CD206 modulates the role of M2 macrophages in the origin of metastatic tumors.

Tumor metastasis is a key factor affecting the life of patients with malignant tumors. For the past hundred years, scientists have focused on how to kill cancer cells and inhibit their metastasis in vivo, but few breakthroughs have been made. Here we hypothesized a novel mode for cancer metastasis. We show that the phagocytosis of apoptotic tumor cells by macrophages leads to their polarization into the M2 phenotype, and that the expression of stem cell related as well as drug resistance related genes was induced. Therefore, it appears that M2 macrophages have "defected" and have been transformed into the initial "metastatic cancer cells", and thus are the source, at least in part, of the distal tissue tumor metastasis. This assumption is supported by the presence of fused cells with characteristics of both macrophage and tumor cell observed in the peripheral blood and ascites of patients with ovarian cancer. By eliminating the expression of CD206 in M2 macrophages using siRNA, we show that the growth and metastasis of tumors was suppressed using both in vitro cell line and with experimental in vivo mouse models. In summary, we show that M2 macrophages in the blood circulation underwent a "change of loyalty" to become "cancer cells" that transformed into distal tissue metastasis, which could be suppressed by the knockdown of CD206 expression.

Uridine alleviates high-carbohydrate diet-induced metabolic syndromes by activating sirt1/AMPK signaling pathway and promoting glycogen synthesis in Nile tilapia (Oreochromis niloticus).

Carbohydrates have a protein sparing effect, but long-term feeding of a high-carbohydrate diet (HCD) leads to metabolic disorders due to the limited utilization efficiency of carbohydrates in fish. How to mitigate the negative effects induced by HCD is crucial for the rapid development of aquaculture. Uridine is a pyrimidine nucleoside that plays a vital role in regulating lipid and glucose metabolism, but whether uridine can alleviate metabolic syndromes induced by HCD remains unknown. In this study, a total of 480 Nile tilapia (Oreochromis niloticus) (average initial weight 5.02 ± 0.03 g) were fed with 4 diets, including a control diet (CON), HCD, HCD + 500 mg/kg uridine (HCUL) and HCD + 5,000 mg/kg uridine (HCUH), for 8 weeks. The results showed that addition of uridine decreased hepatic lipid, serum glucose, triglyceride and cholesterol (P < 0.05). Further analysis indicated that higher concentration of uridine activated the sirtuin1 (sirt1)/adenosine 5-monophosphate-activated protein kinase (AMPK) signaling pathway to increase lipid catabolism and glycolysis while decreasing lipogenesis (P < 0.05). Besides, uridine increased the activity of glycogen synthesis-related enzymes (P < 0.05). This study suggested that uridine could alleviate HCD-induced metabolic syndrome by activating the sirt1/AMPK signaling pathway and promoting glycogen synthesis. This finding reveals the function of uridine in fish metabolism and facilitates the development of new additives in aquatic feeds.

Partial replacement of soybean meal by yellow mealworm (Tenebrio molitor) meal influences the flesh quality of Nile tilapia (Oreochromis niloticus).

This study investigated the effects of yellow mealworm meal (YM) replacing soybean meal (SBM) at different proportions (0%, 15%, 30% and 45%, referred as YM0, YM15, YM30 and YM45, respectively) on the flesh quality of Nile tilapia. A total of 360 fish (70.0 ± 0.12 g) were randomly divided into 4 groups (3 tanks per group). Fish were fed the experimental diet twice daily for 10 wk. The results showed that muscle protein content significantly decreased in YM30 and YM45, while the lipid content significantly decreased in YM45 (P < 0.05). The essential amino acids and flavor amino acids of the muscle were not affected by the YM substitution, while saturated fatty acid content decreased in YM30 and YM45 compared with YM0 (P < 0.05). Fillets in YM45 had higher hardness, gumminess, and a higher proportion of thin myofibers (≤100 µm, P < 0.05) than those in other groups. Further analysis revealed that apoptosis and atrophy related genes were up-regulated, while the muscle antioxidant capacity decreased significantly in YM45 (P < 0.05), which may be related to the high acid value in YM45 diet. Our findings indicated that YM could replace up to 30% SBM without substantially altering the flesh quality. When the replacement ratio increased to 45%, the flesh quality would change. Special attention should be paid to avoid feed rancidity which may affect the flesh quality of fish.

Effects of dietary mannan oligosaccharides (MOS) supplementation on metabolism, inflammatory response and gut microbiota of juvenile Nile tilapia (Oreochromis niloticus) fed with high carbohydrate diet.

High-carbohydrate diet could achieve cost-sparing effect in aquafeed, but it may cause adverse effects on the growth condition or health status of fish. In order to reduce the adverse effects caused by high carbohydrate diet, mannan oligosaccharides (MOS), a commonly used prebiotics, was used as the feed additive to feed juvenile Nile tilapia (Oreochromis niloticus) (1.19 ± 0.01g) for ten weeks. Three treatments including CON (35% carbohydrate diet), HC (45% carbohydrate diet) and HM (45% carbohydrate supplemented diet with 5 g/kg MOS) were involved. The results showed that MOS supplementation increased the weight gain and body length of juvenile Nile tilapia compared with the HC group. Addition of MOS decreased serum glucose and liver glycogen by increasing enzymes activity related to glycolysis. Furthermore, supplementation of MOS decreased the high carbohydrate diet induced triglycerides accumulation in liver by reducing the expression level of genes related to TG synthesis. Dietary MOS also down-regulated the gene expression level of inflammation factors in liver. Intestinal bacterial composition analyses showed that supplementation of MOS in high carbohydrate diet altered the gut microbial composition and enriched pathways related to the glucose metabolism based on KEGG analyses. In general, our results demonstrated that MOS supplementation in high carbohydrate diet could regulate glucose and lipid homeostasis which may be related to the alteration of gut microbiota. These findings shed light on the application of prebiotics to increase the growth performance, alleviate the metabolic disorders and regulate inflammatory response in aquaculture.

Long Non-Coding RNA MCM3AP-AS1: A Crucial Role in Human Malignancies.

The incidence of cancer continues to grow and is one of the leading causes of death in the world. Long noncoding RNAs (LncRNAs) is a group of RNA transcripts greater than 200 nucleotides in length, and although it cannot encode proteins, it can regulate different biological functions by controlling gene expression, transcription factors, etc. LncRNA micro-chromosome maintenance protein 3-associated protein antisense RNA 1 (MCM3AP-AS1) is involved in RNA processing and cell cycle-related functions, and MCM3AP-AS1 is dysregulated in expression in various types of cancers. This biomarker is involved in many processes related to carcinogens, such as cell proliferation, apoptosis, cell cycle, and migration. In this review, we summarize the roles of MCM3AP-AS1 in different human cancers and its biological functions with a view to providing ideas for future research.

Bacillus amyloliquefaciens protects Nile tilapia against Aeromonas hydrophila infection and alleviates liver inflammation induced by high-carbohydrate diet.

Carbohydrates are widely distributed in nature as an important nutritional substance and energy source. However, the utilization efficiency of carbohydrates is very poor in fish. Over consumption of carbohydrates will cause excessive inflammatory response and result in lower pathogen resistance in fish. Probiotics have been widely used to prevent inflammation, but the underlying mechanism still needs more exploration. In this study, three diets, including a control diet (CD), a high-carbohydrate diet (HD) and the HD supplemented with Bacillus amyloliquefaciens SS1 (HDB) were used to feed Nile tilapia for 10 weeks. At the end of the feeding trial, fish were challenged with Aeromonas hydrophila (A. hydrophila) for 7 days. The data showed that the addition of Bacillus amyloliquefaciens SS1 (B. amyloliquefaciens SS1) significantly increased the survival rate and enhanced the respiratory burst activity of head kidney leukocytes in Nile tilapia. B. amyloliquefaciens SS1 treatment significantly elevated the anti-oxidative capability, which was evidenced by higher activities of superoxide dismutase (SOD) and total antioxidant capacity (T-AOC), and higher content of reduced glutathione (GSH) in the serum. Administration with B. amyloliquefaciens SS1 effectively suppressed inflammatory response in the liver by inhibiting nuclear factor kappa-B (NF-κB)/interleukin-1 beta (IL-1ß) inflammatory signaling pathway. In vitro analysis suggested that intestinal bacteria derived-acetate has the antioxidant capability, which may account for the alleviation of inflammation. Overall, this study demonstrated that dietary supplementation with B. amyloliquefaciens SS1 protected Nile Tilapia against A. hydrophila infection and suppressed liver inflammation by enhancing antioxidant capability.

Immunophenotype in acute exacerbation of chronic obstructive pulmonary disease: a cross-sectional study.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a heterogeneous disease, and the immune inflammatory response is thought to play an important role in pathogenesis. However, the immunophenotype of patients with COPD is unknown. Herein, we evaluated the immunophenotype of patients with acute exacerbation of COPD (AECOPD). METHODS: A cross-sectional study was conducted in West China Hospital from September 2018 to October 2019. The proportion of CD4 + T lymphocyte subtypes (Th1, Th2, Th17 and Treg) and levels of serum cytokines in the peripheral blood of patients with AECOPD, stable COPD (SCOPD), healthy smokers (HSs)and healthy controls (HCs) were evaluated. RESULTS: A total of 15 HCs, 19 HSs, 42 patients with SCOPD, and 55 patients with AECOPD were included. Compared to patients with SCOPD, Th1 cells, Th17 cells, Treg cell ratio, Th1/Th2 cell ratio, and the levels of C-reactive protein, interleukin (IL)-6, and IL-10 were significantly increased in patients with AECOPD (P < 0.001), while the proportion of Th2 cells was significantly reduced (P < 0.01). The proportion of Th17 cells was positively correlated with COPD Assessment Test score (r = 0.266, P = 0.009), modified Medical Research Council dyspnea score (r = 0.858, P < 0.0001), and Th1 cell ratio (r = 0.403, P < 0.0001) and negatively correlated with forced vital capacity (r = - 0.367, P = 0.009) and proportion of Th2 cells (r = - 0.655, P < 0.0001). CONCLUSIONS: The immunophenotype of patients with AECOPD shows abnormal activation of Th1, Th17, and Treg cells. There is a correlation between the proportion of Th17 cells and the severity of COPD; therefore, this may represent a novel index for the evaluation of COPD severity. TRIAL REGISTRATION: China Clinical Trials Registry, ChiCTR1800018452, registered 19 September 2018, https://www.chictr.org.cn/index.aspx .

Microbiota derived butyrate affected the muscle texture of Nile tilapia (Oreochromis niloticus) fed with different protein sources.

Flesh quality is influenced by diet components, but the underlying mechanism remains unclear. This study aimed to investigate the effect of replacing soybean meal (SBM) protein with cottonseed protein concentrate (CPC) at different levels (0%, CK; 15%, CPC15; 30%, CPC30 and 45%, CPC45) on the flesh quality of Nile tilapia. The results indicated that different protein sources influenced muscle amino acid composition instead of fatty acid composition. Lower muscle lipid content was found in CPC45, which in turn significantly altered the muscle texture. The hepatic lipid metabolism-related genes were detected and we found that CPC45 significantly suppressed the lipogenesis and promoted lipolysis. Higher content of microbiota-derived butyrate was found in the intestinal content of CPC45 and butyrate could decrease the lipid accumulation in vitro. Replacing SBM with CPC increased the intestinal butyrate to suppress the lipogenesis in the liver which may account for the increased muscle hardness.

Intestinal Microbiota Mediates Gossypol-Induced Intestinal Inflammation, Oxidative Stress, and Apoptosis in Fish.

Gossypol, the main antinutritional factor in cottonseed protein concentrate (CPC), could affect the growth conditions of fish, but the underlying mechanism remains unclear. In this study, an 8-week feeding trial was carried out to investigate the effects of gossypol on Nile tilapia (Oreochromis niloticus). Three experimental diets were designed, including control diet (CON), control diet supplemented with 150 mg/kg gossypol (ML), and 300 mg/kg gossypol (MH). 16S rRNA gene sequencing showed that gossypol significantly reduced the richness and diversity of the gut microbiota. Untargeted metabolite analysis revealed that most metabolites were down-regulated by gossypol, and riboflavin was the key metabolite with significant difference between CON-treated and gossypol-treated groups. Gossypol caused intestinal inflammation, oxidative stress, and apoptosis. Through fecal bacteria transplantation experiments, we demonstrated that intestinal microbiota mediated gossypol-induced negative effects, suggesting that intestinal microbiota and its metabolite may account for the harmful effects of gossypol.

Efficacy of targeted therapy in patients with HER2-positive non-small cell lung cancer: A systematic review and meta-analysis.

Anti-human epidermal growth factor receptor 2 (HER2) therapy is an effective treatment for HER2-positive gastric and breast malignancies. However, the efficacy of HER2-targeted therapy in non-small cell lung cancer (NSCLC) patients with HER2 alterations remains controversial. We searched studies on HER2-targeted therapy in NSCLC patients that reported objective response rate (ORR), disease control rate (DCR) and progressionfree survival (PFS) published from database inception to 30 May 2021. A total of 32 trials involving 958 patients were included. The ORRs of HER2-TKIs targeted therapy, humanised monoclonal antibody, trastuzumab-based treatment and antibody-drug conjugate (ADC) (T-DM1) were 22% (95% CI 11-31), 23% (95% CI 20-65), 26% (95% CI 14-39) and 16% (95% CI _6-37), while that of ADC (DS-8201) was 60% (95% CI 35-85). The DCRs of these groups were 59% (95% CI 49-69), 39% (95% CI _9-88), 63% (95% CI 37-89), 31% (95% CI 4-58) and 87% (95% CI 62-112), respectively. In the subgroup analysis, numerically higher ORRs and DCRs were observed in the poziotinib (38%; 75%) and pyrotinib (35%; 83%) groups. The median PFSs of these groups were 5.51 months, 3.09 months, 4.61 months, 2.65 months and 12.04 months, respectively. HER2-targeted therapy can be considered an acceptable treatment strategy for NSCLC patients with HER2 alterations. In particular, ADC (DS-8201), pyrotinib and poziotinib demonstrated promising anti-tumour activity in HER2-positive NSCLC.

Oligosaccharides improve the flesh quality and nutrition value of Nile tilapia fed with high carbohydrate diet.

High level of carbohydrate in aquafeed could achieve cost-sparing effect, but it may cause adverse effects on flesh quality of aquatic products. An eight-week trial was conducted to investigate whether oligosaccharides-supplementation, including Galacto-oligosaccharides (GOS) and xylo-oligosaccharide (XOS), could systematically improve the growth performance, texture characteristics and nutrition composition of Nile tilapia fed with high-carbohydrate diet. The results indicated that GOS-supplementation improved the amino acid composition, while XOS-supplementation showed beneficial effects on growth performance. High-carbohydrate diet had adverse effects on fillet texture, while oligosaccharide-supplementation regulated the expression of muscle development-related genes to help restoring muscle texture properties. Furthermore, either high-carbohydrate or addition of oligosaccharides could change the intestinal microbiota composition and their metabolites. Further correlation analysis suggested that intestinal microbiota may account for the improvement in fish growth condition and texture characteristics. Application of oligosaccharides may be an innovative strategy for flesh quality modulation in aquaculture.

Long non-coding RNA MIAT promotes gastric cancer proliferation and metastasis via modulating the miR-331-3p/RAB5B pathway.

Gastric cancer (GC) remains a threat to the health of the global population. The present study investigated the effects and mechanisms of the long non-coding RNA myocardial infarction associated transcript (MIAT) on the proliferation, apoptosis and metastasis of GC (HGC-27 and AGS) cells. The expression levels of MIAT, micoRNA (miR)-331-3p and RAB5B mRNA were analyzed using reverse transcription-quantitative PCR analysis. Cell growth, apoptosis, migration and invasion were measured using 5-ethynyl-2'-deoxyuridine, flow cytometry, wound healing and Transwell assays, respectively. A luciferase assay was used to determine whether miR-331-3p targeted MIAT and RAB5B. The results indicated that MIAT levels were significantly upregulated in GC tissues and cells, correlated with RAB5B levels and inversely associated with miR-331-3p levels. MIAT overexpression promoted proliferation and metastasis, and inhibited the apoptosis of GC cells. MIAT knockdown had the opposite effect on GC cells. The rescue experiments revealed that the effects of MIAT knockdown on the biological behaviour of GC cells were attenuated by RAB5B overexpression. These data suggest that MIAT promotes GC progression via modulating miR-331-3p/RAB5B pathway.

Transcriptional mechanism of differential sugar accumulation in pulp of two contrasting mango (Mangifera indica L.) cultivars.

Temporal transcriptome analysis combined with targeted metabolomics was employed to investigate the mechanisms of high sugar accumulation in fruit pulp of two contrasting mango cultivars. Ten sugar metabolites were identified in mango pulp with the most dominant being d-glucose. Analysis of the gene expression patterns revealed that the high-sugar cultivar prioritized the conversion of sucrose to d-glucose by up-regulating invertases and ß-glucosidases and increased other genes directly contributing to the synthesis of sucrose and d-glucose. In contrast, it repressed the expression of genes converting sucrose, d-glucose and other sugars into intermediates compounds for downstream processes. It also strongly increased the expression of alpha-amylases which may promote high degradation of starch into d-glucose. Besides, ¾ of the sugar transporters was strongly up-regulated, indicative of their preponderant role in sugar accumulation in mango fruit. Overall, this study provides a good insight into the regulation pattern of high sugar accumulation in mango pulp.

Caprin-1 promotes HepG2 cell proliferation, invasion and migration and is associated with poor prognosis in patients with liver cancer.

The present study aimed to investigate the role of caprin-1 in liver cancer and its association with the clinicopathological features and prognosis of liver cancer, as well as the underlying mechanism of caprin-1 function. Caprin-1 expression levels in a tissue microarray containing 40 liver cancer tissues, 10 peritumoral tissues and 20 normal liver tissues were analyzed using immunohistochemistry. The clinical data of 154 patients with liver cancer were also collected from The Cancer Genome Atlas database. Kaplan-Meier analysis and a Cox proportional hazards regression model were used to assess the association between caprin-1 expression levels and survival in patients with liver cancer. The effects of caprin-1 knockdown on the mRNA levels of cyclin D1 and cyclin D2 as well as the proliferation, invasion and migration of HepG2 cells were also investigated. The expression level of caprin-1 in liver cancer tissues was significantly higher compared with normal liver tissues or cells (P<0.01). High caprin-1 expression levels were associated with advanced clinical stage (P<0.001) and enhanced tumor invasion (P<0.001). Kaplan-Meier analysis showed that the overall survival time and disease-free survival time in patients with liver cancer with high caprin-1 expression were significantly shorter compared with patients with low caprin-1 expression levels (P=0.002 and P=0.033, respectively). The Cox proportional hazards regression model showed that high caprin-1 expression levels were an independent prognostic factor for liver cancer (P<0.001). Knockdown of caprin-1 in HepG2 cells significantly downregulated mRNA expression levels of cyclin D1 and cyclin D2, inhibited cell proliferation and invasion and the cells were arrested at G0/G1 phase. In conclusion, caprin-1 may be a novel prognostic indicator for patients with liver cancer.

[Promoting tanshinone synthesis of Salvia miltiorrhiza root by a seed endophytic fungus, Phoma herbarum D603].

The interaction of endophytes and host plant is an effective mean to regulate the growth and secondary metabolism of medicinal plants. Here we want to elucidate the effects and mechanism of Phoma herbarum D603 on the root development and tanshinone synthesis in root of Salvia miltiorrhiza by endophyte-plant coculture system. The mycelium of P. herbarum D603 was colonized in the root tissue space, and formed a stable symbiotic relationship with host plant. The in vitro activities analysis showed that the concentration of IAA produced by D603 can reach(6.45±0.23) µg·mL~(-1), and this strain had some abilities of phosphorus solubilization and siderophore production activities. The coculture experiment showed that strain D603 can significantly promote the synthesis and accumulation of tanshinones in the root of S. miltiorrhiza, in which after 8 weeks of treatment with D603, the content of tanshinone Ⅱ_A in the roots reached up to(1.42±0.59) mg·g~(-1). By the qRT-PCR analysis results, we found that D603 could improve the expression levels of some key genes(DXR, DXS, GGPP, HMGR, CPS) of tanshinone biosynthesis pathway in host plant S. miltiorrhiza, but the promoting effect mainly occurred in the early stage of the interaction, and the enzyme activity level decreased in varying degrees of the later stage. In summary, seed-associated endophyte P. herbarum D603 can promote the growth and root development of S. miltiorrhiza by producing hormones, promoting nutrient absorption and siderophore production, and promote the synthesis and accumulation of tanshinones by regulating the expression level of key genes in the synthetic pathway in S. miltiorrhiza.

Efficacy and safety of dupilumab for the treatment of uncontrolled asthma: a meta-analysis of randomized clinical trials.

BACKGROUND: Several recent clinical trials have assessed the effects of dupilumab in uncontrolled asthma, but reached no definite conclusion. We therefore conducted this meta-analysis to evaluate the overall efficacy and safety of dupilumab for the treatment of uncontrolled asthma. METHODS: All randomized controlled trials were included. Standard mean differences (SMD) or relative risks (RR) were calculated using Fixed-or random-effects models. RESULTS: Five studies involving 3369 patients were identified. Pooled analysis showed significant improvements in the first-second forced expiratory volume (FEV1) (SMD = 4.29, 95% CI: 2.78-5.81) and Asthma Quality of Life Questionnaire scores (SMD = 4.39, 95% CI: 1.44-7.34). Dupilumab treatments were also associated with significantly decreased 5-item Asthma Control Questionnaire scores (SMD = - 4.95, 95% CI: - 7.30 to - 2.60), AM and PM asthma symptom scores (SMD = - 5.09, 95% CI: - 6.40 to - 3.77; SMD = - 4.92, 95% CI: - 5.98 to - 3.86, respectively), and severe exacerbation risk (RR = 0.73; 95% CI: 0.67-0.79) compared with placebo, with similar incidence of adverse events (RR = 1.0; 95% CI: 0.96-1.04). CONCLUSION: Dupilumab treatment is relatively well-tolerated and could significantly improve FEV1, symptoms, asthma control, and quality of life, and reduced severe exacerbation risk in patients with uncontrolled asthma.

Peripheral Blood Eosinophil as a Biomarker in Outcomes of Acute Exacerbation of Chronic Obstructive Pulmonary Disease.

Purpose: Mounting evidence suggests that eosinophil levels correlate with the effects of therapy and phenotype for chronic obstructive pulmonary disease (COPD). This study aimed to clarify the relationship between eosinophil levels and clinical outcomes in patients with acute exacerbation of COPD (AECOPD). Methods: A prospective, multicenter, observational cohort study was performed in three teaching hospitals. Patients were grouped by quartile percentage (0, 0.7, 2.55) and absolute blood eosinophils count (0, 0.05×109/L, 0.17×109/L) and divided into four numbered groups ranked from low to high. Results: The study included 493 AECOPD patients. In the percentile-ranked groups, patients in Group 1 experienced significantly longer hospital stays, higher rates of both noninvasive mechanical ventilation (NIMV), and heart failure than those in Group 4 (12 days vs 10 days, p = 0.005; 29.5% vs 23.6%, p = 0.007; 48.4% vs 28.5%, p = 0.001). Group 1 also had higher frequencies of respiratory failure and pulmonary heart disease compared to Groups 3 and 4 (54.8% vs 34.8%, p = 0.002; 54.8% vs 35%, p = 0.003). In the absolute count-ranked groups, patients in Group 1 had significantly higher rates of NIMV than those in Group 3 (41.1% vs 21.7%, p = 0.001), had higher rates of heart failure, respiratory failure, and pulmonary heart disease than those in Group 3 and 4 (48.1% vs 30.2%, p = 0.003; 48.1% vs 30.4%, p = 0.005; 50.8% vs 32.2%, p = 0.004; 50.8% vs 34.1%, p = 0.008; 51.9% vs 34.1%, p = 0.004; 51.9% vs 33%, p = 0.003). There were outcome differences among the admitting hospital of stays in the absolute count groups (p = 0.002), but the differences were not significant in a pairwise comparison. The proportion of ICU admissions and mortality was different in two cohorts with no difference in a pairwise comparison. Conclusion: Patients with lower eosinophil counts experienced poorer clinical outcomes. Eosinophil levels may be a helpful marker to predict outcomes in AECOPD.

Prevalence and Baseline Clinical Characteristics of Eosinophilic Chronic Obstructive Pulmonary Disease: A Meta-Analysis and Systematic Review.

Background: Chronic obstructive pulmonary disease (COPD) is a heterogeneous disease with different clinical and pathophysiological characteristics. Cumulative evidence shows that eosinophil levels may be connected to the therapeutic effects and phenotype of COPD. However, the prevalence of eosinophilic inflammation in COPD and the baseline characteristics of eosinophilic COPD remain unknown. Our study investigated the prevalence of COPD with eosinophil levels of >2% and the characteristics of eosinophilic COPD. Methods: We searched the Cochrane Central Library, Medline, Embase, and the Web of Science for trials of eosinophil and COPD published from database inception to May 1, 2019. Results: In total, 40,112 COPD patients that were involved in 19 trials were included in the final analysis. The prevalence of eosinophilic COPD ranged from 18.84 to 66.88%, with an average prevalence of 54.95% across all studies. We found that men, ex-smokers, individuals with a history of ischemic heart disease, and individuals with a higher body mass index (BMI) were at higher risk of eosinophilic COPD (OR 1.36, 95% CI 1.26-1.46, P < 0.00001; OR 1.23, 1.12-1.34, P < 0.0001; OR 1.31, 1.14-1.50, P = 0.001; MD 0.70, 0.27-1.12, P = 0.001). There was, however, a lower proportion of GOLD stage I patients among those with eosinophilic COPD (OR 0.84, 0.73-0.96, P = 0.01). No significant differences were found in terms of age, current smoker status, pack-years smoked, percent of predicted forced expiratory volume in 1 s, hypertension, diabetes, or other GOLD stages between the two groups (P > 0.05). Conclusions: Our analysis suggests that eosinophilic inflammation is prevalent in COPD. Eosinophilic COPD was more likely to occur in men, ex-smokers, those with a higher BMI, and those with a high risk of some comorbidity; however, a lower proportion of patients with eosinophilic COPD experienced mild airflow limitations.

Efficacy and Safety of CFTR Corrector and Potentiator Combination Therapy in Patients with Cystic Fibrosis for the F508del-CFTR Homozygous Mutation: A Systematic Review and Meta-analysis.

INTRODUCTION: Cystic fibrosis (CF) is a progressive, genetic disease that causes persistent lung infections and limits the ability to breathe over time. The combination of a cystic fibrosis transmembrane conductance regulator (CFTR) corrector and potentiator has provided a benefit by decreasing sweat chloride concentration in CF for the F508del-CFTR homozygous mutation, but it remains controversial in lung function, nutritional status, clinical score and safety. METHODS: The authors performed a systematic review and meta-analysis of randomized controlled trials (RCTs) to evaluate the efficacy and safety of combination therapy on lung function, nutritional status, clinical score and safety in CF for the F508del-CFTR homozygous mutation. Web of Science, Cochrane Central Register of Controlled Trials, Medline, and Embase were searched. The registered PROSPERO number was CRD42018085875. RESULTS: Five RCTs, including a total of 1637 participants with the F508del-CFTR homozygous mutation who accepted CFTR corrector and potentiator combination therapy along with basic treatment were enrolled in this analysis. Primary analysis revealed that combination therapy improved the percent of predicted FEV1 (ppFEV1) (MD 2.38, 1.62-3.15, P < 0.00001), Cystic Fibrosis Questionnaire-Revised (CFQ-R) respiratory domain score (MD 2.59, 0.96-4.22, P = 0.002) and body-mass index (BMI) (MD 0.21, 0.03-0.39, P = 0.02). In the secondary analysis, combination therapy had no impact on the number of participants reporting adverse events (OR 0.88, 0.58-1.33, P = 0.53), but increased the proportion of discontinued treatments due to adverse events (OR 2.71, 1.3-5.63, P = 0.008). CONCLUSIONS: CFTR corrector and potentiator combination therapy effectively improves lung function, nutritional status and clinical score in CF patients with the F508del-CFTR homozygous mutation, and has an acceptable safety profile.

Effects of Tiotropium Combined with Theophylline on Stable COPD Patients of Group B, D and its Impact on Small Airway Function: A Randomized Controlled Trial.

INTRODUCTION: Tiotropium bromide has been widely used in clinical practice, while theophylline is another treatment option for chronic obstructive pulmonary disease (COPD). However, only a few relevant studies have investigated the long-term outcomes and efficacy of both in patients with COPD. We evaluated the effects of tiotropium and low-dose theophylline on stable COPD patients of groups B and D. METHODS: Eligible participants (n = 170) were randomized and received either tiotropium 18 µg once daily with theophylline 100 mg twice daily (Group I) or tiotropium 18 µg once daily (Group II) for 6 months. COPD assessment test (CAT), modified Medical Research Council (mMRC) dyspnea scores and pulmonary function tests were measured before randomization and during the treatment. RESULTS: After 6 months of treatment, the CAT scores in both groups decreased significantly (11.41 ± 3.56 and 11.08 ± 3.05, p < 0.0001). The changes of CAT (p = 0.028) and mMRC scores (p = 0.049) between the two groups differed after 1 month of treatment. In Group I, forced expiratory flow after 25% of the FVC% predicted (MEF25% pred) was significantly improved after 3 months (4.84 ± 8.73%, p < 0.0001) and 6 months (6.21 ± 8.65%, p < 0.0001). There was a significant difference in small airway function tests (MEF50% pred, MEF25% pred, and MMEF% pred) between the two groups after 6 month of treatment (p = 0.003, p < 0.0001, and p = 0.021, respectively). CONCLUSIONS: Tiotropium combined with low-dose theophylline significantly improved the symptoms and general health of patients with stable COPD of groups B and D after 6 months of follow-up. Additionally, this therapy also improved the indicators of small airway function. TRIAL REGISTRATION: Chinese Clinical Trial Registry (Registry ID: ChiCTR1800019027).