Moyamoya vasculopathy (MMV) refers to a chronic cerebrovascular disease characterized by progressive stenosis or occlusion of the arteries around the circle of Willis, accompanied by the formation of collateral vessels. In traditional Chinese medicine (TCM), MMV falls into the categories of “stroke”, “vertigo”, and “headache”, among others. Its core etiology is related to congenital insufficiency and acquired malnourishment, with wind, fire, phlegm, deficiency, and stasis as the key pathogenic factors. Current Western medical diagnosis and treatment of MMV remain suboptimal, and TCM pattern differentiation has yet to be standardized. The most common clinical patterns are liver yang hyperactivity (associated with hemorrhagic symptoms) and qi deficiency with blood stasis (associated with ischemic symptoms). Treatment modalities include acupuncture, Chinese herbal formulas, and TCM–Western medicine integrated therapy. Clinical trial results have confirmed that integrated therapy offers certain benefits for MMV; however, there is a lack of relevant diagnostic and treatment guidelines as well as in-depth mechanistic studies. This article reviews the progress in TCM and Western medicine for the diagnosis and treatment of MMV and proposes a trinity diagnostic and therapeutic approach integrating “disease differentiation–pattern differentiation–staging”, which provides a reference for TCM–Western medicine integration management.

Objective:To investigate the relationship between lipid levels and cognitive impairment in the elderly Chinese population using prospective cohort data.Methods:Based on the China-PAR (Prediction for Atherosclerotic Cardiovascular Disease Risk in China) cohort, this study included 24 380 individuals aged ≥60 years who participated in the cognitive function follow-up survey from 2018 to 2019. Cognitive function was assessed using the Mini-Mental State Examination (MMSE), with cognitive impairment defined according to different educational levels: MMSE ≤17 for illiterate individuals, MMSE ≤20 for those with primary education and MMSE ≤24 for those with secondary education or above. Multivariable linear regression and logistic regression models were employed to examine the associations between six baseline lipid indicators and cognitive scores, as well as cognitive impairment. Additionally, restricted cubic splines were used to explore the exposure-dose relationship between lipid levels and cognitive function.Results:The study population had a median follow-up time of 11.6 years, with a baseline age of (59.7±6.8) years. Among the participants, 9 510 (39.0%) were males, and the mean MMSE score was 24.7±6.8. A total of 3 887 individuals (15.9%) were identified as cognitively impaired. The results of multivariable linear regression and logistic regression indicated that total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C) and non-high-density lipoprotein cholesterol (non-HDL-C) levels were not only significantly positively associated with cognitive scores but also significantly associated with a lower risk of cognitive impairment. Each 1 mmol/L increase in these lipid levels corresponded to β values (95% CI) of 0.267 (0.173-0.361), 0.385(0.271-0.499) and 0.331(0.231-0.431), respectively. Each 1 mmol/L increase in these lipid levels corresponded to odds ratio ( OR) (95% CI) values of 0.915 (0.876-0.956), 0.875 (0.830-0.923) and 0.886 (0.848-0.927), respectively. The dose-response curve demonstrated that the negative association was primarily observed within the guideline-recommended optimal lipid level range. Specifically, when LDL-C was less than 3.4 mmol/L and non-HDL-C was less than 4.1 mmol/L, the corresponding OR (95% CI) values were 0.859 (0.796-0.926) and 0.876 (0.818-0.939). Conclusion:Lipid levels exhibit a certain linear negative association with cognitive impairment in elderly Chinese adults, with LDL-C and non-HDL-C demonstrating a stronger effect, particularly within the guideline-recommended optimal range.

Objective To investigate the effects of Semaglutide injection on glycolipid metabolism and adipokine levels in the treatment of type 2 diabetes mellitus(T2DM)patients with varying body mass index(BMI).Methods A total of 143 patients with T2DM admitted to our hospital between May 2022 and May 2024 were enrolled in this study.Based on their BMI,the patients were categorized into three groups:the normal-weight group(31 cases,18.5 kg/m2≤BMI<24 kg/m2),the super-recombinant group(49 cases,24 kg/m2≤BMI<28 kg/m2),and the obese group(63 cases,28 kg/m2≤BMI).28 kg/m2≤BMI).All participants received standard guideline-based conventional treatment and were additionally administered semaglutide injections for a duration of 12 weeks.The study compared glucose metabolism,islet β-cell function,lipid metabolism,body composition,adipokine levels before treatment and at 12 weeks post-treatment,as well as safety profiles during the treatment period across the three groups.Results After 12 weeks of treatment,the levels of fasting blood glucose(FPG),2-hour postprandial blood glucose(2 h PG),glycated hemoglobin(HbA1c),insulin resistance index(HOMA-IR),serum triglycer-ides(TG),total cholesterol(TC),and low-density lipoprotein cholesterol(LDL-C)decreased in all three groups.Specifically,the reductions were more pronounced in the obesity group compared to the normal group and the super-reorganization group,and the super-reorganization group showed intermediate reductions between the obesity and normal groups(P<0.05).Conversely,fasting C-peptide(FCP),2-hour postprandial C-peptide(2 h CP),irisin,adipsin,and omentin-1 levels increased in all three groups after treatment,with the greatest increases observed in the obesity group,followed by the super-reorganization group,both of which were significantly higher than the normal group(P<0.05).Additionally,high-density lipoprotein cholesterol(HDL-C)levels increased in all three groups after 12 weeks of treatment(P<0.05).BaselineBMI and total body fat mass(WBFM)were significantly higher in the obesity group compared to the super-reorganization group,which in turn were higher than the normal group(P<0.05).After treatment,BMI and WBFM decreased in both the obesity and super-reorganization groups,but remained significantly higher than in the normal group(P<0.05).The incidence of adverse reactions during treatment was 12.90％(4/31),10.20％(5/49),and 11.11％(7/63)in the normal,super-reorganization,and obesity groups,respectively,with no statistically significant differences among the groups(P>0.05).Conclusion Smiglutide injection can improve glucose and lipid metabolism,islet function,and adipokine levels in T2DM patients across different BMI categories,while also regulating body composition.It dem-onstrates a particularly strong improvement effect on glucose and lipid metabolism,islet function,and adipokine levels in overweight and obese T2DM patients.Additionally,smiglutide does not increase safety risks.

Objective To explore the early brain microstructural changes in patients with alcohol use disorder(AUD)and the correlations with cognitive function.Methods Totally 81 AUD patients(AUD group)and 75 healthy volunteers(control group)were retrospectively enrolled.Gray matter volume(GMV)and cortical thickness of brain regions were calculated with voxel-based morphometry and surface-based morphometry,and the correlations of the above indexes of brain regions being significantly different between groups and clinical cognitive function scale scores were analyzed.Results In AUD group,GMV of bilateral hippocampus,insula,inferior parietal angular gyrus,straight gyrus,central posterior gyrus and cerebellar angle 1 area,of left medial superior frontal gyrus,precuneus,anterior cingulated cortex,middle temporal gyrus and middle occipital gyrus,as well as of right lingual gyrus reduced significantly compared with those in control group.The cortical thickness of bilateral superior frontal gyrus,middle frontal gyrus,inferior frontal gyrus,supramarginal gyrus,superior parietal lobule,inferior parietal lobule,central posterior gyrus,central anterior gyrus,temporal superior gyrus and middle temporal gyrus reduced in AUD group.In AUD group,GMV of left medial superior frontal gyrus was positively correlated with Pittsburgh sleep quality index score(r=0.301,P=0.006),while of the left and right straight gyrus were positively correlated with Hopkins verbal learning test-revised score(r=0.328,0.326;both P=0.003)but negatively correlated with trail making test-B score(r=-0.295,-0.312;P=0.008,0.005),while the cortical thickness of the left central anterior gyrus and the lower part of the right middle frontal gyrus were positively correlated with Beck anxiety inventory score(r=0.323,0.289;P=0.003,0.009).Conclusion Prefrontal cortex atrophy could be observed in early stage AUD patients,which was correlated with cognitive function impaired.

Objective To investigate the effects of Semaglutide injection on glycolipid metabolism and adipokine levels in the treatment of type 2 diabetes mellitus(T2DM)patients with varying body mass index(BMI).Methods A total of 143 patients with T2DM admitted to our hospital between May 2022 and May 2024 were enrolled in this study.Based on their BMI,the patients were categorized into three groups:the normal-weight group(31 cases,18.5 kg/m2≤BMI<24 kg/m2),the super-recombinant group(49 cases,24 kg/m2≤BMI<28 kg/m2),and the obese group(63 cases,28 kg/m2≤BMI).28 kg/m2≤BMI).All participants received standard guideline-based conventional treatment and were additionally administered semaglutide injections for a duration of 12 weeks.The study compared glucose metabolism,islet β-cell function,lipid metabolism,body composition,adipokine levels before treatment and at 12 weeks post-treatment,as well as safety profiles during the treatment period across the three groups.Results After 12 weeks of treatment,the levels of fasting blood glucose(FPG),2-hour postprandial blood glucose(2 h PG),glycated hemoglobin(HbA1c),insulin resistance index(HOMA-IR),serum triglycer-ides(TG),total cholesterol(TC),and low-density lipoprotein cholesterol(LDL-C)decreased in all three groups.Specifically,the reductions were more pronounced in the obesity group compared to the normal group and the super-reorganization group,and the super-reorganization group showed intermediate reductions between the obesity and normal groups(P<0.05).Conversely,fasting C-peptide(FCP),2-hour postprandial C-peptide(2 h CP),irisin,adipsin,and omentin-1 levels increased in all three groups after treatment,with the greatest increases observed in the obesity group,followed by the super-reorganization group,both of which were significantly higher than the normal group(P<0.05).Additionally,high-density lipoprotein cholesterol(HDL-C)levels increased in all three groups after 12 weeks of treatment(P<0.05).BaselineBMI and total body fat mass(WBFM)were significantly higher in the obesity group compared to the super-reorganization group,which in turn were higher than the normal group(P<0.05).After treatment,BMI and WBFM decreased in both the obesity and super-reorganization groups,but remained significantly higher than in the normal group(P<0.05).The incidence of adverse reactions during treatment was 12.90％(4/31),10.20％(5/49),and 11.11％(7/63)in the normal,super-reorganization,and obesity groups,respectively,with no statistically significant differences among the groups(P>0.05).Conclusion Smiglutide injection can improve glucose and lipid metabolism,islet function,and adipokine levels in T2DM patients across different BMI categories,while also regulating body composition.It dem-onstrates a particularly strong improvement effect on glucose and lipid metabolism,islet function,and adipokine levels in overweight and obese T2DM patients.Additionally,smiglutide does not increase safety risks.

Objective To explore the early brain microstructural changes in patients with alcohol use disorder(AUD)and the correlations with cognitive function.Methods Totally 81 AUD patients(AUD group)and 75 healthy volunteers(control group)were retrospectively enrolled.Gray matter volume(GMV)and cortical thickness of brain regions were calculated with voxel-based morphometry and surface-based morphometry,and the correlations of the above indexes of brain regions being significantly different between groups and clinical cognitive function scale scores were analyzed.Results In AUD group,GMV of bilateral hippocampus,insula,inferior parietal angular gyrus,straight gyrus,central posterior gyrus and cerebellar angle 1 area,of left medial superior frontal gyrus,precuneus,anterior cingulated cortex,middle temporal gyrus and middle occipital gyrus,as well as of right lingual gyrus reduced significantly compared with those in control group.The cortical thickness of bilateral superior frontal gyrus,middle frontal gyrus,inferior frontal gyrus,supramarginal gyrus,superior parietal lobule,inferior parietal lobule,central posterior gyrus,central anterior gyrus,temporal superior gyrus and middle temporal gyrus reduced in AUD group.In AUD group,GMV of left medial superior frontal gyrus was positively correlated with Pittsburgh sleep quality index score(r=0.301,P=0.006),while of the left and right straight gyrus were positively correlated with Hopkins verbal learning test-revised score(r=0.328,0.326;both P=0.003)but negatively correlated with trail making test-B score(r=-0.295,-0.312;P=0.008,0.005),while the cortical thickness of the left central anterior gyrus and the lower part of the right middle frontal gyrus were positively correlated with Beck anxiety inventory score(r=0.323,0.289;P=0.003,0.009).Conclusion Prefrontal cortex atrophy could be observed in early stage AUD patients,which was correlated with cognitive function impaired.

Objective To investigate the effect of leucine carboxyl methyltransferase 1(LCMT1)knockout on fructose-induced lipid deposition in primary mouse hepatocytes.Methods Primary hepatocytes were isolated from wild-type(WT)and hepatocyte-specific LCMT1 knockout(KO)mice via a two-step hepatic portal vein perfusion method.The cells were divided into four groups:WT-control group,WT-fructose group,KO-control group,and KO-fructose group.Cell viability was determined through Alamar-Blue assays.Hepatocyte injury was evaluated based on alanine aminotransferase and aspartate aminotransferase levels.Lipid deposition was visualized via Oil Red O staining and lipid droplet green fluorescence staining,and the cellular triglyceride content was quantified via a GPO-POD assay.The mRNA expression of lipid metabolism-related genes was detected via quantitative real-time PCR,and the protein expression of LCMT1 and PP2Ac was detected via Western blot.Results Fructose treatment did not alter cell viability significantly in any group,and no significant cell damage was observed(P＞0.05).The WT-fructose group exhibited greater accumulation of lipid droplets in hepatocytes than that in the WT-control group(P＜0.001),with significantly elevated triglyceride contents(P＜0.05).The mRNA levels of the de novo lipid synthesis genes ChREBP,SREBP-1c,and ACC1 were increased significantly(P＜0.05,P＜0.001,P＜0.001),whereas FAS expression did not differ significantly between groups(P＞0.05).The mRNA levels of the lipid uptake genes FABP1 and FATP2 also increased significantly(both P＜0.05).In contrast,the KO-fructose group presented a reduced number of lipid droplets(P＜0.01,P＜0.001),decreased triglyceride content(P＜0.05),and decreased mRNA levels of ChREBP,SREBP-1c,ACC1,FABP1,and FATP2(P＜0.01,P＜0.001,P＜0.001,P＜0.001,P＜0.05);CPT1 mRNA levels were markedly increased(P＜0.01).Total PP2Ac expression was significantly higher(P＜0.05)and PP2Ac demethylation was significantly lower(P＜0.01)in the WT-fructose group than in the WT-control group.In the KO-control group,total PP2Ac expression remained unchanged(P＞0.05),whereas PP2Ac demethylation was markedly elevated(P＜0.001).Compared with levels in the WT-fructose group,the KO-fructose group presented markedly lower total PP2Ac expression and significantly higher PP2Ac demethylation levels(P＜0.05,P＜0.01,respectively).Conclusions LCMT1 knockout alleviates fructose-induced lipid deposition in primary hepatocytes by inhibiting lipid uptake,increasing fatty acid oxidation,and downregulating de novo lipid synthesis.These effects are medicated by the LCMT1 knockout-mediated upregulation of PP2Ac demethylation,thereby modulating PP2A activity.

Objective To investigate the effects of fructose exposure on mitochondrial oxidative damage in M2-type macrophages and elucidate the regulatory role of protein phosphatase 2A(PP2A)in the process using its specific activator ABL127,an inhibitor of protein phosphatase methylesterase-1(PPME-1).Methods ① Immortalized mouse bone marrow-derived macrophages Ana-1 were subjected and grouped into M0(conventional culture),M2(treated with 20 ng/mL IL-4 for 24 h),and M2+Fru groups(IL-4 plus 0.04,0.20,1.00,or 5.00 mmol/L fructose).Cell viability was assessed with CCK-8 assay.Number of mitochondria,total and mitochondrial levels of reactive oxygen species(ROS),and mitochondrial membrane potential(ΔΨM)were measured using fluorescent probes.Total and demethylated PP2Ac protein levels were detected by Western blotting.② Ana-1 cells were also divided into M0,M2,M2+Fru(20 ng/mL IL-4+5.00 mmol/L fructose,24 h),and M2+Fru+ABL127(20 ng/mL IL-4+5.00 mmol/L fructose+1.00 μmol/L ABL127,24 h)to investigate PP2A-mediated mechanisms.Numbers of mitochondria and lysosomes,ROS level,and ΔΨM were detected via fluorescence assays.Expression of mitophagy-related proteins,PTEN induced putative kinase 1(PINK1),P62,microtubule-associated protein light chain 3(LC3),and voltage-dependent anion channel(VDAC)was evaluated by Western blotting,and the mRNA levels of M2 markers,found in inflammatory zone 1(Fizz1),arginase-1(Arg-1),and TGF-β were measured using RT-qPCR.Results ① Compared with the M2 group,fructose treatment at a concentration ranging from 0.04 to 5.00 mmol/L showed no effect on cell viability in M2 macrophages,but increased total ROS level in a dose-dependent manner(P<0.05).Fructose of 5.00 mmol/L resulted in significantly elevated mitochondrial ROS and mitochondrial quantity(P<0.05),reduced ΔΨM(P<0.05),up-regulated demethylated-PP2Ac(P<0.05),and no changed total-PP2Ac protein level.② Compared with the M2+Fru group,the addition of ABL127 led to decreased number of mitochondria but increased number of lysosomes(P<0.01),up-regulation of PINK1,LC3Ⅱ and VDAC proteins,down-regulation of P62(P<0.05),reduced total and mitochondrial ROS levels,and enhanced ΔΨM(P<0.01).The mRNA expression of Fizz1,Arg-1,and TGF-β was notably decreased in the M2+Fru group than the M2 group(P<0.05),and the levels were rescued by ABL127 treatment(P<0.05).Conclusion Fructose induces PP2Ac demethylation and then mitochondrial oxidative damage in M2-type macrophages.PP2A activation promotes mitophagy and reverses fructose-induced damage.

Neuroblastoma is a common extracranial solid tumors in children，and patients with high-risk disease have poor prognosis. Since the pathogenesis of neuroblastoma has not been fully elucidated，early diagnosis and timely，effective clinical intervention are key strategies to improve survival in affected children. As a neuroendocrine tumor，neuroblastoma is characterized by abnormal secretion of catecholamine compounds，the synthesis and release of which are closely associated with both diagnosis and prognosis. This review summarizes the biosynthetic and metabolic pathways of catecholamines and their clinical applications in neuroblastoma，and further discusses the molecular mechanisms by which catecholamines contribute to neuroblastoma progression.

Objective:To investigate the relationship between lipid levels and cognitive impairment in the elderly Chinese population using prospective cohort data.Methods:Based on the China-PAR (Prediction for Atherosclerotic Cardiovascular Disease Risk in China) cohort, this study included 24 380 individuals aged ≥60 years who participated in the cognitive function follow-up survey from 2018 to 2019. Cognitive function was assessed using the Mini-Mental State Examination (MMSE), with cognitive impairment defined according to different educational levels: MMSE ≤17 for illiterate individuals, MMSE ≤20 for those with primary education and MMSE ≤24 for those with secondary education or above. Multivariable linear regression and logistic regression models were employed to examine the associations between six baseline lipid indicators and cognitive scores, as well as cognitive impairment. Additionally, restricted cubic splines were used to explore the exposure-dose relationship between lipid levels and cognitive function.Results:The study population had a median follow-up time of 11.6 years, with a baseline age of (59.7±6.8) years. Among the participants, 9 510 (39.0%) were males, and the mean MMSE score was 24.7±6.8. A total of 3 887 individuals (15.9%) were identified as cognitively impaired. The results of multivariable linear regression and logistic regression indicated that total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C) and non-high-density lipoprotein cholesterol (non-HDL-C) levels were not only significantly positively associated with cognitive scores but also significantly associated with a lower risk of cognitive impairment. Each 1 mmol/L increase in these lipid levels corresponded to β values (95% CI) of 0.267 (0.173-0.361), 0.385(0.271-0.499) and 0.331(0.231-0.431), respectively. Each 1 mmol/L increase in these lipid levels corresponded to odds ratio ( OR) (95% CI) values of 0.915 (0.876-0.956), 0.875 (0.830-0.923) and 0.886 (0.848-0.927), respectively. The dose-response curve demonstrated that the negative association was primarily observed within the guideline-recommended optimal lipid level range. Specifically, when LDL-C was less than 3.4 mmol/L and non-HDL-C was less than 4.1 mmol/L, the corresponding OR (95% CI) values were 0.859 (0.796-0.926) and 0.876 (0.818-0.939). Conclusion:Lipid levels exhibit a certain linear negative association with cognitive impairment in elderly Chinese adults, with LDL-C and non-HDL-C demonstrating a stronger effect, particularly within the guideline-recommended optimal range.