Mitochondria DNA 4977 bp Common Deletion in Peripheral Whole Blood from Healthy Donors

To investigate the distribution of mitochondria ONA 4 977 bp deletion, a common deletion （CD）, in normal populations of Chinese, human peripheral blood samples from sixty healthy donors were collected, and levels of the CD in genomic DNA from the samples were detected using real-time PCR. The results showed that the CD was found in 27 health donors, with its positive rate being 45% （27/60）. The CD ratio was between 0 and 0.000308%, and not affected by age and gender in sixty healthy donors. Our studies indicate that the CD ratio is low, and do not show the age-dependent accumulation and any gender difference in peripheral whole blood from the normal Chinese population.

The clinical significance of detection of specific CK-20 mRNA in peripheral venous blood from patients with bladder carcinoma

Objective To determine the diagnostic significance of detecting the specific epithelial keratin CK-20 mRNA in peripheral venous blood from patients with bladder carcinomas. Methods Reverse transcription coupled with two-step polymerase chain reaction (nested RT-PCR) was used to detect CK-20 mRNA expression in the peripheral blood from patients with blodder carcinomas. Results Detection of CK-20 mRNA expression was positive in 37 of 91 patients with bladder carcinoma (41 % ). Among 20 patients with distant metastasis, 17 were positive (85 % ). CK-20 mRNA was not detectable in the blood samples from 25 normal individuals. The frequency of positive CK-20 mRNA expression was signficantly higher in those with distant metastasis. Conclusion The presence of CK-20 mRNA expression in peripheral blood may be used as an early indicator of hematogenous metastasis of bladder carcinoma cells. 6 refs,1 tab.

Blood from Mosquito Traps Finnish Suspect

Police in Finland believe they have caught a car-thief thanks to a DNA sample taken from a sample of his blood found inside a mosquito.

Blood cell counts and nonalcoholic fatty liver disease: Evidence from Mendelian randomization analysis

BACKGROUND Previous research has highlighted correlations between blood cell counts and chronic liver disease.Nonetheless,the causal relationships remain unknown.AIM To evaluate the causal effect of blood cell traits on liver enzymes and nonalcoholic fatty liver disease(NAFLD)risk.METHODS Independent genetic variants strongly associated with blood cell traits were extracted from a genome-wide association study(GWAS)conducted by the Blood Cell Consortium.Summary-level data for liver enzymes were obtained from the United Kingdom Biobank.NAFLD data were obtained from a GWAS meta-analysis(8434 cases and 770180 controls,discovery dataset)and the Fingen GWAS(2275 cases and 372727 controls,replication dataset).This analysis was conducted using the inverse-variance weighted method,followed by various sensitivity analyses.RESULTS One SD increase in the genetically predicted haemoglobin concentration(HGB)was associated with aβof 0.0078(95%CI:0.0059-0.0096),0.0108(95%CI:0.0080-0.0136),0.0361(95%CI:0.0156-0.0567),and 0.0083(95%CI:00046-0.0121)for alkaline phosphatase(ALP),alanine aminotransferase(ALT),aspartate aminotransferase,and gammaglutamyl transferase,respectively.Genetically predicted haematocrit was associated with ALP(β=0.0078,95%CI:0.0052-0.0104)and ALT(β=0.0057,95%CI:0.0039-0.0075).Genetically determined HGB and the reticulocyte fraction of red blood cells increased the risk of NAFLD[odds ratio(OR)=1.199,95%CI:1.087-1.322]and(OR=1.157,95%CI:1.071-1.250).The results of the sensitivity analyses remained significant.CONCLUSION Novel causal blood cell traits related to liver enzymes and NAFLD development were revealed through Mendelian randomization analysis,which may facilitate the diagnosis and prevention of NAFLD.

Ambient Fine Particulate Matter Exposure and Blood Pressure:Evidence from a Large Chinese Multiple Follow-Up Study

Objective This study aimed to investigate the association of ambient PM_(2.5)exposure with blood pressure(BP)at the population level in China.Methods A total of 14,080 participants who had at least two valid blood pressure records were selected from the China Health and Retirement Longitudinal Survey during 2011–2015.Their long-term PM_(2.5)exposure was assessed at the geographical level,on the basis of a regular 0.1°×0.1°grid over China.A mixed-effects regression model was used to assess associations.Results Each decrease of 10μg/m^(3)in the 1 year-mean PM_(2.5)concentration(FPM1Y)was associated with a decrease of 1.24[95%confidence interval(CI):0.84–1.64]mmHg systolic BP(SBP)and 0.50(95%CI:0.25–0.75)mmHg diastolic BP(DBP),respectively.A robust association was observed between the long-term decrease in PM_(2.5)and decreased BP in the middle-aged and older population.Using a generalized additive mixed model,we further found that SBP increased nonlinearly overall with FPM1Y but in an approximately linear range when the FPM1Y concentration was<70μg/m^(3);In contrast,DBP increased approximately linearly without a clear threshold.Conclusion Efficient control of PM_(2.5)air pollution may promote vascular health in China.Our study provides robust scientific support for making the related air pollution control policies.

Characteristics of traumatic brain injury models:from macroscopic blood flow changes to microscopic mitochondrial changes

Controlled cortical impingement is a widely accepted method to induce traumatic brain injury to establish a traumatic brain injury animal model.A strike depth of 1 mm at a certain speed is recommended for a moderate brain injury and a depth of>2 mm is used to induce severe brain injury.However,the different effects and underlying mechanisms of these two model types have not been proven.This study investigated the changes in cerebral blood flow,differences in the degree of cortical damage,and differences in motor function under different injury parameters of 1 and 2 mm at injury speeds of 3,4,and 5 m/s.We also explored the functional changes and mitochondrial damage between the 1 and 2 mm groups in the acute(7 days)and chronic phases(30 days).The results showed that the cerebral blood flow in the injured area of the 1 mm group was significantly increased,and swelling and bulging of brain tissue,increased vascular permeability,and large-scale exudation occurred.In the 2 mm group,the main pathological changes were decreased cerebral blood flow,brain tissue loss,and cerebral vasospasm occlusion in the injured area.Substantial motor and cognitive impairments were found on day 7 after injury in the 2 mm group;at 30 days after injury,the motor function of the 2 mm group mice recovered significantly while cognitive impairment persisted.Transcriptome sequencing showed that compared with the 1 mm group,the 2 mm group expressed more ferroptosis-related genes.Morphological changes of mitochondria in the two groups on days 7 and 30 using transmission electron microscopy revealed that on day 7,the mitochondria in both groups shrank and the vacuoles became larger;on day 30,the mitochondria in the 1 mm group became larger,and the vacuoles in the 2 mm group remained enlarged.By analyzing the proportion of mitochondrial subgroups in different groups,we found that the model mice had different patterns of mitochondrial composition at different time periods,suggesting that the difference in the degree of damage among traumatic brain injury groups may reflect the mitochondrial changes.Taken together,differences in mitochondrial morphology and function between the 1 and 2 mm groups provide a new direction for the accurate classification of traumatic brain injury.Our results provide reliable data support and evaluation methods for promoting the establishment of standard mouse controlled cortical impingement model guidelines.

Astrocytes dynamically regulate the blood-brain barrier in the healthy brain

The blood-brain barrier(BBB)(discovered and defined by Max Lewandowsky and Lina Stern,and not,as it is universally,and yet erroneously believed,by Paul Ehrlich(Verkhratsky and Pivoriunas,2023))that separates the nervous system from the circulation is evolutionarily conserved from arthropods to man.The primeval BBB of the invertebrates and some early vertebrates was made solely by glial cells and secured(in invertebrates)by septate junctions.

In vivo label-free measurement of blood flow velocity symmetry based on dual line scanning third-harmonic generation microscopy excited at the 1700 nm window

Measurement of bloodflow velocity is key to understanding physiology and pathology in vivo.While most measurements are performed at the middle of the blood vessel,little research has been done on characterizing the instantaneous bloodflow velocity distribution.This is mainly due to the lack of measurement technology with high spatial and temporal resolution.Here,we tackle this problem with our recently developed dual-wavelength line-scan third-harmonic generation(THG)imaging technology.Simultaneous acquisition of dual-wavelength THG line-scanning signals enables measurement of bloodflow velocities at two radially symmetric positions in both venules and arterioles in mouse brain in vivo.Our results clearly show that the instantaneous bloodflow velocity is not symmetric under general conditions.

Clinical nursing value of predictive nursing in reducing complications of pregnant women undergoing short-term massive blood transfusion during cesarean section

BACKGROUND Cesarean hemorrhage is one of the serious complications,and short-term massive blood transfusion can easily cause postoperative infection and physical stress response.However,predictive nursing intervention has important clinical significance for it.AIM To explore the effect of predictive nursing intervention on the stress response and complications of women undergoing short-term mass blood transfusion during cesarean section(CS).METHODS A clinical medical record of 100 pregnant women undergoing rapid mass blood transfusion during sections from June 2019 to June 2021.According to the different nursing methods,patients divided into control group(n=50)and observation group(n=50).Among them,the control group implemented routine nursing,and the observation group implemented predictive nursing intervention based on the control group.Moreover,compared the differences in stress res-ponse,complications,and pain scores before and after the nursing of pregnant women undergoing rapid mass blood transfusion during CS.RESULTS The anxiety and depression scores of pregnant women in the two groups were significantly improved after nursing,and the psychological stress response of the observation group was significantly lower than that of the control group(P<0.05).The heart rate and mean arterial pressure(MAP)of the observation group during delivery were lower than those of the control group,and the MAP at the end of delivery was lower than that of the control group(P<0.05).Moreover,different pain scores improved significantly in both groups,with the observation group considerably less than the control group(P<0.05).After nursing,complications such as skin rash,urinary retention,chills,diarrhea,and anaphylactic shock in the observation group were 18%,which significantly higher than in the control group(4%)(P<0.05).CONCLUSION Predictive nursing intervention can effectively relieve the pain,reduce the incidence of complications,improve mood and stress response,and serve as a reference value for the nursing of women undergoing rapid mass transfusion during CS.

Fever glove hand-shake method safe blood collection from children's fingertips in COVID-19 fever clinic

BACKGROUND During the coronavirus disease 2019(COVID-19)epidemic,the fever clinic is an important link for screening and diagnosing whether a patient is infected with the novel coronavirus.Blood collection from children’s fingertips is a commonly used detection method;however,in children,the blood collection process may cause discomfort and resistance.To address this problem,the use of heating gloves combined with hand swinging can be considered for fingertip blood collection in children.AIM To explore the application of fever gloves with the handshaking method for fingertip blood collection from children in fever clinics during the COVID-19 epidemic.METHODS A total of 100 children were selected for fingertip blood collection at the fever clinic of our hospital from June 2022 to June 2023 and were divided into two groups using a randomized numerical table method,with 50 cases in each group,including the control and observation groups.The patients in the control group followed the doctor's instructions to cooperate with the routine fingertip blood collection method,and the patients in the observation group followed the doctor's instructions to cooperate with the static fever gloves with the shaking hands method of children's fingertip blood collection.The level of the six blood routine and collection indexes,and the satisfaction of the examination of the patients in the peripheral blood group and the fever gloves with the shaking hands method of the children's fingertip blood collection group were compared.RESULTS The red and white blood cell count,hemoglobin,and red blood cell pressure volume in the observation group were higher than those in the control group(P<0.05);the platelet count in the control group was lower than that in the observation group(P<0.05);the number of times of squeezing the fingertip,the average time of blood collection,and the score of puncture pain in the observation group were significantly better than those in the control group(P<0.05);and satisfaction with the routine blood examination in the observation group was greater than that in the control group.CONCLUSION The application value of the fever gloves with shaking hands method for children's fingertip blood collection was better,the accuracy of examination indexes was higher,and patient satisfaction with the examination was greater.

Trends in Bacterial Blood Culture Isolates and Resistance in Children in Two Microbiologic Eras from a Tertiary Health Facility in North East Nigeria

Introduction: Antimicrobial Resistance surveillance is predicated on blood culture as a priority clinical specimen in especially resource limited settings. Establishing trends in blood stream infections and resistance patterns can inform institutional and national policy on antimicrobial stewardship, surveillance, infection prevention and control. Methodology: Blood Culture isolates in children (0 - 18 years) by conventional method from 2008-2012 and Bactec Automated culture system from 2015-2020 were retrieved. Information analyzed included age, sex, month, and year and culture growth/identity of microorganisms and their sensitivity/resistance patterns. Clinical and Laboratory Standards Institute (CLSI) guideline for antibiotic susceptibility testing was used. Results: 20,540 children were admitted: 8964 (44.6%) and 11,630 (55.4%) in the Manual and Bactec blood culture era respectively. Blood cultures were done in 5271 in the manual culture era and 1077 in the Bactec culture era;of these cultures, 514 (9.7%) and 461 (42.8%) were positive for isolates in the respective era (p = 0.01). There were no statistically significant differences in trend between positive and negative blood cultures in males and females. Newborns, followed by children 1 - 5 years had more blood culture performed on them than other age categories. In general, there is no significant relationship in blood culture outcomes between the age categories and sex of the patients. The isolation of Staph aureus, Citrobacter and Alkaligenes increased two-fold with Bactec automated system. Resistance to the quinolones and the penicillin was high. Resistance trend to Genticin, an aminoglycoside was less than 40%. Resistance to Ceftazidime was high. Conclusion: Antimicrobial resistance surveillance is critical to reduce AMR related morbidity and mortality.

Clinical and Therapeutic Evaluation of Hypertensives According to the Practice of Ambulatory Blood Pressure Measurement (ABPM) at the Bel Air International Clinic in Conakry from January 1, 2019 to November 30, 2022

Introduction: Ambulatory Blood Pressure Measurement (ABPM) is a non- invasive examination recommended for subjects at high cardiovascular risk, and those requiring a nocturnal drop in BP such as elderly and obese subjects, those with secondary hypertension or resistant, diabetics, subjects with metabolic syndrome or sleep apnea syndrome. The objective of this study was to evaluate the contribution of ABPM in the diagnosis and evaluation of the level of control of hypertension under treatment at the Bel Air international clinic. Materials and Methods: This is a retrospective, cross-sectional and descriptive study, carried out at the Bel Air International Clinic in Conakry (Guinea) between January 2019 and November 30, 2022. It included a consecutive series of 180 consenting patients recruited through an ambulatory measurement of 24-hour blood pressure from a FUGADA brand device. Results: We collected 180 patients, with a male predominance (sex-ratio M/F = 2.46). The mean age of the patients was 48.48 ± 14.23 years. The most represented age group was that of 32 to 42 years with 50 cases (27.8%) followed by that of 43 to 52 years with 42 cases or 23.3%. The indication was for diagnostic purposes in 106 cases 58.9%, the therapeutic evaluation in 58 patients (32.2%). The examination was prescribed by a cardiologist in 98 cases (54.4%), a general practitioner in 71 cases (39.4%), a neurologist in 11 cases (6.1%). In the therapeutic evaluation, high blood pressure was controlled in 24 patients (13.3%) and uncontrolled in 34 cases (18.9%). In the diagnostic indication, high blood pressure was confirmed in 79 cases (43.9%) with a statistically significant link (Chi2 = 4.57 and p-value = 0.032). The nycthemeral mean was 187.27 ± 26.22 mmHg for systolic blood pressure (SBP) and 110.37 ± 19.06 mmHg for diastolic blood pressure (DBP), during the day, 151.64 ± 21.45 mmHg for SBP and 71.59 ± 8.67 mmHg for diastolic blood pressure. During the study 65 patients (36.1%) were identified as dippers and 115 patients (63.9%) were no-dipping. The antihypertensive protocol used was monotherapy in 68 cases (37.8%), dual therapy in 46 cases (25.6%), triple therapy in 17 cases (9.4%). However 39 patients or 21.7% were not taking any antihypertensive. Conclusion: This preliminary study, despite the modest sample size, showed the importance of ABPM as a tool for diagnosis, monitoring of hypertensive patients and therapeutic adaptation. A large-scale national study would be necessary for the rational use of ambulatory blood pressure measurement in our context in order to improve the management of hypertensive patients.

The effectiveness of physical activity interventions on blood pressure in children and adolescents:A systematic review and network meta-analysis

Background:High blood pressure(BP)is a major contributor to mortality and cardiovascular diseases.Despite the known benefits of exercise for reducing BP,it is crucial to identify the most effective physical activity(PA)intervention.This systematic review and network meta-analysis(NMA)aimed to evaluate the available evidence on the effectiveness of various PA interventions for reducing BP and to determine their hierarchy based on their impact on BP.Methods:A search of PubMed,SPORTDiscus,PsycINFO,Web of Science,CINAHL,Cochrane,and Eric databases was conducted up to December 2022 for this systematic review and NMA.Randomized controlled trials and quasi-experimental studies targeting healthy children and adolescents aged 6-12 years old were included in this study.Only studies that compared controlled and intervention groups using PA or exercise as the major influence were included.We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses(PRISMA)guidelines.Three independent investigators performed the literature screening,data extraction,and risk of bias assessment.We used Bayesian arm-based NMA to synthesize the data.The primary outcomes were systolic BP and diastolic BP.We calculated the mean differences(MDs)in systolic BP and diastolic BP before and after treatment.Mean treatment differences were estimated using NMA and random-effect models.Results:We synthesized 27 studies involving 15,220 children and adolescents.PA combined with nutrition and behavior change was the most effective intervention for reducing both systolic BP and diastolic BP(MD=-8.64,95%credible interval(95%CI):-11.44 to-5.84;MD=-6.75,95%CI:-10.44 to-3.11),followed by interventions with multiple components(MD=-1.39,95%CI:-1.94 to-0.84;MD=-2.54,95%CI:-4.89 to-0.29).Conclusion:Our findings suggest that PA interventions incorporating nutrition and behavior change,followed by interventions with multiple components,are most effective for reducing both systolic BP and diastolic BP in children and adolescents.

Excess dietary Lys reduces feed intake, stimulates jejunal CCK secretion and alters essential and non‑essential blood AA profile in pigs

Background Commercial diets are frequently formulated to meet or exceed nutrient levels including those of lim-iting essential amino acids(AA)covering potential individual variations within the herd.However,the provision of dietary excess of AA,such as Lys,may lead to reduced appetite and growth in pigs.The mechanisms modulat-ing these responses have not been extensively investigated.This study evaluated the effect of Lys dietary excesses on performance and satiety biomarkers in post weaning pigs.Methods Twenty-four pigs aged 21 d and weighing 6.81±0.12kg(mean±SEM)were individually housed and offered 1 of 4 dietary treatments for 3weeks:a diet containing a standardized ileal digestible Lys reaching 100%(T0),120%(T1),150%(T2)or 200%(T3)of the NRC(2012)requirements.At the end of the experiment,blood samples from the cephalic vein of the T0 and T3 groups were obtained for AA analysis.In addition,primary intestinal cultures from T0 pigs were used,following their humane killing,to evaluate the effect of Lys on gut hormone secretion and AA sensors gene expression under ex vivo conditions.Results Feed intake was linearly reduced(P<0.001)and the weight gain to feed ratio reduced(P<0.10)with increased dietary levels of Lys during the third-and first-week post weaning,respectively.Cholecystokinin con-centration(P<0.05)and the metabotropic glutamate receptor 1 and the solute carrier family 7 member 2(P<0.10)gene expression was enhanced in proximal jejunum tissues incubated with Lys at 20mmol/L when compared to the control(Lys 0mmol/L).Plasma Lys and Glu(P<0.05)concentration increased in the T3 compared to T0 pigs.In contrast,plasma levels of His,Val,Thr,Leu(P<0.05)and Gln(P<0.10)were lower in T3 than T0 pigs.Conclusion The present results confirm that excess dietary Lys inhibits hunger in pigs.Moreover,the results provide evidence of pre-and post-absorptive mechanisms modulating these responses.Lys dietary excesses should be nar-rowed,when possible,to avoid negative effects of the AA on appetite in pigs.

Association of Thyroid Nodules with Various Elements in Urine and Blood Serum: A Case-Control Study

Thyroid nodules are a common clinical problem caused by various factors,including environmental and nutritional factors and genetic background.The environment can modulate and influence not only the risk of thyroid nodules but also the severity of disease in humans[1].The environment is awash with elements,and all mineral elements,including heavy metals and trace elements,are considered potentially toxic.A significantly higher incidence of thyroid cancer has been reported in populations exposed to low doses of metallic elements in volcanic areas over a long period[2].As research on thyroid disorders continues,it is becoming clear that abnormalities in trace elements in the body can affect the development of thyroid-related disorders.

Identification of Key Blood Biomarkers Linking Di(2-ethylhexyl)Phthalate and Autoimmune Diseases in Adolescents Mice

Di(2-ethylhexyl)phthalate(DEHP)is a widely used plasticizer known for its reproductive developmental and immune system toxicity,mainly through esophagal,dermal,and respiratory exposure^([1-3]).Maternal exposure to DEHP during pregnancy can lead to adverse birth outcomes in offspring,including impacts on the thyroid system of adolescent offspring^([2-4]).

Sex Disparities in the Association of Blood Pressure Parameters and Arterial Sclerosis Risk

Cardiovascular disease(CVD)is the leading cause of death worldwide[1].Arterial sclerosis(AS)and hypertension are the main risk factors and pathological bases of CVD.Higher pulse wave velocity(PWV)measurements could reflect early progression of atherosclerosis.Based on the structure-function properties of the vascular wall and hemodynamics,strong evidence suggests that any increase in blood pressure levels can mechanically impair the ability of the endothelium to maintain vascular homeostasis[2].High levels of blood pressure parameters,such as systolic blood pressure(SBP),diastolic blood pressure(DBP),pulse pressure(PP),and mean arterial pressure(MAP)have been identified as essential risk biomarkers for atherosclerosis.

Blood biomarkers of Alzheimer’s disease:important considerations for use in clinical practice

Introduction:Fluid and positron emission tomography(PET)biomarkers that enable the detection of the hallmark proteins of Alzheimer’s disease(AD)(amyloid and tau)have revolutionized our approach to the diagnosis of AD.The evolution of AD diagnostic criteria to include biological characterization(Alzheimer’s Association Working Group,2023)provides an appropriate framework to reduce levels of clinico-pathologic mismatch and improve in-vivo diagnostic accuracy.As the therapeutic landscape for neurodegenerative disease evolves,it is increasingly incumbent on clinicians to provide timely,and pathologically precise diagnoses for patients.However,the expensive and invasive nature of these tests limits their scalability.

Blood Pressure Estimation with Phonocardiogram on CNN-Based Approach

Monitoring blood pressure is a critical aspect of safeguarding an individual’s health,as early detection of abnormal blood pressure levels facilitates timely medical intervention,ultimately leading to a reduction in mortality rates associated with cardiovascular diseases.Consequently,the development of a robust and continuous blood pressure monitoring system holds paramount significance.In the context of this research paper,we introduce an innovative deep learning regression model that harnesses phonocardiogram(PCG)data to achieve precise blood pressure estimation.Our novel approach incorporates a convolutional neural network(CNN)-based regression model,which not only enhances its adaptability to spatial variations but also empowers it to capture intricate patterns within the PCG signals.These advancements contribute significantly to the overall accuracy of blood pressure estimation.To substantiate the effectiveness of our proposed method,we meticulously gathered PCG signal data from 78 volunteers,adhering to the ethical guidelines of Suranaree University of Technology(Human Research Ethics number EC-65-78).Subsequently,we rigorously preprocessed the dataset to ensure its integrity.We further employed a K-fold cross-validation procedure for data division and alignment,combining the resulting datasets with a CNNfor blood pressure estimation.The experimental results are highly promising,yielding aMeanAbsolute Error(MAE)and standard deviation(STD)of approximately 10.69±7.23 mmHg for systolic pressure and 6.89±5.22 mmHg for diastolic pressure.Our study underscores the potential for precise blood pressure estimation,particularly using PCG signals,paving the way for a practical,non-invasive method with broad applicability in the healthcare domain.Early detection of abnormal blood pressure levels can facilitate timely medical interventions,ultimately reducing cardiovascular disease-related mortality rates.

Beyond wrecking a wall:revisiting the concept of blood–brain barrier breakdown in ischemic stroke

The blood–brain barrier constitutes a dynamic and interactive boundary separating the central nervous system and the peripheral circulation.It tightly modulates the ion transport and nutrient influx,while restricting the entry of harmful factors,and selectively limiting the migration of immune cells,thereby maintaining brain homeostasis.Despite the well-established association between blood–brain barrier disruption and most neurodegenerative/neuroinflammatory diseases,much remains unknown about the factors influencing its physiology and the mechanisms underlying its breakdown.Moreover,the role of blood–brain barrier breakdown in the translational failure underlying therapies for brain disorders is just starting to be understood.This review aims to revisit this concept of“blood–brain barrier breakdown,”delving into the most controversial aspects,prevalent challenges,and knowledge gaps concerning the lack of blood–brain barrier integrity.By moving beyond the oversimplistic dichotomy of an“open”/“bad”or a“closed”/“good”barrier,our objective is to provide a more comprehensive insight into blood–brain barrier dynamics,to identify novel targets and/or therapeutic approaches aimed at mitigating blood–brain barrier dysfunction.Furthermore,in this review,we advocate for considering the diverse time-and location-dependent alterations in the blood–brain barrier,which go beyond tight-junction disruption or brain endothelial cell breakdown,illustrated through the dynamics of ischemic stroke as a case study.Through this exploration,we seek to underscore the complexity of blood–brain barrier dysfunction and its implications for the pathogenesis and therapy of brain diseases.