OBJECTIVE: To evaluate the differential expression of RNA in blood monocytes in patients with Juvenile idiopathic arthritis (JIA) treated with TNF antagonists (TNFi), and to explore the effect and mechanism of gene expression on the efficacy of JIA. METHODS: A total of 29 children with JIA treated with methotrexate (MTX) and TNFi in Guangzhou Women and Children's Medical Center of Guangzhou Medical University from April 2021 to November 2023 were enrolled. After 6 months, the children were divided into two groups according to the treatment effect, i.e., 13 cases in the ineffective group and 16 cases in the effective group, the peripheral blood of the children was collected, the blood mononuclear cells were isolated for transcriptome sequencing, the differentially expressed genes between the groups were analyzed, the signaling pathways and metabolic pathways related to the efficacy of TNFi were analyzed by GO and KEGG enrichment, and the mechanism related to the efficacy of TNFi was explored. This study was approved by Medical Ethics Committee of the Guangzhou Women and Children's Medical Center of Guangzhou Medical University (Ethics No.: 2023-330B00). RESULTS: There was a statistically significant difference in the gender and age distribution between the two groups of children (P < 0.05), while no statistically significant differences were observed in disease duration, rheumatoid antibody levels, or JIA subtypes (P > 0.05). After sequencing data quality control and comparison of reference genomes, a total of 18 523 protein-coding genes were identified in all children's samples. A total of 705 differentially expressed genes (DEGs) were identified between the effective group and the invalid group through differential analysis, of which 579 were up-regulated in the effective group and 126 in the inactive group. GO function and KEGG pathway enrichment analysis showed that DEG was significantly enriched in 55 GO entries and 32 KEGG metabolic pathways, which were mainly related to IL-1β production and regulation, cytokine production and regulation, cytokine-cytokine receptor interaction, immune response regulation, and Toll-like receptor signaling pathway. CONCLUSION DEG between the effective and ineffective groups of TNFi treatment may be involved in the biological processes such as cytokine production and regulation, cytokine-receptor interaction, and immune response regulation, which will be helpful to predict the efficacy and prognosis of TNFi treatment for JIA.
Humans ; Arthritis, Juvenile/blood* ; Female ; Male ; Child ; Methotrexate/therapeutic use* ; Child, Preschool ; Tumor Necrosis Factor-alpha/antagonists & inhibitors* ; Transcriptome ; Adolescent ; RNA/genetics* ; Signal Transduction ; Gene Expression Profiling

Objective To explore the effects of anticoagulation treatment to postoperative bleeding events in liver cirrhosis patients with gastric varices and portal vein thrombosis.Methods Patients diagnosed with portal vein thrombosis and treated with endoscopic cyanoacrylate injection at Zhongshan Hospital,Fudan University due to gastric variceal bleeding from January 2023 to December 2023 were included.Clinical data of patients were collected,and patients were divided into anticoagulant group and non-anticoagulant group based on whether anticoagulant treatment was performed within 48 h after treatment.Re-bleeding in patients was evaluated in 6 weeks of follow-up.Cox regression was used for univariate and multivariate analysis of re-bleeding within 6 weeks after treatment.Results A total of 160 patients were included,of whom 65 patients received anticoagulation treatment within 48 h after endoscopic cyanoacrylate injection.There were no statistically significant differences in gender,etiology of liver cirrhosis,dosage of cyanoacrylate and sclerosing agents,and Child-Pugh grading between the two groups.There was no statistically significant difference in re-bleeding rate within 6 weeks after treatment between the two groups(1.54％vs 1.05％,P=0.795).Multivariate Cox regression analysis showed that the large amount of cyanoacrylate was a risk factor for re-bleeding within 6 weeks after endoscopic treatment(HR=5.862,P=0.015).Conclusions For patients with liver cirrhosis,gastric varices,and portal vein thrombosis,who receive endoscopic cyanoacrylate injection,early anticoagulation does not increase the risk of re-bleeding after treatment,while a large amount of cyanoacrylate injection may be a risk factor for re-bleeding.However,sample should be increased to verify.

Objective To compare the efficacy and safety of endoscopic ligation treatment and endoscopic tissue glue injection for secondary prevention of gastric variceal bleeding.Methods Patients with cirrhosis and esophagogastric variceal bleeding treated with gastric variceal ligation in Zhongshan Hospital,Fudan University,from January 2017 to December 2019 were screened(ligation group).And during the same period,patients underwent endoscopic cyanoacrylate treatment were also screened(tissue glue group).59 patients were included in the two groups after propensity score matching.Univariate and multivariate Cox proportional hazard regression models were used to anslyze risk factors for re-bleeding.Kaplan-Meier curves were plotted to analyze re-bleeding rate and mortality of the two treatment groups.Results There was no statistically significant difference in the eradication rate of esophagogastric varices between the ligation group and the tissue glue group(83.05％vs 79.66％,P=0.778);the ligation group required fewer median endoscopic treatments for variceal eradication(2 vs 3,P=0.017)and a lower average dosage of cyanoacrylate(0.70 mL vs 2.67 mL,P＜0.001).Multivariate Cox regression analysis showed that portal shunt was a risk factor for esophagogastric varices re-bleeding(HR=3.14,95％CI 1.02-9.68,P=0.046),endoscopic variceal ligation was a protective factor against re-bleeding(HR=0.25,95％CI 0.08-0.71,P=0.010).Compared with endoscopic cyanoacrylate injection,endoscopic ligation treatment did not significantly increase the 2-year risk of esophagogastric variceal re-bleeding(18.69％vs 36.29％,P=0.067)or risk of death(1.69％vs 3.39％,P=1.000);patients with GOV1 type had a significantly lower risk of re-bleeding after endoscopic ligation treatment(0 vs 40.27％,P=0.012)and there was a trend towards a lower re-bleeding risk in patients with GOV2 type after endoscopic ligation treatment(13.27％vs 34.16％,P=0.056).Conclusions Endoscopic ligation treatment has higher eradication rate for esophagogastric varices,and does not increase the risk of re-bleeding,death,or other adverse events.Therefore,it can be considered an effective secondary prevention way for patients with gastric varices.

Objective:To investigate whether discontinuation of previous targeted immunotherapy increases the risk of rebleeding in patients with advanced liver cancer complicated with esophageal and gastric variceal bleeding after endoscopic treatment.Methods:A retrospective cohort study was conducted to include advanced liver cancer patients who were diagnosed with esophageal and gastric variceal bleeding through endoscopic examination and treated under endoscopy at Zhongshan Hospital, Fudan University from March 1, 2020 to March 1, 2022, due to upper gastrointestinal bleeding. We collected clinical data from patients and divided them into targeted immunotherapy group and non targeted immunotherapy group based on whether they received targeted immunotherapy before bleeding; Follow up observation was conducted for 6 months to evaluate the patient′s re bleeding and survival status.Results:A total of 55 patients were included, of which 24 had previously received targeted immunotherapy and 31 had not received targeted immunotherapy. There was no significant difference between the two groups in gender distribution, etiology, hypertension and diabetes (all P>0.05). The age of the target immunotherapy group was younger than that of the non target immunotherapy group, and the level of fibrinogen was higher than that of the non target immunotherapy group, with statistical significance ( P=0.002, 0.017). There was no statistically significant difference in the 6-month re bleeding rate (20.83% vs 22.58%, P=0.269) and 6-month mortality rate (45.83% vs 29.03%, P=0.199) between the targeted and non targeted groups of patients. Further Cox regression multivariate analysis revealed that Child-pugh grading was an independent risk factor for 6-month survival in patients with advanced liver cancer with esophageal and gastric varices ( HR=2.64, P=0.009). Conclusions:Targeted immunotherapy does not increase the rate of rebleeding in patients with advanced unresectable liver cancer after endoscopic treatment of esophageal and gastric varices. Child-pugh grading is a factor that affects the 6-month survival of advanced liver cancer patients after bleeding, and the poorer the liver function, the shorter the survival period.

Objective To investigate whether sarcopenia before concurrent chemoradiotherapy is prone to grade≥3 acute adverse reactions (AAR) and shorten survival in patients with advanced esophageal squamous cell carcinoma (ESCC). Methods Data of advanced patients with pathologically diagnosed ESCC and CCRT (FP regimen) from August 2018 to July 2022 were reviewed retrospectively.Skeletal muscle mass and body composition were measured using pre-treatment CT images, and patients were divided into sarcopenia and non-sarcopenia groups.Grade≥3 AAR was diagnosed based on CTCAE5.0 and acute radiation injury criteria of the US RTOG.Risk factors for developing grade≥3 AAR were analyzed, and survival rates were calculated by Kaplan-Meier method. Results Among 132 patients with ESCC (87 in the sarcopenia group and 45 in the non-sarcopenia group), 23(17.4%) experienced grade≥3 AAR.In multivariate regression analysis, independent risk factors for grade ≥3 AAR included the following: sarcopenia (OR: 6.034, 95%CI: 1.206-30.190, P=0.029), decreased SMD (OR: 0.693, 95%CI: 0.492-0.976, P=0.036), decreased SMI (OR: 0.841, 95%CI: 0.721-0.982, P=0.028), and increased FMI (OR: 2.433, 95%CI: 1.194-4.958;P=0.014).The OS rates were 16.01 months (95%CI: 14.89-17.13) in the sarcopenia group and 19.27 months (95%CI: 14.45-24.09) in the non-sarcopenia group (χ²=5.326, P=0.021) as well as 14.86 months (95%CI: 11.30-18.42) for patients with grade≥3 AAR and 16.67 months (95%CI: 14.91-18.43) for patients with grade 0-2 AAR (χ²=5.47, P=0.019).Among patients with grade≥3 AAR, the OS rates were 12.13 months (95%CI: 10.15-14.11) in the sarcopenia group and 18.69 months (95%CI: 12.85-21.88) in the non-sarcopenia group (χ²=4.466, P=0.035). Conclusion Sarcopenia, decreased skeletal muscle density, and increased fat mass are important predictors of grade≥3 AAR.The OS of patients with sarcopenia and grade≥3 AAR may be reduced.

Humans ; Adult ; Serum Albumin, Human ; Consensus ; Cardiac Surgical Procedures ; Thoracic Surgery

According to the pathophysiological characteristics, upper gastrointestinal bleeding can be divided into acid related disease bleeding and esophageal and gastric varices bleeding. Esophageal and gastric variceal bleeding is a common critical condition of Portal hypertension, with dangerous onset and high mortality. With the improvement of endoscopic treatment technology, endoscopy has become the first line treatment plan for esophageal and gastric variceal bleeding. The commonly used endoscopic management methods for varicose veins include variceal ligation, tissue glue combined with sclerosing agent embolization, ultrasound guided coil combined with tissue glue embolization, and other management measures. Early identification of gastrointestinal bleeding related to varicose veins, stratified diagnosis and treatment of high-risk patients, reasonable selection of endoscopic examination timing, and personalized decision-making of treatment choices are key to improving efficacy.

Basic fibroblast growth factor (bFGF) exhibits superior biological functions by improving periodontal inflammation, promoting the migration and proliferation of periodontal-related stem cells, promoting the formation of blood vessels and periodontal ligament-like tissue, and regulating the formation of bone/cementum. It plays an important role in tooth development, repair and regeneration. bFGF can be combined with seed cells and scaffold materials for periodontal tissue regeneration, which has been verified in a number of experimental studies. However, the application of bFGF alone as a drug in clinical treatment requires further research.

Objective    To evaluate the safety and efficacy of mitral valve surgery and cryoablation in elderly patients with mitral valve disease and persistent or long-term persistent atrial fibrillation. Methods    From May 2014 to July 2018, 144 patients with mitral valve diseases combined with persistent or long-term persistent atrial fibrillation in the Department of Cardiothoracic Surgery, General Hospital of Northern Theater Command were selected. Among them, there were 69 patients in a non-elderly group (<60 years) including 18 males and 51 females aged 52.07±5.56 years, and 75 patients in an elderly group (≥60 years) including 32 males and 43 females aged 65.23±4.29 years. A propensity-score matching (PSM) study was conducted to eliminate confounding factors. Both groups underwent mitral valve surgery and cryoablation at the same time. A 2-year follow-up was conducted after discharge from the hospital, and the perioperative and postoperative efficacy indexes were compared between the two groups. Results    After PSM analysis, there were 56 patients in each group. The sinus rhythm conversion rate of the two groups at each follow-up time point was above 85%, and the cardiac function was graded asⅠorⅡ, which was significantly improved compared with that before the surgery, but there was no statistical difference between the two groups (P>0.05). Among the perioperative indicators of the two groups, the elderly group had more coronary artery bypass graft surgeries and longer postoperative ICU stay time compared with the non-elderly group (P<0.05), and the differences in other indicators were not statistically different (P>0.05). Conclusion    The mitral valve surgery and cryoablation in elderly patients with mitral valve diseases combined with persistent or long-term persistent atrial fibrillation are safe, and the short-term outcome is satisfactory.

Antrodia cinnamomea is extensively used as a traditional medicine to prevention and treatment of liver cancer. However, its comprehensive chemical fingerprint is uncertain, and the mechanisms, especially the potential therapeutic target for anti-hepatocellular carcinoma (HCC) are still unclear. Using UPLC‒Q-TOF/MS, 139 chemical components were identified in A. cinnamomea dropping pills (ACDPs). Based on these chemical components, network pharmacology demonstrated that the targets of active components were significantly enriched in the pathways in cancer, which were closely related with cell proliferation regulation. Next, HCC data was downloaded from Gene Expression Omnibus database (GEO). The Cancer Genome Atlas (TCGA) and DisGeNET were analyzed by bioinformatics, and 79 biomarkers were obtained. Furtherly, nine targets of ACDP active components were revealed, and they were significantly enriched in PI3K/AKT and cell cycle signaling pathways. The affinity between these targets and their corresponding active ingredients was predicted by molecular docking. Finally, in vivo and in vitro experiments showed that ACDPs could reduce the activity of PI3K/AKT signaling pathway and downregulate the expression of cell cycle-related proteins, contributing to the decreased growth of liver cancer. Altogether, PI3K/AKT-cell cycle appears as the significant central node in anti-liver cancer of A. Cinnamomea.