The endothelium modulates vascular homeostasis owing to a variety of vasoconstrictors and vasodilators.Endothelial dysfunction(ED),characterized by impaired vasodilation,inflammation,and thrombosis,triggers future car...The endothelium modulates vascular homeostasis owing to a variety of vasoconstrictors and vasodilators.Endothelial dysfunction(ED),characterized by impaired vasodilation,inflammation,and thrombosis,triggers future cardiovascular(CV)diseases.Chronic kidney disease,a state of chronic inflammation caused by oxidative stress,metabolic abnormalities,infection,and uremic toxins damages the endothelium.ED is also associated with a decline in estimated glomerular filtration rate.After kidney transplantation,endothelial functions undergo immediate but partial restoration,promising graft longevity and enhanced CV health.However,the anticipated CV outcomes do not happen due to various transplant-related and unrelated risk factors for ED,culminating in poor CV health and graft survival.ED in kidney transplant recipients is an underrecognized and poorly studied entity.CV diseases are the leading cause of death among kidney transplant candidates with functioning grafts.ED contributes to the pathogenesis of many of the CV diseases.Various biomarkers and vasoreactivity tests are available to study endothelial functions.With an increasing number of transplants happening every year,and improved graft rejection rates due to the availability of effective immunosuppressants,the focus has now shifted to endothelial protection for the prevention,early recognition,and treatment of CV diseases.展开更多
Stroke,as a highly prevalent cerebrovascular disease,often leads to limb dysfunction in patients,severely affecting their quality of life.Seeking effective rehabilitation nursing methods is of great significance for p...Stroke,as a highly prevalent cerebrovascular disease,often leads to limb dysfunction in patients,severely affecting their quality of life.Seeking effective rehabilitation nursing methods is of great significance for patient recovery.This article deeply analyzes various aspects such as intelligent rehabilitation technology,traditional Chinese medical therapies,Western medical therapies,and rehabilitation training methods.It explores the characteristics,effectiveness,and application prospects of various rehabilitation nursing approaches,providing a reference for clinical rehabilitation nursing of limb dysfunction after stroke,and helping to improve the quality of patient recovery and enhance their self-care ability and quality of life.展开更多
BACKGROUND The development of slow transit constipation(STC)is associated with intestinal barrier damage.Huangqi decoction(HQD)is effective in treating STC,but me-chanisms are unclear.AIM To investigate whether HQD al...BACKGROUND The development of slow transit constipation(STC)is associated with intestinal barrier damage.Huangqi decoction(HQD)is effective in treating STC,but me-chanisms are unclear.AIM To investigate whether HQD alleviates STC by downregulating the nuclear factorκB(NF-κB)signaling pathway and restoring intestinal barrier function.METHODS KM mice were divided into control,model,and HQD treatment groups.Fresh colonic tissues were collected for single-cell RNA sequencing and spatial tra-nscriptome sequencing.The expressions of claudin-1,mucin 2,and NF-κB P65 proteins were detected by immunohistochemistry.In vitro experiments evaluated the effects of HQD on the LS174T cell line.RESULTS HQD improved intestinal motility,restored mucosal epithelium function and morphology.Single-cell RNA sequencing and spatial transcriptome sequencing data showed a reduction in goblet cells,decreased mucin 2 secretion,and activated apoptotic pathways in STC mice.The population of intestinal stem cells was reduced,and proliferation along with Wnt/β-catenin pathways were inhibited.STC also altered the distribution of intestinal cell states,increasing immune-associated Enterocyte_C3.Aberrant NF-κB pathway activation was noted across various cell types.After HQD treatment,NF-κB pathway activity was down-regulated,while cell proliferation pathways were up-regulated,alongside an increase in Enterocyte_C1 related to material transport.Immunocytochemical,Western blot,and immunohistochemistry analyses confirmed NF-κB pathway activation in goblet cells of STC mice,with HQD inhibiting this aberrant activation.CONCLUSION STC involves intestinal mucosal barrier damage.HQD may treat STC by suppressing NF-κB signaling in epithelial cells,restoring intestinal epithelial cell function,and promoting mucosal barrier repair.展开更多
With an increase in global aging,the number of people affected by cerebrovascular diseases is also increasing,and the incidence of vascular dementia-closely related to cerebrovascular risk-is increasing at an epidemic...With an increase in global aging,the number of people affected by cerebrovascular diseases is also increasing,and the incidence of vascular dementia-closely related to cerebrovascular risk-is increasing at an epidemic rate.However,few therapeutic options exist that can markedly improve the cognitive impairment and prognosis of vascular dementia patients.Similarly in Alzheimer’s disease and other neurological disorders,synaptic dysfunction is recognized as the main reason for cognitive decline.Nitric oxide is one of the ubiquitous gaseous cellular messengers involved in multiple physiological and pathological processes of the central nervous system.Recently,nitric oxide has been implicated in regulating synaptic plasticity and plays an important role in the pathogenesis of vascular dementia.This review introduces in detail the emerging role of nitric oxide in physiological and pathological states of vascular dementia and summarizes the diverse effects of nitric oxide on different aspects of synaptic dysfunction,neuroinflammation,oxidative stress,and blood-brain barrier dysfunction that underlie the progress of vascular dementia.Additionally,we propose that targeting the nitric oxide-sGC-cGMP pathway using certain specific approaches may provide a novel therapeutic strategy for vascular dementia.展开更多
Several experimental evidence suggests a link between brain Herpes simplex virus type-1 infection and the occurrence of Alzheimer’s disease.However,the molecular mechanisms underlying this association are not complet...Several experimental evidence suggests a link between brain Herpes simplex virus type-1 infection and the occurrence of Alzheimer’s disease.However,the molecular mechanisms underlying this association are not completely understood.Among the molecular mediators of synaptic and cognitive dysfunction occurring after Herpes simplex virus type-1 infection and reactivation in the brain neuroinflammatory cytokines seem to occupy a central role.Here,we specifically reviewed literature reports dealing with the impact of neuroinflammation on synaptic dysfunction observed after recurrent Herpes simplex virus type-1 reactivation in the brain,highlighting the role of interleukins and,in particular,interleukin 1βas a possible target against Herpes simplex virus type-1-induced neuronal dysfunctions.展开更多
Postoperative cognitive dysfunction is a seve re complication of the central nervous system that occurs after anesthesia and surgery,and has received attention for its high incidence and effect on the quality of life ...Postoperative cognitive dysfunction is a seve re complication of the central nervous system that occurs after anesthesia and surgery,and has received attention for its high incidence and effect on the quality of life of patients.To date,there are no viable treatment options for postoperative cognitive dysfunction.The identification of postoperative cognitive dysfunction hub genes could provide new research directions and therapeutic targets for future research.To identify the signaling mechanisms contributing to postoperative cognitive dysfunction,we first conducted Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses of the Gene Expression Omnibus GSE95426 dataset,which consists of mRNAs and long non-coding RNAs differentially expressed in mouse hippocampus3 days after tibial fracture.The dataset was enriched in genes associated with the biological process"regulation of immune cells,"of which Chill was identified as a hub gene.Therefore,we investigated the contribution of chitinase-3-like protein 1 protein expression changes to postoperative cognitive dysfunction in the mouse model of tibial fractu re surgery.Mice were intraperitoneally injected with vehicle or recombinant chitinase-3-like protein 124 hours post-surgery,and the injection groups were compared with untreated control mice for learning and memory capacities using the Y-maze and fear conditioning tests.In addition,protein expression levels of proinflammatory factors(interleukin-1βand inducible nitric oxide synthase),M2-type macrophage markers(CD206 and arginase-1),and cognition-related proteins(brain-derived neurotropic factor and phosphorylated NMDA receptor subunit NR2B)were measured in hippocampus by western blotting.Treatment with recombinant chitinase-3-like protein 1 prevented surgery-induced cognitive impairment,downregulated interleukin-1βand nducible nitric oxide synthase expression,and upregulated CD206,arginase-1,pNR2B,and brain-derived neurotropic factor expression compared with vehicle treatment.Intraperitoneal administration of the specific ERK inhibitor PD98059 diminished the effects of recombinant chitinase-3-like protein 1.Collectively,our findings suggest that recombinant chitinase-3-like protein 1 ameliorates surgery-induced cognitive decline by attenuating neuroinflammation via M2 microglial polarization in the hippocampus.Therefore,recombinant chitinase-3-like protein1 may have therapeutic potential fo r postoperative cognitive dysfunction.展开更多
Recent work suggests a link betweenα-synuclein(α-syn)and mitochondrial dysfunction;however,the mechanisms of howα-syn influences mitochondrial function are still unclear.Most notably,whetherα-syn plays a direct ro...Recent work suggests a link betweenα-synuclein(α-syn)and mitochondrial dysfunction;however,the mechanisms of howα-syn influences mitochondrial function are still unclear.Most notably,whetherα-syn plays a direct role during mitochondrial function and/or whether diseasedα-syn-mediated mitochondrial dysfunction is a potential modifiable risk factor in Parkinson’s disease(PD)is unknown.To date,mutations in more than eight genes cause familial PD(fPD)and have functions in diverse pathways including synaptic homeostasis,mitochondria maintenance,autophagy/lysosome,and ubiquitin-proteasome pathways.展开更多
Alzheimer’s disease(AD)stands out as the primary manifestation of age-related dementia,portraying a chronic neurodegenerative disorder distinguished by the accumulation of fibrillar amyloid-β(Aβ)plaques and neurofi...Alzheimer’s disease(AD)stands out as the primary manifestation of age-related dementia,portraying a chronic neurodegenerative disorder distinguished by the accumulation of fibrillar amyloid-β(Aβ)plaques and neurofibrillary tangles of hyperphosphorylated tau.However,from a clinical standpoint,AD presents itself as a complex condition with a spectrum of dysfunctions rather than a singular pathological mechanism.An often-overlooked aspect of the disease is the presence of extensive cerebrovascular abnormalities,given that the majority of AD patients experience altered cerebral blood flow,damaged vasculature,increased microinfarcts and microhemorrhages.Animal models of AD further support this observation,showing cerebrovascular dysfunction such as impaired cerebral blood flow and altered cerebrovascular reactivity(Tataryn et al.,2021;Gareau et al.,2023).展开更多
Alzheimer’s disease(AD)is the most common cause of dementia,characterized by progressive cognitive decline,and affects over 55 million people worldwide.AD is pathological featured by the aberrant accumulation of amyl...Alzheimer’s disease(AD)is the most common cause of dementia,characterized by progressive cognitive decline,and affects over 55 million people worldwide.AD is pathological featured by the aberrant accumulation of amyloid-βplaques,neurofibrillary tangles formed by hyperphosphorylated tau,synaptic loss,and dysfunction of neurotransmitter systems.Evidence from in vivo and autopsy studies has consistently shown that synaptic dysfunction and loss are strongly correlated with cognitive decline in AD,particularly in brain regions such as the hippocampus and cortex,which are critical for memory formation and processing.This perspective highlights recent histopathological findings related to synaptic dysfunction in AD,advancements in the development of imaging and fluid-based biomarkers for synaptic loss,and future studies.展开更多
The increasing longevity of patients with transfusion-dependent homozygous beta-thalassemia has brought endocrine complications to the forefront of longterm care.While iron overload remains a central mechanism,additio...The increasing longevity of patients with transfusion-dependent homozygous beta-thalassemia has brought endocrine complications to the forefront of longterm care.While iron overload remains a central mechanism,additional contributors such as hypothalamic dysfunction,neurosecretory disturbances,and chronic inflammation have been identified.Endocrine disorders including hypothyroidism,adrenal insufficiency,hypogonadotropic hypogonadism,hypoparathyroidism,osteoporosis,and growth axis impairment-are prevalent and often underdiagnosed.Diagnostic challenges include normal hormone levels in early stages,necessitating the use of dynamic endocrine testing and pituitary magnetic resonance imaging to detect subclinical dysfunction.Risk is modulated by sex,age,and chelation adherence.Early identification and proactive,multidisciplinary management of endocrine sequelae are essential in reducing morbidity and maintaining functional independence in this aging patient population.展开更多
BACKGROUND End-stage renal disease(ESRD)is associated with a multitude of physical,psychological,and social health challenges,including a profound impact on sexual and reproductive health.Among males with ESRD,erectil...BACKGROUND End-stage renal disease(ESRD)is associated with a multitude of physical,psychological,and social health challenges,including a profound impact on sexual and reproductive health.Among males with ESRD,erectile dysfunction(ED)is highly prevalent due to factors such as underlying comorbidities,including diabetes and hypertension,and the physiological effects of long-term dialysis.Kidney transplantation(KTx)has been proposed as a potential intervention to mitigate the effects of ED by restoring renal function and improving hormonal balance.However,the evidence surrounding the effectiveness of KTx in improving sexual function,specifically erectile function(EF),remains inconclusive.This systematic review and meta-analysis aim to evaluate the effects of KTx on sexual dysfunction(SexDys),particularly ED,in male ESRD patients.AIM To evaluate the benefits and potential harms of KTx compared to other forms of renal replacement therapy in improving EF in adult males with ESRD,assessed using the international index of EF(IIEF),to survey the prevalence of SexDys in this population,and to assess the correlation between various factors and SexDys through regression analysis.METHODS A systematic search of PubMed,EMBASE,Cochrane Library,Scopus,Clinical-Trials.gov,and Google Scholar was conducted,following the PRISMA 2020 guidelines.Prospective and retrospective cohort studies,as well as cross-sectional studies assessing EF pre-and post-transplantation,were included.These studies used validated tools such as the IIEF to measure EF.Meta-analyses were performed using a random-effects model to estimate standardized mean differences(SMD)and hazard ratios(HR)with 95%confidence intervals(CI).Heterogeneity was assessed using the I²statistic,and publication bias was evaluated with a funnel plot and the Egger’s test.RESULTS A total of 2419 studies were identified,with 362 abstracts screened and 193 full-text articles reviewed.Ultimately,11 studies were included for qualitative analysis and 7 for quantitative synthesis.The random effects model for SMD yielded a combined estimate of 0.43(95%CI:-0.20-1.07),indicating a small but non-significant improvement in EF post-transplantation.The heterogeneity across studies was substantial(I²=90%),reflecting significant variability in outcomes.Subgroup analysis showed greater improvements in EF among living-donor transplant recipients compared to those receiving organs from deceased donors.Despite this trend,the overall result for changes in EF was not statistically significant(P=0.15).Additionally,the combined HR from the meta-analysis was 2.87(95%CI:1.76-4.69),suggesting that KTx significantly increases the likelihood of improved EF,though variability between studies persisted(I²=63%).CONCLUSION While KTx offers some promise for improving EF in male ESRD patients,the overall evidence remains inconclusive due to high heterogeneity between studies and a lack of statistical significance in the combined results.Despite this,individual studies suggest that KTx may lead to significant improvements in EF for certain subgroups,particularly living-donor recipients.Future research should focus on larger,well-designed cohort studies with standardized outcome measures to provide more definitive conclusions.Addressing SexDys as part of routine care for ESRD patients undergoing KTx is crucial to improving their overall quality of life.However,adjunct therapies such as phosphodiesterase type 5 inhibitors may be necessary for those who do not experience adequate improvements post-transplantation.展开更多
This article discusses a recent study by Wang et al that sheds light on the metabolic and immunological mechanisms driving the progression of metabolic dysfunction-associated fatty liver disease(MAFLD)to hepatocellula...This article discusses a recent study by Wang et al that sheds light on the metabolic and immunological mechanisms driving the progression of metabolic dysfunction-associated fatty liver disease(MAFLD)to hepatocellular carcinoma(HCC).The study highlights the role of mitochondrial carnitine palmitoyltransferase Ⅱ(CPT Ⅱ)inactivity,which activates liver cancer stem cells marked by cluster of differentiation 44(CD44)and CD24 expression,promoting HCC development.Using dynamic mouse models and clinical samples,Wang et al identified CPT Ⅱ downregulation,mitochondrial membrane potential alterations,and reduced intrahepatic CD4^(+)T cell as key drivers of disease progression.The findings link these changes to steroid biosynthesis and p53 signaling,contributing to T-cell dysfunction and immunosuppression.This article emphasizes the relevance of these results in understanding MAFLD pathogenesis and discusses potential therapeutic strategies targeting CPT Ⅱ activity,mitochondrial function,and immune surveillance to prevent or mitigate HCC development in advanced MAFLD.展开更多
BACKGROUND The prevalence of diabetes and its association with microcirculatory dysfunction presents a significant challenge in contemporary global health.Addressing this nexus is crucial for developing targeted thera...BACKGROUND The prevalence of diabetes and its association with microcirculatory dysfunction presents a significant challenge in contemporary global health.Addressing this nexus is crucial for developing targeted therapeutic interventions.AIM To trace the progression and delineate the current state of interdisciplinary research concerning diabetes and microcirculation.METHODS Employing a bibliometric approach,this study scrutinizes 12886 peer-reviewed publications retrieved from the PubMed and Web of Science databases.The focus is on elucidating the research trajectory and thematic concentrations at the confluence of diabetes and microcirculation.RESULTS Research outputs have surged since 2011,with the United States,China,and the United Kingdom leading in the quantity and quality of publications.This analysis revealed that journals such as Diabetes Care and The New England Journal of Medicine,along with top research institutions,have significantly contributed to advancing the understanding of microvascular processes affected by diabetes.The central themes identified include inflammation,oxidative stress,and endothelial dysfunction,which are critical in mediating the microvascular complications of diabetes.CONCLUSION This bibliometric evaluation reveals an evolving landscape focusing on diabetes and microcirculatory dysfunction.The complexity of diabetic microvascular issues encouraged multidisciplinary research strategies that are imperative for global health outcomes.展开更多
BACKGROUND Liver cirrhosis is a progressive disease with high morbidity and mortality requiring effective management strategies to improve patient outcomes.Various therapies including albumin infusion,volume expanders...BACKGROUND Liver cirrhosis is a progressive disease with high morbidity and mortality requiring effective management strategies to improve patient outcomes.Various therapies including albumin infusion,volume expanders(VEs),and vasoactive agents are used to manage patients with cirrhosis.Despite numerous clinical trials,a comprehensive meta-analysis comparing the effectiveness of albumin infusion against alternative treatments is limited.This study provides the current and comprehensive synthesis of evidence,offering key insights for optimizing therapeutic strategies in patients with liver cirrhosis.AIM To systematically update available data on therapies of liver cirrhosis,we performed a meta-analysis to evaluate and compare the clinical efficacy of albumin infusion vs other VEs and vasoactive agents in patients with liver cirrhosis.METHODS A literature search from the PubMed and Embase databases(inception till June 2024)focused on hyponatremia(primary outcome)and various outcomes such as gastrointestinal bleeding,hepatic encephalopathy,severe infection,post-paracentesis-induced circulatory dysfunction(PICD),ascites reappearance,spontaneous bacterial peritonitis,hepatorenal syndrome,renal impairment,hospital stay,mortality,and safety was performed.The primary analysis pooled studies that compared albumin infusion with control.In the subgroup analysis,comparisons were made within the stratified treatment categories included in the control group.RESULTS Of the 2957 studies retrieved,31 studies(27 randomized controlled trials and 4 observational studies)comprising 6255 patients were included.Albumin use was significant in reducing odds of hyponatremia[odds ratio(OR)=0.67;95%confidence interval(95%CI)=0.53-0.85]and PICD(OR=0.38;95%CI=0.20-0.71),whereas the reduction in severe infection(OR=0.55;95%CI=0.28-1.07)did not reach statistical significance.In the subgroup analysis,albumin demonstrated a favorable improvement in lowering the incidence of hyponatremia vs inactive/standard medical therapy(OR=0.54;95%CI=0.27-1.09).For PICD,albumin use was significant compared with other VEs(OR=0.31;95%CI=0.11-0.85)but not with vasoconstrictors(OR=0.63;95%CI=0.21-1.91).In the overall subgroup analysis,a significant reduction was observed in hyponatremia(OR=0.67;95%CI=0.53-0.85)and PICD(OR=0.38;95%CI=0.20-0.71).CONCLUSION Human albumin has been shown to significantly reduce the incidence of hyponatremia and PICD in patients with liver cirrhosis,whereas its effect on severe infection remains suggestive but not statistically significant.展开更多
BACKGROUND Colorectal cancer(CRC)is one of the most prevalent and lethal malignant tumors worldwide.Currently,surgical intervention was the primary treatment modality for CRC.However,increasing studies have revealed t...BACKGROUND Colorectal cancer(CRC)is one of the most prevalent and lethal malignant tumors worldwide.Currently,surgical intervention was the primary treatment modality for CRC.However,increasing studies have revealed that CRC patients may experience postoperative cognitive dysfunction(POCD).AIM To establish a risk prediction model for POCD in CRC patients and investigate the preventive value of dexmedetomidine(DEX).METHODS A retrospective analysis was conducted on clinical data from 140 CRC patients who underwent surgery at the People’s Hospital of Qian Nan from February 2020 to May 2024.Patients were allocated into a modeling group(n=98)and a validation group(n=42)in a 7:3 ratio.General clinical data were collected.Additionally,in the modeling group,patients who received DEX preoperatively were incorporated into the observation group(n=54),while those who did not were placed in the control group(n=44).The incidence of POCD was recorded for both cohorts.Data analysis was performed using statistical product and service solutions 20.0,with t-tests orχ^(2) tests employed for group comparisons based on the data type.Least absolute shrinkage and selection operator regression was applied to identify influencing factors and reduce the impact of multicollinear predictors among variables.Multivariate analysis was carried out using Logistic regression.Based on the identified risk factors,a risk prediction model for POCD in CRC patients was developed,and the predictive value of these risk factors was evaluated.RESULTS Significant differences were observed between the cognitive dysfunction group and the non-cognitive dysfunction group in diabetes status,alcohol consumption,years of education,anesthesia duration,intraoperative blood loss,intraoperative hypoxemia,use of DEX during surgery,intraoperative use of vasoactive drugs,surgical time,systemic inflammatory response syndrome(SIRS)score(P<0.05).Multivariate Logistic regression analysis identified that diabetes[odds ratio(OR)=4.679,95%confidence interval(CI)=1.382-15.833],alcohol consumption(OR=5.058,95%CI:1.255-20.380),intraoperative hypoxemia(OR=4.697,95%CI:1.380-15.991),no use of DEX during surgery(OR=3.931,95%CI:1.383-11.175),surgery duration≥90 minutes(OR=4.894,95%CI:1.377-17.394),and a SIRS score≥3(OR=4.133,95%CI:1.323-12.907)were independent risk factors for POCD in CRC patients(P<0.05).A risk prediction model for POCD was constructed using diabetes,alcohol consumption,intraoperative hypoxemia,non-use of DEX during surgery,surgery duration,and SIRS score as factors.A receiver operator characteristic curve analysis of these factors revealed the model’s predictive sensitivity(88.56%),specificity(70.64%),and area under the curve(AUC)(AUC=0.852,95%CI:0.773-0.919).The model was validated using 42 CRC patients who met the inclusion criteria,demonstrating sensitivity(80.77%),specificity(81.25%),and accuracy(80.95%),and AUC(0.805)in diagnosing cognitive impairment,with a 95%CI:0.635-0.896.CONCLUSION Logistic regression analysis identified that diabetes,alcohol consumption,intraoperative hypoxemia,non-use of DEX during surgery,surgery duration,and SIRS score vigorously influenced the occurrence of POCD.The risk prediction model based on these factors demonstrated good predictive performance for POCD in CRC individuals.This study offers valuable insights for clinical practice and contributes to the prevention and management of POCD under CRC circumstances.展开更多
Deuterium is a heavy isotope of hydrogen,with an extra neutron,endowing it with unique biophysical and biochemical properties compared to hydrogen.The ATPase pumps in the mitochondria depend upon proton motive force t...Deuterium is a heavy isotope of hydrogen,with an extra neutron,endowing it with unique biophysical and biochemical properties compared to hydrogen.The ATPase pumps in the mitochondria depend upon proton motive force to catalyze the reaction that produces ATP.Deuterons disrupt the pumps,inducing excessive reactive oxygen species and decreased ATP synthesis.The aim of this review is to develop a theory that mitochondrial dysfunction due to deuterium overload,systemically,is a primary cause of Parkinson’s disease(PD).The gut microbes supply deuterium-depleted short chain fatty acids(SCFAs)to the colonocytes,particularly butyrate,and an insufficient supply of butyrate may be a primary driver behind mitochondrial dysfunction in the gut,an early factor in PD.Indeed,low gut butyrate is a characteristic feature of PD.Mitochondrial dysfunction is a factor in many diseases,including all neurodegenerative diseases.Biological organisms have devised sophisticated strategies for protecting the ATPase pumps from deuterium overload.One such strategy may involve capturing deuterons in bis-allylic carbon atoms present in polyunsaturated fatty acids(PUFAs)in cardiolipin.Cardiolipin uniquely localizes to the inner membrane of the intermembrane space,tightly integrated into ATPase proteins.Bis-allylic carbon atoms can capture and retain deuterium,and,interestingly,deuterium doping in PUFAs can quench the chain reaction that causes massive damage upon lipid peroxidation.Neuronal cardiolipin is especially rich in docosahexaenoic acid(DHA),a PUFA with five bisallylic carbon atoms.Upon excessive oxidative stress,cardiolipin migrates to the outer membrane,where it interacts withα-synuclein(α-syn),the amyloidogenic protein that accumulates as fibrils in Lewy bodies in association with PD.Such interaction leads to pore formation and the launch of an apoptotic cascade.α-syn misfolding likely begins in the gut,and misfoldedα-syn travels along nerve fibers,particularly the vagus nerve,to reach the brainstem nuclei,where it can seed misfolding ofα-syn molecules already present there.Mitochondrial dysfunction in the gut may be a primary factor in PD,and low-deuterium nutrients may be therapeutic.展开更多
Mitochondrial dysfunction and oxidative stress are widely regarded as primary drivers of aging and are associated with several neurodegenerative diseases.The degeneration of motor neurons during aging is a critical pa...Mitochondrial dysfunction and oxidative stress are widely regarded as primary drivers of aging and are associated with several neurodegenerative diseases.The degeneration of motor neurons during aging is a critical pathological factor contributing to the progression of sarcopenia.However,the morphological and functional changes in mitochondria and their interplay in the degeneration of the neuromuscular junction during aging remain poorly understood.A defined systematic search of the Pub Med,Web of Science and Embase databases(last accessed on October 30,2024)was conducted with search terms including'mitochondria','aging'and'NMJ'.Clinical and preclinical studies of mitochondrial dysfunction and neuromuscular junction degeneration during aging.Twentyseven studies were included in this systematic review.This systematic review provides a summary of morphological,functional and biological changes in neuromuscular junction,mitochondrial morphology,biosynthesis,respiratory chain function,and mitophagy during aging.We focus on the interactions and mechanisms underlying the relationship between mitochondria and neuromuscular junctions during aging.Aging is characterized by significant reductions in mitochondrial fusion/fission cycles,biosynthesis,and mitochondrial quality control,which may lead to neuromuscular junction dysfunction,denervation and poor physical performance.Motor nerve terminals that exhibit redox sensitivity are among the first to exhibit abnormalities,ultimately leading to an early decline in muscle strength through impaired neuromuscular junction transmission function.Parg coactivator 1 alpha is a crucial molecule that regulates mitochondrial biogenesis and modulates various pathways,including the mitochondrial respiratory chain,energy deficiency,oxidative stress,and inflammation.Mitochondrial dysfunction is correlated with neuromuscular junction denervation and acetylcholine receptor fragmentation,resulting in muscle atrophy and a decrease in strength during aging.Physical therapy,pharmacotherapy,and gene therapy can alleviate the structural degeneration and functional deterioration of neuromuscular junction by restoring mitochondrial function.Therefore,mitochondria are considered potential targets for preserving neuromuscular junction morphology and function during aging to treat sarcopenia.展开更多
In most types of erectile dysfunction,particularly in advanced stages,typical pathological features observed are reduced parenchymal cells coupled with increased tissue fibrosis.However,the current treatment methods h...In most types of erectile dysfunction,particularly in advanced stages,typical pathological features observed are reduced parenchymal cells coupled with increased tissue fibrosis.However,the current treatment methods have shown limited success in reversing these pathologic changes.Recent research has revealed that changes in autophagy levels,along with alterations in apoptosis and fibrosis-related proteins,are linked to the progression of erectile dysfunction,suggesting a significant association.Autophagy,known to significantly affect cell fate and tissue fibrosis,is currently being explored as a potential treatment modality for erectile dysfunction.However,these present studies are still in their nascent stage,and there are limited experimental data available.This review analyzes erectile dysfunction from a pathological perspective.It provides an in-depth overview of how autophagy is involved in the apoptotic processes of smooth muscle and endothelial cells and its role in the fibrotic processes occurring in the cavernosum.This study aimed to develop a theoretical framework for the potential effectiveness of autophagy in preventing and treating erectile dysfunction,thus encouraging further investigation among researchers in this area.展开更多
BACKGROUND To investigate whether seasonal differences in ambient temperature affect the incidence of early postoperative cognitive dysfunction(POCD)among elderly patients undergoing laparoscopic surgery in tropical r...BACKGROUND To investigate whether seasonal differences in ambient temperature affect the incidence of early postoperative cognitive dysfunction(POCD)among elderly patients undergoing laparoscopic surgery in tropical regions.Additionally,it explored the perioperative risk factors associated with early POCD following abdominal laparoscopic surgery.AIM To investigate the influence of seasonal differences in ambient temperature on POCD of elderly patients METHODS A total of 125 patients aged≥65 years from Hainan Province,China,who underwent laparoscopic surgery under general anesthesia with tracheal intubation,were enrolled. All patients completed the Mini-Mental State Examination one day before surgery and onpostoperative days 1, 3, and 7. A decline of ≥ 2 points from baseline was considered indicative of cognitivedysfunction. Serum levels of S100 calcium binding protein B and neuron-specific enolase were measured usingenzyme-linked immunosorbent assay at three time points: Preoperatively, immediately after extubation, and 24hours postoperatively. Perioperative clinical data were collected to identify potential risk factors for POCD.Propensity score matching (PSM) was performed (1:1, caliper = 0.03), resulting in 41 matched patient pairs betweenwinter and summer groups.RESULTSAfter PSM, baseline characteristics including age, gender, body mass index, education level, comorbidities, andsurgical variables were well balanced between groups. There were no significant differences in the incidence ofPOCD on postoperative days 1, 3, and 7 between patients undergoing laparoscopic surgery in winter vs summer.However, multivariable logistic regression revealed that surgical duration (day 1, P value = 0.049), advanced ageand elevated creatinine (day 3, P value = 0.044, P value = 0.008), and hypoalbuminemia (day 3, P value = 0.042;day7, P value = 0.015) were independently associated with early POCD.CONCLUSIONAmbient temperature differences between winter and summer in tropical regions did not significantly affect theincidence of early POCD in elderly patients undergoing laparoscopic surgery. Nonetheless, age, longer surgicalduration, elevated creatinine, and hypoalbuminemia emerged as key risk factors. These findings underscore theimportance of perioperative optimization to reduce the risk of POCD in elderly patients, regardless of seasonaltemperature variations.展开更多
Endocrine disorders frequently lead to metabolic disturbances that significantly affect liver function.Understanding the complex interplay between hormonal imbalances and liver dysfunction is essential for advancing t...Endocrine disorders frequently lead to metabolic disturbances that significantly affect liver function.Understanding the complex interplay between hormonal imbalances and liver dysfunction is essential for advancing targeted therapeutic strategies.This comprehensive review explores the pathophysiological mechanisms linking major endocrine disorders to liver disease,with a focus on the roles of the thyroid,parathyroid,pancreas,adrenal glands,and sex hormones.Thyroid dysfunction is associated with alterations in liver enzyme levels and metabolic regulation,often resulting in hepatic steatosis or cholestasis.Hyperparathyroidism and consequent hypercalcemia have been linked to hepatic calcifications.Insulin resistance,both hepatic and peripheral,contributes to excessive lipid accumulation in the liver,exacerbating steatotic changes.Adrenal gland disorders,particularly in the setting of chronic liver disease,impair cortisol metabolism and may worsen hepatic injury.Additionally,sex hormones such as estrogen and testosterone modulate the progression of liver fibrosis and influence the development of metabolic syndrome.The intricate relationship between endocrine and hepatic systems underscores the need for a multidisciplinary approach in the management of liver disease.Addressing underlying hormonal disturbances may enhance patient outcomes and prevent further hepatic deterioration.Future research should prioritize integrative therapeutic strategies that concurrently target endocrine and liver dysfunction.展开更多
文摘The endothelium modulates vascular homeostasis owing to a variety of vasoconstrictors and vasodilators.Endothelial dysfunction(ED),characterized by impaired vasodilation,inflammation,and thrombosis,triggers future cardiovascular(CV)diseases.Chronic kidney disease,a state of chronic inflammation caused by oxidative stress,metabolic abnormalities,infection,and uremic toxins damages the endothelium.ED is also associated with a decline in estimated glomerular filtration rate.After kidney transplantation,endothelial functions undergo immediate but partial restoration,promising graft longevity and enhanced CV health.However,the anticipated CV outcomes do not happen due to various transplant-related and unrelated risk factors for ED,culminating in poor CV health and graft survival.ED in kidney transplant recipients is an underrecognized and poorly studied entity.CV diseases are the leading cause of death among kidney transplant candidates with functioning grafts.ED contributes to the pathogenesis of many of the CV diseases.Various biomarkers and vasoreactivity tests are available to study endothelial functions.With an increasing number of transplants happening every year,and improved graft rejection rates due to the availability of effective immunosuppressants,the focus has now shifted to endothelial protection for the prevention,early recognition,and treatment of CV diseases.
文摘Stroke,as a highly prevalent cerebrovascular disease,often leads to limb dysfunction in patients,severely affecting their quality of life.Seeking effective rehabilitation nursing methods is of great significance for patient recovery.This article deeply analyzes various aspects such as intelligent rehabilitation technology,traditional Chinese medical therapies,Western medical therapies,and rehabilitation training methods.It explores the characteristics,effectiveness,and application prospects of various rehabilitation nursing approaches,providing a reference for clinical rehabilitation nursing of limb dysfunction after stroke,and helping to improve the quality of patient recovery and enhance their self-care ability and quality of life.
基金Supported by the Natural Science Foundation of Guangdong Province for Distinguished Young Scholars,No.2022B1515020003the National Natural Science Foundation of China,No.82174369,No.82405397,No.82374442,and No.81973847+2 种基金Postdoctoral Fellowship Program of CPSF No.GZC20233247National Key Clinical Disciplineand the Program of Guangdong Provincial Clinical Research Center for Digestive Diseases,No.2020B1111170004.
文摘BACKGROUND The development of slow transit constipation(STC)is associated with intestinal barrier damage.Huangqi decoction(HQD)is effective in treating STC,but me-chanisms are unclear.AIM To investigate whether HQD alleviates STC by downregulating the nuclear factorκB(NF-κB)signaling pathway and restoring intestinal barrier function.METHODS KM mice were divided into control,model,and HQD treatment groups.Fresh colonic tissues were collected for single-cell RNA sequencing and spatial tra-nscriptome sequencing.The expressions of claudin-1,mucin 2,and NF-κB P65 proteins were detected by immunohistochemistry.In vitro experiments evaluated the effects of HQD on the LS174T cell line.RESULTS HQD improved intestinal motility,restored mucosal epithelium function and morphology.Single-cell RNA sequencing and spatial transcriptome sequencing data showed a reduction in goblet cells,decreased mucin 2 secretion,and activated apoptotic pathways in STC mice.The population of intestinal stem cells was reduced,and proliferation along with Wnt/β-catenin pathways were inhibited.STC also altered the distribution of intestinal cell states,increasing immune-associated Enterocyte_C3.Aberrant NF-κB pathway activation was noted across various cell types.After HQD treatment,NF-κB pathway activity was down-regulated,while cell proliferation pathways were up-regulated,alongside an increase in Enterocyte_C1 related to material transport.Immunocytochemical,Western blot,and immunohistochemistry analyses confirmed NF-κB pathway activation in goblet cells of STC mice,with HQD inhibiting this aberrant activation.CONCLUSION STC involves intestinal mucosal barrier damage.HQD may treat STC by suppressing NF-κB signaling in epithelial cells,restoring intestinal epithelial cell function,and promoting mucosal barrier repair.
基金supported by the National Key R&D Program of China,No.2019YFE0121200(to LQZ)the National Natural Science Foundation of China,Nos.82325017(to LQZ),82030032(to LQZ),82261138555(to DL)+2 种基金the Natural Science Foundation of Hubei Province,No.2022CFA004(to LQZ)the Natural Science Foundation of Jiangxi Province,No.20224BAB206040(to XZ)Research Project of Cognitive Science and Transdisciplinary Studies Center of Jiangxi Province,No.RZYB202201(to XZ).
文摘With an increase in global aging,the number of people affected by cerebrovascular diseases is also increasing,and the incidence of vascular dementia-closely related to cerebrovascular risk-is increasing at an epidemic rate.However,few therapeutic options exist that can markedly improve the cognitive impairment and prognosis of vascular dementia patients.Similarly in Alzheimer’s disease and other neurological disorders,synaptic dysfunction is recognized as the main reason for cognitive decline.Nitric oxide is one of the ubiquitous gaseous cellular messengers involved in multiple physiological and pathological processes of the central nervous system.Recently,nitric oxide has been implicated in regulating synaptic plasticity and plays an important role in the pathogenesis of vascular dementia.This review introduces in detail the emerging role of nitric oxide in physiological and pathological states of vascular dementia and summarizes the diverse effects of nitric oxide on different aspects of synaptic dysfunction,neuroinflammation,oxidative stress,and blood-brain barrier dysfunction that underlie the progress of vascular dementia.Additionally,we propose that targeting the nitric oxide-sGC-cGMP pathway using certain specific approaches may provide a novel therapeutic strategy for vascular dementia.
基金supported by UniversitàCattolica(D1 intramural funds to RP)Italian Ministry of University and Research(PRIN 2022ZYLB7B,P2022YW7BP funds to CG).
文摘Several experimental evidence suggests a link between brain Herpes simplex virus type-1 infection and the occurrence of Alzheimer’s disease.However,the molecular mechanisms underlying this association are not completely understood.Among the molecular mediators of synaptic and cognitive dysfunction occurring after Herpes simplex virus type-1 infection and reactivation in the brain neuroinflammatory cytokines seem to occupy a central role.Here,we specifically reviewed literature reports dealing with the impact of neuroinflammation on synaptic dysfunction observed after recurrent Herpes simplex virus type-1 reactivation in the brain,highlighting the role of interleukins and,in particular,interleukin 1βas a possible target against Herpes simplex virus type-1-induced neuronal dysfunctions.
基金supported by the National Natural Science Foundation of China,Nos.81730033,82171193(to XG)the Key Talent Project for Strengthening Health during the 13^(th)Five-Year Plan Period,No.ZDRCA2016069(to XG)+1 种基金the National Key R&D Program of China,No.2018YFC2001901(to XG)Jiangsu Provincial Medical Key Discipline,No.ZDXK202232(to XG)。
文摘Postoperative cognitive dysfunction is a seve re complication of the central nervous system that occurs after anesthesia and surgery,and has received attention for its high incidence and effect on the quality of life of patients.To date,there are no viable treatment options for postoperative cognitive dysfunction.The identification of postoperative cognitive dysfunction hub genes could provide new research directions and therapeutic targets for future research.To identify the signaling mechanisms contributing to postoperative cognitive dysfunction,we first conducted Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses of the Gene Expression Omnibus GSE95426 dataset,which consists of mRNAs and long non-coding RNAs differentially expressed in mouse hippocampus3 days after tibial fracture.The dataset was enriched in genes associated with the biological process"regulation of immune cells,"of which Chill was identified as a hub gene.Therefore,we investigated the contribution of chitinase-3-like protein 1 protein expression changes to postoperative cognitive dysfunction in the mouse model of tibial fractu re surgery.Mice were intraperitoneally injected with vehicle or recombinant chitinase-3-like protein 124 hours post-surgery,and the injection groups were compared with untreated control mice for learning and memory capacities using the Y-maze and fear conditioning tests.In addition,protein expression levels of proinflammatory factors(interleukin-1βand inducible nitric oxide synthase),M2-type macrophage markers(CD206 and arginase-1),and cognition-related proteins(brain-derived neurotropic factor and phosphorylated NMDA receptor subunit NR2B)were measured in hippocampus by western blotting.Treatment with recombinant chitinase-3-like protein 1 prevented surgery-induced cognitive impairment,downregulated interleukin-1βand nducible nitric oxide synthase expression,and upregulated CD206,arginase-1,pNR2B,and brain-derived neurotropic factor expression compared with vehicle treatment.Intraperitoneal administration of the specific ERK inhibitor PD98059 diminished the effects of recombinant chitinase-3-like protein 1.Collectively,our findings suggest that recombinant chitinase-3-like protein 1 ameliorates surgery-induced cognitive decline by attenuating neuroinflammation via M2 microglial polarization in the hippocampus.Therefore,recombinant chitinase-3-like protein1 may have therapeutic potential fo r postoperative cognitive dysfunction.
文摘Recent work suggests a link betweenα-synuclein(α-syn)and mitochondrial dysfunction;however,the mechanisms of howα-syn influences mitochondrial function are still unclear.Most notably,whetherα-syn plays a direct role during mitochondrial function and/or whether diseasedα-syn-mediated mitochondrial dysfunction is a potential modifiable risk factor in Parkinson’s disease(PD)is unknown.To date,mutations in more than eight genes cause familial PD(fPD)and have functions in diverse pathways including synaptic homeostasis,mitochondria maintenance,autophagy/lysosome,and ubiquitin-proteasome pathways.
基金supported by the National Institute of Health NS104386(to HJA)and AG078245(to HJA).
文摘Alzheimer’s disease(AD)stands out as the primary manifestation of age-related dementia,portraying a chronic neurodegenerative disorder distinguished by the accumulation of fibrillar amyloid-β(Aβ)plaques and neurofibrillary tangles of hyperphosphorylated tau.However,from a clinical standpoint,AD presents itself as a complex condition with a spectrum of dysfunctions rather than a singular pathological mechanism.An often-overlooked aspect of the disease is the presence of extensive cerebrovascular abnormalities,given that the majority of AD patients experience altered cerebral blood flow,damaged vasculature,increased microinfarcts and microhemorrhages.Animal models of AD further support this observation,showing cerebrovascular dysfunction such as impaired cerebral blood flow and altered cerebrovascular reactivity(Tataryn et al.,2021;Gareau et al.,2023).
基金supported by Swiss Center for Applied Human Toxicology(SCAHT AP22-01)(to RN).
文摘Alzheimer’s disease(AD)is the most common cause of dementia,characterized by progressive cognitive decline,and affects over 55 million people worldwide.AD is pathological featured by the aberrant accumulation of amyloid-βplaques,neurofibrillary tangles formed by hyperphosphorylated tau,synaptic loss,and dysfunction of neurotransmitter systems.Evidence from in vivo and autopsy studies has consistently shown that synaptic dysfunction and loss are strongly correlated with cognitive decline in AD,particularly in brain regions such as the hippocampus and cortex,which are critical for memory formation and processing.This perspective highlights recent histopathological findings related to synaptic dysfunction in AD,advancements in the development of imaging and fluid-based biomarkers for synaptic loss,and future studies.
文摘The increasing longevity of patients with transfusion-dependent homozygous beta-thalassemia has brought endocrine complications to the forefront of longterm care.While iron overload remains a central mechanism,additional contributors such as hypothalamic dysfunction,neurosecretory disturbances,and chronic inflammation have been identified.Endocrine disorders including hypothyroidism,adrenal insufficiency,hypogonadotropic hypogonadism,hypoparathyroidism,osteoporosis,and growth axis impairment-are prevalent and often underdiagnosed.Diagnostic challenges include normal hormone levels in early stages,necessitating the use of dynamic endocrine testing and pituitary magnetic resonance imaging to detect subclinical dysfunction.Risk is modulated by sex,age,and chelation adherence.Early identification and proactive,multidisciplinary management of endocrine sequelae are essential in reducing morbidity and maintaining functional independence in this aging patient population.
文摘BACKGROUND End-stage renal disease(ESRD)is associated with a multitude of physical,psychological,and social health challenges,including a profound impact on sexual and reproductive health.Among males with ESRD,erectile dysfunction(ED)is highly prevalent due to factors such as underlying comorbidities,including diabetes and hypertension,and the physiological effects of long-term dialysis.Kidney transplantation(KTx)has been proposed as a potential intervention to mitigate the effects of ED by restoring renal function and improving hormonal balance.However,the evidence surrounding the effectiveness of KTx in improving sexual function,specifically erectile function(EF),remains inconclusive.This systematic review and meta-analysis aim to evaluate the effects of KTx on sexual dysfunction(SexDys),particularly ED,in male ESRD patients.AIM To evaluate the benefits and potential harms of KTx compared to other forms of renal replacement therapy in improving EF in adult males with ESRD,assessed using the international index of EF(IIEF),to survey the prevalence of SexDys in this population,and to assess the correlation between various factors and SexDys through regression analysis.METHODS A systematic search of PubMed,EMBASE,Cochrane Library,Scopus,Clinical-Trials.gov,and Google Scholar was conducted,following the PRISMA 2020 guidelines.Prospective and retrospective cohort studies,as well as cross-sectional studies assessing EF pre-and post-transplantation,were included.These studies used validated tools such as the IIEF to measure EF.Meta-analyses were performed using a random-effects model to estimate standardized mean differences(SMD)and hazard ratios(HR)with 95%confidence intervals(CI).Heterogeneity was assessed using the I²statistic,and publication bias was evaluated with a funnel plot and the Egger’s test.RESULTS A total of 2419 studies were identified,with 362 abstracts screened and 193 full-text articles reviewed.Ultimately,11 studies were included for qualitative analysis and 7 for quantitative synthesis.The random effects model for SMD yielded a combined estimate of 0.43(95%CI:-0.20-1.07),indicating a small but non-significant improvement in EF post-transplantation.The heterogeneity across studies was substantial(I²=90%),reflecting significant variability in outcomes.Subgroup analysis showed greater improvements in EF among living-donor transplant recipients compared to those receiving organs from deceased donors.Despite this trend,the overall result for changes in EF was not statistically significant(P=0.15).Additionally,the combined HR from the meta-analysis was 2.87(95%CI:1.76-4.69),suggesting that KTx significantly increases the likelihood of improved EF,though variability between studies persisted(I²=63%).CONCLUSION While KTx offers some promise for improving EF in male ESRD patients,the overall evidence remains inconclusive due to high heterogeneity between studies and a lack of statistical significance in the combined results.Despite this,individual studies suggest that KTx may lead to significant improvements in EF for certain subgroups,particularly living-donor recipients.Future research should focus on larger,well-designed cohort studies with standardized outcome measures to provide more definitive conclusions.Addressing SexDys as part of routine care for ESRD patients undergoing KTx is crucial to improving their overall quality of life.However,adjunct therapies such as phosphodiesterase type 5 inhibitors may be necessary for those who do not experience adequate improvements post-transplantation.
文摘This article discusses a recent study by Wang et al that sheds light on the metabolic and immunological mechanisms driving the progression of metabolic dysfunction-associated fatty liver disease(MAFLD)to hepatocellular carcinoma(HCC).The study highlights the role of mitochondrial carnitine palmitoyltransferase Ⅱ(CPT Ⅱ)inactivity,which activates liver cancer stem cells marked by cluster of differentiation 44(CD44)and CD24 expression,promoting HCC development.Using dynamic mouse models and clinical samples,Wang et al identified CPT Ⅱ downregulation,mitochondrial membrane potential alterations,and reduced intrahepatic CD4^(+)T cell as key drivers of disease progression.The findings link these changes to steroid biosynthesis and p53 signaling,contributing to T-cell dysfunction and immunosuppression.This article emphasizes the relevance of these results in understanding MAFLD pathogenesis and discusses potential therapeutic strategies targeting CPT Ⅱ activity,mitochondrial function,and immune surveillance to prevent or mitigate HCC development in advanced MAFLD.
基金Beijing Municipal Natural Science Foundation,China,No.7212068National Natural Science Foundation of China,No.81900747.
文摘BACKGROUND The prevalence of diabetes and its association with microcirculatory dysfunction presents a significant challenge in contemporary global health.Addressing this nexus is crucial for developing targeted therapeutic interventions.AIM To trace the progression and delineate the current state of interdisciplinary research concerning diabetes and microcirculation.METHODS Employing a bibliometric approach,this study scrutinizes 12886 peer-reviewed publications retrieved from the PubMed and Web of Science databases.The focus is on elucidating the research trajectory and thematic concentrations at the confluence of diabetes and microcirculation.RESULTS Research outputs have surged since 2011,with the United States,China,and the United Kingdom leading in the quantity and quality of publications.This analysis revealed that journals such as Diabetes Care and The New England Journal of Medicine,along with top research institutions,have significantly contributed to advancing the understanding of microvascular processes affected by diabetes.The central themes identified include inflammation,oxidative stress,and endothelial dysfunction,which are critical in mediating the microvascular complications of diabetes.CONCLUSION This bibliometric evaluation reveals an evolving landscape focusing on diabetes and microcirculatory dysfunction.The complexity of diabetic microvascular issues encouraged multidisciplinary research strategies that are imperative for global health outcomes.
基金Supported by National Natural Science Foundation of China,No.82070604 and No.82270618the Shanghai Municipal Key Clinical Specialty,China,No.shslczdzk01103。
文摘BACKGROUND Liver cirrhosis is a progressive disease with high morbidity and mortality requiring effective management strategies to improve patient outcomes.Various therapies including albumin infusion,volume expanders(VEs),and vasoactive agents are used to manage patients with cirrhosis.Despite numerous clinical trials,a comprehensive meta-analysis comparing the effectiveness of albumin infusion against alternative treatments is limited.This study provides the current and comprehensive synthesis of evidence,offering key insights for optimizing therapeutic strategies in patients with liver cirrhosis.AIM To systematically update available data on therapies of liver cirrhosis,we performed a meta-analysis to evaluate and compare the clinical efficacy of albumin infusion vs other VEs and vasoactive agents in patients with liver cirrhosis.METHODS A literature search from the PubMed and Embase databases(inception till June 2024)focused on hyponatremia(primary outcome)and various outcomes such as gastrointestinal bleeding,hepatic encephalopathy,severe infection,post-paracentesis-induced circulatory dysfunction(PICD),ascites reappearance,spontaneous bacterial peritonitis,hepatorenal syndrome,renal impairment,hospital stay,mortality,and safety was performed.The primary analysis pooled studies that compared albumin infusion with control.In the subgroup analysis,comparisons were made within the stratified treatment categories included in the control group.RESULTS Of the 2957 studies retrieved,31 studies(27 randomized controlled trials and 4 observational studies)comprising 6255 patients were included.Albumin use was significant in reducing odds of hyponatremia[odds ratio(OR)=0.67;95%confidence interval(95%CI)=0.53-0.85]and PICD(OR=0.38;95%CI=0.20-0.71),whereas the reduction in severe infection(OR=0.55;95%CI=0.28-1.07)did not reach statistical significance.In the subgroup analysis,albumin demonstrated a favorable improvement in lowering the incidence of hyponatremia vs inactive/standard medical therapy(OR=0.54;95%CI=0.27-1.09).For PICD,albumin use was significant compared with other VEs(OR=0.31;95%CI=0.11-0.85)but not with vasoconstrictors(OR=0.63;95%CI=0.21-1.91).In the overall subgroup analysis,a significant reduction was observed in hyponatremia(OR=0.67;95%CI=0.53-0.85)and PICD(OR=0.38;95%CI=0.20-0.71).CONCLUSION Human albumin has been shown to significantly reduce the incidence of hyponatremia and PICD in patients with liver cirrhosis,whereas its effect on severe infection remains suggestive but not statistically significant.
基金Supported by the Research Fund of Qiannan Medical College for Nationalities,No.Qnyz202222.
文摘BACKGROUND Colorectal cancer(CRC)is one of the most prevalent and lethal malignant tumors worldwide.Currently,surgical intervention was the primary treatment modality for CRC.However,increasing studies have revealed that CRC patients may experience postoperative cognitive dysfunction(POCD).AIM To establish a risk prediction model for POCD in CRC patients and investigate the preventive value of dexmedetomidine(DEX).METHODS A retrospective analysis was conducted on clinical data from 140 CRC patients who underwent surgery at the People’s Hospital of Qian Nan from February 2020 to May 2024.Patients were allocated into a modeling group(n=98)and a validation group(n=42)in a 7:3 ratio.General clinical data were collected.Additionally,in the modeling group,patients who received DEX preoperatively were incorporated into the observation group(n=54),while those who did not were placed in the control group(n=44).The incidence of POCD was recorded for both cohorts.Data analysis was performed using statistical product and service solutions 20.0,with t-tests orχ^(2) tests employed for group comparisons based on the data type.Least absolute shrinkage and selection operator regression was applied to identify influencing factors and reduce the impact of multicollinear predictors among variables.Multivariate analysis was carried out using Logistic regression.Based on the identified risk factors,a risk prediction model for POCD in CRC patients was developed,and the predictive value of these risk factors was evaluated.RESULTS Significant differences were observed between the cognitive dysfunction group and the non-cognitive dysfunction group in diabetes status,alcohol consumption,years of education,anesthesia duration,intraoperative blood loss,intraoperative hypoxemia,use of DEX during surgery,intraoperative use of vasoactive drugs,surgical time,systemic inflammatory response syndrome(SIRS)score(P<0.05).Multivariate Logistic regression analysis identified that diabetes[odds ratio(OR)=4.679,95%confidence interval(CI)=1.382-15.833],alcohol consumption(OR=5.058,95%CI:1.255-20.380),intraoperative hypoxemia(OR=4.697,95%CI:1.380-15.991),no use of DEX during surgery(OR=3.931,95%CI:1.383-11.175),surgery duration≥90 minutes(OR=4.894,95%CI:1.377-17.394),and a SIRS score≥3(OR=4.133,95%CI:1.323-12.907)were independent risk factors for POCD in CRC patients(P<0.05).A risk prediction model for POCD was constructed using diabetes,alcohol consumption,intraoperative hypoxemia,non-use of DEX during surgery,surgery duration,and SIRS score as factors.A receiver operator characteristic curve analysis of these factors revealed the model’s predictive sensitivity(88.56%),specificity(70.64%),and area under the curve(AUC)(AUC=0.852,95%CI:0.773-0.919).The model was validated using 42 CRC patients who met the inclusion criteria,demonstrating sensitivity(80.77%),specificity(81.25%),and accuracy(80.95%),and AUC(0.805)in diagnosing cognitive impairment,with a 95%CI:0.635-0.896.CONCLUSION Logistic regression analysis identified that diabetes,alcohol consumption,intraoperative hypoxemia,non-use of DEX during surgery,surgery duration,and SIRS score vigorously influenced the occurrence of POCD.The risk prediction model based on these factors demonstrated good predictive performance for POCD in CRC individuals.This study offers valuable insights for clinical practice and contributes to the prevention and management of POCD under CRC circumstances.
基金funded in part by Quanta Computer,Inc.,in Tanyuan,Taiwan,under contract number 6950759,as part of the AIR project.
文摘Deuterium is a heavy isotope of hydrogen,with an extra neutron,endowing it with unique biophysical and biochemical properties compared to hydrogen.The ATPase pumps in the mitochondria depend upon proton motive force to catalyze the reaction that produces ATP.Deuterons disrupt the pumps,inducing excessive reactive oxygen species and decreased ATP synthesis.The aim of this review is to develop a theory that mitochondrial dysfunction due to deuterium overload,systemically,is a primary cause of Parkinson’s disease(PD).The gut microbes supply deuterium-depleted short chain fatty acids(SCFAs)to the colonocytes,particularly butyrate,and an insufficient supply of butyrate may be a primary driver behind mitochondrial dysfunction in the gut,an early factor in PD.Indeed,low gut butyrate is a characteristic feature of PD.Mitochondrial dysfunction is a factor in many diseases,including all neurodegenerative diseases.Biological organisms have devised sophisticated strategies for protecting the ATPase pumps from deuterium overload.One such strategy may involve capturing deuterons in bis-allylic carbon atoms present in polyunsaturated fatty acids(PUFAs)in cardiolipin.Cardiolipin uniquely localizes to the inner membrane of the intermembrane space,tightly integrated into ATPase proteins.Bis-allylic carbon atoms can capture and retain deuterium,and,interestingly,deuterium doping in PUFAs can quench the chain reaction that causes massive damage upon lipid peroxidation.Neuronal cardiolipin is especially rich in docosahexaenoic acid(DHA),a PUFA with five bisallylic carbon atoms.Upon excessive oxidative stress,cardiolipin migrates to the outer membrane,where it interacts withα-synuclein(α-syn),the amyloidogenic protein that accumulates as fibrils in Lewy bodies in association with PD.Such interaction leads to pore formation and the launch of an apoptotic cascade.α-syn misfolding likely begins in the gut,and misfoldedα-syn travels along nerve fibers,particularly the vagus nerve,to reach the brainstem nuclei,where it can seed misfolding ofα-syn molecules already present there.Mitochondrial dysfunction in the gut may be a primary factor in PD,and low-deuterium nutrients may be therapeutic.
基金supported by grants from Collaborative Research Fund(Ref:C4032-21GF)General Research Grant(Ref:14114822)+1 种基金Group Research Scheme(Ref:3110146)Area of Excellence(Ref:Ao E/M-402/20)。
文摘Mitochondrial dysfunction and oxidative stress are widely regarded as primary drivers of aging and are associated with several neurodegenerative diseases.The degeneration of motor neurons during aging is a critical pathological factor contributing to the progression of sarcopenia.However,the morphological and functional changes in mitochondria and their interplay in the degeneration of the neuromuscular junction during aging remain poorly understood.A defined systematic search of the Pub Med,Web of Science and Embase databases(last accessed on October 30,2024)was conducted with search terms including'mitochondria','aging'and'NMJ'.Clinical and preclinical studies of mitochondrial dysfunction and neuromuscular junction degeneration during aging.Twentyseven studies were included in this systematic review.This systematic review provides a summary of morphological,functional and biological changes in neuromuscular junction,mitochondrial morphology,biosynthesis,respiratory chain function,and mitophagy during aging.We focus on the interactions and mechanisms underlying the relationship between mitochondria and neuromuscular junctions during aging.Aging is characterized by significant reductions in mitochondrial fusion/fission cycles,biosynthesis,and mitochondrial quality control,which may lead to neuromuscular junction dysfunction,denervation and poor physical performance.Motor nerve terminals that exhibit redox sensitivity are among the first to exhibit abnormalities,ultimately leading to an early decline in muscle strength through impaired neuromuscular junction transmission function.Parg coactivator 1 alpha is a crucial molecule that regulates mitochondrial biogenesis and modulates various pathways,including the mitochondrial respiratory chain,energy deficiency,oxidative stress,and inflammation.Mitochondrial dysfunction is correlated with neuromuscular junction denervation and acetylcholine receptor fragmentation,resulting in muscle atrophy and a decrease in strength during aging.Physical therapy,pharmacotherapy,and gene therapy can alleviate the structural degeneration and functional deterioration of neuromuscular junction by restoring mitochondrial function.Therefore,mitochondria are considered potential targets for preserving neuromuscular junction morphology and function during aging to treat sarcopenia.
基金supported by the Health Commission Research Project of China(No.HDSL202001057)the Jiangxi Provincial Health Commission Research Project(No.SKJP20203656)the Doctoral Start-up Fund of the First Affiliated Hospital of Gannan Medical University(No.QD063).
文摘In most types of erectile dysfunction,particularly in advanced stages,typical pathological features observed are reduced parenchymal cells coupled with increased tissue fibrosis.However,the current treatment methods have shown limited success in reversing these pathologic changes.Recent research has revealed that changes in autophagy levels,along with alterations in apoptosis and fibrosis-related proteins,are linked to the progression of erectile dysfunction,suggesting a significant association.Autophagy,known to significantly affect cell fate and tissue fibrosis,is currently being explored as a potential treatment modality for erectile dysfunction.However,these present studies are still in their nascent stage,and there are limited experimental data available.This review analyzes erectile dysfunction from a pathological perspective.It provides an in-depth overview of how autophagy is involved in the apoptotic processes of smooth muscle and endothelial cells and its role in the fibrotic processes occurring in the cavernosum.This study aimed to develop a theoretical framework for the potential effectiveness of autophagy in preventing and treating erectile dysfunction,thus encouraging further investigation among researchers in this area.
文摘BACKGROUND To investigate whether seasonal differences in ambient temperature affect the incidence of early postoperative cognitive dysfunction(POCD)among elderly patients undergoing laparoscopic surgery in tropical regions.Additionally,it explored the perioperative risk factors associated with early POCD following abdominal laparoscopic surgery.AIM To investigate the influence of seasonal differences in ambient temperature on POCD of elderly patients METHODS A total of 125 patients aged≥65 years from Hainan Province,China,who underwent laparoscopic surgery under general anesthesia with tracheal intubation,were enrolled. All patients completed the Mini-Mental State Examination one day before surgery and onpostoperative days 1, 3, and 7. A decline of ≥ 2 points from baseline was considered indicative of cognitivedysfunction. Serum levels of S100 calcium binding protein B and neuron-specific enolase were measured usingenzyme-linked immunosorbent assay at three time points: Preoperatively, immediately after extubation, and 24hours postoperatively. Perioperative clinical data were collected to identify potential risk factors for POCD.Propensity score matching (PSM) was performed (1:1, caliper = 0.03), resulting in 41 matched patient pairs betweenwinter and summer groups.RESULTSAfter PSM, baseline characteristics including age, gender, body mass index, education level, comorbidities, andsurgical variables were well balanced between groups. There were no significant differences in the incidence ofPOCD on postoperative days 1, 3, and 7 between patients undergoing laparoscopic surgery in winter vs summer.However, multivariable logistic regression revealed that surgical duration (day 1, P value = 0.049), advanced ageand elevated creatinine (day 3, P value = 0.044, P value = 0.008), and hypoalbuminemia (day 3, P value = 0.042;day7, P value = 0.015) were independently associated with early POCD.CONCLUSIONAmbient temperature differences between winter and summer in tropical regions did not significantly affect theincidence of early POCD in elderly patients undergoing laparoscopic surgery. Nonetheless, age, longer surgicalduration, elevated creatinine, and hypoalbuminemia emerged as key risk factors. These findings underscore theimportance of perioperative optimization to reduce the risk of POCD in elderly patients, regardless of seasonaltemperature variations.
文摘Endocrine disorders frequently lead to metabolic disturbances that significantly affect liver function.Understanding the complex interplay between hormonal imbalances and liver dysfunction is essential for advancing targeted therapeutic strategies.This comprehensive review explores the pathophysiological mechanisms linking major endocrine disorders to liver disease,with a focus on the roles of the thyroid,parathyroid,pancreas,adrenal glands,and sex hormones.Thyroid dysfunction is associated with alterations in liver enzyme levels and metabolic regulation,often resulting in hepatic steatosis or cholestasis.Hyperparathyroidism and consequent hypercalcemia have been linked to hepatic calcifications.Insulin resistance,both hepatic and peripheral,contributes to excessive lipid accumulation in the liver,exacerbating steatotic changes.Adrenal gland disorders,particularly in the setting of chronic liver disease,impair cortisol metabolism and may worsen hepatic injury.Additionally,sex hormones such as estrogen and testosterone modulate the progression of liver fibrosis and influence the development of metabolic syndrome.The intricate relationship between endocrine and hepatic systems underscores the need for a multidisciplinary approach in the management of liver disease.Addressing underlying hormonal disturbances may enhance patient outcomes and prevent further hepatic deterioration.Future research should prioritize integrative therapeutic strategies that concurrently target endocrine and liver dysfunction.
