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
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
BACKGROUND Ulcerative colitis(UC)is an inflammatory condition with frequent relapse and recurrence.Evidence suggests the involvement of SLC6A14 in UC pathogenesis,but the central regulator remains unknown.AIM To explo...BACKGROUND Ulcerative colitis(UC)is an inflammatory condition with frequent relapse and recurrence.Evidence suggests the involvement of SLC6A14 in UC pathogenesis,but the central regulator remains unknown.AIM To explore the role of SLC6A14 in UC-associated pyroptosis.METHODS Quantitative real-time polymerase chain reaction(qRT-PCR),immunoblotting,and immunohistochemical were used to assess SLC6A14 in human UC tissues.Lipopolysaccharide(LPS)was used to induce inflammation in FHC and NCM460 cells and model enteritis,and SLC6A14 levels were assessed.Pyroptosis markers were quantified using enzyme-linked immunosorbent assay,Western blotting,and qRT-PCR,and EdU incubation,CCK-8 assays and flow cytometry were used to examine proliferation and apoptosis.Mouse models of UC were used for verification.RESULTS SLC6A14 was increased and correlated with NLRP3 in UC tissues.LPS-induced FHC and NCM460 cells showed increased SLC6A14 levels.Reducing SLC6A14 increased cell proliferation and suppressed apoptosis.Reducing SLC6A14 decreased pyroptosis-associated proteins(ASC,IL-1β,IL-18,NLRP3).NLRP3 overexpression counteracted the effects of sh-SLC6A14 on LPS-induced FHC and NCM460 cell pyroptosis.SLC6A14 improved the mucosa in mice with dextran sulfate sodium-induced colitis.CONCLUSION SLC6A14 promotes UC pyroptosis by regulating NLRP3,suggesting the therapeutic potential of modulating the SLC6A14/NLRP3 axis.展开更多
Objective:Network analysis was used to explore the complex inter-relationships between social participation activities and depressive symptoms among the Chinese older population,and the differences in network structur...Objective:Network analysis was used to explore the complex inter-relationships between social participation activities and depressive symptoms among the Chinese older population,and the differences in network structures among different genders,age groups,and urban-rural residency would be compared.Methods:Based on the 2018 wave of the Chinese Longitudinal Healthy Longevity Survey(CLHLS),12,043 people aged 65 to 105 were included.The 10-item Center for Epidemiologic Studies Depression(CESD)Scale was used to assess depressive symptoms and 10 types of social participation activities were collected,including housework,tai-chi,square dancing,visiting and interacting with friends,garden work,reading newspapers or books,raising domestic animals,playing cards or mahjong,watching TV or listening to radio,and organized social activities.R 4.2.1 software was used to estimate the network model and calculate strength and bridge strength.Results:21.60%(2,601/12,043)of the participants had depressive symptoms.The total social participation score was negatively associated with depressive symptoms after adjusting for sociodemographic factors.The network of social participation and depressive symptoms showed that“D9(Inability to get going)”and“S9(Watching TV and/or listening to the radio)”had the highest strength within depressive symptoms and social participation communities,respectively,and“S1(Housework)”,“S9(Watching TV and/or listening to the radio)”,and“D5(Hopelessness)”were the most prominent bridging nodes between the two communities.Most edges linking the two communities were negative.“S5(Graden work)-D5(Hopelessness)”and“S6(Reading newspapers/books)-D4(Everything was an effort)”were the top 2 strongest negative edges.Older females had significantly denser network structures than older males.Compared to older people aged 65e80,the age group 81e105 showed higher network global strength.Conclusions:This study provides novel insights into the complex relationships between social participation and depressive symptoms.Except for doing housework,other social participation activities were found to be protective for depression levels.Different nursing strategies should be taken to prevent and alleviate depressive symptoms for different genders and older people of different ages.展开更多
Objective:Peyronie’s disease(PD)is an abnormal wound healing in the penile tunica albuginea.After fibrotic plaque excision,different graft materials have been used to repair the defects,but the optimal graft remains ...Objective:Peyronie’s disease(PD)is an abnormal wound healing in the penile tunica albuginea.After fibrotic plaque excision,different graft materials have been used to repair the defects,but the optimal graft remains unknown.This study aimed to compare the functional outcomes of testicular tunica vaginalis grafts and bovine pericardium grafts in patients with severe PD.Methods:A retrospective comparative study was conducted on 33 PD patients undergoing partial plaque excision and grafting from September 2015 to May 2021.The patients were divided into two groups depending on the type of graft used.For 15 patients in Group B,testicular tunica vaginalis grafts were used to repair the defect,while for 18 patients in Group A,bovine pericardium grafts were used.Data of the patient’s age,comorbidities,sexual function,penile curvature,postoperative complications,need for further treatment,change in penile length,and satisfaction were gathered and compared between the groups.Sexual function was evaluated using the 5-item version of the International Index of Erectile Function(IIEF-5),and a functional less than 20-degree penile curvature after surgery was considered a successful intervention.Results:There was no difference in age,comorbidities,degree of curvature,perioperative IIEF-5,operative time,plaque size,or complication rates.After surgery,a statistically significant improvement in curvature degree(p<0.05)and satisfactory penile appearance(p<0.05)were seen in both groups without any superiority between the two groups(p=0.423 and p=0.840,respectively).With a 30-month follow-up,the IIEF-5 was consistent in both groups,with no statistical significance between the groups(p=0.492).The main change in penile length during the operation was increased and still positive in the last follow-up in both groups without statistical significance(p=0.255 and p=0.101,respectively).Conclusion:Partial plaque excision and corporoplasty with both testicular tunica vaginalis or bovine pericardium grafts are equally effective in treating males with clinically significant PD.展开更多
Introduction The Diagnostic and Statistical Manual of Mental Disorders,5th Edition(DSM-5)[1]defines delirium as a disturbance in attention and awareness that develops over a short period and involves fluctuation in se...Introduction The Diagnostic and Statistical Manual of Mental Disorders,5th Edition(DSM-5)[1]defines delirium as a disturbance in attention and awareness that develops over a short period and involves fluctuation in severity.This profile is also accompanied by an additional disturbance in cognition(e.g.,memory),which are not explained by a preexisting neurocognitive disorder.展开更多
Background:Vascular impairment is one of the major contributors to dementia.We aimed to identify blood biomarkers suggestive of potential impairment of the blood-brain barrier(BBB)in subjects with Alzheimer’s disease...Background:Vascular impairment is one of the major contributors to dementia.We aimed to identify blood biomarkers suggestive of potential impairment of the blood-brain barrier(BBB)in subjects with Alzheimer’s disease(AD).Methods:We used administrative data from the VA Informatics and Computing Infrastructure Resource Center to study both inpatients and outpatients with AD.Plasma samples from healthy control and AD individuals were analyzed using enzyme-linked immunosorbent assay and proteomics approaches to identify differentially expressed proteins.Bioinformatic analysis was applied to explore significantly enriched pathways.Results:In the same cohort of patients with AD,we found twice number of subjects with cerebral amyloid angiopathy in the two-year period after the onset of AD,compared to the number of subjects with cerebral amyloid angiopathy in the two-year period prior to AD onset.Different pathways related to BBB,like cell adhesion,extracellular matrix organization and Wnt signaling,were activated and differentially expressed proteins such as ADAM22,PDGFR-α,DKK-4,Neucrin and RSOP-1 were identified.Moreover,matrix metalloproteinase-9,which is implicated in causing degradation of basal lamina and BBB disruption,was significantly increased in the plasma of AD patients.Conclusions:Alteration of proteins found in AD subjects could provide new insights into biomarkers regulating permeability and BBB integrity.展开更多
Background:Skeletal muscle energetics decline with age,and physical activity(PA)has been shown to offset these declines in older adults.Yet,many studies reporting these effects were based on self-reported PA or struct...Background:Skeletal muscle energetics decline with age,and physical activity(PA)has been shown to offset these declines in older adults.Yet,many studies reporting these effects were based on self-reported PA or structured exercise interventions.Therefore,we examined the associations of accelerometry-measured and self-reported PA and sedentary behavior(SB)with skeletal muscle energetics and explored the extent to which PA and sedentary behavior would attenuate the associations of age with muscle energetics.Methods:As part of the Study of Muscle,Mobility and Aging,enrolled older adults(n=879),810(age=76.4±5.0 years old,mean±SD;58%women)had maximal muscle oxidative capacity measured ex vivo via high-resolution re spirometry of permeabilized myofibers(maximal oxidative phosphorylation(maxOXPHOS))and in vivo by ^(31)phosphorus magnetic resonance spectroscopy(maximal adenosine triphosphate(ATP_(max))).Accelerometry-measured sedentary behavior,light activity,and moderate-to-vigorous PA(MVPA)were assessed using a wrist-worn ActiGraph GT9X over 7 days.Self-reported sedentary behavior,MVPA,and all PA were assessed with the Community Healthy Activities Model Program for Seniors(CHAMPS)questionnaire.Linear regression models with progressive covariate adjustments evaluated the associations of sedentary behavior and PA with muscle energetics,as well as the attenuation of the age/muscle energetics association by MVP A and sedentary behavior.As a sensitivity analysis,we also examined activPAL-measured daily step count and time spent in sedentary behavior and their associations with muscle energetics.Results:Every 30 min/day more of ActiGraph-measured MVPA was associated with 0.65 pmol/(s×mg)higher maxOXPHOS and 0.012 mM/s higher ATP_(max)after adjusting for age,site/technician,and sex(p<0.05).Light activity was not associated with maxOXPHOS or ATP_(max).Meanwhile,every 30 min/day spent in ActiGraph-measured sedentary behavior was associated with 0.39 pmol/s×mg lower maxOXPHOS and0.006 mM/s lower ATP_(max)(p<0.05).Only associations with ATP_(max)held after further adjusting for socioeconomic status,body mass index,lifestyle factors,and multimorbidity.CHAMPS MVPA and all PA yielded similar associations with maxOXPHOS and ATP_(max)(p<0.05),but sedentary behavior did not.Higher activPAL step count was associated with higher maxOXHPOS and AT_(Pmax)(p<0.05),but time spent in sedentary behavior was not.Additionally,age was significantly associated with muscle energetics for men only(p<0.05);adjusting for time spent in ActiGraph-measured MVPA attenuated the age association with ATP_(max)by 58%in men.Conclusion:More time spent in accelerometry-measured or self-reported daily PA,especially MVPA,was associated with higher skeletal muscle energetics.Interventions aimed specifically at increasing higher intensity activity might offer potential therapeutic interventions to slow age-related decline in muscle energetics.Our work also emphasizes the importance of taking PA into consideration when evaluating associations related to skeletal muscle energetics.展开更多
Background: The burden of breast cancer in women of different menopausal status has not been assessed in China previously. We aim to evaluate and project the burden of breast cancer in different menopausal status in C...Background: The burden of breast cancer in women of different menopausal status has not been assessed in China previously. We aim to evaluate and project the burden of breast cancer in different menopausal status in China. Methods: The incidence and mortality of breast cancer were estimated using the data of 554 cancer registries in 2017 and the trends of incidence and mortality of 112 cancer registries from 2010 to 2017. Data from 22 continued cancer registries from 2000 to 2017 were applied for long-term trend projection to 2030 using the Bayesian age- period-cohort model. Menopausal status was stratified by age, with premenopause defined as chronological age < 45 years, perimenopause defined as 45-54 years, and postmenopause defined as ≥ 55 years. Results: Approximately 352,300 incident cases and 74,200 deaths of breast cancer occurred in China in 2020, contributing to 2.6 million disability-adjusted life years (DALYs). Perimenopausal women had the highest inci- dence, prevalence, and DALYs rates, with the rates being 100.3 per 100,000, 819.2 per 100,000 and 723.1 per 100,000 persons. While postmenopausal women had the highest mortality rates (25.5 per 100,000 persons). From 2000 to 2017, the largest increase in incidence and mortality for breast cancer was observed in postmenopausal women with an average annual percentage change (AAPC) of 5.6% and 2.94%. The number of breast cancer cases and deaths will increase to 452,000 and 98,800 in 2030, resulting in 3.2 million DALYs. Conclusions: The burden of breast cancer is rapidly increasing in China and varies among different menopausal status. Specific prevention and control strategies for women in different menopausal status will be more helpful in reducing the rapidly growing trends of breast cancer.展开更多
Traumatic spinal cord injury is potentially catastrophic and can lead to permanent disability or even death.China has the largest population of patients with traumatic spinal cord injury.Previous studies of traumatic ...Traumatic spinal cord injury is potentially catastrophic and can lead to permanent disability or even death.China has the largest population of patients with traumatic spinal cord injury.Previous studies of traumatic spinal cord injury in China have mostly been regional in scope;national-level studies have been rare.To the best of our knowledge,no national-level study of treatment status and economic burden has been performed.This retrospective study aimed to examine the epidemiological and clinical features,treatment status,and economic burden of traumatic spinal cord injury in China at the national level.We included 13,465 traumatic spinal cord injury patients who were injured between January 2013 and December 2018 and treated in 30 hospitals in 11 provinces/municipalities representing all geographical divisions of China.Patient epidemiological and clinical features,treatment status,and total and daily costs were recorded.Trends in the percentage of traumatic spinal cord injuries among all hospitalized patients and among patients hospitalized in the orthopedic department and cost of care were assessed by annual percentage change using the Joinpoint Regression Program.The percentage of traumatic spinal cord injuries among all hospitalized patients and among patients hospitalized in the orthopedic department did not significantly change overall(annual percentage change,-0.5%and 2.1%,respectively).A total of 10,053(74.7%)patients underwent surgery.Only 2.8%of patients who underwent surgery did so within 24 hours of injury.A total of 2005(14.9%)patients were treated with high-dose(≥500 mg)methylprednisolone sodium succinate/methylprednisolone(MPSS/MP);615(4.6%)received it within 8 hours.The total cost for acute traumatic spinal cord injury decreased over the study period(-4.7%),while daily cost did not significantly change(1.0%increase).Our findings indicate that public health initiatives should aim at improving hospitals’ability to complete early surgery within 24 hours,which is associated with improved sensorimotor recovery,increasing the awareness rate of clinical guidelines related to high-dose MPSS/MP to reduce the use of the treatment with insufficient evidence.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
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 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.
基金Supported by The Key Research and Development Projects of Sichuan Science and Technology Department,No.2023YFS0285Natural Science Foundation Project of Sichuan Science and Technology Department,No.2023NSFSC0613.
文摘BACKGROUND Ulcerative colitis(UC)is an inflammatory condition with frequent relapse and recurrence.Evidence suggests the involvement of SLC6A14 in UC pathogenesis,but the central regulator remains unknown.AIM To explore the role of SLC6A14 in UC-associated pyroptosis.METHODS Quantitative real-time polymerase chain reaction(qRT-PCR),immunoblotting,and immunohistochemical were used to assess SLC6A14 in human UC tissues.Lipopolysaccharide(LPS)was used to induce inflammation in FHC and NCM460 cells and model enteritis,and SLC6A14 levels were assessed.Pyroptosis markers were quantified using enzyme-linked immunosorbent assay,Western blotting,and qRT-PCR,and EdU incubation,CCK-8 assays and flow cytometry were used to examine proliferation and apoptosis.Mouse models of UC were used for verification.RESULTS SLC6A14 was increased and correlated with NLRP3 in UC tissues.LPS-induced FHC and NCM460 cells showed increased SLC6A14 levels.Reducing SLC6A14 increased cell proliferation and suppressed apoptosis.Reducing SLC6A14 decreased pyroptosis-associated proteins(ASC,IL-1β,IL-18,NLRP3).NLRP3 overexpression counteracted the effects of sh-SLC6A14 on LPS-induced FHC and NCM460 cell pyroptosis.SLC6A14 improved the mucosa in mice with dextran sulfate sodium-induced colitis.CONCLUSION SLC6A14 promotes UC pyroptosis by regulating NLRP3,suggesting the therapeutic potential of modulating the SLC6A14/NLRP3 axis.
基金supported by the National Key Research and Development Plan Project(grant number:2022YFC3600904)The funding organization had no role in the survey’s design,implementation,and analysis.
文摘Objective:Network analysis was used to explore the complex inter-relationships between social participation activities and depressive symptoms among the Chinese older population,and the differences in network structures among different genders,age groups,and urban-rural residency would be compared.Methods:Based on the 2018 wave of the Chinese Longitudinal Healthy Longevity Survey(CLHLS),12,043 people aged 65 to 105 were included.The 10-item Center for Epidemiologic Studies Depression(CESD)Scale was used to assess depressive symptoms and 10 types of social participation activities were collected,including housework,tai-chi,square dancing,visiting and interacting with friends,garden work,reading newspapers or books,raising domestic animals,playing cards or mahjong,watching TV or listening to radio,and organized social activities.R 4.2.1 software was used to estimate the network model and calculate strength and bridge strength.Results:21.60%(2,601/12,043)of the participants had depressive symptoms.The total social participation score was negatively associated with depressive symptoms after adjusting for sociodemographic factors.The network of social participation and depressive symptoms showed that“D9(Inability to get going)”and“S9(Watching TV and/or listening to the radio)”had the highest strength within depressive symptoms and social participation communities,respectively,and“S1(Housework)”,“S9(Watching TV and/or listening to the radio)”,and“D5(Hopelessness)”were the most prominent bridging nodes between the two communities.Most edges linking the two communities were negative.“S5(Graden work)-D5(Hopelessness)”and“S6(Reading newspapers/books)-D4(Everything was an effort)”were the top 2 strongest negative edges.Older females had significantly denser network structures than older males.Compared to older people aged 65e80,the age group 81e105 showed higher network global strength.Conclusions:This study provides novel insights into the complex relationships between social participation and depressive symptoms.Except for doing housework,other social participation activities were found to be protective for depression levels.Different nursing strategies should be taken to prevent and alleviate depressive symptoms for different genders and older people of different ages.
文摘Objective:Peyronie’s disease(PD)is an abnormal wound healing in the penile tunica albuginea.After fibrotic plaque excision,different graft materials have been used to repair the defects,but the optimal graft remains unknown.This study aimed to compare the functional outcomes of testicular tunica vaginalis grafts and bovine pericardium grafts in patients with severe PD.Methods:A retrospective comparative study was conducted on 33 PD patients undergoing partial plaque excision and grafting from September 2015 to May 2021.The patients were divided into two groups depending on the type of graft used.For 15 patients in Group B,testicular tunica vaginalis grafts were used to repair the defect,while for 18 patients in Group A,bovine pericardium grafts were used.Data of the patient’s age,comorbidities,sexual function,penile curvature,postoperative complications,need for further treatment,change in penile length,and satisfaction were gathered and compared between the groups.Sexual function was evaluated using the 5-item version of the International Index of Erectile Function(IIEF-5),and a functional less than 20-degree penile curvature after surgery was considered a successful intervention.Results:There was no difference in age,comorbidities,degree of curvature,perioperative IIEF-5,operative time,plaque size,or complication rates.After surgery,a statistically significant improvement in curvature degree(p<0.05)and satisfactory penile appearance(p<0.05)were seen in both groups without any superiority between the two groups(p=0.423 and p=0.840,respectively).With a 30-month follow-up,the IIEF-5 was consistent in both groups,with no statistical significance between the groups(p=0.492).The main change in penile length during the operation was increased and still positive in the last follow-up in both groups without statistical significance(p=0.255 and p=0.101,respectively).Conclusion:Partial plaque excision and corporoplasty with both testicular tunica vaginalis or bovine pericardium grafts are equally effective in treating males with clinically significant PD.
文摘Introduction The Diagnostic and Statistical Manual of Mental Disorders,5th Edition(DSM-5)[1]defines delirium as a disturbance in attention and awareness that develops over a short period and involves fluctuation in severity.This profile is also accompanied by an additional disturbance in cognition(e.g.,memory),which are not explained by a preexisting neurocognitive disorder.
基金University of Massachusetts Lowell-Bedford VA Healthcare System Pilot Award(NM,WX,EG),I01 BX004730 and I01 BX003527 Merit Awards from the Biomedical Laboratory Research and Development of the Veterans Affairs Office of Research and Development(WX)RF1AG063913 from the NIH(WX).
文摘Background:Vascular impairment is one of the major contributors to dementia.We aimed to identify blood biomarkers suggestive of potential impairment of the blood-brain barrier(BBB)in subjects with Alzheimer’s disease(AD).Methods:We used administrative data from the VA Informatics and Computing Infrastructure Resource Center to study both inpatients and outpatients with AD.Plasma samples from healthy control and AD individuals were analyzed using enzyme-linked immunosorbent assay and proteomics approaches to identify differentially expressed proteins.Bioinformatic analysis was applied to explore significantly enriched pathways.Results:In the same cohort of patients with AD,we found twice number of subjects with cerebral amyloid angiopathy in the two-year period after the onset of AD,compared to the number of subjects with cerebral amyloid angiopathy in the two-year period prior to AD onset.Different pathways related to BBB,like cell adhesion,extracellular matrix organization and Wnt signaling,were activated and differentially expressed proteins such as ADAM22,PDGFR-α,DKK-4,Neucrin and RSOP-1 were identified.Moreover,matrix metalloproteinase-9,which is implicated in causing degradation of basal lamina and BBB disruption,was significantly increased in the plasma of AD patients.Conclusions:Alteration of proteins found in AD subjects could provide new insights into biomarkers regulating permeability and BBB integrity.
基金supported by funding from the National Institute on Aging(NIA,R01 AG059416)funded in part by the NIA Claude D.Pepper Older American Independence Centers at the University of Pittsburgh(P30 AG024827)+1 种基金Wake Forest University(P30 AG021332)the Clinical and Translational Science Institutes,funded by the National Center for Advancing Translational Science,at Wake Forest University(UL1 TR001420)。
文摘Background:Skeletal muscle energetics decline with age,and physical activity(PA)has been shown to offset these declines in older adults.Yet,many studies reporting these effects were based on self-reported PA or structured exercise interventions.Therefore,we examined the associations of accelerometry-measured and self-reported PA and sedentary behavior(SB)with skeletal muscle energetics and explored the extent to which PA and sedentary behavior would attenuate the associations of age with muscle energetics.Methods:As part of the Study of Muscle,Mobility and Aging,enrolled older adults(n=879),810(age=76.4±5.0 years old,mean±SD;58%women)had maximal muscle oxidative capacity measured ex vivo via high-resolution re spirometry of permeabilized myofibers(maximal oxidative phosphorylation(maxOXPHOS))and in vivo by ^(31)phosphorus magnetic resonance spectroscopy(maximal adenosine triphosphate(ATP_(max))).Accelerometry-measured sedentary behavior,light activity,and moderate-to-vigorous PA(MVPA)were assessed using a wrist-worn ActiGraph GT9X over 7 days.Self-reported sedentary behavior,MVPA,and all PA were assessed with the Community Healthy Activities Model Program for Seniors(CHAMPS)questionnaire.Linear regression models with progressive covariate adjustments evaluated the associations of sedentary behavior and PA with muscle energetics,as well as the attenuation of the age/muscle energetics association by MVP A and sedentary behavior.As a sensitivity analysis,we also examined activPAL-measured daily step count and time spent in sedentary behavior and their associations with muscle energetics.Results:Every 30 min/day more of ActiGraph-measured MVPA was associated with 0.65 pmol/(s×mg)higher maxOXPHOS and 0.012 mM/s higher ATP_(max)after adjusting for age,site/technician,and sex(p<0.05).Light activity was not associated with maxOXPHOS or ATP_(max).Meanwhile,every 30 min/day spent in ActiGraph-measured sedentary behavior was associated with 0.39 pmol/s×mg lower maxOXPHOS and0.006 mM/s lower ATP_(max)(p<0.05).Only associations with ATP_(max)held after further adjusting for socioeconomic status,body mass index,lifestyle factors,and multimorbidity.CHAMPS MVPA and all PA yielded similar associations with maxOXPHOS and ATP_(max)(p<0.05),but sedentary behavior did not.Higher activPAL step count was associated with higher maxOXHPOS and AT_(Pmax)(p<0.05),but time spent in sedentary behavior was not.Additionally,age was significantly associated with muscle energetics for men only(p<0.05);adjusting for time spent in ActiGraph-measured MVPA attenuated the age association with ATP_(max)by 58%in men.Conclusion:More time spent in accelerometry-measured or self-reported daily PA,especially MVPA,was associated with higher skeletal muscle energetics.Interventions aimed specifically at increasing higher intensity activity might offer potential therapeutic interventions to slow age-related decline in muscle energetics.Our work also emphasizes the importance of taking PA into consideration when evaluating associations related to skeletal muscle energetics.
基金the local cancer registry staffin China for their contribution to data collection,validation,and routine analyses.We also thank the CAMS Innovation Fund for Medical Sciences(grant number:2021-I2M-1-011)that supported this study.
文摘Background: The burden of breast cancer in women of different menopausal status has not been assessed in China previously. We aim to evaluate and project the burden of breast cancer in different menopausal status in China. Methods: The incidence and mortality of breast cancer were estimated using the data of 554 cancer registries in 2017 and the trends of incidence and mortality of 112 cancer registries from 2010 to 2017. Data from 22 continued cancer registries from 2000 to 2017 were applied for long-term trend projection to 2030 using the Bayesian age- period-cohort model. Menopausal status was stratified by age, with premenopause defined as chronological age < 45 years, perimenopause defined as 45-54 years, and postmenopause defined as ≥ 55 years. Results: Approximately 352,300 incident cases and 74,200 deaths of breast cancer occurred in China in 2020, contributing to 2.6 million disability-adjusted life years (DALYs). Perimenopausal women had the highest inci- dence, prevalence, and DALYs rates, with the rates being 100.3 per 100,000, 819.2 per 100,000 and 723.1 per 100,000 persons. While postmenopausal women had the highest mortality rates (25.5 per 100,000 persons). From 2000 to 2017, the largest increase in incidence and mortality for breast cancer was observed in postmenopausal women with an average annual percentage change (AAPC) of 5.6% and 2.94%. The number of breast cancer cases and deaths will increase to 452,000 and 98,800 in 2030, resulting in 3.2 million DALYs. Conclusions: The burden of breast cancer is rapidly increasing in China and varies among different menopausal status. Specific prevention and control strategies for women in different menopausal status will be more helpful in reducing the rapidly growing trends of breast cancer.
基金supported by the National Key Research and Development Project,No.2019YFA0112100(to SF).
文摘Traumatic spinal cord injury is potentially catastrophic and can lead to permanent disability or even death.China has the largest population of patients with traumatic spinal cord injury.Previous studies of traumatic spinal cord injury in China have mostly been regional in scope;national-level studies have been rare.To the best of our knowledge,no national-level study of treatment status and economic burden has been performed.This retrospective study aimed to examine the epidemiological and clinical features,treatment status,and economic burden of traumatic spinal cord injury in China at the national level.We included 13,465 traumatic spinal cord injury patients who were injured between January 2013 and December 2018 and treated in 30 hospitals in 11 provinces/municipalities representing all geographical divisions of China.Patient epidemiological and clinical features,treatment status,and total and daily costs were recorded.Trends in the percentage of traumatic spinal cord injuries among all hospitalized patients and among patients hospitalized in the orthopedic department and cost of care were assessed by annual percentage change using the Joinpoint Regression Program.The percentage of traumatic spinal cord injuries among all hospitalized patients and among patients hospitalized in the orthopedic department did not significantly change overall(annual percentage change,-0.5%and 2.1%,respectively).A total of 10,053(74.7%)patients underwent surgery.Only 2.8%of patients who underwent surgery did so within 24 hours of injury.A total of 2005(14.9%)patients were treated with high-dose(≥500 mg)methylprednisolone sodium succinate/methylprednisolone(MPSS/MP);615(4.6%)received it within 8 hours.The total cost for acute traumatic spinal cord injury decreased over the study period(-4.7%),while daily cost did not significantly change(1.0%increase).Our findings indicate that public health initiatives should aim at improving hospitals’ability to complete early surgery within 24 hours,which is associated with improved sensorimotor recovery,increasing the awareness rate of clinical guidelines related to high-dose MPSS/MP to reduce the use of the treatment with insufficient evidence.
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.
