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*

BACKGROUND:Cryopreservation can better ensure the integrity of the vascular structure.How to reduce its immunogenicity to improve rejection after transplantation has attracted more and more attention. OBJECTIVE:To review the research progress of freezing treatment to reduce vascular immunogenicity after allogeneic vascular transplantation in order to provide a reference for clinical research. METHODS:A systematic search of Chinese and English databases CNKI,WanFang and PubMed,as well as online websites Baidu and Google Scholar since the establishment of the database has published literature on reducing vascular immunogenicity after allogeneic vascular transplantation.Keywords were"cardiovascular disease,endothelial cells,cryopreservation,blood vessel transplantation or vascular graft,immunogenicity,immune rejection,allograft or allogeneic transplantation or allograft transplantation and cryoprotectant".A total of 68 articles were included according to the inclusion and exclusion criteria. RESULTS AND CONCLUSION:(1)The review found that the rejection of allogeneic vascular transplantation can be reduced by improving the existing freezing technology,which mainly involves the selection of freezing and thawing methods and cryoprotectants.(2)The existing research suggests that the freeze-drying method is superior to the low-temperature cryopreservation,but due to the limited conditions,it is still dominated by low-temperature cryopreservation.Among them,vitrification cryopreservation,slow rewarming and the use of stainless steel and even silver-containing materials are better than programmed cryopreservation and rapid rewarming.(3)The combined selection of permeable and non-permeable cryoprotectants can further reduce the occurrence of rejection while reducing their toxicity.

Neuropathic pain is a chronic disease that severely afflicts the life and emotional status of patients, but currently available treatments are often ineffective. Novel therapeutic targets for the alleviation of neuropathic pain are urgently needed. Rhodojaponin VI, a grayanotoxin from Rhododendron molle, showed remarkable antinociceptive efficacy in models of neuropathic pain, but its biotargets and mechanisms are unknown. Given the reversible action of rhodojaponin VI and the narrow range over which its structure can be modified, we perforwmed thermal proteome profiling of the rat dorsal root ganglion to determine the protein target of rhodojaponin VI. N-Ethylmaleimide-sensitive fusion (NSF) was confirmed as the key target of rhodojaponin VI through biological and biophysical experiments. Functional validation showed for the first time that NSF facilitated trafficking of the Cav2.2 channel to induce an increase in Ca²⁺ current intensity, whereas rhodojaponin VI reversed the effects of NSF. In conclusion, rhodojaponin VI represents a unique class of analgesic natural products targeting Cav2.2 channels via NSF.

Objective:To assess the correlation between circulating chemerin and two indicators of renal function, estimated glomerular filtration rate (eGFR) and urine albumin creatinine ratio (UACR), in individuals with type 2 diabetes and to determine whether chemerin is an independent marker of early renal insufficiency.Methods:A total of 742 patients with type 2 diabetes were recruited into the cross-sectional community study. Basic information, anthropometric parameters, and biochemical parameters of these individuals were determined and collected, and serum chemerin level was measured using enzyme-linked immunosorbent assay.Results:Chemerin levels were significantly higher in the eGFR-impaired group compared with eGFR-normal group, and macroalbuminuria group compared to the normal or microalbuminuria groups. Spearman′ rank correlation analysis showed serum chemerin level was correlated with eGFR ( r=-0.25, P<0.001), UACR ( r=0.23, P<0.001) and some other biochemical indicators such as triglyceride. And univariate and multivariate logistic regression analyses revealed circulating chemerin was an independent risk factor for eGFR impairment or proteinuria after adjusting corresponding covariates. Receiver operating characteristic (ROC) curve analysis showed that the area under curve (AUC) of circulating chemerin for predicting early impaired eGFR in type 2 diabetes was 0.747, while the AUC of circulating chemerin for predicting macroalbuminuria in type 2 diabetes was 0.748. Conclusion:Circulating chemerin is associated with eGFR or UACR and may be a potential diagnostic marker for early renal insufficiency in type 2 diabetes.

Objective:To investigate the relationship between serum lipocalin-2 level and the risk of cardiovascular disease(CVD) in patients with type 2 diabetes.Methods:A total of 279 type 2 diabetic patients were enrolled in this study. Basic information and clinical data were collected. These patients were divided into CVD group and non-CVD group according to their cardiovascular disease status. Serum lipocalin-2 level was assessed by enzyme linked immunosorbent assay.Results:Compared to non-CVD group, serum lipocalin-2 level was significantly higher in CVD group( P<0.01). The Spearman correlation analysis showed that serum lipocalin-2 level was positively correlated with waist circumstance, diastolic blood pressure, uric acid, triglyceride, and HbA 1C( P<0.05), while negatively correlated with high density lipoprotein-cholesterol level( P<0.01). In addition, the univariate and multivariate logistic regression analysis revealed that serum lipocalin-2 was an independent risk factor for CVD( P<0.01)after adjustment for potential confounders. Moreover, receiver operating characteristic curve analysis demonstrated that the area under curve value of lipocalin-2 was 0.74, with the optimal cutoff value of lipocalin-2 66.84 ng/mL. Conclusion:Serum lipocalin-2 is closely associated with CVD in patients with type 2 diabetes, which might be considered as one of the predictors for CVD in type 2 diabetes mellitus.

Objective To explore the effect of nursing project management on reducing the incidence of perioperative pressure injury during laparoscopic pancreaticoduodenectomy. Methods The pressure ulcers conditions of 41 cases undergoing laparoscopic resection of pancreatic duodenal from December 2014 to July 2015 were investigated to find out the causes of the incidence of pressure ulcers, and we made pertinent measures for continuous quality improvement. From August 2015 to March 2016, 45 patients underwent laparoscopic pancreatoduodenectomy received nursing project management nursing care. Two groups of patients in terms of the incidence of pressure ulcers, pressure ulcer risk assessment accuracy and implementation rate of patient skin specification handover were compared. Results The incidences of laparoscopic resection of pancreatic duodenal ulcer decreased from 24.39% before the improvement of the project to 2.22%, the accuracy of nurse on the laparoscopic resection of pancreatic duodenal ulcer risk assessment increased from 75.60% to 95.55%, the implementation rate of patient skin specification handover increased from 82.93% to 97.78%, the differences were statistically significant (P<0.05). Conclusions The implementation of nursing program can reduce the incidence of pressure injury and improve the quality of nursing in perioperative period of laparoscopic pancreaticoduodenectomy.

Objective To summarize the experience of individualized treatment for hepatic artery thrombosis after liver transplantation.Methods From October 2002 to January 2015,5 patients with hepatic artery thrombosis after liver transplantation were treated with surgical exploration,interventional therapy or thrombolytic therapy according to the reasons.Results All the 5 patients were cured without serious complications.Conclusions There are many reasons for the occurrence of hepatic artery thrombosis after liver transplantation.Early diagnosis is the key point,and individual treatment highlights the concept of precision medicine.