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.

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 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.

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.

Autism spectrum disorder (ASD) is a multifactorial disease, with social difficulties and repetitive behaviors as its core symptoms. With the improvement of diagnostic methods, the detection rate of ASD is increasing year by year.Cognitive flexibility impairment is very obvious in most autistic patients.More and more studies have shown that cognitive flexibility impairment is related to the occurrence and development of core symptoms. However, the mechanism of cognitive flexibility impairment in autism remains unclear. The frontal lobe plays an important role in advanced cognition, and its complete development is related to cognitive function. Recent studies have shown that frontal lobe dysfunction is closely related to cognitive flexibility deficits in autistic patients, and the abnormal changes in the frontal lobe, the associated default mode network dysfunction and frontal striatal circuit defects may be the important mechanisms of cognitive flexibility impairment. Based on the recent clinical and basic studies on cognitive flexibility in autism, this article reviews the mechanisms of frontal lobe and related circuits involved in the impairment of cognitive flexibility in autism.

Objective : To investigate the mechanism of AMD3100 reversing the resistance of human hepatocellular carcinoma cells to Sorafenib by regulating carbonic anhydrase IX ( CA9) and chemokine receptor 4 ( CXCR 4 ) . Methods : The Sorafenib resistant cell lines Huh7 / Sor and HepG2 / Sor were established from human hepatocellular carcinoma cells Huh7 and HepG2．The effects of Sorafenib alone or in combination with AMD3100 on the proliferation of Huh7，HepG2，Huh7 / Sor，HepG2 / Sor cells were detected．The difference of invasive ability between Sorafenib resistant cells and non-resistant cells，and the effect of AMD3100 on the invasive ability of hepatocellular carcinoma cells were observed．And the regulation effect of Sorafenib alone or in combination with AMD3100 on the expression of CA9 and CXCR4 proteins in Huh7，HepG2，Huh7 / Sor and HepG2 / Sor cells was detected. Results: Compared with the Control group，AMD3100 (50 μmol / L) increased the inhibitory effect of Sorafenib on the proliferation of Huh7 / Sor and HepG2 / Sor cells (P＜0．05) ．Compared with Huh7 cells，the invasive ability of Sorafenib resistant Huh7 / Sor cells was significantly enhanced (P＜0. 05) ，and AMD 3100 (50 μmol / L) decreased the invasive ability of Huh7 and Huh7 / Sor cells (P＜0．05) ．Compared with Huh7 and HepG2 cells，the protein expression of CA9 and CXCR4 in Huh7 / Sor and HepG2 / Sor cells increased (P＜0. 05) ．AMD3100 (50 μmol / L) down-regulated the protein expression of CA9 and CXCR4 in Huh7，HepG2，Huh7 / Sor and HepG2 / Sor cells (P ＜0. 05 ) . Conclusion AMD3100 can reduce the resistance of human hepatocellular carcinoma cells to Sorafenib by downregulating the expression of CA9 and CXCR4，and enhance the inhibition of Sorafenib on the proliferation and invasion of human hepatocellular carcinoma cells.

ObjectiveTo explore the clinical efficacy and safety of the combination of Erchentang and Bixie Fenqingyin in the treatment of patients with acute cerebral infarction accompanied by hyperuricemia of phlegm and blood stasis blocking collaterals syndrome to provide a new method and evidence for the treatment of acute cerebral infarction with hyperuricemia. MethodA total of 132 eligible patients with acute cerebral infarction accompanied by hyperuricemia of phlegm and blood stasis blocking collaterals syndrome admitted to the Putuo Hospital of Shanghai University of Traditional Chinese Medicine（TCM） from May 2021 to May 2022 were randomly divided into a Chinese medicine group， a western medicine group， and a control group， with 44 cases in each group. All three groups received routine western medical treatment for acute cerebral infarction. Additionally， the Chinese medicine group received Erchentang combined with Bixie Fenqingyin， the western medicine group received Benzbromarone tablets， and the control group did not receive any uric acid-lowering treatment. The treatment duration was four weeks. The modified Rankin Scale （mRS） score after three months of onset， as well as the National Institutes of Health Stroke Scale （NIHSS） scores， TCM syndrome scores， serum uric acid （SUA） levels， serum C-reactive protein （CRP） and interleukin-6 （IL-6） levels， serum superoxide dismutase （SOD） and malondialdehyde （MDA） levels， and other safety indicators were observed before and after treatment. ResultA total of 129 cases completed the trial observation， with 43 cases in the Chinese medicine group， 42 cases in the western medicine group， and 44 cases in the control group. The rate of good prognosis in the Chinese medicine group （83.7%，36/43） was higher than that in the western medicine group （64.3%，27/42） and the control group （40.9%，18/44） （χ²=4.184，16.930，P<0.05）， and the western medicine group was superior to the control group （χ²=4.707，P<0.05）. After treatment， the NIHSS scores， TCM syndrome scores， SUA， CRP， IL-6， and MDA levels of the patients in all three groups decreased， while the SOD levels increased compared with those before treatment （P<0.05）. Among them， the improvement in NIHSS score was better in the Chinese medicine group and the western medicine group than in the control group （P<0.05）. The Chinese medicine group showed the greatest improvement in TCM syndrome （P<0.05）， while the western medicine group showed the greatest reduction in uric acid levels （P<0.05）. No significant abnormalities in safety indicators were observed before and after treatment in the three groups， and no serious adverse reactions were reported. ConclusionThe combination of Erchentang and Bixie Fenqingyin can significantly improve the prognosis， early neurological deficits， and TCM syndromes of patients acute cerebral infarction accompanied by hyperuricemia of phlegm and blood stasis blocking collaterals syndrome. It can also lower uric acid levels and inhibit inflammatory and oxidative stress reactions.

In response to the problem that the traditional lower limb rehabilitation scale assessment method is time-consuming and difficult to use in exoskeleton rehabilitation training, this paper proposes a quantitative assessment method for lower limb walking ability based on lower limb exoskeleton robot training with multimodal synergistic information fusion. The method significantly improves the efficiency and reliability of the rehabilitation assessment process by introducing quantitative synergistic indicators fusing electrophysiological and kinematic level information. First, electromyographic and kinematic data of the lower extremity were collected from subjects trained to walk wearing an exoskeleton. Then, based on muscle synergy theory, a synergistic quantification algorithm was used to construct synergistic index features of electromyography and kinematics. Finally, the electrophysiological and kinematic level information was fused to build a modal feature fusion model and output the lower limb motor function score. The experimental results showed that the correlation coefficients of the constructed synergistic features of electromyography and kinematics with the clinical scale were 0.799 and 0.825, respectively. The results of the fused synergistic features in the K-nearest neighbor (KNN) model yielded higher correlation coefficients ( r = 0.921, P < 0.01). This method can modify the rehabilitation training mode of the exoskeleton robot according to the assessment results, which provides a basis for the synchronized assessment-training mode of "human in the loop" and provides a potential method for remote rehabilitation training and assessment of the lower extremity.
Humans ; Exoskeleton Device ; Reproducibility of Results ; Walking/physiology* ; Lower Extremity ; Algorithms ; Stroke Rehabilitation/methods*