Exposure to Airborne PM2.5 Water-Soluble Inorganic Ions Induces a Wide Array of Reproductive Toxicity.

Water-soluble inorganic ions (WSIIs, primarily NH4+, SO42-, and NO3-) are major components in ambient PM2.5, but their reproductive toxicity remains largely unknown. An animal study was conducted where parental mice were exposed to PM2.5 WSIIs or clean air during preconception and the gestational period. After delivery, all maternal and offspring mice lived in a clean air environment. We assessed reproductive organs, gestation outcome, birth weight, and growth trajectory of the offspring mice. In parallel, we collected birth weight and placenta transcriptome data from 150 mother-infant pairs from the Rhode Island Child Health Study. We found that PM2.5 WSIIs induced a broad range of adverse reproductive outcomes in mice. PM2.5 NH4+, SO42-, and NO3- exposure reduced ovary weight by 24.22% (p = 0.005), 14.45% (p = 0.048), and 16.64% (p = 0.022) relative to the clean air controls. PM2.5 SO42- exposure reduced the weight of testicle by 5.24% (p = 0.025); further, mice in the PM2.5 SO42- exposure group had 1.81 (p = 0.027) fewer offspring than the control group. PM2.5 NH4+, SO42-, and NO3- exposure all led to lower birth than controls. In mice, 557 placenta genes were perturbed by exposure. Integrative analysis of mouse and human data suggested hypoxia response in placenta as an etiological mechanism underlying PM2.5 WSII exposure's reproductive toxicity.

Exploring the microbiota difference of bronchoalveolar lavage fluid between community-acquired pneumonia with or without COPD based on metagenomic sequencing: a retrospective study.

BACKGROUND: Community-acquired pneumonia (CAP) patients with chronic obstructive pulmonary disease (COPD) have higher disease severity and mortality compared to those without COPD. However, deep investigation into microbiome distribution of lower respiratory tract of CAP with or without COPD was unknown. METHODS: So we used metagenomic next generation sequencing (mNGS) to explore the microbiome differences between the two groups. RESULTS: Thirty-six CAP without COPD and 11 CAP with COPD cases were retrieved. Bronchoalveolar lavage fluid (BALF) was collected and analyzed using untargeted mNGS and bioinformatic analysis. mNGS revealed that CAP with COPD group was abundant with Streptococcus, Prevotella, Bordetella at genus level and Cutibacterium acnes, Rothia mucilaginosa, Bordetella genomosp. 6 at species level. While CAP without COPD group was abundant with Ralstonia, Prevotella, Streptococcus at genus level and Ralstonia pickettii, Rothia mucilaginosa, Prevotella melaninogenica at species level. Meanwhile, both alpha and beta microbiome diversity was similar between groups. Linear discriminant analysis found that pa-raburkholderia, corynebacterium tuberculostearicum and staphylococcus hominis were more enriched in CAP without COPD group while the abundance of streptococcus intermedius, streptococcus constellatus, streptococcus milleri, fusarium was higher in CAP with COPD group. CONCLUSIONS: These findings revealed that concomitant COPD have an mild impact on lower airway microbiome of CAP patients.

Comparative study of polymyxin B and colistin sulfate in the treatment of severe comorbid patients infected with CR-GNB.

BACKGROUND: With the difficulties in choosing colistin sulfate and polymyxin B sulfate (PBS) for carbapenem-resistant gram-negative bacteria (CR-GNB), we compared the efficacy and safety of these two old polymyxins in treatment of critically ill patients infected with CR-GNB infection. METHODS: One hundred four patients infected with CR-GNB in ICU were retrospectively grouped by PBS (68 patients) or colistin sulfate (36 patients). Clinical efficacy including symptoms, inflammatory parameters, defervescence, prognosis and microbial efficacy were analyzed. Hepatotoxicity, nephrotoxicity, and hematotoxicity were evaluated by TBiL, ALT, AST, creatinine, and thrombocytes. RESULTS: Demographic characteristics between colistin sulfate and PBS were not significantly different. Most of the CR-GNB were cultured in respiratory tract (91.7% vs 86.8%), and almost all were polymyxin-sensitive (98.2% vs 100%, MIC ≤ 2 µg/ml). The microbial efficacy in colistin sulfate (57.1%) was significantly higher than PBS (30.8%) (p = 0.022), however, no significant difference in clinical success was seen in both groups (33.8% vs 41.7%), as well as mortality, defervescence, imaging remission, days in the hospital, microbial reinfections, and prognosis, and almost all patients defervesce within 7 days (95.6% vs 89.5%). CONCLUSIONS: Both polymyxins can be administrated in critically ill patients infected with CR-GNB and colistin sulfate is superior to PBS in microbial clearance. These results highlight the necessity of identifying CR-GNB patients who may benefit from polymyxin and who are at higher risk of mortality.

Profiling Microbiota from Multiple Sites in the Respiratory Tract to Identify a Biomarker for PM2.5 Nitrate Exposure-Induced Pulmonary Damages.

The microbiota present in the respiratory tract (RT) responds to environmental stimuli and engages in a continuous interaction with the host immune system to maintain homeostasis. A total of 40 C57BL/6 mice were divided into four groups and exposed to varying concentrations of PM2.5 nitrate aerosol and clean air. After 10 weeks of exposure, assessments were conducted on the lung and airway microbiome, lung functions, and pulmonary inflammation. Additionally, we analyzed data from both mouse and human respiratory tract (RT) microbiomes to identify possible biomarkers for PM2.5 exposure-induced pulmonary damages. On average, 1.5 and 13.5% inter-individual microbiome variations in the lung and airway were explained by exposure, respectively. In the airway, among the 60 bacterial OTUs (operational taxonomic units) > 0.05% proportion, 40 OTUs were significantly affected by PM2.5 exposure (FDR ≤ 10%). Further, the airway microbiome was associated with peak expiratory flow (PEF) (p = 0.003), pulmonary neutrophil counts (p = 0.01), and alveolar 8-OHdG oxidative lesions (p = 0.0078). The Clostridiales order bacteria showed the strongest signals. For example, the o_Clostridiales;f_;g_ OTU was elevated by PM2.5 nitrate exposure (p = 4.98 × 10-5) and negatively correlated with PEF (r = -0.585 and p = 2.4 × 10-4). It was also associated with the higher pulmonary neutrophil count (p = 8.47 × 10-5) and oxidative lesion (p = 7.17 × 10-3). In human data, we confirmed the association of airway Clostridiales order bacteria with PM2.5 exposure and lung function. For the first time, this study characterizes the impact of PM2.5 exposure on the microbiome of multiple sites in the respiratory tract (RT) and its relevance to airflow obstructive diseases. By analyzing data from both humans and mice, we have identified bacteria belonging to the Clostridiales order as a promising biomarker for PM2.5 exposure-induced decline in pulmonary function and inflammation.

Effects of spray cryotherapy on cough receptors and airway microenvironment in a canine model of chronic bronchitis.

The aim of this study was to explore the effects of spray cryotherapy (SCT) on cough receptors and airway microenvironment in a canine model of chronic bronchitis. We examined the expression of transient receptor potential vanilloid 1/4 (TRPV1/4) and the neuropeptides substance P (SP) and calcitonin gene-related peptide (CGRP) at the gene and protein levels before and after SCT. In addition, we explored whether TRPV1/4 could regulate inflammatory factors via mediator adenosine triphosphate (ATP). The levels of ATP and cytokines in alveolar lavage fluid and cell supernatant were measured using ELISA. SCT effectively downregulated the expression of TRPV1/4 and SP/CGRP in canine airway tissues with chronic bronchitis and reduced the levels of inflammatory mediators and cytokines that affect cough receptor sensitivity, achieving cough relief. TRPV1/4 - ATP - inflammatory cytokines axis has been demonstrated at the cellular level, which in turn modulate the milieu of the airways and promote the formation of a cough feedback loop. Our study has fully revealed the specific mechanism of SCT in treating cough in a canine model of chronic bronchitis, providing a solid theoretical basis for future clinical treatment.

The diagnosis interval influences risk factors of mortality in patients with co-existent active tuberculosis and lung cancer: a retrospective study.

BACKGROUND: Previous studies reported that tuberculosis (TB) is associated with an increased risk of lung cancer or the survival and mortality of lung cancer. However, the impact of coexisting TB on the survival of lung cancer patients was controversial. We aimed to identify risk factors on the survival rate of patients with co-existent active TB and lung cancer. METHODS: One hundred seventy-three patients diagnosed with active TB and lung cancer from January 2016 to August 2021 in Shanghai pulmonary hospital were selected and divided into two groups (≤ 6 months, > 6 months) according to the diagnosis interval between active TB and lung cancer (the order of diagnosis is not considered). The clinical characteristics and survival were analyzed. Univariate and multivariate logistic regression analyses were used to identify the risk factors for overall survival (OS). RESULTS: One hundred seventy-three patients were diagnosed with lung cancer and active TB. The study population exhibited a median age of 64 years, with a majority of 81.5% being male, 58.0% of patients had a history of smoking. Among those involved, 93.6% had pulmonary TB, 91.9% were diagnosed with non-small cell lung cancer (NSCLC), 76.9% were Eastern Cooperative Oncology Group (ECOG) 0-2 and 12.7% were ECOG 3-4. We observed better survival in the > 6 months group compared with the ≤ 6 months group (hazard ratio [HR] 0.456, 95% confidence interval [CI]:0.234-0.889, P = 0.017). The 1-, 3-, and 5- year OS rates were 94.2%, 80.3%, and 77.6%, respectively, in the > 6 months group and 88.3%, 63.8%, and 58.5%, respectively, in the ≤ 6 months group. Surgery (HR 0.193, [95% CI, 0.038-0.097]; P = 0.046) and ECOG Performance Status (HR 12.866, [95% CI, 2.730-60.638]; P = 0.001) were independent prognostic factors in the > 6 months group. CONCLUSIONS: Patients diagnosed with lung cancer and active TB for more than half a year have a significantly better prognosis than those diagnosed within half a year. ECOG Performance Status and surgery might possibly affect the outcomes of patients with co-existent active TB and lung cancer.

Mucus Hypersecretion in Chronic Obstructive Pulmonary Disease and Its Treatment.

Most patients diagnosed with chronic obstructive pulmonary disease (COPD) present with hallmark features of airway mucus hypersecretion, including cough and expectoration. Airway mucus function as a native immune system of the lung that severs to trap particulate matter and pathogens and allows them to clear from the lung via cough and ciliary transport. Chronic mucus hypersecretion (CMH) is the main factor contributing to the increased risk of morbidity and mortality in specific subsets of COPD patients. It is, therefore, primarily important to develop medications that suppress mucus hypersecretions in these patients. Although there have been some advances in COPD treatment, more work remains to be done to better understand the mechanism underlying airway mucus hypersecretion and seek more effective treatments. This review article discusses the structure and significance of mucus in the lungs focusing on gel-forming mucins and the impacts of CMH in the lungs. Furthermore, we summarize the article with pharmacological and nonpharmacological treatments as well as novel and interventional procedures to control CMH in COPD patients.

Analysis of sputum microbial metagenome in COPD based on exacerbation frequency and lung function: a case control study.

BACKGROUND: The role of the sputum microbiome in chronic obstructive pulmonary disease (COPD) progression remains elusive. As the advent of the new culture-independent microbial sequencing technique makes it possible to disclose the complex microbiome community of the respiratory tract. The aim of this study was to use metagenomic next-generation sequencing (mNGS) to confirm whether there are differences in sputum microbiome of COPD between different exacerbation frequencies and lung function. METHODS: Thirty-nine COPD patients were divided into a frequent exacerbators (FE) group (n = 20) and a non-frequent exacerbators (NFE) (n = 19) group according to their exacerbation history, or a mild group (FEV1/pre ≥ 50%, n = 20) and a severe group (FEV1/pre < 50%, n = 19) according to the lung function. Sputum was collected during their stable phase, followed by DNA extraction, untargeted metagenomic next-generation sequencing (mNGS) and bioinformatic analysis. RESULTS: mNGS identified 3355 bacteria, 71 viruses and 22 fungi at the specie level. It was found that Shannon index and Simpson index in FE group was lower than that in NFE group (p = 0.005, 0.008, respectively) but similar between mild and severe groups. Out of top 10 bacteria taxa, Veillonella, Fusobacterium and Prevotella jejuni had a higher abundance in NFE group, Rothia had a higher abundance in mild group. Linear discriminant analysis revealed that many bacterial taxa were more abundant in NFE group, and they mostly belonged to Actinobacteria, Bacteroidetes and Fusobacteria phyla. Frequency of exacerbations was also found to be negatively correlated with alpha diversity (with Shannon index, r = - 0.423, p = 0.009; with Simpson index, r = - 0.482, p = 0.002). No significant correlation was observed between alpha diversity and FEV1/pre. CONCLUSIONS: Microbiome diversity in FE group was lower than that in NFE group. There was a significant difference in microbiome taxa abundance between FE and NFE groups, or mild and severe groups. These findings demonstrated that sputum microbiome community dysbiosis was associated with different exacerbation frequencies and lung function in stable COPD.

The diagnostic value of metagenomic next⁃generation sequencing in infectious diseases.

BACKGROUND: Although traditional diagnostic techniques of infection are mature and price favorable at present, most of them are time-consuming and with a low positivity. Metagenomic next⁃generation sequencing (mNGS) was studied widely because of identification and typing of all pathogens not rely on culture and retrieving all DNA without bias. Based on this background, we aim to detect the difference between mNGS and traditional culture method, and to explore the relationship between mNGS results and the severity, prognosis of infectious patients. METHODS: 109 adult patients were enrolled in our study in Shanghai Tenth People's Hospital from October 2018 to December 2019. The diagnostic results, negative predictive values, positive predictive values, false positive rate, false negative rate, pathogen and sample types were analyzed by using both traditional culture and mNGS methods. Then, the samples and clinical information of 93 patients in the infected group (ID) were collected. According to whether mNGS detected pathogens, the patients in ID group were divided into the positive group of 67 cases and the negative group of 26 cases. Peripheral blood leukocytes, C-reactive protein (CRP), procalcitonin (PCT) and neutrophil counts were measured, and the concentrations of IL-2, IL-4, IL-6, TNF-α, IL-17A, IL-10 and INF-γ in the serum were determined by ELISA. The correlation between the positive detection of pathogens by mNGS and the severity of illness, hospitalization days, and mortality were analyzed. RESULTS: 109 samples were assigned into infected group (ID, 92/109, 84.4%), non-infected group (NID, 16/109, 14.7%), and unknown group (1/109, 0.9%). Blood was the most abundant type of samples with 37 cases, followed by bronchoalveolar lavage fluid in 36 cases, tissue, sputum, pleural effusion, cerebrospinal fluid (CSF), pus, bone marrow and nasal swab. In the ID group, the majority of patients were diagnosed with lower respiratory system infections (73/109, 67%), followed by bloodstream infections, pleural effusion and central nervous system infections. The sensitivity of mNGS was significantly higher than that of culture method (67.4% vs 23.6%; P < 0.001), especially in sample types of bronchoalveolar lavage fluid (P = 0.002), blood (P < 0.001) and sputum (P = 0.037), while the specificity of mNGS was not significantly different from culture method (68.8% vs 81.3%; P = 0.41). The number of hospitals stays and 28-day-motality in the positive mNGS group were significantly higher than those in the negative group, and the difference was statistically significant (P < 0.05). Age was significant in multivariate logistic analyses of positive results of mNGS. CONCLUSIONS: The study found that mNGS had a higher sensitivity than the traditional method, especially in blood, bronchoalveolar lavage fluid and sputum samples. And positive mNGS group had a higher hospital stay, 28-day-mortality, which means the positive of pathogen nucleic acid sequences detection may be a potential high-risk factor for poor prognosis of adult patients and has significant clinical value. MNGS should be used more in early pathogen diagnosis in the future.

A pilot study of spray cryotherapy effects on airway secretions.

Spray cryotherapy (SCT) is a new transbronchial approach that disrupts epithelial cells by freezing. However, there are limited data addressing the effect of SCT on airway secretion. The aim of this study was to evaluate if SCT effect on airway secretion and the possible mechanism in canines. Fifteen labradors were randomly scheduled SCT or sham operation. Six labradors were scheduled SCT for a short-time observation, and six for a long-time observation, the remaining three received sham operation as control. Lung tissues were harvested for PAS staining. Mucin, MUC5AC and acetylcholine in bronchoalveolar lavage fluid (BALF) were analyzed by enzyme-linked immunosorbent assay (ELISA). CHRM3 and Mucin 5AC (MUC5AC) expressions in the lung tissues were analyzed by immunohistochemistry. MUC5AC mRNA expression was analyzed by rt-PCR. From 0 day to 30 days after SCT, the ratio of PAS positive cells to total bronchial epithelial cells, the average optical density of MUC5AC + by immunohistochemistry, the protein expression of MUC5AC, acetylcholine in BALF decreased compared with that of control group (p < 0.05). The average optical density of CHRM3+ by immunohistochemistry were decreased from 0 day to 7 days after SCT (p < 0.05) compared with control group. In conclusion, SCT was able to reduce the PAS-, MUC5AC- and CHRM3-positive cells in the lung tissue and acetylcholine in BALF, suggesting that SCT may prove to be a beneficial way in mucus excessive production in airway and acetylcholine-CHRM3 pathway may one possible mechanism.

The impact of order with radiation therapy in stage IIIA pathologic N2 NSCLC patients: a population-based study.

BACKGROUND: The aim of this study was to investigate the optimal order of radiation therapy in patients affected by stage IIIA pathologic N2 (IIIA/N2) non-small-cell lung cancer (NSCLC) and to identify its potential risk factors. METHODS: 17,654 (8786 men and 8868 women) diagnosed with NSCLC stage IIIA-N2 from 2004 to 2015 patients were identified in the Surveillance, Epidemiology, and End Results (SEER) database. Among the relevant clinical parameters, we evaluated overall survival (OS), lung cancer-specific survival (LCSS) and other variables such as age, sex and tumor size in patients who were treated with different combinations of surgery and radiotherapy strategies. RESULTS: We discovered that surgery benefit in younger IIIA/N2 NSCLC patients (age ≤ 75), and compared with surgery only, preoperative radiotherapy significantly improved the survival rate most (p < 0.001). When we performed the OS and LCSS analysis in the subgroup of patients' age > 75 years old, who underwent postoperative radiotherapy (PORT) had the highest survival rate (p < 0.001). Multivariate analyses showed that the following parameters had a negative impact on survival: female sex, older age, no chemotherapy, large tumor size, high tumor grade, no surgery or radiotherapy. CONCLUSIONS: In IIIA/N2 NSCLC patients, surgery, radiotherapy and chemotherapy were associated with improved OS and LCSS. Younger patients underwent surgical resection and chemotherapy, the main population we studied, benefited most from preoperative radiotherapy in all orders with radiation therapy (p < 0.001). In patients more than 75 years old, there was no clear benefit from only surgery, and PORT was recommended in case of having surgery.

Risk factors for pulmonary embolism in patients preliminarily diagnosed with community-acquired pneumonia: a prospective cohort study.

D-dimer levels are increased in patients with acute pulmonary embolism (PE). However, D-dimer levels are also increased in patients with community-acquired pneumonia (CAP). The aim of this prospective cohort study was to examine the incidence and clinical features of patients preliminarily diagnosed with CAP and with increased D-dimer levels, and who finally were diagnosed with PE. Patients diagnosed with CAP and hospitalized in the Respiratory Department of the Tenth People's Hospital Affiliated to Tongji University between May 2011 and May 2013 were enrolled. D-dimer levels were measured routinely after admission. For patients with increased D-dimer levels, those suspected with PE underwent computed tomography pulmonary angiography (CTPA). A total of 2387 patients with CAP was included: 724 (30.3 %) had increased D-dimer levels (median of 0.91 mg/L). CTPA was performed for 139 of the 724 patients (median D-dimer levels of 1.99 mg/L). Among the 139 patients, 80 were diagnosed with PE, and 59 without PE; D-dimer levels were 2.83 and 1.41 mg/L, respectively (p < 0.05). Multivariate analysis showed that age, coronary heart disease, chronic obstructive pulmonary disease (COPD), lower limb varicosity, chest pain, shortness of breath, hemoptysis, fever, and increased levels of troponin I were independent risk factors for PE. Presentation of PE and CAP are similar. Nevertheless, these results indicated that for hospitalized patients with CAP and elevated D-dimer levels, PE should be considered for those >60 years; with CHD, COPD, or lower limb varicosity; with chest pain, shortness of breath, hemoptysis, increased troponin I, or low fever.

Preparation of a nano emodin transfersome and study on its anti-obesity mechanism in adipose tissue of diet-induced obese rats.

OBJECTIVE: To describe the preparation of nano emodin transfersome (NET) and investigate its effect on mRNA expression of adipose triglyceride lipase (ATGL) and G0/G1 switch gene 2 (G0S2) in adipose tissue of diet-induced obese rats. METHODS: NET was prepared by film-ultrasonic dispersion method. The effects of emodin components at different ratios on encapsulation efficiency were investigated.The NET envelopment rate was determined by ultraviolet spectrophotometry. The particle size and Zeta potential of NET were evaluated by Zetasizer analyzer. Sixty male SD rats were assigned to groups randomly. After 8-week treatment, body weight, wet weight of visceral fat and the percentage of body fat (PBF) were measured. Fasting blood glucose and serum lipid levels were determined. The adipose tissue section was HE stained, and the cellular diameter and quantity of adipocytes were evaluated by light microscopy. The mRNA expression of ATGL and G0S2 from the peri-renal fat tissue was assayed by RT-PCR. RESULTS: The appropriate formulation was deoxycholic acid sodium salt vs. phospholipids 1:8, cholesterol vs. phospholipids 1:3, vitamin Evs. phospholipids 1:20, and emodin vs. phospholipid 1:6. Zeta potential was -15.11 mV, and the particle size was 292.2 nm. The mean encapsulation efficiency was (69.35 ± 0.25)%. Compared with the obese model group, body weight, wet weight of visceral fat, PBF and mRNA expression of G0S2 from peri-renal fat tissue were decreased significantly after NET treatment (all P < 0.05), while high-density lipoprotein cholesterol (HDL-C), the diameter of adipocytes and mRNA expression of ATGL from peri-renal fat tissue were increased significantly (all P < 0.05). CONCLUSION: The preparation method is simple and reasonable. NET with negative electricity was small and uniform in particle size, with high encapsulation efficiency and stability. NET could reduce body weight and adipocyte size, and this effect was associated with the up-regulation of ATGL, down-regulation of G0S2 expression in the adipose tissue, and improved insulin sensitivity.

Effects of obstructive sleep apnea on cardiac function and clinical outcomes in Chinese patients with ST-elevation myocardial infarction.

AIM: The objective of this study was to investigate the influence of OSA on cardiac function in Chinese patients with ST-elevation myocardial infarction (STEMI) and determine the prognostic impact of OSA among these patients. METHODS: In this retrospective study, 198 STEMI patients were enrolled. Doppler echocardiography was performed to detect the effect of OSA on cardiac function. Major adverse cardiac events (MACE) and cardiac mortality were analyzed to determine whether OSA was a clinical prognostic factor; its prognostic impact was then assessed adjusting for other covariates. RESULTS: The echocardiographic results showed that the myocardium of STEMI patients with OSA appeared to be more hypertrophic and with a poorer cardiac function compared with non-OSA STEMI patients. A Kaplan-Meier survival analysis revealed significantly higher cumulative incidence of MACE and cardiac mortality in the OSA group compared with that in the non-OSA group during a mean follow-up of 24 months. Multivariate Cox regression analysis revealed that OSA was an independent risk factor for MACE and cardiac mortality. CONCLUSION: These results indicate that the OSA is a powerful predictor of decreased survival and exerts negative prognostic impact on cardiac function in STEMI patients.

Higher diagnostic value of metagenomic next-generation sequencing in acute infection than chronic infection: a multicenter retrospective study.

Background: The aim of this study is to compare the diagnostic value of metagenomic next-generation sequencing (mNGS) vs. conventional culture methods (CM) in chronic infection and acute infection. Methods: We retrospectively analyzed the bronchoalveolar lavage fluid (BALF) of 88 patients with acute infection and 105 patients with chronic infection admitted to three hospitals from 2017 to 2022. Results: The results showed that the sensitivity and specificity of mNGS were higher than those of CM. The number of patients who changed the antibiotic treatment in the mNGS positive group was larger than that of patients in the mNGS negative group in both the acute infection group (60.5 vs. 28.0%, P = 0.0022) and chronic infection group (46.2 vs. 22.6%, P = 0.01112). High levels of temperature (OR: 2.02, 95% CI: 1.18-3.70, P: 0.015), C-reactive protein (CRP) (OR: 15, 95% CI: 2.74-280.69, P: 0.011), neutrophil count (OR: 3.09, 95% CI: 1.19-8.43, P: 0.023), and low levels of lymphocyte count (OR: 3.43, 95% CI:1.26-10.21, P: 0.020) may lead to positive mNGS results in the acute infection group while no significant factor was identified to predict positive results in the chronic infection group. Conclusion: mNGS could provide useful guidance on antibiotic strategies in infectious diseases and may be more valuable for the diagnosis and treatment of acute infection vs. chronic infection.

The Valuable Prognostic Impact of Regional Lymph Node Removed on Outcomes for IIIA N0 NSCLC Patients.

Background: Regional lymph nodes (RLNs) removed combined with surgery is a standard option for patients at stage I to IIIA NSCLC. The objective of the study is to clarify the effect of removing different number of RLNs on survival outcomes for patients at stage IIIA N0 NSCLC. Methods: Patients at stage IIIA N0 NSCLC from 2004 to 2015 were identified from Surveillance, Epidemiology, and End Results (SEER) database. Prior propensity score method (PSM), survival time was compared among different number (0, 1-3 and ≥4) of RLNs removed groups. After PSM, lung cancer-specific survival (LCSS) and overall survival (OS) were compared. Kaplan-Meier analysis and Cox regression analyses were used to clarify the impact of the factors on the prognosis with hazard ratio (HR) and 95% confidence interval (CI). Results: A total of 11,583 patients at stage IIIA N0 NSCLC were included. Prior PSM, survival indicators including 1-year mortality rate, 5-year mortality rate, median survival time (MDST) and mean survival time (MST) from good to bad were all: ≥4, 1-3 and none RLNs removed group. After PSM, Kaplan-Meier survival analyses and univariate Cox regression analyses on OS and LCSS revealed a statistically significance on survival curve (P<0.001) between each two of the three groups (none, 1-3 and ≥4 RLNs removed group). Multivariable Cox regression analyses on OS and LCSS showed an independent association of RLNs removed with higher OS (HR, 0.275; 95% CI, 0.259-0.291; P<0.001) and LCSS (HR, 0.239; 95% CI, 0.224-0.256; P<0.001) compared with none RLN removed and no statistical difference with OS (HR, 1.118; 95% CI, 0.983-1.271; P=0.088) and LCSS (HR, 1.107; 95% CI, 0.954-1.284; P=0.179) between 1-3 RLNs removed and ≥4 RLNs removed. Conclusions: Removing RLNs was beneficial to survival outcomes of patients at stage IIIA N0 NSCLC. Compared with 1-3 RLNs removed, ≥4 RLNs removed could bring a better survival time but not an independent prognostic factor (P>0.05).

Brochoscopic Airway Clearance Therapy vs. Conventional Sputum Aspiration: The Future of Flexible Brochoscopes in Intensive Care Units?

(1) Background: The aim of our study is to investigate the effectiveness of bronchoscopic airway clearance therapy (B-ACT) on severe pneumonia (SP) patients with invasive mechanical ventilation (IMV) in the intensive care unit (ICU). (2) Methods: Our study retrospectively enrolled 49 patients with sputum aspiration and 99 patients with B-ACT, and the latter were divided into the ≤once every 3 days group (n = 50) and >once every 3 days group (n = 49). (3) Results: We found most laboratory blood results were significantly improved in the B-ACT group as compared with those in sputum aspiration group (p < 0.05). Patients in the B-ACT group and those in ≤once every 3 days group also had significantly better survival to hospital discharge than those in their counterpart groups (Logrank p < 0.001). In patients with cardiopulmonary diseases or positive cultures for bacteria, the B-ACT group and those in the ≤once every 3 days group had significantly better survival outcomes to discharge than those in their counterpart groups (Logrank p < 0.001). B-ACT and the average frequency of ≤once every 3 days had significantly better impact on survival outcomes than their counterpart groups (HR: 0.444, 95% CI: 0.238-0.829, p = 0.011; HR: 0.285, 95% CI: 0163-0.498, p < 0.001). (4) Conclusions: In the future, flexible bronchoscopes may paly an important role in ACT for SP patients with IMV.

[A Rare Case of Lung Adenocarcinoma with EGFR L833V/H835L Co-mutation 
and Literature Review].

Epidermal growth factor receptor (EGFR) mutations are the most common driver genes in the development of non-small cell lung cancer (NSCLC), of which mutations in exons 18-21 are frequent, especially the loss of exon 19 and exon 21 L858R mutation are the most frequent. Other rare gene mutations are rare. Simultaneous occurrence of two or more rare EGFR mutations are extremely rare in lung cancer, and the incidence of EGFR L833V/H835L rare gene compound mutations is very low, and there is little clinical data and evidence of relevant treatment methods. Some EGFR-tyrosine kinase inhibitors (EGFR-TKIs) are effective in treating lung cancer patients with rare gene mutations. In this article, we reported a case of NSCLC patient with a rare gene compound mutation EGFR L833V/H835L, who responded to Afatinib in combination with Anilotinib treatment well after 5 months of treatment, and computed tomography (CT) showed shrinkage of lung lesions. Meanwhile, we also compiled previously reported NSCLC patients with EGFR L833V/H835L rare gene compound mutation and summarized the characteristics of this group of patients and the effect of applying different kinds of EGFR-TKIs treatment.
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Adjuvant chemotherapy is not a decisive factor in improving the overall survival of pulmonary sarcoma: A population-based study.

Objective: This study aimed to investigate the impact of adjuvant chemotherapy on overall survival (OS) for pulmonary sarcomatoid carcinoma (PSC) and non-small-cell lung cancer (NSCLC) cohorts and to identify its potential risk factors. Methods: A retrospective analysis was performed by querying the Surveillance, Epidemiology, and End Results (SEER) database for patients diagnosed as having PSC (n=460) and NSCLC (n=140,467) from 2004 to 2015. The demographics, tumor characteristics, treatment modes, and survival were included in the scope of statistical analysis. Confounding factors were controlled by propensity score matching (PSM) analysis. Kaplan-Meier survival curves were performed to compare the effects of adjuvant chemotherapy on OS of the patients in the two cohorts (PSC vs. NSCLC). A multivariable Cox regression model was constructed, and Kaplan-Meier analysis on each variate was applied to predict risk factors associated with OS. Results: When adjuvant chemotherapy approach was applied in the treatment of patients with PSC or adjusted NSCLC, respectively, an improved OS could be observed in the NSCLC cohort (p=0.017). For the entire PSC cohort, 1-, 3-, and 5-year OS were 25.43%, 13.04%, and 6.96%, respectively, compared with 41.96%, 17.39%, and 10.00%, respectively, for the new adjusted NSCLC cohort after PSM, which were statistically significant difference (p<0.001). Multivariable Cox regression analysis was performed on OS covering prognostic factors such as primary site (p=0.036), first malignant indicator (p<0.001), age at diagnosis (p<0.001), marital status at diagnosis (p=0.039), and high school education (p=0.045). Additionally, patients with the following parameters had the worse impact on OS: a poorly differentiated pathology (Grade III/IV, p=0.023), older age (p<0.001), liver or lung metastasis (p=0.004, p=0.029), and the number of lymph nodes removed <4 (p<0.001). Conclusions: Adjuvant chemotherapy did not play a decisive role in improving the OS of PSC, while it was associated with improved OS of NSCLC.

Impact of Type 2 Diabetes Mellitus on the Prognosis of Non-Small Cell Lung Cancer.

OBJECTIVE: Type 2 diabetes mellitus (T2DM) is the most common metabolic disease and is characterized by sustained hyperglycemia. The impact of T2DM on the survival of lung cancer patients remains controversial. The aim of this study was to investigate the associations of type 2 diabetes with lung cancer mortality. METHODS: From January 2019 to January 2020, 228 patients with non-small cell lung cancer (NSCLC) staging earlier than IIIA were included. RESULTS: In our study, we found that the overall survival (OS) and progression-free survival (PFS) of lung cancer patients with diabetes was longer than non-diabetes group. Diagnosed T2DM was associated with the prognosis of lung cancer after adjusting for age and covariates. The association between T2DM and OS was influenced by age, stage of cancer and cancer treatment, as well as whether taking metformin was associated with the OS of lung cancer. However, with the adjustment for age and covariates, the relation trended to lose statistical significance. CONCLUSION: T2DM is an independent prognostic factor for patients with NSCLC staging before IIIA. The patients with both NSCLC and T2DM trended to having a longer OS, possibly due to metformin.