Asthma and rhinosinusitis are both common respiratory diseases in children，with a high rate of co-morbidity，and both affect each other.The theory of “same airway，same disease” has been confirmed in recent years.However，rhinosinusitis is often underdiagnosed，and correctly recognizing，diagnosing and treating rhinosinusitis in a timely manner is conducive to asthma control.Both rhinosinusitis and asthma are highly heterogeneous diseases，with diverse and complex inflammatory endotypes and biomarkers，including eosinophils and neutrophils.This article reviews the epidemiology of rhinosinusitis and asthma co-morbidities，the inflammatory endotypes and biomarkers of rhinosinusitis，the impact of rhinosinusitis on asthma and its mechanism of influence，and the impact of treating rhinosinusitis on asthma control.

Objective This study aimed to clarify the anti-influenza virus activity of Bingyanqing(BYQ),as well as to explore the mechanism of BYQ in treating influenza through network pharmacology and experimental verification.Methods The impact of BYQ on mortality,lung index,and viral load in an influenza mouse model was detected.We collected the ingredients and targets of BYQ formula by searching databases including TCMSP,Swiss Target Prediction and consulting the literature.The"ingredients-common target"network for anti-influenza effect of BYQ was constructed using Cytoscape software.The protein-protein interaction(PPI)network was constructed using the STRING database and Cytoscape software,and the core targets were screened.Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analyses were performed for common targets.The effect of BYQ on reducing influenza-induced oxidative damage,the expression of antioxidant and pro-oxidant enzyme,P65 phosphorylation and nuclear factor E2-related factor 2(Nrf2)nuclear translocation in vivo were investigated.Results BYQ significantly reduced mortality,lung index,pulmonary viral load and lung injury in a mouse model of influenza.We obtained one hundred and ninety-three of BYQ active compounds,which corresponded to three hundred and thirty-eight targets.There are 180 influenza-related targets among them.Nine targets,including IκBα kinase α(CHUK),IκBα kinase γ(IKBKG),NF-κB p65(RELA),tumor necrosis factor(TNF)and interleukin 6(IL6),were identified as potential core targets.GO analysis indicated that BYQ is involved in several biological functions,including antibacterial and antioxidant stress responses.KEGG analysis revealed the involvement of several viral and immune-related pathways for BYQ in treating influenza,including herpes simplex virus,influenza A virus,TNFα and toll-like receptor pathways.In vivo studies showed that high-dose BYQ significantly reduced pulmonary malondialdehyde(MDA)levels(P＜0.01)and increased total superoxide dismutase(SOD)activity(P＜0.001)in a mouse mode of influenza compared to oseltamivir phosphate.The treatment group with the combination of BYQ&oseltamivir phosphate had lower levels of NADPH oxidase 2(NOX2)and 4(NOX4)(P＜0.001),and higher levels of catalase(CAT)and glutathione peroxidase 4(GPX4)(P＜0.001)in the lungs than oseltamivir phosphate group.The combined treatment group showed more significant Nrf2 nuclear translocation(P＜0.05)than the oseltamivir phosphate group.However,there was no significant difference in P65 phosphorylation levels between the combination treatment group and the oseltamivir phosphate group(P＜0.05),but P65 phosphorylation levels in both groups were lower than in the model group(P＜0.05).Conclusion BYQ exhibits significant anti-influenza virus activity,manifests a dual effect by inhibiting the synthesis of pro-oxidant enzymes and promoting the antioxidant system,thereby alleviates the oxidative stress damage caused by influenza.

The limitations of antifungal drugs and severe drug resistance make the treatment of invasive fungal infections (IFIs) a great challenge. Itraconazole (ITZ), as a clinical first-line drug, has a wide range of antifungal activity, but it is still limited by adverse reactions such as liver and kidney toxicity, headache and abdominal pain due to its poor water solubility and easy to cause drug accumulation by injection. In this study, the amphiphilic polymer gallic acid-chitosan-cinnamaldehyde (GA-CS-CN) was prepared by amide reaction and Schiff-base reaction. The drug-loaded nanoparticles (GA-CS-CN/ITZ) were prepared by ultrasonic method. The properties of nanoparticles formulations and its in vitro antifungal activity were investigated in the study. Studies have shown that GA-CS-CN/ITZ is spherical, homogeneous and stable, and has good biological safety. The average particle size was 239.57 ± 31.37 nm, ITZ encapsulation efficiency was (93.41 ± 1.12)%, and the cumulative drug release was (62.25 ± 1.88)% at 48 h in vitro. The antifungal activity results of Candida albicans ATCC 10231 (C. albicans) showed that it had the optimal antifungal effect and could significantly enhance the antifungal activity of free drugs. GA-CS-CN/ITZ prepared in this study has excellent biological safety and anti-C. albicans performance, which provides a new choice for the treatment of C. albicans infection and has good application potential in the treatment of this fungal infection.

Iron is indispensable for the viablility of nearly all living organisms, and it is imperative for cells, tissues, and organisms to acquire this essential metal sufficiently and maintain its metabolic stability for survival. Disruption of iron homeostasis can lead to the development of various diseases. There is a robust connection between iron metabolism and infection, immunity, inflammation, and aging, suggesting that disorders in iron metabolism may contribute to the pathogenesis of arthritis. Numerous studies have focused on the significant role of iron metabolism in the development of arthritis and its potential for targeted drug therapy. Targeting iron metabolism offers a promising approach for individualized treatment of arthritis. Therefore, this review aimed to investigate the mechanisms by which the body maintains iron metabolism and the impacts of iron and iron metabolism disorders on arthritis. Furthermore, this review aimed to identify potential therapeutic targets and active substances related to iron metabolism, which could provide promising research directions in this field.

Objective To explore the clinical characteristics and prognostic outcomes of patients with acute myocardial infarction complicated by Coronavirus Disease 2019 (COVID-19). Methods A retrospective study was conducted in 76 patients with acute myocardial infarction. Based on the presence of COVID-19, they were divided into the COVID-19 group (n=42) and the control group (n=34). General clinical conditions, laboratory examination indicators, interventional treatment characteristics, incidence of complications during hospitalization and prognosis were compared between the two groups. Independent influencing factors for coronary thrombotic lesions in acute myocardial infarction patients were analyzed. Results The diastolic blood pressure, left ventricular ejection fraction and lymphocyte count were significantly lower, while lipoprotein a, C-reactive protein, serum ferritin, fibrinogen, and D-dimer were significantly higher in the COVID-19 group than those in the control group (P < 0.05). The proportions of coronary thrombotic lesions, baseline TIMI flow of grade 0 to 1, thrombus burden of grade 4 to 5, use of GP Ⅱb/Ⅲa inhibitors and thrombus aspiration in the COVID-19 group were significantly higher than those in the control group (P < 0.05). Multivariate Logistic regression analysis revealed that COVID-19 and increased D-dimer were independent risk factors for coronary thrombotic lesions in acute myocardial infarction patients. The average length of hospital stay was significantly longer in the COVID-19 group than that in the control group (P < 0.05). A 6-month follow-up showed that the incidence of major adverse cardiac events (MACEs) was significantly higher in the COVID-19 group than that in the control group (P=0.014). Conclusion Patients with acute myocardial infarction complicated by COVID-19 exhibit a higher coronary thrombus load and have a poor prognosis.

Sialyllactose is one of the most abundant sialylated oligosaccharides in human milk oligosaccharides (HMOs), which plays an important role in the healthy development of infants and young children. However, its efficient and cheap production technology is still lacking presently. This study developed a two-step process employing multiple-strains for the production of sialyllactose. In the first step, two engineered strains, E. coli JM109(DE3)/ pET28a-BT0453 and JM109(DE3)/pET28a-nanA, were constructed to synthesize the intermediate N-acetylneuraminic acid. When the ratio of the biomass of the two engineered strains was 1:1 and the reaction time was 32 hours, the maximum yield of N-acetylneuraminic acid was 20.4 g/L. In the second step, E. coli JM109(DE3)/ pET28a-neuA, JM109(DE3)/ pET28a-nst and Baker's yeast were added to the above fermentation broth to synthesize 3'-sialyllactose (3'-SL). Using optimal conditions including 200 mmol/L N-acetyl-glucosamine and lactose, 150 g/L Baker's yeast, 20 mmol/L Mg²⁺, the maximum yield of 3'-SL in the fermentation broth reached 55.04 g/L after 24 hours of fermentation and the conversion rate of the substrate N-acetyl-glucosamine was 43.47%. This research provides an alternative technical route for economical production of 3'-SL.
Child ; Humans ; Child, Preschool ; N-Acetylneuraminic Acid ; Escherichia coli/genetics* ; Lactose ; Fermentation ; Saccharomyces cerevisiae ; Oligosaccharides ; Glucosamine

Limonene and its derivative perillic acid are widely used in food, cosmetics, health products, medicine and other industries as important bioactive natural products. However, inefficient plant extraction and high energy-consuming chemical synthesis hamper the industrial production of limonene and perillic acid. In this study, limonene synthase from Mentha spicata was expressed in Saccharomyces cerevisiae by peroxisome compartmentalization, and the yield of limonene was 0.038 mg/L. The genes involved in limonene synthesis, ERG10, ERG13, tHMGR, ERG12, ERG8, IDI1, MVD1, ERG20ww and tLS, were step-wise expressed via modular engineering to study their effects on limonene yield. The yield of limonene increased to 1.14 mg/L by increasing the precursor module. Using the plasmid with high copy number to express the above key genes, the yield of limonene significantly increased up to 86.74 mg/L, which was 4 337 times higher than that of the original strain. Using the limonene-producing strain as the starting strain, the production of perillic acid was successfully achieved by expressing cytochrome P450 enzyme gene from Salvia miltiorrhiza, and the yield reached 4.42 mg/L. The results may facilitate the construction of cell factory with high yield of monoterpene products by S. cerevisiae.
Saccharomyces cerevisiae/metabolism* ; Limonene/metabolism* ; Metabolic Engineering ; Monoterpenes/metabolism*

Objective: To investigate the clinicopathological features, treatment and prognosis of patients with RET fusion positive non-small cell lung cancer (NSCLC). Methods: A total of 1 089 NSCLCs were retrieved at Affiliated Hospital of Jiangnan University from August 2018 to April 2020. In all cases, multiple gene fusion detection kits (fluorescent PCR method) were used to detect the gene status of RET, EGFR, ALK, ROS1, KRAS, BRAF and HER2; and immunohistochemical method was used to detect the expression of PD-L1 and mismatch repair related proteins. The correlation between RET-fusion and patients' age, gender, smoking history, tumor stage, grade, pathologic type, and PD-L1, mismatch repair related protein expression was analyzed. Results: There were 22 cases (2.02%) detected with RET fusion-positive in 1 089 NSCLC patients, in which 11 males and 11 females; and the median age was 63.5 years. There were 20 adenocarcinomas, including 11 acinar predominant adenocarcinoma (APA), five solid predominant adenocarcinoma (SPA) and four lepidic predominant adenocarcinoma (LPA); There were one case each of squamous cell carcinoma (non-keratinizing type) and sarcomatoid carcinoma (pleomorphic carcinoma). There were 6 and 16 patients with RET fusion-positive who were in stage Ⅰ-Ⅱ and Ⅲ-Ⅳ respectively, and 16 cases with lymph node metastasis, 11 cases with distant metastasis. Among RET fusion-positive cases, one was detected with HER2 co-mutation. The tumor proportion score of PD-L1≥1% in patients with RET fusion positive lung cancer was 54.5% (12/22). Defects in mismatch repair protein expression were not found in patients with RET fusion positive NSCLC. Four patients with RET fusions positive (two cases of APA and two cases of SPA) received pratinib-targeted therapy, and two showed benefits from this targeted therapy. Conclusions: The histological subtypes of RET fusions positive NSCLC are more likely to be APA or SPA. RET fusion-positive NSCLC patients are associated with advanced clinical stage, lymph node metastases, and they may benefit from targeted therapy with RET-specific inhibitors.
Male ; Female ; Humans ; Middle Aged ; Carcinoma, Non-Small-Cell Lung/pathology* ; Lung Neoplasms/pathology* ; B7-H1 Antigen/genetics* ; Protein-Tyrosine Kinases/genetics* ; Proto-Oncogene Proteins c-ret/metabolism* ; Proto-Oncogene Proteins/genetics* ; Adenocarcinoma/pathology* ; Carcinoma, Squamous Cell/genetics* ; Mutation

Ginsenoside Compound K (CK) has anti-cancer and anti-inflammatory pharmacological activities. It has not been isolated from natural ginseng and is mainly prepared by deglycosylation of protopanaxadiol. Compared with the traditional physicochemical preparation methods, the preparation of CK by hydrolysis with protopanaxadiol-type (PPD-type) ginsenoside hydrolases has the advantages of high specificity, environmental-friendliness, high efficiency and high stability. In this review, the PPD-type ginsenoside hydrolases were classified into three categories based on the differences in the glycosyl-linked carbon atoms of the hydrolase action. It was found that most of the hydrolases that could prepare CK were PPD-type ginsenoside hydrolase type Ⅲ. In addition, the applications of hydrolases in the preparation of CK were summarized and evaluated to facilitate large-scale preparation of CK and its development in the food and pharmaceutical industries.
Ginsenosides/pharmacology* ; Hydrolases ; Sapogenins/chemistry*

At present, the incidence of Parkinson's disease (PD) is gradually increasing. This seriously affects the quality of life of patients, and the burden of diagnosis and treatment is increasing. However, the disease is difficult to intervene in early stage as early monitoring means are limited. Aiming to find an effective biomarker of PD, this work extracted correlation between each pair of electroencephalogram (EEG) channels for each frequency band using weighted symbolic mutual information and k-means clustering. The results showed that State1 of Beta frequency band ( P = 0.034) and State5 of Gamma frequency band ( P = 0.010) could be used to differentiate health controls and off-medication Parkinson's disease patients. These findings indicated that there were significant differences in the resting channel-wise correlation states between PD patients and healthy subjects. However, no significant differences were found between PD-on and PD-off patients, and between PD-on patients and healthy controls. This may provide a clinical diagnosis reference for Parkinson's disease.
Humans ; Parkinson Disease/diagnosis* ; Quality of Life ; Cluster Analysis ; Electroencephalography ; Healthy Volunteers