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Abstract Background Pulmonary primitive neuroectodermal tumor (PNET), a member of the Ewing sarcoma family of tumors, is a rare malignancy that is associated with a grim prognosis. To date, fewer than 30 cases of pulmonary PNET have been reported. In this case report, we present the clinical details of a 12-year-old girl with pulmonary PNET who underwent surgical treatment. We also conducted an analysis and summary of other relevant studies and the surgical outcomes. Case presentation In May 2018, a 12-year-old girl was admitted with symptoms of cough and blood-tinged phlegm. A computed tomography scan revealed a large mass, measuring 12.9 cm × 8.1 cm, in the right middle and lower lungs. A percutaneous lung biopsy confirmed poorly differentiated tumor cells with a nested growth pattern. Immunohistochemical staining demonstrated positive expression of CD99, CD56, Vimentin, and Synaptophysin. The patient was diagnosed with pulmonary PNET. Following three cycles of neoadjuvant chemotherapy, a substantial reduction in tumor volume was observed. Subsequently, the patient underwent a surgical procedure involving pneumonectomy and partial resection of the left atrium with the assistance of cardiopulmonary bypass. The patient was discharged 37 days after surgery. During a three-year follow-up period, she exhibited no signs of tumor recurrence and has successfully returned to school. Conclusions This case highlights the successful management of an advanced PNET with neoadjuvant chemotherapy, pneumonectomy, and partial resection of the left atrium employing cardiopulmonary bypass. The patient remained disease-free after three years. Our analysis of surgically treated cases indicates that neoadjuvant chemotherapy can contribute to improved prognoses for PNET patients. It is crucial to emphasize that complete surgical excision remains the cornerstone of treatment, underscoring the importance of surgeons considering radical surgical approaches whenever feasible for patients with pulmonary PNETs.

Cobalt-based amorphous alloys (Co-MG) demonstrate ultra-high permeability and remarkably-low power loss, positioning them as promising candidates for shielding (near-) static magnetic fields and addressing accuracy limitations in extremely-weak magnetic measurements. However, the brittleness and poor understanding about magnetic performance below 100 Hz have impeded their widespread adoption. To integrate satisfied processing, magnetic and mechanical performances, polystyrene-grafted Co-MG composites are developed. Compared with permalloy-1J85, Co-MG-(g-PS_35 %) composite exhibits 40 % increase in initial permeability, 48 % increase in saturation magnetization, 71 % reduction in remanence within shielding area. In contrast to Mn–Zn ferrite, Co-MG-(g-PS_35 %) composite demonstrates the power loss and μ″/μ′2 values lower by an order of magnitude, resulting in magnetic noises 85 % lower at 1 Hz. Furthermore, the resultant composite maintains similar processing-rheological behaviors and mechanical properties compared with bulk polystyrene. It provides an innovative solution to expand real-world applications for biomagnetic detection, and overcome the sensitivity limitation of extremely-weak magnetic measurement.

In the context of spectral hole-burning, normal dispersion with subluminal propagation is usually observed in the spectral hole-burning depth region. However, anomalous dispersion can occur in the continuous absorption peak region, which leads to superluminal light propagation. In this paper, we report an unusual behavior of dispersion at discontinued absorption kink regions. We demonstrate both normal dispersion at the kink absorption region and anomalous dispersion at the spectral hole-burning depth region. The unusual dispersion leads to a positive group index in the absorption kink region and a negative group index in the spectral hole-burning depth region. The spectral hole-burning is due to variation of magnetization rather than the molecular distribution. The outcomes of our work offer promising applications in communication technologies and storage devices.

Abstract Background Hepatocellular carcinoma (HCC) is the fourth leading cause of cancer-related deaths worldwide every year, and most HCC patients are diagnosed with advanced disease and can only receive systemic treatment. TKIs are the most important components of the systemic treatment of HCC and have both good efficacy and adverse events (AEs). Methods This analysis included 207 patients with locally advanced unresectable or metastatic HCC who received oral treatment with apatinib. We analyzed the overall survival (OS) and progression-free survival (PFS) of patients with or without corresponding AEs to evaluate which AEs can predict the efficacy of apatinib. Results Patients with hand-foot syndrome (HFS; p = 0.005), proteinuria (p = 0.006) and diarrhea (p

Nonlinear control of light-matter interaction plays an important role in various optical phenomena, including spin-orbit interaction of light. In this paper, we demonstrate that the spin-orbit interaction of graphene-wrapped nanoparticles can be tuned by the input intensity of light. Typical optical bistable responses are observed in the scattering efficiency and the local electric fields. In the optical bistable regime, the strength of spin-orbit interaction in the near-field is significantly tuned in the switching-up and switching-down branches. The tunability of spin-orbit interaction enables promising nonlinear control schemes in nanophotonic devices.

Tyrosine kinase inhibitors (TKIs), as an important tumor therapy, can induce severe proteinuria that significantly affects anti-tumor therapy. Existing therapies against proteinuria induced by other etiologies are currently ineffective for TKI-induced proteinuria. It has been shown that various types of proteinuria are related to podocyte damage caused by changes in the RelA signaling pathway. Our experiments confirmed that TKIs activate the renal RelA signaling pathway, and induce death of podocytes and destruction of the glomerular filtration barrier. Here we found that Liuwei Dihuang Pill (LDP) attenuated the inflammatory injury of podocytes through inhibiting activation of RelA, and subsequently relieved TKI-related proteinuria and prevented the progression of TMA and FSGS. Our finding indicated that LDP may be effective for the treatment of TKI-induced proteinuria, which is clinically significant.

Abstract Background The diagnosis and treatment of patients with bronchiectasis and nontuberculous mycobacterium (NTM) pulmonary disease are challenging issues and the treatment is also prolonged and depends on the species. There is limited information on patients with bronchiectasis and NTM pulmonary disease in Mainland China. Methods This cross-sectional study was conducted at the China–Japan Friendship Hospital, Beijing, China. Those adult patients who met the diagnostic criteria for bronchiectasis and obtained a culture result of mycobacteria from lower respiratory tract specimens or lung tissue were included in this study. A logistic regression model was used to identify the related factors in patients with NTM pulmonary disease. Results A total of 202 patients with bronchiectasis from 19 cities, 155 without and 47 (23.3%) with NTM pulmonary disease, were included. In all the 47 patients with NTM pulmonary disease, Mycobacterium avium complex was the most common species (66.0%), and 72.3% of them were initiated on standard anti-NTM treatment within 3 months after the diagnosis of NTM pulmonary disease. A larger proportion of patients with NTM pulmonary disease had acute exacerbations of ≥ 3 times within 1 year and were diagnosed bronchiectasis ≥ 50 years among patients with NTM pulmonary disease. The HRCT chest images revealed higher proportions of nodular shadow (100% vs. 35.3%), tree-in-bud sign (97.9% vs. 29.0%), cavities (29.8% vs. 5.8%), and airway dilation of the right middle lobe or the left lingular lobe (63.8% vs. 23.9%) in patients with NTM pulmonary disease than in those without NTM pulmonary disease (all P values = 0.001). The multivariable logistic regression model indicated that three and more abnormal features (OR 33.8; 95% CI 11.1–102.8) and main lesions of bronchial expansion in the middle or lingual lobe (OR 6.4; 95% CI 2.4–16.6) in HRCT chest images were independently associated with NTM pulmonary disease (P values = 0.001). Conclusion In a single center of Mainland China, > 23% of patients with bronchiectasis had NTM pulmonary disease, and most patients were started on standard treatment within 3 months after the diagnosis of NTM pulmonary disease. These findings suggest that patients with bronchiectasis should be thoroughly examined for the presence of NTM pulmonary disease. Trial registration NCT03594032.

Abstract Background Whether procalcitonin (PCT) or C-reactive protein (CRP) combined with certain clinical characteristics can better distinguish viral from bacterial infections remains unclear. The aim of the study was to assess the ability of PCT or CRP combined with clinical characteristics to distinguish between viral and bacterial infections in hospitalized non-intensive care unit (ICU) adults with lower respiratory tract infection (LRTI). Methods This was a post-hoc analysis of a randomized clinical trial previously conducted among LRTI patients. The ability of PCT, CRP and PCT or CRP combined with clinical symptoms to discriminate between viral and bacterial infection were assessed by portraying receiver operating characteristic (ROC) curves among patients with only a viral or a typical bacterial infection. Results In total, 209 infected patients (viral 69%, bacterial 31%) were included in the study. When using CRP or PCT to discriminate between viral and bacterial LRTI, the optimal cut-off points were 22 mg/L and 0.18 ng/mL, respectively. When the optimal cut-off for CRP (≤ 22 mg/L) or PCT (≤ 0.18 ng/mL) combined with rhinorrhea was used to discriminate viral from bacterial LRTI, the AUCs were 0.81 (95% CI: 0.75–0.87) and 0.80 (95% CI: 0.74–0.86), which was statistically significantly better than when CRP or PCT used alone (p

Background Chronic cough is a common complaint, but there are no population-based data on its burden in China. We determined the prevalence of chronic cough and its impact on health status in adults stratified by sex, age and the diagnosis of COPD or the presence of small airway dysfunction (SAD). Methods A representative sample of 57 779 Chinese adults aged 20 years or older was recruited and pulmonary function test was measured. Chronic cough was defined as cough lasting for >3 months in each year. Quality of life was assessed by the 12-item Short Form Health Survey (SF-12), and self-reported history of hospital visits was recorded. Results Chronic cough was found in 3.6% (95% CI 3.1–4.1) of Chinese adults, 2.4% (95% CI 1.9–3.1) of those aged 20–49 years and 6.0% (95% CI 5.3–6.8) of those aged 50 years or older. Individuals with chronic cough had an impaired physical component summary (PCS) score of the SF-12 (p

IntroductionIt is not clear whether polymyxin B/tigecycline (PMB/TGC) combination is better than PMB or TGC alone in the treatment of hospital-acquired pneumonia (HAP) caused by carbapenem-resistant organisms (CROs).MethodsWe conducted a multicenter, retrospective cohort study in patients with HAP caused by CROs. The primary outcome was 28-day mortality, and the secondary outcomes included clinical success and the incidence of acute kidney injury (AKI). Multivariate Cox regression analysis was performed to examine the relationship between antimicrobial treatments and 28-day mortality by adjusting other potential confounding factors.ResultsA total of 364 eligible patients were included in the final analysis, i.e., 99 in the PMB group, 173 in the TGC group, and 92 in the PMB/TGC combination group. The 28-day mortality rate was 28.3% (28/99) in the PMB group, 39.3% (68/173) in the TGC group, and 48.9% (45/92) in the PMB/TGC combination group (p = 0.014). The multivariate Cox regression model showed that there was a statistically significant lower risk of 28-day mortality among participants in the PMB group when compared with the PMB/TGC combination group [hazard ratio (HR) 0.50, 95% confidence interval (CI) 0.31–0.81, p = 0.004] and that participants in the TGC group had a lower risk of 28-day mortality than in the PMB/TGC combination group but without statistical significance. The incidence of AKI in the PMB group (52.5%) and the PMB/TGC combination group (53.3%) was significantly higher than that in the TGC group (33.5%, p = 0.001).ConclusionThe appropriate PMB/TGC combination was not superior to appropriate PMB therapy in the treatment of HAP caused by carbapenem-resistant Enterobacteriaceae/carbapenem-resistant Acinetobacter baumannii (CRE/CRAB) in terms of 28-day mortality.

Seasonal human coronaviruses (HCoVs) including HCoV-229E, -OC43, -NL63, and -HKU1 widely spread in global human populations. However, the relevance of humoral response against seasonal HCoVs to COVID-19 pathogenesis is elusive. In this study, we profiled the temporal changes of IgG antibody against spike proteins (S-IgG) of SARS-CoV-2 and seasonal HCoVs in 838 plasma samples collected from 344 COVID-19 patients. We tested the antigenic cross-reactivities of S protein between SARS-CoV-2 and seasonal HCoVs and evaluated the correlations between the levels of HCoV-OC43 S-IgG and the disease severity in COVID-19 patients. We found that SARS-CoV-2 S-IgG titres mounted until days 22–28, whereas HCoV-OC43 antibody titres increased until days 15–21 and then plateaued until day 46. However, IgG titres against HCoV-NL63, −229E, and -HKU1 showed no significant increase. A two-way cross-reactivity was identified between SARS-CoV-2 and HCoV-OC43. Neutralizing antibodies against SARS-CoV-2 were not detectable in healthy controls who were positive for HCoV-OC43 S-IgG. HCoV-OC43 S-IgG titres were significantly higher in patients with severe disease than those in mild patients at days 1–21 post symptom onset (PSO). Higher levels of HCoV-OC43 S-IgG were also observed in patients requiring mechanical ventilation. At days 1–10 PSO, HCoV-OC43 S-IgG titres correlated to disease severity in the age group over 60. Our data indicate that there is a correlation between cross-reactive antibody against HCoV-OC43 spike protein and disease severity in COVID-19 patients.

BackgroundPatients with features of both asthma and chronic obstructive pulmonary disease (COPD) are seen commonly in the clinic but less is known in the general population. We investigated the prevalence and the heterogeneity of COPD with concomitant features of asthma in Chinese adult population.MethodsCOPD was defined as post-bronchodilator ratio of forced expiratory volume in 1s (FEV1) to forced vital capacity of less than the lower limits of normal. COPD with concomitant features of asthma was defined as either COPD with asthma diagnosed by self-reported physician-diagnosis or by presence of current wheeze, or as COPD with high bronchodilator response (HBR) defined as an increase in FEV1 >15% and >400 ml after bronchodilator.ResultsCOPD with concomitant features of asthma was found in 1.62% (95% CI 1.31–2.00) of adults (≥20 years) or in 15.2% (95% CI 13.0–17.7) of COPD patients. Compared with COPD with HBR, COPD with asthma diagnosis or wheeze were older (61.8 ± 1.1 years vs. 47.4 ± 2.8 years, P < 0.001), and with a lower post-bronchodilator FEV1%pred (68.2 ± 2.3 vs. 96.6 ± 3.4, P < 0.001). Age, smoking status, biomass use and allergic rhinitis were associated with increasing prevalence of COPD with asthma diagnosis or wheeze, and had greater impaired health status, more comorbidities and more acute exacerbations in the preceding 12 months.ConclusionsCOPD with concomitant features of asthma is common in people with COPD and those with COPD with asthma diagnosis or wheeze experience worse clinical severity than COPD with HBR. These findings will help toward the definition of the asthma-COPD overlap condition.

Abstract Background The European Organization for Research and Treatment of Cancer/Mycoses Study Group (EORTC/MSG) criteria are widely used in the diagnosis of invasive pulmonary aspergillosis (IPA), but they only apply to immunocompromised patients. We here aimed to identify clinical characteristics helpful to the diagnosis of IPA in non-immunocompromised patients. Methods This is a multicenter retrospective study. Data were collected from adult patients with IPA admitted to 15 tertiary hospitals in China from 2010 to 2016. Results We included 254 patients in the study, of whom 66 (26.0%) were immunocompromised, and 188 (74.0%) were not. Airway-invasion-associated computed tomography (CT) signs including patchy exudation along the airway (67.6% vs. 45.5%, P = 0.001) and thickened airway wall (42.0% vs. 16.7%, P

ABSTRACTTo identify the association between the kinetics of viral load and clinical outcome in severe coronavirus disease 2019 (COVID-19) patients, a retrospective study was performed by involved 188 hospitalized severe COVID-19 patients in the LOTUS China trial. Among the collected 578 paired throat swab (TS) and anal swab (AS) samples, viral RNA was detected in 193 (33.4%) TS and 121 (20.9%) AS. A higher viral RNA load was found in TS than that of AS, with means of 1.0 × 106 and 2.3 × 105 copies/ml, respectively. In non-survivors, the viral RNA in AS was detected earlier than that in survivors (median of 14 days vs 19 days, P = 0.007). The positivity and viral load in AS were higher in non-survivors than that of survivors at week 2 post symptom onset (P = 0.006). A high initial viral load in AS was associated with death (OR 1.368, 95% CI 1.076–1.741, P = 0.011), admission to the intensive care unit (OR 1.237, 95% CI 1.001–1.528, P = 0.049) and need for invasive mechanical ventilation (OR 1.340, 95% CI 1.076–1.669, P = 0.009). Our findings indicated viral replication in extrapulmonary sites should be monitored intensively during antiviral therapy.

Summary: Background: Kidney damage in COVID-19 patients has been of special concern. The association of acute kidney injury (AKI) with post-acute kidney function among COVID-19 survivors was not sufficiently elucidated. Methods: An ambidirectional cohort study was conducted with enrollment of COVID-19 survivors discharged from hospital between Jan 7, and May 29, 2020. Study participants were invited to follow-up visits at 6 and 12 months after symptom onset. The primary outcome was percentage of estimated glomerular filtration rate (eGFR) decreased from acute phase (between symptom onset and hospital discharge) to follow-up, and secondary outcome was reduced renal function at follow-up. Findings: In total, 1,734 study participants were included in this study. Median follow-up duration was 342.0 days (IQR, 223.0-358.0) after symptom onset. After multivariable adjustment, percentage of eGFR decreased from acute phase to follow-up was 8.30% (95% CI, 5.99-10.61) higher among AKI participants than those without AKI at acute phase. Participants with AKI had an odds ratio (OR) of 4.60 (95% CI, 2.10-10.08) for reduced renal function at follow-up. The percentage of eGFR decreased for participants with AKI stage 1, stage 2, and stage 3 was 6.02% (95% CI, 3.48-8.57), 15.99% (95% CI, 10.77-21.22), and 17.79% (95% CI, 9.14-26.43) higher compared with those without AKI, respectively. Interpretation: AKI at acute phase of COVID-19 was closely related to the longitudinal decline and post-acute status of kidney function at nearly one-year after symptom onset. Earlier and more intense follow-up strategies on kidney function management could be beneficial to COVID-19 survivors. Funding: Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences (CIFMS 2020-I2M-CoV19-005, 2018-I2M-1-003, and 2020-I2M-2-013); National Natural Science Foundation of China (82041011); National Key Research and Development Program of China (2018YFC1200102); Major Projects of National Science and Technology on New Drug Creation and Development of Pulmonary Tuberculosis (2020ZX09201001).

BackgroundCytokine storm observed in patients with severe Coronavirus Disease 2019 (COVID-19) contributes to poor clinical outcomes and increased mortality. Janus kinases (JAKs) are important mediators in the cytokine storm. Therefore, we conduct a living systematic review and meta-analysis of the literature investigating efficacy and safety of JAK inhibitors for patients with COVID-19.MethodsDatabases were searched up to December 1, 2021 for interventional and observational studies comparing JAK inhibitor treatment with concurrent control in patients with COVID-19. Efficacy and safety outcomes were evaluated by pooled risk ratio (RR).ResultsOf 3,170 records retrieved, 15 studies were eligible and 13 were evaluated in the meta-analysis (n = 3,977). Based on data from three randomized controlled trials (RCTs), baricitinib treatment significantly decreased mortality by day 28 in hospitalized patients with COVID-19 (RR = 0.64, 95% CI 0.51–0.80) without increasing the incidence of adverse outcomes. In subgroup analysis, patients who required supplemental oxygen (RR = 0.62, 95% CI 0.41–0.95) or high-flow oxygen/non-invasive ventilation (RR = 0.59, 95% CI 0.42–0.85) at baseline benefited most. Pooled analysis of all eligible studies for JAK inhibitors (baricitinib, ruxolitinib, tofacitinib, and nezulcitinib) demonstrated a significant decrease in mortality (RR = 0.62, 95% CI 0.49–0.78) with no increase in the risk of adverse events.ConclusionBaricitinib probably decreases mortality in hospitalized adult patients with COVID-19, especially for patients who required supplemental oxygen or high-flow oxygen/non-invasive ventilation at baseline. The efficacy and safety of other JAK inhibitors, such as ruxolitinib, tofacitinib, and nezulcitinib, await more evidence.Systematic Review Registrationhttps://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021261414, identifier: CRD42021261414.

Chronic obstructive pulmonary disease (COPD) is a heterogeneous disease characterized by chronic inflammation, emphysema, airway remodeling, and altered lung function. Despite the canonical classification of COPD as a neutrophilic disease, blood and airway eosinophilia are found in COPD patients. Identifying the tools to assess eosinophilic airway inflammation in COPD models during stable disease and exacerbations will enable the development of novel anti-eosinophilic treatments. We developed different animal models to mimic the pathological features of COPD. Our results show that eosinophils accumulated in the lungs of pancreatic porcine elastase-treated mice, with emphysema arising from the alveolar septa. A lipopolysaccharide challenge significantly increased IL-17 levels and induced a swift change from a type-2 response to an IL-17-driven inflammatory response. However, lipopolysaccharides can exacerbate cigarette smoking-induced airway inflammation dominated by neutrophil infiltration and airway remodeling in COPD models. Our results suggest that eosinophils may be associated with emphysema arising from the alveolar septa, which may be different from the small airway disease-associated emphysema that is dominated by neutrophilic inflammation in cigarette smoke-induced models. The characterization of heterogeneity seen in the COPD-associated inflammatory signature could pave the way for personalized medicine to identify new and effective therapeutic approaches for COPD.

The associations of long-term exposure to various constituents of fine particulate matter (≤2.5 μm in aerodynamic diameter, PM2.5) air pollution with lung function were not clearly elucidated in developing countries. The aim was to evaluate the associations of long-term exposure to main constituents of PM2.5 with lung function in China. This is a nationwide, cross-sectional analysis among 50,991 study participants from the China Pulmonary Health study. Multivariable linear regression models were used to obtain differences of forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC), FEV1/FVC, peak expiratory flow (PEF), and forced expiratory flow at 25–75% of exhaled FVC (FEF25-75%) associated with an interquartile range (IQR) change of PM2.5 or its constituents. Residential annual PM2.5 levels varied from 26 μg/m3 to 92 μg/m3 (average: 53 μg/m3). An IQR increase of PM2.5 concentrations was associated with lower FEV1 (19.82 mL, 95% CI: 11.30–28.33), FVC (17.45 mL, 95% CI: 7.16–27.74), PEF (86.64 mL/s, 95% CI: 59.77–113.52), and FEF25-75% (31.93 mL/s, 95% CI: 16.64–47.22). Black carbon, organic matter, ammonium, sulfate, and nitrate were negatively associated with most lung function indicators, with organic matter and nitrate showing consistently larger magnitude of associations than PM2.5 mass. This large-scale study provides first-hand epidemiological evidence that long-term exposure to ambient PM2.5 and some constituents, especially organic matter and nitrate, were associated with lower large- and small- airway function.

At present, establishing a multidimensional characteristic model of a boiler combustion system plays an important role in realizing its dynamic optimization and real-time control, so as to achieve the purpose of reducing environmental pollution and saving coal resources. However, the complexity of the boiler combustion process makes it difficult to model it using traditional mathematical methods. In this paper, a kind of hyper-parameter self-optimized broad learning system by a sparrow search algorithm is proposed to model the NOx, SO2 emissions concentration and thermal efficiency of a circulation fluidized bed boiler (CFBB). A broad learning system (BLS) is a novel neural network algorithm, which shows good performance in multidimensional feature learning. However, the BLS has several hyper-parameters to be set in a wide range, so that the optimal combination between hyper-parameters is difficult to determine. This paper uses a sparrow search algorithm (SSA) to select the optimal hyper-parameters combination of the broad learning system, namely as SSA-BLS. To verify the effectiveness of SSA-BLS, ten benchmark regression datasets are applied. Experimental results show that SSA-BLS obtains good regression accuracy and model stability. Additionally, the proposed SSA-BLS is applied to model the combustion process parameters of a 330 MW circulating fluidized bed boiler. Experimental results reveal that SSA-BLS can establish the accurate prediction models for thermal efficiency, NOx emission concentration and SO2 emission concentration, separately. Altogether, SSA-BLS is an effective modelling method.

Introduction Current antibiotic prescription for acute exacerbation of chronic obstructive pulmonary disease (AECOPD) is generally based on the Anthonisen criteria in The Global Initiative for Chronic Obstructive Pulmonary Disease (GOLD) guideline that have a potential risk of antibiotics overuse. The dilemma is to identify patients who are most likely to benefit from antibiotics while avoiding unnecessary antibiotic use. Procalcitonin (PCT), a more sensitive and specific biomarker of bacterial infection than other conventional laboratory tests, has the potential to determine those patients in whom antibiotics would be beneficial. It is unclear whether PCT-guided antibiotic therapy is safe and effective for patients hospitalised with AECOPD. The study hypothesis is that PCT-guided antibiotic therapy could reduce the antibiotic prescription rate for AECOPD, compared with the GOLD guideline recommendations, without negatively impacting the treatment success rate.Methods and analysis In this multicenter, open-label, randomised controlled trial, we aim to enrol 500 hospitalised patients with AECOPD that will be randomly assigned to either a PCT-guided group or a GOLD guideline-guided group. The coprimary endpoints are antibiotic prescription rate for AECOPD within 30 days post randomisation and treatment success rate at day 30 post randomisation. The secondary outcomes include: antibiotic prescription rate at day 1 post randomisation; hospital antibiotic exposure; length of hospital stay; rate of subsequent exacerbation and hospital readmission; overall mortality within 30 days post randomisation; changes in lung function and the score of COPD assessment test and modified Medical Research Council; and rate of intensive care unit admission.Ethics and dissemination This trial has been approved by the ethic committee of China–Japan Friendship Hospital. The findings of the study will be disseminated in peer-reviewed journals. If the results of the study are positive, PCT-guided antibiotic therapy is likely to change the guidelines for antibiotic recommendations for patients with AECOPD.Trial registration number ClinicalTrials.gov: NCT04682899.

Although peroxiredoxin 2 (PRDX2) plays a vital role in relieving oxidative stress, its physiological function in cartilage development remains almost unknown. In this study, we found that the expression of PRDX2 significantly increased in the chondrocytes compared with pre-chondrocytes. PRDX2 knockdown significantly decreased the expression of extracellular matrix (ECM) protein (Col2a and Aggrecan), which led to blocked cartilage formation. Moreover, PRDX2 knockdown also inhibited the expression of connective tissue growth factor (CTGF). CTGF is an important growth factor that regulates synthesis of ECM proteins. We explored the possible regulatory mechanism by which PRDX2 regulated the expression of CTGF. Our results demonstrated that PRDX2 knockdown downregulated the expression of CTGF by inhibiting Wnt5a/Yes-associated protein 1 (YAP1) pathway. In addition, PRDX2 knockdown promoted the expression of interleukin 6 (IL-6), indicating PRDX2 expression had an anti-inflammatory function during antler growth. Mechanistically, PRDX2 knockdown promoted cartilage matrix degradation by activating the IL-6-mediated Janus Kinase 2/Signal Transducer and Activator of Transcription 3 (JAK2/STAT3) signaling pathway. These results reveal that PRDX2 is a potential regulator that promotes cartilage extracellular matrix synthesis.

Antler growth depends on the proliferation and differentiation of mesenchymal stem cells (MSCs), and this process may be adversely affected by oxidative stress. Melatonin (MLT) has antioxidant functions, but its role in Cervidae remains largely unknown. In this article, flow cytometry, reactive oxygen species (ROS) identification, qPCR, and other methods were used to investigate the protective mechanism of MLT in H2O2-induced oxidative stress of antler MSCs. The results showed that MLT significantly increases cell viability by relieving the oxidative stress of antler MSCs. MLT inhibits cell apoptosis by protecting mitochondrial function. We blocked the melatonin receptor with luzindole (Luz) and found that the receptor blockade significantly increases H2O2-induced hyperoxide levels and causes significant inhibition of mitochondrial function. MLT treatment activates the nuclear factor E2-related factor 2 (Nrf2) antioxidant signaling pathway, up-regulates the expression of NAD(P)H quinone oxidoreductase 1 (NQO1) and other genes and it could inhibit apoptosis. In contrast, the melatonin receptor blockade down-regulates the expression of Nrf2 pathway-related genes, but significantly up-regulates the expression of apoptotic genes. It was indicated that MLT activates the Nrf2 pathway through the melatonin receptor and alleviates H2O2-induced oxidative stress and apoptosis in antler MSCs. This study provides a theoretical basis for further studying the oxidative stress and antioxidant process of antler MSCs and, thereby, increasing antler yields.

Objectives Long-term use of high-dose glucocorticoids can lead to severe immunosuppression and increased risk of treatment-resistant pneumonia and mortality. We investigated the aetiology and prognostic risk factors of mortality in hospitalised patients who developed pneumonia while receiving glucocorticoid therapy alone or glucocorticoid and other immunosuppressant therapies.Design Retrospective cohort study.Setting Six secondary and tertiary academic hospitals in China.Participants Patients receiving glucocorticoids who were hospitalised with pneumonia between 1 January 2013 and 31 December 2019.Main outcomes We analysed the prevalence of comorbidities, microbiology, antibiotic susceptibility patterns, 30-day and 90-day mortality and prognostic risk factors.Results Conclusions A total of 716 patients were included, with pneumonia pathogens identified in 69.8% of patients. Significant morbidities occurred, including respiratory failure (50.8%), intensive care unit transfer (40.8%) and mechanical ventilation (36%), with a 90-day mortality of 26.0%. Diagnosis of pneumonia occurred within 6 months of glucocorticoid initiation for 69.7% of patients with Cytomegalovirus (CMV) pneumonia and 79.0% of patients with Pneumocystis jirovecii pneumonia (PCP). Pathogens, including Pneumocystis, CMV and multidrug-resistant bacteria, were identified more frequently in patients with persistent lymphocytopenia and high-dose glucocorticoid treatment (≥30 mg/day of prednisolone or equivalent within 30 days before admission). The 90-day mortality was significantly lower for non-CMV viral pneumonias than for PCP (p

According to the Third International Consensus Definition for Sepsis and Septic Shock, sepsis is a life-threatening organ dysfunction resulting from dysregulated host responses to infection. Epidemiological data about sepsis from the 2017 Global Burden of Diseases, Injuries and Risk Factor Study showed that the global burden of sepsis was greater than previously estimated. Bacteria have been shown to be the predominant pathogen of sepsis among patients with pathogens detected, while sepsis caused by viruses is underdiagnosed worldwide. The coronavirus disease that emerged in 2019 in China and now in many other countries has brought viral sepsis back into the vision of physicians and researchers worldwide. Although the current understanding of the pathophysiology of sepsis has improved, the differences between viral and bacterial sepsis at the level of pathophysiology are not well understood. Diagnosis methods that can broadly differentiate between bacterial and viral sepsis at the initial stage after the development of sepsis are limited. New treatments that can be applied at clinics for sepsis are scarce and this situation is not consistent with the growing understanding of pathophysiology. This review aims to give a brief summary of current knowledge of the epidemiology, pathophysiology, diagnosis and treatment of viral sepsis.

The sika deer is one type of seasonal breeding animal, and the growth of its antler is affected by light signals. Melatonin (MLT) is a neuroendocrine hormone synthesized by the pineal gland and plays an important role in controlling the circadian rhythm. Although the MLT/MT1 (melatonin 1A receptor) signal has been identified during antler development, its physiological function remains almost unknown. The role of MLT on antler growth in vivo and in vitro is discussed in this paper. In vivo, MLT implantation was found to significantly increase the weight of antlers. The relative growth rate of antlers showed a remarkable increased trend as well. In vitro, the experiment showed MLT accelerated antler mesenchymal cell differentiation. Further, results revealed that MLT regulated the expression of Collage type II (Col2a) through the MT1 binding mediated transcription of Yes-associated protein 1 (YAP1) in antler mesenchymal cells. In addition, treatment with vascular endothelial growth factor (VEGF) promoted chondrocytes degeneration by downregulating the expression of Col2a and Sox9 (SRY-Box Transcription Factor 9). MLT effectively inhibited VEGF-induced degeneration of antler chondrocytes by inhibiting the Signal transducers and activators of transcription 5/Interleukin-6 (STAT5/IL-6) pathway and activating the AKT/CREB (Cyclin AMP response-element binding protein) pathway dependent on Sox9 expression. Together, our results indicate that MLT plays a vital role in the development of antler cartilage.

Precise point positioning (PPP) is of great importance in fields requiring coordinates with high accuracy, such as geophysics, meteorology, and geodesy. Compared with relative positioning restricted by the length of baseline, PPP using a single receiver is more flexible. Carrier phase observations with much higher precision than pseudorange measurements are used in the positioning process of PPP. However, accurate estimation of integer ambiguity associated with carrier phase observations is a prerequisite. Then the integrity of the phase observable can be completed as a range measurement with high precision. With triple-frequency signals of global navigation satellite system (GNSS) available, combinations of original observations with longer wavelengths and lower noises are preferable. In this paper, we propose an improved ambiguity resolution (AR) method based on the traditional bootstrapping method to make it suitable for PPP and increase the precision of AR and positioning. Virtual ambiguities of extra-wide-lane, wide-lane, and modified narrow-lane combinations are resolved first for their relatively better characteristics. Furthermore, extra pseudoranges are included to decrease the ionospheric delay which cannot be ignored as it is in relative positioning. Then, original ambiguities on the three frequencies can be recovered from the combined ambiguities using three linear equations which are independent to each other. Finally, the performance of the improved method is tested with real GPS navigation data on three frequencies which is provided by the international GNSS service. Compared with the traditional bootstrapping method, it shows that the ambiguity residuals of the improved method have decreased which indicates more accurate estimation. The precision of the positioning results has increased accordingly.

Endometritis is the inflammatory response of the endometrial lining of the uterus and is associated with low conception rates, early embryonic mortality, and prolonged inter-calving intervals, and thus poses huge economic losses to the dairy industry worldwide. Ginsenoside Rb1 (GnRb1) is a natural compound obtained from the roots of Panax ginseng, having several pharmacological and biological properties. However, the anti-inflammatory properties of GnRb1 in lipopolysaccharide (LPS)-challenged endometritis through the TLR4-mediated NF-κB signaling pathway has not yet been researched. This study was planned to evaluate the mechanisms of how GnRb1 rescues LPS-induced endometritis. In the present research, histopathological findings revealed that GnRb1 ameliorated LPS-triggered uterine injury. The ELISA and RT-qPCR assay findings indicated that GnRb1 suppressed the expression level of pro-inflammatory molecules (TNF-α, IL-1β and IL-6) and boosted the level of anti-inflammatory (IL-10) cytokine. Furthermore, the molecular study suggested that GnRb1 attenuated TLR4-mediated NF-κB signaling. The results demonstrated the therapeutic efficacy of GnRb1 in the mouse model of LPS-triggered endometritis via the inhibition of the TLR4-associated NF-κB pathway. Taken together, this study provides a baseline for the protective effect of GnRb1 to treat endometritis in both humans and animals.

High precision positioning requires correct carrier phase observation. However, signal block will cause the discontinuity of the carrier phase named as cycle slip, which will severely depress the positioning efficiency and accuracy. Triple-frequency global navigation satellite system measurements bring benefit to the detection and repair of cycle slip. We propose a modified method to detect cycle slip based on combinations of triple-frequency signals. Cycle slips on the three combinations with longer wavelengths and lower noises are determined by the geometry-free model. Then, original cycle slips on three carriers are determined uniquely by the linear equations. To deal with the insensitive cycle slips, an alternative combination is presented as a supplementary. However, the residual of the first-order time-differenced ionospheric error cannot be ignored in this step or will be mistaken as cycle slip if not eliminated. To remove this interference, the residual is compensated by pre-estimations calculated by previous wide-lane combination with no cycle slips have been detected. In the end, real triple-frequency GPS data provided by IGS is processed by this method. The results show that the proposed method can detect all cycle slips in real time even under high ionospheric activity.

Lung ischemia–reperfusion injury is a common clinical concern. As the injury occurs, the pulmonary afferent nerves play a key role in regulating respiratory functions under pathophysiological conditions. The present study was to examine products of oxidative stress and expression of transient receptor potential A1 in the commissural nucleus of the solitary tract after lung ischemia–reperfusion injury; and further to determine molecular mediators linking to activation of oxidative stress and transient receptor potential ankyrin A1. A rat model of lung ischemia–reperfusion injury was used. Enzyme-linked immunosorbent assay and western blot analysis were employed to examine products of oxidative stress (i.e. 8-isoprostaglandin F2α and 8-hydroxy-2′-deoxyguanosine), and expression of transient receptor potential A1, Nrf2-antioxidant response element, and NADPH oxidase. 8-isoprostaglandin F2α and 8-hydroxy-2′-deoxyguanosine were amplified in the commissural nucleus of the solitary tract of lung ischemia–reperfusion injury rats, accompanied with downregulation of Nrf2-antioxidant response element, and upregulation of NOX4 and transient receptor potential A1. Blocking NADPH oxidase (subtype NOX4) decreased products of oxidative stress in the commissural nucleus of the solitary tract and attenuated upregulation of transient receptor potential A1 induced by lung ischemia–reperfusion injury. Our data revealed specific signaling pathways by which lung ischemia–reperfusion injury impairs Nrf2-antioxidant response and activates oxidative stress in the brainstem thereby leading to amplification of transient receptor potential A1 receptor likely via products of oxidative stress. Data suggest the abnormalities in the pulmonary afferent signals at the brainstem level which is likely to affect respiratory functions as lung ischemia–reperfusion injury occurs.

Vascular endothelial growth factor A (VEGFA) and its receptor VEGFR2 are the main targets of antiangiogenic therapies, and proteinuria is one of the common adverse events associated with the inhibition of the VEGFA/VEGFR2 pathway. The proteinuric kidney damage induced by VEGFR2 tyrosine kinase inhibitors (TKIs) is characterized by podocyte foot process effacement. TKI therapy promotes the formation of abnormal endothelial‒podocyte crosstalk, which plays a key role in TKI-induced podocyte injury and proteinuric nephropathy. This review article summarizes the underlying mechanism by which the abnormal endothelial‒podocyte crosstalk mediates podocyte injury and discusses the possible molecules and signal pathways involved in abnormal endothelial‒podocyte crosstalk. What is more, we highlight the molecules involved in podocyte injury and determine the essential roles of Rac1 and Cdc42; this provides evidence for exploring the abnormal endothelial‒podocyte crosstalk in TKI-induced nephrotoxicity.

Polymer grafted inorganic nanoparticles attract significant attention, but pose challenges because of the complexity. In this work, a facile strategy to the graft polymer onto the surface of nanoparticles have been introduced. The vinyl functionalized SiO2 nanoparticles (NPs) were first prepared by the surface modification of the unmodified SiO2 using γ-methacryloxy propyl-trimethoxylsilane. The NPs were then mixed with polyvinylidene fluoride (PVDF), which was followed by the Co-60 Gamma radiation at room temperature. PVDF molecular chains were chemically grafted onto the surface of SiO2 nanoparticles by the linking of the double bond on the NPs. The graft ratio of PVDF on SiO2 NPs surface can be precisely controlled by adjusting the absorbed dose and reactant feed ratio (maximum graft ratio was 31.3 wt%). The strategy is simple and it should be applied to the surface modification of many other nanoparticles. The prepared PVDF-grafted SiO2 NPs were then dispersed in the PVDF matrix to make the nanocomposites. It was found that the modified NPs can be precisely dispersed into the PVDF matrix, as compared with pristine silica. The filling content of modifications SiO2 NPs on the PVDF nanocomposites is almost doubled than the pristine SiO2 counterpart. Accordingly, the mechanical property of the nanocomposites is significantly improved.

In this work, the localization of reactive compatibilizer (RC, containing poly(methyl methacrylate) (PMMA) backbone with randomly distributed glycidyl methacrylate (GMA) on it) at the polyvinylidene fluoride/poly(l-lactic acid) (PVDF/PLLA) interface has been manipulated by means of GMA contents. At the very beginning of mixing, RC tends to stay in the PVDF phase due to the miscibility between PVDF and PMMA. Upon further shearing, more and more PLLA chains have been grafted on PMMA backbone, producing PLLA–g–PMMA copolymer. The balanced stress on two sides accounts for the localization of compatibilizers at the PVDF/PLLA interface. Finally, the stress of the PLLA side has been enhanced remarkably due to the higher graft density of PLLA, resulting in the enrichment of the copolymer in the PLLA matrix. The migration of RC from the PVDF phase to the immiscible interface and PLLA matrix can be accelerated by employing RC with higher GMA content. Furthermore, the compatibilizer localization produces a significant influence on the morphology and ductility of the PVDF/PLLA blend. Only when the compatibilizers precisely localize at the interface, the blend exhibits the smallest domain and highest elongation at break. Our results are of great significance for not only the fabrication of PLLA with high ductility, but also the precise localization of compatibilizers at the interface of the immiscible blend.

Like many other filamentous ascomycetes, Fusarium graminearum contains two genes named CPK1 and CPK2 that encode the catalytic subunits of cyclic AMP (cAMP)-dependent protein kinase A (PKA). To determine the role of cAMP signaling in pathogenesis and development in F. graminearum, we functionally characterized these two genes. In addition, we generated and characterized the cpk1 cpk2 double and fac1 adenylate cyclase gene deletion mutants. The cpk1 mutant was significantly reduced in vegetative growth, conidiation, and deoxynivalenol production but it had increased tolerance to elevated temperatures. It was defective in the production of penetration branches on plant surfaces, colonization of wheat rachises, and spreading in flowering wheat heads. Deletion of CPK1 had no effect on perithecium development but the cpk1 mutant was defective in ascospore maturation and releasing. In contrast, the cpk2 mutant had no detectable phenotypes, suggesting that CPK2 contributes minimally to PKA activities in F. graminearum. Nevertheless, the cpk1 cpk2 double mutant had more severe defects in vegetative growth and rarely produced morphologically abnormal conidia. The double mutant, unlike the cpk1 or cpk2 mutant, was nonpathogenic and failed to form perithecia on self-mating plates. Therefore, CPK1 and CPK2 must have overlapping functions in vegetative growth, differentiation, and plant infection in F. graminearum. The fac1 mutant was also nonpathogenic and had growth defects similar to those of the cpk1 cpk2 mutant. However, deletion of FAC1 had no effect on conidium morphology. These results indicated that CPK1 is the major PKA catalytic subunit gene and that the cAMP-PKA pathway plays critical roles in hyphal growth, conidiation, ascosporogenesis, and plant infection in F. graminearum.

The state-of-the-art lithium-ion capacitors (LICs), consisting of high-capacity battery-type anode and high-rate capacitor-type cathode, can deliver high energy density and large power density when comparing with traditional supercapacitors and lithium-ion batteries, respectively. However, the ion kinetics mismatch between cathode and anode leads to unsatisfied cycling lifetime and anode degradation. Tremendous efforts have been devoted to solving the abovementioned issue. One promising strategy is altering high conductive hard carbon anode with excellent structural stability to match with activated carbon cathode, assembling dual-carbon LIC. In this contribution, one-pot in-situ expansion and heteroatom doping strategy was adopted to prepare sheet-like hard carbon, while activated carbon was obtained involving activation. Ammonium persulfate was used as expanding and doping agent simultaneously. While furfural residues (FR) were served as carbon precursor. The resulting hard carbon (FRNS-HC) and activated carbon (FRNS-AC) show excellent electrochemical performance as negative and positive electrodes in a lithium-ion battery (LIB). To be specific, 374.2 mAh g−1 and 123.1 mAh g−1 can be achieved at 0.1 A g−1 and 5 A g−1 when FRNS-HC was tested as anode. When combined with a highly porous carbon cathode (SBET = 2961 m2 g−1) synthesized from the same precursor, the LIC showed high specific energy of 147.67 Wh kg−1 at approximately 199.93 W kg−1, and outstanding cycling life with negligible capacitance fading over 1000 cycles. This study could lead the way for the development of heteroatom-doped porous carbon nanomaterials applied to Li-based energy storage applications.