BACKGROUND： Moderate hypothermia is one of the effective therapeutic methods for head injury in recent years, there are many mechanisms of moderate hypothermia for brain protection, and its influence on cerebral oxyg...BACKGROUND： Moderate hypothermia is one of the effective therapeutic methods for head injury in recent years, there are many mechanisms of moderate hypothermia for brain protection, and its influence on cerebral oxygenation is also one of them. OBJECTIVE： To observe the influence of moderate hypothermia on cerebral oxygenation of animals with acute intracranial hypertension, and further investigate the protective mechanism of moderate hypothermia. DESIGN： A randomized controlled trial. SETTING： Department of Neurosurgery, Renji Hospital affiliated to the Medical College of Shanghai Jiao Tong University. MATERIALS： Twenty healthy little pigs, either male or female, weighing 4.5-5.5 kg, were used. Neurotrend-typed multiparameter monitoring system （Diametrics Company, British）; CMA/100 micro-injection pump （Carnegie Company, Sweden）. METHODS： The experiment was conducted in the Changzheng Hospital affiliated to the Second Military Medical University of Chinese PLA in November, 2001. The pigs were randomized into two groups： the normothermia group （control group, n =10） and moderate hypothermia group （n =10）. ① Bilateral femoral arteries were separated, one was connected to pressometer for monitoring mean arterial pressure （MEP）, and the other for analysis of blood gases [including peripheral blood pH value, arterial partial pressure of carbon dioxide （PaCO2）, arterial partial pressure of carbon dioxide （PaCO2）, HCO3-]. ② Rectal temperature was monitored with mercurial thermometer. ③ Intracranial pressure was monitored using Camino optic ICP probe placed in the subdural space. ④ Neurotrend multiparameter monitoring sensor was inserted into the white matter for about 4 cm to determine cerebral perfusion pressure （CPP, CPP=MAP（ICP）, brain tissue partial oxygen pressure （PO2）, partial pressure of carbon dioxide （PCO2）, HCO3- and brain temperature. The rectal temperature of animals in the moderate hypothermia group was lowered to 34 ℃ using ice bags, and the body temperature was maintained at 33-35 ℃ for 2 hours. The changes of the parameters were observed continuously, and the pigs in the normothermia group were not treated with cooling. MAIN OUTCOME MEASURES： ① MAP, ICP, rectal temperature, CCP; Indexes of cerebral oxygenation detected with Neurotrend-typed multiparameter monitoring system; ② Results of blood gases analysis in the moderate hypothermia group. RESULTS： All the 20 pigs were involved in the analysis of results. ① MAP, ICP, rectal temperature, CCP and indexes of cerebral oxygenation： In the moderate hypothermia group, the ICP after cooling was obviously lower than that before cooling [（3.31±1.19）, （5.33±0.95） kPa, P 〈 0.05], CCP was higher, brain tissue PCO2 [（12.03±1.73）, （10.59±2.01） kPa, P 〈 0.05], and brain tissue pH value was higher [（7.03± 1.63）, （9.40±1.30） kPa, P 〈 0.05], whereas the brain temperature was decreased as compared with that before cooling [（34.9±0.3）, （37.2±0.2） ℃, P 〈 0.05]. ② Results of blood gases analysis in the moderate hypothermia group： There were no significant differences in the parameters of peripheral arterial blood gases analysis before and after cooling in the moderate hypothermia group （P 〉 0.05） CONCLUSION： Moderate hypothermia will not impair the cerebral oxygenation, and it can reduce brain tissue CO2 and decrease brain tissue acidosis.展开更多
Sepsis-induced lung injury caused by multidrug-resistant Pseudomonas aeruginosa(MDR-PA)remains without effective therapeutic strategies.In this study,we developed a black phosphorus nanomaterial-based delivery system ...Sepsis-induced lung injury caused by multidrug-resistant Pseudomonas aeruginosa(MDR-PA)remains without effective therapeutic strategies.In this study,we developed a black phosphorus nanomaterial-based delivery system modified with the S2P peptide(BPNSs@S2P/CD5L)and elucidated its mechanism in ameliorating MDR-PA sepsis via the cluster of differentiation 36(CD36)/phosphoinositide 3-kinase(PI3K)axis-mediated activation of microtubuleassociated protein light chain 3(LC3)-associated autophagy.Single-cell sequencing and transcriptomic analyses suggested that CD5 Antigen-Like(CD5L)may activate the PI3K axis by binding to CD36,thereby inducing autophagy.Functional assays confirmed that CD5L enhanced autophagic flux in macrophages through activation of the CD36/PI3K axis,which in turn alleviated inflammatory injury and promoted the phagocytosis and clearance of MDR-PA.A BPNSs@S2P/CD5L delivery system was successfully constructed,demonstrating good stability and biocompatibility with efficient targeting to lung tissue.Further investigations revealed that this system significantly attenuated oxidative stress and inflammatory responses in alveolar macrophages in vitro,while in vivo it markedly enhanced autophagic activity,bacterial clearance,and tissue repair,ultimately improving lung function and survival in MDR-PA septic mice.BPNSs@S2P/CD5L activates LC3-associated autophagy in macrophages via the CD36/PI3K axis,thereby enhancing their bacterial phagocytic capacity,reducing inflammatory responses and oxidative stress,and effectively alleviating lung injury induced by MDR-PA sepsis.These findings propose a novel nanomaterial-based immunomodulatory strategy for the treatment of drug-resistant bacterial sepsis,highlighting its potential for clinical translation.展开更多
During the pre-design stage of buildings,reliable long-term prediction of thermal loads is significant for cool-ing/heating system configuration and efficient operation.This paper proposes a surrogate modeling method ...During the pre-design stage of buildings,reliable long-term prediction of thermal loads is significant for cool-ing/heating system configuration and efficient operation.This paper proposes a surrogate modeling method to predict all-year hourly cooling/heating loads in high resolution for retail,hotel,and office buildings.16384 surrogate models are simulated in EnergyPlus to generate the load database,which contains 7 crucial building features as inputs and hourly loads as outputs.K-nearest-neighbors(KNN)is chosen as the data-driven algorithm to approximate the surrogates for load prediction.With test samples from the database,performances of five different spatial metrics for KNN are evaluated and optimized.Results show that the Manhattan distance is the optimal metric with the highest efficient hour rates of 93.57%and 97.14%for cooling and heating loads in office buildings.The method is verified by predicting the thermal loads of a given district in Shanghai,China.The mean absolute percentage errors(MAPE)are 5.26%and 6.88%for cooling/heating loads,respectively,and 5.63%for the annual thermal loads.The proposed surrogate modeling method meets the precision requirement of engineering in the building pre-design stage and achieves the fast prediction of all-year hourly thermal loads at the district level.As a data-driven approximation,it does not require as much detailed building information as the commonly used physics-based methods.And by pre-simulation of sufficient prototypical models,the method overcomes the gaps of data missing in current data-driven methods.展开更多
文摘BACKGROUND： Moderate hypothermia is one of the effective therapeutic methods for head injury in recent years, there are many mechanisms of moderate hypothermia for brain protection, and its influence on cerebral oxygenation is also one of them. OBJECTIVE： To observe the influence of moderate hypothermia on cerebral oxygenation of animals with acute intracranial hypertension, and further investigate the protective mechanism of moderate hypothermia. DESIGN： A randomized controlled trial. SETTING： Department of Neurosurgery, Renji Hospital affiliated to the Medical College of Shanghai Jiao Tong University. MATERIALS： Twenty healthy little pigs, either male or female, weighing 4.5-5.5 kg, were used. Neurotrend-typed multiparameter monitoring system （Diametrics Company, British）; CMA/100 micro-injection pump （Carnegie Company, Sweden）. METHODS： The experiment was conducted in the Changzheng Hospital affiliated to the Second Military Medical University of Chinese PLA in November, 2001. The pigs were randomized into two groups： the normothermia group （control group, n =10） and moderate hypothermia group （n =10）. ① Bilateral femoral arteries were separated, one was connected to pressometer for monitoring mean arterial pressure （MEP）, and the other for analysis of blood gases [including peripheral blood pH value, arterial partial pressure of carbon dioxide （PaCO2）, arterial partial pressure of carbon dioxide （PaCO2）, HCO3-]. ② Rectal temperature was monitored with mercurial thermometer. ③ Intracranial pressure was monitored using Camino optic ICP probe placed in the subdural space. ④ Neurotrend multiparameter monitoring sensor was inserted into the white matter for about 4 cm to determine cerebral perfusion pressure （CPP, CPP=MAP（ICP）, brain tissue partial oxygen pressure （PO2）, partial pressure of carbon dioxide （PCO2）, HCO3- and brain temperature. The rectal temperature of animals in the moderate hypothermia group was lowered to 34 ℃ using ice bags, and the body temperature was maintained at 33-35 ℃ for 2 hours. The changes of the parameters were observed continuously, and the pigs in the normothermia group were not treated with cooling. MAIN OUTCOME MEASURES： ① MAP, ICP, rectal temperature, CCP; Indexes of cerebral oxygenation detected with Neurotrend-typed multiparameter monitoring system; ② Results of blood gases analysis in the moderate hypothermia group. RESULTS： All the 20 pigs were involved in the analysis of results. ① MAP, ICP, rectal temperature, CCP and indexes of cerebral oxygenation： In the moderate hypothermia group, the ICP after cooling was obviously lower than that before cooling [（3.31±1.19）, （5.33±0.95） kPa, P 〈 0.05], CCP was higher, brain tissue PCO2 [（12.03±1.73）, （10.59±2.01） kPa, P 〈 0.05], and brain tissue pH value was higher [（7.03± 1.63）, （9.40±1.30） kPa, P 〈 0.05], whereas the brain temperature was decreased as compared with that before cooling [（34.9±0.3）, （37.2±0.2） ℃, P 〈 0.05]. ② Results of blood gases analysis in the moderate hypothermia group： There were no significant differences in the parameters of peripheral arterial blood gases analysis before and after cooling in the moderate hypothermia group （P 〉 0.05） CONCLUSION： Moderate hypothermia will not impair the cerebral oxygenation, and it can reduce brain tissue CO2 and decrease brain tissue acidosis.
基金supported by 2024 Guangdong Provincial Basic and Applied Basic Research Fund Natural Science Foundation Project-General projec(No.2024A1515010633)2025 Annual Guangzhou City University-Institute-Enterprise Jointly Funded Project(Basic and Applied Basic Research Project)(Nos.2025A03J3603 and 2025A03J3366).
文摘Sepsis-induced lung injury caused by multidrug-resistant Pseudomonas aeruginosa(MDR-PA)remains without effective therapeutic strategies.In this study,we developed a black phosphorus nanomaterial-based delivery system modified with the S2P peptide(BPNSs@S2P/CD5L)and elucidated its mechanism in ameliorating MDR-PA sepsis via the cluster of differentiation 36(CD36)/phosphoinositide 3-kinase(PI3K)axis-mediated activation of microtubuleassociated protein light chain 3(LC3)-associated autophagy.Single-cell sequencing and transcriptomic analyses suggested that CD5 Antigen-Like(CD5L)may activate the PI3K axis by binding to CD36,thereby inducing autophagy.Functional assays confirmed that CD5L enhanced autophagic flux in macrophages through activation of the CD36/PI3K axis,which in turn alleviated inflammatory injury and promoted the phagocytosis and clearance of MDR-PA.A BPNSs@S2P/CD5L delivery system was successfully constructed,demonstrating good stability and biocompatibility with efficient targeting to lung tissue.Further investigations revealed that this system significantly attenuated oxidative stress and inflammatory responses in alveolar macrophages in vitro,while in vivo it markedly enhanced autophagic activity,bacterial clearance,and tissue repair,ultimately improving lung function and survival in MDR-PA septic mice.BPNSs@S2P/CD5L activates LC3-associated autophagy in macrophages via the CD36/PI3K axis,thereby enhancing their bacterial phagocytic capacity,reducing inflammatory responses and oxidative stress,and effectively alleviating lung injury induced by MDR-PA sepsis.These findings propose a novel nanomaterial-based immunomodulatory strategy for the treatment of drug-resistant bacterial sepsis,highlighting its potential for clinical translation.
基金This work was supported by the National Natural Science Foundation of China(Grant No.51978481).
文摘During the pre-design stage of buildings,reliable long-term prediction of thermal loads is significant for cool-ing/heating system configuration and efficient operation.This paper proposes a surrogate modeling method to predict all-year hourly cooling/heating loads in high resolution for retail,hotel,and office buildings.16384 surrogate models are simulated in EnergyPlus to generate the load database,which contains 7 crucial building features as inputs and hourly loads as outputs.K-nearest-neighbors(KNN)is chosen as the data-driven algorithm to approximate the surrogates for load prediction.With test samples from the database,performances of five different spatial metrics for KNN are evaluated and optimized.Results show that the Manhattan distance is the optimal metric with the highest efficient hour rates of 93.57%and 97.14%for cooling and heating loads in office buildings.The method is verified by predicting the thermal loads of a given district in Shanghai,China.The mean absolute percentage errors(MAPE)are 5.26%and 6.88%for cooling/heating loads,respectively,and 5.63%for the annual thermal loads.The proposed surrogate modeling method meets the precision requirement of engineering in the building pre-design stage and achieves the fast prediction of all-year hourly thermal loads at the district level.As a data-driven approximation,it does not require as much detailed building information as the commonly used physics-based methods.And by pre-simulation of sufficient prototypical models,the method overcomes the gaps of data missing in current data-driven methods.
