Objective To observe the effects and safety of semaglutide and saxagliptin combined with metformin in the treatment of type 2 diabetes mellitus(T2DM)with abdominal obesity(AO).Methods The data of patients with T2DM and AO were retrospectively analyzed.Patients with T2DM and AO were divided into semaglutide group and saxagliptin group according to the cohort method.Both groups were given metformin orally,0.5 g a time,tid.On this basis,the semaglutide group was injected with semaglutide,0.25 mg a time,2 weeks later,the dose was adjusted to 0.5 mg a time,qw.The saxagliptin group was given oral administration of saxagliptin on the basis of metformin,5 mg a time,qd.All patients received 3 months of treatment.Glucose metabolism indexes,pancreatic islet function indexes,adipokines and adverse drug reactions were compared between the groups.Results There were 48 cases in semaglutide group and 49 cases in saxagliptin group.After treatment,the levels of fasting plasma glucose(FPG)in the semaglutide group and the saxagliptin group were(7.45±1.22)and(7.98±1.30)mmol·L-1;the levels of 2 h plasma glucose(2 h PG)were(9.78±1.64)and(10.55±1.82)mmol·L-1;the levels of hemoglobin A1c(HbA1c)were(5.66±0.94)and(6.25±0.87)％;the levels of fasting insulin(FINS)were(29.12±2.46)and(34.34±7.15)pmol·L-1;the levels of fasting C-peptide(FC-P)were(292.66±67.53)and(319.03±77.92)pmol·L-1;homeostatic model assessment-insulin resistance(HOMA-IR)were 2.51±0.78 and 2.94±0.89;homeostatic model assessment-β(HOMA-β)were 51.74±15.31 and 43.72±14.56;levels of Irisin were(4.56±0.32)and(4.17±0.54)ng·L-1;the levels of spexin(SPX)were(0.71±0.15)and(0.64±0.17)ng·mL-1;the levels of asprosin(ASP)were(1.22±0.16)and(1.34±0.25)μg·L-1.The above indexes were significantly different between semaglutide group and saxagliptin group(all P＜0.05).The total incidence rates of adverse drug reactions in semaglutide group and saxagliptin group were 10.42％(5 cases/48 cases)and 2.04％(1 case/49 cases),without statistically significant difference(P＞0.05).Conclusion The combination of semaglutide and metformin can lower blood glucose and in patients with T2DM and AO more significantly,and improve pancreatic function and adipokines,with good safety.

ObjectiveCoronavirus is a class of long-standing pathogens, which are enveloped single-stranded positive-sense RNA viruses. The genome all encodes 4 structural proteins: spike protein (S), nucleocapsid protein (N), membrane protein (M), and envelope protein (E). The nucleocapsid protein (NP) serves as a key structural component of coronaviruses, playing a vital function in the viral life cycle. NP acts as an RNA-binding protein, with a critical role in identifying specific sequences within the viral genome RNA, facilitating the formation of ribonucleoprotein (RNP) complexes with viral RNA to stabilize the viral genome and contribute to viral particles assembly. The NP consists of two primary structural domains, the N-terminal domain (NTD) and the C-terminal domain (CTD). The NTD is primarily responsible for RNA binding, whereas the CTD is involved in polymerization. The N protein demonstrated to trigger the host immune response and to modulate the cell cycle of infected cells by interacting with host proteins. The NP, one of the most abundant protein in coronaviruses, is essential in understanding the pathogenic mechanism of coronaviruses through its interaction with host factors, which response for determining the virus pathogenicity. HCoV-229E is a widely distributed coronavirus that typically causes mild upper respiratory tract diseases, accounting for a significant portion of common cold cases. However, its pathogenicity is notably lower compared to other coronaviruses like MERS-CoV, SARS-CoV, and SARS-CoV-2. The exact molecular mechanism behind remains unexplained, and how HCoV-229E N protein influences virus replication, host antiviral immunity, and pathogenesis need to be further explored. MethodsProximity labeling-mass spectrometry technique and bioinformatics analysis were used to screen for potential host factors interacting with the NP of human coronavirus 229E (HCoV-229E). In this study, a recombinant adenovirus Ad-V5-NP^HCoV-229E-TurboID was constructed to express the fusion protein of HCoV-229E NP and biotin ligase (TurboID). A549 cells were infected with the Ad-V5-NP^HCoV-229E-TurboID. After 30 min biotin treatment, NP interacting proteins were labeled with biotin by biotin ligase, and subsequently isolated with streptavidin cross-linked magnetic beads. The potential interacting proteins were identified using label-free proteomic mass spectrometry and further validated through immunoprecipitation and immunofluorescence assays. ResultsWe identified a total of 584 potential interacting proteins. Gene ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis highlighted the enrichment of glycogen synthase kinase (GSK)3A and GSK3B in the glycolysis/gluconeogenesis pathway, indicating HCoV-229E NP connection to diabetes through aberrant activity. Moreover, SARS-CoV-2 infection can exacerbate hyperglycemia and metabolic dysregulation in diabetic individuals by activating the ACE2 receptor. Moreover, SARS-CoV-2 was observed to cause potentially harm to pancreatic β‑cells and leading to insulin deficiency, which not only worsens the condition of diabetic patients but also raises the possibility of new-onset diabetes in non-diabetic individuals. We demonstrated that GSK3A and GSK3B interacted with NP of HCoV-229E, suggesting that the NP may engage in various coronavirus pathogenic processes by interacting with GSK3. ConclusionThese findings suggest that proximity labeling-mass spectrometry technique is a valuable tool for identifying virus-host interaction factors, and lay the foundation for future investigations into the mechanisms underlying coronavirus replication, proliferation, and pathogenesis.

ObjectiveThis study aimed to observe the impact of sinomenine hydrochloride on the proliferation of fibroblasts and the mRNA expression of related genes in knee joint adhesion and contracture in rabbits. Additionally, we sought to explore its potential mechanisms in combating knee joint adhesion and contracture. MethodsFibroblasts were cultured in vitro, and experimental groups with varying concentrations of sinomenine hydrochloride were established alongside a control group. Cell proliferation was assessed using the CCK-8 assay. Changes in the mRNA expression of fibroblast-related genes following sinomenine hydrochloride treatment were evaluated using RT-qPCR. The impact of the drug on serum levels of inflammatory cytokines was determined using the ELISA method, and the expression of related proteins was assessed using Western blot. ResultsSinomenine hydrochloride was found to inhibit fibroblast viability, with viability decreasing as the concentration of sinomenine hydrochloride increased. The effects of sinomenine hydrochloride in all experimental groups were highly significant (P<0.05). At the mRNA expression level, compared to the control group, sinomenine hydrochloride led to a significant downregulation of inflammatory cytokines in all groups (P<0.05). Additionally, the expression levels of apoptosis-related proteins significantly increased, while Bcl-2 mRNA expression decreased (P<0.05). The mRNA expression levels of the PI3K/mTOR/AKT3 signaling pathway also decreased (P<0.05). At the protein expression level, in comparison to the control group, the levels of inflammatory cytokines IL-6, IL-8, IL-1β, and TGF-β were significantly downregulated in the middle and high-dose sinomenine hydrochloride groups (P<0.05). The expression levels of cleaved-PARP, cleaved caspase-3/7, and Bax increased and were positively correlated with the dose, while the expression levels of the anti-apoptotic protein Bcl-2 and the PI3K/AKT3/mTOR signaling pathway were negatively correlated with the dose. Sinomenine hydrochloride exhibited a significant inhibitory effect on the viability of rabbit knee joint fibroblasts, which may be associated with the downregulation of inflammatory cytokines IL-6, IL-8, and IL-1β, promotion of apoptosis-related proteins cleaved-PARP, cleaved caspase-3/7, and Bax, suppression of Bcl-2 expression, and inhibition of gene expression in the downstream PI3K/AKT3/mTOR signaling pathway. ConclusionSinomenine hydrochloride can inhibit the inflammatory response of fibroblasts in adhesive knee joints and accelerate fibroblast apoptosis. This mechanism may offer a novel approach to improving and treating knee joint adhesion.

Airway mucus hypersecretion is one of the important pathophysiological and clinical manifestations of chronic obstructive pulmonary disease. It has been reported in the literature that COPD patients with chronic airway mucus hypersecretion have more frequent acute exacerbations, more severe lung function decline, and higher hospitalizations and mortality. Therefore, it is particularly critical to understand the pathogenesis of hypersecretion of mucus in chronic obstructive pulmonary disease and find out effective treatment. This article focuses on the structure, significance of airway mucus and the mechanism of hypersecretion of mucus in chronic obstructive pulmonary disease (COPD). In addition, we also summarized drug and non-drug therapy for chronic airway mucus hypersecretion in this article. Drug therapy includes traditional drug therapy, some new targeted drug therapy for pathogenesis and traditional Chinese medicine therapy, and non-drug therapy includes smoking cessation, physical therapy and bronchos-copy therapy. We hope that it will provide new ideas and directions for the treatment of mucus hypersecretion in COPD patients.

Airway mucus hypersecretion is one of the important pathophysiological and clinical manifestations of chronic obstructive pulmonary disease.It has been reported in the literature that COPD patients with chronic airway mucus hyperse-cretion have more frequent acute exacerbations,more severe lung function decline,and higher hos-pitalizations and mortality.Therefore,it is particu-larly critical to understand the pathogenesis of hy-persecretion of mucus in chronic obstructive pul-monary disease and find out effective treatment.This article focuses on the structure,significance of airway mucus and the mechanism of hypersecre-tion of mucus in chronic obstructive pulmonary dis-ease(COPD).In addition,we also summarized drug and non-drug therapy for chronic airway mucus hy-persecretion in this article.Drug therapy includes traditional drug therapy,some new targeted drug therapy for pathogenesis and traditional Chinese medicine therapy,and non-drug therapy includes smoking cessation,physical therapy and bronchos-copy therapy.We hope that it will provide new ideas and directions for the treatment of mucus hy-persecretion in COPD patients.

Airway mucus hypersecretion is one of the important pathophysiological and clinical manifestations of chronic obstructive pulmonary disease.It has been reported in the literature that COPD patients with chronic airway mucus hyperse-cretion have more frequent acute exacerbations,more severe lung function decline,and higher hos-pitalizations and mortality.Therefore,it is particu-larly critical to understand the pathogenesis of hy-persecretion of mucus in chronic obstructive pul-monary disease and find out effective treatment.This article focuses on the structure,significance of airway mucus and the mechanism of hypersecre-tion of mucus in chronic obstructive pulmonary dis-ease(COPD).In addition,we also summarized drug and non-drug therapy for chronic airway mucus hy-persecretion in this article.Drug therapy includes traditional drug therapy,some new targeted drug therapy for pathogenesis and traditional Chinese medicine therapy,and non-drug therapy includes smoking cessation,physical therapy and bronchos-copy therapy.We hope that it will provide new ideas and directions for the treatment of mucus hy-persecretion in COPD patients.

Airway mucus hypersecretion is one of the important pathophysiological and clinical manifestations of chronic obstructive pulmonary disease.It has been reported in the literature that COPD patients with chronic airway mucus hyperse-cretion have more frequent acute exacerbations,more severe lung function decline,and higher hos-pitalizations and mortality.Therefore,it is particu-larly critical to understand the pathogenesis of hy-persecretion of mucus in chronic obstructive pul-monary disease and find out effective treatment.This article focuses on the structure,significance of airway mucus and the mechanism of hypersecre-tion of mucus in chronic obstructive pulmonary dis-ease(COPD).In addition,we also summarized drug and non-drug therapy for chronic airway mucus hy-persecretion in this article.Drug therapy includes traditional drug therapy,some new targeted drug therapy for pathogenesis and traditional Chinese medicine therapy,and non-drug therapy includes smoking cessation,physical therapy and bronchos-copy therapy.We hope that it will provide new ideas and directions for the treatment of mucus hy-persecretion in COPD patients.

Airway mucus hypersecretion is one of the important pathophysiological and clinical manifestations of chronic obstructive pulmonary disease.It has been reported in the literature that COPD patients with chronic airway mucus hyperse-cretion have more frequent acute exacerbations,more severe lung function decline,and higher hos-pitalizations and mortality.Therefore,it is particu-larly critical to understand the pathogenesis of hy-persecretion of mucus in chronic obstructive pul-monary disease and find out effective treatment.This article focuses on the structure,significance of airway mucus and the mechanism of hypersecre-tion of mucus in chronic obstructive pulmonary dis-ease(COPD).In addition,we also summarized drug and non-drug therapy for chronic airway mucus hy-persecretion in this article.Drug therapy includes traditional drug therapy,some new targeted drug therapy for pathogenesis and traditional Chinese medicine therapy,and non-drug therapy includes smoking cessation,physical therapy and bronchos-copy therapy.We hope that it will provide new ideas and directions for the treatment of mucus hy-persecretion in COPD patients.

Airway mucus hypersecretion is one of the important pathophysiological and clinical manifestations of chronic obstructive pulmonary disease.It has been reported in the literature that COPD patients with chronic airway mucus hyperse-cretion have more frequent acute exacerbations,more severe lung function decline,and higher hos-pitalizations and mortality.Therefore,it is particu-larly critical to understand the pathogenesis of hy-persecretion of mucus in chronic obstructive pul-monary disease and find out effective treatment.This article focuses on the structure,significance of airway mucus and the mechanism of hypersecre-tion of mucus in chronic obstructive pulmonary dis-ease(COPD).In addition,we also summarized drug and non-drug therapy for chronic airway mucus hy-persecretion in this article.Drug therapy includes traditional drug therapy,some new targeted drug therapy for pathogenesis and traditional Chinese medicine therapy,and non-drug therapy includes smoking cessation,physical therapy and bronchos-copy therapy.We hope that it will provide new ideas and directions for the treatment of mucus hy-persecretion in COPD patients.

Airway mucus hypersecretion is one of the important pathophysiological and clinical manifestations of chronic obstructive pulmonary disease.It has been reported in the literature that COPD patients with chronic airway mucus hyperse-cretion have more frequent acute exacerbations,more severe lung function decline,and higher hos-pitalizations and mortality.Therefore,it is particu-larly critical to understand the pathogenesis of hy-persecretion of mucus in chronic obstructive pul-monary disease and find out effective treatment.This article focuses on the structure,significance of airway mucus and the mechanism of hypersecre-tion of mucus in chronic obstructive pulmonary dis-ease(COPD).In addition,we also summarized drug and non-drug therapy for chronic airway mucus hy-persecretion in this article.Drug therapy includes traditional drug therapy,some new targeted drug therapy for pathogenesis and traditional Chinese medicine therapy,and non-drug therapy includes smoking cessation,physical therapy and bronchos-copy therapy.We hope that it will provide new ideas and directions for the treatment of mucus hy-persecretion in COPD patients.