Advanced LUAD shows limited response to treatment including immune therapy.With the development of sequencing omics,it is urgent to combine high-throughput multi-omics data to identify new immune checkpoint therapeuti...Advanced LUAD shows limited response to treatment including immune therapy.With the development of sequencing omics,it is urgent to combine high-throughput multi-omics data to identify new immune checkpoint therapeutic response markers.Using GSE72094(n=386)and GSE31210(n=226)gene expression profile data in the GEO database,we identified genes associated with lung adenocarcinoma(LUAD)death using tools such as“edgeR”and“maftools”and visualized the characteristics of these genes using the“circlize”R package.We constructed a prognostic model based on death-related genes and optimized the model using LASSO-Cox regression methods.By calculating the cell death index(CDI)of each individual,we divided LUAD patients into high and low CDI groups and examined the relationship between CDI and overall survival time by principal component analysis(PCA)and Kaplan-Meier analysis.We also used the“ConsensusClusterPlus”tool for unsupervised clustering of LUAD subtypes based on model genes.In addition,we collected data on the expression of immunomodulatory genes and model genes for each cohort and performed tumor microenvironment analyses.We also used the TIDE algorithm to predict immunotherapy responses in the CDI cohort.Finally,we studied the effect of PRKCD on the proliferation and migration of LUAD cells through cell culture experiments.The study utilized the TCGA-LUAD cohort(n=493)and identified 2,901 genes that are differentially expressed in patients with LUAD.Through KEGG and GO enrichment analysis,these genes were found to be involved in a wide range of biological pathways.The study also used univariate Cox regression models and LASSO regression analyses to identify 17 candidate genes that were best associated with mortality prognostic risk scores.By comparing the overall survival(OS)outcomes of patients with different CDI values,it was found that increased CDI levels were significantly associated with lower OS rates.In addition,the study used unsupervised cluster analysis to divide 115 LUAD patients into two distinct clusters with significant differences in OS timing.Finally,a prognostic indicator called CDI was established and its feasibility as an independent prognostic indicator was evaluated by Cox proportional risk regression analysis.The immunotherapy efficacy was more sensitive in the group with high expression of programmed cell death models.Relationship between programmed cell death(PCD)signature models and drug reactivity.After evaluating the median inhibitory concentration(IC50)of various drugs in LUAD samples,statistically significant differences in IC50 values were found in cohorts with high and low CDI status.Specifically,Gefitinib and Lapatinib had higher IC50 values in the high-CDI cohort,while Olaparib,Oxaliplatin,SB216763,and Axitinib had lower values.These results suggest that individuals with high CDI levels are sensitive to tyrosine kinase inhibitors and may be resistant to conventional chemotherapy.Therefore,this study constructed a gene model that can evaluate patient immunotherapy by using programmed cell death-related genes based on muti-omics.The CDI index composed of these programmed cell death-related genes reveals the heterogeneity of lung adenocarcinoma tumors and serves as a prognostic indicator for patients.展开更多
The description in the abstract lacks clear logic and a comprehensive summary of this study, so please revise and improve it according to the design theme and main content of this study, and describe it in the order o...The description in the abstract lacks clear logic and a comprehensive summary of this study, so please revise and improve it according to the design theme and main content of this study, and describe it in the order of (research background), purpose/aim, method, results and conclusions. The introduction of the abstract and preface is rather lengthy, but the summary of the whole study and the presentation of the research background are not perfect (mainly because the logic of the context is not clear and orderly), so it will appear a bit messy. Hope to be able to modify (this has been mentioned in the preliminary opinion). Cardiovascular events (CVE) pose a significant threat to individuals with end-stage renal disease (ESRD), yet these patients are often excluded from cardiovascular clinical trials, leaving prognostic factors associated with CVE in ESRD patients largely unexplored. Recent human studies have demonstrated elevated circulating aldosterone levels in ESRD patients, correlating with left ventricular hypertrophy. Additionally, animal models have shown improvements in uremic cardiomyopathy with spironolactone therapy, prompting interest in assessing the efficacy of spironolactone or eplerenone in reducing mortality and improving cardiovascular function in dialysis patients. Clinicians have historically been cautious about prescribing mineralocorticoid receptor antagonists (MRAs) to congestive heart failure patients with chronic kidney disease (CKD) due to hyperkalemia risk. However, the emergence of finerenone, a novel MR antagonist with a favorable safety profile and lower hyperkalemia risk, has renewed interest in MRA therapy in this population. Heart disease, including coronary artery disease, hypertension, and left ventricular failure, is alarmingly prevalent in dialysis patients, contributing significantly to elevated mortality rates compared to the general population. Arterial stiffness, as indicated by pulse wave velocity (PWV), progressively worsens with advancing CKD stages, peaking in severity among ESRD patients undergoing dialysis. High PWV serves as a crucial risk stratification tool in ESRD. Elevated NT-proBNP and BNP levels in ESRD patients are well-documented, with significant associations observed between baseline peptide concentrations and cardiovascular morbidity and mortality. By incorporating finerenone into our study, we aim to investigate its potential benefits in reducing arterial stiffness, lowering blood pressure, and ultimately mitigating heart-related mortality among hemodialysis patients. This study holds substantial implications for hypertension and cardiovascular risk management in this vulnerable patient population. Eligible participants must have been on chronic hemodialysis for at least three months, with ACE inhibitors or angiotensin receptor blockers included in their therapy at maximum tolerable doses. Serum potassium levels 5.7 mmol/L, left ventricular ejection fraction 50%, and PWV higher than age-estimated values are also prerequisites for study entry. Randomized allocation will be conducted using a permuted block design, stratified by center, with allocation communicated via signed study forms during initial examinations. All steps of this research will be conducted in accordance with the principles of the Helsinki Declaration.展开更多
BACKGROUND Metastatic pancreatic ductal adenocarcinoma(PDAC)is a lethal malignancy with dispiriting survival data.Immunotherapy is a promising approach to many cancer types,but achieves poor outcomes in advanced PDAC ...BACKGROUND Metastatic pancreatic ductal adenocarcinoma(PDAC)is a lethal malignancy with dispiriting survival data.Immunotherapy is a promising approach to many cancer types,but achieves poor outcomes in advanced PDAC due to its immunosuppressive tumor microenvironment.We describe a case of metastatic PDAC effectively treated with pembrolizumab.CASE SUMMARY We report the case of a 67-year-old woman with unresectable locally advanced PDAC,treated with gemcitabine plus nab-paclitaxel followed by radiotherapy plus capecitabine.At nine months,pancreatic tumor progression was observed at the level of the hepatic hilum with the appearance of a new pulmonary nodule suggestive of a second primary,confirmed by left lung biopsy.Systemic immunotherapy was then initiated with pembrolizumab,an immune checkpoint inhibitor targeting programmed cell death protein-1 that covers the two tumor types.The patient showed a complete metabolic response that was maintained throughout the treatment.The patient continues to be disease-free at 5.6 years since the start of immunotherapy.CONCLUSION These results suggest that the administration of pembrolizumab after chemoradiotherapy has a beneficial effect in patients with metastatic PDAC.To our knowledge,this is the first reported case of a patient with metastatic PDAC and metastatic lung cancer showing such a long-lasting complete response after pembrolizumab treatment without curative surgery.Further studies are required to determine biomarkers that identify PDAC patients most likely to benefit from this immunotherapy.展开更多
The recent discovery of immune checkpoints inhibitors, especially anti-programmed cell death protein 1(PD-1)and anti-programmed cell death protein ligand 1(PD-L1) monoclonal antibodies, has opened new scenarios in the...The recent discovery of immune checkpoints inhibitors, especially anti-programmed cell death protein 1(PD-1)and anti-programmed cell death protein ligand 1(PD-L1) monoclonal antibodies, has opened new scenarios in the management of non-small cell lung cancer(NSCLC) and this new class of drugs has achieved a rapid development in the treatment of this disease. However, considering the costs of these drugs and the fact that only a subset of patients experience long-term disease control, the identification of predictive biomarkers for the selection of candidates suitable for treatment has become a priority. The research focused mainly on the expression of the PD-L1 receptor on both tumor cells and/or immune infiltrates determined by immunohistochemistry(IHC). However, different checkpoint inhibitors were tested, different IHC assays were used, different targets were considered(tumor cells, immune infiltrates or both) and different expression thresholds were employed in clinical trials. In some trials the assay was used prospectively to select the patients, while in other trials it was evaluated retrospectively. Some confusion emerges, which makes it difficult to easily compare the literature data and to translate them in practice management. This mini-review shows the possibilities and pitfalls of the PD-L1 expression to predict the activity and efficacy of anti PD1/PD-L1 monoclonal antibodies in the treatment of NSCLC.展开更多
Objective A new technique of transthoracic lung ultrasonography(TLS) has emerged and demonstrated promising results in acute heart failure diagnosis at an early stage. However, the diagnostic value of ultrasound lung ...Objective A new technique of transthoracic lung ultrasonography(TLS) has emerged and demonstrated promising results in acute heart failure diagnosis at an early stage. However, the diagnostic value of ultrasound lung comets(ULCs) for acute heart failure(AHF) performed in busy emergency department(ED) is uncertain. The present meta-analysis aimed to assess the diagnostic efficiency of ULCs in AHF. Methods We conducted a search on online journal databases to collect the data on TLS performed for diagnosing AHF published up to the end of July 2017. The sensitivity, specificity, positive likelihood ratio(PLR), negative likelihood ratio(NLR), and summary receiver operating characteristic(SROC) curve were calculated. The post-test probability of AHF was calculated by using Bayes analysis. Results We enrolled a total of 15 studies involving 3,309 patients. The value of sensitivity, specificity, PLR, NLR, DOR, area under the SROC curve, and Q* index was 85%, 91%, 8.94, 0.14, 67.24, 0.9587, and 0.9026, respectively. We detected significant heterogeneity among included studies, and therefore, all these results were analyzed under the random-effect model. We also explored possible sources of heterogeneity among the studies by using meta-regression analysis. Results suggest that the time interval between patient’s admission to bedside TLS examination was closely related to TLS accuracy. Conclusion This meta-analysis demonstrated that detecting ULCs is a convenient bedside tool and has high accuracy for early AHF diagnosis in ED. TLS could be recommended to be applied for early diagnosis of AHF in ED.展开更多
Hydrostatic pulmonary edema is as an abnormal in-crease in extravascular water secondary to elevatedpressure in the pulmonary circulation, due to conges-tive heart failure or intravascular volume overload.Diagnosis of...Hydrostatic pulmonary edema is as an abnormal in-crease in extravascular water secondary to elevatedpressure in the pulmonary circulation, due to conges-tive heart failure or intravascular volume overload.Diagnosis of hydrostatic pulmonary edema is usuallybased on clinical signs associated to conventional ra-diography findings. Interpretation of radiologic signsof cardiogenic pulmonary edema are often question-able and subject. For a bedside prompt evaluation,lung ultrasound(LUS) may assess pulmonary conges-tion through the evaluation of vertical reverberationartifacts, known as B-lines. These artifacts are relatedto multiple minimal acoustic interfaces between smallwater-rich structures and alveolar air, as it happens incase of thickened interlobular septa due to increase of extravascular lung water. The number, diffusion and in-tensity of B lines correlates with both the radiologic andinvasive estimate of extravascular lung water. The inte-gration of conventional chest radiograph with LUS canbe very helpful to obtain the correct diagnosis. Com-puted tomography(CT) is of limited use in the work upof cardiogenic pulmonary edema, due to its high cost,little use in the emergencies and radiation exposure.However, a deep knowledge of CT signs of pulmonaryedema is crucial when other similar pulmonary condi-tions may occasionally be in the differential diagnosis.展开更多
Aim: Recently, there is an increased average of developing cancers. Though, the chemotherapeutic-treatment is unfavorable during pregnancy due to its harmful effects on developing fetuses, physicians have two ways to ...Aim: Recently, there is an increased average of developing cancers. Though, the chemotherapeutic-treatment is unfavorable during pregnancy due to its harmful effects on developing fetuses, physicians have two ways to minimize these effects either by termination of the pregnancy or minimizing its side effects. The present work aimed to illustrate the susceptibility of cardiac, lung and dorsal aorta function to the widely applicable drugs doxorubicin and cisplatin as well as 5-flurouracil. Materials and Methods: Mother albino rats were arranged into four-groups (control, doxorubicin, cisplatin and 5-flurouracil-treated groups). Each pregnant rat received intraperitoneal administration of 0.2 mg/kg body weight at 10th and 14th day of gestation and sacrificed at parturition (two doses). At parturition, serum of mother rats used to assess troponin I, heat shock protein 70, 8-hydroxydeoxyguanosine, vascular endothelial growth factor and adhesion molecules (ICAM-1 & VCAM-1). Isoenzyme electrophoresis of alkaline and acid phosphatases, glucose-6-phosphate dehydrogenase and lactic dehydrogenase were estimated in serum, myocardium and dorsal aorta of mother rats. The myocardium and lung were processed for histopathological investigations for both mothers and their offspring. Single strand (comet assay) and double strand DNA damage were carried out in heart and dorsal aorta of mother rats. Results: The present finding revealed that there are detected alterations of myocardial markers and lung amino acid metabolism as well as disruption of myocardial isoenzymes. DNA damage of myocardium and dorsal aorta were observed. Conclusions: The authors concluded that the metabolic activity of heart and lung is highly susceptible to doxorubicin and cisplatin treatment compared to 5-flurouracil and the therapeutic doses must be degraded.展开更多
Objective:To explore the diagnostic value of PDCD4 on the degree of arterial stenosis in"blood stasis"coronary heart disease.Methods:Select 80 patients with coronary heart disease in the Second Cardiovascula...Objective:To explore the diagnostic value of PDCD4 on the degree of arterial stenosis in"blood stasis"coronary heart disease.Methods:Select 80 patients with coronary heart disease in the Second Cardiovascular Zone of the First Affiliated Hospital of Guangxi University of Traditional Chinese Medicine in April 2020,and divide them into the"phlegm toxin"group(n=40)and the"phlegm stasis"group(n=40)based on the dialectics of traditional Chinese medicine.).Record the gender,age,smoking,and alcohol consumption of the subjects between the two groups,and detect their white blood cell count,neutrophil count,platelet count,platelet volume,platelet distribution width,blood creatinine,uric acid,cystatin,and fibrin The expression levels of original,high-sensitivity C-reactive protein,D-dimer,total cholesterol,triglycerides,high-density lipoprotein,low-density lipoprotein,apolipoprotein a,apolipoprotein b,and PDCD4.Multivariate logistic regression analysis was used to screen out the risk factors that affect coronary plaque formation,and the receiver operating characteristic(ROC)curve of each index was established to evaluate the severity of coronary stenosis in patients with stasis coronary heart disease by each index and combined index Diagnostic efficiency.Results:The two groups of patients were tested in terms of gender,age,smoking,drinking,triglycerides,cholesterol,high-density lipoprotein,low-density lipoprotein,apolipoprotein-a,apolipoprotein-b,white blood cell count,neutrophil The cell count,platelet count,platelet volume width and platelet distribution width were not statistically significant(P>0.05);the expression levels of hypersensitivity-C-reactive protein,serum creatinine,cystatin,uric acid and PDCD4 were statistically significant between the two groups Difference(P<0.05),and the corresponding hypersensitivity-C-reactive protein,creatinine,cystatin,uric acid and PDCD4 expression levels in the blood stasis group were higher than those in the phlegm blood stasis group.After multivariate logistic regression analysis,the level of PDCD4 in peripheral blood[OR=31.088,95%CI(2.498,3.869)]was an independent influencing factor of the"stagnation"type of coronary heart disease,and PDCD4 was diagnosed as the"stagnation"type of coronary heart disease The area under the ROC curve(AUC)is 88.6%,95%CI(1.894,2.532)(P=0.29);the level of PDCD4 in peripheral blood is positively correlated with the number and severity of coronary artery disease,the number of coronary artery disease and stenosis The greater the degree,the higher the detection value of PDCD4,(P<0.05).Conclusion:The expression level of PDCD4 in peripheral blood is closely related to the subtype of"stasis toxin"and the severity of coronary vascular stenosis.It can be used as a quantitative diagnostic index for the diagnosis of"stasis toxin"coronary heart disease and the severity of coronary vascular stenosis.展开更多
Novel coronavirus infection not only damages lung function,but also causes myocardial injury,elevated myocardial enzymes and heart failure,especially for patients with basic heart diseases who develop COVID-19,the fir...Novel coronavirus infection not only damages lung function,but also causes myocardial injury,elevated myocardial enzymes and heart failure,especially for patients with basic heart diseases who develop COVID-19,the first consideration should be the protection of cardiac function.Based on the theory of intermingled phlegm,blood stasis and toxin of heart disease put forward by Master Lei Zhongyi,the dialectical treatment thinking of COVID-19 patients from the concept of damage of phlegm,blood stasis and toxin to the heart were discussed.During the diagnosis,critical stage and recovery period of COVID-19,expectorant and blood-activating agents,heat and detoxification agents can be added to promote lung and asthma,free Bizheng and remove blood stasis,calm the heart and calm the mind,and promote the recovery of cardiopulmonary functions.展开更多
Objective To summarize preservation measures of donor’s heart and lung,and postoperative imrnunotherapy,as well as clinical experience of discrimination and management for graft rejection. Methods Clinical data of 2 ...Objective To summarize preservation measures of donor’s heart and lung,and postoperative imrnunotherapy,as well as clinical experience of discrimination and management for graft rejection. Methods Clinical data of 2 cases of heart - lung transplantation in our depart-展开更多
BACKGROUND Despite sharing similar pathogenic factors,cancer and coronary heart disease(CHD)occur in comparable populations at similar ages and possess similar susceptibility factors.Consequently,it is increasingly co...BACKGROUND Despite sharing similar pathogenic factors,cancer and coronary heart disease(CHD)occur in comparable populations at similar ages and possess similar susceptibility factors.Consequently,it is increasingly commonplace for patients to experience the simultaneous occurrence of cancer and CHD,a trend that is steadily rising.AIM To determine the impacts of continuing care on lung cancer patients with CHD following percutaneous coronary intervention(PCI).METHODS There were 94 lung cancer patients with CHD following PCI who were randomly assigned to the intervention group(n=38)and the control group(n=41).In the intervention group,continuing care was provided,while in the control group,routine care was provided.An evaluation of cardiac and pulmonary function,medication compliance,a 6-min walk test,and patient quality of life was performed.RESULTS Differences between the two groups were significant in left ventricular ejection fraction,6-min walk test,oxygen uptake,quality of life and medication compliance(P<0.05).In comparison with the control group,the enhancement in the intervention group was more significant.The intervention group had more patients with high medication compliance than the control group,with a statistically significant difference(P<0.05).CONCLUSION After undergoing PCI,lung patients with CHD could benefit from continued care in terms of cardiac and pulmonary function,medications compliance,and quality of life.展开更多
In this review,the databases searched were PubMed and Web of Science.It is believed that the main causes of acute lung injury(ALI)and acute respiratory distress syndrome(ARDS)are inflammatory response disorders,excess...In this review,the databases searched were PubMed and Web of Science.It is believed that the main causes of acute lung injury(ALI)and acute respiratory distress syndrome(ARDS)are inflammatory response disorders,excessive oxidative stress,cell death,endoplasmic reticulum stress,coagulation dysfunction,and weakened aquaporin function.展开更多
Background:Lung Adenocarcinoma(LUAD)is the leading cause of death from lung cancer.Cuproptosis is the latest discovered way of programmed cell death,and Cuproptosis-Related Gene(CRG)is associated with the risk of LUAD...Background:Lung Adenocarcinoma(LUAD)is the leading cause of death from lung cancer.Cuproptosis is the latest discovered way of programmed cell death,and Cuproptosis-Related Gene(CRG)is associated with the risk of LUAD.At present,there are few research of LUAD and Cuproptosis focuses on Long non-coding RNA(LncRNA).As genomics advances,LncRNA emerges as a potential target for understanding tumor progression and prognosis,offering prospects for biological targeted therapy.Therefore,this study provides new biomarkers and therapeutic targets for LUAD from the perspective of LncRNA.Methods:Gene expression,clinical outcome and gene mutation data of LUAD patients were downloaded from TCGA database.Spearman correlation was used to analyze the correlation between LncRNA and CRG.Univariate Cox,multivariate Cox and LASSO Cox regression analysis were used to construct a prognostic model of Cuproptosis-LncRNAs.GO and KEGG enrichment and immune function analysis were performed on differentially expressed genes between different risk groups.Then,immune escape analysis was performed on LUAD patients with different TIDE score.Finally,drug sensitivity analysis was performed on these differentially expressed genes.Results:A total of 2244 Cuproptosis-LncRNAs were found.Through the application of univariate Cox regression analysis,multivariate Cox regression analysis,and LASSO Cox regression analysis,a prognostic model was developed,integrating 15 Cuproptosis-LncRNAs to assess the risk of mortality.Following that,the model underwent assessment through risk score analysis,Kaplan-Meier survival analysis,risk distribution,and evaluation of survival outcomes.The results revealed an AUC value of 0.755 for the model,surpassing the AUC of other clinical pathological features.The results of KEGG analysis showed that the differentially expressed genes in different model groups were mainly involved in Amoebiasis,Fat digestion and absorption,and other signaling pathways.The results of TMB showed that the prognostic model of TMB combined with risk score could well evaluate the prognosis of patients.The TIDE scores did not exhibit a notable distinction between the two risk models.Analysis of drug sensitivity revealed that individuals in the low-risk category demonstrated greater responsiveness to 5-Fluorouracil,Axitinib,Bexarotene,and other drugs compared to those in the high-risk group.Conclusion:Our research offers a valuable reference for predicting the prognosis of LUAD,contributing to a better understanding of the future elucidation of the process and mechanism of Cuproptosis-LncRNAs in LUAD.展开更多
Despite a record setting number of heart transplants performed annually,the national donor shortage continues to plague transplant teams across the United States.Here we describe the barriers to adaptation of numerous...Despite a record setting number of heart transplants performed annually,the national donor shortage continues to plague transplant teams across the United States.Here we describe the barriers to adaptation of numerous“non-traditional”orthotopic heart transplant donor characteristics including donors with hepatitis C virus,those meeting criteria for donation after cardiac death,donors with coronavirus disease 19 infection,donors with the human immunodeficiency virus,and grafts with left ventricular systolic dysfunction.Our center’s objective was to increase our transplant volume by expanding our donor pool from“traditional”donors to these“non-traditional”donors.We detail how medical advances such as certain laboratory studies,pharmacologic interventions,and organ care systems have allowed our center to expand the donor pool thereby increasing transplantation volume without adverse effects on outcomes.展开更多
Objective: To evaluate the population attributable risks (PARs) between cigarette smoking and deaths of all causes, all cancers, lung cancer and other chronic diseases in urban Shanghai. Methods: In total, 61,480 ...Objective: To evaluate the population attributable risks (PARs) between cigarette smoking and deaths of all causes, all cancers, lung cancer and other chronic diseases in urban Shanghai. Methods: In total, 61,480 men aged 40-74 years from 2002 to 2006 and 74,941 women aged 40-70 years from 1997 to 2000 were recruited to undergo baseline surveys in urban Shanghai, with response rates of 74.0% and 92.3%, respectively. A Cox proportional hazards regression model was used to estimate relative risks (RRs) and 95% confidence intervals (95% CIs) of deaths associated with cigarette smoking. PARs and 95 % CIs for deaths were estimated from smoking exposure rates and the estimated RRs. Results: Cigarette smoking was responsible for 23.9% (95% CI: 19.4-28.3%) and 2.4% (95% Ch 1.6- 3.2%) of all deaths in men and women, respectively, in our study population. Respiratory disease had the highest PAR in men [37.5% (95% CI: 21.5-51.6%)], followed by cancer [31.3% (95% Ch 24.6-37.7%)] and cardiovascular disease (CVD) [24.1% (95% CI: 16.7-31.2%)]. While the top three PARs were 12.7% (95% CI: 6.1-19.3%), 4.0% (95% CI: 2.4-5.6%), and 1.1% (95% CI: 0.0-2.3%), for respiratory disease, CVD, and cancer, respectively in women. For deaths of lung cancer, the PAR of smoking was 68.4% (95% CI: 58.2- 76.5%) in men. Conclusions: In urban Shanghai, 23.9% and 2.4% of all deaths in men and women could have been prevented if no people had smoked in the area. Effective control programs against cigarette smoking should be strongly advocated to reduce the increasing smoking-related death burden.展开更多
Objective To investigate the expression and regulation of programmed cell death protein 1(PD1),B lymphocyte and T lymphocyte attenuator(BTLA)in peripheral blood of patients with non-small cell lung cancer(NSCLC);to ex...Objective To investigate the expression and regulation of programmed cell death protein 1(PD1),B lymphocyte and T lymphocyte attenuator(BTLA)in peripheral blood of patients with non-small cell lung cancer(NSCLC);to examine the correlation of the mRNA levels between PD and BTLA in NSCLC.Methods Flow cytometry was used to detect the expression of PD1 and BTLA on the surfaces of CD8^+T cells andγδ+T cells in the peripheral blood samples collected from 32 in-patients with stage IV NSCLC and 30 healthy individuals.We compared the expression of PD1 and BTLA on the surfaces ofγδ+T cells in the NSCLC patients with bone metastasis before and after the treatment of zoledronic acid.The correlations of PD1 and BTLA,as well as their ligands were analyzed using Pearson correlation analysis with the cBioPortal data platform.Results The frequency of PD1 on the surfaces of CD8^+T cells was significantly higher than that of theγδT cells in both healthy controls(t=2.324,P=0.024)and NSCLC patients(t=2.498,P=0.015).The frequency of PD1 on CD8^+T cells,rather than onγδ+T cells,was significantly upregulated in advanced NSCLC patients compared with that in healthy controls(t=4.829,P<0.001).The PD1+BTLA+γδT cells of the healthy controls were significantly lower than that of the NSCLC patients(t=2.422,P=0.0185).No differences in percentage of PD1+γδ+and BTLA+γδ+T cells were observed in 7 NSCLC patients with bone metastasis before and after zoledronic acid treatment.PD1 was positively correlated with BTLA in both lung adenocarcinoma(r=0.54;P<0.05)and lung squamous cell carcinoma(r=0.78;P<0.05).Conclusions The upregulation of co-inhibitory molecules occurs on the surfaces of both CD8^+T cells andγδT cells in advanced NSCLC,suggesting that these molecules were involved in regulating the inactivation of CD8^+T cells andγδ+T cells,immune escape and tumor invasion.展开更多
Influenza and other respiratory viral infections account for 80%-90% of infectious pathologies. Influenza A (H5N1) virus has an apparent pneumotropism, and therefore the lung compartment of mononuclear phagocyte syste...Influenza and other respiratory viral infections account for 80%-90% of infectious pathologies. Influenza A (H5N1) virus has an apparent pneumotropism, and therefore the lung compartment of mononuclear phagocyte system plays an important role in antiviral immunity. Lung macrophages are active phagocytes expressing variety of antiviral factors. The investigation of morphofunctional status of lung macrophages and evaluation of their role in mammal antiviral response in a mouse model were performed within the study. Methods: Light microscopy using standard hematoxylin-eosin, and Van-Gizon’s picrofuchsin staining. Immunohistochemistry using influenza A antigen marker specific primary antibodies, myeloperoxidase, cathepsin D, lysozyme, NO synthase, pro-inflammatory cytokines, cells of CD68 macrophage lineage, PCNA proliferative activity. Morphometric and statistical analysis. Results: Influenza A virus antigen was detected in lung macrophages starting from day 1 to day 14 of infection which corresponds with the beginning of convalescence and may be suggestive of prolonged persistence of virus. On the one hand, the cytopathic effects of the virus lead to lung macrophages death mainly via apoptosis through activation of caspase cascade, including caspase-3 and caspase-9. On the other hand, the observed activation of PCNA proliferation marker, perhaps, allows to support the pool of lung macrophages not only by their recruitment from bone marrow but also by their proliferation in situ. The increase of mononuclear phagocyte system cells expressing antiviral factors depended on the stage of infection. In the early stage, there was an increase of number of cells expressing lysozyme, myeloperoxidase, cathepsin D, endothelial NO synthase (eNOS) followed by the increase of number of macrophages expressing inducible NO synthase (iNOS), pro-inflammatory cytokines and interleukins.展开更多
This report introduced and summarized the nursing care experience for a senior patient with lung cancer and developed programmed cell death protein 1(PD-1)immunotherapy-related myocarditis combined with coronary heart...This report introduced and summarized the nursing care experience for a senior patient with lung cancer and developed programmed cell death protein 1(PD-1)immunotherapy-related myocarditis combined with coronary heart disease(CHD)after receiving said treatment.In this case,immune myocarditis with CHD occurred shortly after implementing the PD-1 immunotherapy,yet the patient presented no clinical symptoms.Frequent nursing attention and close observation are so required for monitoring the patient’s status and updating the physicians for a swift control of the myocarditis.For this case,nursing care procedures vital for the successful recovery of the patient included condition observation,position management,pre-and postcoronary angiography care,infection prevention,hemorrhage prevention,venous access port maintenance,pain care,trachea care,psychological care,diet care,environment management,and health education.After receiving effective,successful treatment and care,the patient was discharged after 13 days of treatment with generally satisfying overall conditions.展开更多
Objective:To study the changes in PD-1/PD-L1 pathway function in non-small cell lung cancer tissue before and after125I seed implantation.Methods: Patients with advanced non-small cell lung cancer who were treated in ...Objective:To study the changes in PD-1/PD-L1 pathway function in non-small cell lung cancer tissue before and after125I seed implantation.Methods: Patients with advanced non-small cell lung cancer who were treated in Dongguan Kanghua Hospital between May 2014 and April 2017 were selected and randomly divided into125I group and control group who received125I seed implantation combined bronchial artery infusion chemotherapy embolism and bronchial artery infusion chemotherapy embolism alone respectively. The expression of PD-1, PD-L1, transcription factors and tumor suppressor genes in lung cancer lesions were determined before and after treatment.Results: PD-1, PD-L1 and Foxp3 mRNA expression and protein expression in lesions of both groups after treatment were significantly lower than those before treatment while T-bet, PTEN, TCF21 and LATS1 mRNA expression and protein expression were significantly higher than those before treatment, and PD-1, PD-L1 and Foxp3 mRNA expression and protein expression in lesions of125I group after treatment were significantly lower than those of control group while T-bet, PTEN, TCF21 and LATS1 mRNA expression and protein expression were significantly higher than those of control group. Conclusion:125I seed implantation treatment of advanced non-small cell lung cancer can inhibit the immune escape of cancer cells mediated by PD-1/PD-L1 pathway, and promote the apoptosis of cancer cells.展开更多
The development of the heart-lung machine made repair of intracardiac lesions possible. One of the key requirements of the heart-lung machine was anticoagulation. Heparin was discovered by a medical student, Jay McLea...The development of the heart-lung machine made repair of intracardiac lesions possible. One of the key requirements of the heart-lung machine was anticoagulation. Heparin was discovered by a medical student, Jay McLean, working in the laboratory of Dr. William Howell at Johns Hopkins. John Gibbon contributed more to the successful development of the heart-lung machine than anyone else. His interest began as a young doctor since 1930s. Gibbon's work on the heart-lung machine took place over the next 20 years in laboratories at Massachusetts General Hospital, the University of Pennsylvania, and Thomas Jefferson University In 1937, he reported the first successful demonstration that life could be maintained by an artificial heart and lung, and the native heart and lungs could resume fimction. After World War II, Dr. Gibbon resumed his work and received support from IBM to build a heart-lung machine on a more sophisticated scale. Eventually, the team developed a larger oxygenator that the IBM engineers incorporated into a new machine. On May 6, 1953, Dr. Gibbon performed the first successful operation using an extracorporeal circuit on an 18-year-old girl with a large atrial septal defect. It wasn't until 1958, when a system that involved bubbling blood was perfected, that "heart-lung" machines came of age. Despite so many chill winds and cold rains, "heart-lung" machine, the budding rose of surgery, was eventually blossom brightly in the radiant rays of sunlight. John Gibbon's dream had become a reality. His work serves as an important example to surgeons who are struggling today with the surgical therapies and technologies of tomorrow.展开更多
基金National Natural Science Foundation of China(Grant No.81273297)Shenyang Science and Technology Plan.Public Health R&D Special Project(21-173-9-67).
文摘Advanced LUAD shows limited response to treatment including immune therapy.With the development of sequencing omics,it is urgent to combine high-throughput multi-omics data to identify new immune checkpoint therapeutic response markers.Using GSE72094(n=386)and GSE31210(n=226)gene expression profile data in the GEO database,we identified genes associated with lung adenocarcinoma(LUAD)death using tools such as“edgeR”and“maftools”and visualized the characteristics of these genes using the“circlize”R package.We constructed a prognostic model based on death-related genes and optimized the model using LASSO-Cox regression methods.By calculating the cell death index(CDI)of each individual,we divided LUAD patients into high and low CDI groups and examined the relationship between CDI and overall survival time by principal component analysis(PCA)and Kaplan-Meier analysis.We also used the“ConsensusClusterPlus”tool for unsupervised clustering of LUAD subtypes based on model genes.In addition,we collected data on the expression of immunomodulatory genes and model genes for each cohort and performed tumor microenvironment analyses.We also used the TIDE algorithm to predict immunotherapy responses in the CDI cohort.Finally,we studied the effect of PRKCD on the proliferation and migration of LUAD cells through cell culture experiments.The study utilized the TCGA-LUAD cohort(n=493)and identified 2,901 genes that are differentially expressed in patients with LUAD.Through KEGG and GO enrichment analysis,these genes were found to be involved in a wide range of biological pathways.The study also used univariate Cox regression models and LASSO regression analyses to identify 17 candidate genes that were best associated with mortality prognostic risk scores.By comparing the overall survival(OS)outcomes of patients with different CDI values,it was found that increased CDI levels were significantly associated with lower OS rates.In addition,the study used unsupervised cluster analysis to divide 115 LUAD patients into two distinct clusters with significant differences in OS timing.Finally,a prognostic indicator called CDI was established and its feasibility as an independent prognostic indicator was evaluated by Cox proportional risk regression analysis.The immunotherapy efficacy was more sensitive in the group with high expression of programmed cell death models.Relationship between programmed cell death(PCD)signature models and drug reactivity.After evaluating the median inhibitory concentration(IC50)of various drugs in LUAD samples,statistically significant differences in IC50 values were found in cohorts with high and low CDI status.Specifically,Gefitinib and Lapatinib had higher IC50 values in the high-CDI cohort,while Olaparib,Oxaliplatin,SB216763,and Axitinib had lower values.These results suggest that individuals with high CDI levels are sensitive to tyrosine kinase inhibitors and may be resistant to conventional chemotherapy.Therefore,this study constructed a gene model that can evaluate patient immunotherapy by using programmed cell death-related genes based on muti-omics.The CDI index composed of these programmed cell death-related genes reveals the heterogeneity of lung adenocarcinoma tumors and serves as a prognostic indicator for patients.
文摘The description in the abstract lacks clear logic and a comprehensive summary of this study, so please revise and improve it according to the design theme and main content of this study, and describe it in the order of (research background), purpose/aim, method, results and conclusions. The introduction of the abstract and preface is rather lengthy, but the summary of the whole study and the presentation of the research background are not perfect (mainly because the logic of the context is not clear and orderly), so it will appear a bit messy. Hope to be able to modify (this has been mentioned in the preliminary opinion). Cardiovascular events (CVE) pose a significant threat to individuals with end-stage renal disease (ESRD), yet these patients are often excluded from cardiovascular clinical trials, leaving prognostic factors associated with CVE in ESRD patients largely unexplored. Recent human studies have demonstrated elevated circulating aldosterone levels in ESRD patients, correlating with left ventricular hypertrophy. Additionally, animal models have shown improvements in uremic cardiomyopathy with spironolactone therapy, prompting interest in assessing the efficacy of spironolactone or eplerenone in reducing mortality and improving cardiovascular function in dialysis patients. Clinicians have historically been cautious about prescribing mineralocorticoid receptor antagonists (MRAs) to congestive heart failure patients with chronic kidney disease (CKD) due to hyperkalemia risk. However, the emergence of finerenone, a novel MR antagonist with a favorable safety profile and lower hyperkalemia risk, has renewed interest in MRA therapy in this population. Heart disease, including coronary artery disease, hypertension, and left ventricular failure, is alarmingly prevalent in dialysis patients, contributing significantly to elevated mortality rates compared to the general population. Arterial stiffness, as indicated by pulse wave velocity (PWV), progressively worsens with advancing CKD stages, peaking in severity among ESRD patients undergoing dialysis. High PWV serves as a crucial risk stratification tool in ESRD. Elevated NT-proBNP and BNP levels in ESRD patients are well-documented, with significant associations observed between baseline peptide concentrations and cardiovascular morbidity and mortality. By incorporating finerenone into our study, we aim to investigate its potential benefits in reducing arterial stiffness, lowering blood pressure, and ultimately mitigating heart-related mortality among hemodialysis patients. This study holds substantial implications for hypertension and cardiovascular risk management in this vulnerable patient population. Eligible participants must have been on chronic hemodialysis for at least three months, with ACE inhibitors or angiotensin receptor blockers included in their therapy at maximum tolerable doses. Serum potassium levels 5.7 mmol/L, left ventricular ejection fraction 50%, and PWV higher than age-estimated values are also prerequisites for study entry. Randomized allocation will be conducted using a permuted block design, stratified by center, with allocation communicated via signed study forms during initial examinations. All steps of this research will be conducted in accordance with the principles of the Helsinki Declaration.
文摘BACKGROUND Metastatic pancreatic ductal adenocarcinoma(PDAC)is a lethal malignancy with dispiriting survival data.Immunotherapy is a promising approach to many cancer types,but achieves poor outcomes in advanced PDAC due to its immunosuppressive tumor microenvironment.We describe a case of metastatic PDAC effectively treated with pembrolizumab.CASE SUMMARY We report the case of a 67-year-old woman with unresectable locally advanced PDAC,treated with gemcitabine plus nab-paclitaxel followed by radiotherapy plus capecitabine.At nine months,pancreatic tumor progression was observed at the level of the hepatic hilum with the appearance of a new pulmonary nodule suggestive of a second primary,confirmed by left lung biopsy.Systemic immunotherapy was then initiated with pembrolizumab,an immune checkpoint inhibitor targeting programmed cell death protein-1 that covers the two tumor types.The patient showed a complete metabolic response that was maintained throughout the treatment.The patient continues to be disease-free at 5.6 years since the start of immunotherapy.CONCLUSION These results suggest that the administration of pembrolizumab after chemoradiotherapy has a beneficial effect in patients with metastatic PDAC.To our knowledge,this is the first reported case of a patient with metastatic PDAC and metastatic lung cancer showing such a long-lasting complete response after pembrolizumab treatment without curative surgery.Further studies are required to determine biomarkers that identify PDAC patients most likely to benefit from this immunotherapy.
文摘The recent discovery of immune checkpoints inhibitors, especially anti-programmed cell death protein 1(PD-1)and anti-programmed cell death protein ligand 1(PD-L1) monoclonal antibodies, has opened new scenarios in the management of non-small cell lung cancer(NSCLC) and this new class of drugs has achieved a rapid development in the treatment of this disease. However, considering the costs of these drugs and the fact that only a subset of patients experience long-term disease control, the identification of predictive biomarkers for the selection of candidates suitable for treatment has become a priority. The research focused mainly on the expression of the PD-L1 receptor on both tumor cells and/or immune infiltrates determined by immunohistochemistry(IHC). However, different checkpoint inhibitors were tested, different IHC assays were used, different targets were considered(tumor cells, immune infiltrates or both) and different expression thresholds were employed in clinical trials. In some trials the assay was used prospectively to select the patients, while in other trials it was evaluated retrospectively. Some confusion emerges, which makes it difficult to easily compare the literature data and to translate them in practice management. This mini-review shows the possibilities and pitfalls of the PD-L1 expression to predict the activity and efficacy of anti PD1/PD-L1 monoclonal antibodies in the treatment of NSCLC.
基金supported by the capital characteristic clinic project of China [Z151100004015071]National Natural Science Foundation of China [51573211]ruiyi emergency medical research fund of China [R2017013]
文摘Objective A new technique of transthoracic lung ultrasonography(TLS) has emerged and demonstrated promising results in acute heart failure diagnosis at an early stage. However, the diagnostic value of ultrasound lung comets(ULCs) for acute heart failure(AHF) performed in busy emergency department(ED) is uncertain. The present meta-analysis aimed to assess the diagnostic efficiency of ULCs in AHF. Methods We conducted a search on online journal databases to collect the data on TLS performed for diagnosing AHF published up to the end of July 2017. The sensitivity, specificity, positive likelihood ratio(PLR), negative likelihood ratio(NLR), and summary receiver operating characteristic(SROC) curve were calculated. The post-test probability of AHF was calculated by using Bayes analysis. Results We enrolled a total of 15 studies involving 3,309 patients. The value of sensitivity, specificity, PLR, NLR, DOR, area under the SROC curve, and Q* index was 85%, 91%, 8.94, 0.14, 67.24, 0.9587, and 0.9026, respectively. We detected significant heterogeneity among included studies, and therefore, all these results were analyzed under the random-effect model. We also explored possible sources of heterogeneity among the studies by using meta-regression analysis. Results suggest that the time interval between patient’s admission to bedside TLS examination was closely related to TLS accuracy. Conclusion This meta-analysis demonstrated that detecting ULCs is a convenient bedside tool and has high accuracy for early AHF diagnosis in ED. TLS could be recommended to be applied for early diagnosis of AHF in ED.
文摘Hydrostatic pulmonary edema is as an abnormal in-crease in extravascular water secondary to elevatedpressure in the pulmonary circulation, due to conges-tive heart failure or intravascular volume overload.Diagnosis of hydrostatic pulmonary edema is usuallybased on clinical signs associated to conventional ra-diography findings. Interpretation of radiologic signsof cardiogenic pulmonary edema are often question-able and subject. For a bedside prompt evaluation,lung ultrasound(LUS) may assess pulmonary conges-tion through the evaluation of vertical reverberationartifacts, known as B-lines. These artifacts are relatedto multiple minimal acoustic interfaces between smallwater-rich structures and alveolar air, as it happens incase of thickened interlobular septa due to increase of extravascular lung water. The number, diffusion and in-tensity of B lines correlates with both the radiologic andinvasive estimate of extravascular lung water. The inte-gration of conventional chest radiograph with LUS canbe very helpful to obtain the correct diagnosis. Com-puted tomography(CT) is of limited use in the work upof cardiogenic pulmonary edema, due to its high cost,little use in the emergencies and radiation exposure.However, a deep knowledge of CT signs of pulmonaryedema is crucial when other similar pulmonary condi-tions may occasionally be in the differential diagnosis.
文摘Aim: Recently, there is an increased average of developing cancers. Though, the chemotherapeutic-treatment is unfavorable during pregnancy due to its harmful effects on developing fetuses, physicians have two ways to minimize these effects either by termination of the pregnancy or minimizing its side effects. The present work aimed to illustrate the susceptibility of cardiac, lung and dorsal aorta function to the widely applicable drugs doxorubicin and cisplatin as well as 5-flurouracil. Materials and Methods: Mother albino rats were arranged into four-groups (control, doxorubicin, cisplatin and 5-flurouracil-treated groups). Each pregnant rat received intraperitoneal administration of 0.2 mg/kg body weight at 10th and 14th day of gestation and sacrificed at parturition (two doses). At parturition, serum of mother rats used to assess troponin I, heat shock protein 70, 8-hydroxydeoxyguanosine, vascular endothelial growth factor and adhesion molecules (ICAM-1 & VCAM-1). Isoenzyme electrophoresis of alkaline and acid phosphatases, glucose-6-phosphate dehydrogenase and lactic dehydrogenase were estimated in serum, myocardium and dorsal aorta of mother rats. The myocardium and lung were processed for histopathological investigations for both mothers and their offspring. Single strand (comet assay) and double strand DNA damage were carried out in heart and dorsal aorta of mother rats. Results: The present finding revealed that there are detected alterations of myocardial markers and lung amino acid metabolism as well as disruption of myocardial isoenzymes. DNA damage of myocardium and dorsal aorta were observed. Conclusions: The authors concluded that the metabolic activity of heart and lung is highly susceptible to doxorubicin and cisplatin treatment compared to 5-flurouracil and the therapeutic doses must be degraded.
基金Regional Fund Project of National Natural Science Foundation of China(No.8196086181460712)+1 种基金Guangxi Science Key Research and Development Program(No.AB19110006)Guangxi Support Project for Graduate Education Innovation(No.YCXJ2021052)。
文摘Objective:To explore the diagnostic value of PDCD4 on the degree of arterial stenosis in"blood stasis"coronary heart disease.Methods:Select 80 patients with coronary heart disease in the Second Cardiovascular Zone of the First Affiliated Hospital of Guangxi University of Traditional Chinese Medicine in April 2020,and divide them into the"phlegm toxin"group(n=40)and the"phlegm stasis"group(n=40)based on the dialectics of traditional Chinese medicine.).Record the gender,age,smoking,and alcohol consumption of the subjects between the two groups,and detect their white blood cell count,neutrophil count,platelet count,platelet volume,platelet distribution width,blood creatinine,uric acid,cystatin,and fibrin The expression levels of original,high-sensitivity C-reactive protein,D-dimer,total cholesterol,triglycerides,high-density lipoprotein,low-density lipoprotein,apolipoprotein a,apolipoprotein b,and PDCD4.Multivariate logistic regression analysis was used to screen out the risk factors that affect coronary plaque formation,and the receiver operating characteristic(ROC)curve of each index was established to evaluate the severity of coronary stenosis in patients with stasis coronary heart disease by each index and combined index Diagnostic efficiency.Results:The two groups of patients were tested in terms of gender,age,smoking,drinking,triglycerides,cholesterol,high-density lipoprotein,low-density lipoprotein,apolipoprotein-a,apolipoprotein-b,white blood cell count,neutrophil The cell count,platelet count,platelet volume width and platelet distribution width were not statistically significant(P>0.05);the expression levels of hypersensitivity-C-reactive protein,serum creatinine,cystatin,uric acid and PDCD4 were statistically significant between the two groups Difference(P<0.05),and the corresponding hypersensitivity-C-reactive protein,creatinine,cystatin,uric acid and PDCD4 expression levels in the blood stasis group were higher than those in the phlegm blood stasis group.After multivariate logistic regression analysis,the level of PDCD4 in peripheral blood[OR=31.088,95%CI(2.498,3.869)]was an independent influencing factor of the"stagnation"type of coronary heart disease,and PDCD4 was diagnosed as the"stagnation"type of coronary heart disease The area under the ROC curve(AUC)is 88.6%,95%CI(1.894,2.532)(P=0.29);the level of PDCD4 in peripheral blood is positively correlated with the number and severity of coronary artery disease,the number of coronary artery disease and stenosis The greater the degree,the higher the detection value of PDCD4,(P<0.05).Conclusion:The expression level of PDCD4 in peripheral blood is closely related to the subtype of"stasis toxin"and the severity of coronary vascular stenosis.It can be used as a quantitative diagnostic index for the diagnosis of"stasis toxin"coronary heart disease and the severity of coronary vascular stenosis.
基金the Project of the Third National Master of Traditional Chinese Medicine of National Administration of Traditional Chinese Medicine/National Famous Traditional Chinese Medicine Inheritance Studio Construction(No.119(2018)of Education Letter of the State Office of Traditional Chinese Medicine).
文摘Novel coronavirus infection not only damages lung function,but also causes myocardial injury,elevated myocardial enzymes and heart failure,especially for patients with basic heart diseases who develop COVID-19,the first consideration should be the protection of cardiac function.Based on the theory of intermingled phlegm,blood stasis and toxin of heart disease put forward by Master Lei Zhongyi,the dialectical treatment thinking of COVID-19 patients from the concept of damage of phlegm,blood stasis and toxin to the heart were discussed.During the diagnosis,critical stage and recovery period of COVID-19,expectorant and blood-activating agents,heat and detoxification agents can be added to promote lung and asthma,free Bizheng and remove blood stasis,calm the heart and calm the mind,and promote the recovery of cardiopulmonary functions.
文摘Objective To summarize preservation measures of donor’s heart and lung,and postoperative imrnunotherapy,as well as clinical experience of discrimination and management for graft rejection. Methods Clinical data of 2 cases of heart - lung transplantation in our depart-
文摘BACKGROUND Despite sharing similar pathogenic factors,cancer and coronary heart disease(CHD)occur in comparable populations at similar ages and possess similar susceptibility factors.Consequently,it is increasingly commonplace for patients to experience the simultaneous occurrence of cancer and CHD,a trend that is steadily rising.AIM To determine the impacts of continuing care on lung cancer patients with CHD following percutaneous coronary intervention(PCI).METHODS There were 94 lung cancer patients with CHD following PCI who were randomly assigned to the intervention group(n=38)and the control group(n=41).In the intervention group,continuing care was provided,while in the control group,routine care was provided.An evaluation of cardiac and pulmonary function,medication compliance,a 6-min walk test,and patient quality of life was performed.RESULTS Differences between the two groups were significant in left ventricular ejection fraction,6-min walk test,oxygen uptake,quality of life and medication compliance(P<0.05).In comparison with the control group,the enhancement in the intervention group was more significant.The intervention group had more patients with high medication compliance than the control group,with a statistically significant difference(P<0.05).CONCLUSION After undergoing PCI,lung patients with CHD could benefit from continued care in terms of cardiac and pulmonary function,medications compliance,and quality of life.
基金Yunnan Fundamental Research Projects(202201AU070167,202301AT070258)Yunnan Key Laboratory of Formulated Granules(202105AG070014).
文摘In this review,the databases searched were PubMed and Web of Science.It is believed that the main causes of acute lung injury(ALI)and acute respiratory distress syndrome(ARDS)are inflammatory response disorders,excessive oxidative stress,cell death,endoplasmic reticulum stress,coagulation dysfunction,and weakened aquaporin function.
文摘Background:Lung Adenocarcinoma(LUAD)is the leading cause of death from lung cancer.Cuproptosis is the latest discovered way of programmed cell death,and Cuproptosis-Related Gene(CRG)is associated with the risk of LUAD.At present,there are few research of LUAD and Cuproptosis focuses on Long non-coding RNA(LncRNA).As genomics advances,LncRNA emerges as a potential target for understanding tumor progression and prognosis,offering prospects for biological targeted therapy.Therefore,this study provides new biomarkers and therapeutic targets for LUAD from the perspective of LncRNA.Methods:Gene expression,clinical outcome and gene mutation data of LUAD patients were downloaded from TCGA database.Spearman correlation was used to analyze the correlation between LncRNA and CRG.Univariate Cox,multivariate Cox and LASSO Cox regression analysis were used to construct a prognostic model of Cuproptosis-LncRNAs.GO and KEGG enrichment and immune function analysis were performed on differentially expressed genes between different risk groups.Then,immune escape analysis was performed on LUAD patients with different TIDE score.Finally,drug sensitivity analysis was performed on these differentially expressed genes.Results:A total of 2244 Cuproptosis-LncRNAs were found.Through the application of univariate Cox regression analysis,multivariate Cox regression analysis,and LASSO Cox regression analysis,a prognostic model was developed,integrating 15 Cuproptosis-LncRNAs to assess the risk of mortality.Following that,the model underwent assessment through risk score analysis,Kaplan-Meier survival analysis,risk distribution,and evaluation of survival outcomes.The results revealed an AUC value of 0.755 for the model,surpassing the AUC of other clinical pathological features.The results of KEGG analysis showed that the differentially expressed genes in different model groups were mainly involved in Amoebiasis,Fat digestion and absorption,and other signaling pathways.The results of TMB showed that the prognostic model of TMB combined with risk score could well evaluate the prognosis of patients.The TIDE scores did not exhibit a notable distinction between the two risk models.Analysis of drug sensitivity revealed that individuals in the low-risk category demonstrated greater responsiveness to 5-Fluorouracil,Axitinib,Bexarotene,and other drugs compared to those in the high-risk group.Conclusion:Our research offers a valuable reference for predicting the prognosis of LUAD,contributing to a better understanding of the future elucidation of the process and mechanism of Cuproptosis-LncRNAs in LUAD.
文摘Despite a record setting number of heart transplants performed annually,the national donor shortage continues to plague transplant teams across the United States.Here we describe the barriers to adaptation of numerous“non-traditional”orthotopic heart transplant donor characteristics including donors with hepatitis C virus,those meeting criteria for donation after cardiac death,donors with coronavirus disease 19 infection,donors with the human immunodeficiency virus,and grafts with left ventricular systolic dysfunction.Our center’s objective was to increase our transplant volume by expanding our donor pool from“traditional”donors to these“non-traditional”donors.We detail how medical advances such as certain laboratory studies,pharmacologic interventions,and organ care systems have allowed our center to expand the donor pool thereby increasing transplantation volume without adverse effects on outcomes.
基金supported by the funds of Key Discipline and Specialty Foundation of Shanghai Municipal Commission of Health and Family Planningthe National Key Basic Research Program "973 project" (2015CB554000)grants from US National Institutes of Health (R37 CA070867, R01 CA82729, UM1CA173640, and UM1 CA182910)
文摘Objective: To evaluate the population attributable risks (PARs) between cigarette smoking and deaths of all causes, all cancers, lung cancer and other chronic diseases in urban Shanghai. Methods: In total, 61,480 men aged 40-74 years from 2002 to 2006 and 74,941 women aged 40-70 years from 1997 to 2000 were recruited to undergo baseline surveys in urban Shanghai, with response rates of 74.0% and 92.3%, respectively. A Cox proportional hazards regression model was used to estimate relative risks (RRs) and 95% confidence intervals (95% CIs) of deaths associated with cigarette smoking. PARs and 95 % CIs for deaths were estimated from smoking exposure rates and the estimated RRs. Results: Cigarette smoking was responsible for 23.9% (95% CI: 19.4-28.3%) and 2.4% (95% Ch 1.6- 3.2%) of all deaths in men and women, respectively, in our study population. Respiratory disease had the highest PAR in men [37.5% (95% CI: 21.5-51.6%)], followed by cancer [31.3% (95% Ch 24.6-37.7%)] and cardiovascular disease (CVD) [24.1% (95% CI: 16.7-31.2%)]. While the top three PARs were 12.7% (95% CI: 6.1-19.3%), 4.0% (95% CI: 2.4-5.6%), and 1.1% (95% CI: 0.0-2.3%), for respiratory disease, CVD, and cancer, respectively in women. For deaths of lung cancer, the PAR of smoking was 68.4% (95% CI: 58.2- 76.5%) in men. Conclusions: In urban Shanghai, 23.9% and 2.4% of all deaths in men and women could have been prevented if no people had smoked in the area. Effective control programs against cigarette smoking should be strongly advocated to reduce the increasing smoking-related death burden.
基金Fund supported by the Healthcare Technology Plan of Zhejiang Provincial Health Bureau(No.2016KYB292)the Technology Plan of Science and Technology Bureau of Jiaxing,Zhejiang province(No.2016AY23054)~~
文摘Objective To investigate the expression and regulation of programmed cell death protein 1(PD1),B lymphocyte and T lymphocyte attenuator(BTLA)in peripheral blood of patients with non-small cell lung cancer(NSCLC);to examine the correlation of the mRNA levels between PD and BTLA in NSCLC.Methods Flow cytometry was used to detect the expression of PD1 and BTLA on the surfaces of CD8^+T cells andγδ+T cells in the peripheral blood samples collected from 32 in-patients with stage IV NSCLC and 30 healthy individuals.We compared the expression of PD1 and BTLA on the surfaces ofγδ+T cells in the NSCLC patients with bone metastasis before and after the treatment of zoledronic acid.The correlations of PD1 and BTLA,as well as their ligands were analyzed using Pearson correlation analysis with the cBioPortal data platform.Results The frequency of PD1 on the surfaces of CD8^+T cells was significantly higher than that of theγδT cells in both healthy controls(t=2.324,P=0.024)and NSCLC patients(t=2.498,P=0.015).The frequency of PD1 on CD8^+T cells,rather than onγδ+T cells,was significantly upregulated in advanced NSCLC patients compared with that in healthy controls(t=4.829,P<0.001).The PD1+BTLA+γδT cells of the healthy controls were significantly lower than that of the NSCLC patients(t=2.422,P=0.0185).No differences in percentage of PD1+γδ+and BTLA+γδ+T cells were observed in 7 NSCLC patients with bone metastasis before and after zoledronic acid treatment.PD1 was positively correlated with BTLA in both lung adenocarcinoma(r=0.54;P<0.05)and lung squamous cell carcinoma(r=0.78;P<0.05).Conclusions The upregulation of co-inhibitory molecules occurs on the surfaces of both CD8^+T cells andγδT cells in advanced NSCLC,suggesting that these molecules were involved in regulating the inactivation of CD8^+T cells andγδ+T cells,immune escape and tumor invasion.
文摘Influenza and other respiratory viral infections account for 80%-90% of infectious pathologies. Influenza A (H5N1) virus has an apparent pneumotropism, and therefore the lung compartment of mononuclear phagocyte system plays an important role in antiviral immunity. Lung macrophages are active phagocytes expressing variety of antiviral factors. The investigation of morphofunctional status of lung macrophages and evaluation of their role in mammal antiviral response in a mouse model were performed within the study. Methods: Light microscopy using standard hematoxylin-eosin, and Van-Gizon’s picrofuchsin staining. Immunohistochemistry using influenza A antigen marker specific primary antibodies, myeloperoxidase, cathepsin D, lysozyme, NO synthase, pro-inflammatory cytokines, cells of CD68 macrophage lineage, PCNA proliferative activity. Morphometric and statistical analysis. Results: Influenza A virus antigen was detected in lung macrophages starting from day 1 to day 14 of infection which corresponds with the beginning of convalescence and may be suggestive of prolonged persistence of virus. On the one hand, the cytopathic effects of the virus lead to lung macrophages death mainly via apoptosis through activation of caspase cascade, including caspase-3 and caspase-9. On the other hand, the observed activation of PCNA proliferation marker, perhaps, allows to support the pool of lung macrophages not only by their recruitment from bone marrow but also by their proliferation in situ. The increase of mononuclear phagocyte system cells expressing antiviral factors depended on the stage of infection. In the early stage, there was an increase of number of cells expressing lysozyme, myeloperoxidase, cathepsin D, endothelial NO synthase (eNOS) followed by the increase of number of macrophages expressing inducible NO synthase (iNOS), pro-inflammatory cytokines and interleukins.
文摘This report introduced and summarized the nursing care experience for a senior patient with lung cancer and developed programmed cell death protein 1(PD-1)immunotherapy-related myocarditis combined with coronary heart disease(CHD)after receiving said treatment.In this case,immune myocarditis with CHD occurred shortly after implementing the PD-1 immunotherapy,yet the patient presented no clinical symptoms.Frequent nursing attention and close observation are so required for monitoring the patient’s status and updating the physicians for a swift control of the myocarditis.For this case,nursing care procedures vital for the successful recovery of the patient included condition observation,position management,pre-and postcoronary angiography care,infection prevention,hemorrhage prevention,venous access port maintenance,pain care,trachea care,psychological care,diet care,environment management,and health education.After receiving effective,successful treatment and care,the patient was discharged after 13 days of treatment with generally satisfying overall conditions.
文摘Objective:To study the changes in PD-1/PD-L1 pathway function in non-small cell lung cancer tissue before and after125I seed implantation.Methods: Patients with advanced non-small cell lung cancer who were treated in Dongguan Kanghua Hospital between May 2014 and April 2017 were selected and randomly divided into125I group and control group who received125I seed implantation combined bronchial artery infusion chemotherapy embolism and bronchial artery infusion chemotherapy embolism alone respectively. The expression of PD-1, PD-L1, transcription factors and tumor suppressor genes in lung cancer lesions were determined before and after treatment.Results: PD-1, PD-L1 and Foxp3 mRNA expression and protein expression in lesions of both groups after treatment were significantly lower than those before treatment while T-bet, PTEN, TCF21 and LATS1 mRNA expression and protein expression were significantly higher than those before treatment, and PD-1, PD-L1 and Foxp3 mRNA expression and protein expression in lesions of125I group after treatment were significantly lower than those of control group while T-bet, PTEN, TCF21 and LATS1 mRNA expression and protein expression were significantly higher than those of control group. Conclusion:125I seed implantation treatment of advanced non-small cell lung cancer can inhibit the immune escape of cancer cells mediated by PD-1/PD-L1 pathway, and promote the apoptosis of cancer cells.
文摘The development of the heart-lung machine made repair of intracardiac lesions possible. One of the key requirements of the heart-lung machine was anticoagulation. Heparin was discovered by a medical student, Jay McLean, working in the laboratory of Dr. William Howell at Johns Hopkins. John Gibbon contributed more to the successful development of the heart-lung machine than anyone else. His interest began as a young doctor since 1930s. Gibbon's work on the heart-lung machine took place over the next 20 years in laboratories at Massachusetts General Hospital, the University of Pennsylvania, and Thomas Jefferson University In 1937, he reported the first successful demonstration that life could be maintained by an artificial heart and lung, and the native heart and lungs could resume fimction. After World War II, Dr. Gibbon resumed his work and received support from IBM to build a heart-lung machine on a more sophisticated scale. Eventually, the team developed a larger oxygenator that the IBM engineers incorporated into a new machine. On May 6, 1953, Dr. Gibbon performed the first successful operation using an extracorporeal circuit on an 18-year-old girl with a large atrial septal defect. It wasn't until 1958, when a system that involved bubbling blood was perfected, that "heart-lung" machines came of age. Despite so many chill winds and cold rains, "heart-lung" machine, the budding rose of surgery, was eventually blossom brightly in the radiant rays of sunlight. John Gibbon's dream had become a reality. His work serves as an important example to surgeons who are struggling today with the surgical therapies and technologies of tomorrow.