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

Objective To explore the association between plasma homocysteine (Hcy) level and hyper-uricemia (HUA) in the elderly patients with hypertension.Methods From March to August in 2018,9902 hypertensive patients ≥ 60 years were routinely tested for blood biochemical indicators in Wuyuan county,Jiangxi province.The patients were assigned into a HUA group and a normal uric acid group.Multivariate Logistic regression was adopted to analyze the relationship between Hcy level and the risk of HUA.Results Compared with the normal uric acid group,the HUA group showed increased incidence of hyperhomocysteinemia (99.9% vs.98.7%,P<0.001) and elevated Hcy level[16.8 (13.8-21.5) μmol/L vs.14.4 (12.3-17.7) μmol/L,P<0.001].The multivariate Logistic regression analysis showed that after adjusting for influencing factors,the risk of HUA in the patients with hyperhomocysteinemia was 2.92 times of that in the patients with a normal Hcy level.The threshold effect analysis showed that the Hcy level was positively correlated with the occurrence of HUA in the case of Hcy<20 μmol/L (OR=1.05,95%CI=1.04-1.07,P<0.001).In the case of Hcy ≥ 20 μmol/L,there was no correlation between Hcy level and HUA (OR=1.00,95%CI=0.99-1.00,P=0.055),and the likelihood ratio test showed statistically significant results (P<0.001).Conclusion The elderly with hypertension should pay attention to control the Hcy level,which will be helpful to prevent the occurrence of HUA.
Humans ; Aged ; Hyperuricemia/complications* ; Hyperhomocysteinemia/epidemiology* ; Uric Acid ; Hypertension ; Homocysteine ; Risk Factors

OBJECTIVES: Hyperhomocysteinaemia (Hcy) is an independent risk factor for cardiovascular and cerebrovascular diseases. MicroRNA (miR)-18a-5p is closely related to cardiovascular diseases. This study aims to investigate the effects of miR-18a-5p on homocysteine (Hcy)-induced myocardial cells injury. METHODS: H9c2 cells were transfected with miR-18a-5p mimic/miR-18a-5p mimic negative control (NC) or combined with Hcy for intervention, and untreated cells were set as a control group. The transfection efficiency was verified by real-time RT-PCR, and cell counting kit-8 (CCK-8) assay was used to determine cell viability. Flow cytometry was used to detect apoptosis and reactive oxygen species (ROS) levels. Western blotting was performed to measure the protein levels of microtubule-associated protein 1 light chain 3 (LC3)-I, LC3-II, Beclin1, p62, Bax, Bcl-2, and Notch2. Dual luciferase reporter assay was used to detect the interaction of miR-18a-5p with Notch2. RESULTS: Compared with the control, treatment with Hcy or transfection with miR-18a-5p mimic alone, or combined treatment with Hcy and miR-18a-5p mimic/miR-18a-5p mimic NC significantly reduced the H9c2 cell viability, promoted apoptosis and ROS production, up-regulated the expressions of Bax and Beclin, down-regulated the expressions of Bcl-2, p62, and Notch2, and increased the ratio of LC3-II/LC3-I (all P<0.05). Compared with the combined intervention of miR-18a-5p mimic NC and Hcy group, the above indexes were more significantly changed in the combined intervention of miR-18a-5p mimic and Hcy group, and the difference between the 2 groups was statistically significant (all P<0.05). There is a targeted binding between Notch2 and miR-18a-5p. CONCLUSIONS MiR-18a-5p could induce autophagy and apoptosis via increasing ROS production in cardiomyocytes, and aggravate Hcy-induced myocardial injury. Notch2 is a target of miR-18a-5p.
Apoptosis/genetics* ; Autophagy/genetics* ; bcl-2-Associated X Protein ; MicroRNAs/metabolism* ; Proto-Oncogene Proteins c-bcl-2/genetics* ; Reactive Oxygen Species ; Rats ; Animals ; Myocytes, Cardiac/drug effects* ; Homocysteine/adverse effects* ; Hyperhomocysteinemia

OBJECTIVE: To observe the effects of acupuncture on neurologic function and serum inflammatory factors in patients after thrombolysis in acute ischemic stroke (AIS). METHODS: A total of 102 AIS patients with onset to treatment time (OTT) ≤3 h were randomly divided into an observation group and a control group, 51 cases each group. In the control group, thrombolysis and conventional medical treatment were applied. On the basis of the treatment as the control group, acupuncture at Shuigou (GV 26), Zhongwan (CV 12), Qihai (CV 6), Neiguan (PC 6), etc. was applied in the observation group, 30 min each time, once a day. Both groups were treated for 2 weeks. Before and after treatment, the scores of National Institutes of Health stroke scale (NIHSS), modified Rankin scale (mRS), modified Barthel index (MBI) and serum level of homocysteine (Hcy), hypersensitive C-reactive protein (hs-CRP) were compared, and the clinical efficacy was evaluated in the two groups. RESULTS: After treatment, the scores of NIHSS, mRS and serum level of Hcy, hs-CRP were decreased compared with those before treatment (P<0.05), while the MBI scores were increased (P<0.05) in the two groups. The scores of NIHSS, mRS and serum level of Hcy, hs-CRP in the observation group were lower than those in the control group (P<0.05, P<0.01), the MBI score in the observation group was higher than that in the control group (P<0.01). The total effective rate was 88.2% (45/51) in the observation group, which was superior to 70.6% (36/51) in the control group (P<0.05). CONCLUSION Acupuncture could promote the recovery of neurologic function in patients after thrombolysis in AIS, improve the ability of daily living, which may be related to reducing the level of inflammatory factors, thus inhibiting inflammatory response and improving cerebral ischemia reperfusion injury.
United States ; Humans ; Ischemic Stroke ; C-Reactive Protein ; Acupuncture Therapy ; Inflammation ; Homocysteine ; Hypersensitivity ; Thrombolytic Therapy

Objective: To characterize the relationship between the levels of plasma methyl donor and related metabolites (including choline, betaine, methionine, dimethylglycine and homocysteine) and fetal growth in twin pregnancies. Methods: A hospital-based cohort study was used to collect clinical data of 92 pregnant women with twin pregnancies and their fetuses who were admitted to Peking University Third Hospital from March 2017 to January 2018. Fasting blood was collected from the pregnant women with twin pregnancies (median gestational age: 18.9 weeks). The levels of methyl donors and related metabolites in plasma were quantitatively analyzed by high-performance liquid chromatography combined with mass spectrometry. The generalized estimation equation was used to analyze the relationship between maternal plasma methyl donors and related metabolites levels and neonatal outcomes of twins, and the generalized additive mixed model was used to analyze the relationship between maternal plasma methyl donors and related metabolites levels and fetal growth ultrasound indicators. Results: (1) General clinical data: of the 92 women with twin pregnancies, 66 cases (72%) were dichorionic diamniotic (DCDA) twin pregnancies, and 26 cases (28%) were monochorionic diamniotic (MCDA) twin pregnancies. The comparison of the levels of five plasma methyl donors and related metabolites in twin pregnancies with different basic characteristics showed that the median levels of plasma choline and betaine in pregnant women ≥35 years old were higher than those in pregnant women <35 years old, and the differences were statistically significant (all P<0.05). (2) Correlation between plasma methyl donor and related metabolites levels and neonatal growth indicators: after adjusting for confounding factors, plasma homocysteine level in pregnant women with twins was significantly negatively correlated with neonatal birth weight (β=-47.9, 95%CI:-94.3- -1.6; P=0.043). Elevated methionine level was significantly associated with decreased risks of small for gestational age infants (SGA; OR=0.5, 95%CI: 0.3-0.9; P=0.021) and low birth weight infants (OR=0.6, 95%CI: 0.4-0.9; P=0.020). Increased homocysteine level was associated with increased risks of SGA (OR=1.5, 95%CI: 1.0-2.2; P=0.029) and inconsistent growth in twin fetuses (OR=1.9, 95%CI: 1.0-3.7; P=0.049). (3) Correlation between the levels of plasma methyl donors and related metabolites and intrauterine growth indicators of twins pregnancies: for every 1 standard deviation increase in plasma choline level in pregnant women with twin pregnancies, fetal head circumference, abdominal circumference, femoral length and estimated fetal weight in the second trimester increased by 1.9 mm, 2.6 mm, 0.5 mm and 20.1 g, respectively, and biparietal diameter, abdominal circumference and estimated fetal weight increased by 0.7 mm, 3.0 mm and 38.4 g in the third trimester, respectively, and the differences were statistically significant (all P<0.05). (4) Relationship between plasma methyl donor and related metabolites levels in pregnant women with different chorionicity and neonatal birth weight and length: the negative correlation between plasma homocysteine level and neonatal birth weight was mainly found in DCDA twin pregnancy (β=-65.9, 95%CI:-110.6- -21.1; P=0.004). The levels of choline, betaine and dimethylglycine in plasma of MCDA twin pregnancy were significantly correlated with the birth weight and length of newborns (all P<0.05). Conclusion: Homocysteine level is associated with low birth weight in twins, methionine is associated with decreased risk of SGA, and choline is associated with fetal growth in the second and third trimesters of pregnancy.
Adult ; Female ; Humans ; Infant, Newborn ; Pregnancy/metabolism* ; Betaine/metabolism* ; Birth Weight/physiology* ; Choline/metabolism* ; Cohort Studies ; Fetal Development/physiology* ; Fetal Weight/physiology* ; Homocysteine/metabolism* ; Methionine/metabolism* ; Pregnancy, Twin/physiology* ; Biomarkers/metabolism* ; Pregnancy Trimesters/physiology* ; Pregnancy Outcome

Objective: To investigate the relationship between subchorionic hematoma (SCH) and coagulation status, autoantibodies, and conception method. Methods: A total of 100 pregnant women diagnosed with SCH from June 2020 to December 2021 in the Third Affiliated Hospital of Zhengzhou University were included in the SCH group, while 100 healthy pregnant women during the same period were selected as the control group. The coagulation status (including platelet, prothrombin time, thrombin time, activated partial thromboplastin time, fibrinogen, antithrombin Ⅲ, fibrin degradation products, D-dimer, homocysteine, protein S activity, protein C activity), the positive rate of autoantibodies [including antiphospholipid antibodies (anticardiolipin antibody and anti-β₂ glycoprotein Ⅰ antibody), antinuclear antibody] and the mode of conception of the two groups were analyzed. Results: Compared to the control group, the SCH group had higher levels of platelet [(240±45)×10⁹/L vs (227±37)×10⁹/L], fibrinogen [(4.0±0.8) vs (3.6±0.7) g/L], D-dimer [(0.42±0.18) vs (0.31±0.15) mg/L], blood homocysteine [(8.9±4.2) vs (6.9±2.3) μmol/L], and lower level of protein S activity [(55±14)% vs (68±20)%], and there were significant differences between the two groups (all P<0.05). The SCH group had higher positive rates of autoantibodies [24.0% (24/100) vs 8.0% (8/100)], antiphospholipid antibodies [15.0% (15/100) vs 6.0% (6/100)], anti-β₂ glycoprotein Ⅰ antibody [10.0% (10/100) vs 3.0% (3/100)], antinuclear antibody [11.0% (11/100) vs 2.0% (2/100)] and assisted reproduction rate [10.0% (10/100) vs 2.0% (2/100)] than those of the control group (all P<0.05). Conclusion: The occurrence of SCH is related to blood hypercoagulability, positive autoantibodies, and assisted reproduction.
Pregnancy ; Female ; Humans ; Autoantibodies ; Antibodies, Antinuclear ; Antibodies, Antiphospholipid ; Fibrinogen ; Homocysteine ; Glycoproteins

Objective: By analyzing the prevalence and influencing factors of thyroid nodules (TN) among a population undergoing physical examinations in Nantong region, this study aims to provide theoretical basis for early prevention and intervention of TN. Methods: A cross-sectional study was conducted, including 6 950 participants who underwent physical examinations at the Affiliated Hospital of Nantong University from January 2017 to April 2020. All participants underwent high-resolution ultrasound examination of the thyroid, and measurements of height, body mass index (BMI), blood pressure. Fasting blood glucose (FBG), total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C), uric acid (UA), homocysteine (HCY) and other metabolic indicators were detected. Data analysis was performed using SPSS 26.0 statistical software. The numerical variables with normal distribution were expressed as mean±standard deviation (x¯±s), and the t-test was used for comparison between the two groups. Numerical variables with non-normal distribution were expressed as median (interquartile range), namely M (Q₁, Q₃). The Mann-Whitney U test was used for comparison between two groups, and the Kruskal-Wallis test was used for comparison between multiple groups. Results: The prevalence of thyroid nodules among the 6 950 participants was 53.97% (3 751/6 950), with a rate of 47.08% (2 218/4 711) in males and 68.47% (1 533/2 239) in females, which was significantly higher in females than in males (χ²=278.575, P<0.001). The prevalence of TN increased with age both overall (χ²=552.145, P<0.001), in males (χ²=304.086, P<0.001), and in females (χ²=202.178, P<0.001). The prevalence of TN was higher in females than in males across different age groups (P<0.05). In the comparison between males in the TN and non-TN groups, significant differences were found in terms of alcohol consumption history, BMI, blood pressure, HCY, and FBG (all P<0.05). In the comparison between females in the TN and non-TN groups, significant differences were found in terms of BMI, blood pressure, HCY, FBG, TC, TG, LDL-C, and UA (all P<0.05). Univariate logistic regression model showed that FBG<6.1 mmol/L (P<0.001) and TC<5.2 mmol/L (P=0.013) were protective factors for TN. Normal UA (P=0.013) was a risk factor for TN. After adjusting for gender, smoking, alcohol consumption, BMI, and blood pressure, multivariate logistic regression analysis revealed that FBG<6.1 mmol/L (OR: 0.713, 95%CI: 0.621-0.817, P<0.001) was a protective factor against TN. Conclusion: The prevalence of TN is relatively high in the Nantong region. Gender, age, blood pressure, BMI, and FBG are important influencing factors for TN. Health screening and management should be strengthened for the physical examination population with abnormal indicators.
Female ; Male ; Humans ; Thyroid Nodule/epidemiology* ; Cholesterol, LDL ; Cross-Sectional Studies ; Physical Examination ; Body Mass Index ; Homocysteine