Sepsis management has significantly improved over the past decades,with intensivists playing a pivotal role in its identification and treatment.[1,2]However,resource constraints in large tertiary hospitals in China li...Sepsis management has significantly improved over the past decades,with intensivists playing a pivotal role in its identification and treatment.[1,2]However,resource constraints in large tertiary hospitals in China limit patient admissions,leading to overcrowding in the emergency departments(EDs)with critically ill patients.[3]This highlights the urgent need for enhanced risk stratification and optimized sepsis management in emergency settings.展开更多
Type 2 diabetes markedly elevates fracture risk despite normal or high bone mineral density,a paradox reflecting qualitative skeletal deficits rather than loss of mass.Chronic hyperglycemia fosters the accumulation of...Type 2 diabetes markedly elevates fracture risk despite normal or high bone mineral density,a paradox reflecting qualitative skeletal deficits rather than loss of mass.Chronic hyperglycemia fosters the accumulation of advanced glycation end products in bone;their nonenzymatic crosslinks stiffen type I collagen,impair mineralization,and erode mechanical strength.By engaging the receptor for advanced glycation end products,these adducts activate nuclear factorκB and mitogen-activated protein kinase cascades,amplifying oxidative stress,inflammation,osteoblast dysfunction,and osteoclastogenesis.This review synthesizes epidemiological data from type 1 and type 2 diabetes,highlights the limits of densitybased skeletal assessment,and details the molecular pathology of the glycation-collagen axis.It also appraises antiglycation therapies,including formation inhibitors,crosslink breakers and receptor antagonists,with a particular focus on sodium-glucose cotransporter 2 inhibitors that couple glycemic control with modulation of the glycation pathway.By integrating recent basic and clinical advances,we propose a mechanistic framework for diabetic bone disease and outline strategies to mitigate glycationdriven skeletal fragility.展开更多
The purpose of this study was to investigate the effect of nonadrenergic agents on cardiopulmonary resuscitation (CPR) and end-tidal CO2(ETCO2)during CPR in a rodent model. Our results suggested that: 1) coronary perf...The purpose of this study was to investigate the effect of nonadrenergic agents on cardiopulmonary resuscitation (CPR) and end-tidal CO2(ETCO2)during CPR in a rodent model. Our results suggested that: 1) coronary perfusion pressure (CPP) after drugs infusion was increased significantly by methoxamine, arginine vasopresin (AVP) and angiotension- Ⅱ(ANG- Ⅱ), but not by endothelin-1 (ET-1): 2) ETCO2 prior to defibrillation was decreased significantly by a pure a1 adrenergic agents,methoxamine and were increased significantly by non-adrenergic agents, ANG-Ⅱ and ET-1 during rodent CPR;3) a significant positive correlation between ETCO2 and CPP was observed in AVP group, suggesting that AVP have little effect on pulmonary circulation; and 4) methoxamine, AVP and ANG-Ⅱ have similar effect on resuscitability during rodent CPR.展开更多
BACKGROUND Mechanical ventilation can lead to the severe impairment of the metabolic pathway of alveolar surfactants,inactivating alveolar surfactants and significantly reducing lung-chest compliance.The cardiopulmona...BACKGROUND Mechanical ventilation can lead to the severe impairment of the metabolic pathway of alveolar surfactants,inactivating alveolar surfactants and significantly reducing lung-chest compliance.The cardiopulmonary function of elderly patients usually reduced to a certain extent,and there are lung complications after surgical anesthesia,just like lung barotrauma caused by mechanical ventilation,atelectasis and postoperative hypoxemia.AIM To investigate the effects of different positive end expiratory pressures(PEEPs)and tidal volumes(VTs)on respiratory function,the degree of the inflammatory response and hemodynamic indexes in patients undergoing surgery under general anesthesia.METHODS A total of 120 patients undergoing surgery for gastric or colon cancer under general anesthesia in Xinghua People's Hospital from January 2017 to January 2021 were randomly divided into Group A and Group B,with 60 cases in each group.The ventilation mode in Group A was VT(6.0 mL/kg)+PEEP(5.0 cmH_(2)O),while that in Group B was VT(6.0 mL/kg)+PEEP(8.0 cmH_(2)O).Blood gas parameters,respiratory mechanical parameters,inflammatory response indicators,hemodynamic indicators and related complications were compared between the two groups.RESULTS There were no significant differences in PaCO_(2),PaO_(2),oxygen or the examined indexes at T0 between group A and group B(P>0.05).The measured PaO_(2) value of patients in group A at T3 was higher than that in group B,and the difference was significant(P<0.05).There were no significant differences in peak airway pressure(P_(peak)),mean airway pressure or dynamic pulmonary compliance(Cdyn)at T0 between group A and group B(P>0.05).The measured P_(peak) value of patients in group A at T1 was higher than that in group B,and the difference was significant(P<0.05).The measured Cdyn value at T1 and T2 was greater than that in group B(P<0.05).Before surgery,there were no significant differences in tumor necrosis factor-α(TNF-α),interleukin(IL)-6 or IL-10 between group A and group B(P>0.05).After 4 h,the measured values of TNF-αand IL-6 in group A were lower than those in group B,and the differences were significant(P<0.05).The IL-10 Level in group A was higher than that in group B(P<0.05).At T0,there were no significant differences in cardiac output,cardiac index(CI),stroke volume index(SVI)or mean arterial pressure between group A and group B(P>0.05).The measured values of CI and SVI at T2 in patients in group A were higher than those in group B,and the differences were significant(P<0.05).CONCLUSION For patients undergoing surgery for gastric or colon cancer under general anesthesia,the VT(6.0 mL/kg)+PEEP(5.0 cmH_(2)O)regimen was more effective than the VT(6.0 mL/kg)+PEEP(8.0 cmH_(2)O)regimen in protecting the lung function and ventilatory function of patients,and it had better effects on maintaining hemodynamic stability and reducing inflammatory reactions.展开更多
BACKGROUND: Partial pressure of end-tidal carbon dioxide(PETCO2) has been used to monitor the effectiveness of precordial compression(PC) and regarded as a prognostic value of outcomes in cardiopulmonary resuscitation...BACKGROUND: Partial pressure of end-tidal carbon dioxide(PETCO2) has been used to monitor the effectiveness of precordial compression(PC) and regarded as a prognostic value of outcomes in cardiopulmonary resuscitation(CPR). This study was to investigate changes of PETCO2 during CPR in rats with ventricular fi brillation(VF) versus asphyxial cardiac arrest.METHODS: Sixty-two male Sprague-Dawley(SD) rats were randomly divided into an asphyxial group(n=32) and a VF group(n=30). PETCO2 was measured during CPR from a 6-minute period of VF or asphyxial cardiac arrest.RESULTS: The initial values of PETCO2 immediately after PC in the VF group were signifi cantly lower than those in the asphyxial group(12.8±4.87 mmHg vs. 49.2±8.13 mmHg, P=0.000). In the VF group, the values of PETCO2 after 6 minutes of PC were significantly higher in rats with return of spontaneous circulation(ROSC), compared with those in rats without ROSC(16.5±3.07 mmHg vs. 13.2±2.62 mmHg, P=0.004). In the asphyxial group, the values of PETCO2 after 2 minutes of PC in rats with ROSC were signifi cantly higher than those in rats without ROSC(20.8±3.24 mmHg vs. 13.9±1.50 mmHg, P=0.000). Receiver operator characteristic(ROC) curves of PETCO2 showed signifi cant sensitivity and specifi city for predicting ROSC in VF versus asphyxial cardiac arrest.CONCLUSIONS: The initial values of PETCO2 immediately after CPR may be helpful in differentiating the causes of cardiac arrest. Changes of PETCO2 during CPR can predict outcomes of CPR.展开更多
The incidence of type 2 diabetes mellitus is growing in epidemic proportions and has become one of the most critical public health concerns.Cardiovascular complications associated with diabetes are the leading cause o...The incidence of type 2 diabetes mellitus is growing in epidemic proportions and has become one of the most critical public health concerns.Cardiovascular complications associated with diabetes are the leading cause of morbidity and mortality.The cardiovascular diseases that accompany diabetes include angina,myocardial infarction,stroke,peripheral artery disease,and congestive heart failure.Among the various risk factors generated secondary to hyperglycemic situations,advanced glycation end products(AGEs)are one of the important targets for future diagnosis and prevention of diabetes.In the last decade,AGEs have drawn a lot of attention due to their involvement in diabetic pathophysiology.AGEs can be derived exogenously and endogenously through various pathways.These are a nonhomogeneous,chemically diverse group of compounds formed nonenzymatically by condensation between carbonyl groups of reducing sugars and free amino groups of protein,lipids,and nucleic acid.AGEs mediate their pathological effects at the cellular and extracellular levels by multiple pathways.At the cellular level,they activate signaling cascades via the receptor for AGEs and initiate a complex series of intracellular signaling resulting in reactive oxygen species generation,inflammation,cellular proliferation,and fibrosis that may possibly exacerbate the damaging effects on cardiac functions in diabetics.AGEs also cause covalent modifications and cross-linking of serum and extracellular matrix proteins;altering their structure,stability,and functions.Early diagnosis of diabetes may prevent its progression to complications and decrease its associated comorbidities.In the present review,we recapitulate the role of AGEs as a crucial mediator of hyperglycemia-mediated detrimental effects in diabetes-associated complications.Furthermore,this review presents an overview of future perspectives for new therapeutic interventions to ameliorate cardiovascular complications in diabetes.展开更多
Soluble receptor for advanced glycation end products(sRAGE)acts as a decoy sequestering of RAGE ligands,thus preventing the activation of the ligand-RAGE axis linking human diseases.However,the molecular mechanisms un...Soluble receptor for advanced glycation end products(sRAGE)acts as a decoy sequestering of RAGE ligands,thus preventing the activation of the ligand-RAGE axis linking human diseases.However,the molecular mechanisms underlying sRAGE remain unclear.In this study,THP-1 monocytes were cultured in normal glucose(NG,5.5 mmol/L)and high glucose(HG,15 mmol/L)to investigate the effects of diabetesrelevant glucose concentrations on sRAGE and interleukin-1β(IL-1β)secretion.The modulatory effects of epigallocatechin gallate(EGCG)in response to HG challenge were also evaluated.HG enhanced intracellular reactive oxygen species(ROS)generation and RAGE expression.The secretion of sRAGE,including esRAGE and cRAGE,was reduced under HG conditions,together with the downregulation of a disintegrin and metallopeptidase 10(ADAM10)and nuclear factor erythroid 2-related factor 2(Nrf2)nuclear translocation.Mechanistically,the HG effects were counteracted by siRAGE and exacerbated by siNrf2.Chromatin immunoprecipitation results showed that Nrf2 binding to the ADAM10 promoter and HG interfered with this binding.Our data reinforce the notion that RAGE and Nrf2 might be sRAGE-regulating factors.Under HG conditions,the treatment of EGCG reduced ROS generation and RAGE activation.EGCG-stimulated cRAGE release was likely caused by the upregulation of the Nrf2-ADAM10 pathway.EGCG inhibited HG-mediated NLRP3 inflammasome activation at least partly by stimulating sRAGE,thereby reducing IL-1βrelease.展开更多
Background: We investigated the differences between partial pressure of arterial carbon dioxide and end-tidal carbon dioxide (P(a-ET)CO2) with respect to the Broca-Katsura index (BKI), which is an obesity index, in ob...Background: We investigated the differences between partial pressure of arterial carbon dioxide and end-tidal carbon dioxide (P(a-ET)CO2) with respect to the Broca-Katsura index (BKI), which is an obesity index, in obese patients during general anesthesia. Materials and Methods: From January 2003 to December 2013, we studied 601 patients aged 16 years old or over undergoing general anesthesia. Patients had American Society of Anesthesiology physical status I and II and we reviewed their anesthetic charts. The P(a-ET)CO2 with respect to the BKI divided patients into two groups: 16 to 2 values between the two groups. Results: In patients aged 16 to 2 was 2.2 ± 3.1 mmHg at BKI 2 was 3.2 ± 4.1 mmHg at BKI 2 tends to increase in obese patients during general anesthesia with increasing BKI in patients aged 16 to < 65 years old.展开更多
Obesity and type 2 diabetes mellitus(T2DM)are chronic pathologies with a high incidence worldwide.They share some pathological mechanisms,including hyperinsulinemia,the production and release of hormones,and hyperglyc...Obesity and type 2 diabetes mellitus(T2DM)are chronic pathologies with a high incidence worldwide.They share some pathological mechanisms,including hyperinsulinemia,the production and release of hormones,and hyperglycemia.The above,over time,affects other systems of the human body by causing tissue hypoxia,low-grade inflammation,and oxidative stress,which lay the pathophysiological groundwork for cancer.The leading causes of death globally are T2DM and cancer.Other main alterations of this pathological triad include the accumulation of advanced glycation end products and the release of endogenous alarmins due to cell death(i.e.,damage-associated molecular patterns)such as the intracellular proteins high-mobility group box protein 1 and protein S100 that bind to the receptor for advanced glycation products(RAGE)-a multiligand receptor involved in inflammatory and metabolic and neoplastic processes.This review analyzes the latest advanced reports on the role of RAGE in the development of obesity,T2DM,and cancer,with an aim to understand the intracellular signaling mechanisms linked with cancer initiation.This review also explores inflammation,oxidative stress,hypoxia,cellular senescence,RAGE ligands,tumor microenvironment changes,and the“cancer hallmarks”of the leading tumors associated with T2DM.The assimilation of this information could aid in the development of diagnostic and therapeutic approaches to lower the morbidity and mortality associated with these diseases.展开更多
目的添加转化生长因子-β1（TGF-β1）以及与内脏内胚层样END-2细胞共培养，定向诱导胚胎干细胞（ESCs）分化，探索联合使用化学诱导法与共培养法对ESCs的心肌细胞定向诱导分化作用。方法将ESCs悬浮培养形成2—3d类胚体（EBs），再向培...目的添加转化生长因子-β1（TGF-β1）以及与内脏内胚层样END-2细胞共培养，定向诱导胚胎干细胞（ESCs）分化，探索联合使用化学诱导法与共培养法对ESCs的心肌细胞定向诱导分化作用。方法将ESCs悬浮培养形成2—3d类胚体（EBs），再向培养液内添加TGF-β1，或（和）将2—3 d EBs与END-2细胞或END-2细胞条件培养液共培养。自然分化为对照组。免疫荧光技术检测心肌细胞特异性肌动蛋白（α-actin）及肌钙蛋白T（TnT）的表达，透射电镜观察分化心肌细胞的超微结构。结果向培养液添加TGF-β1或将2—3dEBs与END-2细胞或END-2细胞条件培养液共培养，各自有（43±2．08）％（P〈0．01），（69±3．61）％（P〈0．01），（65±3．06）％（P〈0．01）的EBs出现自发节律性收缩，均表达心肌细胞特异性蛋白α-Actin和TnT，观察到心肌样超微结构。自然分化组发生自发节律性收缩的EBs只有（12±1．53）％，尤其是联合使用两种诱导方法，自发性收缩的EBs高达（91±1．52）％（P〈0．01），收缩区域较单一诱导组大，且细胞形态较单一。结论联合使用化学诱导和共培养2种诱导法对ESCs的心肌细胞定向分化有协同作用。展开更多
Our previous study showed an association between advanced glycation end products （AGEs） and neural tube defects （NTDs）. To understand the molecular mechanisms underlying the effect of AGEs on neural tube developme...Our previous study showed an association between advanced glycation end products （AGEs） and neural tube defects （NTDs）. To understand the molecular mechanisms underlying the effect of AGEs on neural tube development, C57BL/6 female mice were fed for 4 weeks with com- mercial food containing 3% advanced glycation end product bovine serum albumin （AGE-BSA） or 3% bovine serum albumin （BSA） as a control. After mating mice, oxidative stress markers including malondialdehyde and H202 were measured at embryonic day 7.5 （E7.5） of ges- tation, and the level of intracellular reactive oxygen species （ROS） in embryonic cells was determined at E8.5. In addition to evaluating NTDs, an enzyme-linked immunosorbent assay was used to determine the effect of embryonic protein administration on the N-（carboxymethyl） lysine reactivity of acid and carboxyethyl lysine antibodies at E10.5. The results showed a remarkable increase in the incidence of NTDs at El0.5 in embryos of mice fed with AGE-BSA （no hyperglycemia） compared with control mice. Moreover, embryonic protein administration resulted in a noticeable increase in the reactivity of N-（carboxymethyl） lysine and N（ε）-（carboxyethyl） lysine antibodies. Malondialdehyde and H2O2 levels in embryonic cells were increased at E7.5, followed by increased intracellular ROS levels at E8.5. Vitamin E supplementation could partially recover these phenomena. Collectively, these results suggest that AGE-BSA could induce NTDs in the absence of hyperglycemia by an underlying mechanism that is at least partially associated with its capacity to increase embryonic oxidative stress levels.展开更多
BACKGROUND The accumulation of advanced glycation end products(AGEs)have been implicated in the development and progression of diabetic vasculopathy.However,the role of profilin-1 as a multifunctional actin-binding pr...BACKGROUND The accumulation of advanced glycation end products(AGEs)have been implicated in the development and progression of diabetic vasculopathy.However,the role of profilin-1 as a multifunctional actin-binding protein in AGEs-induced atherosclerosis(AS)is largely unknown.AIM To explore the potential role of profilin-1 in the pathogenesis of AS induced by AGEs,particularly in relation to the Janus kinase 2(JAK2)and signal transducer and activator of transcription 3(STAT3)signaling pathway.METHODS Eighty-nine individuals undergoing coronary angiography were enrolled in the study.Plasma cytokine levels were detected using ELISA kits.Rat aortic vascular smooth muscle cells(RASMCs)were incubated with different compounds for different times.Cell proliferation was determined by performing the MTT assay and EdU staining.An AGEs-induced vascular remodeling model was established in rats and histological and immunohistochemical analyses were performed.The mRNA and protein levels were detected using real-time PCR and Western blot analysis,respectively.In vivo,shRNA transfection was performed to verify the role of profilin-1 in AGEs-induced proatherogenic mediator release and aortic remodeling.Statistical analyses were performed using SPSS 22.0 software.RESULTS Compared with the control group,plasma levels of profilin-1 and receptor for AGEs(RAGE)were significantly increased in patients with coronary artery disease,especially in those complicated with diabetes mellitus(P<0.01).The levels of profilin-1 were positively correlated with the levels of RAGE(P<0.01);additionally,the levels of both molecules were positively associated with the degree of coronary artery stenosis(P<0.01).In vivo,tail vein injections of AGEs induced the release of proatherogenic mediators,such as asymmetric dimethylarginine,intercellular adhesion molecule-1,and the N-terminus of procollagen III peptide,concomitant with apparent aortic morphological changes and significantly upregulated expression of the profilin-1 mRNA and protein in the thoracic aorta(P<0.05 or P<0.01).Downregulation of profilin-1 expression with an shRNA significantly attenuated AGEs-induced proatherogenic mediator release(P<0.05)and aortic remodeling.In vitro,incubation of vascular smooth muscle cells(VSMCs)with AGEs significantly promoted cell proliferation and upregulated the expression of the profilin-1 mRNA and protein(P<0.05).AGEs(200μg/mL,24 h)significantly upregulated the expression of the STAT3 mRNA and protein and JAK2 protein,which was blocked by a JAK2 inhibitor(T3042-1)and/or STAT3 inhibitor(T6308-1)(P<0.05).In addition,pretreatment with T3042-1 or T6308-1 significantly inhibited AGEs-induced RASMC proliferation(P<0.05).CONCLUSION AGEs induce proatherogenic events such as VSMC proliferation,proatherogenic mediator release,and vascular remodeling,changes that can be attenuated by silencing profilin-1 expression.These results suggest a crucial role for profilin-1 in AGEs-induced vasculopathy.展开更多
Objectives To study the change in plasma hemoglobin concentration in elderly patients with primary hypertension and/or type 2 diabetes complicated with end-stage renal disease （ESRD） determined by estimated glomerul...Objectives To study the change in plasma hemoglobin concentration in elderly patients with primary hypertension and/or type 2 diabetes complicated with end-stage renal disease （ESRD） determined by estimated glomerular filtration rate. Methods Two hundred and thirty cases of Chinese patients aged 60 years or older with primary hypertension and/or type 2 diabetes complicated with chronic kidney disease were enrolled in the study. Patients with chronic kidney disease were divided into ESRD group with estimated glomemlar filtration rate less than 15 mL . min^-1.1.73 m^-2 （7.80 ± 3. 14 mL. min^-1 . 1.73 m^-2） and non-ESRD group with estimated glomerular filtration rate 15 mL.min^-1 . 1.73 m^-2（29. 76 ± 12. 90 mL.min^-1 . 1.73 m^-2） or higher. The plasma hemoglobin concentration was compared between the above two groups retrospectively. Results There was significant decrease in plasma hemoglobin concentration in ESRD group compared with non-ESRD group （74.4 ± 22. 5 g/L vs 100. 8 ± 23.0 g/L, P 〈 0. 05 ）. After stratification by sex, there was also significant decrease in plasma hemoglobin concentration both in male and female of ESRD groups compared with their respective non-ESRD groups（77. 2±22. 0 g/L vs 104. 9 ±20. 7 g/L; 69. 7 ±22. 8 g/L vs 96.4± 24.8 g/L, P 〈 0. 05, respectively）. Plasma hemoglobin concentration was positively related to estimated glomerular filtration rate significantly in patients with ESRD （ P 〈 0. 05 ）. Conclusions Plasma hemoglobin concentration is decreased significantly, and is positively related to estimated glomerular filtration rate significantly in elderly patients with primary hypertension and/or type 2 diabetes complicated with ESRD determined by estimated glomerular filtration rate.展开更多
Background High positive end-expiratory pressure （PEEP） and low tidal volume （VT） ventilation is thought to be a protective ventilation strategy. It is hypothesized that the stabilization of collapsible alveoli du...Background High positive end-expiratory pressure （PEEP） and low tidal volume （VT） ventilation is thought to be a protective ventilation strategy. It is hypothesized that the stabilization of collapsible alveoli during expiration contributes to lung protection. However, this hypothesis came from analysis of indirect indices like the analysis of the pressure-volume curve of the lung. The purpose of this study was to investigate isolated healthy and injured rat lungs by means of alveolar microscopy, in which combination of PEEP and VT is beneficial with respect to alveolar stability （I-E%）. Methods Alveolar stability was investigated in isolated, non-perfused mechanically ventilated rat lungs. Injured lungs were compared with normal lungs. For both groups three PEEP settings （5, 10, 20 cmH20） were combined with three VT settings （6, 10, 15 ml/kg） resulting in nine PEEP-VT combinations per group. Analysis was performed by alveolar microscopy. Results In normal lungs alveolar stability persisted in all PEEP-VT combinations （I-E% （3.2±11.0）%）. There was no significant difference using different settings （P 〉0.01）. In contrast, alveoli in injured lungs were extremely instable at PEEP levels of 5 cmH20 （mean I-E% 100%） and 10 cmH2O （mean I-E% （30.7±16.8）%）; only at a PEEP of 20 cmH20 were alveoli stabilized （mean I-E% of （0.2±9.3）%）. Conclusions In isolated healthy lungs alveolar stability is almost unaffected by different settings of PEEP and VT. In isolated injured lungs only a high PEEP level of 20 cmH2O resulted in stabilized alveoli whereas lower PEEP levels are associated with alveolar instability.展开更多
The complexity of river-tide interaction poses a significant challenge in predicting discharge in tidal rivers.Long short-term memory(LSTM)networks excel in processing and predicting crucial events with extended inter...The complexity of river-tide interaction poses a significant challenge in predicting discharge in tidal rivers.Long short-term memory(LSTM)networks excel in processing and predicting crucial events with extended intervals and time delays in time series data.Additionally,the sequence-to-sequence(Seq2Seq)model,known for handling temporal relationships,adapting to variable-length sequences,effectively capturing historical information,and accommodating various influencing factors,emerges as a robust and flexible tool in discharge forecasting.In this study,we introduce the application of LSTM-based Seq2Seq models for the first time in forecasting the discharge of a tidal reach of the Changjiang River(Yangtze River)Estuary.This study focuses on discharge forecasting using three key input characteristics:flow velocity,water level,and discharge,which means the structure of multiple input and single output is adopted.The experiment used the discharge data of the whole year of 2020,of which the first 80%is used as the training set,and the last 20%is used as the test set.This means that the data covers different tidal cycles,which helps to test the forecasting effect of different models in different tidal cycles and different runoff.The experimental results indicate that the proposed models demonstrate advantages in long-term,mid-term,and short-term discharge forecasting.The Seq2Seq models improved by 6%-60%and 5%-20%of the relative standard deviation compared to the harmonic analysis models and improved back propagation neural network models in discharge prediction,respectively.In addition,the relative accuracy of the Seq2Seq model is 1%to 3%higher than that of the LSTM model.Analytical assessment of the prediction errors shows that the Seq2Seq models are insensitive to the forecast lead time and they can capture characteristic values such as maximum flood tide flow and maximum ebb tide flow in the tidal cycle well.This indicates the significance of the Seq2Seq models.展开更多
Background Nitric oxide （NO） plays an important role in acute lung injury （ALl）, acute respiratory distress syndrome （ARDS）, and in ventilator-induced lung injury （VILI）. A change in the balance of endothelin...Background Nitric oxide （NO） plays an important role in acute lung injury （ALl）, acute respiratory distress syndrome （ARDS）, and in ventilator-induced lung injury （VILI）. A change in the balance of endothelin-1 （ET-1） and NO in the ALI/ARDS can also add to these problems. However, the profile of ET-1 and the balance of ET-1 and NO are still unknown in a VILI model. Methods Models of oleic acid induced ALl were established in dogs; these models were then randomized into three groups undergone different tidal volume （VT） mechanical ventilation, which included a VT6 group （VT equaled to 6 ml/kg body weight, positive end expiratory pressure （PEEP） equaled to 10 cmH20, n=-6）, a VT10 group （VT equaled to 10 ml/kg body weight, PEEP equaled to 10 cmH20, n=-4） and a VT20 group （VT equaled to 20 ml/kg body weight, PEEP equaled to 10 cmH20, n=-6） for 6-hour ventilation. The levels of ET-1 and NO in serum and tissue homogenates of lung were observed throughout the trial. Results PaO2 was increased after mechanical ventilation, but hypercapnia occurred in the VT6 group. The magnitudes of lung injury in the VT20 group were more severe than those in the VT6 group and the VT10 group. Serum levels of ET-1 and NO increased after ALl models were established and slightly decreased after a 6-hour ventilation in both the VT6 group and the VT20 group. The serum ET-1 level in the VT20 group was higher than that in the VT6 group and the VT10 group after the 6-hour ventilation （P 〈0.05） while the serum NO levels were similar in the three groups （all P 〉0.05）. There was no significant difference in serum ratio of ET-1/NO between any two out of three groups （P 〉0.05）, although there was a significant positive relationship between serum ET-1 and serum NO （r=0.80, P 〈0.01）. The levels of ET-1 and NO in the lung were increased after ventilation. The lung ET-1 level in the VT20 group was significantly higher than that in the VT6 group and VT10 group （both P 〈0.05） while there was no significant difference in lung NO levels between two groups （P〉0.05）. In the lung tissue, the ratio of ET-1/NO was significantly higher in the VT20 group than in the VT6 group and VT10 group after the 6-hour ventilation （P 〈0.05） as there was a significant positive relationship between ET-1 and NO in the lung （r=0.54, P 〈0.05）. Conclusions The production of ET-1 and NO was increased in serum and lung tissue in a VILI model. But the ET-1 levels increased much more than the NO levels in the lung, though there was a significant positive relationship between levels of ET-1 and NO. These results showed that there was an interaction between ET-1 and NO in a VILI model and changing the balance of ET-1 and NO levels might contribute to the pathophysiologic process of VILI.展开更多
基金supported by grants from the Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences(2021-I2M-1-062,to BD).
文摘Sepsis management has significantly improved over the past decades,with intensivists playing a pivotal role in its identification and treatment.[1,2]However,resource constraints in large tertiary hospitals in China limit patient admissions,leading to overcrowding in the emergency departments(EDs)with critically ill patients.[3]This highlights the urgent need for enhanced risk stratification and optimized sepsis management in emergency settings.
基金Supported by Clinical Medical Research Fund of the Zhejiang Medical Association,No.2025ZYC-Z32Henan Provincial Key Research and Development Program,No.231111311000+1 种基金Henan Provincial Science and Technology Research Project,No.232102310411Clinical Medical Research Fund of the Zhejiang Medical Association,2024ZYC-Z30.
文摘Type 2 diabetes markedly elevates fracture risk despite normal or high bone mineral density,a paradox reflecting qualitative skeletal deficits rather than loss of mass.Chronic hyperglycemia fosters the accumulation of advanced glycation end products in bone;their nonenzymatic crosslinks stiffen type I collagen,impair mineralization,and erode mechanical strength.By engaging the receptor for advanced glycation end products,these adducts activate nuclear factorκB and mitogen-activated protein kinase cascades,amplifying oxidative stress,inflammation,osteoblast dysfunction,and osteoclastogenesis.This review synthesizes epidemiological data from type 1 and type 2 diabetes,highlights the limits of densitybased skeletal assessment,and details the molecular pathology of the glycation-collagen axis.It also appraises antiglycation therapies,including formation inhibitors,crosslink breakers and receptor antagonists,with a particular focus on sodium-glucose cotransporter 2 inhibitors that couple glycemic control with modulation of the glycation pathway.By integrating recent basic and clinical advances,we propose a mechanistic framework for diabetic bone disease and outline strategies to mitigate glycationdriven skeletal fragility.
文摘The purpose of this study was to investigate the effect of nonadrenergic agents on cardiopulmonary resuscitation (CPR) and end-tidal CO2(ETCO2)during CPR in a rodent model. Our results suggested that: 1) coronary perfusion pressure (CPP) after drugs infusion was increased significantly by methoxamine, arginine vasopresin (AVP) and angiotension- Ⅱ(ANG- Ⅱ), but not by endothelin-1 (ET-1): 2) ETCO2 prior to defibrillation was decreased significantly by a pure a1 adrenergic agents,methoxamine and were increased significantly by non-adrenergic agents, ANG-Ⅱ and ET-1 during rodent CPR;3) a significant positive correlation between ETCO2 and CPP was observed in AVP group, suggesting that AVP have little effect on pulmonary circulation; and 4) methoxamine, AVP and ANG-Ⅱ have similar effect on resuscitability during rodent CPR.
文摘BACKGROUND Mechanical ventilation can lead to the severe impairment of the metabolic pathway of alveolar surfactants,inactivating alveolar surfactants and significantly reducing lung-chest compliance.The cardiopulmonary function of elderly patients usually reduced to a certain extent,and there are lung complications after surgical anesthesia,just like lung barotrauma caused by mechanical ventilation,atelectasis and postoperative hypoxemia.AIM To investigate the effects of different positive end expiratory pressures(PEEPs)and tidal volumes(VTs)on respiratory function,the degree of the inflammatory response and hemodynamic indexes in patients undergoing surgery under general anesthesia.METHODS A total of 120 patients undergoing surgery for gastric or colon cancer under general anesthesia in Xinghua People's Hospital from January 2017 to January 2021 were randomly divided into Group A and Group B,with 60 cases in each group.The ventilation mode in Group A was VT(6.0 mL/kg)+PEEP(5.0 cmH_(2)O),while that in Group B was VT(6.0 mL/kg)+PEEP(8.0 cmH_(2)O).Blood gas parameters,respiratory mechanical parameters,inflammatory response indicators,hemodynamic indicators and related complications were compared between the two groups.RESULTS There were no significant differences in PaCO_(2),PaO_(2),oxygen or the examined indexes at T0 between group A and group B(P>0.05).The measured PaO_(2) value of patients in group A at T3 was higher than that in group B,and the difference was significant(P<0.05).There were no significant differences in peak airway pressure(P_(peak)),mean airway pressure or dynamic pulmonary compliance(Cdyn)at T0 between group A and group B(P>0.05).The measured P_(peak) value of patients in group A at T1 was higher than that in group B,and the difference was significant(P<0.05).The measured Cdyn value at T1 and T2 was greater than that in group B(P<0.05).Before surgery,there were no significant differences in tumor necrosis factor-α(TNF-α),interleukin(IL)-6 or IL-10 between group A and group B(P>0.05).After 4 h,the measured values of TNF-αand IL-6 in group A were lower than those in group B,and the differences were significant(P<0.05).The IL-10 Level in group A was higher than that in group B(P<0.05).At T0,there were no significant differences in cardiac output,cardiac index(CI),stroke volume index(SVI)or mean arterial pressure between group A and group B(P>0.05).The measured values of CI and SVI at T2 in patients in group A were higher than those in group B,and the differences were significant(P<0.05).CONCLUSION For patients undergoing surgery for gastric or colon cancer under general anesthesia,the VT(6.0 mL/kg)+PEEP(5.0 cmH_(2)O)regimen was more effective than the VT(6.0 mL/kg)+PEEP(8.0 cmH_(2)O)regimen in protecting the lung function and ventilatory function of patients,and it had better effects on maintaining hemodynamic stability and reducing inflammatory reactions.
基金supported in part by grants from the National Natural Science Foundation of China(30700303)the National Clinical Key Subject Construction Project
文摘BACKGROUND: Partial pressure of end-tidal carbon dioxide(PETCO2) has been used to monitor the effectiveness of precordial compression(PC) and regarded as a prognostic value of outcomes in cardiopulmonary resuscitation(CPR). This study was to investigate changes of PETCO2 during CPR in rats with ventricular fi brillation(VF) versus asphyxial cardiac arrest.METHODS: Sixty-two male Sprague-Dawley(SD) rats were randomly divided into an asphyxial group(n=32) and a VF group(n=30). PETCO2 was measured during CPR from a 6-minute period of VF or asphyxial cardiac arrest.RESULTS: The initial values of PETCO2 immediately after PC in the VF group were signifi cantly lower than those in the asphyxial group(12.8±4.87 mmHg vs. 49.2±8.13 mmHg, P=0.000). In the VF group, the values of PETCO2 after 6 minutes of PC were significantly higher in rats with return of spontaneous circulation(ROSC), compared with those in rats without ROSC(16.5±3.07 mmHg vs. 13.2±2.62 mmHg, P=0.004). In the asphyxial group, the values of PETCO2 after 2 minutes of PC in rats with ROSC were signifi cantly higher than those in rats without ROSC(20.8±3.24 mmHg vs. 13.9±1.50 mmHg, P=0.000). Receiver operator characteristic(ROC) curves of PETCO2 showed signifi cant sensitivity and specifi city for predicting ROSC in VF versus asphyxial cardiac arrest.CONCLUSIONS: The initial values of PETCO2 immediately after CPR may be helpful in differentiating the causes of cardiac arrest. Changes of PETCO2 during CPR can predict outcomes of CPR.
文摘The incidence of type 2 diabetes mellitus is growing in epidemic proportions and has become one of the most critical public health concerns.Cardiovascular complications associated with diabetes are the leading cause of morbidity and mortality.The cardiovascular diseases that accompany diabetes include angina,myocardial infarction,stroke,peripheral artery disease,and congestive heart failure.Among the various risk factors generated secondary to hyperglycemic situations,advanced glycation end products(AGEs)are one of the important targets for future diagnosis and prevention of diabetes.In the last decade,AGEs have drawn a lot of attention due to their involvement in diabetic pathophysiology.AGEs can be derived exogenously and endogenously through various pathways.These are a nonhomogeneous,chemically diverse group of compounds formed nonenzymatically by condensation between carbonyl groups of reducing sugars and free amino groups of protein,lipids,and nucleic acid.AGEs mediate their pathological effects at the cellular and extracellular levels by multiple pathways.At the cellular level,they activate signaling cascades via the receptor for AGEs and initiate a complex series of intracellular signaling resulting in reactive oxygen species generation,inflammation,cellular proliferation,and fibrosis that may possibly exacerbate the damaging effects on cardiac functions in diabetics.AGEs also cause covalent modifications and cross-linking of serum and extracellular matrix proteins;altering their structure,stability,and functions.Early diagnosis of diabetes may prevent its progression to complications and decrease its associated comorbidities.In the present review,we recapitulate the role of AGEs as a crucial mediator of hyperglycemia-mediated detrimental effects in diabetes-associated complications.Furthermore,this review presents an overview of future perspectives for new therapeutic interventions to ameliorate cardiovascular complications in diabetes.
文摘Soluble receptor for advanced glycation end products(sRAGE)acts as a decoy sequestering of RAGE ligands,thus preventing the activation of the ligand-RAGE axis linking human diseases.However,the molecular mechanisms underlying sRAGE remain unclear.In this study,THP-1 monocytes were cultured in normal glucose(NG,5.5 mmol/L)and high glucose(HG,15 mmol/L)to investigate the effects of diabetesrelevant glucose concentrations on sRAGE and interleukin-1β(IL-1β)secretion.The modulatory effects of epigallocatechin gallate(EGCG)in response to HG challenge were also evaluated.HG enhanced intracellular reactive oxygen species(ROS)generation and RAGE expression.The secretion of sRAGE,including esRAGE and cRAGE,was reduced under HG conditions,together with the downregulation of a disintegrin and metallopeptidase 10(ADAM10)and nuclear factor erythroid 2-related factor 2(Nrf2)nuclear translocation.Mechanistically,the HG effects were counteracted by siRAGE and exacerbated by siNrf2.Chromatin immunoprecipitation results showed that Nrf2 binding to the ADAM10 promoter and HG interfered with this binding.Our data reinforce the notion that RAGE and Nrf2 might be sRAGE-regulating factors.Under HG conditions,the treatment of EGCG reduced ROS generation and RAGE activation.EGCG-stimulated cRAGE release was likely caused by the upregulation of the Nrf2-ADAM10 pathway.EGCG inhibited HG-mediated NLRP3 inflammasome activation at least partly by stimulating sRAGE,thereby reducing IL-1βrelease.
文摘Background: We investigated the differences between partial pressure of arterial carbon dioxide and end-tidal carbon dioxide (P(a-ET)CO2) with respect to the Broca-Katsura index (BKI), which is an obesity index, in obese patients during general anesthesia. Materials and Methods: From January 2003 to December 2013, we studied 601 patients aged 16 years old or over undergoing general anesthesia. Patients had American Society of Anesthesiology physical status I and II and we reviewed their anesthetic charts. The P(a-ET)CO2 with respect to the BKI divided patients into two groups: 16 to 2 values between the two groups. Results: In patients aged 16 to 2 was 2.2 ± 3.1 mmHg at BKI 2 was 3.2 ± 4.1 mmHg at BKI 2 tends to increase in obese patients during general anesthesia with increasing BKI in patients aged 16 to < 65 years old.
基金Supported by the Founding Proyectos de Impulso a la Investigación to Hernandez-Nazara ZH from Universidad de Guadalajara,Mexico,No.PIN 2020-I.
文摘Obesity and type 2 diabetes mellitus(T2DM)are chronic pathologies with a high incidence worldwide.They share some pathological mechanisms,including hyperinsulinemia,the production and release of hormones,and hyperglycemia.The above,over time,affects other systems of the human body by causing tissue hypoxia,low-grade inflammation,and oxidative stress,which lay the pathophysiological groundwork for cancer.The leading causes of death globally are T2DM and cancer.Other main alterations of this pathological triad include the accumulation of advanced glycation end products and the release of endogenous alarmins due to cell death(i.e.,damage-associated molecular patterns)such as the intracellular proteins high-mobility group box protein 1 and protein S100 that bind to the receptor for advanced glycation products(RAGE)-a multiligand receptor involved in inflammatory and metabolic and neoplastic processes.This review analyzes the latest advanced reports on the role of RAGE in the development of obesity,T2DM,and cancer,with an aim to understand the intracellular signaling mechanisms linked with cancer initiation.This review also explores inflammation,oxidative stress,hypoxia,cellular senescence,RAGE ligands,tumor microenvironment changes,and the“cancer hallmarks”of the leading tumors associated with T2DM.The assimilation of this information could aid in the development of diagnostic and therapeutic approaches to lower the morbidity and mortality associated with these diseases.
文摘目的添加转化生长因子-β1（TGF-β1）以及与内脏内胚层样END-2细胞共培养，定向诱导胚胎干细胞（ESCs）分化，探索联合使用化学诱导法与共培养法对ESCs的心肌细胞定向诱导分化作用。方法将ESCs悬浮培养形成2—3d类胚体（EBs），再向培养液内添加TGF-β1，或（和）将2—3 d EBs与END-2细胞或END-2细胞条件培养液共培养。自然分化为对照组。免疫荧光技术检测心肌细胞特异性肌动蛋白（α-actin）及肌钙蛋白T（TnT）的表达，透射电镜观察分化心肌细胞的超微结构。结果向培养液添加TGF-β1或将2—3dEBs与END-2细胞或END-2细胞条件培养液共培养，各自有（43±2．08）％（P〈0．01），（69±3．61）％（P〈0．01），（65±3．06）％（P〈0．01）的EBs出现自发节律性收缩，均表达心肌细胞特异性蛋白α-Actin和TnT，观察到心肌样超微结构。自然分化组发生自发节律性收缩的EBs只有（12±1．53）％，尤其是联合使用两种诱导方法，自发性收缩的EBs高达（91±1．52）％（P〈0．01），收缩区域较单一诱导组大，且细胞形态较单一。结论联合使用化学诱导和共培养2种诱导法对ESCs的心肌细胞定向分化有协同作用。
基金supported by the grant from Shaanxi Technology Committee of China,No.2013JM4001the China Scholarship Council(CSC)
文摘Our previous study showed an association between advanced glycation end products （AGEs） and neural tube defects （NTDs）. To understand the molecular mechanisms underlying the effect of AGEs on neural tube development, C57BL/6 female mice were fed for 4 weeks with com- mercial food containing 3% advanced glycation end product bovine serum albumin （AGE-BSA） or 3% bovine serum albumin （BSA） as a control. After mating mice, oxidative stress markers including malondialdehyde and H202 were measured at embryonic day 7.5 （E7.5） of ges- tation, and the level of intracellular reactive oxygen species （ROS） in embryonic cells was determined at E8.5. In addition to evaluating NTDs, an enzyme-linked immunosorbent assay was used to determine the effect of embryonic protein administration on the N-（carboxymethyl） lysine reactivity of acid and carboxyethyl lysine antibodies at E10.5. The results showed a remarkable increase in the incidence of NTDs at El0.5 in embryos of mice fed with AGE-BSA （no hyperglycemia） compared with control mice. Moreover, embryonic protein administration resulted in a noticeable increase in the reactivity of N-（carboxymethyl） lysine and N（ε）-（carboxyethyl） lysine antibodies. Malondialdehyde and H2O2 levels in embryonic cells were increased at E7.5, followed by increased intracellular ROS levels at E8.5. Vitamin E supplementation could partially recover these phenomena. Collectively, these results suggest that AGE-BSA could induce NTDs in the absence of hyperglycemia by an underlying mechanism that is at least partially associated with its capacity to increase embryonic oxidative stress levels.
基金the National Natural Science Foundation of China,No.81000140,No.81770358,and No.82000339Natural Science Foundation of Hunan Province,No.2017JJ3486and the Fund for Health Care in Hunan Province,No.B2017-01.
文摘BACKGROUND The accumulation of advanced glycation end products(AGEs)have been implicated in the development and progression of diabetic vasculopathy.However,the role of profilin-1 as a multifunctional actin-binding protein in AGEs-induced atherosclerosis(AS)is largely unknown.AIM To explore the potential role of profilin-1 in the pathogenesis of AS induced by AGEs,particularly in relation to the Janus kinase 2(JAK2)and signal transducer and activator of transcription 3(STAT3)signaling pathway.METHODS Eighty-nine individuals undergoing coronary angiography were enrolled in the study.Plasma cytokine levels were detected using ELISA kits.Rat aortic vascular smooth muscle cells(RASMCs)were incubated with different compounds for different times.Cell proliferation was determined by performing the MTT assay and EdU staining.An AGEs-induced vascular remodeling model was established in rats and histological and immunohistochemical analyses were performed.The mRNA and protein levels were detected using real-time PCR and Western blot analysis,respectively.In vivo,shRNA transfection was performed to verify the role of profilin-1 in AGEs-induced proatherogenic mediator release and aortic remodeling.Statistical analyses were performed using SPSS 22.0 software.RESULTS Compared with the control group,plasma levels of profilin-1 and receptor for AGEs(RAGE)were significantly increased in patients with coronary artery disease,especially in those complicated with diabetes mellitus(P<0.01).The levels of profilin-1 were positively correlated with the levels of RAGE(P<0.01);additionally,the levels of both molecules were positively associated with the degree of coronary artery stenosis(P<0.01).In vivo,tail vein injections of AGEs induced the release of proatherogenic mediators,such as asymmetric dimethylarginine,intercellular adhesion molecule-1,and the N-terminus of procollagen III peptide,concomitant with apparent aortic morphological changes and significantly upregulated expression of the profilin-1 mRNA and protein in the thoracic aorta(P<0.05 or P<0.01).Downregulation of profilin-1 expression with an shRNA significantly attenuated AGEs-induced proatherogenic mediator release(P<0.05)and aortic remodeling.In vitro,incubation of vascular smooth muscle cells(VSMCs)with AGEs significantly promoted cell proliferation and upregulated the expression of the profilin-1 mRNA and protein(P<0.05).AGEs(200μg/mL,24 h)significantly upregulated the expression of the STAT3 mRNA and protein and JAK2 protein,which was blocked by a JAK2 inhibitor(T3042-1)and/or STAT3 inhibitor(T6308-1)(P<0.05).In addition,pretreatment with T3042-1 or T6308-1 significantly inhibited AGEs-induced RASMC proliferation(P<0.05).CONCLUSION AGEs induce proatherogenic events such as VSMC proliferation,proatherogenic mediator release,and vascular remodeling,changes that can be attenuated by silencing profilin-1 expression.These results suggest a crucial role for profilin-1 in AGEs-induced vasculopathy.
基金supported by the medical science & technology research fund of Health Bureau of Chongqing City, China(No.2004(53)04-2-154)the natural science research fund of Chongqing Science & Technology Commission in Chongqing City, China(No.CSTC,2007BB5276)
文摘Objectives To study the change in plasma hemoglobin concentration in elderly patients with primary hypertension and/or type 2 diabetes complicated with end-stage renal disease （ESRD） determined by estimated glomerular filtration rate. Methods Two hundred and thirty cases of Chinese patients aged 60 years or older with primary hypertension and/or type 2 diabetes complicated with chronic kidney disease were enrolled in the study. Patients with chronic kidney disease were divided into ESRD group with estimated glomemlar filtration rate less than 15 mL . min^-1.1.73 m^-2 （7.80 ± 3. 14 mL. min^-1 . 1.73 m^-2） and non-ESRD group with estimated glomerular filtration rate 15 mL.min^-1 . 1.73 m^-2（29. 76 ± 12. 90 mL.min^-1 . 1.73 m^-2） or higher. The plasma hemoglobin concentration was compared between the above two groups retrospectively. Results There was significant decrease in plasma hemoglobin concentration in ESRD group compared with non-ESRD group （74.4 ± 22. 5 g/L vs 100. 8 ± 23.0 g/L, P 〈 0. 05 ）. After stratification by sex, there was also significant decrease in plasma hemoglobin concentration both in male and female of ESRD groups compared with their respective non-ESRD groups（77. 2±22. 0 g/L vs 104. 9 ±20. 7 g/L; 69. 7 ±22. 8 g/L vs 96.4± 24.8 g/L, P 〈 0. 05, respectively）. Plasma hemoglobin concentration was positively related to estimated glomerular filtration rate significantly in patients with ESRD （ P 〈 0. 05 ）. Conclusions Plasma hemoglobin concentration is decreased significantly, and is positively related to estimated glomerular filtration rate significantly in elderly patients with primary hypertension and/or type 2 diabetes complicated with ESRD determined by estimated glomerular filtration rate.
文摘Background High positive end-expiratory pressure （PEEP） and low tidal volume （VT） ventilation is thought to be a protective ventilation strategy. It is hypothesized that the stabilization of collapsible alveoli during expiration contributes to lung protection. However, this hypothesis came from analysis of indirect indices like the analysis of the pressure-volume curve of the lung. The purpose of this study was to investigate isolated healthy and injured rat lungs by means of alveolar microscopy, in which combination of PEEP and VT is beneficial with respect to alveolar stability （I-E%）. Methods Alveolar stability was investigated in isolated, non-perfused mechanically ventilated rat lungs. Injured lungs were compared with normal lungs. For both groups three PEEP settings （5, 10, 20 cmH20） were combined with three VT settings （6, 10, 15 ml/kg） resulting in nine PEEP-VT combinations per group. Analysis was performed by alveolar microscopy. Results In normal lungs alveolar stability persisted in all PEEP-VT combinations （I-E% （3.2±11.0）%）. There was no significant difference using different settings （P 〉0.01）. In contrast, alveoli in injured lungs were extremely instable at PEEP levels of 5 cmH20 （mean I-E% 100%） and 10 cmH2O （mean I-E% （30.7±16.8）%）; only at a PEEP of 20 cmH20 were alveoli stabilized （mean I-E% of （0.2±9.3）%）. Conclusions In isolated healthy lungs alveolar stability is almost unaffected by different settings of PEEP and VT. In isolated injured lungs only a high PEEP level of 20 cmH2O resulted in stabilized alveoli whereas lower PEEP levels are associated with alveolar instability.
基金The National Natural Science Foundation of China under contract Nos 42266006 and 41806114the Jiangxi Provincial Natural Science Foundation under contract Nos 20232BAB204089 and 20202ACBL214019.
文摘The complexity of river-tide interaction poses a significant challenge in predicting discharge in tidal rivers.Long short-term memory(LSTM)networks excel in processing and predicting crucial events with extended intervals and time delays in time series data.Additionally,the sequence-to-sequence(Seq2Seq)model,known for handling temporal relationships,adapting to variable-length sequences,effectively capturing historical information,and accommodating various influencing factors,emerges as a robust and flexible tool in discharge forecasting.In this study,we introduce the application of LSTM-based Seq2Seq models for the first time in forecasting the discharge of a tidal reach of the Changjiang River(Yangtze River)Estuary.This study focuses on discharge forecasting using three key input characteristics:flow velocity,water level,and discharge,which means the structure of multiple input and single output is adopted.The experiment used the discharge data of the whole year of 2020,of which the first 80%is used as the training set,and the last 20%is used as the test set.This means that the data covers different tidal cycles,which helps to test the forecasting effect of different models in different tidal cycles and different runoff.The experimental results indicate that the proposed models demonstrate advantages in long-term,mid-term,and short-term discharge forecasting.The Seq2Seq models improved by 6%-60%and 5%-20%of the relative standard deviation compared to the harmonic analysis models and improved back propagation neural network models in discharge prediction,respectively.In addition,the relative accuracy of the Seq2Seq model is 1%to 3%higher than that of the LSTM model.Analytical assessment of the prediction errors shows that the Seq2Seq models are insensitive to the forecast lead time and they can capture characteristic values such as maximum flood tide flow and maximum ebb tide flow in the tidal cycle well.This indicates the significance of the Seq2Seq models.
文摘Background Nitric oxide （NO） plays an important role in acute lung injury （ALl）, acute respiratory distress syndrome （ARDS）, and in ventilator-induced lung injury （VILI）. A change in the balance of endothelin-1 （ET-1） and NO in the ALI/ARDS can also add to these problems. However, the profile of ET-1 and the balance of ET-1 and NO are still unknown in a VILI model. Methods Models of oleic acid induced ALl were established in dogs; these models were then randomized into three groups undergone different tidal volume （VT） mechanical ventilation, which included a VT6 group （VT equaled to 6 ml/kg body weight, positive end expiratory pressure （PEEP） equaled to 10 cmH20, n=-6）, a VT10 group （VT equaled to 10 ml/kg body weight, PEEP equaled to 10 cmH20, n=-4） and a VT20 group （VT equaled to 20 ml/kg body weight, PEEP equaled to 10 cmH20, n=-6） for 6-hour ventilation. The levels of ET-1 and NO in serum and tissue homogenates of lung were observed throughout the trial. Results PaO2 was increased after mechanical ventilation, but hypercapnia occurred in the VT6 group. The magnitudes of lung injury in the VT20 group were more severe than those in the VT6 group and the VT10 group. Serum levels of ET-1 and NO increased after ALl models were established and slightly decreased after a 6-hour ventilation in both the VT6 group and the VT20 group. The serum ET-1 level in the VT20 group was higher than that in the VT6 group and the VT10 group after the 6-hour ventilation （P 〈0.05） while the serum NO levels were similar in the three groups （all P 〉0.05）. There was no significant difference in serum ratio of ET-1/NO between any two out of three groups （P 〉0.05）, although there was a significant positive relationship between serum ET-1 and serum NO （r=0.80, P 〈0.01）. The levels of ET-1 and NO in the lung were increased after ventilation. The lung ET-1 level in the VT20 group was significantly higher than that in the VT6 group and VT10 group （both P 〈0.05） while there was no significant difference in lung NO levels between two groups （P〉0.05）. In the lung tissue, the ratio of ET-1/NO was significantly higher in the VT20 group than in the VT6 group and VT10 group after the 6-hour ventilation （P 〈0.05） as there was a significant positive relationship between ET-1 and NO in the lung （r=0.54, P 〈0.05）. Conclusions The production of ET-1 and NO was increased in serum and lung tissue in a VILI model. But the ET-1 levels increased much more than the NO levels in the lung, though there was a significant positive relationship between levels of ET-1 and NO. These results showed that there was an interaction between ET-1 and NO in a VILI model and changing the balance of ET-1 and NO levels might contribute to the pathophysiologic process of VILI.
