Alzheimer's disease (AD) is the most prevalent neurodegenerative disorder worldwide, causing dementia and affecting millions of individuals. One prominent characteristic in the brains of AD patients is glucose hypometabolism. In the context of galactose metabolism, intracellular glucose levels are heightened. Galactose mutarotase (GALM) plays a crucial role in maintaining normal galactose metabolism by catalyzing the conversion of β-D-galactose into α-D-galactose (α-D-G). The latter is then converted into glucose-6-phosphate, improving glucose metabolism levels. However, the involvement of GALM in AD progression is still unclear. In the present study, we found that the expression of GALM was significantly increased in AD patients and model mice. Genetic knockdown of GALM using adeno-associated virus did not change the expression of amyloid precursor protein (APP) and APP-cleaving enzymes including a disintegrin and metalloprotease 10 (ADAM10), β-site APP-cleaving enzyme 1 (BACE1), and presenilin-1 (PS1). Interestingly, genetic overexpression of GALM reduced APP and Aβ deposition by increasing the maturation of ADAM10, although it did not alter the expression of BACE1 and PS1. Further electrophysiological and behavioral experiments showed that GALM overexpression significantly ameliorated the deficits in hippocampal CA1 long-term potentiation (LTP) and spatial learning and memory in AD model mice. Importantly, direct α-D-G (20 mg/kg, i.p.) also inhibited Aβ deposition by increasing the maturation of ADAM10, thereby improving hippocampal CA1 LTP and spatial learning and memory in AD model mice. Taken together, our results indicate that GALM shifts APP processing towards α-cleavage, preventing Aβ generation by increasing the level of mature ADAM10. These findings indicate that GALM may be a potential therapeutic target for AD, and α-D-G has the potential to be used as a dietary supplement for the prevention and treatment of AD.
Animals ; ADAM10 Protein/metabolism* ; Alzheimer Disease/pathology* ; Amyloid Precursor Protein Secretases/metabolism* ; Disease Models, Animal ; Humans ; Mice ; Amyloid beta-Peptides/metabolism* ; Male ; Mice, Transgenic ; Membrane Proteins/metabolism* ; Cognitive Dysfunction/pathology* ; Mice, Inbred C57BL ; Amyloid beta-Protein Precursor/metabolism* ; Female ; Hippocampus/metabolism* ; Long-Term Potentiation/physiology*

Humans ; Amyloidosis ; Amyloid ; Cardiomyopathies

As the search for effective treatments for COVID-19 continues, the high mortality rate among critically ill patients in Intensive Care Units (ICU) presents a profound challenge. This study explores the potential benefits of traditional Chinese medicine (TCM) as a supplementary treatment for severe COVID-19. A total of 110 critically ill COVID-19 patients at the Intensive Care Unit (ICU) of Vulcan Hill Hospital between Feb., 2020, and April, 2020 (Wuhan, China) participated in this observational study. All patients received standard supportive care protocols, with a subset of 81 also receiving TCM as an adjunct treatment. Clinical characteristics during the treatment period and the clinical outcome of each patient were closely monitored and analysed. Our findings indicated that the TCM group exhibited a significantly lower mortality rate compared with the non-TCM group (16 of 81 vs 24 of 29; 0.3 vs 2.3 person/month). In the adjusted Cox proportional hazards models, TCM treatment was associated with improved survival odds (P < 0.001). Furthermore, the analysis also revealed that TCM treatment could partially mitigate inflammatory responses, as evidenced by the reduced levels of proinflammatory cytokines, and contribute to the recovery of multiple organic functions, thereby potentially increasing the survival rate of critically ill COVID-19 patients.
Humans ; COVID-19 ; Medicine, Chinese Traditional ; SARS-CoV-2 ; Critical Illness ; Treatment Outcome

Objective To observe the value of 18F-fluoro-dihydroxy-phenylalanine(18F-FDOPA)PET/CT for evaluating the efficacy of radiochemotherapy for advanced glioma.Methods Data of 84 patients with advanced glioma who received precision radiotherapy combined with synchronous chemotherapy were retrospectively analyzed.The patients were divided into effective group(complete remission+partial remission+stable disease,n=60)and ineffective group(progressive disease,n=24)according to the efficacy of radiochemotherapy.18F-FDOPA PET/CT metabolic parameters of tumors,including tumor metabolic tumor volume(MTV),maximum standard uptake value(SUVmax)and mean standard uptake value(SUVmean)were compared between groups,also before and after radiochemotherapy within groups.Spearman correlation analysis was used to observe the correlations of metabolic parameters and the efficacy of radiochemotherapy.Results After radiochemotherapy,MTV,SUVmax and SUVmean of tumors in effective group were lower than those of tumors in ineffective group(all P＜0.05).Significant differences of metabolic parameters were found before and after radiochemotherapy in effective group(all P＜0.05).MTV,SUVmax and SUVmean of advanced glioma were negatively correlated with the efficacy of radiochemotherapy(r=-0.63,-0.52,-0.50,P＜0.001,P=0.007,P=0.010).Conclusion 18F-FDOPA PET/CT was helpful for evaluating the efficacy of radiochemotherapy for advanced glioma.

Objective:To search, evaluate, and summarize the best evidence for difficult peripheral intravenous catheterization in children.Methods:Following the "6S" evidence pyramid model, literature related to the management of difficult peripheral veins in children was searched in both English and Chinese databases including UpToDate, BMJ Best Practice, National Guidelines Clearinghouse, the Joanna Briggs Institute Evidence-Based Health Care Database, PubMed, Medlive, SinoMed, CNKI, and Wanfang Database. The search period was from the establishment of the database to January 2023. Two researchers trained in systematic evidence-based nursing, independently evaluated the quality of included literature and extracted relevant evidence.Results:Five articles were included: two guidelines, two expert consensuses, and one systematic review. 19 best evidence were summarized, covering five aspects: difficult vein quality management, difficult vein assessment, difficult intravenous catheterization site and needle type selection, difficult intravenous catheterization auxiliary methods, and handling of failed difficult intravenous catheterization.Conclusions:This study summarizes the best evidence for difficult peripheral intravenous catheterization in children, demonstrating clinical nursing practicality. It provides evidence-based guidance for pediatric nursing staff performing difficult intravenous catheterization.

Objective To analyze the risk factors of intraoperative hypothermia in patients undergoing radical thyroidectomy under laparoscopy and to construct a nomogram prediction model. Methods A total of 336 patients who underwent laparoscopic radical thyroidectomy were selected as study subjects. According to intraoperative body temperature, they were divided into hypothermia group (195 cases) and normal temperature group (141 cases). The risk factors of intraoperative hypothermia in patients undergoing laparoscopic radical thyroidectomy were analyzed using the Logistic regression model. The nomogram prediction model was constructed using R software. The prediction performance of the nomogram prediction model was evaluated using the receiver operating characteristic (ROC) curve, calibration curve, and Hosmer-Lemeshow goodness-of-fit test. Results There were significant differences in age, intraoperative blood loss, amount of fluid infusion, and operation time between the two groups (P < 0.05). Multivariate Logistic regression analysis showed that age>60 years, intraoperative blood loss >60 mL, amount of fluid infusion>1 000 mL, and operation time>2.5 h were risk factors for intraoperative hypothermia in patients undergoing laparoscopic radical thyroidectomy (P < 0.05). A nomogram prediction model was constructed based on the four risk factors. The ROC curve showed that the area under the curve was 0.912 (95%CI, 0.884 to 0.941). The calibration curve and Hosmer-Lemeshow goodness-of-fit test showed that the slope of the calibration curve was close to 1 (χ²=9.140, P=0.243). Conclusion The nomogram prediction model based on age, intraoperative blood loss, amount of fluid infusion, and operation time has good predictive value for intraoperative hypothermia in patients undergoing laparoscopic radical thyroidectomy.

Objective:To determine S100A10 protein expression in psoriatic lesions, and to investigate its effect on psoriasis-like skin inflammation in imiquimod (IMQ) -induced mouse models.Methods:From January 2020 to June 2022, skin lesions were surgically collected from 28 patients with psoriasis in the Department of Dermatology, the First Affiliated Hospital of Xinxiang Medical University; normal skin tissues were collected from 18 healthy subjects in the Department of General Surgery and Department of Ophthalmology during the same period, and served as a control group. Immunohistochemical staining was performed to determine the S100A10 protein expression in skin lesions from psoriasis patients and normal skin tissues from healthy controls. Ten wild-type (WT) C57BL/6J female mice and 10 S100A10 -/- C57BL/6J female mice were selected to establish the IMQ-induced mouse models of psoriasis-like skin inflammation. Then, the mice were randomly divided into gene knock-out (KO) /IMQ group, WT/IMQ group, KO/vaseline (VAS) group, and WT/VAS group by using a random number table, and there were 5 mice in each group. The mice in the KO/IMQ group and WT/IMQ group were topically treated with IMQ cream (62.5 mg) on the shaved back daily to establish the mouse models of psoriasis-like skin inflammation, while the mice in the KO/VAS group and WT/VAS group were topically treated with vaseline cream (62.5 mg) daily, and both treatments lasted 7 consecutive days. Skin lesions on the back were observed daily. On day 7, the mice were sacrificed by cervical dislocation, and their dorsal skin tissues were excised. The IMQ-induced psoriasis-like skin inflammation was evaluated by the psoriasis area and severity index (PASI), pathological manifestations of skin lesions were observed by hematoxylin and eosin staining, the expression of S100A10 and Ki-67 in skin lesions was determined by immunohistochemical staining, the expression of STAT3, IL-17A and other cytokines was determined by Western blot analysis, and IL-17 mRNA expression was determined by real-time fluorescence-based quantitative PCR (qPCR). Statistical analysis was carried out by using the independent sample t-test, nonparametric U test, and chi-square test. Results:Immunohistochemical staining showed that the S100A10 protein expression was significantly lower in the psoriasis vulgaris lesions than in the normal control skin tissues ( Z = -3.47, P < 0.001). In the mouse models, the S100A10 protein expression was significantly lower in the skin lesions of mice in the WT/IMQ group than in the skin tissues of mice in the WT/VAS group ( t = 3.64, P = 0.007), and the Ki-67 expression was significantly higher in the KO/IMQ group than in the WT/IMQ group ( t = 2.97, P = 0.041). Additionally, the mice in the KO/IMQ group presented with more severe clinical manifestations such as scales and infiltration compared with those in the WT/IMQ group. Western blot analysis showed that the phosphorylated STAT3/STAT3 expression and IL-17A protein expression was significantly higher in the KO/IMQ group than in the WT/IMQ group ( t = 3.27, 3.48, P = 0.031, 0.025, respectively), and qPCR revealed that the IL-17A mRNA expression was also significantly higher in the KO/IMQ group than in the WT/IMQ group ( t = 2.73, P = 0.029) . Conclusion:S100A10 protein was underexpressed in the skin lesions of psoriasis patients, and the deletion of S100A10 protein aggravated IMQ-induced psoriasis-like skin inflammation in mice, possibly by upregulating STAT3 phosphorylation in the epidermis.

Humans ; Neoplasms, Second Primary/epidemiology* ; Neoplasms/epidemiology* ; Risk Factors ; Prognosis

Objective:To investigate the cognitive level of parents' participation in treatment activities during perioperative period and analyze its influencing factors.Methods:A total of 500 parents of perioperative children treated in Jinan Maternity and Child Care Hospital, Children's Hospital Affiliated to Shandong University and Central Hospital Affiliated to Shandong First Medical University from March to October 2021 were selected by the convenient sampling method. The Cognitive Assessment Scale of Inpatients' Participation in Treatment Activities, Caregiver Positive Perception Scale and Overall Health Literacy Scale were used to investigate the patients. A total of 500 questionnaires were sent out in this study and 487 were effectively received, with an effective recovery of 97.4%.Results:The total cognitive score of 487 perioperative Children's parents' participation in treatment activities was (62.25±7.39) , and the average score of each dimension was from high to low as patients' participation cognition, behavior management cognition and treatment cognition. Multiple linear regression analysis showed that parents' age, educational level, marital status, previous caregiving experience, caregivers' positive feelings, health literacy and hospital stay of children were the factors influencing the cognitive level of parents' participation in treatment activities during perioperative period.Conclusions:Parents' age, education level, marital status, previous nursing experience, positive feelings of caregivers, health literacy and length of hospital stay of children are factors that influence the cognitive level of parents' participation in treatment activities during perioperative period. Targeted intervention measures can be taken in the future to improve the cognitive level of parents' participation in treatment activities during perioperative period to promote the recovery of children.

China/epidemiology* ; Humans ; Pemphigoid, Bullous/epidemiology* ; Retrospective Studies