Objective To investigate the application value of occupational therapy in cognitive impairment in patients with cerebral small vessel disease. Methods A total of 84 patients with cerebral small vessel disease who were admitted to our hospital from April 2021 to September 2022 and were found to have cognitive impairment were enrolled as subjects， and they were randomly divided into observation group and control group using a random number table， with 42 patients in each group. The patients in the control group received conventional Western medicine treatment， while those in the observation group received occupational therapy in addition to the treatment in the control group. After 8 weeks of continuous treatment， the two groups were compared in terms of treatment outcome， Mini-Mental State Examination （MMSE） score， Montreal Cognitive Assessment （MoCA） score， brain-derived neurotrophic factor （BDNF）， high-sensitivity C reactive protein （hs-CRP）， homocysteine （Hcy）， and cerebral blood perfusion parameters. Results The treatment group had a higher overall response rate than the control group （95.24% vs 73.81%， P<0.05）. After treatment， the observation group had significantly higher MMSE， MoCA， and MBI scores than the control group （P<0.05）. Compared with the control group， the observation group had a significantly lower MTT and significantly higher CBV and CBF （P<0.05）. Compared with the control group， the observation group had a significantly higher level of BDNF and significantly lower levels of hs-CRP and Hcy （P<0.05）. Conclusion Occupational therapy has a marked clinical effect in patients with cerebral small vessel disease and cognitive impairment and can effectively improve cognitive function and cerebral blood perfusion， upregulate the level of BDNF， and reduce the expression of hs-CRP and Hcy. It is of great significance for improving the quality of life and prognosis of patients.
Homocysteine

摘要 目的 探讨血浆神经胶质细胞原纤维酸性蛋白（GFAP）及同型半胱氨酸（Hcy）水平对肝豆状核变性（又称肝豆状核变性，WD）的诊断及肝脑型鉴别诊断价值。方法 招募安徽中医药大学第一附属医院脑病中心2023年1月—2025年1月收治的WD患者共120例，其中WD脑型63例，WD肝型57例，以及同期在体检中心筛查的30名健康志愿者。采用ELISA法测定纳入对象血浆GFAP、Hcy水平，进行组间差异性比较和ROC曲线分析。并运用Spearman相关分析探讨血浆GFAP、Hcy水平与统一肝豆状核变性评定量表评分（UWDRS）、24 h尿铜及血清铜蓝蛋白（CER）水平的相关性。结果 WD肝型及脑型患者的血浆GFAP水平均显著高于对照组（P<0.05），且WD脑型较WD肝型升高更为显著（P<0.05）。血浆Hcy水平也在WD肝型及脑型患者中明显升高（P<0.05），但在WD肝型、脑型间未表现出显著差异。血浆GFAP诊断WD脑型的曲线下面积（AUC）为0.861，截断值为135.71 pg/ml，敏感度68.3％，特异度82.3％；该指标诊断WD肝型的AUC为0.695，截断值为129.84 pg/ml，敏感度64.7％，特异度83.3％；其在WD肝型及脑型鉴别诊断中的AUC为0.75，截断值为151.12 pg/ml，敏感度73.9％，特异度87.8％。血浆Hcy诊断WD的AUC为0.788，截断值为15.59 μmol/L，敏感性77.9％，特异性66.7％。Spearman相关性分析结果显示，WD肝型及脑型患者血浆GFAP、Hcy水平与UWDRS评分及24 h尿铜水平均呈正相关（P<0.05），与CER水平无显著相关性（P>0.05）。结论 血浆GFAP、Hcy水平与WD神经及肝脏功能受损程度密切相关，且为早期诊断WD以及血浆GFAP对WD各分型的鉴别诊断提供了一定的临床价值。 Abstract Objective To investigate the value of plasma glial fibrillary acidic protein （GFAP） and homocysteine （Hcy） in the diagnosis of hepatolenticular degeneration （also know as Wilson disease， WD） and the differential diagnosis of the hepatic and neurological forms of WD. Methods A total of 120 WD patients who were admitted to Encephalopathy Center of our hospital from January 2023 to January 2025 were enrolled， among whom there were 63 patients with neurological WD and 57 patients with hepatic WD， and 30 healthy volunteers who underwent physical examination during the same period of time were enrolled as control group. ELISA was used to measure the plasma levels of GFAP and Hcy， and the differences between groups were analyzed. The receiver operating characteristic（ROC） curve analysis was performed， and the Spearman correlation analysis was used to investigate the correlation of the plasma levels of GFAP and Hcy with Unified Wilson Disease Rating Scale （UWDRS） score， 24-hour urinary copper， and the serum level of ceruloplasmin （CER）. Results The patients with hepatic or neurological WD had a significantly higher plasma level of GFAP than the control group（P<0.05）， and the patients with neurological WD had a significantly greater increase than those with hepatic WD（P<0.05）. The patients with hepatic or neurological WD also had a significant increase in the plasma level of Hcy（P<0.05）， but with no significant difference between the patients with hepatic WD and those with neurological WD.Plasma GFAP had an area under the ROC curve（AUC） of 0.861 in the diagnosis of neurological WD， with a cut-off value of 135.71 pg/ml， a sensitivity of 68.3%，and a specificity of 82.3%；plasma GFAP had an AUC of 0.695 in the diagnosis of hepatic WD， with a cut-off value of 129.84 pg/ml， a sensitivity of 64.7%， and a specificity of 83.3%； in the differential diagnosis of hepatic and neurological WD， plasma GFAP had an AUC of 0.75， with a cut-off value of 151.12 pg/ml，a sensitivity of 73.9%， and a specificity of 87.8%. Plasma Hcy had an AUC of 0.788 in the diagnosis of WD， with a cut-off value of 15.59 μmol/L， sensitivity of 77.9%， and specificity of 66.7%. The Spearman correlation analysis showed that in the patients with hepatic or neurological WD， the plasma levels of GFAP and Hcy were positively correlated with UWDRS score and 24-hour urinary copper （P<0.05）， but they were not significantly correlated with the level of CER （P>0.05）. Conclusion The plasma levels of GFAP and Hcy are closely associated with the degree of neurological and hepatic impairment in WD， which provides a certain clinical value for the early diagnosis of WD and the differential diagnosis of hepatic and neurological WD.
Homocysteine

Objective To investigate the serum markers for rapid eye movement sleep behavior disorder （RBD） in patients with Parkinson disease （PD） and their predictive value. Methods A total of 132 PD patients who were admitted to Fuxing Hospital， Capital Medical University， from January 2020 to December 2023 were enrolled as subjects， and according to the presence or absence of RBD， they were divided into RBD group with 47 patients and non-RBD group with 85 patients. The two groups were compared in terms of general information and the serum levels of neurofilaments （NFL）， glial fibrillary acidic protein （GFAP）， lipoprotein-associated phospholipase A2 （Lp-PLA2）， neurotrophic factor-3 （NT-3）， and homocysteine （Hcy）.Univariate and multivariate logistic regression analyses were used to investigate independent risk factors for RBD in PD patients， and the receiver operating characteristic （ROC） curve was used to assess their predictive value. Results Compared with the non-RBD group， the RBD group had significantly higher serum levels of NFL， GFAP，Lp-PLA2，and Hcy（P<0.05） and a significantly lower serum level of NT-3（P<0.05）. Serum GFAP （95%CI 0.387‒0.847，P=0.005）， Lp-PLA2（95%CI 0.859‒0.947，P=0.005）， NT-3（95%CI 1.033‒1.180，P=0.003），and Hcy （95%CI 0.259‒0.655，P<0.001） were significant risk factors for RBD in PD patients. The ROC curve analysis showed that GFAP （AUC=0.767），Lp-PLA2 （AUC=0.845）， NT-3 （AUC=0.829）， and Hcy （AUC=0.888） used alone had a good predictive ability， while the combined model of these four indicators had the strongest predictive ability （AUC=0.982）， followed by Lp-PLA2+Hcy （AUC=0.944） and GFAP+Hcy （AUC=0.928）. Conclusion Serum GFAP， Lp-PLA2， NT-3， and Hcy are significant risk factors for RBD in PD patients and have a good predictive value. The combined model of these four indicators has the strongest predictive ability， suggesting that combined measurement of these indicators can be used for early warning of the risk of RBD in PD patients.
Homocysteine

Objective To investigate the effect and mechanism of Efferocytosis Relatived LncRNA (EFRL) on homocysteine-induced atherosclerosis in macrophage efferocytosis. Methods RAW264.7 cells were cultured in vitro, and the Control group (0 μmol/L Hcy) and Hcy intervention group (100 μmol/L Hcy) were set up. After GapmeR transfection of macrophages with Hcy intervention, EFRL knockdown negative control group (Hcy combined with LNA-NC) and EFRL knockdown group (Hcy combined with LNA-EFRL) were set up. High-throughput sequencing was applied for different expression of LncRNA MSTRG. 88917.16 (EFRL), UCSC was used to analyze its conservation, CPC and CPAT were used to analyze its ability to encode proteins, and GO and KEGG were used to analyze related biological functions. The localization of LncRNA EFRL in macrophages was analyzed by nucleoplasmic separation and RNA-FISH. Quantitative real-time PCR was used to detect the expression levels of LncRNA EFRL and its target gene SPAST in Hcy-treated macrophages. The apoptosis rate of Jurkat cells induced by UV was detected by flow cytometry. In vitro efferocytosis assay combined with immunofluorescence technique was used to analyze macrophage efferocytosis. ELISA was used to detect the levels of interleukin 1β(IL-1β) and IL-18. Results The new LncRNA MSTRG.88917.16 was identified and named EFRL(Efferocytosis Relatived LncRNA). UCSC, CPC and CPAT analyses showed that LncEFRL is highly conserved and does not have the ability to encode proteins. GO and KEGG analyses suggested that LncEFRL may be involved in macrophage efferocytosis. LncRNA EFRL was localized in the nucleus of macrophages as determined by nucleoplasmic separation and RNA-FISH. In comparison to the Control group, the expression levels of LncRNA EFRL and its target gene SPAST in the Hcy group were increased. In comparison to the Control group (0 min), the apoptosis rate of the experimental group (15, 30 min) Annexin V is more than 85%. Compared with Hcy combined with LNA-NC group, Hcy combined with LNA-EFRL group had enhanced macrophage efferocytosis and reduced levels of inflammatory factors. Compared with Hcy combined with LNA-NC group, the expression level of SPAST in Hcy combined with LNA-EFRL group was decreased. Conclusion Inhibition of EFRL expression can alleviate the process of Hcy inhibiting macrophage efferocytosis, and the mechanism is related to the regulation of the downstream target gene SPAST by EFRL.
RNA, Long Noncoding/physiology* ; Animals ; Homocysteine ; Mice ; Macrophages/drug effects* ; Humans ; RAW 264.7 Cells ; Atherosclerosis/chemically induced* ; Apoptosis/genetics* ; Phagocytosis/genetics* ; Jurkat Cells ; Interleukin-1beta/genetics* ; Efferocytosis

This study aims to explore the correlation between plasma homocysteine (Hcy) levels and the clinical grading of varicocele (VC) when analyzing the potential pathogenesis of endothelial cells injury by Hcy. A total of 184 VC patients, aged 18-46 years, were included in this study. These patients visited The Second Hospital of Dalian Medical University (Dalian, China), between January 2022 and September 2024. Patients were divided into three groups based on clinical grading: Group A (59 cases, Grade I), Group B (28 cases, Grade II), and Group C (97 cases, Grade III). Additionally, 120 individuals with normal fertility test results during the same period were selected as the control group. Routine blood and biochemical indices were collected from the patients. Differences in clinical indices between groups were compared, and univariate and multivariate linear regression analyses were performed to identify factors associated with clinical grading. The results showed that the median Hcy levels in the control group and in patients with Grade I, II, and III VC were 9.56 (interquartile range [IQR]: 8.66, 14.02) µmol l -1 , 11.28 (IQR: 9.71, 14.55) µmol l -1 , 11.84 (IQR: 10.14, 15.60) µmol l -1 , and 12.27 (IQR: 9.52, 15.40) µmol l -1 , respectively. The differences between the four groups were statistically significant ( χ2 = 12.41, P = 0.006). Multivariate regression analysis indicated that Hcy is a factor associated with the clinical grading of VC ( t = 2.53, P = 0.013). Hcy is associated with the clinical grading and may have clinical value in assessing severity of VC.
Humans ; Varicocele/pathology* ; Male ; Homocysteine/blood* ; Adult ; Middle Aged ; Adolescent ; Young Adult ; Severity of Illness Index ; Case-Control Studies

OBJECTIVE: Data on homocysteine (Hcy) status and its determinants are limited among women during pregnancy and postpartum. This cross-sectional study aimed to investigate Hcy levels during pregnancy and postpartum, and to explore the determinants like geographic factor. METHODS: This study was conducted in women at mid-pregnancy, late-pregnancy and postpartum from southern, central and northern China. Approximately 132 women were included in each stratum by the three phases and regions. Plasma Hcy concentrations were assessed using high-performance liquid chromatography (HPLC), with hyperhomocysteinemia defined as > 10.0 µmol/L. Quantile regression was to estimate medians and interquartile ranges ( IQRs), and logistic regression to examine the determinants of hyperhomocysteinemia. RESULTS: For 1,190 women included, the median (IQR) Hcy concentration was 5.66 (4.62, 7.37) μmol/L. The adjusted median in mid-pregnancy, late-pregnancy and postpartum women was 4.75 (4.13, 5.54), 5.72 (4.81, 6.85) and 7.09 (5.65, 8.75) μmol/L, respectively, showing an increasing trend ( P < 0.001). This increasing trend persisted across the three regions. Higher Hcy concentrations were observed in women residing in northern region and those with younger age or lower economic status. A total of 106 (8.9%) women had hyperhomocysteinemia, with a higher prevalence in those residing in northern region (16.0%), or in postpartum women (16.5%). CONCLUSION Hcy levels, varying with geographic region, maternal age and economic status, are increased from mid-pregnancy to late-pregnancy and postpartum, indicating a need to monitor Hcy levels in pregnant and postpartum women to control potential risks related to elevated Hcy levels.
Humans ; Female ; Pregnancy ; Homocysteine/blood* ; China/epidemiology* ; Adult ; Postpartum Period/blood* ; Cross-Sectional Studies ; Hyperhomocysteinemia/blood* ; Young Adult ; Pregnancy Trimester, Third/blood* ; Pregnancy Trimester, Second ; East Asian People

Objective To investigate the association of the serum levels of ischemia-modified albumin（IMA）and homocysteine（Hcy）with the onset and severity of white matter ischemic lesions（WMIL）. Methods A total of 89 patients who were diagnosed with WMIL by cranial magnetic resonance imaging（MRI）in our hospital from March 2020 to June 2022 were enrolled as WMIL group，and the volunteers with normal cranial MRI results，matched for sex and age，during the same period of time were enrolled as control group. The two groups were compared in terms of general information and laboratory markers，and the conditions of WMIL were evaluated and classified into mild and moderate-to-severe cases. A logistic regression analysis was used to investigate the influencing factors for the onset and severity of WMIL，and the receiver operating characteristic（ROC）curve was used to analyze the value of the serum levels of IMA and Hcy in the diagnosis of WMIL. Results Compared with the control group，the WMIL group had a significantly higher proportion of patients with hypertension or type 2 diabetes and significantly higher levels of uric acid（UA），IMA，and Hcy（P<0.05）. Compared with the control group，the WMIL group had a significantly higher proportion of the patients with moderate-to-severe WMIL who had hypertension or the proportion of type 2 diabetes，significantly higher levels of IMA and Hcy，and a significantly lower level of high-density lipoprotein cholesterol（P<0.05）. The logistic regression analysis showed that hypertension，elevated IMA level，and elevated Hcy level were influencing factors for the onset of WMIL（P<0.05），and hypertension，elevated IMA level，and elevated Hcy level were influencing factors for the increase in WMIL severity（P<0.05）. The ROC curve analysis showed that serum IMA and Hcy had a certain value in the diagnosis of WMIL and moderate-to-severe WMIL. Conclusion Increases in the serum levels of IMA and Hcy are associated with the onset and aggravation of WMIL，and measurement of the serum levels of IMA and Hcy has a certain value in the diagnosis of WMIL and moderate-to-severe WMIL.
Homocysteine

Objective To explore the value of serum homocysteine​（HCY） and cystatin C （Cys-C） levels for evaluating the presence and severity of cognitive impairment in elderly patients with both cerebral small vessel disease （CSVD） and obstructive sleep apnea-hypopnea syndrome （OSAHS）.Methods A retrospective study was performed on 150 elderly patients with both CSVD and OSAHS who were treated in our hospital from January to December 2020. The data about HCY and Cys-C levels were collected. According to the presence or absence of cognitive impairment， they were divided into observation group （with cognitive impairment， 41 cases） and control group （without cognitive impairment， 109 cases）. The serum HCY and Cys-C levels of the two groups were compared. The correlations between serum HCY and Cys-C levels and cognitive impairment in patients with both CSVD and OSAHS were analyzed. A binary Logistic regression analysis was performed to determine independent factors affecting cognitive impairment to establish a predictive logistic regression model. Receiver operating characteristic （ROC） curves were plotted to examine the predictive value of HCY， Cys-C， and their combination for cognitive impairment in patients with both CSVD and OSAHS. According to the severity of cognitive impairment， the patients in the observation group were further divided into mild cognitive impairment group （32 cases） and severe cognitive impairment group （9 cases） to compare HCY and Cys-C levels and analyze the value of HCY， Cys-C， and their combination in evaluating the staging of cognitive impairment by using ROC curves.Results The levels of HCY and Cys-C in the observation group were significantly higher than those in the control group （both P<0.05）. The total score of Montreal Cognitive Assessment was negatively correlated with serum HCY and Cys-C level （r=-0.756， -0.713， both P<0.001）. The logistic regression analysis showed that HCY and Cys-C levels were independent influencing factors for cognitive impairment （both P<0.05）. The area under the curve （AUC） of HCY plus Cys-C for prediction was 0.843（0.747-0.934）， which was higher than that of any single indicator （P < 0.05）， with the sensitivity and specificity being 89.32% and 79.25%， respectively. The levels of HCY and Cys-C were significantly lower in the patients with mild cognitive impairment than in those with severe cognitive impairment （both P < 0.05）. The AUC of HCY plus Cys-C in cognitive impairment staging was 0.925（0.849-0.976）， which was higher than that of any single index （P < 0.05）. The sensitivity and specificity were 95.67% and 89.67%， respectively.Conclusion Serum HCY and Cys-C levels are negatively correlated with the development and progression of cognitive impairment in elderly patients with both CSVD and OSAHS. The combined prediction with the two indicators can facilitate the evaluation of the risk and stage of cognitive impairment.
Homocysteine ; Cystatins

Objective To investigate the risk factors for the early progression of atherosclerosis，whether hyperhomocysteinemia （HHcy） is an independent risk factor for the early progression of atherosclerosis， and whether the reduction in homocysteine （Hcy） can delay the early progression of atherosclerosis. Methods The villagers，aged ≥40 years， from Liulin Town of Hanzhong City， Shaanxi Province， China were selected for structured inquiry， carotid ultrasound examination， and blood test in May 2017 and June 2020. Ultrasound examination was performed to measure carotid intima-media thickness （CIMT）， carotid plaque， and carotid stenosis rate to reflect the degree of arteriosclerosis. Results A total of 500 individuals were included in the final analysis， among whom 451 had no CIMT thickening at baseline， 429 had no carotid plaque at baseline， and 454 had no carotid stenosis at baseline. After 3 years of follow-up， among the 500 individuals， 176 （35.2%） had CIMT thickening， and the multivariate analysis showed that old age， smoking， and a high level of low-density lipoprotein cholesterol （LDL-C） were independent risk factors for CIMT thickening； 252 （50.4%） had new-onset plaques， and the multivariate analysis showed that old age， hypertension， and high LDL-C were independent risk factors for plaque formation； 231（46.2%） had new-onset carotid stenosis， and the multivariate analysis showed that old age， high LDL-C， and elevated triglyceride were independent risk factors for carotid stenosis. There were 364 patients with HHcy （≥15 μmol/L） in the initial examination， and after 3 years， 119 had a reduction in Hcy， while 245 had no reduction in Hcy. After adjustment for sex， previous stroke， smoking， baseline LDL-C， baseline Hcy， and Hcy after 3 years， the multivariate analysis showed that neither HHcy nor the reduction in Hcy was associated with carotid atherosclerosis. Conclusion Old age， high LDL-C， smoking， and hypertension are the main risk factors for atherosclerosis in villagers aged ≥40 years in rural areas of Hanzhong City in Shaanxi Province. There is no significant association between HHcy and carotid atherosclerosis， and the reduction in Hcy cannot delay or reverse the process of carotid atherosclerosis.
Atherosclerosis ; Homocysteine

Hyperhomocysteinemia (HHcy) is considered to be an independent risk factor for cardiovascular diseases, but the molecular mechanisms underlying its pathogenesis are not fully understood. Endothelial dysfunction is a key initiating factor in the pathogenesis of atherosclerosis, which is commonly observed in almost all HHcy-induced vascular diseases. HHcy promotes oxidative stress, inhibits nitric oxide production, suppresses hydrogen sulfide signaling pathway, promotes endothelial mesenchymal transition, activates coagulation pathways, and promotes protein N-homocysteination and cellular hypomethylation, all of which can cause endothelial dysfunction. This article reviews the specific links between HHcy and endothelial dysfunction, and highlights recent evidence that endothelial mesenchymal transition contributes to HHcy-induced vascular damage, with a hope to provide new ideas for the clinical treatment of HHcy-related vascular diseases.
Humans ; Atherosclerosis ; Cardiovascular Diseases ; Endothelium, Vascular ; Homocysteine/metabolism* ; Hyperhomocysteinemia/complications* ; Oxidative Stress ; Risk Factors