Objective To investigate the effect of lysosome biogenesis complex 1 subunit 1(GCN5L1)on myocardial inflammatory injury and regulatory T cell(Treg)infiltration in mice with myocardial infarction(MI).Methods The differentially expressed gene GCN5L1 was screened from the GSE66360 dataset using whole blood samples from healthy controls and MI patients.The correlation between GCN5L1 and IL-10,IL-35 or Treg marker FOXP3 was analyzed.A model of MI was established in C57BL/6 mice by left anterior descending coronary artery ligation.Thirty mice were divided into five groups:sham,MI model,AAV9-NC(control adeno-associated virus),AAV9-GCN5L1 and AAV9-GCN5L1+FOXP3 inhibitor(epirubicin)groups,with 6 mice in each group.MI area was assessed by TTC staining,and histopathological changes were evaluated via HE staining.Immunofluorescence was used to quantify GCN5L1 and FOXP3 positivity;ELISA was used to measure IL-10 and IL-35 levels;Western blot was used to analyze the levels of GCN5L1,Bax,Bcl-2 and PI3K/AKT pathway proteins;transcriptomic sequencing was performed on AAV9-NC and AAV9-GCN5L1 groups,while differential genes subjected to GO and KEGG enrichment analysis.Results GSE66360 dataset showed that GCN5L1 levels were significantly lower in MI patients than in healthy controls,and positively correlated with IL-10,IL-35 and FOXP3 levels(P＜0.01).Compared to the sham group,the MI group exhibited increased infarct area,severe histopathology,reduced GCN5L1/IL-10/IL-35 levels,elevated Bax,and decreased Bcl-2,which could be reversed by AAV9-GCN5L1(P＜0.01).Transcriptomics revealed the enrichment of differential genes in Treg infiltration and PI3K/AKT pathways.The AAV9-GCN5L1 group showed higher FOXP3 positivity and PI3K/AKT expression than the MI group.Co-treatment with AAV9-GCN5L1+epirubicin reduced FOXP3 positivity compared to AAV9-GCN5L1 alone(P＜0.01).Conclusion GCN5L1 overexpression alleviates myocardial inflammatory injury post-MI,activates the PI3K/AKT pathway,and enhances Treg infiltration.

Objective To investigate the effect of lysosome biogenesis complex 1 subunit 1(GCN5L1)on myocardial inflammatory injury and regulatory T cell(Treg)infiltration in mice with myocardial infarction(MI).Methods The differentially expressed gene GCN5L1 was screened from the GSE66360 dataset using whole blood samples from healthy controls and MI patients.The correlation between GCN5L1 and IL-10,IL-35 or Treg marker FOXP3 was analyzed.A model of MI was established in C57BL/6 mice by left anterior descending coronary artery ligation.Thirty mice were divided into five groups:sham,MI model,AAV9-NC(control adeno-associated virus),AAV9-GCN5L1 and AAV9-GCN5L1+FOXP3 inhibitor(epirubicin)groups,with 6 mice in each group.MI area was assessed by TTC staining,and histopathological changes were evaluated via HE staining.Immunofluorescence was used to quantify GCN5L1 and FOXP3 positivity;ELISA was used to measure IL-10 and IL-35 levels;Western blot was used to analyze the levels of GCN5L1,Bax,Bcl-2 and PI3K/AKT pathway proteins;transcriptomic sequencing was performed on AAV9-NC and AAV9-GCN5L1 groups,while differential genes subjected to GO and KEGG enrichment analysis.Results GSE66360 dataset showed that GCN5L1 levels were significantly lower in MI patients than in healthy controls,and positively correlated with IL-10,IL-35 and FOXP3 levels(P＜0.01).Compared to the sham group,the MI group exhibited increased infarct area,severe histopathology,reduced GCN5L1/IL-10/IL-35 levels,elevated Bax,and decreased Bcl-2,which could be reversed by AAV9-GCN5L1(P＜0.01).Transcriptomics revealed the enrichment of differential genes in Treg infiltration and PI3K/AKT pathways.The AAV9-GCN5L1 group showed higher FOXP3 positivity and PI3K/AKT expression than the MI group.Co-treatment with AAV9-GCN5L1+epirubicin reduced FOXP3 positivity compared to AAV9-GCN5L1 alone(P＜0.01).Conclusion GCN5L1 overexpression alleviates myocardial inflammatory injury post-MI,activates the PI3K/AKT pathway,and enhances Treg infiltration.

Objective To analyze the mechanism of Xueshuantong injection combined with intravenous thrombolysis with alteplase in the treatment of patients with acute cerebral infarction (ACI) based on the high mobility group protein B1 (HMGB1)/Toll-like receptor 4 (TLR4) signaling pathway. Methods A total of 106 ACI patients were randomly divided into control group (n=53) and study group (n=53). The control group received intravenous thrombolysis with alteplase, while the study group received Xueshuantong injection treatment on the basis of the control group. Clinical efficacy and adverse reactions, the National Institutes of Health Stroke Scale (NIHSS) scores before treatment and on the 7th and 14th day after treatment, the expression levels of HMGB1 mRNA and TLR4 mRNA in mononuclear cells of peripheral blood before and after treatment as well as the protein contents of HMGB1 and TLR4 in serum, and the levels of inflammatory factors [interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α)] before and after treatment were compared between two groups. Pearson test and Spearman test were used to analyze the correlations of the expression levels of HMGB1 mRNA and TLR4 mRNA in mononuclear cells of peripheral blood and the protein contents of HMGB1 and TLR4 in serum with the NIHSS score and the total effective rate in patients with ACI. Results The NIHSS score of the study group was significantly lower than that of the control group at 7 and 14 days after treatment (P < 0.05); after treatment, the expression levels of HMGB1 mRNA and TLR4 mRNA in both groups decreased significantly when compared to those before treatment, and the expression levels of HMGB1 mRNA and TLR4 mRNA in the study group were significantly lower than those in the control group (P < 0.05); after treatment, the serum protein contents of HMGB1 and TLR4 in both groups decreased significantly when compared to those before treatment, and the serum protein contents of HMGB1 and TLR4 in the study group were significantly lower than those in thecontrol group (P < 0.05); after treatment, the levels of serum TNF-α and IL-6 in both groups decreased significantly when compared to those before treatment, and serum TNF-α and IL-6 levels in the study group were significantly lower than those in the control group (P < 0.05). The total effective rate was 75.47% in the control group and 94.34% in the study group, and there was a significant difference between two groups (P < 0.05); the total incidence of adverse reactions was 9.43% in the control group and 15.09%in the study group, and there was no significant difference between two groups (P>0.05). Pearson test showed that the expression levels of HMGB1 mRNAand TLR4 mRNA in mononuclear cells of peripheral blood and the serum protein contents of HMGB1 and TLR4 in ACI patients were positively correlated with NIHSS score (r=0.431, 0.443, 0.396, 0.375, P < 0.001); Spearman test showed that the expression levels of HMGB1 mRNA and TLR4 mRNA in mononuclear cells of peripheral blood and the serum protein contents of HMGB1 and TLR4 in ACI patients were negatively correlated with the total effective rate of treatment (r=-0.536, -0.481, -0.475, -0.506, P < 0.001). Conclusion Combination of Xueshuantong injection and intravenous thrombolysis with alteplase can effectively improve the neurological function of patients with ACI and reduce the level of inflammation in the body, and the therapeutic mechanism may be related to downregulation of the HMGB1/TLR4 signaling pathway.

Objective:To evaluate the efficacy and safety of ustekinumab (UST) for Crohn′s disease (CD) .Methods:A retrospective cohort study was conducted to collect clinical data of CD patients with active lesions in colonoscopy before the treatment of UST in Renji Hospital of Shanghai Jiaotong University School of Medicine from May 2020 to September 2021. Primary endpoint was the endoscopic response and remission rates at the 24th/32th week after the treatment of UST.Results:A total of 36 CD patients who were endoscopically active at baseline [25 men, 11 women; mean age, 29.8±8.7 years; disease duration, 38.0 (15.5, 66.1) months] were included. According to Montreal classification, 4 patients (11.1%) were L1 type (terminal ileum) , 4 (11.1%) were L2 type (colon) , 28 (77.8%) belonged to L3 type (ileocolon) , and upper digestive tract involvement occurred in 4 (11.1%) . As for disease behavior, 28 patients (77.8%) had non-structuring and non-penetrating lesions; 5 (13.9%) had structuring lesions and 3 (8.3%) had penetrating lesions. (1) Endoscopic activity: At the 24th/32th week, the endoscopic remission rate and response rate were 33.3% (12/36) and 63.9% (23/36) , respectively. There was no statistically significant difference in endoscopic remission rate and response rate between first-line and second-line usages of UST (all P>0.05) . (2) Clinical activity: Among the 36 patients, 16 were in the clinical active phase, and 20 patients were in the clinical remission phase at baseline. The clinical remission rate and clinical response rate of 16 clinical active patients at the 24th/32th week were 81.2% and 93.8% respectively. (3) Radiological activity: Twenty-seven patients completed the radiological evaluation at the 24th/32th week. In 3 patients with L1 lesions, 2 achieved response or partial response and no response in 1. In 24 patients with L3 lesions, radiological response occurred in 5 patients (20.8%) , partial response in 19 (79.2%) , and no response in 5 (20.8%) . In 19 patients with active perianal fistula at baseline, 6 achieved healing fistule at the 24th/32th week, 2 had partial response, 6 remained stable, while progress were seen in the other 5. (4) Serological and nutritive index: Compared with baseline values, the body mass index, hemoglobin and serum albumin levels of patients were significantly improved at the 24th/32th week (all P<0.05) , but the level of C-reactive protein and erythrocyte sedimentation rate at the 24th/32th week showed no significant difference (all P>0.05) . (5) Safety: No serious adverse events and infusion reactions were observed, and adverse events occurred in 2 patients. Conclusion:UST can effectively improve the endoscopic manifestations, clinical symptoms, imaging and nutritive index of CD patients with good safety.

Objective:To evaluate the efficacy and safety of ustekinumab (UST) for Crohn′s disease (CD) .Methods:A retrospective cohort study was conducted to collect clinical data of CD patients with active lesions in colonoscopy before the treatment of UST in Renji Hospital of Shanghai Jiaotong University School of Medicine from May 2020 to September 2021. Primary endpoint was the endoscopic response and remission rates at the 24th/32th week after the treatment of UST.Results:A total of 36 CD patients who were endoscopically active at baseline [25 men, 11 women; mean age, 29.8±8.7 years; disease duration, 38.0 (15.5, 66.1) months] were included. According to Montreal classification, 4 patients (11.1%) were L1 type (terminal ileum) , 4 (11.1%) were L2 type (colon) , 28 (77.8%) belonged to L3 type (ileocolon) , and upper digestive tract involvement occurred in 4 (11.1%) . As for disease behavior, 28 patients (77.8%) had non-structuring and non-penetrating lesions; 5 (13.9%) had structuring lesions and 3 (8.3%) had penetrating lesions. (1) Endoscopic activity: At the 24th/32th week, the endoscopic remission rate and response rate were 33.3% (12/36) and 63.9% (23/36) , respectively. There was no statistically significant difference in endoscopic remission rate and response rate between first-line and second-line usages of UST (all P>0.05) . (2) Clinical activity: Among the 36 patients, 16 were in the clinical active phase, and 20 patients were in the clinical remission phase at baseline. The clinical remission rate and clinical response rate of 16 clinical active patients at the 24th/32th week were 81.2% and 93.8% respectively. (3) Radiological activity: Twenty-seven patients completed the radiological evaluation at the 24th/32th week. In 3 patients with L1 lesions, 2 achieved response or partial response and no response in 1. In 24 patients with L3 lesions, radiological response occurred in 5 patients (20.8%) , partial response in 19 (79.2%) , and no response in 5 (20.8%) . In 19 patients with active perianal fistula at baseline, 6 achieved healing fistule at the 24th/32th week, 2 had partial response, 6 remained stable, while progress were seen in the other 5. (4) Serological and nutritive index: Compared with baseline values, the body mass index, hemoglobin and serum albumin levels of patients were significantly improved at the 24th/32th week (all P<0.05) , but the level of C-reactive protein and erythrocyte sedimentation rate at the 24th/32th week showed no significant difference (all P>0.05) . (5) Safety: No serious adverse events and infusion reactions were observed, and adverse events occurred in 2 patients. Conclusion:UST can effectively improve the endoscopic manifestations, clinical symptoms, imaging and nutritive index of CD patients with good safety.

The complexity of oral ulcerations poses considerable diagnostic and therapeutic challenges to oral specialists. The expert consensus was conducted to summarize the diagnostic work-up for difficult and complicated oral ulcers, based on factors such as detailed clinical medical history inquiry, histopathological examination, and ulceration-related systemic diseases screening. Not only it can provide a standardized procedure of oral ulceration, but also it can improve the diagnostic efficiency, in order to avoid misdiagnosis and missed diagnosis.
Consensus ; Humans ; Oral Ulcer/therapy*