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*

Pyoderma gangrenosum (PG) is an autoinflammatory disorder that belongs to neutrophilic dermatosis. It often presents as a rapidly developing painful cutaneous ulcer, which is characterized by disruption of the border and peripheral erythema. The exact etiology of PG remains unknown, but it is often associated with various immune-mediated disorders. PG is associated with a wide range of underlying disorders, with inflammatory bowel disease, hematological diseases and malignancies, autoinflammatory syndromes and inflammatory arthritis as the most common underlying disorders. This review summarizes PG-related systemic complications.

Objective To compare the effects of Tripterygium wilfordii polyglycosides,cyclophosphamide,and cisplatin on the establishment of a mouse model of diminished ovarian reserve(DOR).Methods Mice were randomly divided into the following treatment groups:control(Ctrl),Tripterygium wilfordii polyglycosides(TWP),cyclophosphamide(CTX),and cisplatin(DDP).Mice in the TWP group received a 50 mg/kg suspension of Tripterygium wilfordii polyglycosides by gavage for 14 days,mice in the CTX group received a 20 mg/kg cyclophosphamide suspension by intraperitoneal injection for 14 days,and mice in the DDP group received a 1.5 mg/kg cisplatin solution by intraperitoneal injection for 14 days.The body weight,uterine index,and ovarian index were recorded,the estrous cycle was monitored using the vaginal smear method,and the levels of anti-Mullerian hormone(AMH),estradiol(E2),follicle stimulating hormone(FSH),and luteinizing hormone(LH)were detected using ELISA.Hematoxylin and eosin staining was used to detect ovarian follicle development.The rates of oocyte maturation and fertility were analyzed.Results The three treatment groups of mice all showed the following:significantly decreased body weight and ovarian index(P＜0.05);apparent disorder of the estrous cycle;significantly decreased levels of AMH and E2(P＜0.05);decreased and increased rates of developing follicles and atretic follicles,respectively(P＜0.05);and significantly decreased rates of oocyte maturation,pregnancy,and live birth(P＜0.05).Conclusions DOR mouse models were successfully constructed using Tripterygium wilfordii polyglycosides,cyclophosphamide,or cisplatin,as evidenced by decreased body weight and ovarian index,disordered estrous cycle and hormones,and DOR function,resulting in reduced rates of oocyte maturation,pregnancy,and total number of live births.These DOR effects were most appropriate in the cyclophosphamide group.

Objective To summarize and analyze the CT or MRI imaging signs of ovarian torsion in children.Methods The CT or MRI data of 24 children surgically confirmed ovarian torsion were analyzed retrospectively,focusing on imaging signs such as ovarian position,size,the relationship with surrounding appendages and uterus.Results In this group of cases,8 cases underwent CT examination and 16 cases underwent MRI examination.Among the age of children,12 cases were in newborns,and 6 cases were in school-age and adolescent children respectively.It was more common in newborns and children aged 10-12 years old.Among the 24 patients,3 cases(12.5％)had primary ovarian torsion,all of which were adolescent children;21 cases(87.5％)had secondary ovarian torsion,with all torsions in the neonatal period were secondary ovarian torsion.Among secondary ovarian torsion,there were 7 cases(33.3％)of ovarian teratoma with torsion,12 cases(57.1％)of simple ovarian cysts,1 case(4.7％)of ovarian serous cystadenoma,and 1 case(4.7％)of ovarian mucinous cyst.Torsion occurred in 9 cases(37.5％)of the left ovary and 15 cases(62.5％)of the right ovary,with right ovarian torsion being more common.Imaging signs included varying degrees of enlargement of the ovaries on the ipsilateral side of the torsion,with 14 cases(58.3％)of ovarian masses had a maximum diameter≥5 cm,and 3-5 cm being more common in the neonatal period.There were 11 cases(45.8％)with the pedicle sign/vortex sign on the ipsilateral side of the torsion,9 cases(37.5％)with mass and hemorrhage,4 cases(16.7％)with mass displacement to the midline or uterine displacement to the ipsilateral side,and 3 cases(12.5％)of the ovarian follicle outward migration showed fruit bowl sign.Conclusion Secondary ovarian torsion is relatively common in children,with distinctive imaging manifestations.Especially when neonatal ovarian cysts show hemorrhagic signals should be alert to the risk of ovarian torsion.CT and MRI examinations can provide a powerful reference for the clinical diagnosis of ovarian torsion in children.

Pyoderma gangrenosum (PG) is an autoinflammatory disorder that belongs to neutrophilic dermatosis. It often presents as a rapidly developing painful cutaneous ulcer, which is characterized by disruption of the border and peripheral erythema. The exact etiology of PG remains unknown, but it is often associated with various immune-mediated disorders. PG is associated with a wide range of underlying disorders, with inflammatory bowel disease, hematological diseases and malignancies, autoinflammatory syndromes and inflammatory arthritis as the most common underlying disorders. This review summarizes PG-related systemic complications.

Objective To compare the effects of Tripterygium wilfordii polyglycosides,cyclophosphamide,and cisplatin on the establishment of a mouse model of diminished ovarian reserve(DOR).Methods Mice were randomly divided into the following treatment groups:control(Ctrl),Tripterygium wilfordii polyglycosides(TWP),cyclophosphamide(CTX),and cisplatin(DDP).Mice in the TWP group received a 50 mg/kg suspension of Tripterygium wilfordii polyglycosides by gavage for 14 days,mice in the CTX group received a 20 mg/kg cyclophosphamide suspension by intraperitoneal injection for 14 days,and mice in the DDP group received a 1.5 mg/kg cisplatin solution by intraperitoneal injection for 14 days.The body weight,uterine index,and ovarian index were recorded,the estrous cycle was monitored using the vaginal smear method,and the levels of anti-Mullerian hormone(AMH),estradiol(E2),follicle stimulating hormone(FSH),and luteinizing hormone(LH)were detected using ELISA.Hematoxylin and eosin staining was used to detect ovarian follicle development.The rates of oocyte maturation and fertility were analyzed.Results The three treatment groups of mice all showed the following:significantly decreased body weight and ovarian index(P＜0.05);apparent disorder of the estrous cycle;significantly decreased levels of AMH and E2(P＜0.05);decreased and increased rates of developing follicles and atretic follicles,respectively(P＜0.05);and significantly decreased rates of oocyte maturation,pregnancy,and live birth(P＜0.05).Conclusions DOR mouse models were successfully constructed using Tripterygium wilfordii polyglycosides,cyclophosphamide,or cisplatin,as evidenced by decreased body weight and ovarian index,disordered estrous cycle and hormones,and DOR function,resulting in reduced rates of oocyte maturation,pregnancy,and total number of live births.These DOR effects were most appropriate in the cyclophosphamide group.

Objective To summarize and analyze the CT or MRI imaging signs of ovarian torsion in children.Methods The CT or MRI data of 24 children surgically confirmed ovarian torsion were analyzed retrospectively,focusing on imaging signs such as ovarian position,size,the relationship with surrounding appendages and uterus.Results In this group of cases,8 cases underwent CT examination and 16 cases underwent MRI examination.Among the age of children,12 cases were in newborns,and 6 cases were in school-age and adolescent children respectively.It was more common in newborns and children aged 10-12 years old.Among the 24 patients,3 cases(12.5％)had primary ovarian torsion,all of which were adolescent children;21 cases(87.5％)had secondary ovarian torsion,with all torsions in the neonatal period were secondary ovarian torsion.Among secondary ovarian torsion,there were 7 cases(33.3％)of ovarian teratoma with torsion,12 cases(57.1％)of simple ovarian cysts,1 case(4.7％)of ovarian serous cystadenoma,and 1 case(4.7％)of ovarian mucinous cyst.Torsion occurred in 9 cases(37.5％)of the left ovary and 15 cases(62.5％)of the right ovary,with right ovarian torsion being more common.Imaging signs included varying degrees of enlargement of the ovaries on the ipsilateral side of the torsion,with 14 cases(58.3％)of ovarian masses had a maximum diameter≥5 cm,and 3-5 cm being more common in the neonatal period.There were 11 cases(45.8％)with the pedicle sign/vortex sign on the ipsilateral side of the torsion,9 cases(37.5％)with mass and hemorrhage,4 cases(16.7％)with mass displacement to the midline or uterine displacement to the ipsilateral side,and 3 cases(12.5％)of the ovarian follicle outward migration showed fruit bowl sign.Conclusion Secondary ovarian torsion is relatively common in children,with distinctive imaging manifestations.Especially when neonatal ovarian cysts show hemorrhagic signals should be alert to the risk of ovarian torsion.CT and MRI examinations can provide a powerful reference for the clinical diagnosis of ovarian torsion in children.

Objective To investigate the mechanism of Guizhi Tongluo Tablets(GZTLP)on improving atherosclerosis in APOE knockout mice by regulating neutrophil extracellular trapping nets(NETs).Methods After modeling,24 APOE knockout mice aged 8 weeks were randomly divided into 4 groups:GZTLP high-dose group,low-dose group,model control group and normal control group,with 6 mice in each group.GZTLP was given 1.87 mg·g-1 and 0.47 mg·g-1 intragastric administration in high-dose group and low-dose group,respectively.The normal control group and model control group were given 0.9%sodium chloride solution intragastric administration for 6 weeks,and the lipid plaque deposition in aorta was observed by gross oil red O staining.Lipid deposition in aortic root was observed by oil red O staining.The pathological changes of lipid plaques in aortic root were observed by HE staining.The levels of interleukin-1β(IL-1β)and tumor necrosis factor α(TNF-α)in peripheral blood of mice were detected by enzyme-linked immunosorbent assay(ELISA).The expression of lymphocyte antigen 6G(Ly6G),myeloperoxidase(MPO)and citrulinated histone(Cit-H3)in plaques of the aortic arch and the colocalization of Ly6G,MPO and Cit-H3 were detected by immunofluorescence assay.Results Compared with the normal control group,the aorta of mice in the model control group showed serious lipid plaque deposition,morphological damage,and a large number of inflammatory cells infiltration,the contents of serum inflammatory factors IL-1β and TNF-α were increased,and the protein expressions of Ly6G,Cit-H3 and MPO were significantly increased.Compared with model control group,GZTLP group reduced the amount of lipid plaque deposition in aorta,the arrangement of aortic cells was more regular,the inflammatory cell infiltration was improved,and the contents of serum inflammatory factors IL-1β and TNF-α were significantly decreased(P<0.05).The colocalization and the protein expression of Ly6G,MPO and Cit-H3 were significantly decreased in aortic tissues(P<0.01).Conclusions GZTLP can improve atherosclerosis,and its mechanism may be related to the inhibition of neutrophil extracellular trapping nets.

Objective To explore the correlation between the total burden of cerebral small vessel disease and poor prognosis of branch atheromatous disease(BAD)in elderly patients.Methods A total of 114 BAD patients admitted to Shanghai Eighth People's Hospital between January 2021 and March 2023 were enrolled,and according to mRS score at 90 d after onset,they were divided into a good prognosis group(mRS score ≤2,67 cases)and a poor prognosis group(mRS score＞2,47 cases).The clinical and imaging characteristics were analyzed,and the relationship between total cerebral small vessel disease burden and clinical prognosis of BAD was investigated using lo-gistic regression analysis.ROC curve analysis was used to determine the threshold of the total cere-bral small vessel disease burden for predicting adverse outcomes and to evaluate its sensitivity and specificity.Results The good prognosis group had younger age,smaller proportion of diabetes,lower SBP,NIHSS score at admission and white matter hyperintensities,and reduced ratio of cerebral microbleeds than the poor prognosis group(P＜0.05,P＜0.01).Statistical difference was observed in the total cerebral small vessel disease burden between the two groups(P＜0.01).Binary logistic regression analysis showed that the total cerebral small vessel disease burden score and NIHSS score at admission were independent predicators of poor prognosis in BAD patients(OR=3.350,95％CI:1.439-7.798,P=0.005;OR=2.814,95％CI:1.586-4.993,P=0.001).ROC curve analysis indicated that the total cerebral small vessel disease burden had a cut-off val-ue of 1.5,and the sensitivity and specificity for predicting poor prognosis was 63.8％and 86.6％,respectively,for BAD patients.Conclusion The total cerebral small vessel disease burden is an in-dependent predictor for poor prognosis of BAD patients.

Objective:To study the influence of different feeding patterns on mother-to-child transmission (MTCT) of hepatitis B virus (HBV) in pregnant women with high viral loads who received antiviral medication during pregnancy to the day of delivery.Methods:This prospective cohort study was conducted in Beijing You'an Hospital. From January 1, 2019, to March 31, 2020, and 574 pregnant women with positive hepatitis B surface antigen (HBsAg) and HBV DNA>2×10 5 IU/ml were enrolled. All participants received tenofovir, telbivudine, lamivudine, or propofol tenofovir from 24-28 weeks of gestation and discontinued on the day of delivery, and their neonates were postnatally given routine passive-active immunoprophylaxis. Based on the feeding patterns, the subjects were divided into three groups: breastfeeding ( n=257), bottle-feeding ( n=241) and mixed feeding groups ( n=76). The follow-up data were obtained from liver functions and HBV DNA level of the mothers at 6-8 weeks postpartum and HBV serological markers of infants at 7-12 months. One-way ANOVA, Student-Newman-Keuls, Chi-square test or Fisher exact test, and repeated measures ANOVA were used to analyze the data. Results:The average maternal HBV DNA levels before antiviral treatment did not differ significantly between the three groups [(7.90±0.67), (7.82±0.70), (7.83±0.70) log 10 IU/ml, F=0.912, P>0.05]. HBV DNA level before delivery in the mixed feeding group was slightly lower than that in the breastfeeding and bottle-feeding group [(3.87 ±1.08) vs (4.21±1.17) and (4.30±1.28) log 10 IU/ml, q= 3.052 and 3.831, both P<0.05], while the comparison between the latter two groups showed no significant differences ( P>0.05). After delivery, HBV DNA level in the bottle-feeding group was slightly lower than that in the breastfeeding group [(7.42±0.93) vs (7.69±0.90) log 10 IU/ml, q=4.583, P<0.05]. Among 580 infants (including six pairs of twins), only one bottle-fed infant (0.4%, 1/243) was infected with HBV through MTCT, and none in the breastfeeding or mixed feeding group ( P=0.553). Conclusions:For pregnant women with high viral loads of HBV who have received antiviral medication during pregnancy, although HBV DNA level will rebound after discontinuation upon delivery, breastfeeding is recommended considering it does not increase the risk of MTCT.