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*

OBJECTIVE: To compare the effectiveness of lower extremity axial distractor (LEAD) and traction table assisted closed reduction and intramedullary nail fixation in treatment of femoral subtrochanteric fracture. METHODS: The clinical data of 117 patients with subtrochanteric fracture of femur treated by closed reduction and intramedullary nail fixation between May 2012 and May 2022 who met the selection criteria were retrospectively analyzed. According to the auxiliary reduction tools used during operation, the patients were divided into LEAD group (62 cases with LEAD reduction) and traction table group (55 cases with traction table reduction). There was no significant difference in baseline data, such as gender, age, injured side, cause of injury, fracture Seinsheimer classification, time from injury to operation, and preoperative visual analogue scale (VAS) score, between the two groups ( P>0.05). Total incision length, operation time, intraoperative blood loss, fluoroscopy frequency, closed reduction rate, fracture reduction quality, fracture healing time, weight-bearing activity time, and incidence of complications, as well as hip flexion and extension range of motion (ROM), Harris score, and VAS score at 1 month and 6 months after operation and last follow-up were recorded and compared between the two groups. RESULTS: There were 14 cases in the LEAD group from closed reduction to limited open reduction, and 43 cases in the traction table group. The incisions in the LEAD group healed by first intention, and no complication such as nerve and vascular injury occurred during operation. In the traction table group, 3 cases had perineal crush injury, which recovered spontaneously in 1 week. The total incision length, operation time, intraoperative blood loss, fluoroscopy frequency, and closed reduction rate in the LEAD group were significantly better than those in the traction table group ( P<0.05). There was no significant difference in the quality of fracture reduction between the two groups ( P>0.05). Patients in both groups were followed up 12-44 months, with an average of 15.8 months. In the LEAD group, 1 patient had delayed fracture union at 6 months after operation, 1 patient had nonunion at 3 years after operation, and 1 patient had incision sinus pus flow at 10 months after operation. In the traction table group, there was 1 patient with fracture nonunion at 15 months after operation. X-ray films of the other patients in the two groups showed that the internal fixator was fixed firmly without loosening and the fractures healed. There was no significant difference in fracture healing time, weight bearing activity time, incidence of complications, and postoperative hip flexion and extension ROM, Harris score, and VAS score at different time points between the two groups ( P>0.05). CONCLUSION For femoral subtrochanteric fracture treated by close reduction and intramedullary nail fixation, compared with traction table, LEAD assisted fracture reduction can significantly shorten the operation time, reduce intraoperative blood loss and fluoroscopy frequency, reduce incision length, effectively improve the success rate of closed reduction, and avoid complications related to traction table reduction. It provides a new method for good reduction of femoral subtrochanteric fracture.
Humans ; Fracture Fixation, Intramedullary ; Bone Nails ; Traction ; Blood Loss, Surgical/prevention & control* ; Retrospective Studies ; Treatment Outcome ; Femoral Fractures ; Hip Fractures/surgery* ; Lower Extremity ; Surgical Wound ; Fracture Fixation, Internal

Xanthocillin is a unique natural product with an isonitrile group and shows remarkable antibacterial activity. In this study, the genome of an endophytic fungus Penicillium chrysogenum MT-40 isolated from Huperzia serrata was sequenced, and the gene clusters with the potential to synthesize xanthocillin analogues were mined by local BLAST and various bioinformatics analysis tools. As a result, a biosynthetic gene cluster (named for) responsible for the biosynthesis of xanthocillin analogues was identified by further heterologous expression of the key genes in Aspergillus oryzae NSAR1. Specifically, the ForB catalyzes the synthesis of 2-formamido-3-(4-hydroxyphenyl) acrylic acid, and the ForG catalyzes the dimerization of 2-formamido-3-(4-hydroxyphenyl) acrylic acid to produce the xanthocillin analogue N, N'-(1, 4-bis (4-hydroxyphenyl) buta-1, 3-diene-2, 3-diyl) diformamide. The results reported here provide a reference for further discovery of xanthocillin analogues from fungi.
Penicillium chrysogenum/genetics* ; Huperzia/microbiology* ; Acrylates ; Multigene Family

Objective:To explore the safety and efficiency of percutaneous coronary intervention (PCI) in maintenance hemodialysis patients combined with non-ST-segment elevation acute coronary syndrome (NSTE-ACS).Methods:The clinical data of 52 maintenance hemodialysis patients combined with NSTE-ACS from January 2010 to January 2015 in Dalian Central Hospital were retrospectively analyzed. Among of them, 25 patients were treated with common drugs (control group), and 27 patients were treated with common drugs combined with PCI (PCI group). The major adverse cardiac events (MACE) duration of hospital stay were record, including hemorrhage, malignant arrhythmia, new heart failure or aggravation, stroke and all-cause death. The dialysis complications within 1 month after treatment were recorded, including hypotension, arrhythmia, heart failure and angina pectoris. The patients were followed up for 12 months, the MACE 1, 6 and 12 months after treatment were recorded, including angina pectoris, heart failure and cardiac death.Results:Duration of hospital stay, the incidences of malignant arrhythmia and new heart failure or aggravation in PCI group were significantly lower than those in control group: 18.5% (5/27) vs. 44.0% (11/25) and 7.4% (2/27) vs. 32.0% (8/25), and there were statistical differences ( P<0.05); there were no statistical difference in the incidences of hemorrhage, stroke and all-cause death between the two groups ( P>0.05). The incidences of dialysis complications such as hypotension, arrhythmia, heart failure and angina pectoris within 1 month after treatment in PCI group were significantly lower than those in control group: 24.0% (6/25) vs. 56.5% (13/23), 16.0% (4/25) vs. 43.5% (10/23), 12.0% (3/25) vs. 47.8% (11/23) and 24.0% (6/25) vs. 52.2% (12/23), and there were statistical differences ( P<0.05 or <0.01). The follow-up results showed that the incidences of angina pectoris and heart failure 1, 6 and 12 months after treatment in PCI group were significantly lower than those in control group, angina pectoris: 28.0% (7/25) vs. 65.2% (15/23), 29.2% (7/24) vs. 76.2% (16/21) and 43.5% (10/23) vs. 17/17, heart failure: 16.0% (4/25) vs. 43.5% (10/23), 8.3% (2/24) vs. 33.3% (7/21) and 21.7% (5/23) vs. 10/17, and there were statistical differences ( P<0.05 or <0.01); there was no statistical difference in the incidence of cardiac death 1 and 6 months after treatment between two groups ( P>0.05), the incidence of cardiogenic death 12 months after treatment in PCI group was significantly lower than that in control group: 8.6% (2/23) vs. 9/17, and there was statistical difference ( P<0.01). Conclusions:PCI is safe and effective for maintenance hemodialysis patients combined with NSTE-ACS.

Objective:To investigate the prevalence and risk factors of depression in patients with acute ST-segment elevation myocardial infarction(STEMI) after percutaneous coronary intervention(PCI).Methods:From January 2019 to December 2019, 205 patients with STEMI who underwent PCI were selected randomly in Department of Cardiology of Heilongjiang Provincial Hospital.And 200 health examined people from our hospital at the same time were selected as health control group.The Zung self-rating depression scale(SDS) was used to score the depression in STEMI patients one week after PCI.The social demographic data were investigated, including age, gender, education status, place of residence, medical payments, monthly income, marital status, smoking history, drinking history, diabetic history, cardiovascular and cerebrovascular diseases history.The clinical indicators were measured, including height, weight, waist circumference(WC), hip circumference(HC), body mass index(BMI), waist-hip rate(WHR), fasting plasma glucose(FPG), fasting serum insulin(FINS), homeostasis model assessment-insulin resistance index(HOMA-IR), serum total cholesterol(TC), total triglyceride(TG), low density lipoprotein-C(LDL-C), high density lipoprotein-C, (HDL-C), systolic blood pressure(SBP) and diastolic blood pressure(DBP).Results:The prevalence of depression in the STEMI group was obviously higher than that in the control group(17.07% vs.9.50%, χ 2=5.025, P=0.025). There was statistically significant difference in the severity of depression between the two groups(χ 2=8.360, P=0.039). Multivariate Logistic regression analysis showed that the risk factors for depression in order of OR values were FPG, gender(female), age(65 or old), BMI, monthly income(<5 000 RMB), HOMA-IR, self-paying for medical services ( OR=1.894, 1.812, 1.545, 1.428, 1.335, 1.285, 1.202). Conclusion:The prevalence of depression in STEMI patients after PCI is increased.The risk factors for depression include female, old age, obesity, low income, insulin resistance and self-paying for medical services.

Spinal cord injury is a catastrophic injury causing lifelong severe disabilities, and poses a great burden to the individuals, families and society. In order to promote the standardization in treatment of traumatic spinal cord injury, the consensus on the evaluation, treatment and rehabilitation of traumatic spinal cord injury was suggested by experts, who came from authoritative multicenter in China. The expert consensus, which formed a standardization process from the first aid clinical treatment to rehabilitation of spinal cord injury, shall give a better practical guide for clinic and rehabilitation physicians.

Objective To introduce a novel femoral distractor which is applied in close reduction and internal fixation (CRIF) with antegrade intramedullary nail for femoral shaft fractures.Methods From September 2010 to March 2015,85 patients with femoral shaft fracture were treated by CRIF with antegrade intramedullary nail in which our self-designed novel distractor was used.They were 64 males and 21 females,with an average age of 36.6 years.By AO classification,we had 32 cases of type 32-A,40 cases of type 32-B,and 13 cases of type 32-C.The intervals between injury and surgery averaged 7.5 days (range,from 1 to 16 days).The fracture was located at the upper shaft in 26 cases,at the middle shaft in 57 cases,at the middle shaft and ipsilateral neck in one,and at the lower shaft and ipsilateral intertrochanteric site in one.Their operation time,intraoperative blood loss,intra-and post-operative complications,and fracture union time were recorded and analyzed.Results Successful close reduction was achieved in all the 85 patients with no iatrogenic injury to major vessels or nerves.Operation time averaged 105.5 minutes;time for X-ray exposure averaged 25.8 seconds;intraoperative blood loss averaged 209.2 mL.The 85 patients received follow-ups from 8 to 24 months (mean,16.3 months).Fracture union was achieved in 83 cases after an average duration of 7.8 weeks (range,from 4 to 12 weeks),but nonunion occurred in 2 cases.One-year follow-ups revealed recovery of normal function of the affected knee in all,with no limb shortening ＞ 10 mm,rotational angulation ＞ 15°,or lateral or anteroposterior angulation ＞ 10°.No incision infection,deep vein thrombosis or pulmonary embolism happened during the entire follow-up.Conclusion Our self-designed novel distractor can facilitate CRIF with antegrade intramedullary nail for femoral shaft fractures,and avoid the complications and inconvenience associated with a traction table.

Two­photon microscopy is a new technique which combines laser scanning con-focal microscopy and two-photon excitation technique. Two-photon fluorescence microscopy has the advantages of little light damage, small bleaching area, strong penetrability, high resolution, high fluorescence collection efficiency, and high image contrast. It is suitable for dark field imaging and multi-labeled compound measurement, and has been widely used in small animals in vivo optical imaging, such as research for tumour, gene therapy, stem cells, drug development, spinal cord injury, etc.

Objective To survey the attitudes and acceptance level of upper limb function reconstruction in patients with cervical spinal cord injury and analyze the related factors. Methods From October, 2013 to June, 2014, a total of 104 patients with cervical spinal cord injury were surveyed with self-designed questionnaire. Results There were 81 valid questionnaires, in which 3 patients (3.7%) heard of upper-extremity reconstructive surgery. The patients longed for upper limb function improvement most. After they had a understanding of the surgery, their willingness improved (P<0.01). No significant difference was found in the satisfaction degree and operation willingness between different hand function groups (P>0.05). The patients focused on the operation cost, the operation risk, recovery time after operation and the satisfaction of assistive devices, however, they were not correlated with the willingness of upper limb function reconstruction (P>0.05). Conclusion There is a clear gap between strong desire for functional improvement of upper limb and surgery awareness. It is important to communicate upper limb among patients with cervical spinal cord injury.