The role of T-helper type 17 (Th17) responses in airway remodeling in asthma is currently unknown. We demonstrate that both parenteral and mucosal allergen sensitization, followed by allergen inhalation, leads to Th17-biased lung immune responses. Unlike Th17 cells generated in vitro, lung Th17 cells did not produce tumor necrosis factor-α or interleukin (IL)-22. Eosinophilia predominated in acute inflammation, while neutrophilia and IL-17 increased in chronic disease. Allergen-induced tolerance involved Foxp3-, Helios-, and glycoprotein-A repetitions predominant-expressing regulatory T cells (Treg) and IL-10/interferon-γ priming. This Treg phenotype was altered in inflamed lungs and abrogated by inhalation of IL-17. Using Th17-deficient mice with genetic disruption of gp130 in T cells, we showed that Th17 cells induce airway remodeling independent of the Th2 response. All-trans retinoic acid administration ameliorated Th17-mediated disease and increased Treg activity, while dexamethasone inhibited eosinophilia but not neutrophilia, and enhanced Th17 development in vitro. Targeting the Th17/Treg axis might therefore be therapeutic in neutrophilic and glucocorticoid-refractory asthma.
Rationale: Endobronchial ultrasound as a powerful diagnostic technology can also be used to perform intratumoral chemotherapy for extraluminal tumor. Patient concerns: A 69-year-old man with chronic obstructive pulmonary disease (COPD) presented with worsening dyspnea. A pulmonary function test showed severe airway obstruction and that forced expiratory volume in 1 s was 43% of the predicted value after a bronchodilator. Diagnoses: A bronchoscopy and histopathological analyses revealed a squamous cell carcinoma mostly located outside of the lumen with central airway obstruction. Interventions: Due to the poor pulmonary function, he cannot tolerate conventional active treatments, such as surgery, full dose systemic chemotherapy, or radiotherapy. Local treatments including argon plasma coagulation, cryotherapy, and bronchoscopic endobronchial intratumoral chemotherapy with cisplatin were performed to debulk intraluminal component of the tumor and recanalize occlusive airways in the left upper lobe. Convex-probe endobronchial ultrasound-guided transbronchial needle injection (EBUS-TBNI) delivered cisplatin into the extraluminal component of the tumor to relieve the symptom of dyspnea and opened up the opportunity for systemic chemotherapy without severe systemic complications. Outcomes: The patient had a good response to the comprehensive therapy of 4 cycles of low-dose intravenous chemotherapy and bronchoscopic interventions. Lessons: EBUS-TBNI is proven an effective and safe method to treat inoperable extraluminal central pulmonary carcinoma complicated with severe COPD. In the future, EBUS-TBNI may offer more treatment indications outlined in the existing publications.
Schistosomiasis is a parasitic disease endemic to freshwater areas of Southeast Asia, Africa, and South America that is capable of causing serious damage to the internal organs. Recent studies have linked exosomes to the progression of schistosomiasis. These structures are important mediators for intercellular communication, assist cells to exchange proteins, lipids, and genetic material and have been shown to play critical roles during host-parasite interactions. This review aims to discuss the pathophysiology of exosomes in schistosomiasis and their roles in regulating the host immune response. Understanding how exosomes are involved in the pathogenesis of schistosomiasis may provide new perspectives in diagnosing and treating this neglected disease.
Background: Associations between glutamine (Gln) enriched nutrition support and surgical patients with gastrointestinal (GI) tumor remain controversy. The purpose of this meta-analysis was to assess the effect of Gln enriched nutrition support on surgical patients with GI tumor in term of relevant biochemical indices, immune indices, and clinical outcomes. Methods: Six databases were systematically searched to find eligible randomized controlled trials (RCTs) from 1966 to May 2014. When estimated the analysis indexes, the relative risk (RR) was used as the effect size of the categorical variable, while the weighted mean difference (MD) was used as the effect size of a continuous variable. Meta-analysis was conducted with Rev Man 5.2. Results: Thirteen RCTs, involving 1034 patients, were included in the meta-analysis. The analysis showed that Gln enriched nutrition support was more effective in increasing serum albumin (MD: 0.10; 95% confidence interval [CI]: 0.02–0.18; P < 0.05), serum prealbumin (MD: 1.98; 95% CI: 1.40–2.55; P < 0.05) and serum transferring (MD: 0.35; 95% CI: 0.12–0.57; P < 0.05), concentration of IgG (MD: 1.26; 95% CI: 0.90–1.63; P < 0.05), IgM (MD: 0.18; 95% CI: 0.11–0.25; P < 0.05), IgA (MD: 0.22; 95% CI: 0.10–0.33; P < 0.05), CD3+ (MD: 3.71; 95% CI: 2.57–4.85; P < 0.05) and CD4/CD8 ratio (MD: 0.27; 95% CI: 0.12–0.42; P < 0.05). Meanwhile, it was more significant in decreasing the incidence of infectious complications (RR: 0.67; 95% CI: 0.50–0.90; P < 0.05) and shortening the length of hospital stay (MD: −1.72; 95% CI: −3.31–−0.13; P < 0.05). Conclusions: Glutamine enriched nutrition support was superior in improving immune function, reducing the incidence of infectious complications and shortening the length of hospital stay, playing an important role in the rehabilitation of surgical GI cancer patients.
Abstract Background The outbreak of coronavirus disease 2019 (COVID-19) has become a global pandemic acute infectious disease, especially with the features of possible asymptomatic carriers and high contagiousness. It causes acute respiratory distress syndrome and results in a high mortality rate if pneumonia is involved. Currently, it is difficult to quickly identify asymptomatic cases or COVID-19 patients with pneumonia due to limited access to reverse transcription-polymerase chain reaction (RT-PCR) nucleic acid tests and CT scans, which facilitates the spread of the disease at the community level, and contributes to the overwhelming of medical resources in intensive care units. Goal This study aimed to develop a scientific and rigorous clinical diagnostic tool for the rapid prediction of COVID-19 cases based on a COVID-19 clinical case database in China, and to assist global frontline doctors to efficiently and precisely diagnose asymptomatic COVID-19 patients and cases who had a false-negative RT-PCR test result. Methods With online consent, and the approval of the ethics committee of Zhongshan Hospital Fudan Unversity (approval number B2020-032R) to ensure that patient privacy is protected, clinical information has been uploaded in real-time through the New Coronavirus Intelligent Auto-diagnostic Assistant Application of cloud plus terminal (nCapp) by doctors from different cities (Wuhan, Shanghai, Harbin, Dalian, Wuxi, Qingdao, Rizhao, and Bengbu) during the COVID-19 outbreak in China. By quality control and data anonymization on the platform, a total of 3,249 cases from COVID-19 high-risk groups were collected. These patients had SARS-CoV-2 RT-PCR test results and chest CT scans, both of which were used as the gold standard for the diagnosis of COVID-19 and COVID-19 pneumonia. In particular, the dataset included 137 indeterminate cases who initially did not have RT-PCR tests and subsequently had positive RT-PCR results, 62 suspected cases who initially had false-negative RT-PCR test results and subsequently had positive RT-PCR results, and 122 asymptomatic cases who had positive RT-PCR test results, amongst whom 31 cases were diagnosed. We also integrated the function of a survey in nCapp to collect user feedback from frontline doctors. Findings We applied the statistical method of a multi-factor regression model to the training dataset (1,624 cases) and developed a prediction model for COVID-19 with 9 clinical indicators that are fast and accessible: ‘Residing or visiting history in epidemic regions’, ‘Exposure history to COVID-19 patient’, ‘Dry cough’, ‘Fatigue’, ‘Breathlessness’, ‘No body temperature decrease after antibiotic treatment’, ‘Fingertip blood oxygen saturation ≤93%’, ‘Lymphopenia’, and ‘C-reactive protein (CRP) increased’. The area under the receiver operating characteristic (ROC) curve (AUC) for the model was 0.88 (95% CI: 0.86, 0.89) in the training dataset and 0.84 (95% CI: 0.82, 0.86) in the validation dataset (1,625 cases). To ensure the sensitivity of the model, we used a cutoff value of 0.09. The sensitivity and specificity of the model were 98.0% (95% CI: 96.9%, 99.1%) and 17.3% (95% CI: 15.0%, 19.6%), respectively, in the training dataset, and 96.5% (95% CI: 95.1%, 98.0%) and 18.8% (95% CI: 16.4%, 21.2%), respectively, in the validation dataset. In the subset of the 137 indeterminate cases who initially did not have RT-PCR tests and subsequently had positive RT-PCR results, the model predicted 132 cases, accounting for 96.4% (95% CI: 91.7%, 98.8%) of the cases. In the subset of the 62 suspected cases who initially had false-negative RT-PCR test results and subsequently had positive RT-PCR results, the model predicted 59 cases, accounting for 95.2% (95% CI: 86.5%, 99.0%) of the cases. Considering the specificity of the model, we used a cutoff value of 0.32. The sensitivity and specificity of the model were 83.5% (95% CI: 80.5%, 86.4%) and 83.2% (95% CI: 80.9%, 85.5%), respectively, in the training dataset, and 79.6% (95% CI: 76.4%, 82.8%) and 81.3% (95% CI: 78.9%, 83.7%), respectively, in the validation dataset, which is very close to the published AI model. The results of the online survey ‘Questionnaire Star’ showed that 90.9% of nCapp users in WeChat mini programs were ‘satisfied’ or ‘very satisfied’ with the tool. The WeChat mini program received a significantly higher satisfaction rate than other platforms, especially for ‘availability and sharing convenience of the App’ and ‘fast speed of log-in and data entry’. Discussion With the assistance of nCapp, a mobile-based diagnostic tool developed from a large database that we collected from COVID-19 high-risk groups in China, frontline doctors can rapidly identify asymptomatic patients and avoid misdiagnoses of cases with false-negative RT-PCR results. These patients require timely isolation or close medical supervision. By applying the model, medical resources can be allocated more reasonably, and missed diagnoses can be reduced. In addition, further education and interaction among medical professionals can improve the diagnostic efficiency for COVID-19, thus avoiding the transmission of the disease from asymptomatic patients at the community level.
Abstract The outstanding mechanical performance and flowability of unidirectionally arrayed chopped strands (UACSs) give them an advantage in the manufacture of engineering structures with complex geometry. For the application of practical structures, the impact responses and damage evolution of material under low‐velocity impact must be investigated in advance. In this study, UACS laminates and continuous carbon fiber laminates with a stacking sequence of [0/90] 4s and a thickness of 2 mm were fabricated for low‐velocity impact tests at 7, 11, 15, and 20 J. The impact responses and postimpact intralaminar damage area were analyzed according to the experimental results, including impact load responses and ultrasound C‐scan inspections. Moreover, to predict the damage evolution of the internal structure, the 3D finite element models were constructed in ABAQUS using a progressive damage model (PDM) through a user‐material subroutine VUMAT. Compared with continuous carbon fiber laminates, the dissipated energy of UACS laminates increases by approximately 10.64% and 57.37% for the 15 and 20 J, respectively. However, the intralaminar damage area of UACS laminates decreased by 29.96% and 28.16% at 15 and 20 J, respectively, since the discontinuous slits in UACS laminates can guide damage paths and suppress damage propagation. Highlights The regularly arrayed short fiber reinforced composite was studied. Revealed the low‐velocity impact responses and predicted the damage evolution. UACS and CFRP laminates have comparable impact performance. Illustrated the slits design can suppress the damage to a relatively small area.
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