This study is designed to develop Artificial Intelligence(AI)based analysis tool that could accurately detect COVID-19 lung infections based on portable chest x-rays(CXRs).The frontline physicians and radiologists suf...This study is designed to develop Artificial Intelligence(AI)based analysis tool that could accurately detect COVID-19 lung infections based on portable chest x-rays(CXRs).The frontline physicians and radiologists suffer from grand challenges for COVID-19 pandemic due to the suboptimal image quality and the large volume of CXRs.In this study,AI-based analysis tools were developed that can precisely classify COVID-19 lung infection.Publicly available datasets of COVID-19(N=1525),non-COVID-19 normal(N=1525),viral pneumonia(N=1342)and bacterial pneumonia(N=2521)from the Italian Society of Medical and Interventional Radiology(SIRM),Radiopaedia,The Cancer Imaging Archive(TCIA)and Kaggle repositories were taken.A multi-approach utilizing deep learning ResNet101 with and without hyperparameters optimization was employed.Additionally,the fea-tures extracted from the average pooling layer of ResNet101 were used as input to machine learning(ML)algorithms,which twice trained the learning algorithms.The ResNet101 with optimized parameters yielded improved performance to default parameters.The extracted features from ResNet101 are fed to the k-nearest neighbor(KNN)and support vector machine(SVM)yielded the highest 3-class classification performance of 99.86%and 99.46%,respectively.The results indicate that the proposed approach can be bet-ter utilized for improving the accuracy and diagnostic efficiency of CXRs.The proposed deep learning model has the potential to improve further the efficiency of the healthcare systems for proper diagnosis and prognosis of COVID-19 lung infection.展开更多
Understanding the pathogenesis of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)and clarifying antiviral immunity in hosts are critical aspects for the development of vaccines and antivirals.Mice are freq...Understanding the pathogenesis of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)and clarifying antiviral immunity in hosts are critical aspects for the development of vaccines and antivirals.Mice are frequently used to generate animal models of infectious diseases due to their convenience and ability to undergo genetic manipulation.However,normal adult mice are not susceptible to SARS-CoV-2.Here,we developed a viral receptor(human angiotensin-converting enzyme 2,hACE2)pulmonary transfection mouse model to establish SARS-CoV-2 infection rapidly in the mouse lung.Based on the model,the virus successfully infected the mouse lung 2 days after transfection.Viral RNA/protein,innate immune cell infiltration,inflammatory cytokine expression,and pathological changes in the infected lungs were observed after infection.Further studies indicated that neutrophils were the first and most abundant leukocytes to infiltrate the infected lungs after viral infection.In addition,using infected CXCL5-knockout mice,chemokine CXCL5 was responsible for neutrophil recruitment.CXCL5 knockout decreased lung inflammation without diminishing viral clearance,suggesting a potential target for controlling pneumonia.展开更多
BACKGROUND Vancomycin and teicoplanin are both antibiotics that have significant antimicrobial effects on Gram-positive cocci.AIM To explore the value of teicoplanin combined with conventional(vancomycin only)anti-inf...BACKGROUND Vancomycin and teicoplanin are both antibiotics that have significant antimicrobial effects on Gram-positive cocci.AIM To explore the value of teicoplanin combined with conventional(vancomycin only)anti-infective therapy for the treatment of methicillin-resistant Staphylococcus aureus and Staphylococcus epidermidis pulmonary infections.METHODS A total of 86 patients with methicillin-resistant Staphylococcus aureus or methicillin-resistant Staphylococcus epidermidis pulmonary infections,treated in our hospital between January 2018 and February 2020,were assigned to the study and control groups using a random number table method,with 43 patients in each group.The control group received conventional treatment(vancomycin),and the study group received both teicoplanin and conventional treatment.The following indicators were assessed in both groups:the time required for symptom relief,treatment effectiveness,serum levels of inflammatory factors(procalcitonin,interleukin-1β,tumor necrosis factor-α,C-reactive protein),clinical pulmonary infection scores before and after treatment,and the incidence of adverse reactions.RESULTS Patients in the study group were observed to have faster cough and expectoration resolution,white blood cell count normalization,body temperature normalization,and rales disappearance than patients in the control group(all P<0.05);the total rate of effectiveness was 93.02%in the study group,higher than the 76.74%in the control group(P<0.05).The pre-treatment serum levels of procalcitonin,interleukin-1β,tumor necrosis factor-α,and C-reactive protein as well as the clinical pulmonary infection scores were similar among the patients in both groups.However,the post-treatment serum levels of procalcitonin,interleukin-1β,tumor necrosis factor-α,and C-reactive protein as well as the clinical pulmonary infection scores were significantly lower in the study group than in the control group(P<0.05).There was no significant difference in the incidence of adverse reactions between the groups.CONCLUSION Compared with conventional(vancomycin only)therapy,teicoplanin and vancomycin combination therapy for patients with pulmonary methicillinresistant Staphylococcus aureus and methicillin-resistant Staphylococcus epidermidis infections can improve patient clinical symptoms,modulate serum inflammatory factor levels,and improve treatment efficacy,without increasing the risk of adverse reactions.展开更多
BACKGROUND Primary anaplastic large cell lymphoma of the lung represents a diagnostic challenge due to diverse manifestations and non-specific radiological findings,particularly in cases that lack extra-pulmonary mani...BACKGROUND Primary anaplastic large cell lymphoma of the lung represents a diagnostic challenge due to diverse manifestations and non-specific radiological findings,particularly in cases that lack extra-pulmonary manifestations and lung biopsy.CASE SUMMARY A 40-year-old woman presented with a 6-d history of fever,dry coughing,and dyspnea.Her white blood cell count was 20100/mm3 with 90%neutrophils.PaO2 was 60 mmHg and SaO2 was 90%when breathing ambient air.Chest computed tomography(CT)identified a solid nodule,15 mm in diameter,with a poorly defined boundary in the upper right lung,and several smaller solid nodules throughout both lungs.Pulmonary artery CT and subsequent bedside X-ray showed diffuse patchy shadows throughout both lungs.Repeated cultures of blood samples and alveolar lavage failed to identify any pathogen.Due to the mismatch between clinical and imaging features,we conducted a bone marrow biopsy,and the results showed proliferation along all three lineages but no atypical or malignant cells.The patient received empirical antibacterial,antiviral,and antifungal treatments,as well as corticosteroids.The patient’s condition deteriorated rapidly despite treatment.The patient died 6 d after hospitalization due to respiratory failure.Post-mortem lung biopsy failed to show inflammation but identified widespread infiltration of alveolar septum by anaplastic lymphoma kinase(ALK)-positive anaplastic cells.CONCLUSION ALK-positive anaplastic large cell lymphoma could present as a primary pulmonary disease without extra-pulmonary manifestations.展开更多
Computerized tomography(CT)scans and X-rays play an important role in the diagnosis of COVID-19 and pneumonia.On the basis of the image analysis results of chest CT and X-rays,the severity of lung infection is monitor...Computerized tomography(CT)scans and X-rays play an important role in the diagnosis of COVID-19 and pneumonia.On the basis of the image analysis results of chest CT and X-rays,the severity of lung infection is monitored using a tool.Many researchers have done in diagnosis of lung infection in an accurate and efficient takes lot of time and inefficient.To overcome these issues,our proposed study implements four cascaded stages.First,for pre-processing,a mean filter is used.Second,texture feature extraction uses principal component analysis(PCA).Third,a modified whale optimization algorithm is used(MWOA)for a feature selection algorithm.The severity of lung infection is detected on the basis of age group.Fourth,image classification is done by using the proposed MWOAwith the salp swarm algorithm(MWOA-SSA).MWOA-SSA has an accuracy of 97%,whereas PCA and MWOA have accuracies of 81%and 86%.The sensitivity rate of the MWOA-SSA algorithm is better that of than PCA(84.4%)and MWOA(95.2%).MWOA-SSA outperforms other algorithms with a specificity of 97.8%.This proposed method improves the effective classification of lung affected images from large datasets.展开更多
BACKGROUND Listeria is a food-borne disease,which is rarely prevalent in the normal population;it mostly occurs in pregnant women,newborns,immunodeficiency patients,and the elderly.The main manifestations of this dise...BACKGROUND Listeria is a food-borne disease,which is rarely prevalent in the normal population;it mostly occurs in pregnant women,newborns,immunodeficiency patients,and the elderly.The main manifestations of this disease in patients include sepsis,meningitis,etc,and the mortality rate remains high,although the onset of meningitis is relatively insidious.CASE SUMMARY A 75-year-old man presented with a fever for 1 wk and was admitted to the hospital for diagnosis and management of a lung infection.His condition improved after receiving anti-infective treatment for 2 wk.However,soon after he was discharged from the hospital,he developed fever again,and gradually developed various neurological symptoms,impaired consciousness,and stiff neck.Thereafter,through the cerebrospinal fluid metagenomic testing and blood culture,the patient was diagnosed with Listeria monocytogenes meningitis and sepsis.The patient died after being given active treatment,which included penicillin application and invasive respiratory support.CONCLUSION This case highlights the ultimate importance of early identification and timely application of the various sensitive antibiotics,such as penicillin,vancomycin,meropenem,etc.Therefore,for high-risk populations with unknown causes of fever,multiple blood cultures,timely cerebrospinal fluid examination,and metagenomic detection technology can assist in confirming the diagnosis quickly,thereby guiding the proper application of antibiotics and improving the prognosis.展开更多
Respiratory antibiotics have been proven clinically beneficial for the treatment of severe lung infections such as Pseudomonas aeruginosa.Maintaining a high local concentration of inhaled antibiotics for an extended t...Respiratory antibiotics have been proven clinically beneficial for the treatment of severe lung infections such as Pseudomonas aeruginosa.Maintaining a high local concentration of inhaled antibiotics for an extended time in the lung is crucial to ensure an adequate antimicrobial efficiency.In this study,we aim to investigate whether an extended exposure of ciprofloxacin(CIP),a model fluoroquinolone drug,in the lung epithelial lining fluid(ELF)could be achieved via a controlled-release formulation strategy.CIP solutions were intratracheally instilled to the rat lungs at 3 different rates,i.e.,T0h(fast),T2h(medium),and T4h(slow),to mimic different release profiles of inhaled CIP formulations in the lung.Subsequently,the concentration-time profiles of CIP in the plasma and the lung ELF were obtained,respectively,to determine topical exposure index(ELF-Plasma AUC Ratio,EPR).The in silico PBPK model,validated based on the in vivo data,was used to identify the key factors that influence the disposition of CIP in the plasma and lungs.The medium and slow rates groups exhibited much higher EPR than that fast instillation group.The ELF AUC of the medium and slow instillation groups were about 200 times higher than their plasma AUC.In contrast,the ELF AUC of the fast instillation group was only about 20 times higher than the plasma AUC.The generated whole-body PBPK rat model,validated by comparison with the in vivo data,revealed that drug pulmonary absorption rate was the key factor that determined pulmonary absorption of CIP.This study suggests that controlled CIP release from inhaled formulations may extend the exposure of CIP in the ELF post pulmonary administration.It also demonstrates that combining the proposed intratracheal installation model and in silico PBPK model is a useful approach to identify the key factors that influence the absorption and disposition of inhaled medicine.展开更多
The lung immune response consists of various cells involved in both innate and adaptive immune processes.Innate immunity participates in immune resistance in a nonspecific manner,whereas adaptive immunity effectively ...The lung immune response consists of various cells involved in both innate and adaptive immune processes.Innate immunity participates in immune resistance in a nonspecific manner,whereas adaptive immunity effectively eliminates pathogens through specific recognition.It was previously believed that adaptive immune memory plays a leading role during secondary infections;however,innate immunity is also involved in immune memory.Trained immunity refers to the long-term functional reprogramming of innate immune cells caused by the first infection,which alters the immune response during the second challenge.Tissue resilience limits the tissue damage caused by infection by controlling excessive inflammation and promoting tissue repair.In this review,we summarize the impact of host immunity on the pathophysiological processes of pulmonary infections and discuss the latest progress in this regard.In addition to the factors influencing pathogenic microorganisms,we emphasize the importance of the host response.展开更多
<strong>Background:</strong> Recently, Coronavirus Disease 2019 (COVID-19) has been affected by the extreme acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and has developed important global health a...<strong>Background:</strong> Recently, Coronavirus Disease 2019 (COVID-19) has been affected by the extreme acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and has developed important global health anxiety. At this time, the treatment options for this disease are only moderately successful. Smoking has been related to COVID-19 and its mortality, and it has the potential to affect bacteriological and viral conversion, clinical effects, and treatment outcomes. <strong>Methods:</strong> The aim of this study was to determine the relationship between critical essential trace {zinc (Zn), iron (Fe), and copper (Cu)} and toxic {cadmium (Cd) and nickel (Ni)} elements in human biological samples such as scalp hair, serum, saliva, blood, nasal fluid, and sputum of smoking and nonsmoking male COVID-19 patients (n = 139, age range 25 - 38 years) from Hyderabad, Pakistan. For comparative purposes, the biological specimens of referent persons (n = 83), pulmonary Tuberculosis (T.B) patients (n = 67), Pneumonia (n = 56) of the same age groups were also be analyzed. Microwave oven mediated digestion method was employed, and digestion of samples was carried out with the help of 2:1 mixture solution of HNO<sub>3</sub> (65%) and H<sub>2</sub>O<sub>2</sub> (30%). Atomic absorption spectrometry was employed for the determination of elemental concentrations from the microwave oven employed digested samples. <strong>Results:</strong> The found average of essential elements (Zn, Fe, and Cu) in biological specimens of smoker and nonsmoker male COVID-19, T.B, and Pneumonia patients was found to lower, whilst cadmium and nickel were found to be higher when compared with samples from referents (p < 0.001). <strong>Conclusions:</strong> Improved elemental (Cu, Fe, Zn) concentrations may also decrease the risk of bacterial co-infection by enhancing the mucociliary clearance and respiratory epithelial barrier function, in addition to providing direct antibacterial effects against <i>S. pneumoniae</i>. Our findings also suggest that higher Cd and Ni concentrations are linked to cigarette smoking, which could lead to COVID-19 and other lung-infected diseased recurrences. However, further clinical and experimental research is required.展开更多
Interleukin-17(IL-17),a member of the IL-17 cytokine family,plays a crucial role in mediating the immune response against extracellular bacteria and fungi in the lung.Although there is increasing evidence that IL-17 i...Interleukin-17(IL-17),a member of the IL-17 cytokine family,plays a crucial role in mediating the immune response against extracellular bacteria and fungi in the lung.Although there is increasing evidence that IL-17 is involved in protective immunity against H1 and H3 influenza virus infections,little is known about the role of IL-17 in the highly pathogenic H5N1 influenza virus infection.In this study,we show that H5N1-infected IL-17 knockout(KO)mice exhibit markedly increased weight loss,more pronounced lung immunopathology and significantly reduced survival rates as compared with infected wild-type controls.Moreover,the frequency of B cells in the lung were substantially decreased in IL-17 KO mice after virus infection,which correlated with reduced CXCR5 expression in B cells and decreased CXCL13 production in the lung tissue of IL-17 KO mice.Consistent with this observation,B cells from IL-17 KO mice exhibited a significant reduction in chemokine-mediated migration in culture.Taken together,these findings demonstrate a critical role for IL-17 in mediating the recruitment of B cells to the site of pulmonary influenza virus infection in mice.展开更多
文摘This study is designed to develop Artificial Intelligence(AI)based analysis tool that could accurately detect COVID-19 lung infections based on portable chest x-rays(CXRs).The frontline physicians and radiologists suffer from grand challenges for COVID-19 pandemic due to the suboptimal image quality and the large volume of CXRs.In this study,AI-based analysis tools were developed that can precisely classify COVID-19 lung infection.Publicly available datasets of COVID-19(N=1525),non-COVID-19 normal(N=1525),viral pneumonia(N=1342)and bacterial pneumonia(N=2521)from the Italian Society of Medical and Interventional Radiology(SIRM),Radiopaedia,The Cancer Imaging Archive(TCIA)and Kaggle repositories were taken.A multi-approach utilizing deep learning ResNet101 with and without hyperparameters optimization was employed.Additionally,the fea-tures extracted from the average pooling layer of ResNet101 were used as input to machine learning(ML)algorithms,which twice trained the learning algorithms.The ResNet101 with optimized parameters yielded improved performance to default parameters.The extracted features from ResNet101 are fed to the k-nearest neighbor(KNN)and support vector machine(SVM)yielded the highest 3-class classification performance of 99.86%and 99.46%,respectively.The results indicate that the proposed approach can be bet-ter utilized for improving the accuracy and diagnostic efficiency of CXRs.The proposed deep learning model has the potential to improve further the efficiency of the healthcare systems for proper diagnosis and prognosis of COVID-19 lung infection.
基金supported by the National Natural Science Foundation of China(82041017)Chinese Academy of Medical Sciences(CAMS)Innovation Fund for Medical Sciences(2016-I2M-1-014)。
文摘Understanding the pathogenesis of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)and clarifying antiviral immunity in hosts are critical aspects for the development of vaccines and antivirals.Mice are frequently used to generate animal models of infectious diseases due to their convenience and ability to undergo genetic manipulation.However,normal adult mice are not susceptible to SARS-CoV-2.Here,we developed a viral receptor(human angiotensin-converting enzyme 2,hACE2)pulmonary transfection mouse model to establish SARS-CoV-2 infection rapidly in the mouse lung.Based on the model,the virus successfully infected the mouse lung 2 days after transfection.Viral RNA/protein,innate immune cell infiltration,inflammatory cytokine expression,and pathological changes in the infected lungs were observed after infection.Further studies indicated that neutrophils were the first and most abundant leukocytes to infiltrate the infected lungs after viral infection.In addition,using infected CXCL5-knockout mice,chemokine CXCL5 was responsible for neutrophil recruitment.CXCL5 knockout decreased lung inflammation without diminishing viral clearance,suggesting a potential target for controlling pneumonia.
基金the Beijing Tongren Hospital,Capital Medical University Institutional Review Board(Approval No.TRECKY2020-100).
文摘BACKGROUND Vancomycin and teicoplanin are both antibiotics that have significant antimicrobial effects on Gram-positive cocci.AIM To explore the value of teicoplanin combined with conventional(vancomycin only)anti-infective therapy for the treatment of methicillin-resistant Staphylococcus aureus and Staphylococcus epidermidis pulmonary infections.METHODS A total of 86 patients with methicillin-resistant Staphylococcus aureus or methicillin-resistant Staphylococcus epidermidis pulmonary infections,treated in our hospital between January 2018 and February 2020,were assigned to the study and control groups using a random number table method,with 43 patients in each group.The control group received conventional treatment(vancomycin),and the study group received both teicoplanin and conventional treatment.The following indicators were assessed in both groups:the time required for symptom relief,treatment effectiveness,serum levels of inflammatory factors(procalcitonin,interleukin-1β,tumor necrosis factor-α,C-reactive protein),clinical pulmonary infection scores before and after treatment,and the incidence of adverse reactions.RESULTS Patients in the study group were observed to have faster cough and expectoration resolution,white blood cell count normalization,body temperature normalization,and rales disappearance than patients in the control group(all P<0.05);the total rate of effectiveness was 93.02%in the study group,higher than the 76.74%in the control group(P<0.05).The pre-treatment serum levels of procalcitonin,interleukin-1β,tumor necrosis factor-α,and C-reactive protein as well as the clinical pulmonary infection scores were similar among the patients in both groups.However,the post-treatment serum levels of procalcitonin,interleukin-1β,tumor necrosis factor-α,and C-reactive protein as well as the clinical pulmonary infection scores were significantly lower in the study group than in the control group(P<0.05).There was no significant difference in the incidence of adverse reactions between the groups.CONCLUSION Compared with conventional(vancomycin only)therapy,teicoplanin and vancomycin combination therapy for patients with pulmonary methicillinresistant Staphylococcus aureus and methicillin-resistant Staphylococcus epidermidis infections can improve patient clinical symptoms,modulate serum inflammatory factor levels,and improve treatment efficacy,without increasing the risk of adverse reactions.
文摘BACKGROUND Primary anaplastic large cell lymphoma of the lung represents a diagnostic challenge due to diverse manifestations and non-specific radiological findings,particularly in cases that lack extra-pulmonary manifestations and lung biopsy.CASE SUMMARY A 40-year-old woman presented with a 6-d history of fever,dry coughing,and dyspnea.Her white blood cell count was 20100/mm3 with 90%neutrophils.PaO2 was 60 mmHg and SaO2 was 90%when breathing ambient air.Chest computed tomography(CT)identified a solid nodule,15 mm in diameter,with a poorly defined boundary in the upper right lung,and several smaller solid nodules throughout both lungs.Pulmonary artery CT and subsequent bedside X-ray showed diffuse patchy shadows throughout both lungs.Repeated cultures of blood samples and alveolar lavage failed to identify any pathogen.Due to the mismatch between clinical and imaging features,we conducted a bone marrow biopsy,and the results showed proliferation along all three lineages but no atypical or malignant cells.The patient received empirical antibacterial,antiviral,and antifungal treatments,as well as corticosteroids.The patient’s condition deteriorated rapidly despite treatment.The patient died 6 d after hospitalization due to respiratory failure.Post-mortem lung biopsy failed to show inflammation but identified widespread infiltration of alveolar septum by anaplastic lymphoma kinase(ALK)-positive anaplastic cells.CONCLUSION ALK-positive anaplastic large cell lymphoma could present as a primary pulmonary disease without extra-pulmonary manifestations.
文摘Computerized tomography(CT)scans and X-rays play an important role in the diagnosis of COVID-19 and pneumonia.On the basis of the image analysis results of chest CT and X-rays,the severity of lung infection is monitored using a tool.Many researchers have done in diagnosis of lung infection in an accurate and efficient takes lot of time and inefficient.To overcome these issues,our proposed study implements four cascaded stages.First,for pre-processing,a mean filter is used.Second,texture feature extraction uses principal component analysis(PCA).Third,a modified whale optimization algorithm is used(MWOA)for a feature selection algorithm.The severity of lung infection is detected on the basis of age group.Fourth,image classification is done by using the proposed MWOAwith the salp swarm algorithm(MWOA-SSA).MWOA-SSA has an accuracy of 97%,whereas PCA and MWOA have accuracies of 81%and 86%.The sensitivity rate of the MWOA-SSA algorithm is better that of than PCA(84.4%)and MWOA(95.2%).MWOA-SSA outperforms other algorithms with a specificity of 97.8%.This proposed method improves the effective classification of lung affected images from large datasets.
文摘BACKGROUND Listeria is a food-borne disease,which is rarely prevalent in the normal population;it mostly occurs in pregnant women,newborns,immunodeficiency patients,and the elderly.The main manifestations of this disease in patients include sepsis,meningitis,etc,and the mortality rate remains high,although the onset of meningitis is relatively insidious.CASE SUMMARY A 75-year-old man presented with a fever for 1 wk and was admitted to the hospital for diagnosis and management of a lung infection.His condition improved after receiving anti-infective treatment for 2 wk.However,soon after he was discharged from the hospital,he developed fever again,and gradually developed various neurological symptoms,impaired consciousness,and stiff neck.Thereafter,through the cerebrospinal fluid metagenomic testing and blood culture,the patient was diagnosed with Listeria monocytogenes meningitis and sepsis.The patient died after being given active treatment,which included penicillin application and invasive respiratory support.CONCLUSION This case highlights the ultimate importance of early identification and timely application of the various sensitive antibiotics,such as penicillin,vancomycin,meropenem,etc.Therefore,for high-risk populations with unknown causes of fever,multiple blood cultures,timely cerebrospinal fluid examination,and metagenomic detection technology can assist in confirming the diagnosis quickly,thereby guiding the proper application of antibiotics and improving the prognosis.
基金financially supported by the Liaoning Pan Deng Xue Zhe Scholar(No.XLYC2002061)the National Natural Science Foundation of China(No.81573380)+3 种基金the Overseas Expertise Introduction Project for Discipline Innovation(“111 Project”)(No.D20029)financial support from the Guiding Project for Science and Technology of Liaoning Province(No.2019-ZD-0448)Ministry of Education Chunhui Program(2020)support from Ministry of Education Science and Technological Development,Republic of Serbia(No.451-03-9/2021-14/200161)。
文摘Respiratory antibiotics have been proven clinically beneficial for the treatment of severe lung infections such as Pseudomonas aeruginosa.Maintaining a high local concentration of inhaled antibiotics for an extended time in the lung is crucial to ensure an adequate antimicrobial efficiency.In this study,we aim to investigate whether an extended exposure of ciprofloxacin(CIP),a model fluoroquinolone drug,in the lung epithelial lining fluid(ELF)could be achieved via a controlled-release formulation strategy.CIP solutions were intratracheally instilled to the rat lungs at 3 different rates,i.e.,T0h(fast),T2h(medium),and T4h(slow),to mimic different release profiles of inhaled CIP formulations in the lung.Subsequently,the concentration-time profiles of CIP in the plasma and the lung ELF were obtained,respectively,to determine topical exposure index(ELF-Plasma AUC Ratio,EPR).The in silico PBPK model,validated based on the in vivo data,was used to identify the key factors that influence the disposition of CIP in the plasma and lungs.The medium and slow rates groups exhibited much higher EPR than that fast instillation group.The ELF AUC of the medium and slow instillation groups were about 200 times higher than their plasma AUC.In contrast,the ELF AUC of the fast instillation group was only about 20 times higher than the plasma AUC.The generated whole-body PBPK rat model,validated by comparison with the in vivo data,revealed that drug pulmonary absorption rate was the key factor that determined pulmonary absorption of CIP.This study suggests that controlled CIP release from inhaled formulations may extend the exposure of CIP in the ELF post pulmonary administration.It also demonstrates that combining the proposed intratracheal installation model and in silico PBPK model is a useful approach to identify the key factors that influence the absorption and disposition of inhaled medicine.
基金National Defense Science and Technology Innovation Fund,Grant/Award Number:20-163-12-ZT-005-003-01。
文摘The lung immune response consists of various cells involved in both innate and adaptive immune processes.Innate immunity participates in immune resistance in a nonspecific manner,whereas adaptive immunity effectively eliminates pathogens through specific recognition.It was previously believed that adaptive immune memory plays a leading role during secondary infections;however,innate immunity is also involved in immune memory.Trained immunity refers to the long-term functional reprogramming of innate immune cells caused by the first infection,which alters the immune response during the second challenge.Tissue resilience limits the tissue damage caused by infection by controlling excessive inflammation and promoting tissue repair.In this review,we summarize the impact of host immunity on the pathophysiological processes of pulmonary infections and discuss the latest progress in this regard.In addition to the factors influencing pathogenic microorganisms,we emphasize the importance of the host response.
文摘<strong>Background:</strong> Recently, Coronavirus Disease 2019 (COVID-19) has been affected by the extreme acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and has developed important global health anxiety. At this time, the treatment options for this disease are only moderately successful. Smoking has been related to COVID-19 and its mortality, and it has the potential to affect bacteriological and viral conversion, clinical effects, and treatment outcomes. <strong>Methods:</strong> The aim of this study was to determine the relationship between critical essential trace {zinc (Zn), iron (Fe), and copper (Cu)} and toxic {cadmium (Cd) and nickel (Ni)} elements in human biological samples such as scalp hair, serum, saliva, blood, nasal fluid, and sputum of smoking and nonsmoking male COVID-19 patients (n = 139, age range 25 - 38 years) from Hyderabad, Pakistan. For comparative purposes, the biological specimens of referent persons (n = 83), pulmonary Tuberculosis (T.B) patients (n = 67), Pneumonia (n = 56) of the same age groups were also be analyzed. Microwave oven mediated digestion method was employed, and digestion of samples was carried out with the help of 2:1 mixture solution of HNO<sub>3</sub> (65%) and H<sub>2</sub>O<sub>2</sub> (30%). Atomic absorption spectrometry was employed for the determination of elemental concentrations from the microwave oven employed digested samples. <strong>Results:</strong> The found average of essential elements (Zn, Fe, and Cu) in biological specimens of smoker and nonsmoker male COVID-19, T.B, and Pneumonia patients was found to lower, whilst cadmium and nickel were found to be higher when compared with samples from referents (p < 0.001). <strong>Conclusions:</strong> Improved elemental (Cu, Fe, Zn) concentrations may also decrease the risk of bacterial co-infection by enhancing the mucociliary clearance and respiratory epithelial barrier function, in addition to providing direct antibacterial effects against <i>S. pneumoniae</i>. Our findings also suggest that higher Cd and Ni concentrations are linked to cigarette smoking, which could lead to COVID-19 and other lung-infected diseased recurrences. However, further clinical and experimental research is required.
基金supported by the Research Fund for the Control of Infectious Diseases(RFCID),Food and Health Bureau,Hong Kong SAR Government(No.10091002).
文摘Interleukin-17(IL-17),a member of the IL-17 cytokine family,plays a crucial role in mediating the immune response against extracellular bacteria and fungi in the lung.Although there is increasing evidence that IL-17 is involved in protective immunity against H1 and H3 influenza virus infections,little is known about the role of IL-17 in the highly pathogenic H5N1 influenza virus infection.In this study,we show that H5N1-infected IL-17 knockout(KO)mice exhibit markedly increased weight loss,more pronounced lung immunopathology and significantly reduced survival rates as compared with infected wild-type controls.Moreover,the frequency of B cells in the lung were substantially decreased in IL-17 KO mice after virus infection,which correlated with reduced CXCR5 expression in B cells and decreased CXCL13 production in the lung tissue of IL-17 KO mice.Consistent with this observation,B cells from IL-17 KO mice exhibited a significant reduction in chemokine-mediated migration in culture.Taken together,these findings demonstrate a critical role for IL-17 in mediating the recruitment of B cells to the site of pulmonary influenza virus infection in mice.
基金financially supported by the National Key R&D Program of China(2020YFA0908900,2018YFA0902600,2022YFB3804700,and 2021YFF1200100)the National Natural Science Foundation of China(22234004)+6 种基金Guangdong Provincial Key Laboratory of Advanced Biomaterials(2022B1212010003)Shenzhen Science and Technology Program(KQTD20190929172743294 and JCYJ20200109141231365)Shenzhen Key Laboratory of Smart Healthcare Engineering(ZDSYS20200811144003009)the Natural Science Foundation of Shenzhen City(JCYJ20190809115005628)Guangdong Innovative and Entrepreneurial Research Team Program(2019ZT08Y191)Guangdong Major Talent Introduction Project(2019CX01Y196)the Tencent Foundation through the XPLORER PRIZE for financial support。
