OBJECTIVE To explore the correlation between serum matrix metalloproteinase-2(MMP-2),interleukin-25(IL-25)expression and mast cell infiltration in patients with recurrent chronic sinusitis with nasal polyps(CRSwNP).METHODS Sixty patients diagnosed with recurrent CRSwNP in our hospital from October 2022 to March 2023 were selected as the CRSwNP group,and 60 patients diagnosed with simple Nasal septal deviation(NSD)in our hospital during the same period were selected as the NSD group.Compare the clinical data,mast cell count,and serum MMP-2 and IL-25 expression levels between two groups of patients.Use local weighted regression(Lowess)to analyze the correlation between MMP-2,IL-25 levels and mast cell count.Apply multiple logistic regression analysis to investigate the independent correlation between MMP-2,IL-25 levels and the risk of CRSwNP recurrence.Establish a restricted cubic spline(RCS)model to analyze the dose-response relationship between serum MMP-2,IL-25 levels and the risk of CRSwNP recurrence.Analyze the interaction and type of interaction between MMP-2,IL-25,and mast cell count on the risk of CRSwNP recurrence using an interaction calculation table.RESULTS The Lund Kennedy endoscopic score,Lund Mackay CT score,total VAS score,peripheral eosinophils,peripheral basophils,inhaled allergens,total IgE levels,smoking,alcohol consumption,and incidence of asthma,mast cell count,serum MMP-2 and IL-25 levels in the CRSwNP group were significantly higher than those in the NSD group,and the differences were statistically significant(P<0.05).Lowess analysis showed that there was a nonlinear relationship between MMP-2,IL-25 and mast cell count.MMP-2 and IL-25 were independently correlated with the recurrence of crswnp.RCS model analysis showed that MMP-2 and IL-25 levels had a nonlinear dose-response relationship with the recurrence risk of crswnp(Pfor non linear=0.002,0.008).The recurrence rates of crswnp corresponding to MMP-2,IL-25 and mast cell count in high-level group were 5.26%,12.54%and 19.08%,respectively,which were significantly higher than those corresponding to MMP-2,IL-25 and mast cell count in low-level group(55.91%,70.83%and 68.05%),and the difference was statistically significant(P<0.05).The results of interaction analysis showed that MMP-2,IL-25 and mast cell count had interaction in the additive model and the multiplicative model,showing a synergistic effect.CONCLUSION The levels of serum MMP-2 and IL-25 in CRSwNP recurrent patients are positively correlated with the degree of mast cell infiltration in the tissue.The higher the levels of MMP-2,IL-25 and Mast cell count,the higher the recurrence rate of CRSwNP.There was an independent correlation between MMP-2,IL-25 and recurrence of CRSwNP,which was a risk factor for recurrence of CRSwNP.

Objective:To investigate the therapeutic effects of the copper chelator ammonium tetrathiomolybdate (TTM) on rheumatoid arthritis (RA) in a mouse model.Methods:Twenty-four male dilution brown non-Agoutia/1 mice were randomly divided into 4 groups: a blank control group (Ctrl group, n=6), a collagen-induced arthritis (CIA) + phosphate buffer saline (PBS) treatment group (PBS group, n=6), a CIA+TTM treatment group (TTM group, n=6), and a CIA+Elesclomol treatment group (Eles group, n=6). Eles, a copper ion carrier, served as a control for administration of TTM, a copper ion chelator. One week after treatment, the swelling of mouse paw was observed, and the clinical scoring of the arthritis in mice was evaluated once a week. Paw mechanical pain detection was performed and photographs were taken to observe the severity of paw swelling before the mice were sacrificed. Catwalk gait analysis system was used to evaluate the gait changes in mice. HE and saffron O solid green staining were used to evaluate pathomorphologic changes in the mice knee joints and paws. Immunostaining techniques were used to detect the protein expression of MMP3, CD31, and VEGF in the mice paws. Luminex technology was used to detect alterations in the serum inflammatory factors. Results:Compared with the Ctrl group, in the PBS and Eles groups, the joints were red, swollen and deformed; the arthritis clinical scores were significantly higher; the bone destruction, synovial hyperplasia and inflammatory cell infiltration and pathological changes in the joint tissues were obvious; the expression levels of inflammatory factors, such as serum MCP-1, IL-1 β, IL-9, and IFN- γ, were significantly higher while the expression level of IL-10 was significantly lower. Simultaneously, the expression of CD31 and VEGF factors was significantly enhanced. Compared with the PBS group, in the TTM group, the joint swelling and deformation were significantly improved, the arthritis clinical score was reduced, and the joint bone destruction, inflammatory cell infiltration and synovial hyperplasia were alleviated, and the levels of serum MCP-1, IL-1 β, IL-9 and IFN- γ were significantly decreased while the level of anti-inflammatory factor IL-10 was increased. There was no significant difference in the expression of MMP-3, CD31 or VEGF factors between the CTRL group and the TTM group. Conclusion:TTM can block synovial inflammation, angiogenesis, and bone destruction multiple times by simultaneously targeting multiple inflammatory factors, VEGF factors, and bone destruction mediators, thereby alleviating the pathological damage to the joint tissues induced by CIA in RA mice.

Objective:To investigate the therapeutic effects of the copper chelator ammonium tetrathiomolybdate (TTM) on rheumatoid arthritis (RA) in a mouse model.Methods:Twenty-four male dilution brown non-Agoutia/1 mice were randomly divided into 4 groups: a blank control group (Ctrl group, n=6), a collagen-induced arthritis (CIA) + phosphate buffer saline (PBS) treatment group (PBS group, n=6), a CIA+TTM treatment group (TTM group, n=6), and a CIA+Elesclomol treatment group (Eles group, n=6). Eles, a copper ion carrier, served as a control for administration of TTM, a copper ion chelator. One week after treatment, the swelling of mouse paw was observed, and the clinical scoring of the arthritis in mice was evaluated once a week. Paw mechanical pain detection was performed and photographs were taken to observe the severity of paw swelling before the mice were sacrificed. Catwalk gait analysis system was used to evaluate the gait changes in mice. HE and saffron O solid green staining were used to evaluate pathomorphologic changes in the mice knee joints and paws. Immunostaining techniques were used to detect the protein expression of MMP3, CD31, and VEGF in the mice paws. Luminex technology was used to detect alterations in the serum inflammatory factors. Results:Compared with the Ctrl group, in the PBS and Eles groups, the joints were red, swollen and deformed; the arthritis clinical scores were significantly higher; the bone destruction, synovial hyperplasia and inflammatory cell infiltration and pathological changes in the joint tissues were obvious; the expression levels of inflammatory factors, such as serum MCP-1, IL-1 β, IL-9, and IFN- γ, were significantly higher while the expression level of IL-10 was significantly lower. Simultaneously, the expression of CD31 and VEGF factors was significantly enhanced. Compared with the PBS group, in the TTM group, the joint swelling and deformation were significantly improved, the arthritis clinical score was reduced, and the joint bone destruction, inflammatory cell infiltration and synovial hyperplasia were alleviated, and the levels of serum MCP-1, IL-1 β, IL-9 and IFN- γ were significantly decreased while the level of anti-inflammatory factor IL-10 was increased. There was no significant difference in the expression of MMP-3, CD31 or VEGF factors between the CTRL group and the TTM group. Conclusion:TTM can block synovial inflammation, angiogenesis, and bone destruction multiple times by simultaneously targeting multiple inflammatory factors, VEGF factors, and bone destruction mediators, thereby alleviating the pathological damage to the joint tissues induced by CIA in RA mice.

Objective To investigate the correlation between eosinophils(Eos)and the recurrence of nasal polyps(NP)after nasal endoscopic surgery.Methods 189 patients with NP who underwent nasal endoscopic surgery from June 2020 to June 2022 were selected and followed up until June 2023.According to the definition of NP recurrence,they were divided into a recurrence group(n=68)and a non-recurrence group(n=121).The demographic distribution and clinical characteristics of the two groups were compared.Using the multivariate Logistic regression model,analyzed the independent risk factors for recurrence after nasal endoscopic surgery in NP patients,and further stepwise regression filter;Using restricted cubic spline model,analyzed the correlation between the Eos count and NP recurrence after nasal endoscopic surgery;Then establishing a model to predict the recurrence of NP after nasal endoscopic surgery.Result In the recurrent group,the degree of lesion(multiple nasal polyps),history of asthma,history of allergic rhinitis,lesion site(nasal septal deviation),Eos type nasal polyps,postoperative infection,intraoperative cavity adhesions,psychological status(adverse),Lund-Mackay score,pre-olfactory fissure score(≥1),post-olfactory fissure score(≥1),Eos count,and long-term use of nasal decongestants,all of them were higher than those in non-recurrence group(P<0.05).Multivariate Logistic regression analysis showed that multiple nasal polyps(O(＾R)=9.92,95%CI:4.70～20.94),history of asthma(O(＾R)=2.20,95%CI:1.05～4.63),history of allergic rhinitis(O(＾R)=3.16,95%CI:1.50～6.66),Eos type nasal polyp(O(＾R)=4.06,95%CI:2.17～7.61),postoperative infection(O(＾R)=8.35,95%CI:2.94～23.74),intraoperative adhesions(O(＾R)=5.08,95%CI:2.67～9.67),Lund-Mackay score≥15 points(O(＾R)=3.46,95%CI:1.05～6.49),pre-olfactory fissure score≥1 point(O(＾R)=2.29,95%CI:1.25～4.22),post-olfactory fissure score≥1 point(O(＾R)=2.60,95%CI:1.40～4.82),Eos count≥0.47×109/L(O(＾R)=4.19,95%CI:1.56～8.74)and long-term use of nasal decongestants(O(＾R)=3.10,95%CI:1.63～5.87)were all independent risk factors for recurrence in NP patients after nasal endoscopic surgery(P<0.05).And further stepwise regression analysis showed that these 11 clinical factors were most closely associated with postoperative recurrence in NP patients after nasal endoscopic surgery.The formula for calculating the risk of recurrence after nasal endoscopic surgery in NP patients was as follows:Logit(P)=1-1/(1+e1.69-lesion degree×2.29-history of asthma×0.79-history of allergic rhinitis×1.15-Eos type nasal polyp×1.40-postoperative infection×2.12-intraoperative cavity adhesion×1.63-Lund-Mackay score×1.24-pre-olfactory fissure score×0.83-post-olfactory fissure score×0.95-Eos count×1.43-long-term use of nasal decongestants×1.13).According to the formula,the probability of recurrence of NP patients after nasal endoscopic surgery was calculated.When probability was 0.80,Youden index was the highest and the prediction effect was relatively best.Conclusion Multiple nasal polyps,history of asthma,history of allergic rhinitis,Eos type nasal polyps,postoperative infection,surgical adhesions,high Lund Mackay score,high score in the pre-and post olfactory fissure area,as well as increased Eos count and long-term use of nasal decongestants are associated with recurrence after nasal endoscopic surgery in NP patients.The established risk prediction model has certain predictive value for the risk of recurrence in NP patients undergoing nasal endoscopic surgery.