Erythropoietin alleviates lung ischemia-reperfusion injury by activating the FGF23/FGFR4/ERK signaling pathway.

Background: The purpose of the present study was to investigate the effect of erythropoietin (EPO) on lung ischemia-reperfusion injury (LIRI). Methods: Sprague Dawley rats and BEAS-2B cells were employed to construct an ischemia-reperfusion (I/R)-induced model in vivo and in vitro, respectively. Afterward, I/R rats and tert-butyl hydroperoxide (TBHP)-induced cells were treated with different concentrations of EPO. Furthermore, 40 patients with LIRI and healthy controls were enrolled in the study. Results: It was observed that lung tissue damage, cell apoptosis and the expression of BAX and caspase-3 were higher in the LIRI model in vivo and in vitro than in the control group, nevertheless, the Bcl-2, FGF23 and FGFR4 expression level was lower than in the control group. EPO administration significantly reduced lung tissue damage and cell apoptosis while also up-regulating the expression of FGF23 and FGFR4. Rescue experiments indicated that EPO exerted a protective role associated with the FGF23/FGFR4/p-ERK1/2 signal pathway. Notably, the expression of serum EPO, FGF23, FGFR4 and Bcl-2 was decreased in patients with LIRI, while the expression of caspase-3 and BAX was higher. Conclusion: EPO could effectively improve LIRI, which might be related to the activation of the FGF23/FGFR4/p-ERK1/2 signaling pathway.

Development of a Pancreatic Fistula Prediction Model After Pancreaticoduodenectomy Based on a Decision Tree and Random Forest Algorithm.

BACKGROUND: The incidence of postoperative pancreatic fistula (POPF) after pancreaticoduodenectomy (PD) is high. We sought to develop a POPF prediction model based on a decision tree (DT) and random forest (RF) algorithm after PD and to explore its clinical value. METHODS: The case data of 257 patients who underwent PD in a tertiary general hospital from 2013 to 2021 were retrospectively collected in China. The RF model was used to select features by ranking the importance of variables, and both algorithms were used to build the prediction model after automatic adjustment of parameters by setting the respective hyperparameter intervals and resampling as a 10-fold cross-validation method, etc. The prediction model's performance was assessed by the receiver operating characteristic curve (ROC) and the area under curve (AUC). RESULTS: Postoperative pancreatic fistula occurred in 56 cases (56/257, 21.8%). The DT model had an AUC of .743 and an accuracy of .840, while the RF model had an AUC of .977 and an accuracy of .883. The DT plot visualized the process of inferring the risk of pancreatic fistula from the DT model on independent individuals. The top 10 important variables were selected for ranking in the RF variable importance ranking. CONCLUSION: This study successfully developed a DT and RF algorithm for the POPF prediction model, which can be used as a reference for clinical health care professionals to optimize treatment strategies to reduce the incidence of POPF.

Application of Acupoint Catgut Embedding Therapy Combined with Liuzijue Breathing Exercise in the Treatment of Patients with Stable Chronic Obstructive Pulmonary Disease.

Objective: To evaluate the application value of acupoint catgut embedding therapy combined with Liuzijue breathing exercise in the treatment of patients with stable chronic obstructive pulmonary disease (COPD) and its impact on immune function and quality of life. Methods: A total of 100 patients with stable COPD admitted to our hospital from February 2020 to February 2021 were included and assigned to the experimental group (n = 50) and the control group (n = 50) according to the order of admission. Both groups of patients received conventional treatment. The control group was given daily inhalation of budesonide and formoterol fumarate powder for inhalation (320 ug/bottle), and the experimental group received additional acupoint catgut embedding therapy combined with Liuzijue breathing exercise. The clinical efficacy, pulmonary function indexes, activities of daily living (ADL) scores, quality of life (QOL) scores, traditional Chinese medicine (TCM) syndrome scores, the number of acute exacerbations, medical expenses, the incidence of adverse reactions, and immune indicators were compared between the two groups of patients. Results: The experimental group yielded a significantly higher effective rate of treatment than the control group (P < 0.05). After the treatment, the experimental group obtained a superior outcome in terms of lung function indexes, immune function indexes, ADL and QOL scores, and the TCM syndrome scores when compared with the control group (P < 0.05). The number of acute exacerbations in the experimental group was remarkably lower than that in the control group (P < 0.05). No serious adverse reactions were observed in the two groups of patients, and no significant difference in the incidence of adverse reactions was found (P > 0.05). Conclusion: Acupoint catgut embedding therapy combined with Liuzijue breathing exercise, with high safety, can improve the treatment effect and the quality of life of patients with stable COPD, which merits clinical promotion.

Zeaxanthin attenuates OVA-induced allergic asthma in mice by regulating the p38 MAPK/ß-catenin signaling pathway.

BACKGROUND: Asthma is a heterogeneous and complex chronic airway disease with a high incidence rate, characterized by chronic airway inflammation. Although the anti-inflammatory effect of zeaxanthin has been demonstrated in various disease models, its explicit role in allergic asthma remains elusive. METHODS: An allergic asthma model was established by ovalbumin (OVA) stimulation in BALB/c nude mice. The pathological examination, collagen deposition and expression of α-smooth muscle actin (α-SMA) in lung tissues were determined by hematoxylin and eosin (H&E), MASSON and immunofluorescence staining, respectively. Besides, the effect of zeaxanthin on inflammation and oxidative stress was assessed by the enzyme-linked immunosorbent assay (ELISA) and spectrophotometry measure. Moreover, the underlying mechanism was analyzed by detecting the expression of phosphorylated p38 (p-p38), p38, ß-catenin, p-c-Jun N-terminal kinase (p-JNK) and JNK with western blot assays. RESULTS: The distinct infiltration of inflammatory cells was observed in the OVA-induced asthma mice model with significantly increased concentrations of immunoglobulin E (IgE), interleukin-4 (IL-4), IL-5, IL-13 and eotaxin (p˂0.001), which were prominently reversed by zeaxanthin treatment (p˂0.001). In addition, zeaxanthin treatment decreased the OVA-induced collagen deposition and α-SMA expression. A similar inhibitory effect of zeaxanthin on the oxidative stress was also observed in the OVA-induced asthma mice model, as evidenced by the prominent decrease of malondialdehyde (MDA) concentration and the remarkable increase of superoxide dismutase (SOD), glutathione S transferase (GST) and Glutathione (GSH) concentrations (p˂0.001). Moreover, zeaxanthin introduction markedly reduced the relative expressions of p-p38/p38, ß-catenin and p-JNK/JNK in the OVA-induced asthma mice model (p˂0.001), indicating that zeaxanthin suppressed the p38 mitogen-activated protein kinase (p38 MAPK)/ß-catenin signaling pathway in the OVA-induced asthma mice model. CONCLUSIONS: Zeaxanthin attenuated OVA-induced allergic asthma in mice via modulating the p38 MAPK/ß-catenin signaling pathway.

IL-4-C-590T locus polymorphism and susceptibility to asthma in children: a meta-analysis

Abstract Objectives The study aimed to evaluate the link between the IL-4-C590T polymorphism and asthma susceptibility in children by meta-analysis. Sources The study collected all the case-control studies found in PubMed, Embase, CNKI, Wanfang, VIP, and other databases until September 2019. Stata v. 15.0 was used to conduct meta-analysis, calculate the combined OR and its 95% CI, and then conduct subgroup analysis. Summary of the findings Seven studies were included in the study, containing 860 cases and 810 controls. Relative to the C allele, the T allele at the IL-4-C590T locus was associated with susceptibility to asthma in children (OR = 1.45, 95% CI: 1.05-2.01). The results of ethnicity subgroup analysis showed that there was statistical significance, with OR = 1.61 (95% CI: 1.01-2.57) in the Asian population. In the dominant and recessive genetic models, the overall test and the Asian population subgroup analysis were statistically significant. In the homozygous model, there was statistical significance, but no statistical significance in heterozygous model. Conclusions The IL-4-C590T polymorphism was associated with asthma susceptibility, and T allele and TT genotype may increase the risk of asthma susceptibility in children, especially in the Asian population.

HIF-1 Inhibitor YC-1 Reverses the Acquired Resistance of EGFR-Mutant HCC827 Cell Line with MET Amplification to Gefitinib.

BACKGROUND: Acquired resistance occurred in the majority of nonsmall cell lung cancer (NSCLC) patients receiving epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) therapy, and this may be related to the activation of the HIF-1 pathway. Therefore, we examined the influence of the hypoxia-inducible factor-1 (HIF-1) pathway inhibition on the sensitivity of HCC827 gefitinib-resistant (HCC827 GR) cells with MET amplification to gefitinib. METHODS: We established HCC827 GR cell line with MET amplification and set four groups with different treatment. An MTT assay, a colony formation analysis, and a wound healing assay were performed to determine the sensitivity change of HCC827 GR cells after different treatments. HIF-1α, p-EGFR, and p-Met levels were detected with western blot. Correlations among HIF-1α, p-EGFR, and p-Met levels of HCC827 GR cells with different treatments were analyzed with Pearson's correlation analysis. RESULTS: HIF-1 inhibitor YC-1 enhanced the sensitivity of HCC827 GR cells to gefitinib. p-Met level was correlated with HIF-1α level, while there was no correlation between p-Met level and p-EGFR level. CONCLUSION: HIF-1 inhibitor YC-1 is able to reverse the acquired resistance of HCC827 GR to gefitinib, and the regulation of the HIF-1 pathway on MET may be one of the mechanisms.

UCH-L3 promotes non-small cell lung cancer proliferation via accelerating cell cycle and inhibiting cell apoptosis.

Ubiquitin C-terminal hydrolase-L3 (UCH-L3) is a deubiquitinase that has a crucial role in oncogenesis. This study was aimed to explore the biological function of UCH-L3 in non-small cell lung cancer (NSCLC). Bioinformatics analysis was used to detect UCH-L3 expression in NSCLC tissues and normal lung tissues, and to analyze the relationship between UCH-L3 expression and survival of patients. qRT-PCR and western blotting assays were used to detect UCH-L3 expression in NSCLC tumor tissues and adjacent normal tissues. CCK-8 assay was performed to examine the effect of UCH-L3 on NSCLC cell proliferation. Flow cytometry assay was conducted to examine the effect of UCH-L3 on NSCLC cell cycle and apoptosis. The expression of UCH-L3 in NSCLC tissues was markedly higher than in normal lung tissues, and high expression of UCH-L3 was positively associated with the poor survival of patients. UCH-L3 knockdown significantly inhibited the proliferation of NSCLC cells, whereas UCH-L3 overexpression had the opposite effect. Moreover, UCH-L3 promoted NSCLC cells proliferation via accelerating cell cycle and inhibiting cell apoptosis. UCH-L3 is upregulated in NSCLC and positively associated with the poor survival, and its expression contributes to NSCLC cell proliferation by accelerating cell cycle and inhibiting cell apoptosis.

IL-4-C-590T locus polymorphism and susceptibility to asthma in children: a meta-analysis.

OBJECTIVES: The study aimed to evaluate the link between the IL-4-C590T polymorphism and asthma susceptibility in children by meta-analysis. SOURCES: The study collected all the case-control studies found in PubMed, Embase, CNKI, Wanfang, VIP, and other databases until September 2019. Stata v. 15.0 was used to conduct meta-analysis, calculate the combined OR and its 95% CI, and then conduct subgroup analysis. SUMMARY OF THE FINDINGS: Seven studies were included in the study, containing 860 cases and 810 controls. Relative to the C allele, the T allele at the IL-4-C590T locus was associated with susceptibility to asthma in children (OR = 1.45, 95% CI: 1.05-2.01). The results of ethnicity subgroup analysis showed that there was statistical significance, with OR = 1.61 (95% CI: 1.01-2.57) in the Asian population. In the dominant and recessive genetic models, the overall test and the Asian population subgroup analysis were statistically significant. In the homozygous model, there was statistical significance, but no statistical significance in heterozygous model. CONCLUSIONS: The IL-4-C590T polymorphism was associated with asthma susceptibility, and T allele and TT genotype may increase the risk of asthma susceptibility in children, especially in the Asian population.

Emodin protects against intestinal and lung injury induced by acute intestinal injury by modulating SP-A and TLR4/NF-κB pathway.

OBJECTIVE: Our aim was to investigate the effect of emodin on intestinal and lung injury induced by acute intestinal injury in rats and explore potential molecular mechanisms. METHODS: Healthy male Sprague-Dawley (SD) rats were randomly divided into five groups (n=10, each group): normal group; saline group; acute intestinal injury model group; model + emodin group; model+NF-κB inhibitor pynolidine dithiocarbamate (PDTC) group. Histopathological changes in intestine/lung tissues were observed by Hematoxylin and Eosin (H&E) and terminal deoxynucleotidyl transferase biotin-dUTP nick-end labeling (TUNEL) staining. Serum IKBα, p-IKBα, surfactant protein-A (SP-A) and toll-like receptor 4 (TLR4) levels were examined using enzyme-linked immunosorbent assay (ELISA). RT-qPCR was performed to detect the mRNA expression levels of IKBα, SP-A and TLR4 in intestine/lung tissues. Furthermore, the protein expression levels of IKBα, p-IKBα, SP-A and TLR4 were detected by Western blot. RESULTS: The pathological injury of intestinal/lung tissues was remarkedly ameliorated in models treated with emodin and PDTC. Furthermore, the intestinal/lung injury scores were significantly decreased after emodin or PDTC treatment. TUNEL results showed that both emodin and PDTC treatment distinctly attenuated the apoptosis of intestine/lung tissues induced by acute intestinal injury. At the mRNA level, emodin significantly increased the expression levels of SP-A and decreased the expression levels of IKBα and TLR4 in intestine/lung tissues. According to ELISA and Western blot, emodin remarkedly inhibited the expression of p-IKBα protein and elevated the expression of SP-A and TLR4 in serum and intestine/lung tissues induced by acute intestinal injury. CONCLUSION: Our findings suggested that emodin could protect against intestinal and lung injury induced by acute intestinal injury by modulating SP-A and TLR4/NF-κB pathway.

Value of Serum Carbohydrate Antigen 19-9 and Carcinoembryonic Antigen in Evaluating Severity and Prognosis of Connective Tissue Disease-Associated Interstitial Lung Disease.

OBJECTIVES: This study aims to detect serum carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA 19-9) levels in connective tissue disease-associated interstitial lung disease (CTD-ILD) patients and to demonstrate their values in evaluating the severity and prognosis of CTD-ILD. PATIENTS AND METHODS: The study included 82 CTD-ILD patients (54 males, 28 females; mean age 67.9 years; range 29 to 91 years) and 82 controls (54 males, 28 females; mean age 68.1 years; range 30 to 92 years). Patients were followed-up for 12 months. Correlations of serum CEA and CA 19-9 with disease severity parameters (pulmonary function, oxygenation index and involvement score on high resolution computed tomography) were analyzed. Survival analysis was used to evaluate significance of serum CEA and CA 19-9 as prognosis predictors. RESULTS: Serum CEA and CA 19-9 levels were higher in CTD-ILD patients compared with controls (both p<0.05) and correlated with disease severity (p<0.05 for all R2). High levels of serum CEA and CA 19-9 were associated with poor survival (both p<0.05). Serum CEA level was indicated as a prognostic factor for cumulative survival (hazard ratio=1.685, 95% confidence interval: 1.405-2.021, p=0.001). CONCLUSION: In CTD-ILD patients, serum CEA and CA 19-9 are elevated and can be indicators of disease severity. Moreover, serum CEA is a significant and independent predictor of survival.