[Protective effect and mechanism of Maiwei Yangfei Decoction on pulmonary fibrosis mice based on Nrf2 regulation of oxidative stress].

This study explored the effect and mechanism of Maiwei Yangfei Decoction(MWYF) on pulmonary fibrosis(PF) mice. MWYF was prepared, and its main components were detected by ultra-high-performance liquid chromatography-triple quadrupole tandem mass spectrometry(UPLC-MS/MS). Male C57BL/6J mice were randomly divided into a control group, a model group, a pirfenidone(PFD) group, and low-, medium-, and high-dose MWYF groups, with 10 mice in each group. The PF model was induced in mice except for those in the control group by intratracheal instillation of bleomycin(BLM), and model mice were treated with saline or MWYF or PFD by gavage the next day. The water consumption, food intake, hair, and activity of mice were observed daily. The pathological changes in lung tissues were observed by hematoxylin-eosin(HE) staining, Masson staining, and CT scanning. The level of hydroxyproline(HYP) in lung tissues was detected by alkaline hydrolysis. Immunohistochemistry was used to observe the expression of collagen type Ⅲ(COL3) and fibronectin. The mRNA expression levels of α-smooth muscle actin(α-SMA), type Ⅰ collagen α1(COL1α1), COL3, and vimentin were detected by reverse transcription real-time fluorescence quantitative polymerase chain reaction(RT-qPCR). Superoxide dismutase(SOD) and malondialdehyde(MDA) kits were used to detect oxidative stress indicators in lung tissues and serum. The nuclear translocation of nuclear factor E2-related factor 2(Nrf2) protein was detected by immunofluorescence. The protein and mRNA expression levels of Nrf2, catalase(CAT), and heme oxygenase 1(HO-1) in lung tissues were detected by Western blot and RT-qPCR. Twelve chemical components were detected by UPLC-MS/MS. Animal experiments showed that MWYF could improve alveolar inflammation, collagen deposition, and fibrosis in PF mice, increase body weight of mice, and down-regulate the expression of fibrosis indexes such as HYP, α-SMA, COL1α1, COL3, fibronectin, and vimentin in lung tissues. In addition, MWYF could potentiate the activity of SOD in lung tissues and serum of PF mice, up-regulate the expression level of Nrf2, and promote its transfer to the nucleus, up-regulate the levels of downstream antioxidant target genes CAT and HO-1, and then reduce the accumulation of lipid metabolite MDA. In summary, MWYF can significantly improve the pathological damage and fibrosis of lung tissues in PF mice, and its mechanism may be related to the activation of the Nrf2 pathway to regulate oxidative stress.

Idiopathic pulmonary fibrosis and diabetes mellitus: a meta-analysis and systematic review.

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a chronic diffuse interstitial lung disease, of which the etiology has been poorly understood. Several studies have focused on the relationship between IPF and diabetes mellitus (DM) in the past years but have failed to reach a consensus. This meta-analysis aimed to examine the association between diabetes to IPF. METHODS: We accumulated studies investigating the association between DM and IPF from databases including Medline, Cochrane Library, Embase, Web of Science, and China National Knowledge Infrastructure. RevMan 5.3 and the Newcastle-Ottawa Scale (NOS) were utilized to analyze the data and assess the quality of the included studies. The value of odds ratio (OR) with 95% confidence interval (CI) was used as the measure to estimate the risk of DM in IPF. Heterogeneity was assessed by I2 statistics. We also performed subgroup analysis, meta-regression, and Egger's test for bias analysis. RESULTS: Nine case-control studies with 5096 IPF patients and 19,095 control subjects were included in the present meta-analysis, which indicated a positive correlation between DM and IPF (OR 1.65, 95% CI 1.30-2.10; P < 0.0001). Meta-regression and subgroup analysis negated the influence of covariates like cigarette smoking, age and gender, but the heterogeneity existed and could not be fully explained. CONCLUSION: IPF and DM may be associated, but the causal relationship remains indeterminate till now. Further rigorously designed studies are required to confirm the present findings and investigate the possible mechanisms behind the effect of DM on IPF.

Citrus Alkaline Extracts Inhibit Senescence of A549 Cells to Alleviate Pulmonary Fibrosis via the ß-Catenin/P53 Pathway.

BACKGROUND Idiopathic pulmonary fibrosis (IPF) is a disease related to aging, which has become increasingly prevalent as the population has aged. However, there remains no effective treatment for the disease. Alveolar epithelial type II cell (AEC II) senescence plays an important role in the occurrence and development of IPF. Therefore, enhancing our understanding of aging AEC IIs might facilitate the development of a new therapeutic strategy for the prevention and treatment of IPF. The aim of this study was to investigate the effect of citrus alkaline extracts (CAE) on senescence in A549 cells and elucidate the mechanism by which CAE function. MATERIAL AND METHODS Adriamycin RD (ARD) induces the senescence of A549 cells. Relevant indicators were identified following administration of 3 concentrations of CAE (50 µg/mL, 100 µg/mL, and 200 µg/mL) to A549 cells. RESULTS CAE inhibited senescence in ARD-induced A549 cells. It inhibited p16, p21, p53, and a senescence-associated secretory phenotype, and reduced expression of the senescence-related positive cells of ß-galactosidase. Further study revealed that activation of the ß-catenin signaling pathway is closely associated with p53. CAE inhibited senescence in A549 cells via the ß-catenin/p53 pathway. Further, inhibition of b-catenin was associated with reduced expression levels of p53 and p21, and the anti-aging effects of CAE were enhanced. When expression of p53 was inhibited, expression levels of ß-catenin also tended to decrease. CONCLUSIONS In summary, our study showed that CAE can inhibit aging in A549 cells to alleviate pulmonary fibrosis, and thus limit the secretion of the extracellular matrix and collagen in lung fibroblasts.

Baduanjin exercise for chronic obstructive pulmonary disease: an updated systematic review and meta-analysis.

OBJECTIVE: To objectively evaluate the effectiveness of Baduanjin exercise on cardiopulmonary function and quality of life in chronic obstructive pulmonary disease patients. DATA SOURCES: Articles published in PubMed, EMBASE, China National Knowledge Infrastructure Database, the Cochrane Library, Wanfang Database, and China Biological Medicine Database from inception to March 2020. REVIEW METHOD: Articles on randomized controlled trials about Baduanjin exercise for the treatment of chronic obstructive pulmonary disease were identified. Cochrane handbook was applied to assess the quality of included trials. Stata (version 14.0) and Review Manager (version 5.3) were employed for data analysis. Mean difference with 95% confidence intervals were calculated for pulmonary function, 6-minute walking distance, and the quality of life. RESULTS: Thirty-one randomized controlled trials including 3045 patients were included. The result of meta-analysis indicated that comparing with any other type of treatment alone, Baduanjin exercise combined other type of treatment revealed well efficacy in improving exercise capability on 6-minute walking distance (mean difference = 43.83, 95% confidence interval (29.47, 58.20), P < 0.00001), forced expiratory volume in 1 second (mean difference = 0.23, 95% confidence interval (0.15, 0.31), P < 0.00001), forced volume vital capacity (mean difference = 0.19, 95% confidence interval (0.08, 0.30), P = 0.0007), the ratio of forced expiratory volume in the first second to forced vital capacity (mean difference = 3.85, 95% confidence interval (2.19, 5.51), P < 0.00001), and the quality of life in chronic obstructive pulmonary disease patients regarding the St. George respiratory questionnaire (mean difference = -7.71, 95% confidence interval (-10.54, -4.89), P < 0.00001) and chronic obstructive pulmonary disease assessment test (mean difference = -2.56, 95% confidence interval (-4.13, -1.00), P = 0.001). CONCLUSIONS: Baduanjin exercise could improve exercise capacity, pulmonary function, and quality of life for patients with chronic obstructive pulmonary disease.

Ganoderic Acid A Inhibits Bleomycin-Induced Lung Fibrosis in Mice.

BACKGROUND: To study the protective effects of ganoderic acid A (GAA) on bleomycin (BLM)-induced pulmonary fibrosis. METHODS: ICR mice were intratracheally instilled with BLM to induce pulmonary fibrosis on day 0. Then the mice were orally given GAA (25, 50 mg/kg) or dexamethasone (2 mg/kg). After treatment for 21 days, the mice were sacrificed. Wet dry weight (W/D) ratio of lung was used to detect pulmonary edema. Myeloperoxidase (MPO), interleukin-1ß (IL-1ß), IL-6, tumor necrosis factor-α (TNF-α), malondialdehyde (MDA), and superoxide dismutase (SOD) were detected by enzyme-linked immunosorbent assay. Hematoxylin and eosin staining was used to evaluate the pathological changes. The levels of transforming growth factor ß (TGF-ß), phosphorylated-smad3 (p-smad3), p-IκB, and p-nuclear factor-kappa B (NF-κB) in lung tissue were detected by western blot. RESULTS: GAA treatment significantly improved MPO activity, W/D ratio, and lung histopathology. The protective effect of GAA may be related to downregulation of TNF-α, IL-1ß, IL-6, MDA and upregulation of SOD. In addition, GAA significantly decreased the levels of TGF-ß, p-smad3, p-IκB, and p-NF-κB, compared with those in BLM group. CONCLUSION: GAA has protective effect on BLM-induced lung injury, and TGF-ß/Smad-3/NF-κB signaling pathway may play an important role in the pathogenesis of BLM-induced lung injury.

[Meta-analysis of Banmao Capsules in adjuvant treatment for non-small cell lung cancer].

To systemically evaluate the efficacy and safety of Banmao Capsules in the adjuvant treatment for non-small cell lung cancer(NSCLC). All of randomized controlled trials(RCT) about Banmao Capsules in adjuvant treatment for non-small cell lung cancer were retrieved in PubMed, EMbase, Cochrane Library, CNKI, VIP, CBM, WanFang database from database inception to August 2019. Two researchers extracted data and assessed literature quality separately, and made a Meta-analysis by RevMan 5.3 software. Thirteen trials involving 1 148 patients, including 595 in treatment group and 553 in control group, were enrolled in the review. The Meta-analysis showed that compared with conventional treatment, adjuvant treatment of NSCLC with Banmao Capsules can enhance the objective tumor response rate(RR=1.43,95%CI[1.30,1.58],P<0.01), and the disease control rate(RR=1.16,95%CI[1.11,1.22],P<0.01); improve the quality of life(RR=1.56,95%CI[1.27,1.92],P<0.01); reduce the incidence of myelosuppression(RR=0.41,95%CI[0.26,0.66],P<0.01), gastrointestinal reactions(RR=0.46,95%CI[0.33,0.65],P<0.01), liver and kidney dysfunction(RR=0.44,95%CI[0.29,0.66],P<0.01). The results showed that in the treatment of NSCLC, Banmao Capsules can increase the short-term efficacy, improve the quality of life of patients, and reduce the side effects of platinum-based chemotherapy drugs. More high-quality and large-scale randomized controlled trials are required in the future.

Gastric Acid and Pepsin Work Together in Simulated Gastric Acid Inhalation Leading to Pulmonary Fibrosis in Rats.

BACKGROUND The clinical association between gastroesophageal reflux disease (GERD) and idiopathic pulmonary fibrosis (IPF) has been known for many years, but it is still unclear. The present study investigated the association between experimentally simulated aspiration and pulmonary fibrosis. MATERIAL AND METHODS A total of 120 male Sprague-Dawley rats were randomly divided into a negative control group, a bleomycin group, and 3 simulated aspiration groups. The bleomycin group was administered a one-time intratracheal injection of bleomycin, whereas the 3 simulated aspiration groups were treated either with an intratracheal instillation of gastric fluid combined with pepsin, with pepsin alone, or with hydrochloric acid, all twice a week, and the negative control group was administered normal saline twice a week. Lung tissues were collected to evaluate pathological changes and the mRNA expression levels of connective tissue growth factor (CTGF), type I collagen, and transforming growth factor. RESULTS The results demonstrated that the degree of fibrosis in the early stage was low in each of the 3 simulated aspiration groups, but gradually increased over time. The expression levels of the downstream factor of fibrosis, CTGF, and type I collagen also reflected this trend. CONCLUSIONS The study demonstrates that aspiration of gastric contents can cause pulmonary fibrosis, and mixed aspiration of pepsin and gastric fluid can accelerate this process. This study provides strong evidence in support of a potential association between human GERD and IPF.

[Meta-analysis of Cinobufacini Injection combined with platinum-contained first-line chemotherapy in treatment of non-small cell lung cancer].

To systemically evaluate the efficacy and safety of Cinobufacini Injection in combination with platinum-contained first-line chemotherapy for treatment of non-small cell lung cancer(NSCLC). The randomized controlled trials(RCT) about the Cinobufacini in combination with platinum-contained first-line chemotherapy(versus chemotherapy alone) were collected through PubMed,Cochrane library,CNKI,VIP,CBM,and Wan Fang Database from database inception to December 2018. Two researchers extracted data and assessed the literature quality separately,and made a Meta-analysis by using Rev Man 5. 3 software. Twenty-seven RCTs were included in the present review,involving 2 125 patients,1 082 in treatment group and 1 043 in control group. The Meta-analysis results showed that as compared with chemotherapy alone,the combination of Cinobufacini and platinum-contained first-line chemotherapy could enhance one year survival rate(RR = 1. 34,95%CI[1. 17,1. 55],P< 0. 01),two year survival rate(RR = 1. 84,95% CI[1. 31,2. 59],P<0. 01),objective tumor response rate(RR = 1. 47,95%CI[1. 33,1. 63],P<0. 01); improve the quality of life for patients(RR =1. 54,95%CI[1. 37,1. 72],P < 0. 01); and reduce the incidences of WBC toxicity(RR = 0. 63,95% CI[0. 49,0. 80],P < 0. 01),platelet toxicity(RR = 0. 54,95%CI[0. 35,0. 84],P<0. 01),gastrointestinal reactions(RR = 0. 60,95%CI[0. 45,0. 80],P<0. 05),pain(RR = 1. 68,95% CI[1. 38,2. 03],P< 0. 01),and hair loss reaction(RR = 0. 76,95% CI[0. 59,0. 98],P < 0. 05). The results showed that for the treatment of NSCLC,the addition of cinofacini to conventional platinum-contained chemotherapy can increase the long-term and short-term efficacy of chemotherapy,improve the quality of life for patients,and reduce the side effects of platinumbased chemotherapy drugs. However,more high quality and large-scale randomized controlled trials are required to verify this conclusion in the future.

Clinical findings in 111 cases of influenza A (H7N9) virus infection.

BACKGROUND: During the spring of 2013, a novel avian-origin influenza A (H7N9) virus emerged and spread among humans in China. Data were lacking on the clinical characteristics of the infections caused by this virus. METHODS: Using medical charts, we collected data on 111 patients with laboratory-confirmed avian-origin influenza A (H7N9) infection through May 10, 2013. RESULTS: Of the 111 patients we studied, 76.6% were admitted to an intensive care unit (ICU), and 27.0% died. The median age was 61 years, and 42.3% were 65 years of age or older; 31.5% were female. A total of 61.3% of the patients had at least one underlying medical condition. Fever and cough were the most common presenting symptoms. On admission, 108 patients (97.3%) had findings consistent with pneumonia. Bilateral ground-glass opacities and consolidation were the typical radiologic findings. Lymphocytopenia was observed in 88.3% of patients, and thrombocytopenia in 73.0%. Treatment with antiviral drugs was initiated in 108 patients (97.3%) at a median of 7 days after the onset of illness. The median times from the onset of illness and from the initiation of antiviral therapy to a negative viral test result on real-time reverse-transcriptase-polymerase-chain-reaction assay were 11 days (interquartile range, 9 to 16) and 6 days (interquartile range, 4 to 7), respectively. Multivariate analysis revealed that the presence of a coexisting medical condition was the only independent risk factor for the acute respiratory distress syndrome (ARDS) (odds ratio, 3.42; 95% confidence interval, 1.21 to 9.70; P=0.02). CONCLUSIONS: During the evaluation period, the novel H7N9 virus caused severe illness, including pneumonia and ARDS, with high rates of ICU admission and death. (Funded by the National Natural Science Foundation of China and others.).

Adjuvant Corticosteroid Treatment in Adults With Influenza A (H7N9) Viral Pneumonia.

OBJECTIVE: To determine the impact of adjuvant corticosteroids administered to patients hospitalized with influenza A (H7N9) viral pneumonia. DESIGN: The effects of adjuvant corticosteroids on mortality were assessed using multivariate Cox regression and a propensity score-matched case-control study. Nosocomial infections and viral shedding were also compared. SETTING: Hospitals with influenza A (H7N9) viral pneumonia patient admission in 84 cities and 16 provinces of Mainland China. PATIENTS: Adolescent and Adult patients aged >14 yr with severe laboratory-confirmed influenza A (H7N9) virus infections were screened from April 2013 to March 2015. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The study population comprised 288 cases who were hospitalized with influenza A (H7N9) viral pneumonia. The median age of the study population was 58 years, 69.8% of the cohort comprised male patients, and 51.4% had at least one type of underlying diseases. The in-hospital mortality was 31.9%. Two hundred and four patients (70.8%) received adjuvant corticosteroids; among them, 193 had hypoxemia and lung infiltrates, 11 had chronic obstructive pulmonary disease, and 11 had pneumonia only. Corticosteroids were initiated within 7 days (interquartile range, 5.0-9.4 d) of the onset of illness and the maximum dose administered was equivalent to 80-mg methylprednisolone (interquartile range, 40-120 mg). The patients were treated with corticosteroids for a median duration of 7 days (interquartile range, 4.0-11.3 d). Cox regression analysis showed that compared with the patients who did not receive corticosteroid, those who received corticosteroid had a significantly higher 60-day mortality (adjusted hazards ratio, 1.98; 95% CI, 1.03-3.79; p = 0.04). Subgroup analysis showed that high-dose corticosteroid therapy (> 150 mg/d methylprednisolone or equivalent) significantly increased both 30-day and 60-day mortality, whereas no significant impact was observed for low-to-moderate doses of corticosteroids (25-150 mg/d methylprednisolone or equivalent). The propensity score-matched case-control analysis showed that the median viral shedding time was much longer in the group that received high-dose corticosteroids (15 d), compared with patients who did not receive corticosteroids (13 d; p = 0.039). CONCLUSIONS: High-dose corticosteroids were associated with increased mortality and longer viral shedding in patients with influenza A (H7N9) viral pneumonia.

Dietary nitrate supplementation to enhance exercise capacity in patients with COPD: Evidence from a meta-analysis of randomized controlled trials and a network pharmacological analysis.

OBJECTIVE: The potential effects of nitrate in patients with chronic obstructive pulmonary disease (COPD) have attracted increased research interest. However, previous clinical trials have reported inconsistent results, and consecutive meta-analyses have failed to reach a consensus. Since some randomized controlled trials have recently been conducted that can provide more evidence, we performed an updated meta-analysis. METHODS: A comprehensive literature search was conducted using PubMed, the Cochrane Library, Embase, and Web of Science databases to identify trials that assessed the efficacy and safety of nitrate in patients with COPD. The Revman 5.3 software was used for data analysis. Mean difference (MD) or standardized mean difference (SMD) with 95 % confidence interval (CI) was used as the effect measure, and forest plots were used to display individual and pooled results. Network pharmacology analysis was conducted to investigate the potential mechanisms of nitrate action in COPD. RESULTS: Eleven studies involving 287 patients were included in this meta-analysis. The results indicated that dietary nitrate supplementation increased plasma nitrate and nitrite concentrations and fractional exhaled nitric oxide in patients with COPD. Nitrate improved exercise capacity [SMD = 0.38, 95 % CI = 0.04-0.72] and endothelial function [MD = 9.41, 95 % CI = 5.30-13.52], and relieved dyspnea in patients with COPD. Network pharmacology identified AKT1, IL1B, MAPK3, and CASP3 as key treatment targets. CONCLUSION: Dietary nitrate supplementation could be used as a potential treatment for patients with COPD, especially to increase their exercise capacity. The underlying mechanisms may be related to AKT1, IL1B, MAPK3, and CASP3.

Mediastinal epithelioid inflammatory myofibroblastic sarcoma with the EML4-ALK fusion: A case report and literature review.

Epithelioid inflammatory myofibroblastic sarcoma (EIMS) is an aggressive subtype of inflammatory myofibroblastic tumour which rarely affects the chest cavity. We, for the first time, report a case of mediastinal EIMS with the EML4-ALK fusion. A young woman presented to our hospital with cough, chest tightness and shortness of breath. Computed tomography (CT) showed a mixed attenuation soft-tissue mass in the right middle and upper mediastinum. Negative results were obtained from bronchoscopy forceps biopsy and endobronchial ultrasound-guided transbronchial fine needle aspiration. CT-guided percutaneous biopsy was finally performed. However, due to the rapidly progressed EIMS that compressed the trachea and right main bronchus, the patient died of respiratory failure 1 day before diagnosis. EIMS progresses rapidly, and an early diagnosis is important. For mediastinal EIMS, CT-guided percutaneous biopsy may be useful. Next-generation sequencing of blood may be instructive to EIMS patients who are intolerant to invasive biopsy.

Clinical efficacy and potential mechanism of ginseng polysaccharides in the treatment of non-small cell lung cancer based on meta-analysis associated with network pharmacology.

Background: The ginseng polysaccharide injection is a well-known traditional Chinese medicine often employed as a supplementary treatment for cancer. This treatment can not only alleviate the adverse effects caused by tumor radiotherapy and chemotherapy but also enhance the immune system of individuals diagnosed with lung cancer. It is important to acknowledge the efficacy of ginseng polysaccharide injection in the treatment of non-small cell lung cancer (NSCLC). However, these small-sample studies may have certain biases, and the underlying mechanisms of ginseng polysaccharides therapy for NSCLC are still unclear. Methods: The present study involved a systematic review of the literature on randomized controlled trials (RCTs) focusing on using ginseng polysaccharide injection as a therapeutic approach for NSCLC. Seven databases were searched for eligible studies published before April 2023. Two researchers independently managed data extraction, risk of bias assessment, and data analyses using RevMan 5.3 software. In network pharmacology, we thoroughly searched the relevant literature on ginseng polysaccharides (GPs) and the PubChem database. This search aimed to identify the main active ingredients and targets associated with ginseng polysaccharides. Subsequently, we compared these targets with those of NSCLC and utilized bioinformatics techniques to analyze and explore their potential interactions. Results: A total of 11 RCTs involving 845 patients with NSCLC were included in the meta-analysis. The meta-analysis revealed that ginseng polysaccharide injection combined significantly improved the objective response rate [RR = 1.45, 95% CI (1.26, 1.67), P < 0.00001]. Furthermore, it was observed that ginseng polysaccharide injection increased the serum levels of CD4+ T-lymphocytes (CD4+ T) [MD = 8.98, 95% CI (5.18, 12.78), P < 0.00001], and decreased the serum levels of CD8+ T-lymphocytes (CD8+ T) [MD = -2.68, 95% CI (-4.66, -0.70), P = 0.008]. Through network pharmacology analysis, a total of 211 target genes of GPs and 81 common targets were identified. GAPDH, EGFR, VEGFA, JUN, SRC, CASP3, STAT3, CCND1, HSP90AA1, and MMP9 were identified as the core target proteins. Additionally, KEGG enrichment analysis revealed 122 relevant signaling pathways, including Pathways in cancer, PD-L1 expression and PD-1 checkpoint pathway in cancer, and Proteoglycans in cancer. Conclusion: Ginseng polysaccharide injection can improve the ORR of patients with NSCLC, increase the serum levels of CD4+ T, and decrease the serum levels of CD8+ T. The potential mechanism may be associated with the PD-1/PD-L1 signaling pathway.

The causal relationship between genetically predicted blood metabolites and idiopathic pulmonary fibrosis: A bidirectional two-sample Mendelian randomization study.

BACKGROUND: Numerous metabolomic studies have confirmed the pivotal role of metabolic abnormalities in the development of idiopathic pulmonary fibrosis (IPF). Nevertheless, there is a lack of evidence on the causal relationship between circulating metabolites and the risk of IPF. METHODS: The potential causality between 486 blood metabolites and IPF was determined through a bidirectional two-sample Mendelian randomization (TSMR) analysis. A genome-wide association study (GWAS) involving 7,824 participants was performed to analyze metabolite data, and a GWAS meta-analysis involving 6,257 IPF cases and 947,616 control European subjects was conducted to analyze IPF data. The TSMR analysis was performed primarily with the inverse variance weighted model, supplemented by weighted mode, MR-Egger regression, and weighted median estimators. A battery of sensitivity analyses was performed, including horizontal pleiotropy assessment, heterogeneity test, Steiger test, and leave-one-out analysis. Furthermore, replication analysis and meta-analysis were conducted with another GWAS dataset of IPF containing 4,125 IPF cases and 20,464 control subjects. Mediation analyses were used to identify the mediating role of confounders in the effect of metabolites on IPF. RESULTS: There were four metabolites associated with the elevated risk of IPF, namely glucose (odds ratio [OR] = 2.49, 95% confidence interval [95%CI] = 1.13-5.49, P = 0.024), urea (OR = 6.24, 95% CI = 1.77-22.02, P = 0.004), guanosine (OR = 1.57, 95%CI = 1.07-2.30, P = 0.021), and ADpSGEGDFXAEGGGVR (OR = 1.70, 95%CI = 1.00-2.88, P = 0.0496). Of note, the effect of guanosine on IPF was found to be mediated by gastroesophageal reflux disease. Reverse Mendelian randomization analysis displayed that IPF might slightly elevate guanosine levels in the blood. CONCLUSION: Conclusively, hyperglycemia may confer a promoting effect on IPF, highlighting that attention should be paid to the relationship between diabetes and IPF, not solely to the diagnosis of diabetes. Additionally, urea, guanosine, and ADpSGEGDFXAEGGGVR also facilitate the development of IPF. This study may provide a reference for analyzing the potential mechanism of IPF and carry implications for the prevention and treatment of IPF.

Retinal microvascular changes in patients with pancreatitis and their clinical significance.

Acute pancreatitis, a common exocrine inflammatory disease affecting the pancreas, is characterized by intense abdominal pain and multiple organ dysfunction. However, the alterations in retinal blood vessels among individuals with acute pancreatitis remain poorly understood. This study employed optical coherence tomography angiography (OCTA) to examine the superficial and deep retinal blood vessels in patients with pancreatitis. Sixteen patients diagnosed with pancreatitis (32 eyes) and 16 healthy controls (32 eyes) were recruited from the First Affiliated Hospital of Nanchang University for participation in the study. Various ophthalmic parameters, such as visual acuity, intraocular pressure, and OCTA image for retina consisting of the superficial retinal layer (SRL) and the deep retinal layer (DRL), were recorded for each eye. The study observed the superficial and deep retinal microvascular ring (MIR), macrovascular ring (MAR), and total microvessels (TMI) were observed. Changes in retinal vascular density in the macula through annular partitioning (C1-C6), hemispheric quadrant partitioning (SR, SL, IL, and IR), and early diabetic retinopathy treatment studies (ETDRS) partitioning methods (R, S, L, and I). Correlation analysis was employed to investigate the relationship between retinal capillary density and clinical indicators. Our study revealed that in the superficial retinal layer, the vascular density of TMI, MIR, MAR, SR, IR, S, C2, C3 regions were significantly decreased in patients group compared with the normal group. For the deep retinal layer, the vascular density of MIR, SR, S, C1, C2 regions also reduced in patient group. The ROC analysis demonstrated that OCTA possesses significant diagnostic performance for pancreatitis. In conclusion, patients with pancreatitis may have retinal microvascular dysfunction, and OCTA can be a valuable tool for detecting alterations in ocular microcirculation in pancreatitis patients in clinical practice.

Exploration of Molecular Targets and Mechanisms of Curcumin in the Treatment of COVID-19 with Depression by an Integrative Pharmacology Strategy.

BACKGROUND: Coronavirus disease 2019 (COVID-19) not only causes a range of respiratory symptoms but also has a great impact on individual mental health. With the global pandemic of SARS-CoV-2, the incidence of COVID-19 comorbid with depression has increased significantly. Curcumin, a natural polyphenol compound, has been shown to have antidepressant and anti-coronavirus activities. METHODS: This study aimed to explore the molecular targets and underlying biological mechanisms of curcumin in the treatment of COVID-19 with depression through an integrative pharmacology strategy, including target prediction, network analysis, PPI analysis, GO and KEGG enrichment analyses, and molecular docking. RESULTS: After a comprehensive search and thorough analysis, 8 core targets (ALB, AKT1, CASP3, STAT3, EGFR, PTGS2, FOS, and SERPINE1) were identified. GO and KEGG enrichment analysis results revealed that the pathways related to viral infection, immune regulation, neuronal reorganization, apoptosis, and secretion of inflammatory cytokines were involved in the pathological process. Furthermore, molecular docking showed that curcumin could spontaneously bind to the SARS-CoV-2-related receptor proteins and the core targets with a strong binding force. CONCLUSION: The potential pharmacological mechanisms of curcumin in COVID-19 comorbid depression were evaluated. Curcumin can be used as a therapeutic agent for COVID-19 comorbid depression. One of the potential mechanisms may be to reduce the inflammatory response and suppress the cytokine storm by regulating the JAK-STAT signaling pathway and MAPK signaling pathway. These findings may help to overcome the impact of the COVID-19 pandemic on psychological health.

Efficacy evaluation and potential pharmacological mechanism of tanreqing injection in the treatment of COPD combined with respiratory failure based on meta-analysis and network pharmacology.

Background: Tanreqing injection (TRQI) is a Chinese patent medicine. It is commonly used in the treatment of acute exacerbation of COPD in China. It substantially improves the partial pressure of oxygen (PaO2), partial pressure of carbon dioxide (PaCO2), and lung function in patients with COPD combined with respiratory failure (RF) and improves the total clinical effective rate. Materials and methods: Relevant randomized controlled trials (RCTs) on the treatment of COPD combined with RF with TRQI were collected through search of PubMed, Web of Science, Embase, Cochrane Library, CBM, VIP, Wanfang, and CNKI up to October 2, 022. Two investigators in this study independently evaluated the quality of the literature and utilized RevMan 5.4 software for analysis. In network pharmacology, TCMSP database, PubChem database, DisGeNet, Genecards, and other databases were searched to screen the chemical components and targets of TRQI and mapped with COPD-RF targets to obtain potential action targets, which were then analyzed using bioinformatics techniques to initially explore their effects. Result: A total of 18 RCTs containing 1485 patients, showed that TRQI combined with conventional treatment improved the total clinical efficiency of patients with COPD combined with RF compared with that of the conventional treatment group ([RR = 1.33, 95% CI (1.25, 1.41), P < 0.01]), PaCO2 [SMD = -1.29, 95% CI (-1.41, -1.17), P < 0.00001], PaO2 [SMD = 1.19, 95% CI (1.06, 1.31), P < 0.00001], pulmonary function [SMD = 1.00, 95% CI (0.79, 1.21), P < 0.00001]. Through network pharmacology analysis, 284 potential TRQI and 19 common targets were identified. TNF, TP53, SIRT1, SRC, CCND1, IL-10, NF-κB, MAPK14, STAT3, SMAD3 are core targets proteins. In addition, 56 related pathways of TRQI were identified, such as the TNF, MAPK, IL-17, NF-κB signaling pathways. Conclusion: In conclusion, the efficacy of TRQI combined with conventional treatment for COPD combined with RF was higher than that of conventional treatment alone. These findings suggest that TRQI acts on COPD-RF through a multi-target, multi-component, and multi-pathway mechanism. Future studies may explore the active components of TRQI.

Leukotriene Receptor Antagonists and Risk of Neuropsychiatric Entities: A Meta-Analysis of Observational Studies.

BACKGROUND: Leukotriene receptor antagonists (LTRAs) are commonly prescribed to patients with allergic diseases. Several case reports and pharmacovigilance studies have indicated that LTRAs might increase the risk of neuropsychiatric (NP) entities. However, the results are mixed in observational studies. Thus, the association between LTRAs and NP entities remains controversial. OBJECTIVE: To quantitatively evaluate the NP risk with LTRAs based on current observational studies to provide a reference for clinical practice. METHODS: We systematically reviewed the literature in Medline, Embase, Web of Science, Cochrane Library, Scopus, and PsycINFO. A meta-analysis of observational studies that investigated the association between LTRA use and the risk of NP entities was performed. Odds ratios (OR) with 95% confidence intervals (CI) were used to measure the effect; heterogeneity was evaluated using I-squared (I2) statistics. Subgroup and sensitivity analyses were conducted to assess bias. RESULTS: Eleven articles were included in the primary analysis. No significant association was found between LTRA use and NP entities (OR: 1.08, 95% CI: 0.93-1.24, I2 = 93.7%). In patients with allergic rhinitis (AR), a mildly increased NP risk was found (OR: 1.099, 95% CI: 1.004-1.202). The association between LTRA use and NP entities was not significant in patients with asthma (OR: 1.06, 95% CI: 0.90-1.26). LTRAs increased the risk of NP entities in a single study using data from an asthma clinic (OR: 9.00, 95% CI: 1.20-69.50), but not in studies from databases (OR: 1.07, 95% CI: 0.93-1.23). CONCLUSION: At the population level, LTRAs and NP entities were unrelated. However, the association may exist in particular groups (eg, patients with AR or NP history). Subject-specific studies are required to further examine the relationship between LTRAs and NP entities and identify the underlying mechanisms.

Effect of Cinobufacini plus platinum-based chemotherapy regimen on the immune function of patients with non-small-cell lung cancer: A meta-analysis.

Background: Cinobufacini is a Chinese medicinal preparation extracted from the traditional Chinese medicine toad skin and is commonly used clinically as an adjuvant treatment for malignant tumours. Purpose: To systematically evaluate the effects of Cinobufacini combined with a first-line platinum-based chemotherapy regimen in patients with non-small-cell lung cancer (NSCLC), especially in terms of immune function. Materials and methods: Eight electronic databases were searched for randomised controlled trials (RCTs) investigating Cinobufacini in conjunction with platinum-based chemotherapy for NSCLC (stage III-IV) published from 2012 to the present. GRADE Pro GDT was used to assess RCT quality and meta-analysis was performed mainly using Review Manager version 5.4, with the assistance of Stata version 16.0 (StataCorp LLC, College Station, TX, USA), and trial sequential analysis software. Results: A total of 35 studies were included. Meta-analysis revealed that the combination therapy group exhibited a better disease control rate (DCR) [OR = 2.63, 95%CI (2.15, 3.21), P < 0.00001], with a higher one-year [OR = 2.41,95% CI (1.75,3.33), P < 0.00001], and two-year [OR = 2.28, 95% CI (1.56,3.33), P < 0.00001] survival rate, plus lower leukocyte toxicity [OR = 0.40, 95%CI (0.33,0.49), P < 0.00001]. For immune function, the combination of chemotherapy with Cinobufacini effectively increased the proportion of CD3+ [SMD = 1.15, 95% CI (0.89,1.42), P < 0.00001], CD4+ [SMD = 1.60, 95%CI (1.26,1.94), P < 0.00001] and the CD4+/CD8+ ratio [SMD = 2.15, 95% CI (1.45,2.86), P < 0.00001] in peripheral blood. Conclusion: The addition of Cinobufacini to platinum-based chemotherapies for advanced NSCLC significantly improved clinical efficacy, enhanced immune function, and reduced chemotherapeutic toxicity, irrespective of administration and treatment duration.

Molecular mechanism of quercetin in treating RA-ILD based on network pharmacology, molecular docking, and experimental validation.

Rheumatoid arthritis (RA) is an autoimmune disease that is associated with systemic complications. Interstitial lung disease (ILD) is the most common pulmonary complication and second leading cause of death in patients with RA. In this study, we used network pharmacology and experimental validation to identify the targets and pathways of quercetin (Que) in the treatment of RA-associated ILD (RA-ILD). A total of 32 potential targets of Que for RA-ILD treatment were screened from six databases, and 10 core targets were screened using protein-protein interaction network analysis. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis, and molecular docking were employed to explore the potential mechanisms of Que in RA-ILD treatment. The results suggested the IL-17 signaling pathway as an important pathway through which Que alleviates RA-ILD. Subsequently, LPS (1 µg/ml) was used to establish an inflammation model on RAW 264.7 cells, and different concentrations of Que (25, 50, and 100 µM) were used for intervention. Que significantly reduced the expression levels of IL-17, TNF-α, IL-6, and IL-1ß in RAW 264.7 cells. Our findings suggest that Que alleviates RA-ILD by regulating the IL-17 signaling pathway and reducing inflammation.