OBJECTIVES: To analyze the efficacy and safety of concomitant left atrial appendage clipping during heart valve surgery for valvular heart disease patients with atrial fibrillation. METHODS: Fifty-eight patients who underwent concomitant left atrial appendage clipping during cardiac valve surgery in the Second Affiliated Hospital of Nanchang University from January 2017 to June 2023 were included in the analysis, including 1 case who underwent aortic valve replacement, 49 cases who underwent mitral valve replace-ment (or valvuloplasty)+tricuspid valvuloplasty, and 8 cases who underwent double valve replacement+tricuspid valvuloplasty (3 cases combined with coronary artery bypass grafting). The patients were followed up for 3-36 months [(16.69±6.61) months] after operation, and the changes of cardiac function and the occurrence of serious adverse complications were evaluated. RESULTS: The cardiopulmonary bypass time ranged from 75 to 145 min [(102.50±21.03) min], and the aortic cross-clamp time ranged from 35 to 80 min [(58.02±14.63) min]. The length of postoperative intensive care unit stay was 1 to 5 days [(2.47±0.82) d], and the length of postoperative hospital stay was 7 to 22 days [(10.84±2.69) d]. Cardiac ultrasound indicated complete closure of the left atrial appendage in all cases. During the follow-up, New York Heart Association (NYHA) functional classifications were improved in 54 patients. No left atrial appendage-related bleeding events or other perioperative complications were observed; and no cerebral infarction, limb embolism events, or mortality cases occurred during the follow-up. CONCLUSIONS For valvular heart disease patients with atrial fibrillation, concomitant left atrial appendage clipping during cardiac valve surgery demonstrates efficacy and safety, with no severe adverse events during a medium-term follow-up.
Humans ; Atrial Appendage/surgery* ; Atrial Fibrillation/complications* ; Male ; Female ; Heart Valve Diseases/complications* ; Aged ; Middle Aged ; Heart Valve Prosthesis Implantation/methods* ; Treatment Outcome ; Cardiac Surgical Procedures/methods* ; Mitral Valve/surgery*

N6-Methyladenosine (m6A) modification is a crucial post-transcriptional regulatory mechanism and the most abundant and highly conserved RNA epigenetic modification in eukaryotes. Previous studies have indicated the involvement of m6A modification in various tissue regeneration processes, including liver regeneration. Vir-like m6A methyltransferase associated protein (VIRMA) is an m6A methyltransferase with robust methylation capability. However, its role in liver regeneration remains poorly understood. In this study, we generated liver-specific Virma knockout mice using the Cre-loxP system and investigated the biological functions of VIRMA in liver regeneration using both the Associating Liver Partition and Portal vein Ligation for Staged Hepatectomy (ALPPS) mouse model and the carbon tetrachloride (CCl₄) mouse model. The expression level of VIRMA was rapidly up-regulated after ALPPS surgery and gradually down-regulated during liver repair. Virma deficiency significantly impaired liver regeneration capacity and disrupted cell cycle progression. Methylated RNA immunoprecipitation sequencing (MeRIP-seq) analysis revealed that Shq1 is an effective downstream target of VIRMA-mediated m6A modification. The upregulation of Shq1 enhanced the proliferation ability of cells, which was attenuated by the specific AKT inhibitor ipatasertib. Supplementation of Shq1 in vivo alleviated the liver cell proliferation inhibition caused by Virma deficiency. Furthermore, the m6A-binding protein heterogeneous nuclear ribonucleoprotein a2b1 (HNRNPA2B1) enhanced the mRNA stability of Shq1. Mechanistically, Virma deficiency resulted in decreased m6A modification on Shq1 mRNA, leading to reduced binding ability of m6A-binding protein HNRNPA2B1 with Shq1, thereby decreasing the mRNA stability of Shq1 and reducing its protein expression level. Downregulation of Shq1 inhibited the PI3K/AKT pathway, thereby suppressing cell proliferation and cell cycle progression, ultimately impeding liver regeneration. In summary, our results demonstrate that VIRMA plays a critical role in promoting liver regeneration by regulating m6A modification, providing valuable insights into the epigenetic regulation during liver regeneration.

Objective:To analyze the gender difference in behavioral and psychological symptoms of dementia (BPSD) of amnestic mild cognitive impairment (aMCI) and Alzheimer′s disease (AD).Methods:It was a cross-sectional study. The clinical data of 201 patients with aMCI and 146 patients with AD were continuously collected from the Chinese Imaging, Biomarkers and Lifestyle Study of Alzheimer′s Disease (CIBL) cohort between June 1, 2021 to February 1, 2023 in Beijing Tiantan Hospital, Capital Medical University. The BPSD subtypes were compared between different gender. The gender-different BPSD subtypes were divided into depression group (126 cases) and non-depression group (221 cases), anxiety group (140 cases) and non-anxiety group (207 cases), indifference group (131 cases) and non-indifference group (216 cases). The sociodemographic data (age, sex, education level, marital status), hypertension, diabetes, stroke, heart disease, hyperlipidemia, smoking history, drinking history, carrier status of apolipoprotein E epsilon4 allele (APOE ε4), and the scores of the Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA), Neuropsychiatric Inventory (NPI), Activity of Daily Living (ADL) were compared by using hypothesis testing. Multivariate logistic regression was used to analyze the gender differences of BPSD in aMCI and AD patients.Results:The incidence rates of depression and anxiety in female were both significantly higher than those in male (44.93% vs 23.57%, 44.93% vs 33.57%), and the incidence rate of apathy was significantly lower than that in male (32.37% vs 45.71%) (all P<0.05). The proportion of female and ADL scores in depression group were both significantly higher than those in non-depression group [73.81% vs 51.58%, 22.00 (20.00, 30.00) vs 20.00 (20.00, 26.00) points], and the proportion of smoking and drinking history and MoCA scores in depression group were all significantly lower than those in non-depression group [13.49% vs 25.79%, 19.84% vs 35.75%, 16.00 (10.00, 22.00) vs 19.00 (13.00, 24.00) points] (all P<0.05). The proportion of female and ADL scores in anxiety group were both significantly higher than those in non-anxiety group [66.43% vs 55.07%, 23.00 (20.00, 30.75) vs 20.00 (20.00, 25.00) points], and the MMSE and MoCA scores in anxiety group were both significantly lower than those in non-anxiety group [23.00 (16.00, 27.00) vs 24.00 (19.00, 28.00) points, 16.00 (10.00, 21.00) vs 20.00 (13.00, 13.00) points] (all P<0.05). The proportion of female and the MMSE and MoCA scores in apathy group were all significantly lower than those in non-apathy group [51.15% vs 64.81%, 19.00 (11.00, 25.00) vs 26.00 (22.00, 28.00) points, 14.00 (7.00, 19.00) vs 21.00 (15.25, 24.00) points], and the age, proportion of APOE ε4 carriers and ADL scores in apathy group were all significantly higher [67.0 (61.0, 76.0) vs 66.0 (60.0, 71.0) years, 42.74% vs 31.31%, 27.00 (22.00, 38.00) vs 20.00 (20.00, 22.00) points] (all P<0.05). Female ( OR=2.384, 95% CI: 1.274-4.459) and decrease in MoCA score ( OR=0.955, 95% CI: 0.914-0.998) were positively correlated with risk of depression. Female ( OR=1.704, 95% CI: 1.077-2.695) was positively correlated with risk of anxiety. Male ( OR=0.558, 95% CI: 0.333-0.936), decrease in MoCA scores ( OR=0.937, 95% CI: 0.894-0.983) and increase in ADL scores ( OR=1.070, 95% CI: 1.027-1.116) were positively correlated with risk of apathy (all P<0.05). Conclusions:There are significant gender differences in BPSD in aMCI and AD patients. Female is positively correlated with risk of depression and anxiety, while male is positively correlated with the occurrence of apathy. Clinical attention should be paid to hierarchical management of BPSD patients of different gender.

Objective:To analyze the correlation between blood pressure variability (BPV) and behavioral and psychological symptoms of dementia (BPSD) in patients with Alzheimer′s disease (AD).Methods:In this retrospective cohort study, sixty-nine patients with AD from Beijing Tiantan Hospital, Capital Medical University, the Chinese Imaging, Biomarkers and Lifestyle Study of Alzheimer′s Disease were consecutively collected from February 1 to August 31, 2023. The patients were divided into the BPSD group (50 patients) and the control group (19 patients) according to with or without BPSD. The patients′ general information were collected, such as age at enrolment, gender, duration of education, and history of hypertension, diabetes, cerebral infarction, hyperlipoidemia, smoking, alcohol consumption, and carrier status of apolipoprotein E epsilon4 allele (APOE ε4). The 24-hour ambulatory blood pressure monitoring instruments were also used to collect the patients′ mean systolic blood pressure, mean diastolic blood pressure and 12 BPV indicators, which covered standard deviation (SD) and coefficient of variation (CV) of systolic and diastolic blood pressure throughout the day, daytime and nighttime. The Montreal Cognitive Assessment (MoCA) was used to assess their cognitive function, and the Activity of Daily Living (ADL)-14 items was used to assess their daily living abilities; hypothesis tests were used to compare the general information, MoCA scores, ADL-14 items scores, mean blood pressure and BPV indicators between the two groups; the multivariate logistic regression analysis was conducted to explore the related factors of BPSD in AD patients; Spearman correlation analysis was used to test the correlation between the total score of neuropsychiatric inventory (NPI) and BPV indicators in AD patients with BPSD.Results:In the BPSD group, the incidence rate of hypertension and MoCA scores were both significantly lower than those in the control group [44.00% vs 73.70%, (9.72±5.60) vs (14.53±5.52) points], but ADL-14 items scores and nocturnal systolic blood pressure CV were both significantly higher [23.00 (17.00, 29.25) vs 14.00 (14.00, 17.00) points, 8.89%±2.26% vs 7.52%±2.30%] (all P<0.05). Elevated ADL-14 items scores ( OR=1.379, 95% CI: 1.131-1.681) and nocturnal systolic blood pressure CV ( OR=1.387, 95% CI: 1.003-1.918) were positive correlation factors for the risk of BPSD in AD patients (all P<0.05). The daytime systolic blood pressure SD ( r=0.375) and CV ( r=0.357) were both positively correlated with total NPI scores in AD patients with BPSD (all P<0.05). Conclusion:BPV is correlated with BPSD in AD patients. Nocturnal systolic blood pressure CV is a positive correlation factor for the risk of BPSD in AD patients, and the total scores of NPI in AD patients are positively correlated with daytime systolic blood pressure SD and CV. It suggests that controlling BPV is a potential therapeutic measure to improve the BPSD of AD patients.

Objective To investigate the interaction between serum uric acid(SUA)and islet β cell function,and its influence in the development of diabetic peripheral neuropathy(DPN)in patients with type 2 diabetes mellitus(T2DM).Methods A total of 122 patients with T2DM who visited General Medicine Department of our hospital from January 2019 to May 2023 were enrolled in this study and divided into two groups according to whether they had DPN:T2DM group(n=30)and DPN group(n=92).Patients in DPN group were further divided into three groups according to the severity of DPN:mild DPN group(L-DPN,n=30),moderate DPN group(M-DPN,n=36)and severe DPN group(H-DPN,n=26).The clinical data and biochemical indexes were compared and analyzed among the four groups.Logistic multivariate analysis was used to analyze the relationship between SUA and islet β cell secretory function and severe DPN.Multivariate logistic regression was used to analyze the risk factors for the severity of DPN.Stepwise regression method was used to screen the most important related factors for the severity of DPN,and a nomogram model was constructed and validated.The interaction between SUA and islet β cell function,and its influence in the development of DPN in T2DM patients were analyzed.Results Multivariate logistic regression analysis showed that age,SUA,aspartate aminotransferase,HDL-C,HbAlc,islet β cell secretion function(C2/C0)and insulin resistance index(HOMA-IR)were all independent influencing factors for the severity of DPN(P<0.05).The C indices of SUA,C2/C0,HOMA-IR,HbAlc and HDL-C prediction models were 0.776 and 0.769 on the training set and validation set respectively,which were most correlated with the aggravation of DPN degree.The area under the curve of the nomogram model for predicting the risk of DPN severity was 0.928(95%CI 0.856～0.986)and 0.917(95%CI 0.856～0.986)before and after validation respectively.The mean absolute error of the calibration curve was 0.013,which could be used as a risk tool to predict the risk of DPN aggravation.The results of interaction analysis showed that there were multiplicative and additive interactions between SUA and islet β cell secretion.Conclusions There is an interaction between SUA and islet β cell secretion function,which is a risk factor for the aggravation of DPN.The risk factors can be early warned according to the nomogram model,so as to carry out targeted prevention and treatment for T2DM patients.

Background::Few evidence is available in the early prediction models of behavioral and psychological symptoms of dementia (BPSD) in Alzheimer’s disease (AD). This study aimed to develop and validate a novel genetic-clinical-radiological nomogram for evaluating BPSD in patients with AD and explore its underlying nutritional mechanism.Methods::This retrospective study included 165 patients with AD from the Chinese Imaging, Biomarkers, and Lifestyle (CIBL) cohort between June 1, 2021, and March 31, 2022. Data on demographics, neuropsychological assessments, single-nucleotide polymorphisms of AD risk genes, and regional brain volumes were collected. A multivariate logistic regression model identified BPSD-associated factors, for subsequently constructing a diagnostic nomogram. This nomogram was internally validated through 1000-bootstrap resampling and externally validated using a time-series split based on the CIBL cohort data between June 1, 2022, and February 1, 2023. Area under receiver operating characteristic (ROC) curves, calibration curves, and decision curve analysis (DCA) were used to assess the discrimination, calibration, and clinical applicability of the nomogram.Results::Factors independently associated with BPSD were: CETP rs1800775 (odds ratio [OR] = 4.137, 95% confidence interval [CI]: 1.276-13.415, P = 0.018), decreased Mini Nutritional Assessment score (OR = 0.187, 95% CI: 0.086-0.405, P <0.001), increased caregiver burden inventory score (OR = 8.993, 95% CI: 3.830-21.119, P <0.001), and decreased brain stem volume (OR = 0.006, 95% CI: 0.001-0.191, P = 0.004). These variables were incorporated into the nomogram. The area under the ROC curve was 0.925 (95% CI: 0.884-0.967, P <0.001) in the internal validation and 0.791 (95% CI: 0.686-0.895, P <0.001) in the external validation. The calibration plots showed favorable consistency between the prediction of nomogram and actual observations, and the DCA showed that the model was clinically useful in both validations. Conclusion::A novel nomogram was established and validated based on lipid metabolism-related genes, nutritional status, and brain stem volumes, which may allow patients with AD to benefit from early triage and more intensive monitoring of BPSD.Registration::Chictr.org.cn, ChiCTR2100049131.

Objective:To explore the factors on malnutrition or risk of malnutrition in patients with Alzheimer′s disease (AD)-related cognitive impairment,and to further analyze the association between the severity of behavioral and psychological symptoms in dementia (BPSD) and nutritional status.Methods:The clinical data of 247 patients with AD-related cognitive impairment were collected continuously from the Chinese Imaging, Biomarkers and Lifestyle Study of Alzheimer′s Disease (CIBL) cohort between June 1, 2021 and August 31, 2022. The patients were divided into well-nourished group ( n=128) and malnourished group ( n=119) according to the scores of Mini-Nutritional Assessment scale (MNA). The sociodemographic data (sex, age, body mass index, waist-to-hip ratio, education level), the medical history of olfactory dysfunction, combination with more than two chronic diseases, and gastrointestinal diseases, presenting BPSD, and the scores of the Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA), Neuropsychiatric Inventory (NPI), Activity of Daily Living (ADL), Caregiver Burden Inventory (CBI) and Dietary Diversity Score (DDS) were compared between the two groups. The factors with statistically significant differences in hypothesis test and univariate Logistic regression analysis were enrolled in multivariate Logistic regression analysis to further identify independent factors associated with malnutrition in patients with AD-related cognitive impairment. Furthermore, the association between NPI scores and MNA scores was analyzed by Spearman′s rank correlation test. Results:Compared with those in the well-nourished group, patients in the malnourished group had higher age [(66.70±7.01) years vs (69.14±8.87) years, t=-2.39, P=0.018], lower body mass index [(24.68±2.84) kg/m 2vs (22.69±3.63) kg/m 2, t=4.78, P<0.001], and higher proportion of presenting BPSD [22.66% (29/128) vs 76.47% (91/119), χ 2=71.49, P<0.001]; lower scores of MMSE, MoCA, and DDS [24.27±4.69 vs 18.95±8.40, t=6.09; 20.29±5.18 vs 14.55±8.12, t=6.56; 8.00 (8.00, 9.00) vs 8.00 (7.00, 8.00), Z=-4.66; all P<0.001], and higher scores of NPI, ADL and CBI [1.00 (0, 6.00) vs 10.00 (2.00, 25.00), Z=-6.50; 20.00 (20.00, 22.00) vs 27.00 (20.00, 40.00), Z=-7.08; 1.00 (0, 14.75) vs 12.00 (2.00, 35.00), Z=-5.13; all P<0.001]. There were no statistically significant differences in the sex, waist-to-hip ratio, education level, and the medical history of olfactory dysfunction, combination with more than two chronic diseases, and gastrointestinal diseases between the two groups. The multiple Logistic regression analysis demonstrated that the decreased body mass index ( OR=0.79, 95% CI 0.70-0.89, P<0.001), presenting BPSD ( OR=7.84, 95% CI 3.67-16.73, P<0.001), elevated ADL scores ( OR=1.15, 95% CI 1.06-1.24, P<0.001) and CBI scores ( OR=0.98, 95% CI 0.97-1.00, P=0.026), and decreased scores of DDS ( OR=0.66, 95% CI 0.51-0.84, P=0.001) were independently associated with malnutrition in patients with AD-related cognitive impairment. The MNA scores were significantly negatively associated with NPI scores ( r=-0.483,95% CI -0.58--0.38, P<0.001). Conclusions:The decreased body mass index, dietary diversity, and ability of daily living, and presenting BPSD and heavy burden of caregivers can independently contribute to the malnutrition in patients with AD-related cognitive impairment. The more serious the BPSD, the worse the nutritional status.

Objective:To characterize clinical and neuroimaging features, etiologies, and mechanisms of bilateral middle cerebellar peduncle (MCP) infarctions.Methods:Consecutive patients with bilateral MCP infarctions treated in the Beijing Tiantan Hospital, Capital Medical University between January 1, 2020 and April 30, 2022 were enrolled in this retrospective study. The demographic data, vascular risk factors, clincial manifestations and the National Institutes of Health Stroke Scale (NIHSS) scores were collected. Brain diffusion-weighted imaging was used to assess the regions of cerebral infarction, and the extracranial and intracranial segments of the vertebrobasilar artery were evaluated using magnetic resonance angiography, or computed tomography angiography. The stroke etiology and underlying mechanism were evaluated according to the Chinese Ischemic Stroke Subclassification.Results:Ten patients with bilateral MCP infarctions (8 men and 2 women) were analyzed ultimately. The onset age were 51.0-86.0 (64.8±11.4) years. NIHSS scores were 2.0-12.0 (4.9±2.9) points at admission. All patients had vascular risk factors, most of which were hypertension (10 cases) and dyslipoproteinemia (8 cases). The most common clinical manifestations were vertigo (10 cases), followed by ataxia (9 cases) and dysarthria (8 cases). Four cases were isolated bilateral MCP infarctions, while 6 patients were combined with other vertebrobasilar artery infarctions, 4 of which were combined with cerebellar hemisphere infarctions, consistent with the clinical symptoms. The etiology in all patients was large atherosclerosis (severe stenosis or occlusion of V4 segment of vertebral artery and anterior inferior cerebellar artery; 9 cases). Five patients were classified as hypoperfusion/impaired emboli clearance, while 4 patients were considered as artery-to-artery embolism, and 1 was considered as the parent artery (plaque or thrombosis) occluding penetrating artery.Conclusions:Bilateral MCP infarctions are an extremely rare cerebrovascular disease characterized by vertigo, ataxia, and dysarthria. Cerebral infarction can be isolated or often combined with cerebellar hemisphere infarction. The etiology was mostly stenosis or occlusion of V4 segment of vertebral artery and anterior inferior cerebellar artery.

Objective:To analyze the influencing factors of post stroke cognitive impairment (PSCI) and their correlation with cognitive scores in patients with acute ischemic stroke.Methods:In this cross-section study, 36 patients diagnosed with acute ischemic stroke and post stroke cognitive impairment (PSCI) admitted to the Department of Vascular Neurology of Beijing Tiantian Hospital Affiliated to Capital Medical University from June 1, 2022 to September 30, 2022 were selected as the PSCI group. And one to one matching was performed for patients without PSCI (PSNCI group) with an age±1 year and same gender admitted to the hospital during the same period (as control, 36 cases). Basic clinical data of the two groups were collected, the laboratory and imaging examinations were completed. Mini Mental State Examination (MMSE) and Montreal Cognitive Assessment Scale (MoCA) were used for cognitive evaluation by neuropsychologists. Hypothesis testing was used to compare the differences in basic data, laboratory tests and lesion sites between the two groups. Multi-factor conditional logistic regression was performed to analyze the influencing factors of PSCI, and Spearman correlation analysis was carried out to analyze the correlation between influencing factors of PSCI and the cognitive scores.Results:Compared with those in PSNCI group, the proportion of patients with stroke/transient ischemic attack history, hyperhomocysteinemia (HHcy), apolipoprotein E(ApoE) ε4 carriers and the ratio of temporal lobe and thalamus infarction were higher in PSCI group (41.7% vs 13.9%, 36.1% vs 2.8%, 30.6% vs 5.6%, 22.3% vs 2.8%, 25.0% vs 5.6%), the MMSE and MoCA scores were lower in PSCI group [16.50 (8.25, 19.00) vs 28.00 (27.00, 30.00), 10.00 (4.25, 14.50) vs 27.00 (25.00, 28.00)] (all P<0.05). Logistic regression analysis showed that HHcy was a positive correlation factor for PSCI ( OR=2.342, 95% CI=1.186-4.622, P=0.014). Spearman correlation analysis showed that MMSE ( r=-0.415) and MoCA ( r=-0.417) scores were negatively correlated with homocysteine (Hcy) (both P<0.05). Conclusion:HHcy is an important factor affecting the occurrence and development of PSCI in patients with acute ischemic stroke, and Hcy level is negatively correlated with cognitive scores in those patients.

Objectives:To analyze the potential biomarkers of behavioral and psychological symptoms of dementia (BPSD) in patients with Alzheimer′s disease (AD) continuum.Methods:A prospective cohort study was consecutively conducted on 179 patients with AD continuum (135 presented with BPSD, 44 patients without BPSD as control) from Capital Medical University, Beijing Tiantan Hospital, the Chinese imaging biomarkers and lifestyle cohort between January 1, 2021 and December 31, 2022. Gender, age, body max index, education level, diagnosis, the apolipoprotein E epsilon4 allele (APOE ε4) carrier status, the scores of the Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA), cerebrospinal fluid (CSF) AD-related pathological biomarkers (Aβ 42, Aβ 40, Aβ 42/40, tTau, pTau181), and blood biomarkers (white blood cell count, red blood cell count, hemoglobin, platelet, total bilirubin, albumin, total cholesterol, triglyceride, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, fasting glucose, erythrocyte sedimentation rate, homocysteine, vitamin B 12, folate) were compared between the two groups by using hypothesis testing and univariate logistic regression analysis. Multivariate logistic regression analysis was used to analyze the potential biomarkers associated with BPSD in patients with AD. Results:Among the 179 patients with AD continuum in the final analysis, 77 patients were men, 102 cases were women; 35 patients were identified with mild cognitive impairment (MCI) due to AD and 144 patients with AD dementia stage, the mean age was (66.54±9.75) years. Compared with those in control group, patients with BPSD had lower cerebrospinal fluid (CSF) Aβ 40 and blood hemoglobin levels [7.08 (4.42, 15.42) vs 9.62 (6.45, 12.12) pg/L, (132.70±13.37) vs (138.80±14.38) g/L] ( U=-1.856, t=2.579, P<0.05). The levels of CSF Aβ 40 ( OR=0.030, 95% CI: 0.001-0.760) and blood hemoglobin ( OR=0.051, 95% CI: 0.004-0.670) were independently negatively associated with BPSD in patients with AD continuum (both P<0.05). Conclusion:The decreased levels of CSF Aβ 40 and blood hemoglobin could be considered as potential biomarkers in detecting BPSD in patients with AD continuum.