Microglial pyroptosis and neuroinflammation have been implicated in the pathogenesis of sepsis-associated encephalopathy (SAE). OGT-mediated O-GlcNAcylation is involved in neurodevelopment and injury. However, its regulatory function in microglial pyroptosis and involvement in SAE remains unclear. In this study, we demonstrated that OGT deficiency augmented microglial pyroptosis and exacerbated secondary neuronal injury. Furthermore, OGT inhibition impaired cognitive function in healthy mice and accelerated the progression in SAE mice. Mechanistically, OGT-mediated O-GlcNAcylation of ATF2 at Ser44 inhibited its phosphorylation and nuclear translocation, thereby amplifying NLRP3 inflammasome activation and promoting inflammatory cytokine production in microglia in response to LPS/Nigericin stimulation. In conclusion, this study uncovers the critical role of OGT-mediated O-GlcNAcylation in modulating microglial activity through the regulation of ATF2 and thus protects against SAE progression.
Animals ; Microglia/metabolism* ; Pyroptosis/physiology* ; Mice ; Sepsis-Associated Encephalopathy/prevention & control* ; Activating Transcription Factor 2/metabolism* ; N-Acetylglucosaminyltransferases/genetics* ; Mice, Inbred C57BL ; Male ; Mice, Knockout

Malignant peritoneal mesothelioma (MPM), as a highly aggressive primary malignant tumor of the peritoneum, often leads to structural damage and functional impairment of female reproductive organs during its treatment course. This study presents a clinical case of an MPM patient who underwent cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC), subsequently achieving successful live birth through in vitro fertilization and embryo transfer. A comprehensive review of relevant literature was conducted to analyze both the potential benefits and associated risks. While the possibility of successful pregnancy exists for MPM patients following combined CRS and HIPEC treatment, significant clinical risks during the gestational process cannot be overlooked. Current evidence remains limited, necessitating more robust clinical data to substantiate these findings.

Malignant peritoneal mesothelioma (MPM), as a highly aggressive primary malignant tumor of the peritoneum, often leads to structural damage and functional impairment of female reproductive organs during its treatment course. This study presents a clinical case of an MPM patient who underwent cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC), subsequently achieving successful live birth through in vitro fertilization and embryo transfer. A comprehensive review of relevant literature was conducted to analyze both the potential benefits and associated risks. While the possibility of successful pregnancy exists for MPM patients following combined CRS and HIPEC treatment, significant clinical risks during the gestational process cannot be overlooked. Current evidence remains limited, necessitating more robust clinical data to substantiate these findings.

Objective:To explore the symptom clusters, core symptoms and bridging symptoms in the symptom network of early postoperative patients with laryngeal cancer.Methods:From January 2021 to April 2024, convenience sampling was used to select early postoperative patients with laryngeal cancer admitted to the Department of Otolaryngology at the First Affiliated Hospital of the University of Science and Technology of China as participants. The General Information Questionnaire and M.D. Anderson Symptom Inventory-Head & Neck were used for the survey. R language software was used to analyze symptom clusters, core symptoms, and bridging symptoms in early postoperative patients with laryngeal cancer.Results:A total of 300 questionnaires were distributed and 287 valid questionnaires were collected, with a valid response rate of 95.7%. Network analysis extracted three symptom clusters (oropharyngeal specific symptom cluster, shortness of breath and fatigue symptom cluster, and sleep emotion symptom cluster), among which the oropharyngeal specific symptom cluster was the most severe. Symptom network analysis showed a strong correlation between oropharyngeal pain and swallowing difficulties, distress and fatigue, and restless sleep and sadness. Shortness of breath exhibited the highest intensity centrality ( rs=1.29) and mediation centrality ( rb=96) in the symptom network. It was the core symptom and bridging symptom in the symptom network of early postoperative patients with laryngeal cancer. Conclusions:Early postoperative patients with laryngeal cancer have a severe oropharyngeal-specific symptom cluster, with shortness of breath being the core symptom and bridging symptom in the symptom network. Medical and nursing staff should focus on the mutual influence between early symptoms of patients after laryngectomy and correctly identify core symptoms and bridging symptoms to improve symptom management accuracy.

Objective:To explore the symptom clusters, core symptoms and bridging symptoms in the symptom network of early postoperative patients with laryngeal cancer.Methods:From January 2021 to April 2024, convenience sampling was used to select early postoperative patients with laryngeal cancer admitted to the Department of Otolaryngology at the First Affiliated Hospital of the University of Science and Technology of China as participants. The General Information Questionnaire and M.D. Anderson Symptom Inventory-Head & Neck were used for the survey. R language software was used to analyze symptom clusters, core symptoms, and bridging symptoms in early postoperative patients with laryngeal cancer.Results:A total of 300 questionnaires were distributed and 287 valid questionnaires were collected, with a valid response rate of 95.7%. Network analysis extracted three symptom clusters (oropharyngeal specific symptom cluster, shortness of breath and fatigue symptom cluster, and sleep emotion symptom cluster), among which the oropharyngeal specific symptom cluster was the most severe. Symptom network analysis showed a strong correlation between oropharyngeal pain and swallowing difficulties, distress and fatigue, and restless sleep and sadness. Shortness of breath exhibited the highest intensity centrality ( rs=1.29) and mediation centrality ( rb=96) in the symptom network. It was the core symptom and bridging symptom in the symptom network of early postoperative patients with laryngeal cancer. Conclusions:Early postoperative patients with laryngeal cancer have a severe oropharyngeal-specific symptom cluster, with shortness of breath being the core symptom and bridging symptom in the symptom network. Medical and nursing staff should focus on the mutual influence between early symptoms of patients after laryngectomy and correctly identify core symptoms and bridging symptoms to improve symptom management accuracy.

Objective: To analyze the prevalence trend of scoliosis among myopic students in Inner Mongolia Autonomous Region during 2019-2022, to explore the common etiology of myopia and scoliosis co-morbidities, so as to provide a reference for the development of relevant measures. Methods: The method of stratified random cluster sampling was used to select 181 533, 141 552 , 200 987, 190 918 primary and secondary school students from 12 leagues(103 banners) in Inner Mongolia Atuonomous Region in September each year from 2019 to 2022. And scoliosis screening, vision examination and questionnaire survey were conducted among students in the included studies. The χ 2 test was used to analyze the data, and the binary multivariate Logistic regression model was used to screen the influencing factors of scoliosis and myopia co-morbidities. Results: From 2019 to 2022, the myopia rate of primary and secondary school students in Inner Mongolia Autonomous Region was 55.55%-59.72%, scoliosis rate was 1.56 %-2.81% and the rates of scoliosis and myopia co-morbidities were 1.14%-1.95%, and the difference between different years was statistically significant ( χ 2=595.01, 775.56, 461.84, P < 0.05 ). In 2022, the co-morbidity rate was higher in girls than in boys(1.32% vs 0.97%), the rate of urban areas was higher than that of rural areas(2.57% vs 0.62%), the rate of students in vocational high school and high school was higher than that in junior high school and primary school (3.82%,2.47% vs 1.70%,0.42%), the rate of over developed areas was higher than that of poor areas (1.21% vs 0.99%)( χ 2=52.19, 1 269.82, 1 361.52, 17.29, P < 0.05 ). Logistic regression analysis showed that at least 1 h of moderate and high intensity exercise every day on weekends, the number of physical education classes per week was more than 3 sessions, the height of desks and chairs was adjusted according to height, resting outdoors, limiting screen time, and strictly requiring standing and sitting posture were the negative correlated with scoliosis and myopia, and the OR value was 0.65-0.90, reading books or electronic screens while participating in cram classes, walking or riding in the car were positively correlated with comorbid scoliosis and myopia, and the OR values were 1.27 and 1.13 ( P < 0.05), respectively. Conclusion Behavioral habits severely affect scoliosis and myopic of students. Prevention and control of scoliosis and myopia co-morbidity should start with students behavioral habits, early screening and early intervention.

Objective: To describe the current status of the prevalence of co-morbid myopia and obesity among 7-18 years students in the Inner Mongolia Autonomous Region in 2021 and to analyze the moderating effect of lifestyle in this association ，so as to provide scientific basis for the establishment of the mechanism of Co-morbidity，Shared Etiology，and Shared Prevention of common diseases in children and adolescents. Methods: A total of 139 630 primary and secondary school students aged 7-18 years from Inner Mongolia Autonomous Region were selected by stratified random cluster sampling method in September,2021. Myopia was determined using distance visual acuity examination and refractive error examination, and obesity was determined according to the BMI classification criteria for overweight, obesity screening of Chinese school age children and adolescents. Used a questionnaire, healthy lifestyles were determined according to the American Heart Association s Healthy Lifestyle Score by totaling the six scores for smoking, alcohol consumption, diet, exercise, screen time, and sleep duration.The χ 2 test was used to compare the association between group differences in the co-morbidity rate of myopia and obesity. The multivariable Logistic regression model was used to explore the influencing factors of the co-morbidity of myopia and obesity, and the stratified analysis was used to analyze the moderating effect of lifestyles on the prevalence of the co-morbidity. Results: The prevalence of myopia and obesity co-morbidity among students aged 7-18 years old in the Inner Mongolia Autonmous Region in 2021 was 13.7%, higher among boys than girls ( 15.5 % vs. 11.8%), higher among those aged 10-12 years old than 7-9,13-15,and 16-18 years old (14.7%,13.7%, 13.3%, 12.0%), higher among other ethnic minorities than Han Chinese and Mongolians (15.3%, 14.0%, 12.5%), higher in urban areas than that in suburban areas(15.3%, 13.0%), and middle economic level tracts were higher than poor and good tracts (14.8%, 12.9 %, 12.6%) ( χ 2=392.37，115.73，62.80，119.02，121.60, P <0.05). Multivariable Logistic regression modeling showed that unhealthy lifestyles ( OR=1.24, 95%CI=1.19-1.29 ) and middle level of lifestyle score ( OR=1.15, 95%CI=1.10-1.19 ) students had higher prevalence of co-morbidity, and the results were statistically significant among both boys and girls, the age groups of 10- 12, 13-15, and 16-18 years old, as well as the Han and Mongolian ethnic groups (all P <0.05). Conclusion In 2021, the current situation of myopia and obesity co-morbidity and unhealthy lifestyles among primary and secondary school students in the Inner Mongolia Autonomous Region are not optimistic.

Objective: To analyze the prevalence of overweight, obesity and depression among students in the Inner Mongolia Autonomous Region in 2019-2022 and explore the relevant factors affecting the co-morbidity of overweight,obesity and depression among students, so as to provide scientific basis for the prevention of co-morbidity. Methods: From September 2019 to 2022, used stratified random cluster sampling, 90 519,71 560,90 079,91 089 students were selected from all 12 leagues in Inner Mongolia Autonomous Region for questionnaire survey and physical examination. The χ 2 test was used for demographic characteristics and univariate analysis, and a binary Logistic regression model was used to explore the association between lifestyle behaviors and co-morbidity. Results: The detection rate of overweight,obesity among students from 2019-2022 was 29.21%,34.38%,35.20%,34.61%, the detection rate of depression was 18.35%，17.53%，16.43%，16.00%, and the co-morbidity detection rate of the two was 5.52%，5.93%，5.76%，5.46%. The number of overweight,obesity and depression co-morbidity students in 2022 was 4 978 students, and the co-morbidity detection rates of the students were significantly different in terms of the school segments and the family structures ( χ 2=103.51, 99.90, P <0.01). Multivariate Logistic regression analysis showed that consuming sugar sweetened beverages or fried food ≥1 time/d, sometimes or never eat breakfast, watching computer or TV ≥2 h/d, and less than 1 h of moderate-to-vigorous physical activity on weekends were positively correlated with the occurrence of the co-morbidity of overweight,obesity and depression, with the value of OR ranging from 1.17 to 1.59 ( P <0.05). Eated fresh fruits or drinking milk and soy milk ≥1 time/d, outdoor activities ≥1 h/d, sleep ≥8 h/d, not smoking and not drinking alcohol were negatively correlated with the occurrence of comorbid overweight,obesity and depression, with the value of OR ranging from 0.47 to 0.92 ( P < 0.05). Conclusion The occurrence of overweight,obesity and depressive symptoms co-morbidity in students is associated with dietary, exercise and lifestyle behavior. Targeted measures should be taken to maintain students healthy weight and prevent the occurrence of depression from the aspects of diet, exercise and life habits.

Glioblastoma (GBM) is the most common and aggressive malignant brain tumor in adults and is poorly controlled. Previous studies have shown that both macrophages and angiogenesis play significant roles in GBM progression, and co-targeting of CSF1R and VEGFR is likely to be an effective strategy for GBM treatment. Therefore, this study developed a novel and selective inhibitor of CSF1R and VEGFR, SYHA1813, possessing potent antitumor activity against GBM. SYHA1813 inhibited VEGFR and CSF1R kinase activities with high potency and selectivity and thus blocked the cell viability of HUVECs and macrophages and exhibited anti-angiogenetic effects both in vitro and in vivo. SYHA1813 also displayed potent in vivo antitumor activity against GBM in immune-competent and immune-deficient mouse models, including temozolomide (TMZ) insensitive tumors. Notably, SYHA1813 could penetrate the blood-brain barrier (BBB) and prolong the survival time of mice bearing intracranial GBM xenografts. Moreover, SYHA1813 treatment resulted in a synergistic antitumor efficacy in combination with the PD-1 antibody. As a clinical proof of concept, SYHA1813 achieved confirmed responses in patients with recurrent GBM in an ongoing first-in-human phase I trial. The data of this study support the rationale for an ongoing phase I clinical study (ChiCTR2100045380).

Objective:To assess the safety and effectiveness of amphotericin B cholesteryl sulfate complex for injection in the context of empirical and diagnostic antifungal therapy for patients with hematological malignancies in addition to invasive fungal illness.Methods:This single-arm clinical study enrolled 30 patients who received empirical and diagnostic-driven antifungal therapy for hematological malignancies combined with invasive fungal disease. The primary endpoint was safety. Response rate, fever duration, and treatment completion rate were all considered secondary objectives.Results:30 participants were eventually enrolled in the study, and the treatment completion rate was 80.0% . Most adverse events were in grades 1-2. Infusion response was the most frequent adverse event (24/30, 80% ) . The overall response rate was 80.0% (24/30) . In 24 patients (80.0% ) , the fever persisted for 1 day.Conclusions:Treatment of invasive fungal illness in conjunction with hematological malignancies showed good efficacy and safety with amphotericin B cholesteryl sulfate complex for injection.