Evaluation of the antitumor effect of neoantigen peptide vaccines derived from the translatome of lung cancer.

Emerging evidence suggests that tumor-specific neoantigens are ideal targets for cancer immunotherapy. However, how to predict tumor neoantigens based on translatome data remains obscure. Through the extraction of ribosome-nascent chain complexes (RNCs) from LLC cells, followed by RNC-mRNA extraction, RNC-mRNA sequencing, and comprehensive bioinformatic analysis, we successfully identified proteins undergoing translatome and exhibiting mutations in the cells. Subsequently, novel antigens identification was analyzed by the interaction between their high affinity and the Major Histocompatibility Complex (MHC). Neoantigens immunogenicity was analyzed by enzyme-linked immunospot assay (ELISpot). Finally, in vivo experiments in mice were conducted to evaluate the antitumor effects of translatome-derived neoantigen peptides on lung cancer. The results showed that ten neoantigen peptides were identified and synthesized by translatome data from LLC cells; 8 out of the 10 neoantigens had strong immunogenicity. The neoantigen peptide vaccine group exhibited significant tumor growth inhibition effect. In conclusion, neoantigen peptide vaccine derived from the translatome of lung cancer exhibited significant tumor growth inhibition effect.

Preventing CXCL12 elevation helps to reduce acute exacerbation of COPD in individuals co-existing type-2 diabetes: A bioinformatics and clinical pharmacology study.

AIMS: To investigate the immunology shared mechanisms underlying chronic obstructive pulmonary disease (COPD) and type 2 diabetes mellitus (T2DM) and examine the impact of anti-diabetic drugs on acute exacerbation of COPD (AECOPD). METHODS: We analyzed GSE76925, GSE76894, GSE37768, and GSE25724 to identify differentially expressed genes. Hub-genes were identified through protein-protein interaction network analysis and evaluated by the receiver operating characteristic curve. CXCL12 emerged as a robust biomarker, and its correlation with lung function and CD8+ T cells were further quantified and validated. The activated signaling pathways were inferred through Gene set enrichment analysis (GSEA). The retrospective clinical analysis was executed to identify the influence of dipeptidyl peptidase-4 inhibitors (DPP-4i) on CXCL12 and evaluate the drug's efficacy in AECOPD. RESULTS: The significant up-regulation of CXCL12 expression in patients with two diseases were revealed. CXCL12 exhibited a negative correlation with pulmonary function (r = -0.551, p < 0.05). Consistent with analysis in GSE76925 and GSE76894, the positive correlation between the proportion of CD8+ T cells was demonstrated(r=0.469, p<0.05). GSEA identified "cytokines interaction" as an activated signaling pathway, and the clinical study revealed the correlation between CXCL12 and IL-6 (r=0.668, p<0.05). In patients with COPD and T2DM, DDP-4i treatment exhibited significantly higher serum CXCL12, compared to GLP-1RA. Analysis of 187 COPD patients with T2DM indicated that the DPP-4i group had a higher frequency of AECOPD compared to the GLP-1RA group (OR 1.287, 95%CI [1.018-2.136]). CONCLUSIONS: CXCL12 may represent a therapeutic target for COPD and T2DM. GLP-1RA treatment may be associated with lower CXCL12 levels and a lower risk of AECOPD compared to DPP-4i treatment. CLINICAL TRIAL REGISTRATION: China Clinical Trial Registration Center（ChiCTR2200055611）.

Hospitalization, case fatality, comorbidities, and isolated pathogens of adult inpatients with pneumonia from 2013 to 2022: a real-world study in Guangzhou, China.

BACKGROUND: In the context of increasing population aging, ongoing drug-resistant pathogens and the COVID-19 epidemic, the changes in the epidemiological and clinical characteristics of patients with pneumonia remain unclear. This study aimed to assess the trends in hospitalization, case fatality, comorbidities, and isolated pathogens of pneumonia-related adult inpatients in Guangzhou during the last decade. METHODS: We retrospectively enrolled hospitalized adults who had doctor-diagnosed pneumonia in the First Affiliated Hospital of Guangzhou Medical University from January 1, 2013 to December 31, 2022. A natural language processing system was applied to automatically extract the clinical data from electronic health records. We evaluated the proportion of pneumonia-related hospitalizations in total hospitalizations, pneumonia-related in-hospital case fatality, comorbidities, and species of isolated pathogens during the last decade. Binary logistic regression analysis was used to assess predictors for patients with prolonged length of stay (LOS). RESULTS: A total of 38,870 cases were finally included in this study, with 70% males, median age of 64 (53, 73) years and median LOS of 7.9 (5.1, 12.8) days. Although the number of pneumonia-related hospitalizations showed an upward trend, the proportion of pneumonia-related hospitalizations decreased from 199.6 per 1000 inpatients in 2013 to 123.4 per 1000 in 2021, and the case fatality decreased from 50.2 per 1000 in 2013 to 23.9 per 1000 in 2022 (all P < 0.05). The most common comorbidities were chronic obstructive pulmonary disease, lung malignancy, cardiovascular diseases and diabetes. The most common pathogens were Pseudomonas aeruginosa, Candida albicans, Acinetobacter baumannii, Stenotrophomonas maltophilia, Klebsiella pneumoniae, and Staphylococcus aureus. Glucocorticoid use during hospitalization (Odd Ratio [OR] = 1.86, 95% Confidence Interval (CI): 1.14-3.06), immunosuppressant use during hospitalization (OR = 1.99, 1.14-3.46), ICU admission (OR = 16.23, 95%CI: 11.25-23.83), receiving mechanical ventilation (OR = 3.58, 95%CI: 2.60-4.97), presence of other underlying diseases (OR = 1.54, 95%CI: 1.15-2.06), and elevated procalcitonin (OR = 1.61, 95%CI: 1.19-2.19) were identified as independent predictors for prolonged LOS. CONCLUSION: The proportion of pneumonia-related hospitalizations and the in-hospital case fatality showed downward trends during the last decade. Pneumonia inpatients were often complicated by chronic underlying diseases and isolated with gram-negative bacteria. ICU admission was a significant predictor for prolonged LOS in pneumonia inpatients.

Personalized neoantigen vaccine enhances the therapeutic efficacy of bevacizumab and anti-PD-1 antibody in advanced non-small cell lung cancer.

Clinically, a considerable number of non-small cell lung cancer (NSCLC) patients are unable to receive or resist chemotherapy, and the efficacy of non-chemotherapy treatment strategies based on anti-angiogenic agents combined with immune checkpoint blockade is still unsatisfactory. Neoantigen vaccine, based on personalized tumor DNA mutations, could elicit tumor specific T cell infiltration into the tumor site, exerting potent anti-tumor efficacy. Here, we evaluated the feasibility and safety of a new antitumor strategy by adding neoantigen vaccine to the regimen of bevacizumab and anti-PD-1 antibody. Firstly, 7 novel immunogenic neoantigen peptides were identified and developed for neoantigen vaccine (LLCvac), which can elicit strong antitumor immune response in vivo. Then, in orthotopic lung cancer model, LLCvac further combining with bevacizumab and anti-PD-1 antibody exerted a stronger antitumor effect, exhibiting significant decrease of tumor volume without obvious toxicity. Furthermore, tumor immune microenvironment assessment also showed that the proportion of neoantigen-specific T cells in blood could be induced dramatically by the combined therapy. And a large amount of neoantigen-specific Ki67-positive CD8+ T cells were found in tumor tissues, which infiltrated tumor tissues effectively to kill tumor cells expressing identified neoantigens. Overall, these results suggested that this combined therapy could safely induce robust antitumor efficacy, serving as an effective chemotherapy-free strategy for NSCLC treatment.

Clinical characteristics and predictors of delayed discharge among children with SARS­CoV­2 Omicron variant infection.

The present study investigated the epidemiology and clinical characteristics of infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant and determined the risk factors for delayed discharge or release from isolation for pediatric patients in Quanzhou, China in 2022. There were 145, 254 and 23 patients in the asymptomatic, mildly symptomatic and moderately symptomatic categories, respectively. The proportion of pediatric patients in the moderately symptomatic category increased with increasing age. No child aged <1 year and 9.02% of patients aged 13-18 years were in the moderately symptomatic category. The proportion of patients with asymptomatic infection did not differ significantly by vaccination status. The median days until the first negative conversion of viral RNA was 11 days, and the median hospitalization duration was 16 days. Most symptoms appeared in the upper respiratory tract. Notably, ~33.23% of patients showed elevated aspartate aminotransferase levels. C-reactive protein and interleukin-6 (IL-6) levels, and lymphocyte counts were consistently lower in asymptomatic patients than those in in symptomatic patients. Adjusted logistic regression analyses indicated that IL-6 levels and time to the first negative conversion of viral RNA were independent risk factors for delayed discharge. The area under the curve of the regression model for predicting delayed discharge was 0.760. In conclusion, these results could facilitate the formulation of global epidemic prevention policies for pediatric patients.

Characteristics of innate, humoral and cellular immunity in children with non-severe SARS-CoV-2 infection.

The symptoms of children infected with SARS-CoV-2 are mainly asymptomatic, mild, moderate, and a few severe cases. To understand the immune response characteristics of children infected with SARS-COV-2 who do not develop severe cases, 82 children infected with the SARS-CoV-2 delta strain were recruited in this study. Our results showed that high levels of IgG, IgM, and neutralization antibodies appeared in children infected with SARS-CoV-2. SARS-CoV-2 induced upregulation of both pro-inflammatory factors including TNF-α and anti-inflammatory factors including IL-4 and IL-13 in the children, even IL-10. The expression of INF-α in infected children also showed a significant increase compared to healthy children. However, IL-6, one of the important inflammatory factors, did not show an increase in infected children. It is worth noting that a large number of chemokines reduced in the SARS-CoV-2-infected children. Subsequently, TCR Repertoire, TCRß bias, and preferential usage were analyzed on data of TCR next-generation sequencing from 8 SARS-CoV-2-infected children and 8 healthy controls. We found a significant decrease in TCR clonal diversity and a significant increase in TCR clonal expansion in SARS-CoV-2-infected children compared to healthy children. The most frequent V and J genes in SARS-CoV-2 children were TRBV28 and TRBJ2-1. The most frequently VßJ gene pairing in SARS-CoV-2 infected children was TRBV20-1-TRBJ2-1. The strong antiviral antibody levels, low expression of key pro-inflammatory factors, significant elevation of anti-inflammatory factors, and downregulation of many chemokines jointly determine that SARS-CoV-2-infected children rarely develop severe cases. Overall, our findings shed a light on the immune response of non-severe children infected with SARS-CoV-2.

Distinguishing COVID-19 from seasonal influenza in patients under age 65 years-a retrospective observational cohort study comparing the 2009 influenza A (H1N1) and 2022 SARS-CoV-2 pandemics.

Introduction: This study explored the differences in clinical characteristics between the 2009 pandemic influenza A (H1N1) and SARS-CoV-2 BA.2 variant (Omicron) infections in patients younger than age 65 years, to improve identification of these diseases and better respond to the current epidemic. Methods: Data from 127 patients with the 2009 pandemic influenza A (H1N1) diagnosed between May and July of 2009 and 3,265 patients with Omicron diagnosed between March and May of 2022 were collected. Using a 1:2 match based on age (difference <2 years), sex, and underlying diseases, data from 115 patients with the 2009 pandemic influenza A (H1N1) infection (H1N1 group) and 230 patients with SARS-CoV-2 Omicron BA.2 infection (Omicron group) were analyzed. The clinical manifestations were compared between the groups, logistic regression was performed to identify possible independent risk factors for each group, and multiple linear regression was used to analyze the factors predicting time for nucleic acid negativization (NAN). Results: The median [interquartile range] age of the two groups was 21 [11, 26] years. Compared with the H1N1 group, the Omicron group had: lower white blood cell counts and C-reactive protein levels; less fever, nasal congestion, sore throat, cough, sputum, and headache; and more olfactory loss, muscle soreness, and lactate dehydrogenase (LDH) abnormalities. Patients in the Omicron group used fewer antibiotics and antiviral drugs, and the time for NAN was longer (17 [14,20] VS 4 [3,5] days, P<0.001). Logistic regression showed that fever, cough, headache, and increased white blood cell count were more strongly correlated with the H1N1 group, while muscle soreness and LDH abnormalities were more strongly correlated with the Omicron group. Fever (B 1.529, 95% confidence interval [0.149,2.909], P=0.030) significantly predicted a longer time for NAN in patients with Omicron. Discussion: There are significant differences in clinical characteristics between SARS-CoV-2 Omicron infection and the 2009 pandemic influenza A (H1N1) infection. Recognition of these differences has important implications for clinical practice.

Chinese expert consensus on interventional diagnosis and management of acquired digestive-respiratory tract fistulas (second edition).

Acquired digestive-respiratory tract fistulas occur with abnormal communication between the respiratory tract and digestive tract caused by a variety of benign or malignant diseases, leading to the alimentary canal contents in the respiratory tract. Although various departments have been actively exploring advanced fistula closure techniques, including surgical methods and multimodal therapy, some of which have gotten good clinical effects, there are few large-scale evidence-based medical data to guide clinical diagnosis and treatment. The guidelines update the etiology, classification, pathogenesis, diagnosis, and management of acquired digestive-respiratory tract fistulas. It has been proved that the implantation of the respiratory and digestive stent is the most important and best treatment for acquired digestive-respiratory tract fistulas. The guidelines conduct an in-depth review of the current evidence and introduce in detail the selection of stents, implantation methods, postoperative management and efficacy evaluation.

Risk factors associated with Pneumocystis jirovecii pneumonia in non-HIV immunocompromised patients and co-pathogens analysis by metagenomic next-generation sequencing.

BACKGROUND: Pneumocystis jirovecii pneumonia (PJP) is one of the most common opportunistic infections in immunocompromised patients. However, the accurate prediction of the development of PJP in non-HIV immunocompromised patients is still unclear. METHODS: Non-HIV immunocompromised patients confirmed diagnosis of PJP by the clinical symptoms, chest computed tomography and etiological results of metagenomic next-generation sequencing (mNGS) were enrolled as observation group. Another group of matched non-HIV immunocompromised patients with non-PJP pneumonia were enrolled to control group. The risk factors for the development of PJP and the co-pathogens in the bronchoalveolar lavage fluid (BALF) detected by mNGS were analyzed.  RESULTS: A total of 67 (33 PJP, 34 non-PJP) participants were enrolled from Fujian Provincial Hospital. The ages, males and underlying illnesses were not significantly different between the two groups. Compared to non-PJP patients, PJP patients were more tends to have the symptoms of fever and dyspnea. The LYM and ALB were significantly lower in PJP patients than in non-PJP patients. Conversely, LDH and serum BDG in PJP patients were significantly higher than in non-PJP controls. For immunological indicators, the levels of immunoglobulin A, G, M and complement C3, C4, the numbers of T, B, and NK cells, had no statistical difference between these two groups. Logistic multivariate analysis showed that concomitant use of corticosteroids and immunosuppressant (OR 14.146, P = 0.004) and the lymphocyte counts < 0.7 × 109/L (OR 6.882, P = 0.011) were risk factors for the development of PJP in non-HIV immunocompromised patients. 81.82% (27/33) and 64.71% (22/34) mixed infections were identified by mNGS in the PJP group and non-PJP group separately. CMV, EBV and Candida were the leading co-pathogens in PJP patients. The percentages of CMV and EBV identified by mNGS in PJP group were significantly higher than those in the control group(p < 0.005).  CONCLUSIONS: Clinicians should pay close attention to the development of PJP in non-HIV immunocompromised patients who possess the risk factors of concomitant use of corticosteroids and immunosuppressant and the lymphocyte counts < 0.7 × 109/L. Prophylaxis for PJP cannot rely solely on CD4+ T counts in non-HIV immunocompromised patients. Whether CMV infection increases the risk of PJP remains to be further investigated.

The effects of vaccination on the disease severity and factors for viral clearance and hospitalization in Omicron-infected patients: A retrospective observational cohort study from recent regional outbreaks in China.

Object: This study attempted to explore the effects of vaccination on disease severity and the factors for viral clearance and hospitalization in omicron-infected patients. Methods: The clinical manifestations of 3,265 Omicron-infected patients (BA.2 lineage variant; the Omicron group) were compared with those of 226 Delta-infected patients (the Delta group). A Multi-class logistic regression model was employed to analyze the impacts of vaccination doses and intervals on disease severity; a logistic regression model to evaluate the risk factors for hospitalization; R 4.1.2 data analysis to investigate the factors for time for nucleic acid negativization (NAN). Results: Compared with the Delta group, the Omicron group reported a fast transmission, mild symptoms, and lower severity incidence, and a significant inverse correlation of vaccination dose with clinical severity (OR: 0.803, 95%CI: 0.742-0.868, p<0.001). Of the 7 or 5 categories of vaccination status, the risk of severity significantly decreased only at ≥21 days after three doses (OR: 0.618, 95% CI: 0.475-0.803, p<0.001; OR: 0.627, 95% CI: 0.482-0.815, p<0.001, respectively). The Omicron group also reported underlying illness as an independent factor for hospitalization, sore throat as a protective factor, and much shorter time for NAN [15 (12,19) vs. 16 (12,22), p<0.05]. NAN was associated positively with age, female gender, fever, cough, and disease severity, but negatively with vaccination doses. Conclusion: Booster vaccination should be advocated for COVID-19 pandemic-related control and prevention policies and adequate precautions should be taken for patients with underlying conditions.

Ipratropium bromide and noninvasive ventilation treatment for COPD.

OBJECTIVE: To explore the effects of ipratropium bromide combined with non-invasive ventilation for patients with both chronic obstructive pulmonary disease (COPD) and respiratory failure. METHODS: A total of 110 patients with both COPD and respiratory failure who were admitted to our hospital from April 2018 to August 2019 were enrolled in this study; of which 52 patients were treated with a noninvasive ventilator as Group A, and the rest were treated with ipratropium bromide combined with noninvasive ventilation as Group B. The two groups were compared for blood gas indexes, pulmonary function, and treatment efficacy, and adverse reactions. RESULTS: After treatment, Group B showed better blood gas indexes and pulmonary function than Group A (both P < 0.05), and Group B also showed significantly lower levels of inflammatory factors than Group A (P < 0.05). In addition, the efficacy and life quality of Group B were better than those of Group A, and adverse reactions of Group B were less than those of Group A (all P < 0.05). CONCLUSION: Ipratropium bromide combined with noninvasive ventilation is effective in the treatment of patients with both COPD and respiratory failure.

Unvaccinated Children Are an Important Link in the Transmission of SARS-CoV-2 Delta Variant (B1.617.2): Comparative Clinical Evidence From a Recent Community Surge.

Objective: To evaluate the necessity of Covid-19 vaccination in children aged < 12 y by comparing the clinical characteristics between unvaccinated children aged < 12 y and vaccinated patients aged ≥ 12y during the Delta surge (B.1.617.2) in Putian, Fujian, China. Methods: A total of 226 patients with SARS-Cov-2 Delta variant (B.1.167.2; confirmed by Real-time PCR positivity and sequencing) were enrolled from Sep 10th to Oct 20th, 2021, including 77 unvaccinated children (aged < 12y) and 149 people aged ≥ 12y, mostly vaccinated. The transmission route was explored and the clinical data of two groups were compared; The effect factors for the time of the nucleic acid negativization (NAN) were examined by R statistical analysis. Results: The Delta surge in Putian spread from children in schools to factories, mostly through family contact. Compared with those aged ≥ 12y, patients aged < 12y accounted for 34.07% of the total and showed milder fever, less cough and fatigue; they reported higher peripheral blood lymphocyte counts [1.84 (1.32, 2.71)×10^9/L vs. 1.31 (0.94, 1.85)×10^9/L; p<0.05), higher normal CRP rate (92.21% vs. 57.72%), lower IL-6 levels [5.28 (3.31, 8.13) vs. 9.10 (4.37, 15.14); p<0.05]. Upon admission, their COVID19 antibodies (IgM and IgG) and IgG in convalescence were lower [0.13 (0.00, 0.09) vs. 0.12 (0.03, 0.41), p<0.05; 0.02 (0.00, 0.14) vs. 1.94 (0.54, 6.40), p<0.05; 5.46 (2.41, 9.26) vs. 73.63 (54.63, 86.55), p<0.05, respectively], but longer NAN time (18 days vs. 16 days, p=0.13). Conclusion: Unvaccinated children may be an important link in the transmission of SARS-CoV-2 delta variant (B1.617.2), which indicated an urgent need of vaccination for this particular population.

Anti-inflammatory effects of brucea javanica oil via inhibition of NF-κB activation.

OBJECTIVE: As a traditional herbal medicine extracted from the seeds of Brucea javanica, Brucea javanica oil (BJO) has been clinically used to treat wart, chronic gastroenteritis and a variety of malignant tumors, including gastrointestinal cancer and lung cancer. We have recently reported the anti-tumor role and possible molecular mechanisms of BJO in treatment of lung cancer. However, it remains elusive whether BJO also has an anti-inflammatory effect. METHODS: The pneumonia-related inflammatory factors of macrophages under LPS treatment were investigated by real-time PCR and ELISA assays. LPS-induced acute pneumonia rat model was established. Hematoxylin and eosin (HE) examination was performed to detect histopathological changes in the lung tissues. Real-time PCR and ELISA assays were also used to detect the pneumonia-related inflammatory factors in lung tissues. RESULTS: LPS-induced expression and secretion of pneumonia-related inflammatory factors (TNF-α, IL-1ß, IL-6 and IL-8) were significantly suppressed by BJO in a concentration-dependent manner in RAW264.7 cells. However, BJO did not affect cell proliferation and survival rate. Further mechanistic studies revealed that BJO down-regulated the phosphorylation of IκB and p65, thereby inhibiting NF-κB pathway of macrophages and exerting its anti-inflammatory function. Western blot analysis showed that the phosphorylation levels of IκB and p65 were significantly up-regulated while the protein level of IκB was inhibited upon LPS stimulation in RAW264.7 cells and in lung tissue. Notably, LPS stimulation levels of IκB and p65 were effectively reversed under BJO co-treatment. The expression level of p65 was not influenced by LPS and BJO treatment. HE staining results showed that BJO can reduce the infiltration of inflammatory cells in lung. CONCLUSION: BJO can reduce the level of inflammatory factors in lung tissue, which provides a theoretical basis for BJO emulsion as an adjuvant therapy for pneumonia.

Diagnostic value of conventional tumor markers in young patients with pulmonary nodules.

BACKGROUND: Lung cancer is one of the most common malignancies, and there is a trend of increasing incidence in young patients. The preoperative diagnosis of pulmonary nodules is mainly based on the combination of imaging and tumor markers. There is no relevant report on the diagnostic value of tumor markers in young pulmonary nodules. Our study was designed to explore the value of five tumor markers in young patients with pulmonary nodules. METHODS: We reviewed the medical records of 390 young patients (age ≤45 years) with pulmonary nodules treated at two separate centers from January 1, 2015, to January 1, 2021. Malignant pulmonary nodules were confirmed in 318 patients, and the other 72 patients were diagnosed with benign pulmonary nodules. The gold standard for diagnosis of pulmonary nodules was surgical biopsy. The conventional serum biomarkers included cytokeratin 19 (CYFRA21-1), pro-gastrin-releasing-peptide (ProGRP), carcinoembryonic antigen (CEA), neuron-specific enolase (NSE), and squamous cell carcinoma-associated antigen (SCCA). The diagnostic values of five tumor markers were analyzed by receiver operating characteristic (ROC) curves. RESULTS: There were no significant differences in the expression of five tumor markers between the groups (p > 0.05). Single tumor marker (CYFRA21-1, ProGRP, CEA, NSE, and SCCA) showed a limited value in the diagnosis of malignant pulmonary nodules, with the AUC of 0.506, 0.503 0.532, 0.548, and 0.562, respectively. The AUC of the combined examination was only 0.502~0.596, which did not improve the diagnostic value. CONCLUSIONS: Five conventional tumor markers had a limited diagnostic value in young patients with pulmonary nodules.

Etanercept Protected Against Cigarette Smoke Extract-Induced Inflammation and Apoptosis of Human Pulmonary Artery Endothelial Cells via Regulating TNFR1.

PURPOSE: Etanercept (ETN), a tumor necrosis factor-α (TNF-α) inhibitor, has been applied in the treatment of many diseases. However, whether it has effects on chronic obstructive pulmonary disease (COPD) and its interaction with tumor necrosis factor receptor 1 (TNFR1) remained unknown. METHODS: Histopathological analysis of lung tissues from non-smokers and smokers with or without COPD was conducted using hematoxylin-eosin (H&E) staining, Van Gieson (VG) staining, and terminal transferase-mediated biotin dUTP nick end labeling (TUNEL). TNF-α content was measured using Immunohistochemistry. Correlation analysis among apoptosis rate, smoke index, the FEV1/FVC ratio, and TNF-α-positive cells was performed. After ETN treatment and transfection of overexpressed or silenced TNFR1, levels of inflammatory cytokines, apoptosis and related genes expressions in cigarette smoke extract (CSE)-treated human pulmonary artery endothelial cells (HPAECs) were detected using enzyme-linked immunosorbent assay (ELISA), Hoechst 33342 staining, flow cytometry, quantitative real-time PCR (qRT-PCR) and Western blot. RESULTS: Pulmonary arterial remodeling and increased apoptotic and TNF-α+ HPAECs were found in lung tissue of smokers with or without COPD, with higher degrees in smokers with COPD. The numbers of apoptotic and TNF-α+ HPAECs were positively correlated with smoke index, while the FEV1/FVC ratio was negatively correlated with apoptotic HPAECs. In HPAECs, ETN downregulated the expressions of proteins related to CSE-induced apoptosis and the TNF receptor family, decreased CSE-induced cell apoptosis and inflammatory cytokine levels, and inhibited TNFR1 expression and p65 phosphorylation. Overexpressed TNFR1 reversed the effects of ETN on CSE-treated HPAECs, whereas silencing TNFR1 did the opposite. CONCLUSION: ETN protected HPAECs against CSE-induced inflammation and apoptosis via downregulating TNFR1, thus providing a potential therapy for smoking-induced COPD.

Are glucagon-like peptide 1 analogues effective and safe in severe COVID-19 patients with type 2 diabetes?-a case report.

Many cases of novel coronavirus 2019 (COVID-19) have confirmed in many countries around the world. Due to the disorders of the immune system, diabetic patients are more likely to suffer from severe COVID-19. Glucagon-like peptide 1 analogues (GLP-1 analogues) commonly can be used to reduce blood sugar. There is no clear evidence that it can be safely and effectively used in patients with diabetes merged severe COVID-19. In this case, we described A 65-year-old male with hypertension and diabetes was diagnosed with severe COVID-19, he took liraglutide at doses ranging from 0.8 to 1.8 mg. Before admission, liraglutide was not used to reduce blood glucose. Hydroxychloroquine sulfate and abidol were used to antivirus and supportive treatment were used simultaneously during hospitalization. During treatment, the patient's own state was paid attention to, and blood glucose, liver function, kidney function, white blood cells, lymphocytes and other indicators were checked and chest CT was reviewed regularly, which could reflect changes in disease. After treatment, the patient's blood glucose was under control, and his liver function, renal function, white blood cells, lymphocytes and other indicators were normal and chest CT also improved. The case showed that liraglutide may be effective and safe used in patients with severe COVID-19 combined with type 2 diabetes, but more clinical trials are needed.

The chest CT features of coronavirus disease 2019 (COVID-19) in China: a meta-analysis of 19 retrospective studies.

OBJECTIVE: Aimed to summarize the characteristics of chest CT imaging in Chinese hospitalized patients with Coronavirus Disease 2019 (COVID-19) to provide reliable evidence for further guiding clinical routine. METHODS: PubMed, Embase and Web of Science databases were searched to identify relevant articles involving the features of chest CT imaging in Chinese patients with COVID-19. All data were analyzed utilizing R i386 4.0.0 software. Random-effects models were employed to calculate pooled mean differences. RESULTS: 19 retrospective studies (1332 cases) were included. The results demonstrated that the combined proportion of ground-glass opacities (GGO) was 0.79 (95% CI 0.68, 0.89), consolidation was 0.34 (95% CI 0.23, 0.47); mixed GGO and consolidation was 0.46 (95% CI 0.37; 0.56); air bronchogram sign was 0.41 (95% CI 0.26; 0.55); crazy paving pattern was 0.32 (95% CI 0.17, 0.47); interlobular septal thickening was 0.55 (95% CI 0.42, 0.67); reticulation was 0.30 (95% CI 0.12, 0.48); bronchial wall thickening was 0.24 (95% CI 0.11, 0.40); vascular enlargement was 0.74 (95% CI 0.64, 0.86); subpleural linear opacity was 0.28 (95% CI 0.12, 0.48); intrathoracic lymph node enlargement was 0.03 (95% CI 0.00, 0.07); pleural effusions was 0.03 (95% CI 0.02, 0.06). The distribution in lung: the combined proportion of central was 0.05 (95% CI 0.01, 0.11); peripheral was 0.74 (95% CI 0.62, 0.84); peripheral involving central was 0.38 (95% CI 0.19, 0.75); diffuse was 0.19 (95% CI 0.06, 0.32); unifocal involvement was 0.09 (95% CI 0.05, 0.14); multifocal involvement was 0.57 (95% CI 0.48, 0.68); unilateral was 0.16 (95% CI 0.10, 0.23); bilateral was 0.83 (95% CI 0.78, 0.89); The combined proportion of lobes involved (> 2) was 0.70 (95% CI 0.61, 0.78); lobes involved (≦ 2) was 0.35 (95% CI 0.26, 0.44). CONCLUSION: GGO, vascular enlargement, interlobular septal thickening more frequently occurred in patients with COVID-19, which distribution features were peripheral, bilateral, involved lobes > 2. Therefore, based on chest CT features of COVID-19 mentioned, it might be a promising means for identifying COVID-19.

Enhanced Antitumor Efficacy of Docetaxel-Loaded Monomethoxy Poly(ethylene glycol)-Poly(D, L-lactide-co-glycolide) Amphiphilic Copolymer Against Non-Small Cell Lung Cancer.

Lung cancer, including non-small cell lung cancer (NSCLC), is one of the mainly diagnosed cancer and becomes as the leading cause of death induced by cancer worldwide. Conventional antitumor drugs, such as docetaxel (DTX), exhibit excellent therapeutic efficacy, however, serious adverse effects have occurred due to their side effect, which limits their clinical use. Therefore, it is necessary to develop the novel drug delivery systems for antitumor therapy. Herein, we successfully developed mPEG-PLGA nanoparticles for the encapsulation of the clinically relevant drug DTX (NP-DTX) via an improved green method by emulsion. The mPEG-PLGA nanoparticles could target A549 and increased the cytotoxicity of DTX, NP-DTX showed significantly enhanced antitumor effect and therapeutic efficacy on NSCLC in vitro and in vivo. Compared with free DTX, NP-DTX significantly inhibited tumor growth and reduced the side effect of DTX. Therefore, we have shown a promising strategy to construct a novel therapeutic platform for targeted anti-tumor drug delivery.

The potential markers involved in newly diagnosed graves' disease and the development of active graves' orbitopathy.

BACKGROUND: Graves' disease (GD) patients experience two major issues: one is the severe hyperthyroidism associated with newly diagnosed GD, and the other involves the disfiguring and dysfunctional features of active Graves' orbitopathy (GO). Therefore, the aim of our study was to identify potential markers involved in the initial phase of GD dysfunction and the development of active GO. METHODS: Seventy-eight subjects were recruited: 40 with newly diagnosed GD, 20 with inactive GO and 18 with active GO. GO activity was evaluated by the clinical activity score (CAS, active GO = CAS ≥ 3), and severity was assessed according to the NOSPECS classification. Plasma selenium concentrations were determined by dual channel hydride generation atomic fluorescence photometry. A liquid chip assay was used to measure plasma Th1 cytokines IFN-γ and TNF-α; Th2 cytokines IL4, IL5 and IL6; Th17 cytokine IL23; Treg cytokines IL10 and TGF-ß; and two chemokines, CCL2 (Th2 chemokine) and CXCL10 (Th1 chemokine). RESULTS: Among the three groups, newly diagnosed GD patients showed significantly elevated plasma levels of CXCL10 and IL-23 (all p < 0.05). Both CXCL10 and IL23 were significantly correlated with hyperthyroidism severity, specifically, increasing FT3 and FT4 and decreasing TSH. Notably, a very strong positive relationship between IL23 and CXCL10 was revealed (adjusted R square = 0.795; p < 0.001). Moreover, the selenium level was lower, while that of CCL2 was higher, in active GO than in inactive GO (p = 0.007, p < 0.001, respectively). Likewise, we also discovered that increasing CCL2 levels and decreasing selenium levels were associated with high CAS. Remarkably, after adjusting for potential confounding factors, selenium (OR, 0.919) and CCL2 (OR, 1.042) were still independent predictors for the diagnosis of active GO, and similar conclusions were drawn by receiver operating characteristic (ROC) curve analysis. CONCLUSION: Pro-inflammatory cytokines, especially Th17-associated cytokines (e.g., IL23) and Th1 chemokines (e.g., CXCL10), appear to be involved in the initial phase of GD dysfunction. Moreover, we revealed for the first time that decreased plasma selenium levels and increased concentrations of Th2 chemokines (e.g., CCL2) may reflect GO disease activity, shedding light on the diagnosis and evaluation of active GO.