VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) syndrome is an adult-onset, X-linked clonal autoinflammatory disease caused by somatic mutations in the UBA1 gene, characterized by systemic inflammation accompanied by hematologic clonal abnormalities. Somatic UBA1 mutations result in impaired ubiquitination, disruption of protein homeostasis, and sustained activation of inflammatory signaling pathways, including nuclear factor-κB and Janus kinase-signal transducer and activator of transcription (JAK-STAT), which together constitute the core pathogenic mechanism. The disease involves multiple systems and tissues including the hematologic system, skin, cartilage and respiratory system, showing remarkable clinical heterogeneity. Diagnosis depends primarily on the combination of characteristic clinical manifestations and molecular confirmation of UBA1 mutations. Current therapeutic strategies lack a unified standard: glucocorticoids can rapidly control inflammation but are associated with high relapse rates, whereas targeted therapies such as JAK inhibitors, interleukin inhibitors, and hypomethylating agents show variable efficacy, and allogeneic hematopoietic stem cell transplantation offers curative potential in patients with concomitant myelodysplastic syndrome. This review systematically summarizes the genetic background, molecular mechanisms, clinical spectrum, diagnostic criteria, and therapeutic advances of VEXAS syndrome.

Purpose: Due to the preservation of the entire stomach after endoscopic resection, the occurrence of metachronous gastric cancer (MGC) remains a possibility. In this study, we investigated the incidence and risk factors for MGC in patients with early gastric cancer who underwent endoscopic submucosal dissection (ESD) and successfully eradicatedHelicobacter pylori. Materials and Methods: A retrospective analysis was conducted of 1,191 patients who underwent ESD and successfully eradicated H. pylori at the Affiliated Drum Tower Hospital of Nanjing University. Endoscopic surveillance was performed at 3, 6, and 12 months post-resection, and annually thereafter. MGC was defined as the development of a new cancer at a site other than the primary gastric cancer site, at least 1 year after the initial endoscopic resection. Results: A total of 77 patients were diagnosed with MGC during a median follow-up of 41.5 months. Kaplan-Meier analysis showed a 5-year cumulative incidence of MGC of 9.4% after successful H. pylori eradication. Multivariate analysis of the training set using Cox proportional hazards models identified male sex, severe atrophic gastritis, multiple gastric cancers before H. pylori eradication, and smoking history as independent risk factors for MGC.The nomogram exhibited favorable discrimination, with area under the curves of 0.767 and 0.822 in the training set and 0.724 and 0.745 in the testing set at 3 and 5 years, respectively. Conclusions Patients with gastric cancer who undergo endoscopic resection, even after successful H. pylori eradication, should undergo annual and continuous endoscopic surveillance for MGC.

BACKGROUND:In orthodontic treatment,full-mouth treatment is usually used to treat single-root severely twisted teeth,and single-tooth treatment is less common.OBJECTIVE:To design a personalized orthodontic device based on biomechanical principles to address the rotation of teeth 11,12,13,21,22,and 23,and evaluate the device's impact on tooth movement using three-dimensional finite element method.METHODS:Based on the biomechanical principle of tooth rotation and movement,a personalized orthodontic device was made by digital design combined with three-dimensional printing,so that the personalized orthodontic device and the tooth formed an anchorage system.The absolute anchorage of the micro-implant was used to precisely control the single-root twisted tooth in the three-dimensional direction.The CBCT data of the maxillary alveolar bone and tooth tissue of a female volunteer were collected.The three-dimensional finite element models of the twisted tooth-periodontal ligament-maxillary bone-personalized orthodontic device were established using Mimics,Geomagic Wrap,SolidWorks,3-matic Research 15.0,and Ansys Workbench software.The equivalent stress distribution characteristics of the personalized orthodontic device,the movement trend of the tooth,and the equivalent stress distribution characteristics of the periodontal ligament were calculated under a thrust of 60 g.RESULTS AND CONCLUSION:(1)The maximum equivalent stress observed on the personalized orthodontic device was 47.71 MPa.(2)The initial tooth displacement under the device demonstrated a rotational trend.The peak equivalent stress in the periodontal ligament was concentrated at the neck,while lower stress was observed in the apex region.(3)The safety and feasibility of the personalized orthodontic device designed in this study for severely rotated single-rooted teeth were preliminarily verified through finite element analysis.

Objective To explore the clinical efficacy of endoscopic electrocoagulation resection and cold resection techniques in the treatment of elderly patients with complex colonic polyps.Methods A retrospective selection was made of 100 elderly patients with colonic polyps who underwent endoscopic electrocoagulation resection and cold resection of colonic polyps in the Department of Gastroenterology of Yiwu Central Hospital from August 2021 to August 2023.According to the different surgical methods,the patients were divided into the electrocoagulation group(50 cases)and the cold resection group(50 cases).The polyp resection status,intraoperative and postoperative treatment conditions,postoperative pain degree,gastrointestinal quality of life index(GIQLI)score,length of hospital stay,total treatment cost,and recurrence situation after 1-year follow-up of the elderly patients with colonic polyps in the two groups were statistically analyzed.Results 108 polyps were resected in the electrocoagulation group and 113 in the cold resection group.The complete resection rate of polyps in the cold resection group was higher than that in the electrocoagulation group,the specimen damage rate was lower than that in the electrocoagulation group,the differences were statistically significant(P<0.05).There were no statistically significant difference in the average number of polyps removed and the recovery rate of polyp specimens between the two groups(P>0.05).The operation time and hospital stay of the cold resection group were shorter than those of the electrocoagulation group,the total treatment cost was less than that of the electrocoagulation group,and the usage rate of titanium clips during the operation was lower than that of the electrocoagulation group.The differences were all statistically significant(P<0.05).The incidences of intraoperative bleeding,delayed bleeding,perforation and abdominal pain in the electrocoagulation group were 6.00%,2.00%,2.00%and 6.00%respectively,which were higher than those in the cold resection group(2.00%,0.00%,0.00%and 2.00%),and there was statistically significant difference in the total incidence of complications between the two groups of patients(P<0.05).The visual analogue scale(VAS)scores of the cold resection group at 24 and 48 h after surgery were lower than those of the electrocoagulation group,and the differences were statistically significant(P<0.05).The GIQLI score of the cold resection group 3 months after the operation was higher than that of the electrocoagulation group,and the difference was statistically significant(P<0.05).The recurrence rate of the cold resection group at 1 year was lower than that of the electrocoagulation group,but the difference was not statistically significant(P>0.05).Conclusion The clinical efficacy of endoscopic cold resection technique in the treatment of elderly complex colonic polyps patients is better than that of electrocoagulation resection,and it has high safety and low treatment cost.It is worthy of clinical promotion and application.

Objective To compare and analyze the epidemiological characteristics of the adverse events following immunization (AEFI) with measles containing vaccine (MCV) in Zibo City from 2018-2022, and to provide reference data for evaluating the safety of the immunization strategy adjustment. Methods AEFI surveillance data related to MCV in Zibo City from 2018 to 2022 were collected from the China Disease Prevention and Control Information System Immunization Planning System and Shandong Provincial Vaccination Information System. The AEFI reports and epidemic characteristics after adjusting the immunization strategy about MCV were compared. Results Before adjusting immunization strategy of MCV in Zibo City (January 1, 2018 to May 31, 2020), 114 cases of AEFI were reported in the first dose of measles and rubella combined attenuated live vaccine (MR), with a reported incidence rate of 131.50/100 000. After adjusting the immunization strategy (June 1, 2020- December 31, 2022), 156 cases of AEFI were reported in the first dose of MMR, with a reported incidence of 162.97/100,000. There was no statistically significant difference in the reported incidence of AEFI (χ²=3.049, P=0.081). AEFI cases were mainly characterized by general reactions, and the reported incidence rate of MR (88.82/100,000) was lower than that of MMR (137.90/100,000) (χ²=9.576, P=0.002). Their most common clinical manifestation was fever, with 71 cases reported (81.90/100 000) and 114 cases reported (119.10/100 000), respectively. The reported incidence of abnormal reactions in MR (42.68/100 000) was higher than that in MMR (22.98/100,000) (χ²=5.458, P=0.019). Among them, allergic rash was the most common, with 16 and 11 cases reported, respectively, and the reported incidence rates were 18.46/100 000 and 11.49/100 000, respectively. The proportion of reported cases in the age group ≥ 1 year old was higher in MMR than in MR (χ²=41.089, P<0.001). The proportion of reported cases in the first quarter was higher in MR than in MMR (29.82%, 17.95%), while the proportion in the third quarter was higher in MMR than in MR (34.64%, 17.54%) (χ²=14.197, P=0.003). Conclusion After adjusting the MCV immunization strategy in Zibo City, the report on AEFI is within the expected range, and no adverse changes have been found in the epidemic characteristics of MCV related AEFI.

Objective To introduce a modified technique of right ventricular outflow tract (RVOT) reconstruction using a handmade bicuspid pulmonary valve crafted from expanded polytetrafluoroethylene (ePTFE) and to summarize the early single-center experience. Methods Patients with complex congenital heart diseases (CHD) who underwent RVOT reconstruction with a handmade ePTFE bicuspid pulmonary valve due to pulmonary regurgitation at Guangdong Provincial People’s Hospital from April 2021 to February 2022 were selected. Postoperative artificial valve function and right heart function indicators were evaluated. Results A total of 17 patients were included, comprising 10 males and 7 females, with a mean age of (18.18±12.14) years and a mean body weight of (40.94±19.45) kg. Sixteen patients underwent reconstruction with a handmade valved conduit, with conduit sizes ranging from 18 to 24 mm. No patients required mechanical circulatory support, and no in-hospital deaths occurred. During a mean follow-up period of 12.89 months, only one patient developed valve dysfunction, and no related complications or adverse events were observed. The degree of pulmonary regurgitation was significantly improved post-RVOT reconstruction and during follow-up compared to preoperative levels (P<0.001). Postoperative right atrial diameter, right ventricular diameter, and tricuspid regurgitation area were all significantly reduced compared to preoperative values (P<0.05). Conclusion The use of a 0.1 mm ePTFE handmade bicuspid pulmonary valve for RVOT reconstruction in complex CHD is a feasible, effective, and safe technique.

Objective To explore the clinical efficacy of endoscopic electrocoagulation resection and cold resection techniques in the treatment of elderly patients with complex colonic polyps.Methods A retrospective selection was made of 100 elderly patients with colonic polyps who underwent endoscopic electrocoagulation resection and cold resection of colonic polyps in the Department of Gastroenterology of Yiwu Central Hospital from August 2021 to August 2023.According to the different surgical methods,the patients were divided into the electrocoagulation group(50 cases)and the cold resection group(50 cases).The polyp resection status,intraoperative and postoperative treatment conditions,postoperative pain degree,gastrointestinal quality of life index(GIQLI)score,length of hospital stay,total treatment cost,and recurrence situation after 1-year follow-up of the elderly patients with colonic polyps in the two groups were statistically analyzed.Results 108 polyps were resected in the electrocoagulation group and 113 in the cold resection group.The complete resection rate of polyps in the cold resection group was higher than that in the electrocoagulation group,the specimen damage rate was lower than that in the electrocoagulation group,the differences were statistically significant(P<0.05).There were no statistically significant difference in the average number of polyps removed and the recovery rate of polyp specimens between the two groups(P>0.05).The operation time and hospital stay of the cold resection group were shorter than those of the electrocoagulation group,the total treatment cost was less than that of the electrocoagulation group,and the usage rate of titanium clips during the operation was lower than that of the electrocoagulation group.The differences were all statistically significant(P<0.05).The incidences of intraoperative bleeding,delayed bleeding,perforation and abdominal pain in the electrocoagulation group were 6.00%,2.00%,2.00%and 6.00%respectively,which were higher than those in the cold resection group(2.00%,0.00%,0.00%and 2.00%),and there was statistically significant difference in the total incidence of complications between the two groups of patients(P<0.05).The visual analogue scale(VAS)scores of the cold resection group at 24 and 48 h after surgery were lower than those of the electrocoagulation group,and the differences were statistically significant(P<0.05).The GIQLI score of the cold resection group 3 months after the operation was higher than that of the electrocoagulation group,and the difference was statistically significant(P<0.05).The recurrence rate of the cold resection group at 1 year was lower than that of the electrocoagulation group,but the difference was not statistically significant(P>0.05).Conclusion The clinical efficacy of endoscopic cold resection technique in the treatment of elderly complex colonic polyps patients is better than that of electrocoagulation resection,and it has high safety and low treatment cost.It is worthy of clinical promotion and application.

Objective: To systematically analyzes the impact of blood donor characteristics on red blood cell (RBC) quality and transfusion outcomes, and to provide a scientific basis for optimizing donor selection criteria and developing personalized transfusion strategies. Methods: A literature search was conducted across electronic databases including CNKI, VIP, Wanfang Data, PubMed, and Embase using combinations of keywords such as "donor characteristics", "blood storage lesion", "blood quality", and "transfusion outcomes" for summary and analysis. Results: Factors associated with the blood donor characteristics including demographic characteristics (sex, age, body mass index), lifestyle habits (smoking, alcohol consumption, exercise), and dietary or pharmacological exposures significantly influence blood storage stability and transfusion efficacy by modulating erythrocyte metabolism, oxidative stress levels, and immune properties. Conclusion: The complexity and diversity of the blood donor characteristics are associated with blood quality and transfusion outcomes. Future efforts should focus on refining donor selection criteria and establishing personalized transfusion strategies to enhance blood product quality and improve patient outcomes.

OBJECTIVE: To explore the impact of age on the genetic variant spectrum and prognosis of patients with previously untreated Diffuse large B-cell lymphoma (DLBCL). METHODS: A retrospective analysis was conducted on the clinical data and follow-up information of 254 previously untreated DLBCL patients from 14 hospitals in the Jiangsu Cooperative Lymphoma Group (JCLG) enrolled from July 2018 and July 2023. Following extraction of DNA from tumor tissue samples, next-generation sequencing (NGS) technique was employed to analyze the genetic variant spectrum of the DLBCL patients, with an evaluation of the relationship between age and genetic variants as well as prognosis. This study was approved by the Medical Ethics Committee of the Affiliated Hospital of Nantong University (Ethics No.: 2023-K048-01). RESULTS: The median age of the 254 DLBCL patients was 62 years old, with 55% of patients aged 60 years or above. Clinical evaluation showed that younger (< 60 years) patients had higher complete response (CR) (70% vs. 59%), and objective response rate (ORR) (88% vs. 79%) than older patients, though the difference between the two groups was not statistically. Survival analysis indicated that both the five-year overall survival (OS) (82.7% vs. 71.7%, P = 0.006) and progression-free survival (PFS) (70.6% vs. 50.2%, P < 0.05) rates were significantly higher in younger patients. NGS showed that 99.6% of the patients harbored genetic variants, with PIM1, KMT2D, TP53, MYD88, and CD79B being the most common genes. Age significantly affected the variant frequency of certain genes, with MYC variants serving an adverse prognostic factor for OS in younger patients (P = 0.002), while TP53 (P = 0.024) and BCL2 (P = 0.002) variants significantly impacted OS in older patients. Prognostic analysis identified age ≥ 60 years (HR = 3.439, 95%CI: 1.318~9.874), presence of B symptoms (HR = 2.871, 95%CI = 1.133~7.307), and elevated lactate dehydrogenase (HR = 3.528, 95%CI = 1.231~10.66) as independent adverse prognostic factors. CONCLUSION Age, genetic variants, and clinical factors may significantly affect the prognosis of the DLBCL patients. Younger patients have better survival compared to older patients. Variants of the MYC, BCL2, and TP53 genes are closely associated with poor prognosis.
Humans ; Lymphoma, Large B-Cell, Diffuse/diagnosis* ; Middle Aged ; Female ; Male ; Retrospective Studies ; Aged ; Prognosis ; Adult ; Aged, 80 and over ; High-Throughput Nucleotide Sequencing ; Young Adult ; Adolescent ; Genetic Variation

Allergic rhinitis (AR), a globally prevalent immune-mediated inflammatory condition, is still an incurable disease. In the present study, we have validated the impact of the Kelch-like ECH associated protein 1 (Keap1)-related oxidative stress and inflammatory response in clinical AR patient peripheral blood and nasal swab samples, emphasizing the biological relevance of Keap1 and AR. Targeting Keap1 -nuclear factor erythroid 2-related factor 2 (Nrf2) related anti-oxidative stress may be effective for AR intervention. Drawing inspiration from the Keap1 homodimerization and the E3 ligase characteristics, we herein present a design of novel bivalent molecules for chemical knockdown of Keap1. For the first time, we characterized ternary complexes of Keap1 dimer and one molecule of bivalent compounds. The best bivalent molecule 8 encompasses robust capacity to degrade Keap1 as a homoPROTAC^KEAP1. It efficaciously suppresses inflammatory cytokines in extensively different cells, including human nasal epithelial cells. Moreover, in an AR mouse model, we confirmed that the chemical degradation induced by homoPROTAC^KEAP1 led to therapeutic benefits in managing AR symptoms, oxidative stress and inflammation. In summary, our findings underscore the efficacy of targeting the Keap1 system through the homoPROTAC-ing technology as an innovative and promising treatment strategy for the incurable allergic disorders.