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1.
Nature ; 626(8000): 808-818, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38326612

RESUMO

Neuronal signals that are relevant for spatial navigation have been described in many species1-10. However, a circuit-level understanding of how such signals interact to guide navigational behaviour is lacking. Here we characterize a neuronal circuit in the Drosophila central complex that compares internally generated estimates of the heading and goal angles of the fly-both of which are encoded in world-centred (allocentric) coordinates-to generate a body-centred (egocentric) steering signal. Past work has suggested that the activity of EPG neurons represents the fly's moment-to-moment angular orientation, or heading angle, during navigation2,11. An animal's moment-to-moment heading angle, however, is not always aligned with its goal angle-that is, the allocentric direction in which it wishes to progress forward. We describe FC2 cells12, a second set of neurons in the Drosophila brain with activity that correlates with the fly's goal angle. Focal optogenetic activation of FC2 neurons induces flies to orient along experimenter-defined directions as they walk forward. EPG and FC2 neurons connect monosynaptically to a third neuronal class, PFL3 cells12,13. We found that individual PFL3 cells show conjunctive, spike-rate tuning to both the heading angle and the goal angle during goal-directed navigation. Informed by the anatomy and physiology of these three cell classes, we develop a model that explains how this circuit compares allocentric heading and goal angles to build an egocentric steering signal in the PFL3 output terminals. Quantitative analyses and optogenetic manipulations of PFL3 activity support the model. Finally, using a new navigational memory task, we show that flies expressing disruptors of synaptic transmission in subsets of PFL3 cells have a reduced ability to orient along arbitrary goal directions, with an effect size in quantitative accordance with the prediction of our model. The biological circuit described here reveals how two population-level allocentric signals are compared in the brain to produce an egocentric output signal that is appropriate for motor control.


Assuntos
Encéfalo , Drosophila melanogaster , Objetivos , Cabeça , Vias Neurais , Orientação Espacial , Navegação Espacial , Animais , Potenciais de Ação , Encéfalo/citologia , Encéfalo/fisiologia , Drosophila melanogaster/citologia , Drosophila melanogaster/fisiologia , Cabeça/fisiologia , Locomoção , Neurônios/metabolismo , Optogenética , Orientação Espacial/fisiologia , Percepção Espacial/fisiologia , Memória Espacial/fisiologia , Navegação Espacial/fisiologia , Transmissão Sináptica
2.
Curr Biol ; 34(5): 1023-1033.e5, 2024 03 11.
Artigo em Inglês | MEDLINE | ID: mdl-38366594

RESUMO

Flexible and context-dependent behaviors require animals, including humans, to identify their current contextual state for proper rules to apply, especially when information that defines these states is partially observable. Depending on behavioral needs, contextual states usually persist for prolonged periods and across other events, including sensory stimuli, actions, and rewards, highlighting prominent challenges of holding a reliable state representation. The orbitofrontal cortex (OFC) is crucial in behaviors requiring the identification of the current context (e.g., reversal learning); however, how single units in the OFC accomplish this function has not been assessed. Do they maintain such information persistently, in separate populations from those responding phasically to events within a task, or is contextual information dynamic and embedded in these phasic responses? Here, we investigated this question by recording single units from OFC in rats performing a task that required them to identify the current contextual state related to estimated proximity to future reward with distracting olfactory cues. We found that while some OFC neurons encode contextual states, most change their selectivity upon the transition of task events. Nevertheless, despite dynamic activities in single neurons, the neural populations maintain persistent representations regarding current contextual states within particular neural subspaces.


Assuntos
Sinais (Psicologia) , Córtex Pré-Frontal , Humanos , Ratos , Animais , Ratos Long-Evans , Córtex Pré-Frontal/fisiologia , Recompensa , Neurônios/fisiologia
3.
Nanomaterials (Basel) ; 14(3)2024 Jan 27.
Artigo em Inglês | MEDLINE | ID: mdl-38334543

RESUMO

Lithium-sulfur batteries offer the potential for significantly higher energy density and cost-effectiveness. However, their progress has been hindered by challenges such as the "shuttle effect" caused by lithium polysulfides and the volume expansion of sulfur during the lithiation process. These limitations have impeded the widespread adoption of lithium-sulfur batteries in various applications. It is urgent to explore the high-performance sulfur host to improve the electrochemical performance of the sulfur electrode. Herein, bimetallic NiFe hydroxide (NiFe-LDH)-modified carbon nanotubes (CNTs) are prepared as the sulfur host materials (NiFe-CNT@S) for loading of sulfur. On the one hand, the crosslinked CNTs can increase the electron conductivity of the sulfur host as well as disperse NiFe-LDHs nanosheets. On the other hand, NiFe-LDHs command the capability of strongly adsorbing lithium polysulfides and also accelerate their conversion, which effectively suppresses the shuttle effect problem in lithium polysulfides. Hence, the electrochemical properties of NiFe-CNT@S exhibit significant enhancements when compared with those of the sulfur-supported pure NiFe-LDHs (NiFe-LDH@S). The initial capacity of NiFe-CNT@S is reported to be 1010 mAh g-1. This value represents the maximum amount of charge that the material can store per gram when it is first synthesized or used in a battery. After undergoing 500 cycles at a rate of 2 C (1 C = 1675 mA g-1), the NiFe-CNT@S composite demonstrates a sustained capacity of 876 mAh g-1. Capacity retention is a measure of how well a battery or electrode material can maintain its capacity over repeated charge-discharge cycles, and a higher retention percentage indicates better durability and stability of the material.

4.
Front Surg ; 10: 1219835, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37711137

RESUMO

Background: Core decompression and allogenic non-vascularized bone grafting are used in the early stage of osteonecrosis of the femoral head for a period. Since the comparison of the core decompression and allogenic non-vascularized bone grafting are less reported, the purpose of our study was to investigate the difference of two procedures in patients with the osteonecrosis of the femoral head. Methods: Between January 2018 and January 2019, 59 patients (64 hips) were divided into core decompression group and non-vascularized bone grafting group according to their procedures. The primary outcomes are visual analog score (VAS) and Harris hip score. Survivorship was analyzed with the collapse of the femoral head or conversion to total hip arthroplasty (THA) as the endpoint. Results: At the final follow-up, two hips underwent THA in the core decompression group and three hips in the allogenic non-vascularized bone grafting group. The radiographic survival rates were 76.9% and 77.3%, respectively, in both groups. The VAS of the core decompression group was 6.08 ± 1.164 and 3.30 ± 1.431 before and 2 years after operation (P < 0.05), respectively. The VAS of the allogenic non-vascularized bone grafting group was 6.00 ± 1.209 and 3.15 ± 1.537 before and 2 years after operation (P < 0.05), respectively. The Harris hip score of the core decompression group was 52.49 ± 6.496 before operation, and 2 years after operation, it increased by 81.14 ± 8.548 (P < 0.05); The Harris hip score of allogenic the non-vascularized bone grafting group was 53.56 ± 5.925 and 81.33 ± 7.243 before and 2 years after operation (P < 0.05), respectively. In the core decompression group, body mass index (BMI) >25 kg/m2 was correlated with the collapse of femoral head or conversion to THA [P < 0.05; 95% confidence interval (CI), 0.006-1.334], and Association Research Circulation Osseous (ARCO) III was correlated with the collapse of femoral head or conversion to THA (P < 0.05; 95% CI, 2.514-809.650). In the allogenic non-vascularized bone grafting group, age, BMI, and ARCO stage were significantly associated with the collapse of femoral head or conversion to THA (P > 0.05). Conclusion: The clinical survival rate of the femoral head in the core decompression group was slightly better than that in the allogenic non-vascularized bone grafting group. There was no significant difference in the radiographic survival rate of the femoral head between the two groups. Both groups can alleviate pain and improve functional of patients, but there was no significant difference in the degree of improvement. In the core decompression group, BMI >25 kg/m2 and ARCO III correlated with the collapse of femoral head or conversion to THA. In the allogenic non-vascularized bone grafting group, no association was found between age, BMI, and ARCO stage and the collapse of femoral head or conversion to THA. Level of evidence: III.

5.
Signal Transduct Target Ther ; 8(1): 96, 2023 03 06.
Artigo em Inglês | MEDLINE | ID: mdl-36872366

RESUMO

Constitutive activation of RAS-RAF-MEK-ERK signaling pathway (MAPK pathway) frequently occurs in many cancers harboring RAS or RAF oncogenic mutations. Because of the paradoxical activation induced by a single use of BRAF or MEK inhibitors, dual-target RAF and MEK treatment is thought to be a promising strategy. In this work, we evaluated erianin is a novel inhibitor of CRAF and MEK1/2 kinases, thus suppressing constitutive activation of the MAPK signaling pathway induced by BRAF V600E or RAS mutations. KinaseProfiler enzyme profiling, surface plasmon resonance (SPR), isothermal titration calorimetry (ITC), cellular thermal shift assay, computational docking, and molecular dynamics simulations were utilized to screen and identify erianin binding to CRAF and MEK1/2. Kinase assay, luminescent ADP detection assay, and enzyme kinetics assay were investigated to identify the efficiency of erianin in CRAF and MEK1/2 kinase activity. Notably, erianin suppressed BRAF V600E or RAS mutant melanoma and colorectal cancer cell by inhibiting MEK1/2 and CRAF but not BRAF kinase activity. Moreover, erianin attenuated melanoma and colorectal cancer in vivo. Overall, we provide a promising leading compound for BRAF V600E or RAS mutant melanoma and colorectal cancer through dual targeting of CRAF and MEK1/2.


Assuntos
Neoplasias Colorretais , Melanoma , Humanos , Transdução de Sinais , Quinases de Proteína Quinase Ativadas por Mitógeno
7.
World J Clin Cases ; 10(32): 11861-11868, 2022 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-36405297

RESUMO

BACKGROUND: Cardiac arrest after noncardiac surgery is a dangerous complication that may contribute to mortality. Because of the high mortality rate and many complications of cardiac arrest, it is very important to identify and correct a reversible etiology early. By reporting the treatment process of this case, we aimed to broaden the diagnosis and treatment of cardiac arrest after noncardiac surgery and describe how cardiopulmonary resuscitation using extracorporeal membrane oxygenation (ECMO) can improve a patient's chance of survival. CASE SUMMARY: A 69-year-old man visited our hospital complaining of low back pain on July 12, 2021. Magnetic resonance imaging showed lumbar disc herniation. Two hours after lumbar disc herniation surgery, the patient developed cardiac arrest. Cardiopulmonary resuscitation was performed, and ECMO was started 60 min after the initiation of cardiopulmonary resuscitation. Regarding the etiology of early cardiac arrest after surgery, acute myocardial infarction and pulmonary embolism were considered first. Based on ultrasound evaluation, acute myocardial infarction appeared more likely. Coronary angiography confirmed occlusion of the left anterior descending branch, and coronary artery stenting was performed. Pulmonary artery angiography was performed to exclude pulmonary embolism. Due to heparinization during ECMO and coronary angiography, there was a large amount of oozing blood in the surgical incision. Therefore, heparin-free ECMO was performed in the early stage, and routine heparinized ECMO was performed after hemorrhage stabilization. Eventually, the patient was discharged and made a full neurologic recovery. CONCLUSION: For early postoperative cardiac arrest, acute myocardial infarction should be considered first, and heparin should be used with caution.

8.
PeerJ ; 10: e14164, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36225906

RESUMO

Due to high salinity and low nutrient concentrations, the coastal zone is considered as one of the most vulnerable of the earth's habitats. Thus, the effect of salt and nitrogen on growth and development of coastal halophytes has been extensively investigated in recent years, but insufficient attention has been paid to the crucial stages of plant establishment, such as seed germination and seedling growth. Thus, we carried out a field experiment to evaluate the effects of salt stress (6, 10 and 20 g/kg NaCl) and nitrogen supply (0, 6 and 12 gm-2year-1) on seed germination and seedling growth of three coastal halophytes (including two dominant herb species Glehnia littoralis and Calystegia soldanella, one constructive shrub species Vitex rotundifolia) from September 2020 to June 2021. The results of our experiment showed that seeds of G. littoralis exhibited an explosive germination strategy in the early spring of 2021 with 70% of the seeds germinating. Conversely, the seeds of V. rotundifolia exhibited slow germination in the late spring of 2021 with only 60% of the seeds germinating. C. soldanella seed germination exhibited two obvious peak periods, but only 6% of the seeds germinated, which means that most seeds may be stored in the soil by stratification or died. All three halophytes showed greater sensitivity to nitrogen than salt stress during the seed germination stage. Nitrogen supply significantly delayed seed germination and reduced the cumulative germination percentage, particularly for G. littoralis. Despite the large impact of nitrogen on seed germination, nitrogen had a larger impact on seedling growth suggesting that the seedling growth stage of halophytes is more vulnerable to changes in nitrogen supply. Moreover, nitrogen supply significantly reduced the individual biomass of G. littoralis, C. soldanella and V. rotundifolia, with greater decreases seen in the dominant species than in the constructive species. Conversely, nitrogen supply increased underground biomass allocation of G. littoralis and C. soldanella, suggesting that the constructive species were less sensitive to nitrogen and exhibited a stronger anti-interference ability than the dominant species. Therefore, increasing nitrogen supply may firstly affect the seed germination and seedling growth of the dominant species, but not the constructive species.


Assuntos
Germinação , Plântula , Plantas Tolerantes a Sal , Sementes , Estresse Salino
9.
Plants (Basel) ; 10(8)2021 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-34451688

RESUMO

Future climate is projected to increase in the intensity and frequency of extreme precipitation events, and the resulting ecological consequences are often more serious than those of normal precipitation events. In particular, in desert ecosystems, due to the low frequency and strong fluctuation of extreme precipitation, the destructive consequences for desert plants caused by extreme precipitation have not received enough attention for some time. Based on statistics of extreme precipitation events (1965-2018) in the Gurbantunggut Desert, we investigated the effects of extreme precipitation (+0%, CK; +50%, W1; +100%, W2; +200%, W3; maintenance of field capacity, W4) on the plant life-history of the spring-germinated (SG) and autumn-germinated (AG) ephemeral plant Erodium oxyrhynchum by monitoring seedling emergence, survival, phenology, organ size, biomass accumulation, and allocation. The results showed that extreme precipitation caused about 2.5% seedling emergence of E. oxyrhynchum in autumn 2018 and 3.0% seedling emergence in early spring 2019, which means that most seeds may be stored in the soil or have died. Meanwhile, extreme precipitation significantly improved the survival, organ size, and biomass accumulation of SG and AG plants, and W3 was close to the precipitation threshold of SG (326.70 mm) and AG (560.10 mm) plants corresponding to the maximum individual biomass; thus, AG plants with a longer life cycle need more water for growth. Conversely, W4 caused AG plants to enter the leaf stage in advance and led to death in winter, which indicates that extreme precipitation may not be good for AG plants. Root and reproduction biomass allocation of SG and AG plants showed a significantly opposite trend under extreme precipitation treatments, which might be related to their different life-history strategies. Therefore, when only taking into account the changing trend of extreme precipitation from the Coupled Model Intercomparison Project 6 (CMIP6) climate projections data, we speculate that extreme precipitation may promote the growth of SG and AG plants from the beginning to the middle of this century, but extreme precipitation in autumn exceeding a certain threshold may adversely affect the survival of AG plants at the end of the century.

10.
Biology (Basel) ; 10(8)2021 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-34440013

RESUMO

Interannual seasonal variability in precipitation may strongly affect the life history and growth of desert annual plants. We compared the effects of dry and wet springs and dry and wet autumns on growth and F2 seed dormancy of plants from spring (SG)- and autumn (AG)-germinated seeds of the cold desert annual Erodium oxyrhinchum. Vegetative and reproductive growth and F2 seed dormancy and germination were monitored from September 2016 to November 2020 in the sandy Gurbantunggut Desert in NW China in Central Asia. Dry autumns decreased the density of AG plants, and dry springs decreased the density of SG plants and growth of SG and AG plants. In dry springs, SG plants were more sensitive to precipitation than AG plants, while in wet springs SG and AG plants had similar responses to precipitation. During growth in both dry and wet springs, most morphological characters of SG and AG plants initially increased rapidly in size/number and then plateaued or decreased, except for SG plants in dry springs. In dry springs, most morphological characters of AG plants were larger or more numerous than those of SG plants, and they were larger/more numerous for SG plants in wet than in dry springs. The percentage biomass allocated to reproduction in SG plants was slightly higher in a wet than in a dry spring. A much higher proportion of dormant seeds was produced by AG plants in a wet spring than in a dry spring. Projected changes in precipitation due to climate change in NW China are not likely to have much of an effect on the biology of this common desert annual plant.

11.
Sensors (Basel) ; 21(12)2021 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-34204238

RESUMO

Mechanical ventilation is an essential life-support treatment for patients who cannot breathe independently. Patient-ventilator asynchrony (PVA) occurs when ventilatory support does not match the needs of the patient and is associated with a series of adverse clinical outcomes. Deep learning methods have shown a strong discriminative ability for PVA detection, but they require a large number of annotated data for model training, which hampers their application to this task. We developed a transfer learning architecture based on pretrained convolutional neural networks (CNN) and used it for PVA recognition based on small datasets. The one-dimensional signal was converted to a two-dimensional image, and features were extracted by the CNN using pretrained weights for classification. A partial dropping cross-validation technique was developed to evaluate model performance on small datasets. When using large datasets, the performance of the proposed method was similar to that of non-transfer learning methods. However, when the amount of data was reduced to 1%, the accuracy of transfer learning was approximately 90%, whereas the accuracy of the non-transfer learning was less than 80%. The findings suggest that the proposed transfer learning method can obtain satisfactory accuracies for PVA detection when using small datasets. Such a method can promote the application of deep learning to detect more types of PVA under various ventilation modes.


Assuntos
Serviços de Assistência Domiciliar , Redes Neurais de Computação , Humanos , Aprendizado de Máquina , Respiração Artificial , Ventiladores Mecânicos
12.
Comput Methods Programs Biomed ; 204: 106057, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33836375

RESUMO

BACKGROUND AND OBJECTIVE: Patient-ventilator asynchrony (PVA) is the result of a mismatch between the need of patients and the assistance provided by the ventilator during mechanical ventilation. Because the poor interaction between the patient and the ventilator is associated with inferior clinical outcomes, effort should be made to identify and correct their occurrence. Deep learning has shown promising ability in PVA detection; however, lack of network interpretability hampers its application in clinic. METHODS: We proposed an interpretable one-dimensional convolutional neural network (1DCNN) to detect four most manifestation types of PVA (double triggering, ineffective efforts during expiration, premature cycling and delayed cycling) under pressure control ventilation mode and pressure support ventilation mode. A global average pooling (GAP) layer was incorporated with the 1DCNN model to highlight the sections of the respiratory waveform the model focused on when making a classification. Dilation convolution and batch normalization were introduced to the 1DCNN model for compensating the reduction of performance caused by the GAP layer. RESULTS: The proposed interpretable 1DCNN exhibited comparable performance with the state-of-the-art deep learning model in PVA detection. The F1 scores for the detection of four types of PVA under pressure control ventilation and pressure support ventilation modes were greater than 0.96. The critical sections of the waveform used to detect PVA were highlighted, and found to be well consistent with the understanding of the respective type of PVA by experts. CONCLUSIONS: The findings suggest that the proposed 1DCNN can help detect PVA, and enhance the interpretability of the classification process to help clinicians better understand the results obtained from deep learning technology.


Assuntos
Serviços de Assistência Domiciliar , Respiração Artificial , Humanos , Redes Neurais de Computação , Respiração com Pressão Positiva , Ventiladores Mecânicos
13.
J Anesth ; 35(1): 3-9, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-32886200

RESUMO

PURPOSE: Although uniportal video-assisted thoracoscopic surgery (VATS) has been widely used, the associated postoperative pain is still severe. Currently, a variety of regional anesthesia methods have been used to relieve postoperative pain. In our study, we wanted to evaluate the effectiveness of ultrasound-guided erector spinae plane block (ESPB) as a postoperative analgesia after uniportal VATS. METHODS: Eighty patients scheduled to undergo uniportal VATS were randomly divided into Group ESP and Group C. In Group ESP, the patients underwent ultrasound-guided ESPB under general anesthesia before surgery, while Group C was set as blank control group without ESPB. The primary outcome was the sufentanil dose within 24 h after surgery. The secondary outcomes mainly included postoperative pain scores at 2, 4, 8, and 24 h evaluated using a numeric rating scale (NRS), intraoperative opioid dosage, levels of inflammatory cytokines, including tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and interleukin-10 (IL-10) in the plasma, side effect profile, and length of postoperative hospital stay. RESULTS: Postoperative sufentanil consumption (32.5 ± 6.3 µg vs. 42.8 ± 7.6 µg, P < 0.001) was significantly lower in Group ESP than in Group C. Intraoperative sufentanil consumption was significantly lower in Group ESP than in Group C (P < 0.001). The postoperative NRS score and levels of inflammatory cytokines were significantly lower in Group ESP than in Group C (P < 0.05). CONCLUSIONS: Ultrasound-guided ESPB decreased the consumption of sufentanil both postoperatively and intraoperatively for patients undergoing uniportal VATS and appeared to be an effective treatment option.


Assuntos
Analgesia , Anestesia por Condução , Bloqueio Nervoso , Citocinas , Humanos , Plasma , Estudos Prospectivos , Ultrassonografia de Intervenção
14.
PeerJ ; 8: e10497, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33312774

RESUMO

BACKGROUND AND OBJECTIVES: The timing of invasive mechanical ventilation (IMV) is controversial in COVID-19 patients with acute respiratory hypoxemia. The study aimed to develop a novel predictor called cumulative oxygen deficit (COD) for the risk stratification. METHODS: The study was conducted in four designated hospitals for treating COVID-19 patients in Jingmen, Wuhan, from January to March 2020. COD was defined to account for both the magnitude and duration of hypoxemia. A higher value of COD indicated more oxygen deficit. The predictive performance of COD was calculated in multivariable Cox regression models. RESULTS: A number of 111 patients including 80 in the non-IMV group and 31 in the IMV group were included. Patients with IMV had substantially lower PaO2 (62 (49, 89) vs. 90.5 (68, 125.25) mmHg; p < 0.001), and higher COD (-6.87 (-29.36, 52.38) vs. -231.68 (-1040.78, 119.83) mmHg·day) than patients without IMV. As compared to patients with COD < 0, patients with COD > 30 mmHg·day had higher risk of fatality (HR: 3.79, 95% CI [2.57-16.93]; p = 0.037), and those with COD > 50 mmHg·day were 10 times more likely to die (HR: 10.45, 95% CI [1.28-85.37]; p = 0.029). CONCLUSIONS: The study developed a novel predictor COD which considered both magnitude and duration of hypoxemia, to assist risk stratification of COVID-19 patients with acute respiratory distress.

15.
Front Med (Lausanne) ; 7: 597406, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33324663

RESUMO

Background and objectives: Patient-ventilator asynchronies (PVAs) are common in mechanically ventilated patients. However, the epidemiology of PVAs and its impact on clinical outcome remains controversial. The current study aims to evaluate the epidemiology and risk factors of PVAs and their impact on clinical outcomes using big data analytics. Methods: The study was conducted in a tertiary care hospital; all patients with mechanical ventilation from June to December 2019 were included for analysis. Negative binomial regression and distributed lag non-linear models (DLNM) were used to explore risk factors for PVAs. PVAs were included as a time-varying covariate into Cox regression models to investigate its influence on the hazard of mortality and ventilator-associated events (VAEs). Results: A total of 146 patients involving 50,124 h and 51,451,138 respiratory cycles were analyzed. The overall mortality rate was 15.6%. Double triggering was less likely to occur during day hours (RR: 0.88; 95% CI: 0.85-0.90; p < 0.001) and occurred most frequently in pressure control ventilation (PCV) mode (median: 3; IQR: 1-9 per hour). Ineffective effort was more likely to occur during day time (RR: 1.09; 95% CI: 1.05-1.13; p < 0.001), and occurred most frequently in PSV mode (median: 8; IQR: 2-29 per hour). The effect of sedatives and analgesics showed temporal patterns in DLNM. PVAs were not associated mortality and VAE in Cox regression models with time-varying covariates. Conclusions: Our study showed that counts of PVAs were significantly influenced by time of the day, ventilation mode, ventilation settings (e.g., tidal volume and plateau pressure), and sedatives and analgesics. However, PVAs were not associated with the hazard of VAE or mortality after adjusting for protective ventilation strategies such as tidal volume, plateau pressure, and positive end expiratory pressure (PEEP).

16.
Front Med (Lausanne) ; 7: 541, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32974375

RESUMO

Background: Lung mechanics during invasive mechanical ventilation (IMV) for both prognostic and therapeutic implications; however, the full trajectory lung mechanics has never been described for novel coronavirus disease 2019 (COVID-19) patients requiring IMV. The study aimed to describe the full trajectory of lung mechanics of mechanically ventilated COVID-19 patients. The clinical and ventilator setting that can influence patient-ventilator asynchrony (PVA) and compliance were explored. Post-extubation spirometry test was performed to assess the pulmonary function after COVID-19 induced ARDS. Methods: This was a retrospective study conducted in a tertiary care hospital. All patients with IMV due to COVID-19 induced ARDS were included. High-granularity ventilator waveforms were analyzed with deep learning algorithm to obtain PVAs. Asynchrony index (AI) was calculated as the number of asynchronous events divided by the number of ventilator cycles and wasted efforts. Mortality was recorded as the vital status on hospital discharge. Results: A total of 3,923,450 respiratory cycles in 2,778 h were analyzed (average: 24 cycles/min) for seven patients. Higher plateau pressure (Coefficient: -0.90; 95% CI: -1.02 to -0.78) and neuromuscular blockades (Coefficient: -6.54; 95% CI: -9.92 to -3.16) were associated with lower AI. Survivors showed increasing compliance over time, whereas non-survivors showed persistently low compliance. Recruitment maneuver was not able to improve lung compliance. Patients were on supine position in 1,422 h (51%), followed by prone positioning (499 h, 18%), left positioning (453 h, 16%), and right positioning (404 h, 15%). As compared with supine positioning, prone positioning was associated with 2.31 ml/cmH2O (95% CI: 1.75 to 2.86; p < 0.001) increase in lung compliance. Spirometry tests showed that pulmonary functions were reduced to one third of the predicted values after extubation. Conclusions: The study for the first time described full trajectory of lung mechanics of patients with COVID-19. The result showed that prone positioning was associated with improved compliance; higher plateau pressure and use of neuromuscular blockades were associated with lower risk of AI.

17.
Comput Biol Med ; 120: 103721, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32250853

RESUMO

BACKGROUND AND OBJECTIVE: Mismatch between invasive mechanical ventilation and the requirements of patients results in patient-ventilator asynchrony (PVA), which is associated with a series of adverse clinical outcomes. Although the efficiency of the available approaches for automatically detecting various types of PVA from the ventilator waveforms is unsatisfactory, the feasibility of powerful deep learning approaches in addressing this problem has not been investigated. METHODS: We propose a 2-layer long short-term memory (LSTM) network to detect two most frequently encountered types of PVA, namely, double triggering (DT) and ineffective inspiratory effort during expiration (IEE), on two datasets. The performance of the networks is evaluated first using cross-validation on the combined dataset, and then using a cross testing scheme, in which the LSTM networks are established on one dataset and tested on the other. RESULTS: Compared with the reported rule-based algorithms and the machine learning models, the proposed 2-layer LSTM network exhibits the best overall performance, with the F1 scores of 0.983 and 0.979 for DT and IEE detection, respectively, on the combined dataset. Furthermore, it outperforms the other approaches in cross testing. CONCLUSIONS: The findings suggest that LSTM is an excellent technique for accurate recognition of PVA in clinics. Such a technique can help detect and correct PVA for a better patient ventilator interaction.


Assuntos
Memória de Curto Prazo , Respiração Artificial , Humanos , Aprendizado de Máquina , Redes Neurais de Computação , Ventiladores Mecânicos
18.
Ying Yong Sheng Tai Xue Bao ; 31(1): 9-16, 2020 Jan.
Artigo em Chinês | MEDLINE | ID: mdl-31957375

RESUMO

Ephemeral plants are a major component of biodiversity in the deserts of Northwest China, with important ecological functions. Information on plant morphological characteristics and biomass accumulation and allocation during different growth stages could enhance our understanding of the functional features and survival strategy of ephemeral plants. We examined the effects of increased precipitation on ephemeral species Eremopyrum distans and Nepeta micrantha in the Gurbantunggut Desert. Changes in morphological characteristics and biomass accumulation and allocation were analyzed under increasing precipitation 30% and 50% treatments. The results showed that increased precipitation 30% and 50% treatments promoted the growth of E. distans, with leaf area and reproductive organ biomass being increased by 14.2%-188.5% and 55.9%, respectively. The effects of increased precipitation on the growth of N. micrantha varied across different growth stages. At leaf expansion stage, increased precipitation promoted growth of N. micrantha, while at fruit ripening stage, increased precipitation 50% treatment reduced leaf area, plant height, and reproduction biomass by 54.9%, 20.5%, 43.2%, respectively. Thus, the responses of the two species to increased precipitation was species-specific. Increased precipitation would change the survival strategies of the two species, with consequence on the species composition and structure of desert community.


Assuntos
Clima Desértico , Plantas , Biodiversidade , Biomassa , China
19.
Acta Pharmacol Sin ; 41(4): 535-545, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31776448

RESUMO

Our previous study shows that nicotinamide adenine dinucleotide phosphate (NADPH) plays an important role in protecting against cerebral ischemia injury. In this study we investigated whether NADPH exerted cardioprotection against myocardial ischemia/reperfusion (I/R) injury. To induce myocardial I/R injury, rats were subjected to ligation of the left anterior descending branch of coronary artery for 30 min followed by reperfusion for 2 h. At the onset of reperfusion, NADPH (4, 8, 16 mg· kg-1· d-1, iv) was administered to the rats. We found that NADPH concentrations in plasma and heart were significantly increased at 4 h after intravenous administration. Exogenous NADPH (8-16 mg/kg) significantly decreased myocardial infarct size and reduced serum levels of lactate dehydrogenase (LDH) and cardiac troponin I (cTn-I). Exogenous NADPH significantly decreased the apoptotic rate of cardiomyocytes, and reduced the cleavage of PARP and caspase-3. In addition, exogenous NADPH reduced mitochondrial vacuolation and increased mitochondrial membrane protein COXIV and TOM20, decreased BNIP3L and increased Bcl-2 to protect mitochondrial function. We conducted in vitro experiments in neonatal rat cardiomyocytes (NRCM) subjected to oxygen-glucose deprivation/restoration (OGD/R). Pretreatment with NADPH (60, 500 nM) significantly rescued the cell viability and inhibited OGD/R-induced apoptosis. Pretreatment with NADPH significantly increased the phosphorylation of AMPK and downregulated the phosphorylation of mTOR in OGD/R-treated NRCM. Compound C, an AMPK inhibitor, abolished NADPH-induced AMPK phosphorylation and cardioprotection in OGD/R-treated NRCM. In conclusion, exogenous NADPH exerts cardioprotection against myocardial I/R injury through the activation of AMPK/mTOR pathway and inhibiting mitochondrial damage and cardiomyocyte apoptosis. NADPH may be a potential candidate for the prevention and treatment of myocardial ischemic diseases.


Assuntos
Proteínas Quinases Ativadas por AMP/metabolismo , Traumatismo por Reperfusão Miocárdica/tratamento farmacológico , NADP/farmacologia , Substâncias Protetoras/farmacologia , Serina-Treonina Quinases TOR/antagonistas & inibidores , Animais , Apoptose/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Modelos Animais de Doenças , Glucose/deficiência , Glucose/metabolismo , Injeções Intravenosas , Masculino , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Traumatismo por Reperfusão Miocárdica/metabolismo , NADP/administração & dosagem , NADP/sangue , Oxigênio/metabolismo , Fosforilação/efeitos dos fármacos , Substâncias Protetoras/administração & dosagem , Ratos , Ratos Sprague-Dawley , Serina-Treonina Quinases TOR/metabolismo
20.
J Neurochem ; 153(3): 413-425, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-31603990

RESUMO

Cystatin C, a well-established biomarker of renal function, has been associated with a protective effect against stroke. However, the potential neuroprotective mechanism of cystatin C in ischemic brain injury remains unclear. Our study hypothesized that cystatin C can ameliorate blood-brain barrier (BBB) disruption by up-regulating caveolin-1 expression, thereby improving neurological outcomes in cerebral ischemic injury. Western blotting, immunohistochemistry, immunofluorescence staining, and immunoprecipitation were performed to investigate target proteins. Evans Blue and gelatin zymography were used to examine the effect of cystatin C on BBB disruption. Plasmid and small interfering RNA transfection was used to observe alterations in caveolin-1 and occludin expression induced by changes in cystatin C expression. Intriguingly, our study showed that the expression of both cystatin C and caveolin-1 was increased in middle cerebral artery occlusion-injured mice, and pretreatment with exogenous cystatin C significantly increased caveolin-1 expression, reduced Evans Blue leakage in the injured brain region, and decreased the enzymatic activity of matrix metallopeptidase-9. Meanwhile, our study also showed that the over-expression of cystatin C greatly enhanced caveolin-1 expression, which later increased occludin expression in oxygen-glucose deprivation-exposed brain microvascular endothelial cells. The knockdown of cystatin C induced the opposite outcomes. These experimental results indicate a positive role for cystatin C in the regulation of caveolin-1 and occludin expression in cerebral ischemic injury. Taken together, these data unveil a new mechanism of the regulation of caveolin-1 expression by cystatin C in the maintenance of BBB integrity after ischemic brain injury and provide new clues for the identification of potential therapeutic strategies for stroke.


Assuntos
Barreira Hematoencefálica/metabolismo , Lesões Encefálicas/metabolismo , Isquemia Encefálica/metabolismo , Cistatina C/administração & dosagem , Cistatina C/biossíntese , Animais , Barreira Hematoencefálica/efeitos dos fármacos , Barreira Hematoencefálica/patologia , Lesões Encefálicas/tratamento farmacológico , Lesões Encefálicas/patologia , Isquemia Encefálica/tratamento farmacológico , Isquemia Encefálica/patologia , Infusões Intraventriculares , Masculino , Camundongos , Camundongos Endogâmicos ICR
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