Gestational diabetes is typically diagnosed in the late second or third trimester of pregnancy.It is one of the most common metabolic disorders among expectant mothers,with potential serious short-and long-term compli...Gestational diabetes is typically diagnosed in the late second or third trimester of pregnancy.It is one of the most common metabolic disorders among expectant mothers,with potential serious short-and long-term complications for both maternal and offspring health.C-peptide is secreted from pancreatic beta-cells into circulation in equimolar amounts with insulin.It is a useful biomarker to estimate the beta-cell function because it undergoes negligible hepatic clearance and consequently it has a longer half-life compared to insulin.Pregnancy induces increased insulin resistance due to physiological changes in hormonal and metabolic homeostasis.Inadequate compensation by islet beta-cells results in hyperglycemia.The standard oral glucose tolerance test at 24-28 wk of gestation sets the diagnosis.Accumulated evidence from prospective studies indicates a link between early pregnancy C-peptide levels and the risk of subsequent gestational diabetes.Elevated C-peptide levels and surrogate glycemic indices at the beginning of pregnancy could prompt appropriate strategies for secondary prevention.展开更多
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...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.展开更多
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 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.展开更多
BACKGROUND Intramuscular corticosteroid injection may cause adverse effects such as dermal and/or subcutaneous atrophy,alopecia,hypopigmentation,and hyperpigmentation.Although cutaneous atrophy can spontaneously resol...BACKGROUND Intramuscular corticosteroid injection may cause adverse effects such as dermal and/or subcutaneous atrophy,alopecia,hypopigmentation,and hyperpigmentation.Although cutaneous atrophy can spontaneously resolve,several treatment options have been suggested for this condition.CASE SUMMARY In this paper,we report a case of corticosteroid injection induced lipoatrophy treated with autologous whole blood(AWB)injection,as the condition had been unresponsive to fractional laser therapy.A 29-year-old female patient visited the dermatology clinic complaining of skin depression on her right buttock area,which had appeared six months earlier.There had been only subtle improvement at the margins after fractional CO_(2) laser treatment;therefore,after obtaining informed consent from the patient,AWB treatment was initiated.One month after the first AWB injection,the size and depth of the lesion had noticeably improved,and a slight improvement was also observed in discoloration.CONCLUSION Close observation is the initial treatment of choice for steroid induced skin atrophy;however,for patients in need of immediate cosmetic improvement,AWB injection may be a safe and cost-effective alternative.展开更多
BACKGROUND Red blood cell distribution width(RDW)is associated with the development and progression of various diseases.AIM To explore the association between pretreatment RDW and short-term outcomes after laparoscopi...BACKGROUND Red blood cell distribution width(RDW)is associated with the development and progression of various diseases.AIM To explore the association between pretreatment RDW and short-term outcomes after laparoscopic pancreatoduodenectomy(LPD).METHODS A total of 804 consecutive patients who underwent LPD at our hospital between March 2017 and November 2021 were retrospectively analyzed.Correlations between pretreatment RDW and clinicopathological characteristics and short-term outcomes were investigated.RESULTS Patients with higher pretreatment RDW were older,had higher Eastern Cooperative Oncology Group scores and were associated with poorer short-term outcomes than those with normal RDW.High pretreatment RDW was an independent risk factor for postoperative complications(POCs)(hazard ratio=2.973,95%confidence interval:2.032-4.350,P<0.001)and severe POCs of grade IIIa or higher(hazard ratio=3.138,95%confidence interval:2.042-4.824,P<0.001)based on the Clavien-Dino classification system.Subgroup analysis showed that high pretreatment RDW was an independent risk factor for Clavien-Dino classi-fication grade IIIb or higher POCs,a comprehensive complication index score≥26.2,severe postoperative pancreatic fistula,severe bile leakage and severe hemorrhage.High pretreatment RDW was positively associated with the neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio and was negatively associated with albumin and the prognostic nutritional index.CONCLUSION Pretreatment RDW was a special parameter for patients who underwent LPD.It was associated with malnutrition,severe inflammatory status and poorer short-term outcomes.RDW could be a surrogate marker for nutritional and inflammatory status in identifying patients who were at high risk of developing POCs after LPD.展开更多
Amyotrophic lateral sclerosis is a devastating neurodegenerative disease for which the current treatment approaches remain severely limited.The principal pathological alterations of the disease include the selective d...Amyotrophic lateral sclerosis is a devastating neurodegenerative disease for which the current treatment approaches remain severely limited.The principal pathological alterations of the disease include the selective degeneration of motor neurons in the brain,brainstem,and spinal cord,as well as abnormal protein deposition in the cytoplasm of neurons and glial cells.The biological markers under extensive scrutiny are predominantly located in the cerebrospinal fluid,blood,and even urine.Among these biomarke rs,neurofilament proteins and glial fibrillary acidic protein most accurately reflect the pathologic changes in the central nervous system,while creatinine and creatine kinase mainly indicate pathological alterations in the peripheral nerves and muscles.Neurofilament light chain levels serve as an indicator of neuronal axonal injury that remain stable throughout disease progression and are a promising diagnostic and prognostic biomarker with high specificity and sensitivity.However,there are challenges in using neurofilament light chain to diffe rentiate amyotrophic lateral sclerosis from other central nervous system diseases with axonal injury.Glial fibrillary acidic protein predominantly reflects the degree of neuronal demyelination and is linked to non-motor symptoms of amyotrophic lateral sclerosis such as cognitive impairment,oxygen saturation,and the glomerular filtration rate.TAR DNA-binding protein 43,a pathological protein associated with amyotrophic lateral sclerosis,is emerging as a promising biomarker,particularly with advancements in exosome-related research.Evidence is currently lacking for the value of creatinine and creatine kinase as diagnostic markers;however,they show potential in predicting disease prognosis.Despite the vigorous progress made in the identification of amyotrophic lateral sclerosis biomarkers in recent years,the quest for definitive diagnostic and prognostic biomarke rs remains a formidable challenge.This review summarizes the latest research achievements concerning blood biomarkers in amyotrophic lateral sclerosis that can provide a more direct basis for the differential diagnosis and prognostic assessment of the disease beyond a reliance on clinical manifestations and electromyography findings.展开更多
Degenerative cervical myelopathy is a common cause of spinal cord injury,with longer symptom duration and higher myelopathy severity indicating a worse prognosis.While numerous studies have investigated serological bi...Degenerative cervical myelopathy is a common cause of spinal cord injury,with longer symptom duration and higher myelopathy severity indicating a worse prognosis.While numerous studies have investigated serological biomarkers for acute spinal cord injury,few studies have explored such biomarkers for diagnosing degenerative cervical myelopathy.This study involved 30 patients with degenerative cervical myelopathy(51.3±7.3 years old,12 women and 18 men),seven healthy controls(25.7±1.7 years old,one woman and six men),and nine patients with cervical spondylotic radiculopathy(51.9±8.6 years old,three women and six men).Analysis of blood samples from the three groups showed clear differences in transcriptomic characteristics.Enrichment analysis identified 128 differentially expressed genes that were enriched in patients with neurological disabilities.Using least absolute shrinkage and selection operator analysis,we constructed a five-gene model(TBCD,TPM2,PNKD,EIF4G2,and AP5Z1)to diagnose degenerative cervical myelopathy with an accuracy of 93.5%.One-gene models(TCAP and SDHA)identified mild and severe degenerative cervical myelopathy with accuracies of 83.3%and 76.7%,respectively.Signatures of two immune cell types(memory B cells and memory-activated CD4^(+)T cells)predicted levels of lesions in degenerative cervical myelopathy with 80%accuracy.Our results suggest that peripheral blood RNA biomarkers could be used to predict lesion severity in degenerative cervical myelopathy.展开更多
BACKGROUND Cellular therapies have started an important new therapeutic direction in autistic spectrum disorder(ASD),and the ample diversity of ASD pathophysiology and the different types of cell therapies prompt an e...BACKGROUND Cellular therapies have started an important new therapeutic direction in autistic spectrum disorder(ASD),and the ample diversity of ASD pathophysiology and the different types of cell therapies prompt an equally ample effort to employ clinical studies for studying the ASD causes and cell therapies.Stem cells have yielded so far mixed results in clinical trials,and at patient level the results varied from impressive to no improvement.In this context we have administered autologous cord blood(ACB)and a non-placebo,material intervention repre-sented by an individualized combination of supplements(ICS)to ASD children.METHODS CORDUS clinical study is a crossover study in which both oral ICS and intravenous ACB were sequentially administered to 56 children;ACB was infused as an inpatient procedure.Treatment efficacy was evaluated pre-treatment and post-treatment at 6 months by an independent psychotherapist with Autism Treatment Evaluation Checklist,Quantitative Checklist for Autism in Toddlers and a 16-item comparative table score,after interviewing the children’s parents and therapists.Before and after each intervention participants had a set of blood tests including inflammatory,metabolic and oxidative markers,and the neuronal specific enolase.RESULTS No serious adverse reactions were noted during and after cord blood or supplement administration.ACB improved evaluation scores in 78%of children with age 3–7-years(n=28),but was much less effective in kids older than 8 years or with body weight of more than 35 kg(n=28;only 11%of children improved scores).ICS yielded better results than ACB in 5 cases out of 28,while in 23 kids ACB brought more improvement than ICS(P<0.05);high initial levels of inflammation and ferritin were associated with no improvement.Ample individual differences were noted in children's progress,and statistically significant improvements were seen after ACB on areas such as verbalization and social interaction,but not on irritability or aggressive behavior.CONCLUSION ACB has superior efficacy to ICS in ASD;high inflammation,ferritin,age and body weight predict less improvement;more clinical studies are needed for studying ACB efficacy in ASD.展开更多
With the changes of life style, diabetes and its complications have become a major cause of morbidity and mortality. It is reasonable to anticipate a continued rise in the incidence of diabetes and its complications a...With the changes of life style, diabetes and its complications have become a major cause of morbidity and mortality. It is reasonable to anticipate a continued rise in the incidence of diabetes and its complications along with the aging of the population, increase in adult obesity rate, and other risk factors. Diabetic en- cephalopathy is one of the severe microvascular complications of diabetes, characterized by impaired cogni- tive functions, and electrophysiological, neurochemical, and structural abnormalities. It may involve direct neuronal damage caused by intracellular glucose. However, the pathogenesis of this disease is complex and its diagnosis is not very clear. Previous researches have suggested that chronic metabolic alterations, vascular changes, and neuronal apoptosis may play important roles in neuronai loss and damaged cognitive functions. Multiple factors are responsible for neuronal apoptosis, such as disturbed insulin growth factor (IGF) system, hyperglycemia, and the aging process. Recent data suggest that insulin/C-peptide deficiency may exert a primary and key effect in diabetic encephalopathy. Administration of C-peptide partially improves the condition of the IGF system in the brain and prevents neuronal apoptosis in the hippocampus of diabetic patients. Those findings provide a basis for application of C-peptide as a potentially effective therapy for diabetes and diabetic encephalopathy.展开更多
AIM To determine whether fasting C-peptide is an independent predictor for non-alcoholic fatty liver disease(NAFLD) in United States population.METHODS Using the National Health and Nutrition Examination Survey(NHANES...AIM To determine whether fasting C-peptide is an independent predictor for non-alcoholic fatty liver disease(NAFLD) in United States population.METHODS Using the National Health and Nutrition Examination Survey(NHANES) 1988-1994, NAFLD participants aged 20 or greater without any other liver diseases were included in this study. Excessive alcohol intake is defined as > 2 drinks per day for males and > 1 drink per day for females. C-peptide and 27 other factors known to be associated with NAFLD(e.g., age, gender, body mass index, waist circumference, race/ethnicity, liver chemistries, and other diabetes tests) were tested in both univariate and multivariate level using logistic regression with a P-value 0.05.RESULTS Of 18825 participants aged ≥ 20, 3235 participants(n = 3235) met inclusion criteria. There were 23 factors associated with NAFLD by univariate analysis. 9 factors, ranked by the highest change in pseudo R2, were found to be significant predictors of NAFLD in multivariate model: waist circumference, fasting C-peptide, natural log of alanine aminotransferase(ALT), total protein, beingMexican American, natural log of glycated hemoglobin, triglyceride level, being non-Hispanic white, and ferritin level. CONCLUSION Together with waist circumference and ALT, fasting C-peptide is among three most important predictors of NAFLD in United States population in the NHANES data set. Further study is needed to validate the clinical utility of fasting C-peptide in diagnosis or monitoring insulin resistance in NAFLD patients.展开更多
Diabetes is associated with several complications such as retinopathy, nephropathy, neuropathy and cardiovascular diseases. Currently, insulin is the main used medication for management of insulin-dependentdiabetes me...Diabetes is associated with several complications such as retinopathy, nephropathy, neuropathy and cardiovascular diseases. Currently, insulin is the main used medication for management of insulin-dependentdiabetes mellitus(type-1 diabetes). In this metabolic syndrome, in addition to decrease of endogenous insulin, the plasma level of connecting peptide(C-peptide) is also reduced due to beta cell destruction. Studies in the past decade have shown that C-peptide is much more than a byproduct of insulin biosynthesis and possess different biological activities. Therefore, it may be possible that C-peptide deficiency be involved, at least in part, in the development of different complications of diabetes. It has been shown that a small level of remaining C-peptide is associated with significant metabolic benefit. The purpose of this review is to describe beneficial effects of C-peptide replacement on pathological features associated with insulin-dependent diabetes. Also, experimental and clinical findings on the effects of C-peptide on wholebody glucose utilization, adipose tissue metabolism and tissues blood flow are summarized and discussed. The hypoglycemic, antilipolytic and vasodilator effects of C-peptide suggest that it may contribute to fine-tuning of the tissues metabolism under different physiologic or pathologic conditions. Therefore, C-peptide replacement together with the classic insulin therapy may prevent, retard, or ameliorate diabetic complications in patients with type-1 diabetes.展开更多
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 nervo...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.展开更多
This comprehensive review embarks on a captivating journey into the complex relationship between cardiology and normal-tension glaucoma(NTG),a condition that continues to baffle clinicians and researchers alike.NTG,ch...This comprehensive review embarks on a captivating journey into the complex relationship between cardiology and normal-tension glaucoma(NTG),a condition that continues to baffle clinicians and researchers alike.NTG,characterized by optic nerve damage and visual field loss despite normal intraocular pressure,has long puzzled clinicians.One emerging perspective suggests that alterations in ocular blood flow,particularly within the optic nerve head,may play a pivotal role in its pathogenesis.While NTG shares commonalities with its high-tension counterpart,its unique pathogenesis and potential ties to cardiovascular health make it a fascinating subject of exploration.It navigates through the complex web of vascular dysregulation,blood pressure and perfusion pressure,neurovascular coupling,and oxidative stress,seeking to uncover the hidden threads that tie the heart and eyes together in NTG.This review explores into the intricate mechanisms connecting cardiovascular factors to NTG,shedding light on how cardiac dynamics can influence ocular health,particularly in cases where intraocular pressure remains within the normal range.NTG's enigmatic nature,often characterized by seemingly contradictory risk factors and clinical profiles,underscores the need for a holistic approach to patient care.Drawing parallels to cardiac health,we examine into the shared vascular terrain connecting the heart and the eyes.Cardiovascular factors,including systemic blood flow,endothelial dysfunction,and microcirculatory anomalies,may exert a profound influence on ocular perfusion,impacting the delicate balance within the optic nerve head.By elucidating the subtle clues and potential associations between cardiology and NTG,this review invites clinicians to consider a broader perspective in their evaluation and management of this elusive condition.As the understanding of these connections evolves,so too may the prospects for early diagnosis and tailored interventions,ultimately enhancing the quality of life for those living with NTG.展开更多
As a product in the process of insulin synthesis, C-peptide’s physiological function is still not very clear. Recent studies have shown that C-peptide has many potential cell targets and has biological effects on a v...As a product in the process of insulin synthesis, C-peptide’s physiological function is still not very clear. Recent studies have shown that C-peptide has many potential cell targets and has biological effects on a variety of tissue systems in humans and other animals. In this paper, the effects of C-peptide on diabetic complications, reproductive endocrine system, blood system, tissue repair, and neoplastic diseases were reviewed to provide references for further clarification of c-peptide related problems.展开更多
Objective: In this study, we assessed the level of fasting C-peptide as a predictor of β-cell function and insulin resistance in patients with Type 2 diabetes mellitus (T2DM), Gezira State-Sudan. Methods: In this cro...Objective: In this study, we assessed the level of fasting C-peptide as a predictor of β-cell function and insulin resistance in patients with Type 2 diabetes mellitus (T2DM), Gezira State-Sudan. Methods: In this cross-sectional study, 100 T2DM patients attending the Diabetic patients care Centre were recruited, thirty five patients were males and sixty five were females, the mean age of the patients was 50.29 ± 0.456 years, and body mass index (BMI) was 26.54 ± 0.437. We estimated β-cell function using fasting C-peptide levels;homeostatic model assessment for β-cell function (HOMA-B) and insulin resistance (HOMA-IR) were calculated from C-peptide and fasting blood glucose (FBG). Results: C-peptide was significantly and positively correlated with HOMA-B and HOMA-IR. FBG also showed significant negative correlation with HOMA-B, but was positively and significantly correlated with HOMA-IR. HbA1c was negatively and significantly correlated with HOMA-B. Patients with low C-peptide levels had increased FBG and HbA1c level, while patients with high C-peptide levels were having high HOMA-IR and HOMA-B. Conclusions: Fasting C-peptide is a useful marker of pancreatic β-cell function, and its circulating levels could be used to evaluate insulin secretion and insulin resistance. Moreover, HOMA-IR is an effective index to achieve glycemic control by appropriate pharmacologic treatment of T2DM.展开更多
Background: Increased glomerular filtration rate (GFR) commonly develops in early diabetes and is closely correlated with the development of diabetic nephropathy. Objective: The aim was to study the relationship betwe...Background: Increased glomerular filtration rate (GFR) commonly develops in early diabetes and is closely correlated with the development of diabetic nephropathy. Objective: The aim was to study the relationship between GFR, C-peptide level and other parameters at diagnosis of Type 1 diabetes. Methods: We determined GFR, Cpeptide level, glycated hemoglobin (HbA1c), body mass index (BMI) SDS and loss of weight at diagnosis of Type 1 diabetes in 495 children (231 females). Linear and multiple regression analysis was used to test for the associations between GFR and other parameters. Results: In the 495 patients, GFR median (interquartile range) was increased vs normal values (p = 0.0001). GFR was significantly negatively correlated with age (p < 0.001) and C-peptide level (p = 0.001), and positively correlated with weight loss (p = 0.02). The multiple regression analysis showed that age (p = 0.001) and C-peptide level (p = 0.05) were independently and negatively related to GFR. Conclusions: This study shows that, at onset of Type 1 diabetes, higher the GFR, younger the age and lower the C-peptide level are. The role of this hyperfiltration in the development of later nephropathy and the putative preventive effect of C-peptide administration need to be evaluated.展开更多
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 in...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.展开更多
BACKGROUND Previous studies have reported that low hematocrit levels indicate poor survival in patients with ovarian cancer and cervical cancer,the prognostic value of hematocrit for colorectal cancer(CRC)patients has...BACKGROUND Previous studies have reported that low hematocrit levels indicate poor survival in patients with ovarian cancer and cervical cancer,the prognostic value of hematocrit for colorectal cancer(CRC)patients has not been determined.The prognostic value of red blood cell distribution width(RDW)for CRC patients was controversial.AIM To investigate the impact of RDW and hematocrit on the short-term outcomes and long-term prognosis of CRC patients who underwent radical surgery.METHODS Patients who were diagnosed with CRC and underwent radical CRC resection between January 2011 and January 2020 at a single clinical center were included.The short-term outcomes,overall survival(OS)and disease-free survival(DFS)were compared among the different groups.Cox analysis was also conducted to identify independent risk factors for OS and DFS.RESULTS There were 4258 CRC patients who underwent radical surgery included in our study.A total of 1573 patients were in the lower RDW group and 2685 patients were in the higher RDW group.There were 2166 and 2092 patients in the higher hematocrit group and lower hematocrit group,respectively.Patients in the higher RDW group had more intraoperative blood loss(P<0.01)and more overall complications(P<0.01)than did those in the lower RDW group.Similarly,patients in the lower hematocrit group had more intraoperative blood loss(P=0.012),longer hospital stay(P=0.016)and overall complications(P<0.01)than did those in the higher hematocrit group.The higher RDW group had a worse OS and DFS than did the lower RDW group for tumor node metastasis(TNM)stage I(OS,P<0.05;DFS,P=0.001)and stage II(OS,P=0.004;DFS,P=0.01)than the lower RDW group;the lower hematocrit group had worse OS and DFS for TNM stage II(OS,P<0.05;DFS,P=0.001)and stage III(OS,P=0.001;DFS,P=0.001)than did the higher hematocrit group.Preoperative hematocrit was an independent risk factor for OS[P=0.017,hazard ratio(HR)=1.256,95%confidence interval(CI):1.041-1.515]and DFS(P=0.035,HR=1.194,95%CI:1.013-1.408).CONCLUSION A higher preoperative RDW and lower hematocrit were associated with more postoperative complications.However,only hematocrit was an independent risk factor for OS and DFS in CRC patients who underwent radical surgery,while RDW was not.展开更多
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
Red blood cell(RBC)aggregation as well as their deformation significantly affects blood microrheology.These processes depend on various factors,one of which is concentration of the nitric oxide,one of the main signali...Red blood cell(RBC)aggregation as well as their deformation significantly affects blood microrheology.These processes depend on various factors,one of which is concentration of the nitric oxide,one of the main signaling molecule in the bloodstream.The purpose of this study was to investigate the effect of nitric oxide on the microrheological properties of red blood cells(RBCs)in RBC samples of various media after the addition of nitric oxide donor sodium nitroprusside in vitro.Microrheological properties were measured using laser aggregometer and ektacytometer based on diffuse light scattering and diffraction of laser light on a suspension of RBCs,respectively.The study found that heparin-stabilized blood showed increased RBC aggregation and deformation with sodium nitroprusside concentrations of 100,and 200M,while EDTA-stabilized blood showed slightly decreased aggregation and unchanged deformation.With washed RBCs in dextran solution,the addition of sodium nitroprusside(in the concentrations of 100,and 200M)resulted in decreased aggregation and increased deformation.These-ndings aid in our understanding of nitric oxide's effect on RBC microrheological properties.展开更多
文摘Gestational diabetes is typically diagnosed in the late second or third trimester of pregnancy.It is one of the most common metabolic disorders among expectant mothers,with potential serious short-and long-term complications for both maternal and offspring health.C-peptide is secreted from pancreatic beta-cells into circulation in equimolar amounts with insulin.It is a useful biomarker to estimate the beta-cell function because it undergoes negligible hepatic clearance and consequently it has a longer half-life compared to insulin.Pregnancy induces increased insulin resistance due to physiological changes in hormonal and metabolic homeostasis.Inadequate compensation by islet beta-cells results in hyperglycemia.The standard oral glucose tolerance test at 24-28 wk of gestation sets the diagnosis.Accumulated evidence from prospective studies indicates a link between early pregnancy C-peptide levels and the risk of subsequent gestational diabetes.Elevated C-peptide levels and surrogate glycemic indices at the beginning of pregnancy could prompt appropriate strategies for secondary prevention.
文摘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.
基金supported by the grants from the Spanish Ministry of Economy and Competitiveness(SAF2017-85602-R)the Spanish Ministry of Science and Innovation(PID2020-119638RB-I00 to EGR)FPU-program(FPU17/02616 to JCG)。
文摘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.
基金Supported by The New Faculty Research Grant of Pusan National University,2023The Research Grant of the Chungbuk National University in 2023.
文摘BACKGROUND Intramuscular corticosteroid injection may cause adverse effects such as dermal and/or subcutaneous atrophy,alopecia,hypopigmentation,and hyperpigmentation.Although cutaneous atrophy can spontaneously resolve,several treatment options have been suggested for this condition.CASE SUMMARY In this paper,we report a case of corticosteroid injection induced lipoatrophy treated with autologous whole blood(AWB)injection,as the condition had been unresponsive to fractional laser therapy.A 29-year-old female patient visited the dermatology clinic complaining of skin depression on her right buttock area,which had appeared six months earlier.There had been only subtle improvement at the margins after fractional CO_(2) laser treatment;therefore,after obtaining informed consent from the patient,AWB treatment was initiated.One month after the first AWB injection,the size and depth of the lesion had noticeably improved,and a slight improvement was also observed in discoloration.CONCLUSION Close observation is the initial treatment of choice for steroid induced skin atrophy;however,for patients in need of immediate cosmetic improvement,AWB injection may be a safe and cost-effective alternative.
基金Supported by the National Natural Science Foundation of China,No.81302124.
文摘BACKGROUND Red blood cell distribution width(RDW)is associated with the development and progression of various diseases.AIM To explore the association between pretreatment RDW and short-term outcomes after laparoscopic pancreatoduodenectomy(LPD).METHODS A total of 804 consecutive patients who underwent LPD at our hospital between March 2017 and November 2021 were retrospectively analyzed.Correlations between pretreatment RDW and clinicopathological characteristics and short-term outcomes were investigated.RESULTS Patients with higher pretreatment RDW were older,had higher Eastern Cooperative Oncology Group scores and were associated with poorer short-term outcomes than those with normal RDW.High pretreatment RDW was an independent risk factor for postoperative complications(POCs)(hazard ratio=2.973,95%confidence interval:2.032-4.350,P<0.001)and severe POCs of grade IIIa or higher(hazard ratio=3.138,95%confidence interval:2.042-4.824,P<0.001)based on the Clavien-Dino classification system.Subgroup analysis showed that high pretreatment RDW was an independent risk factor for Clavien-Dino classi-fication grade IIIb or higher POCs,a comprehensive complication index score≥26.2,severe postoperative pancreatic fistula,severe bile leakage and severe hemorrhage.High pretreatment RDW was positively associated with the neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio and was negatively associated with albumin and the prognostic nutritional index.CONCLUSION Pretreatment RDW was a special parameter for patients who underwent LPD.It was associated with malnutrition,severe inflammatory status and poorer short-term outcomes.RDW could be a surrogate marker for nutritional and inflammatory status in identifying patients who were at high risk of developing POCs after LPD.
文摘Amyotrophic lateral sclerosis is a devastating neurodegenerative disease for which the current treatment approaches remain severely limited.The principal pathological alterations of the disease include the selective degeneration of motor neurons in the brain,brainstem,and spinal cord,as well as abnormal protein deposition in the cytoplasm of neurons and glial cells.The biological markers under extensive scrutiny are predominantly located in the cerebrospinal fluid,blood,and even urine.Among these biomarke rs,neurofilament proteins and glial fibrillary acidic protein most accurately reflect the pathologic changes in the central nervous system,while creatinine and creatine kinase mainly indicate pathological alterations in the peripheral nerves and muscles.Neurofilament light chain levels serve as an indicator of neuronal axonal injury that remain stable throughout disease progression and are a promising diagnostic and prognostic biomarker with high specificity and sensitivity.However,there are challenges in using neurofilament light chain to diffe rentiate amyotrophic lateral sclerosis from other central nervous system diseases with axonal injury.Glial fibrillary acidic protein predominantly reflects the degree of neuronal demyelination and is linked to non-motor symptoms of amyotrophic lateral sclerosis such as cognitive impairment,oxygen saturation,and the glomerular filtration rate.TAR DNA-binding protein 43,a pathological protein associated with amyotrophic lateral sclerosis,is emerging as a promising biomarker,particularly with advancements in exosome-related research.Evidence is currently lacking for the value of creatinine and creatine kinase as diagnostic markers;however,they show potential in predicting disease prognosis.Despite the vigorous progress made in the identification of amyotrophic lateral sclerosis biomarkers in recent years,the quest for definitive diagnostic and prognostic biomarke rs remains a formidable challenge.This review summarizes the latest research achievements concerning blood biomarkers in amyotrophic lateral sclerosis that can provide a more direct basis for the differential diagnosis and prognostic assessment of the disease beyond a reliance on clinical manifestations and electromyography findings.
基金supported by Hunan Provincial Key Research and Development Program,No.2021SK2002(to BW)the Natural Science Foundation of Hunan Province of China(General Program),No.2021JJ30938(to YL)。
文摘Degenerative cervical myelopathy is a common cause of spinal cord injury,with longer symptom duration and higher myelopathy severity indicating a worse prognosis.While numerous studies have investigated serological biomarkers for acute spinal cord injury,few studies have explored such biomarkers for diagnosing degenerative cervical myelopathy.This study involved 30 patients with degenerative cervical myelopathy(51.3±7.3 years old,12 women and 18 men),seven healthy controls(25.7±1.7 years old,one woman and six men),and nine patients with cervical spondylotic radiculopathy(51.9±8.6 years old,three women and six men).Analysis of blood samples from the three groups showed clear differences in transcriptomic characteristics.Enrichment analysis identified 128 differentially expressed genes that were enriched in patients with neurological disabilities.Using least absolute shrinkage and selection operator analysis,we constructed a five-gene model(TBCD,TPM2,PNKD,EIF4G2,and AP5Z1)to diagnose degenerative cervical myelopathy with an accuracy of 93.5%.One-gene models(TCAP and SDHA)identified mild and severe degenerative cervical myelopathy with accuracies of 83.3%and 76.7%,respectively.Signatures of two immune cell types(memory B cells and memory-activated CD4^(+)T cells)predicted levels of lesions in degenerative cervical myelopathy with 80%accuracy.Our results suggest that peripheral blood RNA biomarkers could be used to predict lesion severity in degenerative cervical myelopathy.
文摘BACKGROUND Cellular therapies have started an important new therapeutic direction in autistic spectrum disorder(ASD),and the ample diversity of ASD pathophysiology and the different types of cell therapies prompt an equally ample effort to employ clinical studies for studying the ASD causes and cell therapies.Stem cells have yielded so far mixed results in clinical trials,and at patient level the results varied from impressive to no improvement.In this context we have administered autologous cord blood(ACB)and a non-placebo,material intervention repre-sented by an individualized combination of supplements(ICS)to ASD children.METHODS CORDUS clinical study is a crossover study in which both oral ICS and intravenous ACB were sequentially administered to 56 children;ACB was infused as an inpatient procedure.Treatment efficacy was evaluated pre-treatment and post-treatment at 6 months by an independent psychotherapist with Autism Treatment Evaluation Checklist,Quantitative Checklist for Autism in Toddlers and a 16-item comparative table score,after interviewing the children’s parents and therapists.Before and after each intervention participants had a set of blood tests including inflammatory,metabolic and oxidative markers,and the neuronal specific enolase.RESULTS No serious adverse reactions were noted during and after cord blood or supplement administration.ACB improved evaluation scores in 78%of children with age 3–7-years(n=28),but was much less effective in kids older than 8 years or with body weight of more than 35 kg(n=28;only 11%of children improved scores).ICS yielded better results than ACB in 5 cases out of 28,while in 23 kids ACB brought more improvement than ICS(P<0.05);high initial levels of inflammation and ferritin were associated with no improvement.Ample individual differences were noted in children's progress,and statistically significant improvements were seen after ACB on areas such as verbalization and social interaction,but not on irritability or aggressive behavior.CONCLUSION ACB has superior efficacy to ICS in ASD;high inflammation,ferritin,age and body weight predict less improvement;more clinical studies are needed for studying ACB efficacy in ASD.
文摘With the changes of life style, diabetes and its complications have become a major cause of morbidity and mortality. It is reasonable to anticipate a continued rise in the incidence of diabetes and its complications along with the aging of the population, increase in adult obesity rate, and other risk factors. Diabetic en- cephalopathy is one of the severe microvascular complications of diabetes, characterized by impaired cogni- tive functions, and electrophysiological, neurochemical, and structural abnormalities. It may involve direct neuronal damage caused by intracellular glucose. However, the pathogenesis of this disease is complex and its diagnosis is not very clear. Previous researches have suggested that chronic metabolic alterations, vascular changes, and neuronal apoptosis may play important roles in neuronai loss and damaged cognitive functions. Multiple factors are responsible for neuronal apoptosis, such as disturbed insulin growth factor (IGF) system, hyperglycemia, and the aging process. Recent data suggest that insulin/C-peptide deficiency may exert a primary and key effect in diabetic encephalopathy. Administration of C-peptide partially improves the condition of the IGF system in the brain and prevents neuronal apoptosis in the hippocampus of diabetic patients. Those findings provide a basis for application of C-peptide as a potentially effective therapy for diabetes and diabetic encephalopathy.
文摘AIM To determine whether fasting C-peptide is an independent predictor for non-alcoholic fatty liver disease(NAFLD) in United States population.METHODS Using the National Health and Nutrition Examination Survey(NHANES) 1988-1994, NAFLD participants aged 20 or greater without any other liver diseases were included in this study. Excessive alcohol intake is defined as > 2 drinks per day for males and > 1 drink per day for females. C-peptide and 27 other factors known to be associated with NAFLD(e.g., age, gender, body mass index, waist circumference, race/ethnicity, liver chemistries, and other diabetes tests) were tested in both univariate and multivariate level using logistic regression with a P-value 0.05.RESULTS Of 18825 participants aged ≥ 20, 3235 participants(n = 3235) met inclusion criteria. There were 23 factors associated with NAFLD by univariate analysis. 9 factors, ranked by the highest change in pseudo R2, were found to be significant predictors of NAFLD in multivariate model: waist circumference, fasting C-peptide, natural log of alanine aminotransferase(ALT), total protein, beingMexican American, natural log of glycated hemoglobin, triglyceride level, being non-Hispanic white, and ferritin level. CONCLUSION Together with waist circumference and ALT, fasting C-peptide is among three most important predictors of NAFLD in United States population in the NHANES data set. Further study is needed to validate the clinical utility of fasting C-peptide in diagnosis or monitoring insulin resistance in NAFLD patients.
基金Supported by Mashhad University of Medical Sciences
文摘Diabetes is associated with several complications such as retinopathy, nephropathy, neuropathy and cardiovascular diseases. Currently, insulin is the main used medication for management of insulin-dependentdiabetes mellitus(type-1 diabetes). In this metabolic syndrome, in addition to decrease of endogenous insulin, the plasma level of connecting peptide(C-peptide) is also reduced due to beta cell destruction. Studies in the past decade have shown that C-peptide is much more than a byproduct of insulin biosynthesis and possess different biological activities. Therefore, it may be possible that C-peptide deficiency be involved, at least in part, in the development of different complications of diabetes. It has been shown that a small level of remaining C-peptide is associated with significant metabolic benefit. The purpose of this review is to describe beneficial effects of C-peptide replacement on pathological features associated with insulin-dependent diabetes. Also, experimental and clinical findings on the effects of C-peptide on wholebody glucose utilization, adipose tissue metabolism and tissues blood flow are summarized and discussed. The hypoglycemic, antilipolytic and vasodilator effects of C-peptide suggest that it may contribute to fine-tuning of the tissues metabolism under different physiologic or pathologic conditions. Therefore, C-peptide replacement together with the classic insulin therapy may prevent, retard, or ameliorate diabetic complications in patients with type-1 diabetes.
基金funding from European Regional Development Fund(project No 13.1.1-LMT-K-718-05-0005)under grant agreement with the Research Council of Lithuania(LMTLT)。
文摘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.
文摘This comprehensive review embarks on a captivating journey into the complex relationship between cardiology and normal-tension glaucoma(NTG),a condition that continues to baffle clinicians and researchers alike.NTG,characterized by optic nerve damage and visual field loss despite normal intraocular pressure,has long puzzled clinicians.One emerging perspective suggests that alterations in ocular blood flow,particularly within the optic nerve head,may play a pivotal role in its pathogenesis.While NTG shares commonalities with its high-tension counterpart,its unique pathogenesis and potential ties to cardiovascular health make it a fascinating subject of exploration.It navigates through the complex web of vascular dysregulation,blood pressure and perfusion pressure,neurovascular coupling,and oxidative stress,seeking to uncover the hidden threads that tie the heart and eyes together in NTG.This review explores into the intricate mechanisms connecting cardiovascular factors to NTG,shedding light on how cardiac dynamics can influence ocular health,particularly in cases where intraocular pressure remains within the normal range.NTG's enigmatic nature,often characterized by seemingly contradictory risk factors and clinical profiles,underscores the need for a holistic approach to patient care.Drawing parallels to cardiac health,we examine into the shared vascular terrain connecting the heart and the eyes.Cardiovascular factors,including systemic blood flow,endothelial dysfunction,and microcirculatory anomalies,may exert a profound influence on ocular perfusion,impacting the delicate balance within the optic nerve head.By elucidating the subtle clues and potential associations between cardiology and NTG,this review invites clinicians to consider a broader perspective in their evaluation and management of this elusive condition.As the understanding of these connections evolves,so too may the prospects for early diagnosis and tailored interventions,ultimately enhancing the quality of life for those living with NTG.
文摘As a product in the process of insulin synthesis, C-peptide’s physiological function is still not very clear. Recent studies have shown that C-peptide has many potential cell targets and has biological effects on a variety of tissue systems in humans and other animals. In this paper, the effects of C-peptide on diabetic complications, reproductive endocrine system, blood system, tissue repair, and neoplastic diseases were reviewed to provide references for further clarification of c-peptide related problems.
文摘Objective: In this study, we assessed the level of fasting C-peptide as a predictor of β-cell function and insulin resistance in patients with Type 2 diabetes mellitus (T2DM), Gezira State-Sudan. Methods: In this cross-sectional study, 100 T2DM patients attending the Diabetic patients care Centre were recruited, thirty five patients were males and sixty five were females, the mean age of the patients was 50.29 ± 0.456 years, and body mass index (BMI) was 26.54 ± 0.437. We estimated β-cell function using fasting C-peptide levels;homeostatic model assessment for β-cell function (HOMA-B) and insulin resistance (HOMA-IR) were calculated from C-peptide and fasting blood glucose (FBG). Results: C-peptide was significantly and positively correlated with HOMA-B and HOMA-IR. FBG also showed significant negative correlation with HOMA-B, but was positively and significantly correlated with HOMA-IR. HbA1c was negatively and significantly correlated with HOMA-B. Patients with low C-peptide levels had increased FBG and HbA1c level, while patients with high C-peptide levels were having high HOMA-IR and HOMA-B. Conclusions: Fasting C-peptide is a useful marker of pancreatic β-cell function, and its circulating levels could be used to evaluate insulin secretion and insulin resistance. Moreover, HOMA-IR is an effective index to achieve glycemic control by appropriate pharmacologic treatment of T2DM.
文摘Background: Increased glomerular filtration rate (GFR) commonly develops in early diabetes and is closely correlated with the development of diabetic nephropathy. Objective: The aim was to study the relationship between GFR, C-peptide level and other parameters at diagnosis of Type 1 diabetes. Methods: We determined GFR, Cpeptide level, glycated hemoglobin (HbA1c), body mass index (BMI) SDS and loss of weight at diagnosis of Type 1 diabetes in 495 children (231 females). Linear and multiple regression analysis was used to test for the associations between GFR and other parameters. Results: In the 495 patients, GFR median (interquartile range) was increased vs normal values (p = 0.0001). GFR was significantly negatively correlated with age (p < 0.001) and C-peptide level (p = 0.001), and positively correlated with weight loss (p = 0.02). The multiple regression analysis showed that age (p = 0.001) and C-peptide level (p = 0.05) were independently and negatively related to GFR. Conclusions: This study shows that, at onset of Type 1 diabetes, higher the GFR, younger the age and lower the C-peptide level are. The role of this hyperfiltration in the development of later nephropathy and the putative preventive effect of C-peptide administration need to be evaluated.
基金funded by the National Natural Science Foundation of China(Grant/Award Numbers 62075135 and 61975126)the Science and Technology Innovation Commission of Shenzhen(Grant/Award Numbers JCYJ20190808174819083 and JCYJ20190808175201640)Shenzhen Science and Technology Planning Project(ZDSYS 20210623092006020).
文摘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.
基金The study was approved by the ethics committee of the First Affiliated Hospital of Chongqing Medical University(2022-K205),this study was conducted in accordance with the World Medical Association Declaration of Helsinki as well。
文摘BACKGROUND Previous studies have reported that low hematocrit levels indicate poor survival in patients with ovarian cancer and cervical cancer,the prognostic value of hematocrit for colorectal cancer(CRC)patients has not been determined.The prognostic value of red blood cell distribution width(RDW)for CRC patients was controversial.AIM To investigate the impact of RDW and hematocrit on the short-term outcomes and long-term prognosis of CRC patients who underwent radical surgery.METHODS Patients who were diagnosed with CRC and underwent radical CRC resection between January 2011 and January 2020 at a single clinical center were included.The short-term outcomes,overall survival(OS)and disease-free survival(DFS)were compared among the different groups.Cox analysis was also conducted to identify independent risk factors for OS and DFS.RESULTS There were 4258 CRC patients who underwent radical surgery included in our study.A total of 1573 patients were in the lower RDW group and 2685 patients were in the higher RDW group.There were 2166 and 2092 patients in the higher hematocrit group and lower hematocrit group,respectively.Patients in the higher RDW group had more intraoperative blood loss(P<0.01)and more overall complications(P<0.01)than did those in the lower RDW group.Similarly,patients in the lower hematocrit group had more intraoperative blood loss(P=0.012),longer hospital stay(P=0.016)and overall complications(P<0.01)than did those in the higher hematocrit group.The higher RDW group had a worse OS and DFS than did the lower RDW group for tumor node metastasis(TNM)stage I(OS,P<0.05;DFS,P=0.001)and stage II(OS,P=0.004;DFS,P=0.01)than the lower RDW group;the lower hematocrit group had worse OS and DFS for TNM stage II(OS,P<0.05;DFS,P=0.001)and stage III(OS,P=0.001;DFS,P=0.001)than did the higher hematocrit group.Preoperative hematocrit was an independent risk factor for OS[P=0.017,hazard ratio(HR)=1.256,95%confidence interval(CI):1.041-1.515]and DFS(P=0.035,HR=1.194,95%CI:1.013-1.408).CONCLUSION A higher preoperative RDW and lower hematocrit were associated with more postoperative complications.However,only hematocrit was an independent risk factor for OS and DFS in CRC patients who underwent radical surgery,while RDW was not.
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 Russian Science Foundation grant(No.22-15-00120)supported by the grant(No.21-2-10-59-1)from the Foundation for the Development of Theoretical Physics and Mathematics BASIS.
文摘Red blood cell(RBC)aggregation as well as their deformation significantly affects blood microrheology.These processes depend on various factors,one of which is concentration of the nitric oxide,one of the main signaling molecule in the bloodstream.The purpose of this study was to investigate the effect of nitric oxide on the microrheological properties of red blood cells(RBCs)in RBC samples of various media after the addition of nitric oxide donor sodium nitroprusside in vitro.Microrheological properties were measured using laser aggregometer and ektacytometer based on diffuse light scattering and diffraction of laser light on a suspension of RBCs,respectively.The study found that heparin-stabilized blood showed increased RBC aggregation and deformation with sodium nitroprusside concentrations of 100,and 200M,while EDTA-stabilized blood showed slightly decreased aggregation and unchanged deformation.With washed RBCs in dextran solution,the addition of sodium nitroprusside(in the concentrations of 100,and 200M)resulted in decreased aggregation and increased deformation.These-ndings aid in our understanding of nitric oxide's effect on RBC microrheological properties.