Load-Balancing Routing for LEO Satellite Network with Distributed Hops-Based Back-Pressure Strategy.

With the expansion of user scale in LEO satellite networks, unbalanced regional load and bursty network traffic lead to the problem of load disequilibrium. A distributed hops-based back-pressure (DHBP) routing is proposed. DHBP theoretically derives a fast solution for the minimum end-to-end propagation hops between satellite nodes in inclined-orbit LEO satellite networks; hence, link weights are determined based on remaining hops between the next hop and destination satellites. In order to control the number of available retransmission paths, the permitted propagation region is restricted to a rectangular region consisting of source-destination nodes to reduce the propagation cost. Finally, DHBP is designed distributedly, to realize a dynamic selection of the shortest link with low congestion and balanced traffic distribution without obtaining the whole network topology. Network simulation results demonstrate that DHBP has higher throughput and lower delay under high load conditions compared with state-of-the-art routing protocols.

Empyema caused by Eikenella halliae diagnosed by metagenomic next-generation sequencing (mNGS) after pulmonary surgery: A case report.

Background: Empyema is one of the complications of pulmonary surgery for lung cancer, the incidence of which is not very high, but in severe cases, it can even lead to death, and it is always difficult to diagnose the cause by conventional methods. Case presentation: In this study, we report a clinical case of empyema caused by Eikenella halliae after pulmonary surgery in a 55-year-old man. He had a fever, cough, and expectoration for 3 days and was diagnosed with right hydropneumothorax and empyema, pneumonia, postoperative malignant tumor of the right lower lobe (adenocarcinoma), and hypertension. The microbiology laboratory reported Gram-negative bacteria in pleural effusion, which was preliminarily considered as Eikenella based on culture and 16S rRNA sequencing. Furthermore, metagenomic next-generation sequencing (mNGS) of sputum samples was performed two times and reported negative results and the presence of E. halliae, respectively. The pathogen was finally confirmed as E. halliae by whole genome sequencing, suggesting the high-resolution ability of mNGS in the clinical diagnosis of this case. Conclusion: To our knowledge, this is the first case report of E. halliae infection in China, indicating increased pathogenicity of Eikenella sp. in immunocompromised patients, especially after invasive operations. Our findings emphasize that mNGS allows bacterial diagnosis of empyema and can significantly improve the accuracy of the diagnosis.

Angiotensin-(1-7) alleviates acute lung injury by activating the Mas receptor in neutrophil.

Background: Acute lung injury (ALI) is a major cause of mortality and morbidity in the clinic. None of the current pharmacological interventions has achieved a detectable benefit. The renin-angiotensin system (RAS) is a complex humoral system essentially involved in the regulation of ALI. In the RAS family, angiotensin (Ang)-(1-7) was found to provide protection by counteracting the effects of Ang II in various cardiopulmonary disease models. The downstream receptor of Ang-(1-7) is the G protein-coupled receptor (GPCR) Mas. We hypothesize that the Ang-(1-7)-Mas pathway would protect patients from ALI. Methods: To establish a 2-hit ALI model, the mice underwent intratracheal instillation of hydrochloric acid followed by ventilator-induced lung injury (VILI). ALI was evaluated based on lung edema, histology, myeloperoxidase activity, and proinflammatory cytokine production. The effects of the infusion or inhalation of Ang-(1-7) and Mas receptor blocker A779 were examined. The human neutrophils were isolated, and Mas receptor expression was examined. The neutrophil responses to platelet-activating factor (PAF) stimulation were tested by measuring the formation of reactive oxygen species (ROS), neutrophil adhesion, and chemotaxis. Next, in the mouse model, the neutrophils were depleted using an anti-ly6G antibody. Results: The infusion or inhalation of Ang-(1-7) protected mice from ALI as evidenced by decreases in lung edema, the histological lung injury score, myeloperoxidase activity, and proinflammatory cytokine production. Such effects were largely blocked by the Mas receptor blocker A779. Mas receptor expression in the neutrophils was identified at both the messenger ribonucleic acid and protein levels. Ang-(1-7) prevented neutrophil responses to PAF stimulation, including the formation of ROS, neutrophil adhesion, and chemotaxis, while A779 alleviated these effects. The importance of neutrophils in ALI was further confirmed by neutrophil depletion using the anti-ly6G antibody; however, A779 partially reversed the protective role of neutrophil depletion in ALI, indicating the critical role of Ang-(1-7)-Mas signaling in other pulmonary cells. Conclusions: Ang-(1-7)/Mas receptor attenuates the key features of ALI by regulating neutrophil activation. Our study provides new evidence of their role in the pathogenesis of ALI and may lead to the development of a promising therapeutic strategy.

Possible involvement of the Hedgehog and PDPK1-Akt pathways in the growth and migration of small-cell lung cancer.

BACKGROUND: Small-cell lung cancer (SCLC) accounts for approximately 15% to 20% of all lung cancers, and it is the leading cause of tumor-related deaths globally. This study explored the molecular mechanisms underlying the development of SCLC. METHODS: The correlations of phosphoinositide-dependent kinase-1 (PDPK1), p-Akt, and Hedgehog expression with patient characteristics were analyzed using SCLC specimens, and their expression was measured in BEAS-2B cells (control) and the SCLC cell lines H82, H69, H446, H146, and H526. Transfection experiments were performed to inhibit or activate gene expression in cells. We then measured the proliferation and migration of H146 cells. RESULTS: PDPK1, p-Akt, and Hedgehog expression was significantly higher in SCLC tissues, and their expression was correlated with patient characteristics. p-Akt expression was significantly correlated with Hedgehog expression. In H146 cells, PDPK1 and p-Akt were significantly upregulated. Silencing of PDPK1 or Akt and inhibition of Hedgehog significantly inhibited the proliferation and migration of H146 cells. PDPK1 and Akt affected Hedgehog expression, but Hedgehog did not affect PDPK1 or p-Akt expression. CONCLUSIONS: The interaction between the PDPK1-Akt pathway and the Hedgehog pathway influences the prognosis, growth, and migration of SCLC.

Assessment of knowledge, attitude, and practice towards pulmonary rehabilitation among COPD patients: A multicenter and cross-sectional survey in China.

BACKGROUND: Pulmonary rehabilitation (PR) has been recognized to be an evidence-based treatment recommended for chronic obstructive pulmonary disease (COPD). The aim of this study was to investigate COPD patients' knowledge, attitudes and practices towards PR in China. METHODS: 1138 COPD patients from 13 hospitals were enrolled in this cross-sectional study. A questionnaire designed based on an official statement was completed by the participants. Effects of PR in patients were investigated. RESULTS: Mean score of the knowledge portion was only 7.76, while 46.22% of the participants believed they needed PR. Attendance rate was 24.69%. Financial conditions and hospitalization were contributing factors for scores, attendance rate, and belief in demands for PR therapy. Severe pulmonary function impairment indicated more demands for PR (OR = 0.18) and higher uptake rate (OR = 0.30). There was a weak correlation between smoking status (rho = -0.060), diagnosis year (rho = 0.094), frequency of exacerbations (rho = 0.059) and grades. High CAT score is a facilitator for attitudes towards PR (OR = 0.022). 93.24% of patients claimed that their exercise tolerance improved with PR therapy. The improvements were positively associated with needs (rho = 0.20), family support (rho = 0.22), grades (rho = 0.18), and monthly income of the family (rho = 0.14), but negatively correlated with age (rho = -0.16), exacerbations (rho = -0.15), and CAT score (rho = -0.13). CONCLUSIONS: This study suggested poor perception, disbelief in the need for PR, and limited uptake of PR among COPD patients in China, and revealed the significant factors involved. The findings of this study may assist health professionals in developing targeted strategies to promote PR and improve access and uptake of PR.

Assessing risk factors for SARS-CoV-2 infection in patients presenting with symptoms in Shanghai, China: a multicentre, observational cohort study.

Background: The outbreak of COVID-19 has led to international concern. We aimed to establish an effective screening strategy in Shanghai, China, to aid early identification of patients with COVID-19. Methods: We did a multicentre, observational cohort study in fever clinics of 25 hospitals in 16 districts of Shanghai. All patients visiting the clinics within the study period were included. A strategy for COVID-19 screening was presented and then suspected cases were monitored and analysed until they were confirmed as cases or excluded. Logistic regression was used to determine the risk factors of COVID-19. Findings: We enrolled patients visiting fever clinics from Jan 17 to Feb 16, 2020. Among 53 617 patients visiting fever clinics, 1004 (1·9%) were considered as suspected cases, with 188 (0·4% of all patients, 18·7% of suspected cases) eventually diagnosed as confirmed cases. 154 patients with missing data were excluded from the analysis. Exposure history (odds ratio [OR] 4·16, 95% CI 2·74-6·33; p<0·0001), fatigue (OR 1·56, 1·01-2·41; p=0·043), white blood cell count less than 4 × 109 per L (OR 2·44, 1·28-4·64; p=0·0066), lymphocyte count less than 0·8 × 109 per L (OR 1·82, 1·00-3·31; p=0·049), ground glass opacity (OR 1·95, 1·32-2·89; p=0·0009), and having both lungs affected (OR 1·54, 1·04-2·28; p=0·032) were independent risk factors for confirmed COVID-19. Interpretation: The screening strategy was effective for confirming or excluding COVID-19 during the spread of this contagious disease. Relevant independent risk factors identified in this study might be helpful for early recognition of the disease. Funding: National Natural Science Foundation of China.

Phase unwrapping method based on improved quadratic pseudo-Boolean optimization.

Maximum a posteriori estimation of Markov random fields (MRFs) is a popular research area in computer vision, and many algorithms have been proposed to deal with these types of problems. The phase-unwrapping problem is modeled as the optimization of MRFs in this research, and the binary algorithm, improved quadratic pseudo-Boolean optimization, is utilized to solve the phase-unwrapping problem. Both the interferometric phases generated from the commonly used computer simulated surfaces and also real terrains are researched in the experimental section, and the unwrapping results are compared. The proposed algorithm achieves unwrapping results comparable to the state-of-the-art unwrapping method but costs less time for large-scale phase images.

Tiotropium in Early-Stage Chronic Obstructive Pulmonary Disease.

BACKGROUND: Patients with mild or moderate chronic obstructive pulmonary disease (COPD) rarely receive medications, because they have few symptoms. We hypothesized that long-term use of tiotropium would improve lung function and ameliorate the decline in lung function in patients with mild or moderate COPD. METHODS: In a multicenter, randomized, double-blind, placebo-controlled trial that was conducted in China, we randomly assigned 841 patients with COPD of Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage 1 (mild) or 2 (moderate) severity to receive a once-daily inhaled dose (18 µg) of tiotropium (419 patients) or matching placebo (422) for 2 years. The primary end point was the between-group difference in the change from baseline to 24 months in the forced expiratory volume in 1 second (FEV1) before bronchodilator use. Secondary end points included the between-group difference in the change from baseline to 24 months in the FEV1 after bronchodilator use and the between-group difference in the annual decline in the FEV1 before and after bronchodilator use from day 30 to month 24. RESULTS: Of 841 patients who underwent randomization, 388 patients in the tiotropium group and 383 in the placebo group were included in the full analysis set. The FEV1 in patients who received tiotropium was higher than in those who received placebo throughout the trial (ranges of mean differences, 127 to 169 ml before bronchodilator use and 71 to 133 ml after bronchodilator use; P<0.001 for all comparisons). There was no significant amelioration of the mean (±SE) annual decline in the FEV1 before bronchodilator use: the decline was 38±6 ml per year in the tiotropium group and 53±6 ml per year in the placebo group (difference, 15 ml per year; 95% confidence interval [CI], -1 to 31; P=0.06). In contrast, the annual decline in the FEV1 after bronchodilator use was significantly less in the tiotropium group than in the placebo group (29±5 ml per year vs. 51±6 ml per year; difference, 22 ml per year [95% CI, 6 to 37]; P=0.006). The incidence of adverse events was generally similar in the two groups. CONCLUSIONS: Tiotropium resulted in a higher FEV1 than placebo at 24 months and ameliorated the annual decline in the FEV1 after bronchodilator use in patients with COPD of GOLD stage 1 or 2. (Funded by Boehringer Ingelheim and others; Tie-COPD ClinicalTrials.gov number, NCT01455129 .).

1α,25-Dihydroxyvitamin D3 Induces Neutrophil Apoptosis through the p38 MAPK Signaling Pathway in Chronic Obstructive Pulmonary Disease Patients.

BACKGROUND: Reduced neutrophil apoptosis plays an important role in the pathogenesis of acute exacerbation chronic obstructive pulmonary disease (AECOPD). The p38 mitogen-activated protein kinase (MAPK) signaling pathway is involved in neutrophil apoptosis. 1α,25-Dihydroxyvitamin D3 (1α,25VitD3) can induce tumor cell apoptosis. The aim of this study was to assess the effects of 1α,25VitD3 on peripheral blood neutrophil apoptosis in AECOPD and examine the role of the p38 MAPK signaling pathway. METHODS: The study enrolled 36 AECOPD patients and 36 healthy volunteers. Venous blood samples were obtained from both groups. Serum 25-hydroxyvitamin D (25-(OH) D) levels in peripheral venous blood were assayed using liquid chromatography-tandem mass spectrometry (LC-MS/MS); the neutrophils were separated and cultured with SB203580 (a p38 inhibitor) and 1α,25VitD3. Neutrophil apoptosis was measured using flow cytometry, and phospho-p38 MAPK protein expression was detected by Western blot. Statistical analysis was performed using analysis of variance. Student's t-test and Pearson's correlation coefficient were used for the between-group differences and correlation analysis, respectively. RESULTS: The 25-(OH) D levels were lower in AECOPD patients than in healthy controls, and the peripheral blood neutrophil apoptosis results were similar. 1α,25VitD3 increased the apoptosis rate and the level of phospho-p38 MAPK in peripheral blood neutrophils of AECOPD patients. SB203580 partly inhibited 1α,25VitD3-induced peripheral blood neutrophil apoptosis and phospho-p38 MAPK overexpression. The 25-(OH) D levels were positively correlated with increased peripheral blood neutrophil apoptosis and phospho-p38 MAPK levels. In addition, expression of the phospho-p38 MAPK protein was also positively correlated with peripheral blood neutrophil apoptosis. CONCLUSION: Our results suggest that 1α,25VitD3 induces peripheral blood neutrophil apoptosis through the p38 MAPK signaling pathway in AECOPD patients.

The immunoprotective activity of baicalin in mouse model of cecal ligation and puncture-induced sepsis.

The purpose of the study was to probe the therapeutic effect of baicalin on immunosuppression in the mouse model of cecal ligation and puncture (CLP)-induced sepsis. Mouse model was established by employing the procedure of CLP. The proliferation of T lymphocytes was measured using CFDA-SE staining and MTT method, and the proliferation index was determined to assess the proliferation status of the outer peripheral and mesenteric cells of the lymph node in various treatment groups. Griess reagent was used to detect serum NO concentrations. The CLP mice treated with baicalin showed reduced mortality and improved physical appearance as compared to the untreated animals. The locomotion and coat color of the baicalin-treated mice were normal compared to those of untreated CLP mice. Additionally, upon dissecting, only little abscess and adhesions were observed in their peritoneal cavity. The atrophy of thymus gland and spleen in the septic mice was significantly ameliorated in baicalin-treated CLP mice. Baicalin also suppressed the serum NO levels and promoted the proliferation of peripheral lymphocytes in CLP mice. Baicalin reduced the mortality in septic mice, exhibiting a thymus gland and spleen protecting effect. The results suggest that baicalin mediated its protective effect against CLP-induced sepsis by inhibiting T lymphocytes apoptosis and serum NO concentrations.

Lysyl oxidase promotes bleomycin-induced lung fibrosis through modulating inflammation.

Enzymes involved in collagen biosynthesis, including lysyl oxidase (LOX), have been proposed as potential therapeutic targets for idiopathic pulmonary fibrosis. LOX expression is significantly upregulated in bleomycin (BLM)-induced lung fibrosis, and knockdown of LOX expression or inhibition of LOX activity alleviates the lung fibrosis. Unexpectedly, treatment of the mice with LOX inhibitor at the inflammatory stage, but not the fibrogenic stage, efficiently reduces collagen deposition and normalizes lung architecture. Inhibition of LOX impairs inflammatory cell infiltration, TGF-ß signaling, and myofibroblast accumulation. Furthermore, ectopic expression of LOX sensitizes the fibrosis-resistant Balb/c mice to BLM-induced inflammation and lung fibrosis. These results suggest that LOX is indispensable for the progression of BLM-induced experimental lung fibrosis by aggravating the inflammatory response and subsequent fibrosis process after lung injury.

Thiamine deficiency promotes T cell infiltration in experimental autoimmune encephalomyelitis: the involvement of CCL2.

Multiple sclerosis (MS) is a complex multifactorial disease that results from the interplay between environmental factors and a susceptible genetic background. Experimental autoimmune encephalomyelitis (EAE) has been widely used to investigate the mechanisms underlying MS pathogenesis. Chemokines, such as CCL2, are involved in the development of EAE. We have previously shown that thiamine deficiency (TD) induced CCL2 in neurons. We hypothesized that TD may affect the pathogenesis of EAE. In this study, EAE was induced in C57BL/6J mice by the injection of myelin oligodendroglial glycoprotein (MOG) peptides 35-55 with or without TD. TD aggravated the development of EAE, which was indicated by clinical scores and pathologic alterations in the spinal cord. TD also accelerated the development of EAE in an adoptive transfer EAE model. TD caused microglial activation and a drastic increase (up 140%) in leukocyte infiltration in the spinal cord of the EAE mice; specifically, TD increased Th1 and Th17 cells. TD upregulated the expression of CCL2 and its receptor CCR2 in the spinal cord of EAE mice. Cells in peripheral lymph node and spleen isolated from MOG-primed TD mice showed much stronger proliferative responses to MOG. CCL2 stimulated the proliferation and migration of T lymphocytes in vitro. Our results suggested that TD exacerbated the development of EAE through activating CCL2 and inducing pathologic inflammation.

Quantitative assessment of the influence of common variations (rs8034191 and rs1051730) at 15q25 and lung cancer risk.

Several genome-wide association studies on lung cancer (LC) have reported similar findings of a new susceptibility locus, 15q25. After that, a number of studies reported that rs8034191 and rs1051730 polymorphisms at chromosome 15q25 have been implicated in LC risk. However, studies have yielded contradictory results. To derive a more precise estimation of the relationship, a meta-analysis of 43,742 LC cases and 58,967 controls from 17 published case-control studies was performed. Overall, significantly elevated LC risk was associated with rs8034191-C (OR = 1.26, 95% CI 1.22-1.31, P < 10(-5)) and rs105173-A variant (OR = 1.28, 95% CI 1.20-1.36, P < 10(-5)) when all studies were pooled into the meta-analysis. In the subgroup analysis by ethnicity, significantly increased risks were found for rs8034191 and rs105173 polymorphisms among Caucasians and African American, while no significant associations were observed for the two polymorphisms in East Asians. In addition, we found that rs8034191 and rs105173 confer risk, for both adenocarcinoma and squamous cell carcinoma when stratified by histological types of LC. Furthermore, our results on stratified analysis according to smoking status showed an increased LC risk in ever-smokers, while no associations were detected among never-smokers for the two polymorphisms. In conclusion, this meta-analysis demonstrated that the two common variations (rs8034191 and rs1051730) at 15q25 are a risk factor associated with increased LC susceptibility, but these associations vary in different ethnic populations.