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 retrieve and summarize the best evidence for cognitive function improvement in Alzheimer's disease patients, so as to provide reference for clinical practice.Methods:Following the "6S" evidence model, guidelines, expert consensus, clinical decision, and systematic reviews on cognitive function improvement in Alzheimer's disease patients were systematically retrieved from domestic and foreign databases and websites. The search keywords included "Alzheimer's disease, cognitive function, improvement". Evidence-based nursing methods were used to evaluate the quality of literature and extract evidence. The search period was from July 1, 2000 to July 31, 2024.Results:A total of 15 articles were included, including five guidelines, four expert consensus, two clinical decision, and four systematic reviews. Sixteen pieces of best evidence were summarized from four aspects of evaluation and identification, pharmacological intervention, non-pharmacological intervention, and caregiver support.Conclusions:Patients with Alzheimer's disease require timely identification of symptoms related to cognitive impairment and assessment using standardized scales. Multiple intervention methods, such as pharmacological intervention, non-pharmacological intervention, and caregiver support, should be used to enhance patients' quality of life. Evidence application should be tailored to each patient's specific circumstances through individualized selection and adjustment to ensure the effectiveness and scientific rigor of cognitive function improvement strategies, thereby facilitating the translation of optimal evidence into clinical practice.

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 retrieve and summarize the best evidence for cognitive function improvement in Alzheimer's disease patients, so as to provide reference for clinical practice.Methods:Following the "6S" evidence model, guidelines, expert consensus, clinical decision, and systematic reviews on cognitive function improvement in Alzheimer's disease patients were systematically retrieved from domestic and foreign databases and websites. The search keywords included "Alzheimer's disease, cognitive function, improvement". Evidence-based nursing methods were used to evaluate the quality of literature and extract evidence. The search period was from July 1, 2000 to July 31, 2024.Results:A total of 15 articles were included, including five guidelines, four expert consensus, two clinical decision, and four systematic reviews. Sixteen pieces of best evidence were summarized from four aspects of evaluation and identification, pharmacological intervention, non-pharmacological intervention, and caregiver support.Conclusions:Patients with Alzheimer's disease require timely identification of symptoms related to cognitive impairment and assessment using standardized scales. Multiple intervention methods, such as pharmacological intervention, non-pharmacological intervention, and caregiver support, should be used to enhance patients' quality of life. Evidence application should be tailored to each patient's specific circumstances through individualized selection and adjustment to ensure the effectiveness and scientific rigor of cognitive function improvement strategies, thereby facilitating the translation of optimal evidence into clinical practice.

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 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 analyze the clinical characteristics of adverse reactions caused by dinutuximab β for the treatment of neuro-blastoma(NB)in China and to provide safety evidence for the rational use of dinutuximab β in clinical practice.Methods:Clinical data were retrospectively collected from 16 pediatric patients with NB who had been treated with dinutuximab β at Shanghai Children's Medical Center Affiliated to Shanghai Jiao Tong University School of Medicine from January 2022 to November 2023,and the adverse reactions caused by dinutuximab β were summarized and analyzed.Results:The male-to-female ratio was 5:3 among the 16 children with NB.The retroperitoneum was the main initial site of involvement,accounting for 75%.Thirteen(81.25%)patients had high-risk NB.The adverse reactions caused by dinutuximab β mainly included decreased hemoglobin,fever,vomiting,and diarrhea.The inci-dence of adverse reactions was highest in the first course of treatment,and the median time of adverse reactions was 2-5 days.Conclu-sion:Targeted monitoring should be carried out at an early stage during dinutuximab β administration.Adverse reactions should be de-tected and managed early to ensure the safety of medication for children.

INTRODUCTION: Radiofrequency ablation (RFA) avoids the complications of general anaesthesia, reduces length of hospitalisation and reduces morbidity from surgery. As such, it is a strong alternative treatment for patients with comorbidities who are not surgical candidates. However, to our knowledge, there have only been 1 systematic review and 3 combined systematic review and meta-analyses on this topic to date. This systematic review and meta-analysis seeks to evaluate the efficacy and safety of RFA in the treatment of papillary thyroid carcinoma (PTC) with longer follow-up durations. METHOD: PubMed, Embase and Cochrane databases were searched for relevant studies published from 1990 to 2021; 13 studies with a total of 1366 patients were included. The Preferred Reporting Items for Systematic reviews and Meta-Analyses guidelines and Sandelowski et al.'s approach1 to "negotiated consensual validation" were used to achieve consensus on the final list of articles to be included. All authors then assessed each study using a rating scheme modified from the Oxford Centre for Evidence-Based Medicine. RESULTS: Pooled volume reduction rates (VRRs) from 1 to 48 months after RFA, complete disappearance rates (CDR) and complications were assessed. Pooled mean VRRs were 96.59 (95% confidence interval [CI] 91.05-102.13, I2=0%) at 12 months2-6 and 99.31 (95% CI 93.74-104.88, I2=not applicable) at 48 months.2,5 Five studies showed an eventual CDR of 100%.2,4,7-9 No life-threatening complications were recorded. The most common complications included pain, transient voice hoarseness, fever and less commonly, first-degree burn. CONCLUSION RFA may be an effective and safe alternative to treating PTC. Larger clinical trials with longer follow-up are needed to further evaluate the effectiveness of RFA in treating PTC.
Humans ; Radiofrequency Ablation/methods* ; Thyroid Cancer, Papillary/surgery* ; Thyroid Neoplasms/surgery* ; Treatment Outcome ; Postoperative Complications/etiology*