The Value of γδ T Cells in Lung Infections and Advances in Diagnosis and Treatment

Lung infections are usually caused by pathogenic microorganisms and are a disease with high morbidity and mortality. In clinical practice, the use of broad-spectrum antibiotics has become increasingly common, but this has also led to the problem of antibiotic abuse and irrational use, which in turn has spawned the emergence of multidrug-resistant bacteria, making the treatment of lung infections more complex and difficult. In the human immune system, γδ T cells play a crucial role in defense against foreign pathogens and regulation of autoimmune responses. These cells act as a bridge between innate and adaptive immunity and can be rapidly activated in the early stages of infection to produce inflammatory factors and chemokines that attract other immune cells to the site of infection. Recent advances have shown that γδ T cells not only play a direct role in the innate immunity of pathogen infection, but are also involved in regulating the subsequent adaptive immune response. The aim of this review is to explore the mechanism of γδ T cells in lung infections and to summarize the current progress of clinical research, with the aim of providing new scientific basis and therapeutic strategies for the treatment of lung infections.

Deep Learning ResNet101 Deep Features of Portable Chest X-Ray Accurately Classify COVID-19 Lung Infection

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.

Treatment of Severe Post-kidney-transplant Lung Infection by Integrative Chinese and Western Medicine

Objective： To explore treatments of severe post-kidney-transplant lung infection by integrative Chinese and Western medicine （ICWM）, in order to elevate the curing rate as well as to lower the death rate. Methods： Based on conventional ways of Western medical treatments of 18 cases of severe post-kidney-transplant lung infection, such as putting the patients in single individual ward, antibiotics to prevent infection, respiratory machines, blood filtration, nutritional support, steroids, and maintaining electrolytes balance, we applied integrated Chinese medicinal treatments, like altering conventional prescription ＂pneumonia Ⅲ ＂, and conducted clinical observation of effectiveness, and indexes including white blood cell （WBC）, neutrophilic granulocyte, blood urea nitrogen （BUN）, blood creatinine （Or）, etc. Results： Of the 18 cases studied, 7 were already cured, 8 proved the treatment effective, 3 died. All clinical indexes had statistically significant changes compared with those of before treatment （P〈0. 01 ）. Cenclusien. ICWM can increase curing rate and lower death rate.

Role of neutrophil chemoattractant CXCL5 in SARS-CoV-2 infection-induced lung inflammatory innate immune response in an in vivo hACE2 transfection mouse model

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.

Intravenous infusion of mesenteric lymph from severe intraperitoneal infection rats causes lung injury in healthy rats

AIM: To investigate whether mesenteric lymph from rats with severe intraperitoneal infection (SII) induces lung injury in healthy rats.

Prolonged course of Paxlovid administration in a centenarian with COVID-19:A case report

BACKGROUND According to the population statistics in 2023,there were 110000 people aged over 100 years in China,and the experience of using Paxlovid(nirmatrelvir/ritonavir)for centenarians is particularly valuable.This article reports our experience of using Paxlovid in a centenarian with the novel coronavirus disease 2019(COVID-19)infection.CASE SUMMARY A 103-year-old female with mild COVID-19 and renal insufficiency was given sufficient Paxlovid for 2 days and a half dose for 3 days.During treatment,the patient was complicated with lung infection and heart failure,and nucleic acid remained positive.After expert consultation,a full dose of Paxlovid was given again on the 9th day of admission for 2 days and a half dose for 3 days.Meanwhile,anti-heart failure and antibiotics were administered;the heart failure and pulmonary infection were improved.Finally,on the 33^(th) day of admission,nucleic acid turned negative,body temperature returned to normal,cough and sputum,fatigue,poor appetite and other symptoms basically improved.The patient was given Paxlovid via nasal feeding for 2 courses without deterioration of liver and kidney function,diarrhea,nausea and vomiting,myalgia,chest tightness and other side effects,and was discharged from hospital with good recovery.CONCLUSION This case suggests that Paxlovid can be used cautiously in centenarians with renal insufficiency and two courses of treatment can be considered in patients with persistent positive nucleic acid.

Teicoplanin combined with conventional vancomycin therapy for the treatment of pulmonary methicillin-resistant Staphylococcus aureus and Staphylococcus epidermidis infections

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.

Rapidly progressing primary pulmonary lymphoma masquerading as lung infectious disease:A case report and review of the literature

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.

MORPHOLOGICAL SURVEY ON ENDOGENOUS C-TYPE VIRUSES INFECTING A HUMAN LUNG SQUAMOUS CARCINOMA PASSAGED IN NUDE MICE

A human lung squamous carcinoma was transplanted and passaged in Swiss-DF nude mice, called LSX-83, for more than five years in our laboratory. The morphological characteristics of the original tumor were maintained in passages from 4 to 33. But from the 35th generation, an increasing amount of tonofilaments and nuclear segregation with typical features was found with electron microscopy. The C-type virus particles were first detected in extra cellular space after 40 passages. The viruses were observed in different stages of growth, but their distribution and number did not show apparent change up to 54 passages. Such findings suggest that LSX-83 cells probably possess certain barrier of resistance against C-type viruses. The relation between C-type viruses and the morphological changes of LSX-83 cells was discussed.

COVID-19 Severity Prediction Using Enhanced Whale with Salp Swarm Feature Classification

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.

Treatment failure in a patient infected with Listeria sepsis combined with latent meningitis:A case report

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.

Evaluating the pharmacokinetics of intrapulmonary administered ciprofloxacin solution for respiratory infections using in vivo and in silico PBPK rat model studies

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.

Advances in immune response to pulmonary infection:Nonspecificity,specificity and memory

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.

Elemental Concentrations in Biological Samples of Coronavirus Disease (COVID-19) and Other Pulmonary Disease Patients

Background: 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. Methods: 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 HNO3 (65%) and H2O2 (30%). Atomic absorption spectrometry was employed for the determination of elemental concentrations from the microwave oven employed digested samples. Results: 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). Conclusions: 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 S. pneumoniae. 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.

A critical role of IL-17 in modulating the B-cell response during H5N1 influenza virus infection

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.

利用双金属纳米颗粒协同提高抗生素对耐碳青霉烯类细菌的疗效

细菌对碳青霉烯类抗生素耐药性的日益增加,已成为一个备受关注的问题.联合治疗是应对耐药细菌感染的有效策略.在本研究中,双金属纳米颗粒(AuRh NPs)与小分子抗生素(亚胺培南)具有协同抗菌作用,它们通过增加细菌胞内的活性氧水平和增强细菌膜的渗透性表现出优异的抗菌效果.特别地,联合治疗恢复了亚胺培南对耐碳青霉烯类肺炎克雷伯菌(CRKP)的疗效,最低抑菌浓度降低了128倍.在治疗肺部感染时,AuRh NPs与亚胺培南联合使用能更有效地抑制CRKP感染,与单独使用亚胺培南或AuRh NPs实验组相比,小鼠的存活率提升了50%.体外和体内安全性研究表明,AuRh NPs与亚胺培南联合使用没有明显的毒性.这种联合疗法为耐药细菌感染提供了有效的治疗策略.

Jinye Baidu granule for wind-warmth lung-heat disease(heat in the lung-wei)： protocol for a randomized, double-blind, parallel, controlled trial

OBJECTIVE: To observe the curative effect of Jinye Baidu granule in the treatment of fever and swollen and sore throat caused by wind-warmth lung-heat disease(heat in the lung-wei) to further identify the indications.METHODS: This randomized, double-blind, parallel, controlled trial will include patients with acute upper respiratory infection and wind-warmth lung-heat disease(heat in the lung-wei). Patientswith serious bacterial infection(white blood cell count > 12 × 10~9, neutrophils > 80%) will be excluded. Patients will be divided into three categories(blocks) according to their condition: fever only, a swollen and sore throat, and combined fever plus a swollen and sore throat. Patients within each of the three blocks will be further divided into a treatment group and a control group via stratified blocked randomization. The treatment group will be treated with Jinye Baidu granule, and the control group will be treated with Fufang Shuanghua granule. The primary outcome measure will be body temperature recovery time for patients with fever, throat symptom score for patients with a swollen and sore throat, and body temperature recovery time and throat symptom score for patients with combined fever plus a swollen and sore throat. Routine blood testing, urine testing, liver function, kidney function and ECG data of all patients will be collected as safety indices before and after enrollment, and adverse events will be recorded during the whole trial course.CONCLUSION: This study protocol will include stratified block analysis according to patients' symptoms, and identify the accurate clinical indications of Jinye Baidu granule. It will also enable safety evaluation from laboratory indices and adverse events, which will provide reliable evidence for clinical treatment.