OBJECTIVE To investigate the improvement effect and mechanism of desloratadine citrate disodium in mice with hypersensitivity pneumonitis （HP）. METHODS Sixty mice were randomly divided into blank control group （normal saline）， model group （normal saline）， prednisone group （positive control， 20 mg/kg） and desloratadine citrate disodium low-， medium- and high-dose groups （0.5， 1， 2 mg/kg）， with 10 mice in each group. Except for the blank control group， mice in other groups were intraperitoneally injected with ovalbumin （OVA） and exposed to OVA inhalation to establish the HP model. On day 22 post- modeling， mice in each group were administered the corresponding drugs or normal saline， once a day， for 11 consecutive days. After the last administration， lung function and airway hyperreactivity were assessed. The levels of interleukin-1β （IL-1β）， IL-4 and IL-6 in serum as well as the levels of IL-8， IL-13 and IL-17A in bronchoalveolar lavage fluid were determined. Pathological changes in lung tissue of mice were evaluated using Masson staining. Furthermore， the expressions of fibrosis-related proteins， including transforming growth factor β1 （TGF-β1）， type Ⅲ collagen （Col-Ⅲ） and fibronectin （FN） were determined in lung tissues. RESULTS Compared with the blank control group， the model group showed significant deterioration in lung function （P＜ 0.01）， while airway resistance and serum levels of IL-1β， IL-4， IL-6 and the levels of IL-8， IL-13 and IL-17A in the bronchoalveolar lavage fluid were increased significantly （P＜0.01）. The lung tissues exhibited alveolar collapse， atrophy， and structural disarray， along with the formation of extensive deposits of blue collagen fibers， the percentage of positive staining increased significantly （P＜0.01）. Additionally， the expression levels of TGF-β1， Col-Ⅲ， and FN proteins in the lung tissues were also increased significantly （P＜0.01）. After intervention with desloratadine citrate disodium， the pathological changes in the lung tissues of mice in each dosage group of desloratadine citrate disodium showed varying degrees of improvement， and most of the aforementioned indicator levels were significantly reversed （P＜0.05 or P＜0.01）. CONCLUSIONS Desloratadine citrate disodium can improve the lung function and airway hyperreactivity of HP mice， inhibit the release of inflammatory factors in serum and bronchoalveolar lavage fluid， and reduce the deposition of collagen fibers. Its mechanism of action may be related to anti-inflammatory， immunomodulatory， and antifibrotic effects.

Myocardial infarction (MI) is the leading cause of cardiovascular disease-related death worldwide. Nonetheless, existing therapeutic approaches for MI are hampered by issues such as reliance on pharmacological agents and suboptimal patient adherence. Caffeic acid (CA) is a bioactive polyphenolic compound with important anti-inflammatory, anti-bacterial and anti-oxidant functions. Still, its specific role and mechanism in treating cardiovascular disease remain to be further studied. In recent years, a large number of studies have shown that the kelch-like ECH-associated protein 1/nuclear factor erythroid 2 related factor 2 (Keap1/Nrf2) pathway is a key factor in the occurrence and development of cardiovascular diseases. In this study, H₂O₂-induced oxidative stress model of H9c2 cells and left anterior descending branch (LAD) conjunctival induced acute myocardial infarction reperfusion (AMI/R) model were used to evaluate the protective effect of CA on the heart. The interaction between CA and Keap1 was analyzed by CA-labeled fluorescence probe, target fishing, isothermal titration calorimetry (ITC), protein crystallography and surface plasmon resonance (SPR). Our results suggested that CA binds Keap1 and degrades Keap1 in a p62-dependent manner, further promoting nuclear transcription of Nrf2 and thus effectively reducing oxidative stress. In addition, based on the three-dimensional eutectic structure, it was confirmed that CA directly targets Keap1 protein by interacting with residues M550 and N532, inducing conformation changes in Keap1 protein. We also found that the CA analog chlorogenic acid (GCA) can bind Keap1. In conclusion, this study elucidates a novel molecular mechanism and structural basis for the protective effects of CA against oxidative damage via the Keap1-Nrf2 pathway.

Guided by molecular networking, nine novel curvularin derivatives (1-9) and 16 known analogs (10-25) were isolated from the hydrothermal vent sediment fungus Penicillium sp. HL-50. Notably, compounds 5-7 represented a hybrid of curvularin and purine. The structures and absolute configurations of compounds 1-9 were elucidated via nuclear magnetic resonance (NMR) spectroscopy, X-ray diffraction, electronic circular dichroism (ECD) calculations, ¹³C NMR calculation, modified Mosher's method, and chemical derivatization. Investigation of anti-inflammatory activities revealed that compounds 7-9, 11, 12, 14, 15, and 18 exhibited significant suppressive effects against lipopolysaccharide (LPS)-induced nitric oxide (NO) production in murine macrophage RAW264.7 cells, with IC₅₀ values ranging from 0.44 to 4.40 μmol·L^-1. Furthermore, these bioactive compounds were found to suppress the expression of inflammation-related proteins, including inducible NO synthase (iNOS), cyclooxygenase-2 (COX-2), NLR family pyrin domain-containing protein 3 (NLRP3), and nuclear factor kappa-B (NF-κB). Additional studies demonstrated that the novel compound 7 possessed potent anti-inflammatory activity by inhibiting the transcription of inflammation-related genes, downregulating the expression of inflammation-related proteins, and inhibiting the release of inflammatory cytokines, indicating its potential application in the treatment of inflammatory diseases.
Penicillium/chemistry* ; Mice ; Animals ; Anti-Inflammatory Agents/isolation & purification* ; RAW 264.7 Cells ; Nitric Oxide/metabolism* ; Hydrothermal Vents/microbiology* ; Macrophages/immunology* ; Molecular Structure ; Nitric Oxide Synthase Type II/immunology* ; Cyclooxygenase 2/immunology* ; Geologic Sediments/microbiology* ; NF-kappa B/immunology* ; NLR Family, Pyrin Domain-Containing 3 Protein/immunology*

Objective:To analyze the expression of FAT1 gene in pancreatic adenocarcinoma and its relationship with clinicopathological features, prognosis, and immunotherapy for pancreatic adenocarcinoma.Methods:(1) Bioinformatics analysis: based on FAT1 mRNA expression and clinical data of 179 cases of pancreatic adenocarcinoma in the TCGA database, and FAT1 mRNA expression data of 328 cases of normal pancreatic tissues in the GTEx database. We analyzed the differences in FAT1 mRNA expression in pancreatic adenocarcinoma and normal pancreatic tissues and the relationship between FAT1 mRNA expression and the degree of differentiation, clinical stage, prognosis, immune cell infiltration, and immune checkpoint-associated genes in pancreatic adenocarcinoma. FAT1-related differentially expressed genes were analyzed by applying Limma 3.40.2 software package, and GO and KEGG enrichment analysis was performed on the differentially expressed genes. Immunohistochemical (IHC) of FAT1 in pancreatic adenocarcinoma and normal pancreatic tissues was analyzed by HPA database. (2) Validation of own tissue samples: tissue samples and clinical and prognostic data of 192 patients with pancreatic ductal adenocarcinoma admitted to Zhejiang Cancer Hospital from March 8, 2010 to September 30, 2020 were collected. IHC was performed on the tissue samples to verify the protein expression of FAT1 in pancreatic adenocarcinoma and its relationship with immune-related proteins, the degree of differentiation of pancreatic adenocarcinoma, clinical staging, and prognosis.Results:(1) Bioinformatics analysis: the FAT1 mRNA expression of 179 pancreatic adenocarcinoma tissues from the TCGA database was 5.55±1.04, which was higher than that of 328 normal pancreatic tissues with FAT1 mRNA from the GTEx database (2.95±0.53, P＜0.001). FAT1-specific IHC images showed that FAT1 expression was generally high in pancreatic adenocarcinoma tissues, and FAT1 expression shifted from the cell membrane to the cytoplasm. The FAT1 mRNA expression in the highly differentiated group (31 cases), the moderately differentiated group (96 cases), and the lowly differentiated group (52 cases) were 4.99±1.46, 5.51±0.80, and 5.68±1.08, the expression of pancreatic adenocarcinoma tissues were all higher than that of normal pancreatic tissues (all P＜0.001), and the FAT1 mRNA expression of the moderately differentiated group and the poorly differentiated group were all higher than that of the highly differentiated group (all P＜0.001). The median progression-free survival time (PFS) and median overall survival time (OS) of the 90 patients in the FAT1 mRNA low-expression group were 16.5 and 24 months, respectively, which were longer than those of the 89 patients in the FAT1 mRNA high-expression group (median PFS and OS were 13 and 18 months, respectively; P-values were 0.011 and 0.005, respectively). Multifactorial Cox regression analysis showed that FAT1 mRNA expression level was an independent influencing factor for OS in pancreatic adenocarcinoma patients ( HR=1.47, 95% CI: 1.09-1.99). Correlation analysis showed that FAT1 mRNA expression in pancreatic adenocarcinoma was positively correlated with B-cell infiltration, CD8+ T-cell infiltration, neutrophil infiltration, macrophage infiltration, and myeloid dendritic cell infiltration ( ρ=0.27, P＜0.001; ρ=0.28, P＜0.001; ρ=0.32, P＜0.001; ρ=0.21, P=0.004; ρ=0.32, P＜0.001), and also positively correlated with mRNA expression of CD274, HAVCR2, and PDCD1LG2 ( r=0.327, P＜0.001; r=0.231, P=0.002; r=0.258, P＜0.001). GO and KEGG enrichment analyses showed that FAT1 mRNA expression levels were associated with activation of the Wnt signaling pathway ( P=0.029), the PI3K/Akt pathway ( P<0.001), and other tumor microenvironment-related pathways. (2) Validation of own tissue samples: among 192 pancreatic adenocarcinoma tissues, FAT1 was highly expressed in 58 cases (30.21%), and the proportion of FAT1-expressing positive tumor cells was positively correlated with the combined positive score of PD-L1 and the number of CD3+ T-cells infiltration ( r=0.154, P=0.032; r=0.287, P＜0.001), and the protein expression of FAT1 had no correlation with the differentiation degree of pancreatic adenocarcinoma ( ρ=0.082, P=0.254). The median OS of 58 patients in the FAT1 high-expression group and 134 patients in the FAT1 low-expression group were 18.89 and 25.84 months, respectively, and the difference was not statistically significant (χ2=1.93, P=0.165). Conclusion:FAT1 gene is highly expressed in pancreatic adenocarcinoma tissues, may play an oncogenic role in pancreatic adenocarcinoma, may be an adverse influence on overall survival and progression-free survival of patients; FAT1 gene may be involved in multiple immune-related pathways and promote tumor immune escape.

Objective:To understand the impact of diet on glycemic control in community-managed patients with type 2 diabetes mellitus (T2DM) and provide evidence for implementing prevention strategies and measures for diabetes patients.Methods:Eight communities were randomly selected from Changshu and Wuhan in 2015, and T2DM patients managed in the community were selected to conduct questionnaire surveys, physical measurements, and blood glucose testing. Factor analysis was used to obtain dietary patterns. A binary logistic regression model was used to analyze the factors affecting glycemic control.Results:Finally, 1 818 T2DM patients were included, and the control rate of FPG was 57.59% (95% CI: 55.30%-59.86%), and the control rate of 2 h postprandial blood glucose (2 h PBG) was 24.90% (95% CI: 22.93%- 26.91%). Five dietary patterns were obtained by factor analysis: animal food pattern, fruit-aquatic products-potato patterns, vegetable-grain pattern, egg-milk-bean pattern, and oil-salt patterns. No-conditional multivariate logistic regression analysis showed that after adjusting for confounding factors, the reduced probability of FPG control was related to animal food pattern ( OR=0.71, 95% CI: 0.52-0.98) and fruit-aquatic products-potato patterns ( OR=0.71, 95% CI: 0.51-0.97). The decrease in the 2 h PBG control probability was related to fruit-aquatic products-potato patterns ( OR=0.60, 95% CI: 0.40-0.90). The increased probability of FPG and 2 h postprandial glucose control were both related to vegetable-grain pattern ( OR=1.41, 95% CI: 1.03-1.94; OR=1.68, 95% CI: 1.13-2.51) and egg-milk-bean pattern ( OR=1.75, 95% CI: 1.25-2.46; OR=1.56, 95% CI: 1.00-2.42). Compared with the Q4 group of egg-milk-bean pattern, the FPG control rate of the combination of "fruit-aquatic products-potato pattern ( Q4 group), vegetable-grain pattern ( Q2 group), egg-milk-bean pattern ( Q3 group)" was higher ( OR=6.79, 95% CI: 1.15-40.23, P=0.035). Compared with the Q4 group of vegetable-grain pattern, the combination of "fruit-aquatic products-potato pattern ( Q4 group), vegetable-grain pattern ( Q3 group), egg-milk-bean pattern ( Q2 group), oil-salt pattern ( Q2 group)" had higher control rate of 2 h PBG ( OR=12.78, 95% CI: 1.26-130.05, P=0.031). Conclusions:A proper combination of dietary patterns and dietary patterns are more conducive to the control of FPG and 2 h PBG in T2DM patients managed in the communities of Wuhan and Changshu. Patient nutrition education should be strengthened, and the food-matching ability of patients should be improved.

Objective: To explore the relationship of sleep quality and emotional regulation difficulties in middle school students, and to analyze its mediating role of daytime dysfunction, social rejection and selfcontrol ability, so as to provide a scientific reference for improving middle school students mental health. Methods: From October to November, 2023, the Pittsburgh Sleep Quality Index, Adolescent Social Rejection Questionnaire, Brief Selfcontrol Scale and Difficulties in Emotion Regulation Scaleshort Form (DERS-16) were used to assess 806 students recruited from four middle schools in Bengbu City by a convenient cluster random sampling method. And model-6 of PROCESS and 5 000 Bootstraps were used to make a chainmediating model analysis. Results: Daytime dysfunction was positively correlated with sleep quality(r=0.57), social rejection(r=0.19), selfcontrol(r=0.29, P＜0.01). Selfcontrol was positively correlated with emotional regulation difficulties(r=0.54, P<0.01).Poor sleep quality showed a significant positive association with on daytime dysfunction, and daytime dysfunction further affected social rejection, selfcontrol ability and emotional regulation difficulties (β=0.86, 0.60, 1.27, 1.56, P<0.05). Meanwhile, daytime dysfunction, social rejection and selfcontrol played a serial mediating role in the relationship between sleep quality and emotional regulation difficulties (Estimate=0.11,95%CI=0.04-0.20,P<0.05). Conclusion The study reveals the complex relationship between sleep quality and emotional regulation difficulties in middle school students and provides a new theoretical basis for adolescent sleep improvement and mental health interventions.

Objectives:To investigate the impact of baseline non-high-density lipoprotein cholesterol(non-HDL-C)levels on new-onset cardiovascular disease(CVD)in postmenopausal women. Methods:This prospective cohort study selected 8 893 postmenopausal women who participated from 2006 to 2018 employee health examination of Kailuan Group and had complete total cholesterol(TC)and HDL-C data and no history of CVD.Participants were followed up to 31 December,2021.The primary endpoint was the occurrence of CVD or death.According to the Chinese Lipid Management Guidelines(2023),the participants were divided into non-HDL-C<4.1 mmol/L group(n=6 079),4.1 mmol/L≤non-HDL-C<4.9 mmol/L group(n=1 824)and non-HDL-C≥4.9 mmol/L group(n=990).The cumulative incidence of CVD in different groups of non-HDL-C levels was calculated using the Kaplan-Meier method and tested by log-rank analysis.Multivariate Cox regression model was used to analyze the effects of different non-HDL-C levels on CVD. Results:The mean follow-up time was(10.78±4.48)years,the cumulative incidence of CVD in different non-HDL-C level groups was 1.82%,3.24%and 2.89%,respectively.Kaplan-Meier survival curve showed a statistically significant difference in cumulative incidence among the three groups(log-rank P<0.0001).The results of Cox regression analysis showed that after adjusting for confounding factors such as age and sex,the HR(95%CI)values for CVD in the 4.1≤non-HDL-C<4.9 mmol/L group and the non-HDL-C≥4.9 mmol/L group were 1.40(1.13-1.74)and 1.35(1.03-1.78),respectively. Conclusions:High non-HDL-C levels are an independent risk factor for new-onset CVD in postmenopausal women.

COVID-19 associated Guillain-Barré syndrome (GBS) caused by peripheral nerve damage after SARS-CoV-2 infection is one of the most common COVID-19 related nervous system inflammatory diseases, with high incidence of respiratory failure and mortality. Positive SARS-CoV-2 RNA in cerebrospinal fluid of COVID-19 associated GBS patients has been rarely reported. This paper reports 4 patients with COVID-19 associated GBS in China who developed neurological symptoms 4-15 days after fever and were confirmed SARS-CoV-2 infection. All patients presented with progressive weakness of both lower limbs, 3 patients with autonomic dysfunction such as defecation and urination disorders, and 1 patient with polycranial neuritis and Miller-Fisher syndrome such as bilateral facial palsy, dysphagia, diplopia and ataxia. Nerve conduction velocity and F wave were abnormal in 3 patients, and motor conduction pathway was abnormal in 1 patient. Anti-ganglioside antibodies were tested in 3 patients, and GD1a-IgG was positive in 1 patient. All 4 patients underwent metagenomic next-generation sequencing examination in blood and cerebrospinal fluid. SARS-CoV-2 RNA was positive in blood and cerebrospinal fluid of 3 patients, and SARS-CoV-2 RNA was positive in cerebrospinal fluid of 1 patient.

Objective:To explore the feasibility and application value of indocyanine green(ICG)lymph node tracer in clinical early stage cervical cancer staging surgery.Methods:A retrospective analysis was performed on 31 patients with early clinical stage(ⅠA1-ⅡA1)cervical cancer who underwent laparoscopic radical hysterectomy,pelvic lymph node resection and para-aortic lymph node sampling were selected as the study subjects in Sichuan Provincial Maternal and Child Health Care Hospital from April 1,2022 to July 31,2023.They were divided into the ICG fluorescence tracer group(ICG group,17 cases)and the conventional surgery group(control group,14 ca-ses)based on whether ICG was injected or not.The resected lymph nodes were classified and submitted for ex-amination according to location and whether they presented visualization.The method of contingency coefficient was used to analyze the correlations between lymph node visualization patterns and lymph node metastasis and clinicopathological characteristics,and the perioperative data of the two groups were compared.Results:①The postoperative stage of 8 patients(25.8％)(4 in each group)were improved compared with the preoperative clini-cal stage.The number of resected lymph nodes in the ICG group was less than that in the control group(18±9 nodes/person vs.26±11 nodes/person,P＜0.05).There were no statistically significant differences in operation time,intraoperative blood loss,postoperative FIGO(2018)staging,lymph node metastasis rate,and positive rate of resected lymph nodes between the two groups(P＞0.05).②The visualization rate in the ICG group was 64.71％(11/17).There was no statistically significant difference in the positive rate between the visualized and non-visualized lymph nodes(P＞0.05).There was a significant correlation between lymph node visualization and lymph node metastasis(C=0.707,P＜0.05),and a significant correlation was found between lymph node visual-ization and lymph node metastasis in the same patient(C=0.557,P＜0.05).Conclusions:The rate of lymph node metastasis in clinical early stage cervical cancer is low.ICG fluorescence visualization can trace lymph nodes and predict the risk of metastasis.By only resecting the visualized lymph nodes under the guidance of ICG tracer,the lymph node metastasis status of early-stage cervical cancer can be fully evaluated,which is worthy of further research.