up their application into clinical practice. Complexity of living beings and fractality of several physio-anatomic structures suggest fractal analysis as a promising approach to quantify morphofunctional changes in both aging and pathology. In this particular context, fractal lacunarity seems to be the proper tool to characterize TBA texture as it is able to describe both discontinuity of bone network and sizes of bone marrow spaces, whose changes are an index of bone fracture risk. In this paper, an original method of MRI texture analysis, based on TBA fractal lacunarity is described and discussed in the light of new perspectives for early diagnosis of osteoporotic fractures.展开更多
Objective To investigate the occurrence and possible mechanisms of apoptosis in cochlear epithelium and spiral ganglion neurons after mefloquine treatment. Methods We used quantitative RT-PCR apoptosis-focused gene ar...Objective To investigate the occurrence and possible mechanisms of apoptosis in cochlear epithelium and spiral ganglion neurons after mefloquine treatment. Methods We used quantitative RT-PCR apoptosis-focused gene arrays （96-well, 84 apoptosis related genes） to assess changes of gene expression in the cochlear basilar membrane （hair cells-supporting cells） and spiral ganglion neurons of rat cochlear organotypic cultures treated with 100 IxM mefloquine for 3 h. Results Significant up-or down-regulation in gene expression was detected in 23 genes in the cochlear basilar membrane, and in 32 genes in the spiral ganglion neurons compared with time-matched controls. The responding genes could be classified as pro-or anti-apoptotic, and were mainly implicated in the Bcl-2, Caspase, Card, IAP, TNF ligand / TNF receptor, Death domain / Death effector domain, DNA damage / p53, and NF-kappa B families. Synthetic analysis suggested that these families could be revised to two major pathways mainly involved in t]he death receptor-mediated signaling pathway and apoptotic mitochondrial pathway. In addition, it was found that numerous anti-apoptotic genes such as Bcl2al, Birclb, Birc3, Birc4, Bnipl, Cflar, II10, Lhx4, Mcll, Nfkbl, Prlr, Prok2, and TNF were greatly up-regulated in the cochlear tissue, which might imply the co-existence of protective response in the ceils at the early stage of mefloquine-induced damage.展开更多
In the present study, we hypothesized that 5-hydroxymethyl-2-furfural could attenuate ischemic brain damage by reducing oxidative injury. Thus, mice were subjected to bilateral common carotid artery occlusion to estab...In the present study, we hypothesized that 5-hydroxymethyl-2-furfural could attenuate ischemic brain damage by reducing oxidative injury. Thus, mice were subjected to bilateral common carotid artery occlusion to establish a model of permanent forebrain ischemia. The mice were intraperitoneally injected with 5-hydroxymethyl-2-furfura130 minutes before ischemia or 5 minutes after ischemia. The survival time of mice injected with 5-hydroxymethyl-2-furfural was longer compared with untreated mice. The mice subjected to ischemia for 30 minutes and reperfusion for 5 minutes were intraperitoneally injected with 5-hydroxymethyl-2-furfural 5 minutes prior to reperfusion, which increased superoxide dismutase content and reduced malondialdehyde content, similar to the effects of Edaravone, a hydroxyl radical scavenger used for the treatment of stroke. These findings indicate that intraperitoneal injection of 5-hydroxymethyl-2-furfural can prolong the survival of mice with permanent forebrain ischemia. This outcome may be mediated by its antioxidative effects.展开更多
Background:Although self-management approaches have shown strong evidence of positive outcomes for urinary incontinence prevention and management,few programs have been developed for Korean rural communities.Objective...Background:Although self-management approaches have shown strong evidence of positive outcomes for urinary incontinence prevention and management,few programs have been developed for Korean rural communities.Objectives:This pilot study aimed to develop,implement,and evaluate a urinary incontinence self-management program for community-dwelling women aged 55 and older with urinary incontinence in rural South Korea.Methods:This study used a one-group pre-post-test design to measure the effects of the intervention using standardized urinary incontinence symptom,knowledge,and attitude measures.Seventeen community-dwelling older women completed weekly 90-min group sessions for 5 weeks.Descriptive statistics and paired t-tests and were used to analyze data.Results:The mean of the overall interference on daily life from urine leakage(pre-test:M=5.76±2.68,post-test:M=2.29±1.93,t=4.609,p<0.001)and the sum of International Consultation on Incontinence Questionnaire scores(pre-test:M=11.59±3.00,post-test:M=5.29±3.02,t=-5.881,p<0.001)indicated significant improvement after the intervention.Improvement was also noted on the mean knowledge(pre-test:M=19.07±3.34,post-test:M=23.15±2.60,t=7.550,p<0.001)and attitude scores(pre-test:M=2.64±0.19,post-test:M=3.08±0.41,t=5.150,p<0.001).Weekly assignments were completed 82.4%of the time.Participants showed a high satisfaction level(M=26.82±1.74,range 22e28)with the group program.Conclusions:Implementation of a urinary incontinence self-management program was accompanied by improved outcomes for Korean older women living in rural communities who have scarce resources for urinary incontinence management and treatment.Urinary incontinence self-management education approaches have potential for widespread implementation in nursing practice.展开更多
Salivary gland(SG)dysfunction,due to radiotherapy,disease,or aging,is a clinical manifestation that has the potential to cause severe oral and/or systemic diseases and compromise quality of life.Currently,the standard...Salivary gland(SG)dysfunction,due to radiotherapy,disease,or aging,is a clinical manifestation that has the potential to cause severe oral and/or systemic diseases and compromise quality of life.Currently,the standard-of-care for this condition remains palliative.A variety of approaches have been employed to restore saliva production,but they have largely failed due to damage to both secretory cells and the extracellular matrix(niche).展开更多
Diabetic muscle infarction(DMI) refers to spontaneous ischemic necrosis of skeletal muscle among people with diabetes mellitus, unrelated to arterial occlusion. People with DMI may have coexisting end-stage renal dise...Diabetic muscle infarction(DMI) refers to spontaneous ischemic necrosis of skeletal muscle among people with diabetes mellitus, unrelated to arterial occlusion. People with DMI may have coexisting end-stage renal disease(ESRD) but little is known about its epidemiology and clinical outcomes in this setting. This scoping review seeks to investigate the characteristics, clinical features, diagnostic evaluation, management and outcomes of DMI among people with ESRD. Electronic database (Pub Med/MEDLINE, CINAHL, SCOPUS and and EMBASE) searches were conducted for ("diabetic muscle infarction" or "diabetic myonecrosis") and("chronic kidney disease" or "renal impairment" or "dialysis" or "renal replacement therapy" or "kidney transplant ") from January 1980 to June 2017. Relevant cases from reviewed bibliographies in reports retrieved were also included. Data were extracted in a standardized form. A total of 24 publications with 41 patients who have ESRD were included. The mean age at the time of presentation with DMI was 44.2 years. Type 2 diabetes was present in 53.7% of patients while type 1 in 41.5%. In this cohort, 60.1% were receiving hemodialysis, 21% on peritoneal dialysis and 12.2% had kidney transplantation. The proximal lower limb musculature was the most commonly affected site. Muscle pain and swelling were the most frequent manifestation on presentation. Magnetic resonance imaging (MRI) provided the most specific findings for DMI. Laboratory investigation findings are usually non-specific. Non-surgical therapy is usually used in the management of DMI. Short-term prognosis of DMI is good but recurrence occurred in 43.9%. DMI is an uncommon complication in patients with diabetes mellitus, including those affected by ESRD. In comparison with unselected patients with DMI, the characteristics and outcomes of those with ESRD are generally similar. DMI may also occur inkidney transplant recipients, including pancreas-kidney transplantation. MRI is the most useful diagnostic investigation. Non-surgical treatment involving analgesia, optimization of glycemic control and initial bed rest can help to improve recovery rate. However, recurrence of DMI is relatively frequent.展开更多
基金supported by the National Natural Science Foundation of China,No.81921006(to GHL)。
文摘The oral cavity is a complex physiological community encompassing a wide range of microorganisms.Dysbiosis of oral microbiota can lead to various oral infectious diseases,such as periodontitis and tooth decay,and even affect systemic health,including brain aging and neurodegenerative diseases.Recent studies have highlighted how oral microbes might be involved in brain aging and neurodegeneration,indicating potential avenues for intervention strategies.In this review,we summarize clinical evidence demonstrating a link between oral microbes/oral infectious diseases and brain aging/neurodegenerative diseases,and dissect potential mechanisms by which oral microbes contribute to brain aging and neurodegeneration.We also highlight advances in therapeutic development grounded in the realm of oral microbes,with the goal of advancing brain health and promoting healthy aging.
基金Supported by the Shenyang Science and Technology,No.22-321-32-15Department of Science and Technology of Liaoning Province,No.2023JH2/101600015.
文摘BACKGROUND Gastric subepithelial lesions(SELs)are elevated lesions originating from the muscularis mucosa,submucosa,or muscularis propria,and may also include extraluminal lesions.For small SELs(less than 5 cm),complete endoscopic excision is the preferred treatment.Endoscopic full-thickness resection(EFTR)has proven to be an effective approach.AIM To evaluate the efficacy of the interrupted closure technique compared to the traditional closure technique in EFTR for gastric SELs.METHODS This single-center,prospective,randomized controlled trial was conducted at a tertiary hospital from September 2023 to September 2024.A total of 90 patients who underwent EFTR for gastric SELs were randomly allocated to either the interrupted closure group(n=44)or the traditional closure group(n=46).RESULTS All patients had complete resection and wound closure without any severe postoperative complications.The incidence of intraoperative gas-related complications was significantly lower in the interrupted closure group than in the traditional closure group(2.27%vs 26.09%,P=0.001),demonstrating interrupted closure technique can reduce the incidence of gas-related issues.Statistical analysis revealed that the incidence of postoperative infection was significantly lower in the experimental group than in the control group(15.91%vs 41.30%,P=0.008).Additionally,the median duration of antibiotic use was lower in the experimental group(3.5 days vs 5 days,P=0.013).Abdominal pain levels on postoperative days 1 and 4 were also lower in the experimental group compared to the control group(P<0.001).CONCLUSION The interrupted closure technique in EFTR for treating gastric SELs is safe and effective,reducing the incidence of intraoperative gas complications and postoperative infections.
基金supported by the National Key Research&Development Program of China,Nos.2021YFC2501205(to YC),2022YFC24069004(to JL)the STI2030-Major Project,Nos.2021ZD0201101(to YC),2022ZD0211800(to YH)+2 种基金the National Natural Science Foundation of China(Major International Joint Research Project),No.82020108013(to YH)the Sino-German Center for Research Promotion,No.M-0759(to YH)a grant from Beijing Municipal Science&Technology Commission(Beijing Brain Initiative),No.Z201100005520018(to JL)。
文摘Several promising plasma biomarker proteins,such as amyloid-β(Aβ),tau,neurofilament light chain,and glial fibrillary acidic protein,are widely used for the diagnosis of neurodegenerative diseases.However,little is known about the long-term stability of these biomarker proteins in plasma samples stored at-80°C.We aimed to explore how storage time would affect the diagnostic accuracy of these biomarkers using a large cohort.Plasma samples from 229 cognitively unimpaired individuals,encompassing healthy controls and those experiencing subjective cognitive decline,as well as 99 patients with cognitive impairment,comprising those with mild cognitive impairment and dementia,were acquired from the Sino Longitudinal Study on Cognitive Decline project.These samples were stored at-80°C for up to 6 years before being used in this study.Our results showed that plasma levels of Aβ42,Aβ40,neurofilament light chain,and glial fibrillary acidic protein were not significantly correlated with sample storage time.However,the level of total tau showed a negative correlation with sample storage time.Notably,in individuals without cognitive impairment,plasma levels of total protein and tau phosphorylated protein threonine 181(p-tau181)also showed a negative correlation with sample storage time.This was not observed in individuals with cognitive impairment.Consequently,we speculate that the diagnostic accuracy of plasma p-tau181 and the p-tau181 to total tau ratio may be influenced by sample storage time.Therefore,caution is advised when using these plasma biomarkers for the identification of neurodegenerative diseases,such as Alzheimer's disease.Furthermore,in cohort studies,it is important to consider the impact of storage time on the overall results.
基金supported by the U.S.Department of Veterans Affairs through the Translational Research Center for TBI and Stress Disorders(TRACTS B3001-C),a VA Rehabilitation Research and Development Traumatic Brain Injury National Network Research Center,and the Boston University Chobanian&Avedisian School of Medicine’s Medical Student Summer Research Program,with funding from the Gabriel Family Foundation CTE Research Fund(MA).
文摘Background:Poor sleep quality has been associated with changes in brain volume among veterans,particularly those who have experienced mild traumatic brain injury(mTBI)and post-traumatic stress disorder(PTSD).This study sought to investigate:1)whether poor sleep quality is associated with decreased cortical thickness in Iraq and Afghanistan war veterans,and 2)whether these associations differ topographically depending on the presence or absence of mTBI and PTSD.Methods:A sample of 440 post-9/11 era U.S.veterans enrolled in the Translational Research Center for Traumatic Brain Injury and Stress Disorders study at VA Boston,MA from 2010 to 2022 was included in the study.We examined the relationship between sleep quality,as measured by the Pittsburgh Sleep Quality Index(PSQI),and cortical thickness in veterans with mTBI(n=57),PTSD(n=110),comorbid mTBI and PTSD(n=129),and neither PTSD nor mTBI(n=144).To determine the topographical relationship between subjective sleep quality and cortical thickness in each diagnostic group,we employed a General Linear Model(GLM)at each vertex on the cortical mantle.The extent of topographical overlap between the resulting statistical maps was assessed using Dice coefficients.Results:There were no significant associations between PSQI and cortical thickness in the group without PTSD or mTBI(n=144)or in the PTSD-only group(n=110).In the mTBI-only group(n=57),lower sleep quality was significantly associated with reduced thickness bilaterally in frontal,cingulate,and precuneus regions,as well as in the right parietal and temporal regions(β=-0.0137,P<0.0005).In the comorbid mTBI and PTSD group(n=129),significant associations were observed bilaterally in frontal,precentral,and precuneus regions,in the left cingulate and the right parietal regions(β=-0.0094,P<0.0005).Interaction analysis revealed that there was a stronger relationship between poor sleep quality and decreased cortical thickness in individuals with mTBI(n=186)compared with those without mTBI(n=254)specifically in the frontal and cingulate regions(β=-0.0077,P<0.0005).Conclusions:This study demonstrates a significant relationship between poor sleep quality and lower cortical thickness primarily within frontal regions among individuals with both isolated mTBI or comorbid diagnoses of mTBI and PTSD.Thus,if directionality is established in longitudinal and interventional studies,it may be crucial to consider addressing sleep in the treatment of veterans who have sustained mTBI.
基金supported by the Jiangsu Provincial Department of Science and Technology Social Development Project(No.BE2020787)。
文摘Objectives Diabetes remains a major global health challenge in China.Artificial intelligence(AI)has demonstrated considerable potential in improving diabetes management.This study aimed to assess healthcare providers’perceptions regarding AI in diabetes care across China.Methods A cross-sectional survey was conducted using snowball sampling from November 12 to November 24,2024.We selected 514 physicians and nurses by a snowball sampling method from healthcare providers across 30 cities or provinces in China.The self-developed questionnaire comprised five sections with 19 questions assessing medical workers’demographic characteristics,AI-related experience and interest,awareness,attitudes,and concerns regarding AI in diabetes care.Statistical analysis was performed using t-test,analysis of variance(ANOVA),and linear regression.Results Among them,20.0%and 48.1%of respondents had participated in AI-related research and training,while 85.4%expressed moderate to high interest in AI training for diabetes care.Most respondents reported partial awareness of AI in diabetes care,and only 12.6%exhibited a comprehensive or substantial understanding.Attitudes toward AI in diabetes care were generally positive,with a mean score of 24.50±3.38.Nurses demonstrated significantly higher scores than physicians(P<0.05).Greater awareness,prior AI training experience,and higher interest in AI training in diabetes care were strongly associated with more positive attitudes(P<0.05).Key concerns regarding AI included trust issues from AI-clinician inconsistencies(77.2%),increased workload and clinical workflow disruptions(63.4%),and incomplete legal and regulatory frameworks(60.3%).Only 34.2%of respondents expressed concerns about job displacement,indicating general confidence in their professional roles.Conclusions While Chinese healthcare providers show moderate awareness of AI in diabetes care,their attitudes are generally positive,and they are considerably interested in future training.Tailored,role-specific AI training is essential for equitable and effective integration into clinical practice.Additionally,transparent,reliable,ethical AI models must be prioritized to alleviate practitioners’concerns.
基金supported by the National Key Research and Development Program of China,No.2021YFC2501205(to YC)the Science and Technology Innovation 2030 project,No.2021ZD0201101(to YC)+1 种基金the National Natural Science Foundation of China,Nos.82201409(to YL),82201401(to CH)the Xuanwu Youth Development Project,No.QNPY2021011(to CH)。
文摘In clinical specialties focusing on neurological disorders,there is a need for comprehensive and integrated non-invasive,sensitive,and specific testing methods.Both Parkinson's disease and multiple system atrophy are classified asα-synucleinopathies,characterized by abnormal accumulation ofα-synuclein protein,which provides a shared pathological background for their comparative study.In addition,both Parkinson's disease and multiple system atrophy involve neuronal death,a process that may release circulating cell–free DNA(cfDNA)into the bloodstream,leading to specific alterations.This premise formed the basis for investigating cell–free DNA as a potential biomarker.Cellfree DNA has garnered attention for its potential pathological significance,yet its characteristics in the context of Parkinson's disease and multiple system atrophy are not fully understood.This study investigated the total concentration,nonapoptotic level,integrity,and cellfree DNA relative telomere length of cell-free DNA in the peripheral blood of 171 participants,comprising 76 normal controls,62 patients with Parkinson's disease,and 33 patients with multiple system atrophy.In our cohort,75.8%of patients with Parkinson's disease(stage 1–2 of Hoehn&Yahr)and 60.6%of patients with multiple system atrophy(disease duration less than 3 years)were in the early stages.The diagnostic potential of the cell-free DNA parameters was evaluated using receiver operating characteristic(ROC)analysis,and their association with disease prevalence was examined through logistic regression models,adjusting for confounders such as age,sex,body mass index,and education level.The results showed that cell-free DNA integrity was significantly elevated in both Parkinson's disease and multiple system atrophy patients compared with normal controls(P<0.001 for both groups),whereas cell-free DNA relative telomere length was markedly shorter(P=0.003 for Parkinson's disease and P=0.010 for multiple system atrophy).Receiver operating characteristic analysis indicated that both cell-free DNA integrity and cell-free DNA relative telomere length possessed good diagnostic accuracy for differentiating Parkinson's disease and multiple system atrophy from normal controls.Specifically,higher cell-free DNA integrity was associated with increased risk of Parkinson's disease(odds ratio[OR]:5.72;95%confidence interval[CI]:1.54–24.19)and multiple system atrophy(OR:10.10;95%CI:1.55–122.98).Conversely,longer cell-free DNA relative telomere length was linked to reduced risk of Parkinson's disease(OR:0.16;95%CI:0.04–0.54)and multiple system atrophy(OR:0.10;95%CI:0.01–0.57).These findings suggest that cell-free DNA integrity and cellfree DNA relative telomere length may serve as promising biomarkers for the early diagnosis of Parkinson's disease and multiple system atrophy,potentially reflecting specific underlying pathophysiological processes of these neurodegenerative disorders.
基金supported by the Strategic Priority Research Program of the Chinese Academy of Sciences(XDC0200000)the National Natural Science Foundation of China(82322025,82488301,82125011,82271600,82361148131)+15 种基金the National Key Research and Development Pro-gram of China(2022YFA1103700,2020YFA0804000)the Stra-tegic Priority Research Program of the Chinese Academy of Sci-ences(XDA0460403)the National Natural Science Foundation of China(92168201,82330044,32341001,32121001,82192863,82361148130,8231101626)Non-Communicable Chronic Diseases-National Science and Technology Major Project(2024ZD0530400)Youth Innovation Promotion Association of CAS(2022083)Young Elite Scientists Sponsorship Program by CAST(2021QNRC001)International Partnership Program of Chinese Academy of Sciences(073GJHZ2023019FN)he Program of the Beijing Natural Science Foundation(JQ24044,Z240018,F251011,Z230011)Shenzhen Medi-cal Research Fund(C2406001)CAS Project for Young Scientists in Basic Research(YSBR-076,YSBR-012)the Informatization Plan of Chinese Academy of Sciences(CAS-WX2022SDC-XK14)New Cor-nerstone Science Foundation through the XPLORER PRIZE(2021-1045)Beijing Municipal Public Welfare Development and Reform Pilot Project for Medical Research Institutes(JYY2023-13)CAS Youth Interdisciplinary Team,Key Laboratory of Alzheimer's Disease of Zhejiang Province(ZJAD-2024001)Initiative Scientific Research Program,Institute of Zoology,CAS(2023IOZ0102,2023IOZ0202,2024IOZ0103)Beijing Anzhen Hospital High Level Research Funding(2024AZB3002).
文摘Our study introduces scITDG,a tool designed for the analysis of time-dependent gene expression in single-cell transcriptomic sequencing data,effectively filling a gap in current analytical resources.A key advantage of scITDG is its ability to identify dynamic gene expression patterns across multiple time points at single-cell resolution,which is pivotal for deciphering com-plex biological processes such as aging and tissue regeneration.The tool is compatible with widely used single-cell analysis platforms such as Seurat and Scanpy.By integrating natural cubic splines regression with bootstrapping resampling,scITDG enhances the functionality of these platforms and broadens their applicability.In this study,based on scITDG,we revealed intricate gene expression modules in mice aging and axolotl limb regeneration,providing valuable insights into cellular function and response mechanisms.The versatility of scITDG makes it applicable to a wide range of biological contexts,including development,circadian rhythms,disease progression,and therapeutic responses.
基金supported by grants from National Natural Science Foundation of China(81720108012,82001118)Ministry of Science and Technology of China(2021ZD0202003)+1 种基金Shanghai‘Rising Stars of Medical Talents’Youth Development Program(SHWSRS(2023)-62)Henry K.Beecher Professorship from Harvard University。
文摘Background Postoperative delirium is one of the most common complications in the older surgical population,but its pathogenesis and biomarkers are largely undetermined.Retinal layer thickness has been demonstrated to be associated with cognitive function in mild cognitive impairment and patients with Alzheimer’s disease.However,relatively little is known about possible retinal layer thickness among patients with postoperative delirium.Aims We aimed to investigate the relationship between retinal layer thickness and postoperative delirium in this cross-sectional study.Methods The participants(≥65 years old)having elective surgery under general anaesthesia were screened via medical records from Shanghai 10th People’s Hospital.Preoperative macular thickness and peripapillary retinal nerve fibre layer(RNFL)thickness were measured using optical coherence tomography(OCT).The Confusion Assessment Method(CAM)algorithm and CAM-Severity(CAM-S)were used to assess the incidence and severity of postoperative delirium on the first,second and third days after surgery.Results Among 169 participants(mean(standard deviation(SD)71.15(4.36)years),40(24%)developed postoperative delirium.Notably,individuals who developed postoperative delirium exhibited thicker preoperative macular thickness in the right eye compared with those who did not(mean(SD)283.35(27.97)µm vs 273.84(20.14)µm,p=0.013).Furthermore,the thicker preoperative macular thickness of the right eye was associated with a higher incidence of postoperative delirium(adjusted odds ratio 1.593,95%confidence interval(CI)1.093 to 2.322,p=0.015)and greater severity(adjusted mean difference(β)=0.256,95%CI 0.037 to 0.476,p=0.022)after adjustment for age,sex and Mini-Mental State Examination(MMSE)scores.However,such a difference or association did not appear in the left macular or bilateral peripapillary RNFL thicknesses.Conclusions Current findings demonstrated that preoperative macular thickness might serve as a potential non-invasive marker for the vulnerability of developing postoperative delirium in older surgical patients.Further large-scale validation studies should be performed to confirm these results.
基金Supported by Veterans Affairs(VA)Merit Review GrantSenior VA Research Career Scientist Award,Miami
文摘Complex circuitry and limited regenerative power make central nervous system(CNS)disorders the most challenging and difficult for functional repair.With elusive disease mechanisms,traditional surgical and medical interventions merely slow down the progression of the neurodegenerative diseases.However,the number of neurons still diminishes in many patients.Recently,stem cell therapy has been proposed as a viable option.Mesenchymal stem cells(MSCs),a widely-studied human adult stem cell population,have been discovered for more than 20 years.MSCs have been found all over the body and can be conveniently obtained from different accessible tissues:bone marrow,blood,and adipose and dental tissue.MSCs have high proliferative and differentiation abilities,providing an inexhaustible source of neurons and glia for cell replacement therapy.Moreover,MSCs also show neuroprotective effects without any genetic modification or reprogramming.In addition,the extraordinary immunomodulatory properties of MSCs enable autologous and heterologous transplantation.These qualities heighten the clinical applicability of MSCs when dealing with the pathologies of CNS disorders.Here,we summarize the latest progress of MSC experimental research as well as human clinical trials for neural and retinal diseases.This review article will focus on multiple sclerosis,spinal cord injury,autism,glaucoma,retinitis pigmentosa and age-related macular degeneration.
基金Support was provided by the University of Florida Claude D.Pepper Older Americans Independence Center(NIH/ NIA P30AG028740)Clinical and Translational Science Institute(NIH/NCRR UL1TR000064)+1 种基金Stephen Anton is supported by a K23 AT004251-01A2,an Early Career Investigator Award from the American Heart Association (09CRP2390173)Thomas H.Maren Foundation
文摘Due to safety concerns and side effects of many antidepressant medications, herbal psychopharmacology research has increased, and herbal remedies are becoming increasingly popular as alternatives to prescribed medications for the treatment of major depressive disorder （MDD）. Of these, accumulating trials reveal positive effects of the spice saffron （Crocus sativus L.） for the treatment of depression. A comprehensive and statistical review of the clinical trials examining the effects of saffron for treatment of MDD is warranted. OBJECTIVE： The purpose of this study was to conduct a meta-analysis of published randomized controlled trials examining the effects of saffron supplementation on symptoms of depression among participants with MDD. SEARCH STRATEGY： We conducted electronic and non-electronic searches to identify all relevant randomized, double-blind controlled trials. Reference lists of all retrieved articles were searched for relevant studies. INCLUSION CRITERIA： The criteria for study selection included the following： （1） adults （aged 18 and older） with symptoms of depression, （2） randomized controlled trial, （3） effects of saffron supplementation on depressive symptoms examined, and （4） study had either a placebo control or antidepressant comparison group. DATA EXTRACTION AND ANALYSIS： Using random effects modeling procedures, we calculated weighted mean effect sizes separately for the saffron supplementation vs placebo control groups, and for the saffron supplementation vs antidepressant groups. The methodological quality of all studies was assessed using the Jadad score. The computer software Comprehensive Meta- analysis 2 was used to analyze the data. RESULTS： Based on our pre-specified criteria, five randomized controlled trials （n = 2 placebo controlled trials, n = 3 antidepressant controlled trials） were included in our review. A large effect size was found for saffron supplementation vs placebo control in treating depressive symptoms （M ES = 1.62, P 〈 0.001）, revealing that saffron supplementation significantly reduced depression symptoms compared to the placebo control. A null effect size was evidenced between saffron supplementation and the antidepressant groups （M ES = -0.15） indicating that both treatments were similarly effective in reducing depression symptoms. The mean Jadad score was 5 indicating high quality of trials. CONCLUSION： Findings from clinical trials conducted to date indicate that saffron supplementation can improve symptoms of depression in adults with MDD. Larger clinical trials, conducted by research teams outside of Iran, with long-term follow-ups are needed before firm conclusions can be made regarding saffron＇s efficacy and safety for treating depressive symptoms.
文摘Carboplatin, a second-generation platinum chemotherapeutic drug, is considerably less ototoxic than cisplatin. While common laboratory species such as mice, guinea pigs and rats are highly resistant to carboplatin ototoxicity, the chinchilla stands out as highly susceptible. Moreover, carboplatin causes an unusual gradient of cell death in chinchillas. Moderate doses selectively damage type I spiral ganglion neurons (SGN) and inner hair cells (IHC) and the lesion tends to be relatively uniform along the length of the cochlea. Higher doses eventually damage outer hair cells (OHC), but the lesion follows the traditional gradient in which damage is more severe in the base than the apex. While carboplatin ototoxicity has been well documented in adult animals in vivo, little is known about its in vitro toxicity. To elucidate the ototoxic effects of carboplatin in vitro, we prepared cochlear and vestibular organotypic cultures from postnatal day 3 rats and adult chinchillas. Chinchilla cochlear and vestibular cultures were treated with carboplatin concentrations ranging from 50 μM to 10 mM for 48 h. Consistent with in vivo data, carboplatin selectively damaged IHC at low concentrations (50-100 μM). Surprisingly, IHC loss decreased at higher doses and IHC were intact at doses exceeding 500 μM. The mechanisms underlying this nonlinear response are unclear but could be related to a decrease in carboplatin uptake via active transport mechanisms (e.g., copper). Unlike the cochlea, the carboplatin dose-response function increased with dose with the highest dose destroying all chinchilla vestibular hair cells. Cochlear hair cells and auditory nerve fibers in rat cochlear organotypic cultures were unaffected by carboplatin concentrations <10 μM; however, the damage in OHC were more severe than IHC once the dose reached 100 μM. A dose at 500 μM destroyed all the cochlear hair cells, but hair cell loss decreased at high concentrations and nearly all the cochlear hair cells were present at the highest dose, 5 mM. Unlike the nonlinear dose-response seen with cochlear hair cells, rat auditory nerve fiber and spiral ganglion losses increased with doses above 50 μM with the highest dose destroying virtually all SGN. The remarkable species differences seen in vitro suggest that chinchilla IHC and type I SGN posse some unique biological mechanism that makes them especially vulnerable to carboplatin toxicity.
基金supported by 2013 Beijing NOVA Program(Z131107000413044)
文摘Objective The inhalation anesthetic isoflurane has been shown to induce mitochondrial dysfunction and caspase activation, which may lead to learning and memory impairment. Ginsenoside Rgl is reported to be neuroprotective. We therefore set out to determine whether ginsenoside Rgl can attenuate isoflurane-induced caspase activation via inhibiting mitochondrial dysfunction. Methods We investigated the effects of ginsenoside Rgl at concentrations of 12.5, 25, and 50 μmol/L and pretreatment times of 12 h and 24 h on isoflurane-induced caspase-3 activation in H4 naive and stably transfected H4 human neuroglioma cells that express full-length human amyloid precursor protein （APP） （H4-APP cells）. For mitochondrial dysfunction, we assessed mitochondrial permeability transition pore （mPTP） and adenosine-5＇-triphosphate （ATP） levels. We employed Western blot analysis, chemiluminescence, and flowcytometry. Results Here we show that pretreatment with 50 μmol/L ginsenoside Rgl for 12 h attenuated isoflurane-induced caspase-3 activation and mitochondrial dysfunction in H4-APP cells, while pretreatment with 25 and 50 μmol/L ginsenoside Rgl for 24 h attenuated isoflurane-induced caspase-3 activation and mitochondrial dysfunction in both H4 naive and H4-APP cells. Conclusion These data suggest that ginsenoside Rgl may ameliorate isoflurane-induced caspase-3 activation by inhibiting mitochondrial dysfunction. Pending further studies, these findings might recommend the use of ginsenoside Rgl in preventing and treating isoflurane-induced neurotoxicity.
基金supported by the National Natural Science Foundation of China,Nos.82274611(to LZ),82104419(to DM)Capital Science and Technology Leading Talent Training Project,No.Z191100006119017(to LZ)+3 种基金Beijing Hospitals Authority Ascent Plan,No.DFL20190803(to LZ)Cultivation Fund of Hospital Management Center in Beijing,No.PZ2022006(to DM)R&D Program of Beijing Municipal Education Commission,No.KM202210025017(to DM)Beijing Gold-Bridge Project,No.ZZ20145(to DM)。
文摘Hypertension is a primary risk factor for the progression of cognitive impairment caused by cerebral small vessel disease,the most common cerebrovascular disease.Howeve r,the causal relationship between hypertension and cerebral small vessel disease remains unclear.Hypertension has substantial negative impacts on brain health and is recognized as a risk factor for cerebrovascular disease.Chronic hypertension and lifestyle factors are associated with risks for stro ke and dementia,and cerebral small vessel disease can cause dementia and stroke.Hypertension is the main driver of cerebral small vessel disease,which changes the structure and function of cerebral vessels via various mechanisms and leads to lacunar infarction,leukoaraiosis,white matter lesions,and intracerebral hemorrhage,ultimately res ulting in cognitive decline and demonstrating that the brain is the to rget organ of hypertension.This review updates our understanding of the pathogenesis of hypertensioninduced cerebral small vessel disease and the res ulting changes in brain structure and function and declines in cognitive ability.We also discuss drugs to treat cerebral small vessel disease and cognitive impairment.
文摘Osteoporosis represents one major health condition for our growing elderly population. It accounts for severe morbidity and increased mortality in postmenopausal women and it is becoming an emerging health concern even in aging men. Screening of the population at risk for bone degeneration and treatment assessment of osteoporotic patients to prevent bone fragility fractures represent useful tools to improve quality of life in the elderly and to lighten the related socio-economic impact. Bone mineral density(BMD) estimate by means of dual-energy X-ray absorptiometry is normally used in clinical practice for osteoporosis diagnosis. Nevertheless, BMD alone does not represent a good predictor of fracture risk. From a clinical point of view, bone microarchitecture seems to be an intriguing aspect to characterize bone alteration patterns in aging and pathology. The widening into clinical practice of medical imaging techniques and the impressive advances in information technologies together with enhanced capacity of power calculation have promoted proliferation of new methods to assess changes of trabecular bone architecture(TBA) during aging and osteoporosis. Magnetic resonance imaging(MRI) has recently arisen as a useful tool to measure bone structure in vivo. In particular, high-resolution MRI techniques have introduced new perspectives for TBA characterization by non-invasive non-ionizing methods. However, texture analysis methods have not found favor with clinicians as they produce quite a few parameters whose interpretation is difficult. The introduction in biomedical field of paradigms, such as theory of complexity, chaos, and fractals, suggests new approaches and provides innovative tools to develop computerized methods that, by producing a limited number of parameters sensitive to pathology onset and progression, would speed up their application into clinical practice. Complexity of living beings and fractality of several physio-anatomic structures suggest fractal analysis as a promising approach to quantify morphofunctional changes in both aging and pathology. In this particular context, fractal lacunarity seems to be the proper tool to characterize TBA texture as it is able to describe both discontinuity of bone network and sizes of bone marrow spaces, whose changes are an index of bone fracture risk. In this paper, an original method of MRI texture analysis, based on TBA fractal lacunarity is described and discussed in the light of new perspectives for early diagnosis of osteoporotic fractures.
文摘Objective To investigate the occurrence and possible mechanisms of apoptosis in cochlear epithelium and spiral ganglion neurons after mefloquine treatment. Methods We used quantitative RT-PCR apoptosis-focused gene arrays （96-well, 84 apoptosis related genes） to assess changes of gene expression in the cochlear basilar membrane （hair cells-supporting cells） and spiral ganglion neurons of rat cochlear organotypic cultures treated with 100 IxM mefloquine for 3 h. Results Significant up-or down-regulation in gene expression was detected in 23 genes in the cochlear basilar membrane, and in 32 genes in the spiral ganglion neurons compared with time-matched controls. The responding genes could be classified as pro-or anti-apoptotic, and were mainly implicated in the Bcl-2, Caspase, Card, IAP, TNF ligand / TNF receptor, Death domain / Death effector domain, DNA damage / p53, and NF-kappa B families. Synthetic analysis suggested that these families could be revised to two major pathways mainly involved in t]he death receptor-mediated signaling pathway and apoptotic mitochondrial pathway. In addition, it was found that numerous anti-apoptotic genes such as Bcl2al, Birclb, Birc3, Birc4, Bnipl, Cflar, II10, Lhx4, Mcll, Nfkbl, Prlr, Prok2, and TNF were greatly up-regulated in the cochlear tissue, which might imply the co-existence of protective response in the ceils at the early stage of mefloquine-induced damage.
基金supported by the National Basic Research Program of China (973 Program),No.2003CB517104the National Natural Science Foundation of China,No.30973513+3 种基金Beijing Municipal Science and Technology Program,No.D0206001043191the Natural Science Foundation of Beijing,No.7112061Beijing Key Foundation of Traditional Chinese Medicine,No.KJTS2011-04Beijing Health and Technical Personal of High-Level Plan,No.2009-3-66
文摘In the present study, we hypothesized that 5-hydroxymethyl-2-furfural could attenuate ischemic brain damage by reducing oxidative injury. Thus, mice were subjected to bilateral common carotid artery occlusion to establish a model of permanent forebrain ischemia. The mice were intraperitoneally injected with 5-hydroxymethyl-2-furfura130 minutes before ischemia or 5 minutes after ischemia. The survival time of mice injected with 5-hydroxymethyl-2-furfural was longer compared with untreated mice. The mice subjected to ischemia for 30 minutes and reperfusion for 5 minutes were intraperitoneally injected with 5-hydroxymethyl-2-furfural 5 minutes prior to reperfusion, which increased superoxide dismutase content and reduced malondialdehyde content, similar to the effects of Edaravone, a hydroxyl radical scavenger used for the treatment of stroke. These findings indicate that intraperitoneal injection of 5-hydroxymethyl-2-furfural can prolong the survival of mice with permanent forebrain ischemia. This outcome may be mediated by its antioxidative effects.
基金This study was supported by the Mary Hester Scholarship Endowment Award of Duke University School of Nursing and by the Asian American/Pacific Islander Nurses Association's Nursing Scholarship.
文摘Background:Although self-management approaches have shown strong evidence of positive outcomes for urinary incontinence prevention and management,few programs have been developed for Korean rural communities.Objectives:This pilot study aimed to develop,implement,and evaluate a urinary incontinence self-management program for community-dwelling women aged 55 and older with urinary incontinence in rural South Korea.Methods:This study used a one-group pre-post-test design to measure the effects of the intervention using standardized urinary incontinence symptom,knowledge,and attitude measures.Seventeen community-dwelling older women completed weekly 90-min group sessions for 5 weeks.Descriptive statistics and paired t-tests and were used to analyze data.Results:The mean of the overall interference on daily life from urine leakage(pre-test:M=5.76±2.68,post-test:M=2.29±1.93,t=4.609,p<0.001)and the sum of International Consultation on Incontinence Questionnaire scores(pre-test:M=11.59±3.00,post-test:M=5.29±3.02,t=-5.881,p<0.001)indicated significant improvement after the intervention.Improvement was also noted on the mean knowledge(pre-test:M=19.07±3.34,post-test:M=23.15±2.60,t=7.550,p<0.001)and attitude scores(pre-test:M=2.64±0.19,post-test:M=3.08±0.41,t=5.150,p<0.001).Weekly assignments were completed 82.4%of the time.Participants showed a high satisfaction level(M=26.82±1.74,range 22e28)with the group program.Conclusions:Implementation of a urinary incontinence self-management program was accompanied by improved outcomes for Korean older women living in rural communities who have scarce resources for urinary incontinence management and treatment.Urinary incontinence self-management education approaches have potential for widespread implementation in nursing practice.
基金supported by NIDCR/NIH R01DE025286(C-K.Y.&X-D.C.),R21 DE028271A(C-K.Y.)VA Merit Review 1I01BX002145-01(X-D.C.)VA Career Development Award 1IK2BX005694-01(M.M.)。
文摘Salivary gland(SG)dysfunction,due to radiotherapy,disease,or aging,is a clinical manifestation that has the potential to cause severe oral and/or systemic diseases and compromise quality of life.Currently,the standard-of-care for this condition remains palliative.A variety of approaches have been employed to restore saliva production,but they have largely failed due to damage to both secretory cells and the extracellular matrix(niche).
基金supported by a K23 AT004251-01A2, an Early Stage Investigator Grant from the American Heart Association and the Thomas H.Maren Foundationpartially supported by grants 1UL1RR029890 and U54RR025208 from the National Institute of Research Resources,National Institutes of Health,USA
文摘Diabetic muscle infarction(DMI) refers to spontaneous ischemic necrosis of skeletal muscle among people with diabetes mellitus, unrelated to arterial occlusion. People with DMI may have coexisting end-stage renal disease(ESRD) but little is known about its epidemiology and clinical outcomes in this setting. This scoping review seeks to investigate the characteristics, clinical features, diagnostic evaluation, management and outcomes of DMI among people with ESRD. Electronic database (Pub Med/MEDLINE, CINAHL, SCOPUS and and EMBASE) searches were conducted for ("diabetic muscle infarction" or "diabetic myonecrosis") and("chronic kidney disease" or "renal impairment" or "dialysis" or "renal replacement therapy" or "kidney transplant ") from January 1980 to June 2017. Relevant cases from reviewed bibliographies in reports retrieved were also included. Data were extracted in a standardized form. A total of 24 publications with 41 patients who have ESRD were included. The mean age at the time of presentation with DMI was 44.2 years. Type 2 diabetes was present in 53.7% of patients while type 1 in 41.5%. In this cohort, 60.1% were receiving hemodialysis, 21% on peritoneal dialysis and 12.2% had kidney transplantation. The proximal lower limb musculature was the most commonly affected site. Muscle pain and swelling were the most frequent manifestation on presentation. Magnetic resonance imaging (MRI) provided the most specific findings for DMI. Laboratory investigation findings are usually non-specific. Non-surgical therapy is usually used in the management of DMI. Short-term prognosis of DMI is good but recurrence occurred in 43.9%. DMI is an uncommon complication in patients with diabetes mellitus, including those affected by ESRD. In comparison with unselected patients with DMI, the characteristics and outcomes of those with ESRD are generally similar. DMI may also occur inkidney transplant recipients, including pancreas-kidney transplantation. MRI is the most useful diagnostic investigation. Non-surgical treatment involving analgesia, optimization of glycemic control and initial bed rest can help to improve recovery rate. However, recurrence of DMI is relatively frequent.
