Objectives . Early warning prediction of massive hemorrhages can greatly reduce mortality in trauma patients. This study aimed to develop and validate dynamic prediction models for massive hemorrhage in trauma patients. Methods . Based on vital signs (e.g., heart rate, respiratory rate, pulse pressure, and peripheral oxygen saturation) time-series data and the gated recurrent unit algorithm, we characterized a group of models to flexibly and dynamically predict the occurrence of massive hemorrhages in the subsequent T hours (where T = 1, 2, and 3). Models were evaluated in terms of accuracy, sensitivity, specificity, positive predictive value, negative predictive value, F 1 score, and the area under the curve (AUC). Results . Results show that of the 2205 trauma patients selected for model development, a total of 265 (12.02%) had a massive hemorrhage. The AUCs of the model in the 1-h-group, 2-h-group, and 3-h-group were 0.763 (95% CI: 0.708–0.820), 0.775 (95% CI: 0.728–0.823), and 0.756 (95% CI: 0.715–0.797), respectively. Finally, the models were used in a web calculator and information system for the hospital emergency department. Conclusions . This study developed and validated a group of dynamic prediction models based on vital sign time-series data and a deep-learning algorithm to assist medical staff in the early diagnosis and dynamic prediction of a future massive hemorrhage in trauma.
With aging of population and improvement of medical technology,the number of elderly patients receiving surgical treatment is increasing.Cardiovascular events after noncardiac surgery are one of the leading causes of death.Perioperative cardiovascular events have a high risk and incidence rate,thus severely affecting the prognosis of patients.In recent years,a growing number of studies have focused on the prevention and treatment of perioperative cardiovascular events in elderly patients.Assessing the risk of perioperative cardiovascular events and using effective interventions can effectively reduce the incidence of cardiovascular events and improve the prognosis of elderly patients.This article discusses cardiovascular risk assessment and management in elderly patients during noncardiac surgeries from the perspective of preoperative,intraoperative,postoperative periods,and perioperative medication used to provide assistance to clinical practice.
For axial spondyloarthritis/ankylosing spondylitis,rehabilitation is very important for controlling disease activity,preventing disease progression and improving quality of life.Initiated by China Spine Alliance and jointly formulated by Air Force Specialty Medical Center and Chinese PLA General Hospital,the current guidelines were developed according to World Health Organization Guidelines Development Manual and the Basic Methods and Procedures for the Development/Revision of the Clinical Diagnosis and Treatment Guidelines,Appraisal of Guidelines for Research and Evaluation Ⅱ(AGREE Ⅱ),Grading of Recommendations Assessment,Development and Evaluation(GRADE).Two basic princlples and 12 suggestions were made for important issues such as diagnosis,rehabilitation assessment,rehabilitation intervention and management for axial spondyloarthritis/ankylosing spondylitis.
Dexmedetomidine is a highly selective α2 adrenergic receptor agonist,exerting anti-sympathetic,sedative,analgesic and anti-anxiety effects,with minimal impact on respiration.In recent years,dexmedetomidine has been widely used in clinical anesthesia,perioperative treatment,and intensive care.Organ-protection is an important focus of anesthesia and perioperative medicine,with clinical significance in reducing complications and improving short-and long-term outcomes.Increasing clinical evidence and basic research have shown that the application of dexmedetomidine could protect the heart,brain,lung,kidney,liver,gastrointestinal tract and other important organs.The mechanism may be related to dexmedetomidine's effects of anti-inflammation,anti-oxidation,anti-apoptosis,and autophagy regulation.From our perspectives,clinical use should follow the principle of individualization,and the dose should be adjusted in time according to patients'responses,so as to avoid adverse reactions such as hypotension and bradycardia while protecting the organs.Moreover,more strictly designed clinical studies and in-depth mechanistic investigations are needed for the optimal dexmedetomidine therapy and better organ protection during the perioperative course.In order to facilitate better understanding of clinicians,this paper reviews the organ-protective effects and underlying mechanisms of dexmedetomidine.
Objective To explore the change of brain functional connectivity strength in patients with type 2 diabetes mellitus(T2DM)and its neuropathological mechanism.Methods Fifty-six T2DM patients who visited Gansu Provincial Hospital from October 2017 to March 2021 were selected as T2DM group,and 48 healthy controls were selected as control group.A prospective study was conducted on the changes in brain function in T2DM patients by analysis of resting state functional connectivity strength(FCS)and functional connectivity(FC)based on seed points.Brain functional magnetic resonance imaging,clinical variable collection,and neuropsychological testing of patients in two groups were performed.We calculate the FCS value,evaluate the brain function changes of the two groups in the resting state,take the brain regions with significant differences between the groups as the seed points and perform functional connectivity analysis with the whole brain.Correlation analysis was conducted between the FCS,FC values of the different brain regions and clinical variables such as fasting blood glucose(FPG),glycosylated hemoglobin(HbA1c),thyroid hormone(TSH)levels,as well as the scores of mini mental state examination(MMSE),Montreal cognitive assessment(MoCA),clock drawing test(CDT),Hamilton Depression Rating Scale(HAMD-24)and Hamilton Anxiety Scale(HAMA).Results Compared with control group,the HAMD-24 and HAMA scores in T2DM group significantly increased(P<0.01),while the MoCA scores decreased(P<0.05);In T2DM group,the FCS value of the right middle temporal gyrus increased(GRF correction,voxel level P<0.001,clustering level P<0.05),and the FC value of the right middle temporal gyrus-left anterior cingulate cortex decreased(GRF correction,voxel level P<0.001,clustering level P<0.05).Correlation analysis showed that the FC value of right middle temporal gyrus-left anterior cingulate cortex in T2DM patients was negatively correlated with HAMD-24 score(r=-0.395,P=0.003),HbA1c level(r=-0.303,P=0.023),and positively correlated with TSH level(r=0.324,P=0.017).Conclusions The increase of FCS value in the right middle temporal gyrus and the decrease of FC value in the right middle temporal gyrus-left anterior cingulate cortex may be important neuroimaging features of brain function damage in T2DM patients.HbA1c may play an important role in the process of brain damage in T2DM patients.
Objective To evaluate the efficacy and safety of modified decompressive craniectomy in treatment of traumatic brain injury and its impact on the serum levels of inflammatory mediators and prognosis.Methods According to different surgical methods,82 patients with traumatic brain injury admitted to the department of neurosurgery of Nanyang Central Hospital from June 2020 to January 2022 were divided into standard group(n=41)and modified group(n=41).The standard group was given standard decompressive craniectomy,and the modified group was given modified decompressive craniectomy.The intraoperative blood loss,operation time and hospital stay,the levels of neuron-specific enolase(NSE),S-100 calcium binding protein B(S-100β),C-reaction protein(CRP),procalcitonin(PCT),and interleukin-6(IL-6)before operation,6 hours after operation,and 3 days after operation,Glasgow Outcome Scale(GOS),incidence of complications,and incision healing grade 1 month after operation were compared between two groups.Results Compared with standard group,the hospital stay was significant shorter in modified group(P<0.05),and intraoperative blood loss and operation time were no significant difference in modified group(P>0.05).At 6 hours and 3 days after operation,the levels of NSE,S-100β,CRP,PCT and IL-6 in modified group were lower than those in standard group(P<0.05).Compared with standard group,the good prognosis rate based of GOS was higher in modified group[82.9%(34/41)vs.63.4%(26/41),P<0.05];the total incidence of complications was lower in modified group[2.4%(1/41)vs.19.5%(26/41),P<0.05];and the grade of incision healing was better in modified group(P<0.05).Conclusions Modified decompressive craniectomy in the treatment of traumatic brain injury could reduce stress of brain injury and surgical trauma,and the incidence of complications,help to speed up the postoperative recovery process,improve the rate of good prognosis and the grade of incision healing.Its efficacy and safety is better than standard decompressive craniectomy.
Chronic obstructive pulmonary disease(COPD)is a frequent and common disease of the respiratory system.The problem of low early diagnosis rate,low treatment compliance,and low treatment standardization has persisted in the diagnosis and treatment of COPD.Heterogeneity found in clinical practice is one of the reasons why COPD is difficult to treat.In recent years,it has been gradually recognized that the occurrence and development of COPD are closely related to the immune state of the body.At present,it become one of the hot spots in clinical and basic research that searching for specific and sensitive cell and molecular biomarkers to early diagnose acute exacerbation and subtype differentiation of COPD,which ultimately provide individual diagnosis and treatment strategies for COPD patients.This review focuses on the research progress of immunocytes and immunologic factors as biomarkers to different phenotypes and progression of COPD in recent years,providing a reference for the research on diagnosis and treatment of COPD.
Objective To explore the association between triglyceride glucose(TyG)index and TyG-body mass index(TyG-BMI)and the prevalence of metabolic associated fatty liver disease(MAFLD)in the elderly men.Methods Totally 2290 elderly men were selected from January to December in 2021 in the Second Medical Center of Chinese PLA General Hospital,and divided into MAFLD group(n=1322)and non-MAFLD group(n=968).Multivariate logistic regression was used to analyze the association between TyG index,TyG-BMI and MAFLD.The receiver operating characteristic(ROC)curve was drawn to explore the predictive value of TyG index and TyG-BMI with MAFLD in the elderly men.Results Two thousand two hundred and ninety elderly men were(74.3±10.1)years old,and an average BMI of(24.63±2.70)kg/m2.BMI,γ-glutamyl transaminase(γ-GT),alanine aminotransferase(ALT),aspartate aminotransferase(AST),serum creatinine(Scr),thyroid stimulating hormone(TSH),free triiodothyronine(FT3),the rate of smoking and drinking,and the prevalence of hypertension,diabetes,hyperuricemia,high triglyceride(TG),low high density lipoprotein cholesterol(HDL-C),hyperuricemia,thyroid nodules and cholelithiasis were all significantly higher in non-MAFLD group than those in MAFLD group(P<0.05),while the age of MAFLD group was lower than that of non-MAFLD group(P=0.003).Multivariate logistic regression analysis showed that the risk of MAFLD in patients of TyG quartile groups Q2,Q3,Q4 was 1.667(95%CI 1.257-2.236,P<0.001),2.004(95%CI 1.482-2.710,P<0.001)and 5.420(95%CI 3.266-8.995,P<0.001)times higher than that of TyG Q1,respectively.The risk of MAFLD in patients of TyG-BMI Q2,Q3,Q4 was 2.215(95%CI 1.549-3.167,P<0.001),2.809(95%CI 1.723-4.580,P<0.001)and 2.513(95%CI 1.253-5.040,P=0.009)times higher than that of TyG-BMI Q1,respectively.The ROC curve showed that areas under the curve(AUC)of MAFLD predicted by TyG index and TyG-BMI were 0.717(95%CI 0.696-0.738)and 0.840(95%CI 0.823-0.856),and the best cut-off values were 8.63 and 205.20,respectively.Moreover,the ROC curve showed that AUC of MAFLD in the elderly men without hyperlipidemia or diabetes predicted by TyG index and TyG-BMI were 0.653(95%CI 0.622-0.684)and 0.840(95%CI 0.818-0.862),and the best cut-off values were 8.42 and 202.66,respectively.In addition,AUC,accuracy,specificity,sensitivity,positive predictive value and negative predictive value predicted by TyG-BMI were higher than those by TyG index.Conclusions TyG index and TyG-BMI are significantly associated with MAFLD in the elderly men.Both TyG index and TyG-BMI have certain predictive value for the prevalence of MAFLD in the elderly men,and TyG-BMI may be better.
Objective To investigate the release of enterogenic and hepatogenic high mobility group protein B1(HMGB1)through exosomes and its regulatory pathway.Methods We used wild-type(WT)and ASC-/-mice for this study.We randomly selected five mice per group from each strain and fed them either a normal diet(ND)or a high-fat diet(HFD)for eight weeks.The control group consisted of WT mice fed with the normal diet;the HFD group were WT mice with the HFD;the microflora disturbance(MD)group were ASC-/-mice fed with the normal diet;the high-lipid microflora disturbance(HLMD)group were ASC-/-mice with HFD.We used confocal microscopy to detect the co-localization of liver and intestinal exosome markers with HMGB1.We then measured the expression level of HMGB1 content in exosomes by Western blotting and PCR.The AML12 cells were treated with palmitic acid(PA)and lipopolysaccharide(LPS)for 24 h to build an in vitro model.We also detected HMGB1/CD63 levels using Western blotting.To understand the regulatory mechanism of exosome release,we employed siRNA intervention.Results The secretion of exosomes increased significantly in HFD group compared with control group[(3.5±0.2)ng/ml vs.(1.1±0.3)ng/ml,P<0.05],HLMD group compared with those in MD group[(3.2±0.2)ng/ml vs.(1.9±0.4)ng/ml,P<0.05].Using immunofluorescence detection,we observed increased co-localization of exosome markers(ALP or VPS16)with HMGB1 in HFD group compared with control group.We also observed this in AML12 cells treated with PA and LPS compared with blank control.The PCR data showed that HMGB1 in hepatocyte exosomes was higher in HFD group compared with control group(41.5±10.2 vs.1.3±0.3,P<0.05),HLMD group was significantly higher than that in MD group(48.6±7.2 vs.1.5±0.5,P<0.05).TLR4 expression was higher in HFD group compared with control group(13.8±6.2 vs.2.8±0.9,P<0.05),HLMD group compared with MD group(22.6±4.1 vs.2.5±1.5,P<0.05).In intestinal mucosal cells,the co-location of HMGB1 and exosome marker CD63 was significantly higher in HFD group compared with control group(0.6±0.2 vs.0.4±0.1,P<0.05),and HLMD group compared with MD group(0.9±0.2 vs.0.5±0.1,P<0.05).In vitro,the HMGB1 of exosomes was increased in endotoxin group(5.1±0.8)and high lipid endotoxin group(5.5±0.7)compared with control group(3.8±0.6,P<0.05).On the other hand,the HMGB1 of exosomes in the cell siRNA intervention group was not increased compared with control group(3.7±0.6 vs.3.8±0.6,P>0.05).Conclusion HMGB1 is released by exosomes in hepatocytes and intestinal cells,and regulated by Toll-like receptor 4(TLR4)under a high-fat diet and intestinal flora disorder,which may be one of the contributing factors in promoting the development of steatohepatitis.
Neurological impairment in the form of stroke,cognitive dysfunction and delirium is a common complication after cardiac surgery and a major cause of postoperative death and long-term disability in patients undergoing cardiac surgery.There have been many studies attempting to identify intervention and treatment strategies,but no standardized protocols for neurological protection have been developed.The purpose of this article is to discuss the risk factors,mechanisms and neuroprotective measures to improve patient prognosis of neurological injury after cardiac surgery,and to review the recent research progress from three aspects:preoperative assessment and intervention,intraoperative management and monitoring,and postoperative diagnosis and treatment,emphasizing that the focus of perioperative prevention and treatment should be on the prevention of ischemic-hypoxic injury.Future research directions should focus on translational research of preclinical experiments and the development of novel imaging techniques to reduce the incidence of neurological complications and improve clinical outcome.
Heatstroke is a fatal disease caused by heat injury.With global warming,the incidence of heatstroke has been increasing year by year.Combined coagulation dysfunction is an important factor in the mortality of heatstroke.So far,there is no standard for the diagnosis and treatment of heatstroke-induced coagulopathy at home and abroad.Therefore,Expert Group of Heatstroke Prevention and Treatment of Chinese People's Liberation Army;People's Liberation Army Professional Committee of Critical Care Medicine;Chinese Society of Thrombosis,Hemostasis and Critical Care,Chinese Medicine Education Association;Chinese Society of Thrombosis and Hemostasis,Chinese Research Hospital Association jointly organized experts to develop a expert consensus on the diagnosis and treatment of heatstroke-induced coagulopathy in China.This consensus includes five parts:the definition,pathogenesis,diagnosis and evaluation,treatment and control of complications of heatstroke-induced coagulopathy,with a total of 15 recommended opinions to guide clinical work.
Objective To investigate the effects and mechanisms of TAR DNA-binding protein 43(TDP-43)on oxygen-glucose deprivation(OGD)-induced apoptosis in mouse atrial myocytes(HL-1 cells).Methods The in vitro cultured mouse atrial myocytes(HL-1 cells)were divided into:(1)control group and groups with different OGD treatment times(2,4,8,16 h),and cell viability was detected by CCK-8 assay,and TDP-43 protein expression level was detected by Western blotting,which was used to determine the time point of OGD induction for the subsequent study;(2)control and OGD groups,flow cytometry was used to detect apoptosis,JC-1 staining to detect mitochondrial membrane potential,chemiluminescence to detect adenosine triphosphate(ATP)relative content,microplate method to detect malondialdehyde(MDA)content,and WST-1 method to detect superoxide dismutase(SOD)content.Mouse atrial myocytes(HL-1 cells)transfected with lentivirus were divided into:(1)negative control lentiviral intervention group(NC-shRNA),TDP-43 knockdown lentiviral intervention group(TDP-43-shRNA1,TDP-43-shRNA2,TDP-43-shRNA3),and Western blotting was used to detect the TDP-43 protein expression level,and the group with the highest lentiviral knockdown efficiency was selected as the TDP-43-shRNA for subsequent experiments;(2)NC-shRNA group,TDP-43-shRNA group,OGD+NC-shRNA group,OGD+TDP-43-shRNA group,under normoxic and OGD conditions,flow cytometry was used to detect the apoptosis rate,MitoTracker staining to detect mitochondrial morphology,JC-1 staining to detect mitochondrial membrane potential,chemiluminescence to detect the relative content of ATP,flow cytometry to detect the fluorescence intensity of reactive oxygen species(ROS),microplate to detect the content of MDA,and WST-1 to detect the content of SOD.Results CCK-8 method showed that,with the prolongation of OGD time,the viability of mouse atrial myocytes(HL-1 cells)gradually decreased;Western blotting assay showed that the expression level of TDP-43 protein gradually increased,and both of them showed a strong time-dependence.Compared with control group,mouse atrial myocytes(HL-1 cells)viability was the lowest(P<0.05)and TDP-43 protein expression was the highest(P<0.05)at 16 h of OGD,accordingly,OGD 16 h was chosen as the induction time point for subsequent experiments.Compared with control group,the apoptosis rate,the fluorescence intensity ratio of mitochondrial membrane potential and the content of MDA increased,the relative content of ATP and SOD decreased in OGD group,and the differences were all statistically significant(P<0.05).Western blotting detection showed that compared with NC-shRNA group,the TDP-43-shRNA2 group had the most obvious reduction in TDP-43 protein expression level(P<0.05)and the highest knockdown efficiency,so the TDP-43-shRNA2 group was selected for subsequent experiments.The results of flow cytometry showed that under normoxic conditions,there was no significant change in the apoptosis rate in TDP-43-shRNA group compared with NC-shRNA group(P>0.05);and under OGD conditions,the apoptosis rate in OGD+TDP-43-shRNA group reduced when compared with OGD+NC-shRNA group(P<0.05).MitoTracker staining results showed that the mitochondrial morphology of TDP-43-shRNA group was intact without significant changes compared with NC-shRNA group;the mitochondria of OGD+NC-shRNA group increased in number,most of which were fragmented and scattered in distribution;compared with OGD+NC-shRNA group,the mitochondrial morphology of OGD+TDP-43-shRNA group was restored.Under normoxic conditions,there were no significant changes in mitochondrial membrane potential,relative ATP content,ROS fluorescence intensity,MDA content,and SOD content in TDP-43-shRNA group compared with NC-shRNA group(P>0.05);however,under OGD conditions,the ratio of fluorescence intensity of mitochondrial membrane potential of cells the fluorescence intensity of ROS,and the content of MDA decreased,and the relative content of ATP and the content of SOD increased in OGD+TDP-43-shRNA group compared with that of OGD+NC-shRNA group,and all of these differences was statistically significant(P<0.05).Conclusion TDP-43 exacerbates OGD-induced mitochondrial dysfunction by regulating cardiomyocyte apoptosis;therefore,knockdown of TDP-43 expression is expected to be a potential therapeutic strategy for ischemic cardiomyopathy.
With the continuous development and progress of medicine,the total number of general anesthetic surgery is increasing,and postoperative complications are also on the rise,especially postoperative pulmonary complications(PPCs)caused by perioperative lung injury.PPCs are the main cause of prolonged hospitalization,increased morbidity and mortality,poor prognosis,and increased medical burden in patients undergoing general anesthesia.With the enhancement of awareness of mechanical ventilation and the implementation of the enhanced recovery after surgery(ERAS)concept,lung-protective ventilation strategies(LPVS)are receiving more and more attention.However,the debate continues on how to apply the LPVS effectively.The recent introduction of diaphragm-protective ventilation as a novel concept has led to the realization that the application of protective ventilation strategies should limit the adverse effects of mechanical ventilation on diaphragm function within the context of lung protective ventilation.How to apply protective ventilation strategies effectively to prevent the development of ventilator-induced lung injury(VILI)and ventilator-induced diaphragm dysfunction(VIDD),reduce the incidence of PPCs,improve patient prognosis,and reduce the medical burden is an important challenge in the management of mechanically ventilated patients.In this paper,we will focus on ventilation strategies of lung and diaphragm combined with the latest progress of LPVS,to elaborate the research on the application of individualized ventilation strategies and the mechanisms of VILI and VIDD occurrence.Finally,prospecting the future research direction of protective ventilation strategies.
Objective To explore the risk factors for renal injury in tumors patients treated with programmed death receptor-1(PD-1)inhibitor,and further construct a column chart model to predict the likelihood of renal injury in patients.Methods The present study is a single center retrospective analysis.447 patients with tumors treated with PD-1 inhibitors in the Third Affiliated Hospital of Soochow University between January 2018 and January 2021 were included and followed up until January 2022.Kidney injury was defined as acute kidney disease(AKD).All patients were divided into AKD group(n=71)and non-AKD group(n=376 according to whether PD-1 inhibitor associated with AKD development at the end of follow-up.Basic information,disease and medication situation,laboratory indicators,and the incidence of extrarenal immune related adverse events(irAEs)during follow-up period were compared between the two groups.Univariate and multivariate logistic regression models were used to identify independent risk factors for PD-1 inhibitor associated AKD.The present study randomly divided all samples(n=447)into training set(n=313)and validation set(n=134)in a 7:3 ratio,built nomogram prediction models in the training set according to the screened independent risk factors,drawn the receiver operating characteristic(ROC)curves to evaluate the discrimination of the models,drawn calibration curves to evaluate the calibration of the models,and drawn clinical decision curve analysis(DCA)to explore the clinical validity and benefit rate of the models.Results The combination of antibiotics,diabetes,hypertension,extrarenal irAEs and cystatin C(Cys C)in AKD group were significantly higher than those in non-AKD group(P<0.05),but hemoglobin(Hb)was significantly lower than that in non-AKD group(P<0.05).Single factor logistic regression analysis showed that combination of antibiotics,diabetes,hypertension,extrarenal irAEs,lower Hb,estimated glomerular filtration rate(eGFR),higher blood urea nitrogen(BUN),serum creatinine(SCr),Cys C,fasting blood glucose(FBG),and alanine transaminase(ALT)were risk factors for PD-1 inhibitor related AKD(P<0.05).Multivariate logistic regression analysis showed that concomitant extrarenal irAEs,lower Hb,higher SCr,and direct bilirubin(DBIL)were independent risk factors for PD-1 inhibitor associated AKD(P<0.05).Based on the independent risk factors mentioned above,a column chart prediction model was further established and validated.The results showed that the area under the ROC curve(AUC)of the training and validation sets of the model were 0.703(95%CI 0.628-0.777)and 0.791(95%CI 0.671-0.911),respectively,indicating good discrimination.The calibration curves of both the training and validation sets hover around the ideal line of 45°,indicating that the model has good calibration.DCA shows that the constructed model curve is far away from the two polar lines(the curve with a net benefit of 0 and the curve with all samples being positive),indicating that the model has good clinical benefits.Conclusion The combination of extrarenal irAEs,lower Hb,higher SCr,and higher DBIL are independent risk factors for the occurrence of PD-1 inhibitor related AKD;The established column chart model has good discrimination and calibration,which can provide guidance for clinical practice.
Objective To investigate the effect and mechanism of angiopoietin 1 （Ang1） on choroidal neovascularization （CNV）. Methods A total of 30 Norwegian（BN） rats aged 6-8 weeks were randomly divided into three groups of ten in each group: normal group， model group， Ang1 treatment group. The normal group was not processed， and the other two groups used multi-wavelength krypton laser to model the eyes of BN rats; fundus fluorescein angiography was performed on the 14th day after molding， and on the first day after successful molding， Ang1 treatment group was injected with vitreous cavity 200 μmol/L Ang1 20 μl， FFA was performed 10 days after injection， the area was measured by choroidal patching using FITC-labeled dextran （FITC-dextran） cardiac perfusion， and the retinal-choroidal structure changes of rats were observed by Hematoxylin-eddyr staining （HE） staining; rat retinal-choroidal-sclera complex was taken， and the expression of Ang1， Rap1， GAPRap1 and vascular endothelial-cadherin （VE-cadherin） was detected by Western blotting method. Rat choroidal vascular endothelial cells （RCVECs） in logarithmic growth phase were taken， stimulated and cultured with VEGF for 24 hours， and then divided into GAPRap1-siRNA negative control group （siRNA NC group）， GAPRap1 small interfering RNA （GAPRap1-siRNA group）， GAPRap1-siRNA+Ang1 group. GAPRap1siRNA group and GAPRap1-siRNA+Ang1 group were transfected with GAPRap1-siRNA reagent， while cells in siRNA-NC group were transfected with siRNA-NC reagent; 6 hours after transfection， 200 μmol/L Ang1 was added to GAPRap1-siRNA+Ang1 group， after culturing for 24 hours， the cell protein was extracted and the expression of GAPRap1， Rap1 and VE-cadherin in the cells was detected by Western blotting. Detection of fluorescent expression of VE cadherin in transfected cells by immunofluorescence. Results Compared with the normal group， the neovascular leakage area and choroidal damage degree of rats in the model group were significantly increased （P＜0.01）. the expression of GAPRap1 and VE-cadherin proteins in the model groups was significantly reduced （both P＜0.05）， and the expression of Rap1 protein was significantly increased， and the difference was statistically significant. Compared with the model group， the neovascular leakage area and choroidal damage degree of rats in the Ang1 treatment group were significantly reduced （P＜0.01）， the expression of GAPRap1 and VE-cadherin proteins in the choroid and cells was significantly increased （both P＜0.01）， and the expression of Rap1 protein was significantly reduced， and the difference was statistically significant. In choroidal tissue， the expression of Ang1 protein in Ang1 treatment group was significantly higher than that in the other two groups （P＜0.01）. In the cell experiment， the expressions of GAPRap1 and VE-cadherin in the GAPRap1-siRNA group were significantly lower than those in the GAPRap1-siRNA+Ang1 group and the siRNA-NC group （P＜0.01）， while the expression of Rap1 had no significant change. The results of immunofluorescence showed that the fluorescence of VE cadherin in GAPRap1 siRNA group was significantly lower than that in GAPRap1 SiRNA+Ang1 group and siRNA-NC group （P＜0.001）. Conclusion Ang1 can reduce the leakage of choroidal neovascularization in rats， which has a certain inhibitory effect on choroidal neovascular growth， and its mechanism may be related to the enhancement of cell adhesion through the GAPRap1-VE-cadherin pathway to reduce leakage.
帕金森病(PD)是一种常见的神经退行性疾病,其发病率随年龄增长而增高.α-突触核蛋白的错误折叠和异常聚集是帕金森病关键的神经病理标志.近期研究显示,外泌体也可能通过其运输与转载功能推动病理性α-突触核蛋白在大脑中传播,进一步促进帕金森病的发展,从而参与帕金森病的致病机制.外泌体是一种纳米级囊泡,其直径较小的优势在帕金森病治疗中有望发挥较大作用.本文综述了外泌体在帕金森病发生中的作用和具有潜在临床应用价值的研究进展.
Esophagogastric variceal bleeding in cirrhotic patients is associated with high mortality if not adequately managed. Standardized treatment of esophagogastric variceal bleeding includes adequate resuscitation maneuvers， restrictive transfusion policy， antibiotic prophylaxis， pharmacologic therapy， and endoscopic therapy. After this initial approach， the most appropriate therapy to prevent both early and late rebleeding must be instituted following a risk stratification strategy. Placing a preemptive trans jugular intrahepatic portosystemic shunt in high-risk patients， as soon as possible after admission， to achieve early control of bleeding has proved to improve survival. The present review will focus on the initial management of patients with acute esophagogastric variceal bleeding， including general management and assessment， pharmacotherapy， as well as the available endoscopic， interventional and salvage treatments， trying to provide reference for standardizing the treatment process of such patients， in order to improve their survival rate.
目的 探讨外周血白细胞计数(WBC)和中性粒细胞与淋巴细胞比值(NLR)对肥胖症合并胃食管反流病(GERD)的临床诊断价值.方法 回顾性分析2020年1月-2022年1月新疆维吾尔自治区人民医院收治的118例肥胖症患者的临床资料.根据病史及检查结果分为肥胖症合并GERD组(n=57)与未合并GERD组(n=61).采用单因素和多因素logistic回归分析肥胖症合并GERD的危险因素.采用受试者工作特征(ROC)曲线评估外周血WBC和NLR单独与联合检测对肥胖症合并GERD的临床诊断价值.结果 合并GERD组吸烟史(31.6%vs.14.8%,P=0.030)、GERD家族史(43.9%vs.24.6%,P=0.027)占比,外周血WBC[(10.25±1.81)×109/L vs.(8.72±2.11)×109/L,P<0.001]、NLR(3.55±0.71 vs.3.00±0.64,P<0.001),以及空腹血糖[(6.39±2.21)mmol/L vs.(5.76±0.85)mmol/L,P=0.041]均高于未合并GERD组.多因素logistic回归分析结果显示,外周血WBC和NLR是肥胖症合并GERD的独立危险因素(P<0.05).ROC曲线分析显示,外周血WBC(AUC=0.707)和NLR(AUC=0.722)对肥胖症合并GERD具有较高的临床诊断价值(P<0.001),且两者联合能够提高诊断效能(AUC=0.786).结论 外周血WBC和NLR是肥胖症合并GERD的独立危险因素,对肥胖症合并GERD具有较高的诊断价值,两者联合能够提高诊断效能,具有一定的临床应用价值.
目的 分析博来霉素诱导的肺纤维化模型小鼠肺组织铁死亡相关基因的表达谱并探讨其可能的作用机制.方法 取12只6～7周龄雄性C57BL/6小鼠,随机分为模型组与对照组,每组6只,分别构建肺纤维化模型及进行对照处理.3周后处死小鼠,采用HE与Masson染色评估其肺部病理改变和胶原纤维堆积状况,普鲁士蓝染色观察肺组织铁聚集水平.应用小鼠铁死亡通路PCR Array筛选差异表达基因,采用生物信息学分析方法对差异基因进行GO功能富集与KEGG信号通路预测.运用实时定量PCR验证模型组与对照组肺组织铁死亡相关差异基因的表达水平.结果 与对照组比较,模型组小鼠肺组织出现纤维化改变及明显的铁沉积.PCR Array检测结果显示,与对照组比较,模型组碳酸酐酶9(CA9)、半胱氨酰-tRNA合成酶1(CARS1)、热休克转录因子(HSF1)、NADPH氧化酶3(NOX3)、线粒体铁蛋白(FTMT)等5个铁死亡相关基因的表达量明显降低(P<0.05).GO功能富集分析与KEGG信号通路预测结果显示,肺纤维化模型小鼠肺组织的差异表达基因主要与体温内稳态、NADPH氧化酶复合体、碳酸脱氢酶活性等功能有关,并在氮素代谢、氨酰合成、军团菌病等通路中富集.实时定量PCR验证结果显示,模型组小鼠肺组织中CA9、CARS1、HSF1及FTMT的表达量均明显低于对照组(P<0.05).结论 博来霉素诱导的肺纤维化模型小鼠肺组织中多个铁死亡相关基因的表达水平发生明显变化,提示铁死亡在特发性肺纤维化中发挥重要作用,其中的差异基因或可为临床治疗提供潜在靶点.
Objective To investigate the effect of acid-sensitive ion channel 3 （ASIC3） expression on visceral sensitivity in irritable bowel syndrome （IBS） rats and the possible regulatory mechanisms of signalling pathways. Methods From the 2nd day postpartum， 6 puppies and dams were kept in their original cages as control group; the rest of the puppies were separated from their mother to make IBS models. After the puppies grow into rats， use abdominal withdrawal reflex （AWR） score to screen 16 rats that were successful in IBS modeling， and they were randomly divided into 2 groups， the neonatal maternal separation （NMS） group and the NMS+APETx2 group， with 8 rats in each group. NMS+APETx2 group was given the ASIC3-specific blockerAPETx2 100 μg/kg intraperitoneally for 1 week while NMS group and control group were intraperitoneally injected with same amount of normal saline. Visceral pain response was measured by abdominal withdraw reflex （AWR） score， the intestinal transmission rate was measured by ink staining， the level of 5-HT in colonic tissue was measured by enzyme-linked immunosorbent assay （ELISA）， and the expression levels of 5-HT4R and ASIC3 in colonic tissue were measured by immunohistochemistry. Results Compared with control group， rats in NMS group showed significantly increased AWR scores at colorectal pressures of 40， 60， 80 mmHg， decreased intestinal transmission rate， intestinal 5-HT levels was increased and ASIC3 and 5-HT4 receptor expression was enhanced， all with statistically significant differences （P＜0.01）. There was no significant difference in AWR score and intestinal propulsion rate in NMS+APETx2 group compared with control group （P＞0.05）， but 5-HT level was elevated with significant difference， weaker expression of ASIC3 and 5-HT4R receptors compared with control group， significant difference （P＜0.01）. Compared with the NMS group， the application of the ASIC3-specific blocker APETx2 in the NMS+APETx2 group resulted in lower AWR scores， enhanced intestinal transmission rate， 5-HT levels decreased， and ASIC3 and 5-HT4R receptor expression was diminished， and the differences were statistically significant （P＜0.05 or P＜0.01）. Conclusion ASIC3 expression is involved in visceral hypersensitivity in IBS mice induced by neonatal maternal separation， which may be related to the up-regulation of 5-HT pathway.
