Cerebral small vessel disease is a neurological disease that affects the brain microvasculature and which is commonly observed among the elderly.Although at first it was considered innocuous,small vessel disease is no...Cerebral small vessel disease is a neurological disease that affects the brain microvasculature and which is commonly observed among the elderly.Although at first it was considered innocuous,small vessel disease is nowadays regarded as one of the major vascular causes of dementia.Radiological signs of small vessel disease include small subcortical infarcts,white matter magnetic resonance imaging hyperintensities,lacunes,enlarged perivascular spaces,cerebral microbleeds,and brain atrophy;however,great heterogeneity in clinical symptoms is observed in small vessel disease patients.The pathophysiology of these lesions has been linked to multiple processes,such as hypoperfusion,defective cerebrovascular reactivity,and blood-brain barrier dysfunction.Notably,studies on small vessel disease suggest that blood-brain barrier dysfunction is among the earliest mechanisms in small vessel disease and might contribute to the development of the hallmarks of small vessel disease.Therefore,the purpose of this review is to provide a new foundation in the study of small vessel disease pathology.First,we discuss the main structural domains and functions of the blood-brain barrier.Secondly,we review the most recent evidence on blood-brain barrier dysfunction linked to small vessel disease.Finally,we conclude with a discussion on future perspectives and propose potential treatment targets and interventions.展开更多
Stroke is a major disorder of the central nervous system that poses a serious threat to human life and quality of life.Many stro ke victims are left with long-term neurological dysfunction,which adversely affects the ...Stroke is a major disorder of the central nervous system that poses a serious threat to human life and quality of life.Many stro ke victims are left with long-term neurological dysfunction,which adversely affects the well-being of the individual and the broader socioeconomic impact.Currently,poststroke brain dysfunction is a major and difficult area of treatment.Vagus nerve stimulation is a Food and Drug Administration-approved exploratory treatment option for autis m,refractory depression,epilepsy,and Alzheimer’s disease.It is expected to be a novel therapeutic technique for the treatment of stroke owing to its association with multiple mechanisms such as alte ring neurotransmitters and the plasticity of central neuro ns.In animal models of acute ischemic stroke,vagus nerve stimulation has been shown to reduce infarct size,reduce post-stroke neurological damage,and improve learning and memory capacity in rats with stroke by reducing the inflammatory response,regulating bloodbrain barrier permeability,and promoting angiogenesis and neurogenesis.At present,vagus nerve stimulation includes both invasive and non-invasive vagus nerve stimulation.Clinical studies have found that invasive vagus nerve stimulation combined with rehabilitation therapy is effective in im proving upper limb motor and cognitive abilities in stroke patients.Further clinical studies have shown that non-invasive vagus nerve stimulation,including ear/ce rvical vagus nerve stimulation,can stimulate vagal projections to the central nervous system similarly to invasive vagus nerve stimulation and can have the same effect.In this paper,we first describe the multiple effects of vagus nerve stimulation in stroke,and then discuss in depth its neuroprotective mechanisms in ischemic stroke.We go on to outline the res ults of the current major clinical applications of invasive and non-invasive vagus nerve stimulation.Finally,we provide a more comprehensive evaluation of the advantages and disadvantages of different types of vagus nerve stimulation in the treatment of cerebral ischemia and provide an outlook on the developmental trends.We believe that vagus nerve stimulation,as an effective treatment for stroke,will be widely used in clinical practice to promote the recovery of stroke patients and reduce the incidence of disability.展开更多
Ce rebral palsy is a diagnostic term utilized to describe a group of permanent disorders affecting movement and posture.Patients with cerebral palsy are often only capable of limited activity,resulting from non-progre...Ce rebral palsy is a diagnostic term utilized to describe a group of permanent disorders affecting movement and posture.Patients with cerebral palsy are often only capable of limited activity,resulting from non-progressive disturbances in the fetal or neonatal brain.These disturbances severely impact the child’s daily life and impose a substantial economic burden on the family.Although cerebral palsy encompasses various brain injuries leading to similar clinical outcomes,the unde rstanding of its etiological pathways remains incomplete owing to its complexity and heterogeneity.This review aims to summarize the current knowledge on the genetic factors influencing cerebral palsy development.It is now widely acknowledged that genetic mutations and alterations play a pivotal role in cerebral palsy development,which can be further influenced by environmental fa ctors.Des pite continuous research endeavors,the underlying fa ctors contributing to cerebral palsy remain are still elusive.However,significant progress has been made in genetic research that has markedly enhanced our comprehension of the genetic factors underlying cerebral palsy development.Moreove r,these genetic factors have been categorized based on the identified gene mutations in patients through clinical genotyping,including thrombosis,angiogenesis,mitochondrial and oxidative phosphorylation function,neuronal migration,and cellular autophagy.Furthermore,exploring targeted genotypes holds potential for precision treatment.In conclusion,advancements in genetic research have substantially improved our understanding of the genetic causes underlying cerebral palsy.These breakthroughs have the potential to pave the way for new treatments and therapies,consequently shaping the future of cerebral palsy research and its clinical management.The investigation of cerebral palsy genetics holds the potential to significantly advance treatments and management strategies.By elucidating the underlying cellular mechanisms,we can develop to rgeted interventions to optimize outcomes.A continued collaboration between researchers and clinicians is imperative to comprehensively unravel the intricate genetic etiology of cerebral palsy.展开更多
β-Sitosterol is a type of phytosterol that occurs naturally in plants.Previous studies have shown that it has anti-oxidant,anti-hyperlipidemic,anti-inflammatory,immunomodulatory,and anti-tumor effects,but it is unkno...β-Sitosterol is a type of phytosterol that occurs naturally in plants.Previous studies have shown that it has anti-oxidant,anti-hyperlipidemic,anti-inflammatory,immunomodulatory,and anti-tumor effects,but it is unknown whetherβ-sitosterol treatment reduces the effects of ischemic stroke.Here we found that,in a mouse model of ischemic stroke induced by middle cerebral artery occlusion,β-sitosterol reduced the volume of cerebral infarction and brain edema,reduced neuronal apoptosis in brain tissue,and alleviated neurological dysfunction;moreover,β-sitosterol increased the activity of oxygen-and glucose-deprived cerebral cortex neurons and reduced apoptosis.Further investigation showed that the neuroprotective effects ofβ-sitosterol may be related to inhibition of endoplasmic reticulum stress caused by intracellular cholesterol accumulation after ischemic stroke.In addition,β-sitosterol showed high affinity for NPC1L1,a key transporter of cholesterol,and antagonized its activity.In conclusion,β-sitosterol may help treat ischemic stroke by inhibiting neuronal intracellular cholesterol overload/endoplasmic reticulum stress/apoptosis signaling pathways.展开更多
Brain functional impairment after stroke is common;however,the molecular mechanisms of post-stroke recovery remain unclear.It is well-recognized that age is the most important independent predictor of poor outcomes af...Brain functional impairment after stroke is common;however,the molecular mechanisms of post-stroke recovery remain unclear.It is well-recognized that age is the most important independent predictor of poor outcomes after stroke as older patients show poorer functional outcomes following stroke.Mounting evidence suggests that axonal regeneration and angiogenesis,the major forms of brain plasticity responsible for post-stroke recovery,diminished with advanced age.Previous studies suggest that Ras-related C3 botulinum toxin substrate(Rac)1 enhances stroke recovery as activation of Rac1 improved behavior recovery in a young mice stroke model.Here,we investigated the role of Rac1 signaling in long-term functional recovery and brain plasticity in an aged(male,18 to 22 months old C57BL/6J)brain after ischemic stroke.We found that as mice aged,Rac1 expression declined in the brain.Delayed overexpression of Rac1,using lentivirus encoding Rac1 injected day 1 after ischemic stroke,promoted cognitive(assessed using novel object recognition test)and sensorimotor(assessed using adhesive removal tests)recovery on days 14–28.This was accompanied by the increase of neurite and proliferative endothelial cells in the periinfarct zone assessed by immunostaining.In a reverse approach,pharmacological inhibition of Rac1 by intraperitoneal injection of Rac1 inhibitor NSC23766 for 14 successive days after ischemic stroke worsened the outcome with the reduction of neurite and proliferative endothelial cells.Furthermore,Rac1 inhibition reduced the activation of p21-activated kinase 1,the protein level of brain-derived neurotrophic factor,and increased the protein level of glial fibrillary acidic protein in the ischemic brain on day 28 after stroke.Our work provided insight into the mechanisms behind the diminished plasticity after cerebral ischemia in aged brains and identified Rac1 as a potential therapeutic target for improving functional recovery in the older adults after stroke.展开更多
BACKGROUND Hypertensive cerebral hemorrhage(HCH),the most common chronic diseases,has become a topic of global public health discussions.AIM To investigate the role of rehabilitative nursing interventions in optimizin...BACKGROUND Hypertensive cerebral hemorrhage(HCH),the most common chronic diseases,has become a topic of global public health discussions.AIM To investigate the role of rehabilitative nursing interventions in optimizing the postoperative mental status recovery phase and to provide clinical value for future rehabilitation of patients with HCH.METHODS This randomized controlled study included 120 patients with cerebral HCH who were contained to our neurosurgery department between May 2021–May 2023 as the participants.The participants have randomly sampled and grouped into the observation and control groups.The observation group received the rehabilitation nursing model,whereas the control group have given conventional nursing.The conscious state of the patients was assessed at 7,14,21,and 30 d postoperatively.After one month of care,sleep quality,anxiety,and depression were compared between the two groups.Patient and family satisfaction were assessed using a nursing care model.RESULTS The results showed that the state of consciousness scores of the patients in both groups significantly increased(P<0.05)after surgical treatment.From the 14th day onwards,differences in the state of consciousness scores between the two groups of patients began to appear(P<0.05).After one month of care,the sleep quality,anxiety state,and depression state of patients were significantly better in the observation group than in the control group(P<0.05).Satisfaction with nursing care was higher in the observation group than in the control group(P<0.05).CONCLUSION The rehabilitation nursing model has a more complete system compared to conventional nursing,which can effectively improve the postoperative quality of life of patients with cerebral hemorrhage and improve the efficiency of mental state recovery;however,further analysis and research are needed to provide more scientific evidence.展开更多
Studies have shown that C1q/tumor necrosis factor-related protein-6 (CTRP6) can alleviate renal ischemia/reperfusion injury in mice. However, its role in the brain remains poorly understood. To investigate the role of...Studies have shown that C1q/tumor necrosis factor-related protein-6 (CTRP6) can alleviate renal ischemia/reperfusion injury in mice. However, its role in the brain remains poorly understood. To investigate the role of CTRP6 in cerebral ischemia/reperfusion injury associated with diabetes mellitus, a diabetes mellitus mouse model of cerebral ischemia/reperfusion injury was established by occlusion of the middle cerebral artery. To overexpress CTRP6 in the brain, an adeno-associated virus carrying CTRP6 was injected into the lateral ventricle. The result was that oxygen injury and inflammation in brain tissue were clearly attenuated, and the number of neurons was greatly reduced. In vitro experiments showed that CTRP6 knockout exacerbated oxidative damage, inflammatory reaction, and apoptosis in cerebral cortical neurons in high glucose hypoxia-simulated diabetic cerebral ischemia/reperfusion injury. CTRP6 overexpression enhanced the sirtuin-1 signaling pathway in diabetic brains after ischemia/reperfusion injury. To investigate the mechanism underlying these effects, we examined mice with depletion of brain tissue-specific sirtuin-1. CTRP6-like protection was achieved by activating the sirtuin-1 signaling pathway. Taken together, these results indicate that CTRP6 likely attenuates cerebral ischemia/reperfusion injury through activation of the sirtuin-1 signaling pathway.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
Calcium influx into neurons triggers neuronal death during cerebral ischemia/reperfusion injury.Various calcium channels are involved in cerebral ischemia/reperfusion injury.Cav3.2 channel is a main subtype of T-type ...Calcium influx into neurons triggers neuronal death during cerebral ischemia/reperfusion injury.Various calcium channels are involved in cerebral ischemia/reperfusion injury.Cav3.2 channel is a main subtype of T-type calcium channels.T-type calcium channel blockers,such as pimozide and mibefradil,have been shown to prevent cerebral ischemia/reperfusion injury-induced brain injury.However,the role of Cav3.2 channels in cerebral ischemia/reperfusion injury remains unclear.Here,in vitro and in vivo models of cerebral ischemia/reperfusion injury were established using middle cerebral artery occlusion in mice and high glucose hypoxia/reoxygenation exposure in primary hippocampal neurons.The results showed that Cav3.2 expression was significantly upregulated in injured hippocampal tissue and primary hippocampal neurons.We further established a Cav3.2 gene-knockout mouse model of cerebral ischemia/reperfusion injury.Cav3.2 knockout markedly reduced infarct volume and brain water content,and alleviated neurological dysfunction after cerebral ischemia/reperfusion injury.Additionally,Cav3.2 knockout attenuated cerebral ischemia/reperfusion injury-induced oxidative stress,inflammatory response,and neuronal apoptosis.In the hippocampus of Cav3.2-knockout mice,calcineurin overexpression offset the beneficial effect of Cav3.2 knockout after cerebral ischemia/reperfusion injury.These findings suggest that the neuroprotective function of Cav3.2 knockout is mediated by calcineurin/nuclear factor of activated T cells 3 signaling.Findings from this study suggest that Cav3.2 could be a promising target for treatment of cerebral ischemia/reperfusion injury.展开更多
BACKGROUND Diabetic intracerebral hemorrhage(ICH)is a serious complication of diabetes.The role and mechanism of bone marrow mesenchymal stem cell(BMSC)-derived exosomes(BMSC-exo)in neuroinflammation post-ICH in patie...BACKGROUND Diabetic intracerebral hemorrhage(ICH)is a serious complication of diabetes.The role and mechanism of bone marrow mesenchymal stem cell(BMSC)-derived exosomes(BMSC-exo)in neuroinflammation post-ICH in patients with diabetes are unknown.In this study,we investigated the regulation of BMSC-exo on hyperglycemia-induced neuroinflammation.AIM To study the mechanism of BMSC-exo on nerve function damage after diabetes complicated with cerebral hemorrhage.METHODS BMSC-exo were isolated from mouse BMSC media.This was followed by transfection with microRNA-129-5p(miR-129-5p).BMSC-exo or miR-129-5poverexpressing BMSC-exo were intravitreally injected into a diabetes mouse model with ICH for in vivo analyses and were cocultured with high glucoseaffected BV2 cells for in vitro analyses.The dual luciferase test and RNA immunoprecipitation test verified the targeted binding relationship between miR-129-5p and high-mobility group box 1(HMGB1).Quantitative polymerase chain reaction,western blotting,and enzyme-linked immunosorbent assay were conducted to assess the levels of some inflammation factors,such as HMGB1,interleukin 6,interleukin 1β,toll-like receptor 4,and tumor necrosis factorα.Brain water content,neural function deficit score,and Evans blue were used to measure the neural function of mice.RESULTS Our findings indicated that BMSC-exo can promote neuroinflammation and functional recovery.MicroRNA chip analysis of BMSC-exo identified miR-129-5p as the specific microRNA with a protective role in neuroinflammation.Overexpression of miR-129-5p in BMSC-exo reduced the inflammatory response and neurological impairment in comorbid diabetes and ICH cases.Furthermore,we found that miR-129-5p had a targeted binding relationship with HMGB1 mRNA.CONCLUSION We demonstrated that BMSC-exo can reduce the inflammatory response after ICH with diabetes,thereby improving the neurological function of the brain.展开更多
AIM:To compare and analyse the diagnostic efficacy of the College of Optometrists Vision Development Quality of Life Questionnaire(COVD-QOL)and the Convergence Insufficiency Symptom Survey(CISS)in detecting convergenc...AIM:To compare and analyse the diagnostic efficacy of the College of Optometrists Vision Development Quality of Life Questionnaire(COVD-QOL)and the Convergence Insufficiency Symptom Survey(CISS)in detecting convergence insufficiency and to compare their diagnostic value in clinical applications.METHODS:Using the diagnostic test method,62 adult patients with convergence insufficiency(age:24.74±3.75y)and 62 normal participants(age:23.61±3.13y)who visited the Optometry Clinic of West China Hospital of Sichuan University from April 2021 to January 2023 were included.All subjects completed the CISS and COVD-QOL.Statistical analysis of the sensitivity and specificity of the CISS and COVD-QOL and comparison and joint experimental analysis of their diagnostic efficacy were performed.RESULTS:The sensitivity of the CISS and COVD-QOL for convergence insufficiency was 64.5%and 71.0%,respectively,while the specificity was 96.8%and 67.7%,respectively.Compared to the CISS alone,the combination of the CISS and COVD-QOL demonstrated lower sensitivity and specificity.The areas under the receiver operating characteristic curve of CISS,COVD-QOL and CISS combined with COVD-QOL were 0.806,0.694 and 0.782,respectively.CONCLUSION:Considering the low sensitivity of the CISS and the low specificity of the COVD-QOL,it is recommended to supplement these questionnaires with other screening tests for the detection of convergence insufficiency.展开更多
Alzheimer’s disease(AD)is the most common neurodegenerative disorder characterized by slow and progressive decline of cognitive and memory functions.In only approximately 5%of the cases,AD is familial,as often predis...Alzheimer’s disease(AD)is the most common neurodegenerative disorder characterized by slow and progressive decline of cognitive and memory functions.In only approximately 5%of the cases,AD is familial,as often predisposed by genetic mutations(Hoogmartens et al.,2021),while sporadic AD accounts for approximately 95%of the cases.The amyloid cascade hypothesis is one of the fundamental hypotheses put out to explain AD pathogenesis as dysregulated homeostasis of amyloid-β(Aβ)peptides that leads to the accumulation of Aβplaques in the parenchyma,an anatomical hallmark of AD.展开更多
Near-infrared spectroscopy(NIRS)has been increasingly utilized in both sport and health sciences to assess various physiological parameters related to exercise performance.1 NIRS methods coupled with the recent develo...Near-infrared spectroscopy(NIRS)has been increasingly utilized in both sport and health sciences to assess various physiological parameters related to exercise performance.1 NIRS methods coupled with the recent development of portable and wearable devices suitable for field-based measurements have revolutionized the study of exercise physiology and the determinants of exercise performance by providing real-time,non-invasive,and spatially localized measurements of tissue oxygenation dynamics.展开更多
The cerebral cortex is comprised of properly localized cell types that exert their specific functions.In the developing brain,cells migrate from the germinal region to their functional locations(Silva et al.,2019;Coss...The cerebral cortex is comprised of properly localized cell types that exert their specific functions.In the developing brain,cells migrate from the germinal region to their functional locations(Silva et al.,2019;Cossart and Garel,2022).For example,neocortical excitatory neurons are generated in the cerebral ventricular and subventricular zones,move to the developing cortical plate via radial migration,and reside in a radial array of six neuronal layers(Oishi and Nakajima,2018).On the other hand,cortical interneurons are mainly generated in ganglionic eminences,migrate tangentially across the cerebral cortex,and reach their final destinations in the cortex(Lim et al.,2018).The failure of neuronal migration leads to defects in cortical layer formation.While the mechanisms of neuronal distribution have been well examined,how astrocytes are diffusely distributed in the cortex is still unclear.Astrocytes are glial cells in the cerebral cortex with several functions,including metabolic support and synapse formation(Abbott et al.,2006;Bosworth and Allen,2017;Allen and Lyons,2018).For example,astrocytes establish synaptic connectivity in the developing brain while they contact numerous synapses and maintain optimal neuronal activity in the adult brain.In the developing brain,astrocytes are primarily generated from radial glia after the neurogenic period.While a certain type of astrocyte called fibrous astrocytes populates the white matter,protoplasmic astrocytes migrate to the cortical plate during neural network formation.展开更多
Cell adhesion plays pivotal roles in the morphogenesis of multicellular organisms.Epithelial cells form several types of cell-to-cell adhesion,including zonula occludens(tight junctions),zonula adhaerens(adherens junc...Cell adhesion plays pivotal roles in the morphogenesis of multicellular organisms.Epithelial cells form several types of cell-to-cell adhesion,including zonula occludens(tight junctions),zonula adhaerens(adherens junctions),and macula adhaerens(desmosomes).Although these adhesion complexes are basically observed only in epithelial cells,cadherins,which are the major cell adhesion molecules of adherens junctions,are expressed in both epithelial and non-epithelial tissues,including neural tissues(Kawauchi,2012).The cadherin superfamily consists of more than 100 members,but classic cadherins.展开更多
Background: Chronic venous insufficiency (CVI) describes a condition that affects the venous system of the lower extremities due to venous hypertension (VH. The prevalence is between 5% - 30%. CVI is associated with o...Background: Chronic venous insufficiency (CVI) describes a condition that affects the venous system of the lower extremities due to venous hypertension (VH. The prevalence is between 5% - 30%. CVI is associated with older age, smoking, lower extremity trauma, presence of an arteriovenous shunt, and elevated estrogen levels. All patients should be initially treated with conservative management. Venoactive drugs like calcium dobesilate are useful. Objectives: The primary objective compared the clinical improvement in patients with CVI, grades 0 - 3 of the CEAP classification of chronic venous disease, produced by two formulations of calcium dobesilate: calcium dobesilate LP 1 g OD vs calcium dobesilate 500 mg BID, immediate release. The secondary objective assessed the side effects of both formulations. Method: All patients took one tablet and one capsule at 7 am, and one capsule at 7 pm, for 8 weeks. One group received dobesilate 1 g OD and the other group received dobesilate 500 md BID. They were evaluated after 15, 30 and 60 days of treatment, using the symptom evaluation scale. Results: In both groups, there was a significant decrease in the symptom score after 15 days. Four patients in the Dobesilate OD group: had adverse effects, which did not require suspension of treatment. In the BID dobesilate group, there was one therapeutic failure, and one case of gastric discomfort. Conclusions: Prolonged-release Calcium dobesilate 1 g OD is as effective as calcium dobesilate 500 mg BID for the treatment of patients with chronic venous insufficiency.展开更多
Pain is a common complaint among patients seeking medical care.If left un-treated,pain can become chronic,significantly affecting patients’quality of life.An accurate diagnosis of the underlying cause of pain is cruc...Pain is a common complaint among patients seeking medical care.If left un-treated,pain can become chronic,significantly affecting patients’quality of life.An accurate diagnosis of the underlying cause of pain is crucial for effective treatment.Chronic venous insufficiency(CVI)is frequently overlooked by pain physicians.Moreover,many pain physicians lack sufficient knowledge about CVI.CVI is a common condition resulting from malfunctioning or damaged valves in lower limb veins.Symptoms of CVI,ranging from mild to severe,include pain,heaviness,fatigue,itching,swelling,skin color changes,and ulcers in the lower limbs.Recently,it has become more widely known that these symptoms can be attributed to CVI.Even slight or mild CVI can cause related symptoms.Pain physicians primarily consider neuromusculoskeletal disorders when assessing patients with leg pain,and often neglect the possibility of CVI.In clinical practice,when pain physicians encounter patients with unresolved leg pain,they must assess whether the patients exhibit symptoms of CVI and conduct tests to differ-entiate CVI from other potential causes.展开更多
Background: Addison’s disease is a rare disorder of the adrenal cortex that leads to inadequate production of cortisol initially followed by aldosterone and androgens. Its manifestations are usually slow and non-spec...Background: Addison’s disease is a rare disorder of the adrenal cortex that leads to inadequate production of cortisol initially followed by aldosterone and androgens. Its manifestations are usually slow and non-specific with potential for life-threatening adrenal crisis following hypermetabolic demands (infection, trauma, surgery). Patients: Over the past 10 years, 19 CRD-patients were diagnosed with occult PAI in our center. Results: Unprovoked hypotension was the most common manifestations of occult PAI and was the unmasking event in 11 (58%). It was without significant cardiac and/or severe systemic sepsis and was refractory to isotonic saline infusions. Equal number of the remaining patients (n = 2) presented with persistent and inexplicable electrolytes abnormalities viz. 1) hyponatremia despite restricted oral fluid intake, lack of dehydration and massive fluid overload, as well as 2) hyperkalemia despite potassium-restricted diet, hyperkalemic drugs and adequate therapy with Furosemide and low-potassium dialysis-baths. On the other hand, similar proportions presented with unprovoked 3) progressive weight loss, decrease appetite and cachexia as well as 4) frequent hypoglycemic attacks. All patients were treated and were medically stable after 29 (2 - 60) months of follow up. Autoantibodies to 21-hydroxylase enzyme were positive in 16 (90%). At diagnosis, and subsequent follow up, only 7 patients (37%) had multi-endocrine dysfunction of whom 2 with type 1 and 5 with type 2. Conclusion: High index of suspicion should be exerted in diagnosis of PAI in patients with CRD, since its clinical picture is similar to CRD manifestations and complications. In those patients, confirmatory tests and specific management can save their lives. .展开更多
BACKGROUND Intracerebral hemorrhage mainly occurs in middle-aged and elderly patients with hypertension,and surgery is currently the main treatment for hypertensive cerebral hemorrhage,but the bleeding caused by surge...BACKGROUND Intracerebral hemorrhage mainly occurs in middle-aged and elderly patients with hypertension,and surgery is currently the main treatment for hypertensive cerebral hemorrhage,but the bleeding caused by surgery will cause damage to the patient's nerve cells,resulting in cognitive and motor dysfunction,resulting in a decline in the patient's quality of life.AIM To investigate associations between cerebral arterial blood flow and executive and cognitive functions in depressed patients after acute hypertensive cerebral hemorrhage.METHODS Eighty-nine patients with depression after acute hypertensive cerebral hemorrhage who were admitted to our hospital between January 2019 and July 2021 were selected as the observation group,while 100 patients without depression who had acute hypertensive cerebral hemorrhage were selected as the control group.The attention span of the patients was assessed using the Paddle Pin Test while executive function was assessed using the Wisconsin Card Sorting Test(WCST)and cognitive function was assessed using the Montreal Cognitive Assessment Scale(MoCA).The Hamilton Depression Rating Scale(HAMD-24)was used to evaluate the severity of depression of involved patients.Cerebral arterial blood flow was measured in both groups.RESULTS The MoCA score,net scores I,II,III,IV,and the total net score of the scratch test in the observation group were significantly lower than those in the control group(P<0.05).Concurrently,the total number of responses,number of incorrect responses,number of persistent errors,and number of completed responses of the first classification in the WCST test were significantly higher in the observation group than those in the control group(P<0.05).Blood flow in the basilar artery,left middle cerebral artery,right middle cerebral artery,left anterior cerebral artery,and right anterior cerebral artery was significantly lower in the observation group than in the control group(P<0.05).The basilar artery,left middle cerebral artery,right middle cerebral artery,left anterior cerebral artery,and right anterior cerebral artery were positively correlated with the net and total net scores of each part of the Paddle Pin test and the MoCA score(P<0.05),and negatively correlated with each part of the WCST test(P<0.05).In the observation group,the post-treatment improvement was more prominent in the Paddle Pin test,WCST test,HAMD-24 score,and MoCA score compared with those in the pre-treatment period(P<0.05).Blood flow in the basilar artery,left middle cerebral artery,right middle cerebral artery,left anterior cerebral artery,and right anterior cerebral artery significantly improved in the observation group after treatment(P<0.05).CONCLUSION Impaired attention,and executive and cognitive functions are correlated with cerebral artery blood flow in patients with depression after acute hypertensive cerebral hemorrhage and warrant further study.展开更多
The incidence of premature ovarian insufficiency(POI)is increasing worldwide,particularly among younger women,posing a significant challenge to fertility.In addition to menopausal symptoms,POI leads to several complic...The incidence of premature ovarian insufficiency(POI)is increasing worldwide,particularly among younger women,posing a significant challenge to fertility.In addition to menopausal symptoms,POI leads to several complications that profoundly affect female reproductive function and overall health.Unfortunately,current clinical treatment strategies for this condition are limited and often yield unsatisfactory outcomes.These approaches typically involve hormone repla-cement therapy combined with psychological support.Recently,mesenchymal stem cell(MSC)therapies for POI have garnered considerable attention in global research.MSCs can restore ovarian reproductive and endocrine functions through diverse mechanisms,including controlling differentiation,promoting angiogenesis,regulating ovarian fibrosis,inhibiting apoptosis,enhancing autocrine and paracrine effects,suppressing inflammation,modulating the immune system,and genetic regulation.This editorial offers a succinct summary of the application of MSC therapy in the context of POI,providing evidence for groundbreaking medical approaches that have potential to enhance reproductive health and overall well-being for women.展开更多
基金supported by China Scholarship Council(202208210093,to RJ)。
文摘Cerebral small vessel disease is a neurological disease that affects the brain microvasculature and which is commonly observed among the elderly.Although at first it was considered innocuous,small vessel disease is nowadays regarded as one of the major vascular causes of dementia.Radiological signs of small vessel disease include small subcortical infarcts,white matter magnetic resonance imaging hyperintensities,lacunes,enlarged perivascular spaces,cerebral microbleeds,and brain atrophy;however,great heterogeneity in clinical symptoms is observed in small vessel disease patients.The pathophysiology of these lesions has been linked to multiple processes,such as hypoperfusion,defective cerebrovascular reactivity,and blood-brain barrier dysfunction.Notably,studies on small vessel disease suggest that blood-brain barrier dysfunction is among the earliest mechanisms in small vessel disease and might contribute to the development of the hallmarks of small vessel disease.Therefore,the purpose of this review is to provide a new foundation in the study of small vessel disease pathology.First,we discuss the main structural domains and functions of the blood-brain barrier.Secondly,we review the most recent evidence on blood-brain barrier dysfunction linked to small vessel disease.Finally,we conclude with a discussion on future perspectives and propose potential treatment targets and interventions.
基金supported by the Natural Science Foundation of Hubei Province,No.2022CBF680Independent Scientific Research Project of Wuhan University,No.2042022kf1119(both to LD)。
文摘Stroke is a major disorder of the central nervous system that poses a serious threat to human life and quality of life.Many stro ke victims are left with long-term neurological dysfunction,which adversely affects the well-being of the individual and the broader socioeconomic impact.Currently,poststroke brain dysfunction is a major and difficult area of treatment.Vagus nerve stimulation is a Food and Drug Administration-approved exploratory treatment option for autis m,refractory depression,epilepsy,and Alzheimer’s disease.It is expected to be a novel therapeutic technique for the treatment of stroke owing to its association with multiple mechanisms such as alte ring neurotransmitters and the plasticity of central neuro ns.In animal models of acute ischemic stroke,vagus nerve stimulation has been shown to reduce infarct size,reduce post-stroke neurological damage,and improve learning and memory capacity in rats with stroke by reducing the inflammatory response,regulating bloodbrain barrier permeability,and promoting angiogenesis and neurogenesis.At present,vagus nerve stimulation includes both invasive and non-invasive vagus nerve stimulation.Clinical studies have found that invasive vagus nerve stimulation combined with rehabilitation therapy is effective in im proving upper limb motor and cognitive abilities in stroke patients.Further clinical studies have shown that non-invasive vagus nerve stimulation,including ear/ce rvical vagus nerve stimulation,can stimulate vagal projections to the central nervous system similarly to invasive vagus nerve stimulation and can have the same effect.In this paper,we first describe the multiple effects of vagus nerve stimulation in stroke,and then discuss in depth its neuroprotective mechanisms in ischemic stroke.We go on to outline the res ults of the current major clinical applications of invasive and non-invasive vagus nerve stimulation.Finally,we provide a more comprehensive evaluation of the advantages and disadvantages of different types of vagus nerve stimulation in the treatment of cerebral ischemia and provide an outlook on the developmental trends.We believe that vagus nerve stimulation,as an effective treatment for stroke,will be widely used in clinical practice to promote the recovery of stroke patients and reduce the incidence of disability.
基金supported by the National Natural Science Foundation of China,No.U21A20347(to CZ)the National Key Research and Development Program of China,No.2022YFC2704801(to CZ)+1 种基金the Henan Key Laboratory of Population Defects Prevention,No.ZD202103(to YX)the Department of Science and Technology of Henan Province of China,No.212102310221(to YX)。
文摘Ce rebral palsy is a diagnostic term utilized to describe a group of permanent disorders affecting movement and posture.Patients with cerebral palsy are often only capable of limited activity,resulting from non-progressive disturbances in the fetal or neonatal brain.These disturbances severely impact the child’s daily life and impose a substantial economic burden on the family.Although cerebral palsy encompasses various brain injuries leading to similar clinical outcomes,the unde rstanding of its etiological pathways remains incomplete owing to its complexity and heterogeneity.This review aims to summarize the current knowledge on the genetic factors influencing cerebral palsy development.It is now widely acknowledged that genetic mutations and alterations play a pivotal role in cerebral palsy development,which can be further influenced by environmental fa ctors.Des pite continuous research endeavors,the underlying fa ctors contributing to cerebral palsy remain are still elusive.However,significant progress has been made in genetic research that has markedly enhanced our comprehension of the genetic factors underlying cerebral palsy development.Moreove r,these genetic factors have been categorized based on the identified gene mutations in patients through clinical genotyping,including thrombosis,angiogenesis,mitochondrial and oxidative phosphorylation function,neuronal migration,and cellular autophagy.Furthermore,exploring targeted genotypes holds potential for precision treatment.In conclusion,advancements in genetic research have substantially improved our understanding of the genetic causes underlying cerebral palsy.These breakthroughs have the potential to pave the way for new treatments and therapies,consequently shaping the future of cerebral palsy research and its clinical management.The investigation of cerebral palsy genetics holds the potential to significantly advance treatments and management strategies.By elucidating the underlying cellular mechanisms,we can develop to rgeted interventions to optimize outcomes.A continued collaboration between researchers and clinicians is imperative to comprehensively unravel the intricate genetic etiology of cerebral palsy.
基金supported by the National Natural Science Foundation of China,Nos.82104158(to XT),31800887(to LY),31972902(to LY),82001422(to YL)China Postdoctoral Science Foundation,No.2020M683750(to LY)partially by Young Talent Fund of University Association for Science and Technology in Shaanxi Province of China,No.20200307(to LY).
文摘β-Sitosterol is a type of phytosterol that occurs naturally in plants.Previous studies have shown that it has anti-oxidant,anti-hyperlipidemic,anti-inflammatory,immunomodulatory,and anti-tumor effects,but it is unknown whetherβ-sitosterol treatment reduces the effects of ischemic stroke.Here we found that,in a mouse model of ischemic stroke induced by middle cerebral artery occlusion,β-sitosterol reduced the volume of cerebral infarction and brain edema,reduced neuronal apoptosis in brain tissue,and alleviated neurological dysfunction;moreover,β-sitosterol increased the activity of oxygen-and glucose-deprived cerebral cortex neurons and reduced apoptosis.Further investigation showed that the neuroprotective effects ofβ-sitosterol may be related to inhibition of endoplasmic reticulum stress caused by intracellular cholesterol accumulation after ischemic stroke.In addition,β-sitosterol showed high affinity for NPC1L1,a key transporter of cholesterol,and antagonized its activity.In conclusion,β-sitosterol may help treat ischemic stroke by inhibiting neuronal intracellular cholesterol overload/endoplasmic reticulum stress/apoptosis signaling pathways.
基金supported by NIH grants RF1 AG069466(to JL and LDM),R01 NS099628(to JL),and AG069466(to JL and LDM)the American Heart Association award 20POST35180172(to FB)。
文摘Brain functional impairment after stroke is common;however,the molecular mechanisms of post-stroke recovery remain unclear.It is well-recognized that age is the most important independent predictor of poor outcomes after stroke as older patients show poorer functional outcomes following stroke.Mounting evidence suggests that axonal regeneration and angiogenesis,the major forms of brain plasticity responsible for post-stroke recovery,diminished with advanced age.Previous studies suggest that Ras-related C3 botulinum toxin substrate(Rac)1 enhances stroke recovery as activation of Rac1 improved behavior recovery in a young mice stroke model.Here,we investigated the role of Rac1 signaling in long-term functional recovery and brain plasticity in an aged(male,18 to 22 months old C57BL/6J)brain after ischemic stroke.We found that as mice aged,Rac1 expression declined in the brain.Delayed overexpression of Rac1,using lentivirus encoding Rac1 injected day 1 after ischemic stroke,promoted cognitive(assessed using novel object recognition test)and sensorimotor(assessed using adhesive removal tests)recovery on days 14–28.This was accompanied by the increase of neurite and proliferative endothelial cells in the periinfarct zone assessed by immunostaining.In a reverse approach,pharmacological inhibition of Rac1 by intraperitoneal injection of Rac1 inhibitor NSC23766 for 14 successive days after ischemic stroke worsened the outcome with the reduction of neurite and proliferative endothelial cells.Furthermore,Rac1 inhibition reduced the activation of p21-activated kinase 1,the protein level of brain-derived neurotrophic factor,and increased the protein level of glial fibrillary acidic protein in the ischemic brain on day 28 after stroke.Our work provided insight into the mechanisms behind the diminished plasticity after cerebral ischemia in aged brains and identified Rac1 as a potential therapeutic target for improving functional recovery in the older adults after stroke.
文摘BACKGROUND Hypertensive cerebral hemorrhage(HCH),the most common chronic diseases,has become a topic of global public health discussions.AIM To investigate the role of rehabilitative nursing interventions in optimizing the postoperative mental status recovery phase and to provide clinical value for future rehabilitation of patients with HCH.METHODS This randomized controlled study included 120 patients with cerebral HCH who were contained to our neurosurgery department between May 2021–May 2023 as the participants.The participants have randomly sampled and grouped into the observation and control groups.The observation group received the rehabilitation nursing model,whereas the control group have given conventional nursing.The conscious state of the patients was assessed at 7,14,21,and 30 d postoperatively.After one month of care,sleep quality,anxiety,and depression were compared between the two groups.Patient and family satisfaction were assessed using a nursing care model.RESULTS The results showed that the state of consciousness scores of the patients in both groups significantly increased(P<0.05)after surgical treatment.From the 14th day onwards,differences in the state of consciousness scores between the two groups of patients began to appear(P<0.05).After one month of care,the sleep quality,anxiety state,and depression state of patients were significantly better in the observation group than in the control group(P<0.05).Satisfaction with nursing care was higher in the observation group than in the control group(P<0.05).CONCLUSION The rehabilitation nursing model has a more complete system compared to conventional nursing,which can effectively improve the postoperative quality of life of patients with cerebral hemorrhage and improve the efficiency of mental state recovery;however,further analysis and research are needed to provide more scientific evidence.
基金supported by the National Natural Science Foundation of China,Nos.82102295(to WG),82071339(to LG),82001119(to JH),and 81901994(to BZ).
文摘Studies have shown that C1q/tumor necrosis factor-related protein-6 (CTRP6) can alleviate renal ischemia/reperfusion injury in mice. However, its role in the brain remains poorly understood. To investigate the role of CTRP6 in cerebral ischemia/reperfusion injury associated with diabetes mellitus, a diabetes mellitus mouse model of cerebral ischemia/reperfusion injury was established by occlusion of the middle cerebral artery. To overexpress CTRP6 in the brain, an adeno-associated virus carrying CTRP6 was injected into the lateral ventricle. The result was that oxygen injury and inflammation in brain tissue were clearly attenuated, and the number of neurons was greatly reduced. In vitro experiments showed that CTRP6 knockout exacerbated oxidative damage, inflammatory reaction, and apoptosis in cerebral cortical neurons in high glucose hypoxia-simulated diabetic cerebral ischemia/reperfusion injury. CTRP6 overexpression enhanced the sirtuin-1 signaling pathway in diabetic brains after ischemia/reperfusion injury. To investigate the mechanism underlying these effects, we examined mice with depletion of brain tissue-specific sirtuin-1. CTRP6-like protection was achieved by activating the sirtuin-1 signaling pathway. Taken together, these results indicate that CTRP6 likely attenuates cerebral ischemia/reperfusion injury through activation of the sirtuin-1 signaling pathway.
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.Z1 91100006119017 (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 Natural Science Foundation of Anhui Province of China,No.2208085Y32Scientific Research Plan Project of Anhui Province of China,No.2022AH020076the Chen Xiao-Ping Foundation for the Development of Science and Technology of Hubei Province,No.CXPJJH12000005-07-115(all to CT).
文摘Calcium influx into neurons triggers neuronal death during cerebral ischemia/reperfusion injury.Various calcium channels are involved in cerebral ischemia/reperfusion injury.Cav3.2 channel is a main subtype of T-type calcium channels.T-type calcium channel blockers,such as pimozide and mibefradil,have been shown to prevent cerebral ischemia/reperfusion injury-induced brain injury.However,the role of Cav3.2 channels in cerebral ischemia/reperfusion injury remains unclear.Here,in vitro and in vivo models of cerebral ischemia/reperfusion injury were established using middle cerebral artery occlusion in mice and high glucose hypoxia/reoxygenation exposure in primary hippocampal neurons.The results showed that Cav3.2 expression was significantly upregulated in injured hippocampal tissue and primary hippocampal neurons.We further established a Cav3.2 gene-knockout mouse model of cerebral ischemia/reperfusion injury.Cav3.2 knockout markedly reduced infarct volume and brain water content,and alleviated neurological dysfunction after cerebral ischemia/reperfusion injury.Additionally,Cav3.2 knockout attenuated cerebral ischemia/reperfusion injury-induced oxidative stress,inflammatory response,and neuronal apoptosis.In the hippocampus of Cav3.2-knockout mice,calcineurin overexpression offset the beneficial effect of Cav3.2 knockout after cerebral ischemia/reperfusion injury.These findings suggest that the neuroprotective function of Cav3.2 knockout is mediated by calcineurin/nuclear factor of activated T cells 3 signaling.Findings from this study suggest that Cav3.2 could be a promising target for treatment of cerebral ischemia/reperfusion injury.
基金Supported by the National Natural Science Foundation of China,No.81900743Heilongjiang Province Outstanding Young Medical Talents Training Grant Project,China,No.HYD2020YQ0007.
文摘BACKGROUND Diabetic intracerebral hemorrhage(ICH)is a serious complication of diabetes.The role and mechanism of bone marrow mesenchymal stem cell(BMSC)-derived exosomes(BMSC-exo)in neuroinflammation post-ICH in patients with diabetes are unknown.In this study,we investigated the regulation of BMSC-exo on hyperglycemia-induced neuroinflammation.AIM To study the mechanism of BMSC-exo on nerve function damage after diabetes complicated with cerebral hemorrhage.METHODS BMSC-exo were isolated from mouse BMSC media.This was followed by transfection with microRNA-129-5p(miR-129-5p).BMSC-exo or miR-129-5poverexpressing BMSC-exo were intravitreally injected into a diabetes mouse model with ICH for in vivo analyses and were cocultured with high glucoseaffected BV2 cells for in vitro analyses.The dual luciferase test and RNA immunoprecipitation test verified the targeted binding relationship between miR-129-5p and high-mobility group box 1(HMGB1).Quantitative polymerase chain reaction,western blotting,and enzyme-linked immunosorbent assay were conducted to assess the levels of some inflammation factors,such as HMGB1,interleukin 6,interleukin 1β,toll-like receptor 4,and tumor necrosis factorα.Brain water content,neural function deficit score,and Evans blue were used to measure the neural function of mice.RESULTS Our findings indicated that BMSC-exo can promote neuroinflammation and functional recovery.MicroRNA chip analysis of BMSC-exo identified miR-129-5p as the specific microRNA with a protective role in neuroinflammation.Overexpression of miR-129-5p in BMSC-exo reduced the inflammatory response and neurological impairment in comorbid diabetes and ICH cases.Furthermore,we found that miR-129-5p had a targeted binding relationship with HMGB1 mRNA.CONCLUSION We demonstrated that BMSC-exo can reduce the inflammatory response after ICH with diabetes,thereby improving the neurological function of the brain.
文摘AIM:To compare and analyse the diagnostic efficacy of the College of Optometrists Vision Development Quality of Life Questionnaire(COVD-QOL)and the Convergence Insufficiency Symptom Survey(CISS)in detecting convergence insufficiency and to compare their diagnostic value in clinical applications.METHODS:Using the diagnostic test method,62 adult patients with convergence insufficiency(age:24.74±3.75y)and 62 normal participants(age:23.61±3.13y)who visited the Optometry Clinic of West China Hospital of Sichuan University from April 2021 to January 2023 were included.All subjects completed the CISS and COVD-QOL.Statistical analysis of the sensitivity and specificity of the CISS and COVD-QOL and comparison and joint experimental analysis of their diagnostic efficacy were performed.RESULTS:The sensitivity of the CISS and COVD-QOL for convergence insufficiency was 64.5%and 71.0%,respectively,while the specificity was 96.8%and 67.7%,respectively.Compared to the CISS alone,the combination of the CISS and COVD-QOL demonstrated lower sensitivity and specificity.The areas under the receiver operating characteristic curve of CISS,COVD-QOL and CISS combined with COVD-QOL were 0.806,0.694 and 0.782,respectively.CONCLUSION:Considering the low sensitivity of the CISS and the low specificity of the COVD-QOL,it is recommended to supplement these questionnaires with other screening tests for the detection of convergence insufficiency.
基金funded by the Deutsche Forschungsgemeinschaft(DFG),the BONFOR program of the Medical Faculty of the University of Bonn,and the Alexander-von-Humboldt Foundation.
文摘Alzheimer’s disease(AD)is the most common neurodegenerative disorder characterized by slow and progressive decline of cognitive and memory functions.In only approximately 5%of the cases,AD is familial,as often predisposed by genetic mutations(Hoogmartens et al.,2021),while sporadic AD accounts for approximately 95%of the cases.The amyloid cascade hypothesis is one of the fundamental hypotheses put out to explain AD pathogenesis as dysregulated homeostasis of amyloid-β(Aβ)peptides that leads to the accumulation of Aβplaques in the parenchyma,an anatomical hallmark of AD.
文摘Near-infrared spectroscopy(NIRS)has been increasingly utilized in both sport and health sciences to assess various physiological parameters related to exercise performance.1 NIRS methods coupled with the recent development of portable and wearable devices suitable for field-based measurements have revolutionized the study of exercise physiology and the determinants of exercise performance by providing real-time,non-invasive,and spatially localized measurements of tissue oxygenation dynamics.
基金supported by the Japan Science and Technology Agency-Precursory Research for Embryonic Science and Technology (JPMJPR22SA to MM)Japan Society for the Promotion of Science KA KENHI Grant-in-Aid for Scientific Research(JP21K07309 to HT,JP20H05688 and JP22K19365 to KN)+2 种基金Takeda Science Foundation (to KN)Keio Gijuku Academic Development Funds (to KN)Keio Gijuku Fukuzawa Memorial Fund (to KN)
文摘The cerebral cortex is comprised of properly localized cell types that exert their specific functions.In the developing brain,cells migrate from the germinal region to their functional locations(Silva et al.,2019;Cossart and Garel,2022).For example,neocortical excitatory neurons are generated in the cerebral ventricular and subventricular zones,move to the developing cortical plate via radial migration,and reside in a radial array of six neuronal layers(Oishi and Nakajima,2018).On the other hand,cortical interneurons are mainly generated in ganglionic eminences,migrate tangentially across the cerebral cortex,and reach their final destinations in the cortex(Lim et al.,2018).The failure of neuronal migration leads to defects in cortical layer formation.While the mechanisms of neuronal distribution have been well examined,how astrocytes are diffusely distributed in the cortex is still unclear.Astrocytes are glial cells in the cerebral cortex with several functions,including metabolic support and synapse formation(Abbott et al.,2006;Bosworth and Allen,2017;Allen and Lyons,2018).For example,astrocytes establish synaptic connectivity in the developing brain while they contact numerous synapses and maintain optimal neuronal activity in the adult brain.In the developing brain,astrocytes are primarily generated from radial glia after the neurogenic period.While a certain type of astrocyte called fibrous astrocytes populates the white matter,protoplasmic astrocytes migrate to the cortical plate during neural network formation.
基金funded by JSPS KAKENHI Grant Numbers JP26290015 and JP21H02655(to TK)from Ministry of Education,Culture,Sports,Science,and Technology of Japan(MEXT)。
文摘Cell adhesion plays pivotal roles in the morphogenesis of multicellular organisms.Epithelial cells form several types of cell-to-cell adhesion,including zonula occludens(tight junctions),zonula adhaerens(adherens junctions),and macula adhaerens(desmosomes).Although these adhesion complexes are basically observed only in epithelial cells,cadherins,which are the major cell adhesion molecules of adherens junctions,are expressed in both epithelial and non-epithelial tissues,including neural tissues(Kawauchi,2012).The cadherin superfamily consists of more than 100 members,but classic cadherins.
文摘Background: Chronic venous insufficiency (CVI) describes a condition that affects the venous system of the lower extremities due to venous hypertension (VH. The prevalence is between 5% - 30%. CVI is associated with older age, smoking, lower extremity trauma, presence of an arteriovenous shunt, and elevated estrogen levels. All patients should be initially treated with conservative management. Venoactive drugs like calcium dobesilate are useful. Objectives: The primary objective compared the clinical improvement in patients with CVI, grades 0 - 3 of the CEAP classification of chronic venous disease, produced by two formulations of calcium dobesilate: calcium dobesilate LP 1 g OD vs calcium dobesilate 500 mg BID, immediate release. The secondary objective assessed the side effects of both formulations. Method: All patients took one tablet and one capsule at 7 am, and one capsule at 7 pm, for 8 weeks. One group received dobesilate 1 g OD and the other group received dobesilate 500 md BID. They were evaluated after 15, 30 and 60 days of treatment, using the symptom evaluation scale. Results: In both groups, there was a significant decrease in the symptom score after 15 days. Four patients in the Dobesilate OD group: had adverse effects, which did not require suspension of treatment. In the BID dobesilate group, there was one therapeutic failure, and one case of gastric discomfort. Conclusions: Prolonged-release Calcium dobesilate 1 g OD is as effective as calcium dobesilate 500 mg BID for the treatment of patients with chronic venous insufficiency.
基金Supported by The National Research Foundation of Korea Grant Funded by The Korea Government(MSIT),No.00219725.
文摘Pain is a common complaint among patients seeking medical care.If left un-treated,pain can become chronic,significantly affecting patients’quality of life.An accurate diagnosis of the underlying cause of pain is crucial for effective treatment.Chronic venous insufficiency(CVI)is frequently overlooked by pain physicians.Moreover,many pain physicians lack sufficient knowledge about CVI.CVI is a common condition resulting from malfunctioning or damaged valves in lower limb veins.Symptoms of CVI,ranging from mild to severe,include pain,heaviness,fatigue,itching,swelling,skin color changes,and ulcers in the lower limbs.Recently,it has become more widely known that these symptoms can be attributed to CVI.Even slight or mild CVI can cause related symptoms.Pain physicians primarily consider neuromusculoskeletal disorders when assessing patients with leg pain,and often neglect the possibility of CVI.In clinical practice,when pain physicians encounter patients with unresolved leg pain,they must assess whether the patients exhibit symptoms of CVI and conduct tests to differ-entiate CVI from other potential causes.
文摘Background: Addison’s disease is a rare disorder of the adrenal cortex that leads to inadequate production of cortisol initially followed by aldosterone and androgens. Its manifestations are usually slow and non-specific with potential for life-threatening adrenal crisis following hypermetabolic demands (infection, trauma, surgery). Patients: Over the past 10 years, 19 CRD-patients were diagnosed with occult PAI in our center. Results: Unprovoked hypotension was the most common manifestations of occult PAI and was the unmasking event in 11 (58%). It was without significant cardiac and/or severe systemic sepsis and was refractory to isotonic saline infusions. Equal number of the remaining patients (n = 2) presented with persistent and inexplicable electrolytes abnormalities viz. 1) hyponatremia despite restricted oral fluid intake, lack of dehydration and massive fluid overload, as well as 2) hyperkalemia despite potassium-restricted diet, hyperkalemic drugs and adequate therapy with Furosemide and low-potassium dialysis-baths. On the other hand, similar proportions presented with unprovoked 3) progressive weight loss, decrease appetite and cachexia as well as 4) frequent hypoglycemic attacks. All patients were treated and were medically stable after 29 (2 - 60) months of follow up. Autoantibodies to 21-hydroxylase enzyme were positive in 16 (90%). At diagnosis, and subsequent follow up, only 7 patients (37%) had multi-endocrine dysfunction of whom 2 with type 1 and 5 with type 2. Conclusion: High index of suspicion should be exerted in diagnosis of PAI in patients with CRD, since its clinical picture is similar to CRD manifestations and complications. In those patients, confirmatory tests and specific management can save their lives. .
文摘BACKGROUND Intracerebral hemorrhage mainly occurs in middle-aged and elderly patients with hypertension,and surgery is currently the main treatment for hypertensive cerebral hemorrhage,but the bleeding caused by surgery will cause damage to the patient's nerve cells,resulting in cognitive and motor dysfunction,resulting in a decline in the patient's quality of life.AIM To investigate associations between cerebral arterial blood flow and executive and cognitive functions in depressed patients after acute hypertensive cerebral hemorrhage.METHODS Eighty-nine patients with depression after acute hypertensive cerebral hemorrhage who were admitted to our hospital between January 2019 and July 2021 were selected as the observation group,while 100 patients without depression who had acute hypertensive cerebral hemorrhage were selected as the control group.The attention span of the patients was assessed using the Paddle Pin Test while executive function was assessed using the Wisconsin Card Sorting Test(WCST)and cognitive function was assessed using the Montreal Cognitive Assessment Scale(MoCA).The Hamilton Depression Rating Scale(HAMD-24)was used to evaluate the severity of depression of involved patients.Cerebral arterial blood flow was measured in both groups.RESULTS The MoCA score,net scores I,II,III,IV,and the total net score of the scratch test in the observation group were significantly lower than those in the control group(P<0.05).Concurrently,the total number of responses,number of incorrect responses,number of persistent errors,and number of completed responses of the first classification in the WCST test were significantly higher in the observation group than those in the control group(P<0.05).Blood flow in the basilar artery,left middle cerebral artery,right middle cerebral artery,left anterior cerebral artery,and right anterior cerebral artery was significantly lower in the observation group than in the control group(P<0.05).The basilar artery,left middle cerebral artery,right middle cerebral artery,left anterior cerebral artery,and right anterior cerebral artery were positively correlated with the net and total net scores of each part of the Paddle Pin test and the MoCA score(P<0.05),and negatively correlated with each part of the WCST test(P<0.05).In the observation group,the post-treatment improvement was more prominent in the Paddle Pin test,WCST test,HAMD-24 score,and MoCA score compared with those in the pre-treatment period(P<0.05).Blood flow in the basilar artery,left middle cerebral artery,right middle cerebral artery,left anterior cerebral artery,and right anterior cerebral artery significantly improved in the observation group after treatment(P<0.05).CONCLUSION Impaired attention,and executive and cognitive functions are correlated with cerebral artery blood flow in patients with depression after acute hypertensive cerebral hemorrhage and warrant further study.
基金Supported by the Cohort Construction Project of Peking University Third Hospital,No.BYSYDL2022013Clinical Key Project of Peking University Third Hospital,No.BYSY2023049+1 种基金Special Grant for Capital Health Research and Development,No.2022-2-4097and Funding from State Key Laboratory of Female Fertility Promotion,Center for Reproductive Medicine,Department of Obstetrics and Gynecology,Peking University Third Hospital,No.BYSYSZKF2023027.
文摘The incidence of premature ovarian insufficiency(POI)is increasing worldwide,particularly among younger women,posing a significant challenge to fertility.In addition to menopausal symptoms,POI leads to several complications that profoundly affect female reproductive function and overall health.Unfortunately,current clinical treatment strategies for this condition are limited and often yield unsatisfactory outcomes.These approaches typically involve hormone repla-cement therapy combined with psychological support.Recently,mesenchymal stem cell(MSC)therapies for POI have garnered considerable attention in global research.MSCs can restore ovarian reproductive and endocrine functions through diverse mechanisms,including controlling differentiation,promoting angiogenesis,regulating ovarian fibrosis,inhibiting apoptosis,enhancing autocrine and paracrine effects,suppressing inflammation,modulating the immune system,and genetic regulation.This editorial offers a succinct summary of the application of MSC therapy in the context of POI,providing evidence for groundbreaking medical approaches that have potential to enhance reproductive health and overall well-being for women.