Objective To explore the value of diffusion tensor imaging analysis index along the perivascular space(DTI-ALPS)for assessing age-related functional changes in glymphatic system(GS).Methods Totally 27 healthy subjects from Meizhou People's Hospital and 100 healthy subjects from neuroimaging informatics tools and resources collaborator database who underwent T1-weighted magnetization-prepared rapid gradient echo(T1-MPRAGE)and DTI scanning were retrospectively enrolled and divided into youth group(n=38),middle-aged group(n=57)and elderly group(n=32).Automated DTI-ALPS index analysis procedure was used to minimize manual errors and derive DTI-ALPS index.The general data,neuropsychological assessment results and DTI-ALPS indices were compared among groups.Spearman correlation analysis was performed to observe the relationships of DTI-ALPS index and age,gender,as well as neuropsychological scores.Results The average age in youth group,middle-aged group and elderly group was(28.5±5.8),(53.7±6.8)and(73.8±2.3)years,respectively.No significant difference of DTI-ALPS index was found between middle-aged group and elderly group(P＞0.05),which were both lower than that in youth group(both P＜0.05).DTI-ALPS index was weakly negatively correlated with age(rs=-0.340,P＜0.001),but not significantly correlated with gender nor neuropsychological assessment results(both P＞0.05).Conclusion DTI-ALPS index was negatively correlated with age in healthy individuals,hence having potential utility for assessing age-related functional changes in GS.

Type 2 diabetes (T2D) is an independent risk factor for cognitive impairment. The dysregulation of hypoxia inducible factor (HIF) signaling in T2D patients results in impaired adaptive responses to hypoxia, thereby accelerating the progression of complications. However, limited knowledge is available regarding its precise function in diabetes-associated cognitive impairment (DACI). Here, elevated HIF-1α levels were observed in brain endothelial cells (ECs) of db/db mice. Functionally, brain ECs-specific knockdown of H if1 a significantly ameliorated T2D-induced memory loss and neuronal damage. Glycolysis in brain ECs was inhibited in this process, as indicated by RNA-seq, leading to decreased hippocampal lactate production through reduced LDHA expression. Notably, T2D patients showed increased cerebrospinal fluid lactate levels, which were strongly associated with their cognitive dysfunction. Intrahippocampal injection of lactate accelerated cognitive dysfunction and impaired adult hippocampal neurogenesis (AHN) in db/db mice. Conversely, reducing hippocampal lactate levels through the intrahippocampal injection of oxamate delayed the onset of memory deficits. Furthermore, asiatic acid was discovered to protect db/db mice from cognitive impairment by decreasing brain endothelial HIF-1α expression and subsequently reducing hippocampal lactate-induced AHN damage. Overall, this study elucidates the inhibiting role played by endothelial HIF-1α-driven lactate in AHN and highlights a potential tactic of targeting HIF-1α in brain ECs for treating cognitive impairment.

Objective To investigate the function of glymphatic system in patients with mild traumatic brain injury via diffusion tensor imaging analysis along the perivascular space(DTI-ALPS)index and its relationship with clinical features.Methods The clinical and imaging data from 163 patients with mild traumatic brain injury were retrospectively collected,including 31 cases with MRI-negative findings and 132 cases with MRI-positive findings.In addition,29 healthy individuals underwent physical examinations were included as a control group.The differences in DTI-ALPS index and clinical features between mild traumatic brain injury and control group,as well as among subgroups of traumatic brain injury were analyzed.Results The DTI-ALPS index in patients with mild traumatic brain injury were significantly higher than those in control group(P＜0.05).Subgroup analysis showed that DTI-ALPS index of traumatic brain injury patients with MRI-negative findings and MRI-positive findings were all significantly higher than those of control group(P=0.023 and 0.004,respectively).Compared to control group,DTI-ALPS index in mild traumatic brain injury patients gradually increased with the progression of injury,and the difference was statistically significant(P=0.008).Conclusion Patients with mild traumatic brain injury exhibit increased functional activity of glymphatic system,as indicated by increased DTI-ALPS index,which further increase with the progression of injury.

Objective To investigate the function of glymphatic system in patients with mild traumatic brain injury via diffusion tensor imaging analysis along the perivascular space(DTI-ALPS)index and its relationship with clinical features.Methods The clinical and imaging data from 163 patients with mild traumatic brain injury were retrospectively collected,including 31 cases with MRI-negative findings and 132 cases with MRI-positive findings.In addition,29 healthy individuals underwent physical examinations were included as a control group.The differences in DTI-ALPS index and clinical features between mild traumatic brain injury and control group,as well as among subgroups of traumatic brain injury were analyzed.Results The DTI-ALPS index in patients with mild traumatic brain injury were significantly higher than those in control group(P＜0.05).Subgroup analysis showed that DTI-ALPS index of traumatic brain injury patients with MRI-negative findings and MRI-positive findings were all significantly higher than those of control group(P=0.023 and 0.004,respectively).Compared to control group,DTI-ALPS index in mild traumatic brain injury patients gradually increased with the progression of injury,and the difference was statistically significant(P=0.008).Conclusion Patients with mild traumatic brain injury exhibit increased functional activity of glymphatic system,as indicated by increased DTI-ALPS index,which further increase with the progression of injury.

Objective To explore the value of diffusion tensor imaging analysis index along the perivascular space(DTI-ALPS)for assessing age-related functional changes in glymphatic system(GS).Methods Totally 27 healthy subjects from Meizhou People's Hospital and 100 healthy subjects from neuroimaging informatics tools and resources collaborator database who underwent T1-weighted magnetization-prepared rapid gradient echo(T1-MPRAGE)and DTI scanning were retrospectively enrolled and divided into youth group(n=38),middle-aged group(n=57)and elderly group(n=32).Automated DTI-ALPS index analysis procedure was used to minimize manual errors and derive DTI-ALPS index.The general data,neuropsychological assessment results and DTI-ALPS indices were compared among groups.Spearman correlation analysis was performed to observe the relationships of DTI-ALPS index and age,gender,as well as neuropsychological scores.Results The average age in youth group,middle-aged group and elderly group was(28.5±5.8),(53.7±6.8)and(73.8±2.3)years,respectively.No significant difference of DTI-ALPS index was found between middle-aged group and elderly group(P＞0.05),which were both lower than that in youth group(both P＜0.05).DTI-ALPS index was weakly negatively correlated with age(rs=-0.340,P＜0.001),but not significantly correlated with gender nor neuropsychological assessment results(both P＞0.05).Conclusion DTI-ALPS index was negatively correlated with age in healthy individuals,hence having potential utility for assessing age-related functional changes in GS.

Objective To investigate the difference of CT features of gastrointestinal stromal tumors(GIST),neurogenic tumors,and leiomyomas in stomach.Methods A retrospective analysis was performed on clinical and CT features from 312 cases of GIST,21 cases of neurogenic tumors,and 35 cases of leiomyomas in stomach.Results GIST were most commonly found in the body of stomach and exhibited large tumor sizes and late onset.CT showed GIST predominantly showed intraluminal and mixed growth pattern with irregular or round shapes and uneven density,and cystic degeneration and calcification were frequently observed.The CT values of GIST in the arterial phase and the degree of arterial enhancement were higher,with light to moderate arterial phase enhancement and moderate to marked venous phase enhancement.Gastric leiomyomas had smaller tumor sizes and presented mainly in the cardia,gastric fundus,and lesser curvature of gastric body.CT showed the intraluminal growth pattern,primarily in round shapes with uniform density,lower incidence of cystic degeneration and calcification,both the arterial and venous phase CT values and the extent of enhancement in these phases were lower,showed no or slight enhancement during the arterial phase and light to moderate enhancement during the venous phase.Gastric neurogenic tumors were predominantly located in the gastric body and antrum.CT showed the tumors demonstrated extraluminal and mixed growth patterns,most with oval-shaped appearace,uniform density and the venous phase CT values and the degree of enhancement were higher,with light to moderate arterial enhancement and moderate to marked venous enhancement.Conclusion GIST,neurogenic tumors,and leiomyomas in stomach can be differentiated based on their distinct CT features.Accurate recognition of these features aids in the differential diagnosis of these kinds of tumors.

Objective To analyze the distribution of common allergens in children with allergic rhinitis(AR)in Hangzhou,and to provide reference for its prevention and treatment.Methods From January 2020 to December 2022,13 521 children who were diagnosed with AR and underwent in vitro serum specific immunoglobulin E(sIgE)detection in Affiliated Hangzhou First People's Hospital,School of Medicine,Westlake University were selected as the research objects.The positive rates of allergens in children with AR of different genders,ages and seasons were compared.Results Among 13 521 children,the positive rate of sIgE was 54.49%(7367/13 521),of which 64.82%were allergic to only one allergen.Among the 19 common allergens,the top three overall positive rates were household dust mite(44.27%),milk(14.62%),and mixed grass(4.82%).The positive rates of allergens of house dust mites,cat hair dander,mulberry,mold combination,tree pollen combination,amaranth,cockroach,milk,shrimp,crab,pineapple,shellfish and mango in male children were significantly higher than those in female children(P<0.05).The positive rates of allergens of house dust mite,mixed grass,cat hair dander,mulberry,mold combination,egg white,shrimp,crab,pineapple,cashew nuts and shellfish in different age groups were statistically significant(P<0.05).July and August were the two months with the highest allergen positive rate.The allergen positive rates of house dust mite,dog and cat hair dander were the highest in summer,and the allergen positive rate of plants was consistent with the flowering season.The sIgE concentration of house dust mite(77.87%)was mainly grade 3 and above.The sIgE concentration of other allergens was mainly grade 1 and 2.Conclusion Dust mites and milk are the most common allergens in children with AR in Hangzhou,and the distribution of allergens varies with gender,age and season.Allergen detection can provide a more accurate plan for the diagnosis,prevention and treatment of AR.

Polyphyllin Ⅰ(PPⅠ)and polyphyllin Ⅱ(PⅡ)are the main active substances in the Paris polyphylla.However,liver toxicity of these compounds has impeded their clinical application and the potential hepatotoxicity mechanisms remain to be elucidated.In this work,we found that PPⅠ and PⅡ exposure could induce significant hepatotoxicity in human liver cell line L-02 and zebrafish in a dose-dependent manner.The results of the proteomic analysis in L-02 cells and transcriptome in zebrafish indicated that the hepa-totoxicity of PPⅡ and PⅡwas associated with the cholesterol biosynthetic pathway disorders,which were alleviated by the cholesterol biosynthesis inhibitor lovastatin.Additionally,3-hydroxy-3-methy-lglutaryl CoA reductase(HMGCR)and squalene epoxidase(SQLE),the two rate-limiting enzymes in the choles-terol synthesis,selected as the potential targets,were confirmed by the molecular docking,the over-expression,and knockdown of HMGCR or SQLE with siRNA.Finally,the pull-down and surface plasmon resonance technology revealed that PPⅠ could directly bind with SQLE but not with HMGCR.Collectively,these data demonstrated that PPⅠ-induced hepatotoxicity resulted from the direct binding with SQLE protein and impaired the sterol-regulatory element binding protein 2/HMGCR/SQLE/lanosterol synthase pathways,thus disturbing the cholesterol biosynthesis pathway.The findings of this research can contribute to a better understanding of the key role of SQLE as a potential target in drug-induced hepatotoxicity and provide a therapeutic strategy for the prevention of drug toxic effects with similar structures in the future.

This study investigated the anti-angiogenic activities of two diarylheptanoids, together with a structure analogue, curcumin. The activity and toxicity of these three compounds were compared using transgenic zebrafish as in vivo model and human umbilical vein endothelial cell(HUVEC)as in vitro model. Anti-angiogenic index(AI)was used as the ratio between LC50 and EC50. The results suggested that in both in vitro and in vivo assay, curcumin exerted the most potent anti-angiogenic effect but with lowest toxicity among these compounds; Yakuchinone A was the second potent; Yakuchinone B has the lowest activity but with the highest toxicity in all three compounds. Taken together, curcumin was the best angiogenic inhibitor in these three diarylheptanoids.