Extracorporeal membrane oxygenation for COVID-19 and influenza associated acute respiratory distress syndrome: a systematic review.

BACKGROUND: Extracorporeal membrane oxygenation (ECMO) has been used extensively for H1N1 influenza and coronavirus disease 2019 (COVID-19)-related acute respiratory distress syndrome (ARDS) to improve gas exchange and quickly correct hypoxemia and hypercapnia. This systematic review summarized the evidence on ECMO for the treatment of COVID-19 and influenza-associated ARDS. RESEARCH DESIGN AND METHODS: This is a systematic review and meta-analysis of studies to compare the efficacy and safety of ECMO with conventional mechanical ventilation in adults with COVID-19 and influenza-associated ARDS. The study performed a structured search on PubMed, Embase, Web of Science, Scopus and The Cochrane Library. The primary outcome was hospital mortality. RESULTS: The study included 15 observational studies with 5239 patients with COVID-19 and influenza-associated ARDS. The use of ECMO significantly reduced in-hospital mortality in COVID-19-associated ARDS (OR = 0.40; 95% CI = 0.27-0.58; P < 0.00001) but did not reduce influenza-related mortality (OR = 1.08; 95% CI = 0.41-2.87; P = 0.87). Moreover, ECMO treatment meaningfully increased the incidence of bleeding complications (OR = 7.66; 95% CI = 2.47-23.72; P = 0.0004). CONCLUSION: The use of ECMO significantly reduced in-hospital mortality in COVID-19- associated ARDS, which may be related to the advances in ECMO-related techniques and the increased experience of clinicians. However, the incidence of bleeding complications remains high. [Figure: see text].

Spin in the abstracts of randomized controlled trials of nurse-led care: A cross-sectional study.

BACKGROUND: Nurse-led models of care had been reported as effective intervention approaches for improving health management and reducing hospitalizations of target patients in a number of studies. However, the reporting quality of studies in the field varied and there was a lack of literature evaluation. OBJECTIVE: The objective of the study was to assess the reporting quality and spin of abstracts of published randomized controlled trials which had statistically not significant primary outcomes. Moreover, potential factors associated with the presence of spin were also assessed. METHODS: Studies on nurse-led care were retrieved from PubMed from January 1st, 2017, to December 31st, 2021. Only randomized controlled trials with statistically not significant primary outcomes were included. Study screening and data extraction were carried out by two reviewers independently. The reporting quality of each abstract was evaluated by the Consolidated Standards of Reporting Trials statement, and spin strategies were analyzed using a pre-designed assessment form. Potential predictors for the presence of spin were analyzed by multivariate logistic regressions. RESULTS: The overall reporting quality of the included 75 randomized controlled trial abstracts was not satisfying, with a median score of 16-item Consolidated Standards of Reporting Trials statement at 6 (IQR 5, 8). Forty abstracts used at least one spin strategy in abstracts. Among them, 18 (45.0 %) used spin strategies in the result section and 39 (97.5 %) had spin in the conclusion section. The most common spin strategy identified in abstracts was focusing on statistically significant secondary outcomes (12/40, 30.0 %) in the result section and claiming benefit with no consideration of statistically not significant results for the primary outcomes (32/40, 80.0 %) in the conclusion section. Based on the definition, 29 (72.5 %) abstracts were assessed to have high level of spin in the conclusions of abstracts. By multivariate logistic regression analyses, it was found that only geographic origin (reference: studies from Asian countries, OR = 0.118, 95 % CI 0.027 to 0.511, P = 0.004) and the Consolidated Standards of Reporting Trials statement score (reference: lower score, OR = 0.625, 95 % CI 0.470 to 0.829, P = 0.001) were significantly associated with the presence of spin in abstracts. CONCLUSION: Among the randomized controlled trials with statistically not significant primary outcomes in the field of nurse-led care, the reporting quality of abstracts needs to be improved. Trials from Asian countries and with lower Consolidated Standards of Reporting Trials statement scores are more likely to present spin in abstracts. Findings reported in the result and conclusion sections of these abstracts need to be interpreted with caution.

AAV9-Tspyl2 gene therapy retards bleomycin-induced pulmonary fibrosis by modulating downstream TGF-ß signaling in mice.

Idiopathic pulmonary fibrosis (IPF) is a devastating fibrotic lung disease characterized by scarring and destruction of the lung architecture, with limited treatment options. Targeted gene therapy to restore cell division autoantigen-1 (CDA1) expression may be a potential treatment approach to delay the progression of pulmonary fibrosis (PF). Here, we focused on CDA1, which was significantly decreased in human IPF, in a mouse model of bleomycin (BLM)-induced PF, and in transforming growth factor (TGF-ß)-challenged lung fibroblasts. In vitro, CDA1 overexpression by lentivirus infection in human embryonic lung fibroblasts (HFL1 cells) inhibited the production of pro-fibrotic and pro-inflammatory cytokines, lung fibroblast-to-myofibroblast transition, and extracellular matrix protein expression induced by exogenous TGF-ß1 treatment, whereas CDA1 knockdown with small interfering RNA promoted this effect. CDA1 overexpression also inhibited cell proliferation and migration. In a mouse model of BLM-induced PF, we provided novel evidence that the intratracheal delivery of adeno-associated virus serotype 9 carrying the mouse Tspyl2 gene reduced lung tissue inflammation and fibrosis. Mechanistically, CDA1, as a transcription regulator, could repress the TGF-ß signal transduction in vivo and in vitro. In conclusion, our results show that Tspyl2 gene therapy plays an antifibrotic role by inhibiting the lung fibroblast-to-myofibroblast transition and downstream TGF-ß/Smad3 signaling transduction in BLM-induced PF in mice, suggesting that CDA1 is an appropriate and promising therapeutic target for PF.

The role of immunometabolism in macrophage polarization and its impact on acute lung injury/acute respiratory distress syndrome.

Lung macrophages constitute the first line of defense against airborne particles and microbes and are key to maintaining pulmonary immune homeostasis. There is increasing evidence suggesting that macrophages also participate in the pathogenesis of acute lung injury (ALI)/acute respiratory distress syndrome (ARDS), including the modulation of inflammatory responses and the repair of damaged lung tissues. The diversity of their functions may be attributed to their polarized states. Classically activated or inflammatory (M1) macrophages and alternatively activated or anti-inflammatory (M2) macrophages are the two main polarized macrophage phenotypes. The precise regulatory mechanism of macrophage polarization is a complex process that is not completely understood. A growing body of literature on immunometabolism has demonstrated the essential role of immunometabolism and its metabolic intermediates in macrophage polarization. In this review, we summarize macrophage polarization phenotypes, the role of immunometabolism, and its metabolic intermediates in macrophage polarization and ALI/ARDS, which may represent a new target and therapeutic direction.

Alignment technology based on a central small aperture for the AIMS telescope.

The accurate infrared solar magnetic field measurement system (AIMS) is a 1 m off-axis Gregorian alt-azimuth solar telescope and will be dedicated to measuring the solar magnetic field in mid-infrared. How to align the large-aperture off-axis system is a significant issue. Sub-aperture stitching with the small-aperture standard flat mirror can be applied to the alignment of the large-aperture off-axis system. However, this method is time-consuming and inefficient. We propose an alignment method based on the Zernike polynomials of the central small aperture to solve the low efficiency of sub-aperture stitching. Theoretical simulation shows that the RMS residual error of the system after using the central small-aperture alignment method will be less than 4.5∗10-6λ at 632.8 nm. Practical alignment suggests that our method can make the RMS value of full-aperture wave aberration quickly converge to 0.12λ at 632.8 nm. Compared with the sub-aperture stitching method, our method can significantly reduce the times of sub-aperture stitching and save the alignment time.

Clinical characteristics and risk factors for 90-day overall survival among 204 adult patients with secondary hemophagocytic lymphohistiocytosis: Experience from a single-center retrospective study.

Objectives: To describe the clinical characteristics of secondary hemophagocytic lymphohistiocytosis (HLH) among adult patients, investigate its risk factors for 90-day overall survival (OS) from diagnosis, and establish a new prognostic model applicable to adult patients with secondary HLH. Methods: We conducted a retrospective cohort study of 204 adult patients with secondary HLH, between January 2010 and December 2020. All patients met at least five HLH-2004 criteria. Clinical features, laboratory results, treatments, and clinical outcomes of the patients were reviewed. Prognostic factors associated with 90-day overall survival from diagnosis were screened using Cox proportional hazard models. Results: The most common trigger was malignancy (61.3%). Multivariate analysis showed that age, coagulopathy, levels of hemoglobin, aspartate aminotransferase (AST), lactate dehydrogenase (LDH), creatinine, ferritin, and prothrombin time (PT) were independent prognostic factors for 90-day OS from the diagnosis of HLH. Based on the above risk factors, the patients were further divided into two groups: low-risk (≤4 risk factors) and high-risk (>4 risk factors), with overall 90-day survival rates of 82.7 and 28.1%, respectively (P < 0.001). Conclusion: Patients with older age, coagulopathy, lower hemoglobin, and AST levels, elevated LDH, creatinine and ferritin levels, and prolonged PT tended to have a worse prognosis. Moreover, our prognostic model provides the possibility of forecasting the clinical outcome of adult secondary HLH patients, although a larger sample, multicenter, randomized controlled clinical study is needed to verify the accuracy of the prognostic model.

Facile Synthesis of Fe@C Loaded on g-C3N4 for CO2 Electrochemical Reduction to CO with Low Overpotential.

Electrochemical CO2 reduction has been acknowledged as a hopeful tactic to alleviate environmental and global energy crises. Herein, we designed an Fe@C/g-C3N4 heterogeneous nanocomposite material by a simple one-pot method, which we applied to the electrocatalytic CO2 reduction reaction (ECR). Our optimized 20 mg-Fe@C/g-C3N4-1100 catalyst displays excellent performance for the ECR and a maximum Faradaic efficiency (FE) of 88% with a low overpotential of -0.38 V vs. RHE. The Tafel slope reveals that the first electron transfer, which involves a surface-adsorbed *COOH intermediate, is the rate-determining step for 20 mg-Fe@C/C3N4-1100 during the ECR. More precisely, the coordinating capability of the g-C3N4 framework and Fe@C species as a highly active site promote the intermediate product transmission. These results indicate that the combination of temperature adjustment and precursor optimization is key to facilitating the ECR of an iron-based catalyst.

The Roles of Dipeptidyl Peptidase 4 (DPP4) and DPP4 Inhibitors in Different Lung Diseases: New Evidence.

CD26/Dipeptidyl peptidase 4 (DPP4) is a type II transmembrane glycoprotein that is widely expressed in various organs and cells. It can also exist in body fluids in a soluble form. DPP4 participates in various physiological and pathological processes by regulating energy metabolism, inflammation, and immune function. DPP4 inhibitors have been approved by the Food and Drug Administration (FDA) for the treatment of type 2 diabetes mellitus. More evidence has shown the role of DPP4 in the pathogenesis of lung diseases, since it is highly expressed in the lung parenchyma and the surface of the epithelium, vascular endothelium, and fibroblasts of human bronchi. It is a potential biomarker and therapeutic target for various lung diseases. During the coronavirus disease-19 (COVID-19) global pandemic, DPP4 was found to be an important marker that may play a significant role in disease progression. Some clinical trials on DPP4 inhibitors in COVID-19 are ongoing. DPP4 also affects other infectious respiratory diseases such as Middle East respiratory syndrome and non-infectious lung diseases such as pulmonary fibrosis, lung cancer, chronic obstructive pulmonary disease (COPD), and asthma. This review aims to summarize the roles of DPP4 and its inhibitors in infectious lung diseases and non-infectious diseases to provide new insights for clinical physicians.

Azithromycin Attenuates Bleomycin-Induced Pulmonary Fibrosis Partly by Inhibiting the Expression of LOX and LOXL-2.

Pulmonary fibrosis (PF) is a chronic and progressive process of tissue repair. Azithromycin (AZM) may be beneficial for the treatment of PF because AZM has anti-inflammatory and immune regulatory roles and inhibits remodeling, but the mechanism is not entirely clear. In this study, we established a mouse PF model induced by bleomycin (BLM) and primary mouse lung fibroblasts stimulated by transforming growth factor (TGF)-ß1 to explore the possible mechanisms of AZM in PF. Results showed that AZM reduces mortality and lung inflammation and attenuates BLM-induced PF in mice. AZM effectively reduced the expression of α-smooth muscle actin (SMA) and type I collagen. Meanwhile, expression of lysyl oxidase (LOX) and lysyl oxidase-like protein (LOXL)-2 in the lung tissue of mice after AZM treatment was significantly lower than in the BLM group. In addition, this study found that AZM significantly inhibits the TGF-ß1/Smad and JNK/c-Jun signaling pathways in vivo, and expression of a-SMA, type I collagen, LOX and LOXL-2 in the lung tissue of mice treated with AZM was significantly lower than that in the BLM group. In vitro, AZM also effectively inhibited type I collagen, LOX, LOXL-2 and JNK-c-Jun signaling pathways in TGF-ß1-stimulated primary mouse fibroblasts, and this effect was similar to that of a JNK-specific inhibitor (SP600125). In conclusion, AZM effectively attenuated BLM-induced PF in mice, which may play a role by partially inhibiting the JNK/c-Jun and TGF-ß1/Smad signaling pathways and reducing production of LOX and LOXL2.

Artificial Intelligence for COVID-19: A Systematic Review.

Background: Recently, Coronavirus Disease 2019 (COVID-19), caused by severe acute respiratory syndrome virus 2 (SARS-CoV-2), has affected more than 200 countries and lead to enormous losses. This study systematically reviews the application of Artificial Intelligence (AI) techniques in COVID-19, especially for diagnosis, estimation of epidemic trends, prognosis, and exploration of effective and safe drugs and vaccines; and discusses the potential limitations. Methods: We report this systematic review following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. We searched PubMed, Embase and the Cochrane Library from inception to 19 September 2020 for published studies of AI applications in COVID-19. We used PROBAST (prediction model risk of bias assessment tool) to assess the quality of literature related to the diagnosis and prognosis of COVID-19. We registered the protocol (PROSPERO CRD42020211555). Results: We included 78 studies: 46 articles discussed AI-assisted diagnosis for COVID-19 with total accuracy of 70.00 to 99.92%, sensitivity of 73.00 to 100.00%, specificity of 25 to 100.00%, and area under the curve of 0.732 to 1.000. Fourteen articles evaluated prognosis based on clinical characteristics at hospital admission, such as clinical, laboratory and radiological characteristics, reaching accuracy of 74.4 to 95.20%, sensitivity of 72.8 to 98.00%, specificity of 55 to 96.87% and AUC of 0.66 to 0.997 in predicting critical COVID-19. Nine articles used AI models to predict the epidemic of the COVID-19, such as epidemic peak, infection rate, number of infected cases, transmission laws, and development trend. Eight articles used AI to explore potential effective drugs, primarily through drug repurposing and drug development. Finally, 1 article predicted vaccine targets that have the potential to develop COVID-19 vaccines. Conclusions: In this review, we have shown that AI achieved high performance in diagnosis, prognosis evaluation, epidemic prediction and drug discovery for COVID-19. AI has the potential to enhance significantly existing medical and healthcare system efficiency during the COVID-19 pandemic.

Clinical Characteristics and Prognostic Analysis of Patients With Pulmonary Tuberculosis and Type 2 Diabetes Comorbidity in China: A Retrospective Analysis.

Background: Tuberculosis (TB) is one of the leading communicable diseases, with significant morbidity and mortality. Diabetes can increase the risk of developing TB and the related adverse outcomes. This study retrospectively analyzed the clinical characteristics and prognosis of patients with pulmonary TB and type 2 diabetes comorbidity. Methods: About 282 cases with pulmonary TB and type 2 diabetes comorbidity were identified from West China Hospital between January 1, 2010, and December 31, 2016, and were followed up for at least 3 years. We further used Kaplan-Meier methods and COX regression analysis to identify the influence factors for all-cause death. Results: Compared to the survival patients, patients who died were older, exhibited significantly lower albumin and hemoglobin levels, but higher Charlson Comorbidity Index (CCI) score at admission, and had a lower usage rate of metformin. The all-cause mortality rates at 1 and 5 years were 5.67 and 20.59%, separately. For 1-year all-cause death, higher albumin level (HR = 0.90, 95% CI: 0.81-0.99) was the independently protective factor, but older age (HR = 1.07, 95% CI: 1.01-1.13) and CCI score ≥3 (HR = 6.77, 95% CI: 1.40-32.69) were the independent risk factors. For long-term all-cause death, higher albumin level (HR = 0.94, 95% CI: 0.88-1.00), the use of metformin (HR = 0.21, 95% CI: 0.07-0.59), insulin (HR = 0.27, 95% CI: 0.10-0.74), or sulfonylureas (HR = 0.23, 95% CI: 0.07-0.74) were the independently protective factors, but older age (HR = 1.03, 95% CI: 1.00-1.07) and CCI score ≥3 (HR = 7.15, 95% CI: 2.56-19.92) were the independent risk factors. Conclusions: The lower albumin level, older age, and CCI score ≥3 were predictors of all-cause death in patients with pulmonary TB and type 2 diabetes comorbidity. In the long run, patients who use metformin, insulin, or sulfonylureas as hypoglycemic agents may have a lower incidence of death.

Abstracts for reports of randomised trials of COVID-19 interventions had low quality and high spin.

OBJECTIVES: To assess the reporting quality of abstracts for published randomized controlled trials (RCTs) of interventions for coronavirus disease 2019 (COVID-19), including the use of spin strategies and the level of spin for RCTs with statistically non-significant primary outcomes, and to explore potential predictors for reporting quality and the severity of spin. STUDY DESIGN AND SETTING: PubMed was searched to find RCTs that tested interventions for COVID-19, and the reporting quality and spin in the abstracts were assessed. Linear regression analyses were used to identify potential predictors. RESULTS: Forty RCT abstracts were included in our assessment of reporting quality, and a higher word count in the abstract was significantly correlated with higher reporting scores (95% CI 0.044 to 0.658, P=0.026). Multiple spin strategies were identified. Our multivariate analyses showed that geographical origin was associated with severity of spin, with research from non-Asian regions containing fewer spin strategies (95% CI -0.760 to -0.099, P=0.013). CONCLUSIONS: The reporting quality of abstracts of RCTs of interventions for COVID-19 is far from satisfactory. A relatively high proportion of the abstracts contained spin, and the findings reported in the results and conclusion sections of these abstracts need to be interpreted with caution.

Mesangial IgM deposition predicts renal outcome in patients with IgA nephropathy: a multicenter, observational study.

Mesangial IgM deposition is found in patients with immunoglobulin A nephropathy (IgAN). This study aims to investigate the relationships between mesangial IgM deposition and disease progression in IgAN patients. A total of 1239 patients with biopsy-proven primary IgAN were enrolled in this multicenter, observational study between January 2013 and August 2017. According to the degree of IgM deposition, 1239 patients were divided into three groups: Grade 0 (no or trace; n = 713, 57.55%), Grade 1 (mild; n = 414, 33.41%), Grades 2 + 3 (moderate and marked; n = 112, 9.04%). Using a 1:1 propensity score matching (PSM) method identifying age, gender and treatment modality to minimize confounding factors, 1042 matched patients (out of 1239) with different degrees of IgM deposition were enrolled to evaluate the severity of baseline clinicopathological features and renal outcome: Grade 0 (n = 521, 50.00%), Grade 1 (n = 409, 39.25%), Grades 2 + 3 (n = 112, 10.75%). Kaplan-Meier and Cox proportional hazards analyses were performed to determine whether different degrees of mesangial IgM deposition are associated with varying renal outcomes in IgAN. During a mean follow-up of 48.90 ± 23.86 and 49.01 ± 23.73 months, before and after adjusting for propensity scores, respectively, the rate of complete remission (CR) was progressively lower with increased IgM deposition in both unmatched (63.39%, 46.14%, 45.54%) and matched cohort (61.80%, 46.45%, 45.54%), whereas the proportion of patients progressing to end-stage renal disease (ESRD) showed reverse correlation (P < 0.001). Kaplan-Meier analysis indicated negative correlation between the intensity of mesangial IgM deposits and cumulative renal survival (all P < 0.05). Moreover, Cox regression analysis revealed that the degree of mesangial IgM deposition predicted renal outcome independent of MESTC score and clinical variables in the unmatched (Grade 1, HR, 1.59; 95% CI, 1.11-2.29; P = 0.01; Grades 2 + 3, HR, 1.69; 95% CI, 1.02-2.08; P = 0.04) and matched cohort (Grade 1, HR, 1.84; 95% CI, 1.19-2.85; P = 0.01; Grades 2 + 3, HR, 1.91; 95% CI, 1.01-3.24; P = 0.04). Mesangial IgM deposition is associated with histological activity, clinical severity and renal outcome and is an independent risk factor for poor renal prognosis in IgAN. TRIAL REGISTRATION: TCTR, TCTR20140515001. Registered May 15, 2014, http://www.clinicaltrials.in.th/index.php?tp=regtrials&menu=trialsearch&smenu=fulltext&task=search&task2=view1&id=1074 .

Effective Visible Light-Driven Photocatalytic Degradation of Ciprofloxacin over Flower-like Fe3O4/Bi2WO6 Composites.

Photocatalytic degradation of organic pollution is a vital path to deal with environmental problems. Here, a direct Z-scheme 2D/2D heterojunction of a Fe3O4/Bi2WO6 photocatalyst is fabricated for the degradation of ciprofloxacin by a self-assembly strategy. Furthermore, to characterize the morphology of the obtained composite photocatalysts, various kinds of characterization methods were employed like XRD, XPS, SEM, and TEM. It is indicated that the flower-like photocatalyst is composed of nanosheets. Comparable photocatalysts were prepared by controlling the hydrothermal temperature and the iron content. In the photocatalytic degradation of ciprofloxacin (CIP) in water, under visible light irradiation, FB-180 (synthesized at 180 °C with 4% iron content) presents approximately 99.7% degradation efficiency in only 15 min. Meanwhile, during photocatalytic degradation reactions, the Fe3O4/Bi2WO6 heterojunction also displayed excellent stability, which still kept above 90% degradation efficiency after five consecutive cycles. UV-Vis DRS and M-S analyses showed that the Fe3O4/Bi2WO6 catalyst has a strong visible light absorption capacity and the transfer pathway of photo-induced charge carriers. PL, EIS, and TPR showed that Fe3O4/Bi2WO6 has an efficient separation and transfer rate of the photo-generated carriers. ESR analysis proved that the superoxide radical (•O2 -) and hydroxyl radical (•OH) play a major role in the Fe3O4/Bi2WO6 photocatalytic system. This special 2D/2D heterojunction we proposed may have huge potential for marine pollution treatment by photocatalysis degradation with dramatically boosted activities.

Clinical Characteristics and Prognostic Risk Factors of Patients With Proven Invasive Pulmonary Aspergillosis: A Single-Institution Retrospective Study.

Background: The mortality and burden of medical costs associated with invasive pulmonary aspergillosis (IPA) is very high. Currently, the clinical features and prognostic factors of patients with proven IPA are not very clear, especially in the Chinese population. In this retrospective analysis, we aimed to identify the clinical features and prognostic factors of patients with proven IPA. Methods: The diagnostic criteria for proven IPA were based on the international consensus of the EORTC/MSG. Data of patients with proven IPA at the West China Hospital of Sichuan University between January 2012 and December 2018 were collected. The optimal cut-off value of continuous variables was determined by Receiver Operating Characteristic curve and maximum Youden's index. Finally, using the Cox regression analysis to identify correlations between the clinical parameters associated with morbidity. Results: A total of 117 patients with proven IPA were included in the study, and 32 (27.4%) patients died during the follow-up period. Compared with the survivor group, elderly, patients with comorbidities, and patients undergoing chemotherapy and the level of inflammatory biomarkers [erythrocyte sedimentation rate, platelet count, interleukin-6, C-reactive protein (CRP)] in the non-survivor group were higher, while the albumin level was lower (P = 0.018). The imaging features were consolidation, nodules, cavities, pleural effusion, ground-glass shadows, and halo signs in order. Overall, 41.0% patients had mixed imaging features. The results suggested the most appropriate cut-off value of age and CRP were 60 years and 14.1 mg/L, respectively. The multivariate Cox regression analysis suggested that advanced age (>60 years) [hazard ratio (HR): 10.7, confidence interval (CI): 2.5-44.9, P < 0.001), undergoing chemotherapy (HR: 9.5, CI: 2.7-32.9, P < 0.001), presence of pleural effusion (HR: 5.74, CI: 1.6-20.8, P = 0.008), and increased CRP levels (>14.1 mg/L) (HR: 6.3, CI: 1.2-34.3, P = 0.033) were risk factors for all-cause mortality in patients with proven aspergillosis. Conclusions: This study showed that the prognosis of proven IPA is poor, and the age >60 years, undergoing chemotherapy, pleural effusion on CT image, and CRP levels >14.1 mg/L may be as risk factors for mortality in patients with proven IPA. large samples and real-world studies are needed to confirm these results in the future.

Prevalence of Sarcoidosis-Associated Pulmonary Hypertension: A Systematic Review and Meta-Analysis.

BACKGROUND: Sarcoidosis-associated pulmonary hypertension (SAPH) is associated with poor prognosis, conferring up to a 10-fold increase in mortality in patients with sarcoidosis, but the actual prevalence of SAPH is unknown. METHODS: The PubMed, Embase, and Cochrane Library databases were systematically searched for epidemiological studies reporting the prevalence of SAPH up to July 2021. Two reviewers independently performed the study selection, data extraction, and quality assessment. Studies were pooled using random-effects meta-analysis. RESULTS: This meta-analysis included 25 high-quality studies from 12 countries, with a pooled sample of 632,368 patients with sarcoidosis. The prevalence of SAPH by transthoracic echocardiography in Europe, the United States and Asia was 18.8% [95% confidence interval (CI): 11.1-26.5%], 13.9% (95% CI: 5.4-22.4%) and 16.2% (95% CI: 7.1-25.4%) separately, and the overall pooled prevalence was 16.4% (95%CI: 12.2-20.5%). By right heart catheterization (RHC), the pooled prevalence of SAPH was 6.4% (95% CI: 3.6-9.1%) in general sarcoidosis population, and subgroup analyses showed that the prevalence of SAPH was 6.7% (95% CI: 2.4-11.0%) in Europe and 8.6% (95% CI: -4.1 to 21.3%) in the United States. Further, the prevalence of pre-capillary PH was 6.5% (95% CI: 2.9-10.2%). For the population with advanced sarcoidosis, the pooled prevalence of SAPH and pre-capillary PH by RHC was as high as 62.3% (95% CI: 46.9-77.6%) and 55.9% (95% CI: 20.1-91.7%), respectively. Finally, the pooled prevalence of SAPH in large databases with documented diagnoses (6.1%, 95% CI: 2.6-9.5%) was similar to that of RHC. Substantial heterogeneity across studies was observed for all analyses (I 2 > 80%, P < 0.001). CONCLUSIONS: The sarcoidosis population has a relatively low burden of PH, mainly pre-capillary PH. However, as the disease progresses to advanced sarcoidosis, the prevalence of SAPH increases significantly.

The association between osteopontin and tuberculosis: A systematic review and meta-analysis.

OBJECTIVE: We examined the data reported in the studies for comparison of osteopontin (OPN) levels in tuberculosis and healthy participants, and to discuss whether OPN could be extended to disease diagnosis, severity assessment and therapeutic effect monitering. METHODS: A systematic literature search was conducted in PubMed, EMBASE, Scopus, the Cochrane Library, Web of Science, the China National Knowledge Infrastructure (CNKI) and WanFang databases. The pooled risk estimates were shown in standardized mean difference (SMD) with 95% confidence interval (CI) for OPN levels. The random effect model was used according to the test of heterogeneity among studies. Subgroup analyses and meta-regression models were performed to identify the possible sources of heterogeneity. RESULTS: 17 retrospective studies with 933 tuberculosis participants and 786 healthy controls were finally included in this article. In the primary meta-analysis, higher serum/plasma OPN levels were found in tuberculosis patients (SMD = 2.58, 95%CI = 2.09~3.08, P<0.001). Besides, pooled results from positive acid-fast bacilli (AFB) staining and imaging-severe tuberculosis group demonstrated higher OPN concentrations (SMD = 0.90, 95%CI = 0.58~1.21, P<0.001; SMD = 1.11, 95%CI = 0.90~1.33, P<0.001; respectively), and OPN levels decreased after two months of standard anti-tuberculosis therapy (SMD = 2.10, 95%CI = 1.36~2.85, P<0.001). CONCLUSIONS: Elevated serum/plasma OPN levels may be associated with an increased risk of tuberculosis, while further well-designed studies are needed. Moreover, OPN could be considered as a potential biomarker for tuberculosis surveillance and severity assessment.

Fisetin Alleviated Bleomycin-Induced Pulmonary Fibrosis Partly by Rescuing Alveolar Epithelial Cells From Senescence.

Idiopathic pulmonary fibrosis is an aging-associated disease, satisfactory therapies are not yet available. Accelerated senescence of alveolar epithelial cells plays an important part in Idiopathic pulmonary fibrosis pathogenesis. Fisetin (FIS) is a natural non-toxic flavonoid, which has many pharmacological functions. However, the role of FIS in pulmonary fibrosis has not been established. In this study, we found that FIS treatment apparently alleviated BLM-induced weight loss, inflammatory cells infiltration, inflammatory factors expression, collagen deposition and alveolar epithelial cell senescence, along with AMPK activation and the down regulation of NF-κB and TGF-ß/Smad3 in vivo. In vitro, FIS administration significantly inhibited the senescence of alveolar epithelial cells and senescence-associated secretory phenotype, followed by reduced transdifferentiation of fibroblasts to myofibroblasts as well as collagen deposition in fibroblasts, which was blocked by an AMPK inhibitor, Compound C. Together, these results suggest that FIS can alleviate the development of BLM-induced pulmonary fibrosis, which is related to the inhibition of TGF-ß/Smad3 signaling and the reduction of alveolar epithelium cell senescence by regulating AMPK/NF-κB signaling pathway. FIS may be a promising candidate for patients with pulmonary fibrosis.

Hyperoside Attenuates Bleomycin-Induced Pulmonary Fibrosis Development in Mice.

Idiopathic pulmonary fibrosis (IPF) is a progressive, lethal, and chronic lung disease. There are no effective drug therapies for IPF. Hyperoside, a flavonoid glycoside, has been proven to have anti-inflammatory, anti-fibrosis, antioxidant, and anti-cancer effects. The aim of this study was to explore the role of hyperoside in bleomycin-induced pulmonary fibrosis development in mice. We established the pulmonary fibrosis model by a single intratracheal aerosol injection of bleomycin. Seven days after the bleomycin treatment, the mice were intraperitoneally administered with hyperoside for 14 days. We found that hyperoside treatment ameliorated fibrotic pathological changes and collagen deposition in the lungs of mice with bleomycin-induced pulmonary fibrosis. Hyperoside treatment also reduced the levels of MDA, TNF-α, and IL-6 and increased the activity of SOD. In addition, hyperoside might inhibit the epithelial-mesenchymal transition (EMT) via the AKT/GSK3ß pathway. Based on these findings, hyperoside attenuated pulmonary fibrosis development by inhibiting oxidative stress, inflammation, and EMT in the lung tissues of mice with pulmonary fibrosis. Therefore, hyperoside might be a promising candidate drug for the treatment of pulmonary fibrosis.

Soluble intercellular cell adhesion molecule-1 in lung cancer: A meta-analysis.

BACKGROUND: Many recent studies have investigated the prognostic, diagnostic, and progressive features of soluble intercellular cell adhesion molecule-1 (sICAM-1) in lung cancer patients, but the results remained inconsistent. This study aimed to explore the value of serum sICAM-1 in patients with lung cancer. METHODS: A comprehensive systematic literature search in the Wanfang databases, china national knowledge infrastructure, Pubmed, and Embase was carried out update to June 15, 2019. The standard mean difference (SMD), hazard ratio (HR), and 95% confidence interval (95% CI) were applied to investigate the effect sizes. RESULTS: 23 observational studies were included. According to our results, the serum sICAM-1 concentrations in patients with lung cancer were significantly higher than that in controls (healthy controls: SMD: 4.08, 95% CI: 3.14-5.02, P < 0.001; benign lung diseases controls : SMD: 1.48, 95% CI: 0.23-2.73,P = 0.02). Fortunately, a subgroup analysis was performed by language, treatment status, and lung cancer types, and the statistical results were similar. Serum sICAM-1 levels were markedly higher in stage III/IV than stage I/II (SMD: 1.96, 95% CI: 1.08-2.84, P < 0.001), Additionally, lung cancer patients with lymph node metastasis had a higher concentrations of serum sICAM-1(SMD: 1.83, 95% CI: 0.95-2.72, P < 0.001), as well as with distant metastasis (SMD: 0.86, 95% CI: 0.47-1.25, P < 0.001). Additionally, patients with higher sICAM-1 levels were related to a significantly poorer prognosis (progression free survival: HR: 1.16, 95% CI: 1.07-1.26, P < 0.001; overall survival: HR: 1.45, 95% CI: 1.17-1.79, P = 0.001). CONCLUSIONS: Our study suggested that serum sICAM-1 levels may act as a potential marker for diagnosing lung cancer and predicting its staging, and were negatively correlated with prognosis of lung cancer.