Systemic Inflammatory Response Index (SIRI) is associated with all-cause mortality and cardiovascular mortality in population with chronic kidney disease: evidence from NHANES (2001-2018).

Objective: To examine the correlation between SIRI and the probability of cardiovascular mortality as well as all-cause mortality in individuals with chronic kidney disease. Methods: A cohort of 3,262 participants from the US National Health and Nutrition Examination Survey (NHANES) database were included in the study. We categorized participants into five groups based on the stage of chronic kidney disease. A weighted Cox regression model was applied to assess the relationship between SIRI and mortality. Subgroup analyses, Kaplan-Meier survival curves, and ROC curves were conducted. Additionally, restricted cubic spline analysis was employed to elucidate the detailed association between SIRI and hazard ratio (HR). Results: This study included a cohort of 3,262 individuals, of whom 1,535 were male (weighted proportion: 42%), and 2,216 were aged 60 or above (weighted proportion: 59%). Following adjustments for covariates like age, sex, race, and education, elevated SIRI remained a significant independent risk factor for cardiovascular mortality (HR=2.50, 95%CI: 1.62-3.84, p<0.001) and all-cause mortality (HR=3.02, 95%CI: 2.03-4.51, p<0.001) in CKD patients. The restricted cubic spline analysis indicated a nonlinear relationship between SIRI and cardiovascular mortality, with SIRI>1.2 identified as an independent risk factor for cardiovascular mortality in CKD patients. Conclusion: Heightened SIRI independently poses a risk for both all-cause and cardiovascular mortality in chronic kidney disease patients, with potentially heightened significance in the early stages (Stage I to Stage III) of chronic kidney disease.

Analysis of necroptosis-related prognostic genes and immune infiltration in idiopathic pulmonary fibrosis.

Background: IPF is an undetermined, progressive lung disease. Necroptosis is a type of programmed apoptosis, which involved in the pathogenesis of lung diseases like COPD and ARDS. However, necroptosis in IPF have not been adequately studied. This study aimed to investigate the necroptosis in IPF and the relationship between necroptosis and immune infiltration, to construct a prognostic prediction model of IPF based on necroptosis-related genes. Methods: GSE110147 was downloaded from the GEO database and utilized to analyze the expression of necroptosis-related differentially expressed genes (NRDEGs). Then NRDEGs were used to construct protein-protein interaction (PPI) networks in the STRING database, and Cytoscape software was used to identify and visualize hub genes. Necroptosis-related prognosticgenes were explored in GSE70866, and a prognostic prediction model was constructed. The ImmuCellAI algorithm was utilized to analyze the landscape of immune infiltration in GSE110147. The single-cell RNA sequencing dataset GSE122960 was used to explore the association between necroptosis and type II alveolar epithelial cells (AT II) in IPF. The GSE213001 and GSE93606 were used for external validation. The expression of prognostic genes was quantified using RT-qPCRin the IPF A549 cell model, and was further verified by western blotting in the bleomycin-induced pulmonary fibrosis mouse model. Results: It was observed that necroptosis-related signaling pathways were abundantly enriched in IPF. 29 NRDEGs were screened, of which 12 showed consistent expression trends in GSE213001. Spearman correlation analysis showed that the expression of NRDEGs was positively correlated with the infiltration of proinflammatory immune cells, and negatively correlated with the infiltration of anti-inflammatory immune cells. NRDEGs, including MLKL, were highly expressed in AT II of fibrotic lung tissue. A necroptosis-related prediction model was constructed based on 4 NRDEGsby the cox stepwise regression. In the validation dataset GSE93606, the prognostic prediction model showed good applicability. The verification results of RT-qPCR and western blotting showed the reliability of most of the conclusions. Conclusions: This study revealed that necroptosis existed in IPF and might occur in AT II. Necroptosis was associated with immune infiltration, suggesting that necroptosis of AT II might involve in IPF by activating immune infiltration and immune response.

The Core Role of Neutrophil-Lymphocyte Ratio to Predict All-Cause and Cardiovascular Mortality: A Research of the 2005-2014 National Health and Nutrition Examination Survey.

Objective: To further supplement the previous research on the relationship between neutrophil-lymphocyte ratio (NLR) and all-cause and cardiovascular mortality, and construct clinical models to predict mortality. Methods: A total number of 2,827 observers were included from the National Health and Nutrition Examination Survey (NHANES) database in our research. NLR was calculated from complete blood count. According to the quartile of baseline NLR, those observers were divided into four groups. A multivariate weighted Cox regression model was used to analyze the association of NLR with mortality. We constructed simple clinical prognosis models by nomograms. Kaplan-Meier survival curves were used to depict cause-specific mortality. Restricted cubic spline regression was used to make explicit relationships between NLR and mortality. Results: This study recruited 2,827 subjects aged ≥ 18 years from 2005 to 2014. The average age of these observers was 51.55 ± 17.62, and 57.69% were male. NLR is still an independent predictor, adjusted for age, gender, race, drinking, smoking, dyslipidemia, and other laboratory covariates. The area under the receiver operating characteristic curves (AUCs) of NLR for predicting all-cause mortality and cardiovascular mortality were 0.632(95% CI [0599, 0.664]) and 0.653(95% CI [0.581, 0.725]), respectively, which were superior to C-reactive protein (AUCs: 0.609 and 0.533) and WBC (AUCs: 0.522 and 0.513). The calibration and discrimination of the nomograms were validated by calibration plots and concordance index (C-index), and the C-indexes (95% CIs) of nomograms for all-cause and cardiovascular mortality were 0.839[0.819,0.859] and 0.877[0.844,0.910], respectively. The restricted cubic spline showed a non-linear relationship between NLR and mortality. NLR > 2.053 might be a risk factor for mortality. Conclusion: There is a non-linear relationship between NLR and mortality. NLR is an independent factor related to mortality, and NLR > 2.053 will be a risk factor for prognosis. NLR and nomogram should be promoted to medical use for practicality and convenience.

Early stage of antibody-mediated rejection after lung transplantation： A case report and literature review. / 肺移植术后早期抗体介导排斥反应1ä¾‹åŠæ–‡çŒ®å¤ä¹ .

Antibody-mediated rejection (AMR) is a rare and serious complication after lung transplantation, with no characteristic of pathological manifestation, no systematic standard treatment, and the poor efficacy and prognosis. We reported a case of early AMR after lung transplantation and the relevant literature has been reviewed. A male patient presented with symptoms of cold 99 days after transplantation and resolved after symptomatic treatment. He admitted to the hospital 14 days later because of a sudden dyspnea and fever. Anti-bacteria, anti-fungi, anti-virus, and anti-pneumocystis carinii treatment were ineffective, and a dose of 1 000 mg methylprednisolone did not work too. The patient's condition deteriorated rapidly and tracheal intubation was done to maintain breathing. Serum panel reactive antibody and donor specific antibody showed postive in humen leukocyte antigen (HLA) II antibody. Pathological examination after transbronchial transplantation lung biopsy showed acute rejection. Clinical AMR was diagnosed combined the donor-specific antibody with the pathological result. The patient was functionally recovered after combined treatment with thymoglobuline, rituximab, plasmapheresis, and immunoglobulin. No chronic lung allograft dysfunction was found after 3 years follow up. We should alert the occurrence of AMR in lung transplantation recipient who admitted to hospital with a sudden dyspnea and fever while showed no effect after common anti-infection and anti-rejection treatment. Transbronchial transplantation lung biopsy and the presence of serum donor-specific antibody are helpful to the diagnosis. The treatment should be preemptive and a comprehensive approach should be adopted.

Formation, contents, functions of exosomes and their potential in lung cancer diagnostics and therapeutics.

Lung cancer is the leading cause of cancer-related death worldwide due to diagnosis in the advanced stage and drug resistance in the subsequent treatments. Development of novel diagnostic and therapeutic methods is urged to improve the disease outcome. Exosomes are nano-sized vehicles which transport different types of biomolecules intercellularly, including DNA, RNA and proteins, and are implicated in cross-talk between cells and their surrounding microenvironment. Tumor-derived exosomes (TEXs) have been revealed to strongly influence the tumor microenvironment, antitumor immunoregulatory activities, tumor progression and metastasis. Potential of TEXs as biomarkers for lung cancer diagnosis, prognosis and treatment prediction is supported by numerous studies. Moreover, exosomes have been proposed to be promising drug carriers. Here, we review the mechanisms of exosomal formation and uptake, the functions of exosomes in carcinogenesis, and potential clinical utility of exosomes as biomarkers, tumor vaccine and drug delivery vehicles in the diagnosis and therapeutics of lung cancer.

A localization-independent approach for invisible and impalpable ground-glass opacity nodules detection in an in vitro lung specimen: two case reports.

A growing number of ground-glass opacity (GGO) nodules are screened out in lungs. Small GGOs are frequently neither visible nor palpable, thus undetectable during operation. Various nodule localization techniques have been developed to facilitate the intraoperative detection of GGO nodules; however, general localization techniques are infeasible or inappropriate in some cases. The detection of small GGO is a great challenge, even within a surgical specimen in the absence of preoperative localization. A localization-independent approach for GGO detection is urgently needed. Herein, we report two cases with invisible and impalpable small GGO which were not appropriate for preoperative localization. The lesions were anatomically resected under the guidance of three-dimensional (3D) reconstruction and got an adequate margin distance. A vessel (artery, vein, or bronchus) which had advanced into or immediately adjacent to the nodule was assigned as a reference vessel. By dissecting and tracing the reference vessel from proximal to distal, the GGO lesions were successfully detected in the surgical specimens, to the eventual obtainment of an accurate pathological diagnosis. Via the two case reports, we introduced an easily handled approach, namely dissecting and tracing a reference vessel, for GGO detection. The novel approach was first described. Combined with precise anatomical segmentectomy guided by 3D reconstruction, it provides an alternative scheme for GGO resection with no need for preoperative localization.