ObjectiveTo develop and validate a nomogram for predicting the risk of concurrent cognitive impairment in older adults with heart disease. MethodsSelf-reported data from 2 673 respondents in the 2020 China Health and Retirement Longitudinal Study were analyzed. The participants were randomly divided into a training set (n = 1 871) and a validation set (n = 802). Heart disease status was determined using a self-report questionnaire. Logistic regression analysis was performed to identify predictors, and a nomogram for predicting the risk of concurrent cognitive impairment in older adults with heart disease was developed using R software. Bootstrap resampling was used for internal validation, and model performance was further evaluated in the randomly split validation set. The predictive performance of the model was assessed using the area under the receiver operating characteristic curve (AUC) and calibration curves.. ResultsA total of 2 673 older adults with heart disease were included, out of whom 315 participants in the training set had cognitive impairment. Lasso regression analysis identified age, education level, place of residence, instrumental activities of daily living and depression as predictors of concurrent cognitive impairment. A prediction model incorporating these five variables was constructed. The AUC were 0.827 (95%CI 0.804 to 0.850) in the training set and 0.847 (95%CI 0.812 to 0.882) in the validation set. The Hosmer-Lemeshow test yielded P = 0.154 and P = 0.716 in the training and validation sets, respectively. Calibration curves showed good agreement between predicted and observed probabilities. Decision curve analysis indicated that the model provided favorable net benefit and predictive performance. ConclusionThe nomogram may provide a useful reference for risk screening and early intervention for cognitive impairment in older adults with heart disease.

Successful cloning through somatic cell nuclear transfer (SCNT) faces significant challenges due to epigenetic obstacles. Recent studies have highlighted the roles of H3K4me3 and H3K27me3 as potential contributors to these obstacles. However, the underlying mechanisms remain largely unclear. In this study, we generated genome-wide maps of H3K4me3 and H3K27me3 in mouse pre-implantation NT embryos. Our analysis revealed that aberrantly over-represented broad H3K4me3 domain and H3K27me3 signal lead to increased bivalent marks at gene promoters in NT embryos compared with naturally fertilized (NF) embryos at the 2-cell stage, which may link to relatively low levels of H3K36me3 in NT 2-cell embryos. Notably, the overexpression of Setd2, a H3K36me3 methyltransferase, successfully restored multiple epigenetic marks, including H3K36me3, H3K4me3, and H3K27me3. In addition, it reinstated the expression levels of ZGA-related genes by reestablishing H3K36me3 at gene body regions, which excluded H3K27me3 from bivalent promoters, ultimately improving cloning efficiency. These findings highlight the excessive bivalent state at gene promoters as a potent barrier and emphasize the removal of these barriers as a promising approach for achieving higher cloning efficiency.
Animals ; Mice ; Histone-Lysine N-Methyltransferase/biosynthesis* ; Histones/genetics* ; Nuclear Transfer Techniques ; Female ; Gene Expression Regulation, Developmental ; Promoter Regions, Genetic ; Epigenesis, Genetic ; Embryo, Mammalian/metabolism*

OBJECTIVES: This study aimed to investigate the potential mediating role of plasma phosphorylated tau217 (p-tau217) in the association between periodontitis and mild cognitive impairment (MCI). METHODS: In this case-control study, patients diagnosed with MCI in the Neurology Department of the First Affiliated Hospital of Shandong Second Medical University from November 2023 to May 2024 were selected as the case group (MCI group). Cognitively normal (CN) volunteers, matched for age and education level and recruited from the physical examination center during the same period, served as the control group (CN group). The general demographic data of the study participants were collected. The Beijing versions of the Montreal Cognitive Assessment (MoCA), clinical dementia rating (CDR), and activities of daily living scale (ADL) were used to assess neuropsychological functions. Clinical periodontal examinations were conducted, the periodontal inflamed surface area (PISA) was calculated, and the periodontitis stage was determined in accordance with the 2018 classification. Fasting elbow venous blood samples were collected in the morning, and blood biochemical indicators were measured. Plasma p-tau217 levels were detected using enzyme-linked immunosorbent assay (ELISA). Statistical analyses were performed using t-test, Mann-Whitney U test, chi-square test, partial correlation analysis, multivariate Logistic regression analysis, multiple linear regression analysis, restricted cubic spline (RCS) regression analysis, and mediation effect analysis. RESULTS: Among the 192 participants, 96 belong to the MCI group and 96 to the CN group. The prevalence of periodontitis was 63.5% in the MCI group and 43.8% in the CN group, with a statistically significant difference (χ²=7.561, P=0.006). The plasma p-tau217 levels in the MCI group were significantly higher than those in the CN group [7.00 (4.27-9.65) ng/mL versus 2.02 (0.80-3.81) ng/mL, Z=-8.108, P<0.001]. Partial correlation analysis revealed that plasma p-tau217 levels were positively correlated with all the clinical periodontal indices (all P<0.001). After adjustments for baseline covariates, multivariate Logistic regression indicated that periodontitis was an independent risk factor for MCI. Patients with periodontitis had a 1.977-fold higher MCI risk than those without periodontitis (OR=1.977, 95%CI: 1.088-3.594, P=0.025). Moreover, the MCI risk for stage Ⅰ/Ⅱ periodontitis and stage Ⅲ/Ⅳ periodontitis was 1.878 times (OR=1.878, 95%CI: 1.029-3.425, P=0.040) and 2.625 times (OR=2.625, 95%CI: 1.073-6.246, P=0.035) higher than that for patients without periodontitis, respectively. Trend test showed that the MCI risk increased with periodontitis severity (P_trend=0.016). After adjustments for baseline covariates, multiple linear regression analysis showed that periodontitis was an independent risk factor for increased plasma p-tau217 levels (β=3.309, 95%CI: 2.363-4.254, P<0.001). Compared with patients without periodontitis, those with stage Ⅰ/Ⅱ periodontitis (β=1.838, 95%CI: 0.869-2.806, P<0.001) and stage Ⅲ/Ⅳ periodontitis (β=5.539, 95%CI: 4.442-6.636, P<0.001) had significantly higher plasma p-tau217 levels. In addition, trend test indicated that plasma p-tau217 levels increased with periodontitis severity (P_trend<0.001). After adjustments for baseline covariates, RCS regression analysis further revealed that PISA had a positive linear dose-response relationship with MCI risk (P_overall=0.002, P_nonlinear=0.344) and plasma p-tau217 levels (P_overall<0.001, P_nonlinear=0.140). After adjustments for baseline covariates, mediation analysis showed that plasma p-tau217 mediated the association between periodontitis and MCI, with a mediation proportion of 13.99% (95% Bootstrap CI: 0.38%-49.39%, P=0.038). CONCLUSIONS Periodontitis was independently positively associated with MCI risk, and plasma p-tau217 plays a mediating role in this association.
Humans ; Cognitive Dysfunction/complications* ; tau Proteins/blood* ; Periodontitis/complications* ; Case-Control Studies ; Male ; Female ; Phosphorylation ; Aged ; Middle Aged ; Activities of Daily Living

Background: Condyloma acuminatum (CA) is a common sexually transmitted disease caused by human papillomavirus (HPV). In recent years, research on anal CA has primarily focused on treatment rather than underlying mechanisms. The mechanism of HPV persistence and recurrence in CA require further exploration. It needs multiple researches in mechanisms to focalize treatment targets. Objective: To investigate the relationship between intestinal mucosal immunity and the relapse of anal CA and persistent infection. Methods: Levels of interferon gamma (IFN-γ) and secretory immunoglobulin A (sIgA) were measured using enzyme-linked immunosorbnent assay in anal mucosal cells obtained from patients treated at Tianjin Union Medical Center from September 2022 to December 2024. All the participants signed Informed Consent and the whole plan was approved by Institutional Review Board in Tianjin Union Medical Center (No. B155). Results: The levels of IFN-γ and sIgA significantly decreased after infection, and persistent infection exhibited even lower levels. These two factors increased following treatment, reaching peak concentrations at 4 weeks before decreasing again. Conclusion These findings demonstrate a significant association between persistent anal CA infection and dysregulation of intestinal mucosal immunity.

BACKGROUND:Exercise as a form of active rehabilitation can improve the dysfunction caused by peripheral nerve injury,and different exercise modalities target different lesion sites and recovery mechanisms. OBJECTIVE:To comprehensively analyze the application and mechanisms of different exercise modalities in functional recovery from peripheral nerve injury. METHODS:A computerized search was conducted in PubMed and CNKI databases for relevant literature published before January 2024.The search terms used were"peripheral nerve injury,spinal cord,exercise,cerebral cortex,muscle atrophy,mirror therapy,blood flow restriction training"in both English and Chinese.Finally,77 articles were included for review. RESULTS AND CONCLUSION:Peripheral nerve injury can cause systemic pathological changes such as skeletal muscle atrophy,corresponding spinal cord segmental lesions,and sensorimotor cortex remodeling.Aerobic exercise can improve dysfunction by enhancing the immune response,promoting glial cell polarization,and promoting the release of nerve growth factor.Blood flow restriction exercise can regulate the secretion of muscle growth factor,promote muscle growth and enhance muscle strength.Mirror movement has a good effect in activating the cerebral cortex and reducing cortical remodeling.Different exercise modalities have potential benefits in functional recovery after peripheral nerve injury;however,there are still some problems and challenges,such as the choice of exercise modalities,the control of exercise intensity and frequency,and the detailed analysis of mechanisms.

Objective:Using ecological niche width and situation model,the operation and management of public Traditional Chinese Medicine(TCM)hospitals in 16 cities in Shandong Province were evaluated to put forward countermeasures.Methods:The relevant index data of public TCM hospitals in 16 cities in Shandong Province from 2019 to 2022 were collected to analyze the development status.The ecological niche width model and niche situation model were applied to evaluate the operation and management of public TCM hospitals in 16 cities in Shandong.Results:The top three public TCM hospitals in terms of average ecological niche width were City G,City P and City F.The ecological niche situation value of public TCM hospitals in City K,City A and City J ranked the top three.Conclusion:The dimensions of operation management structure of public TCM hospitals in Shandong need to be enhanced and the development of operation management space needs to be balanced.It is feasible to evaluate operation management by using ecological niche width and situation model.It is suggested to improve the allocation efficiency of health personnel,facilities,funds and other resources;promote the spatial balanced development of operation management;promote the application of ecological niche width and situation model in the field of medicine and health management.

BACKGROUND:Cervical disc degeneration is a common degenerative disease,and inflammatory proteins play an important role in cervical disc degeneration,but the specific mechanisms involved remain to be thoroughly investigated.OBJECTIVE:Using the Mendelian randomization method to assess the potential causal relationship between 91 inflammatory proteins and cervical disc degeneration.METHODS:Genome-wide association analysis statistics for 91 inflammatory proteins(from GCST90274758 to GCST90274848)were obtained from the Genome-Wide Association Analysis Catalog of publicly available genome-wide association analysis data and genome-wide association analysis data for cervical disc degeneration from the Finngen database(finngen_R10_M13_CERVICDISCV).Inverse variance weighting,MR-Egger regression,weighted median,weighted modeling,and simple modeling were used to investigate the causal relationship between inflammatory proteins and cervical disc degeneration.Sensitivity analyses were performed to test whether the results of the Mendelian randomization analysis were reliable,and then the inverse Mendelian randomization analysis was performed in the same way.RESULTS AND CONCLUSION:The results of the forward analysis showed that a total of six inflammatory proteins were significantly and causally associated with cervical disc degeneration,of which glial cell lineage-derived neurotrophic factor(odds ratio(OR)=1.095,95%confidence interval(CI):1.012-1.184,P=0.023),interleukin 4(OR=1.094,95%CI:1.002-1.194,P=0.045)and monocyte chemotactic protein-1 levels(OR=1.062,95%CI:1.001-1.127,P=0.048)showed a direct positive causal association with the risk of cervical disc degeneration;interleukin 17C(OR=0.906,95%CI:0.839-0.979,P=0.013),interleukin 18(OR=0.924,95%CI:0.866-0.986,P=0.017)and interleukin 2 levels(OR=0.894,95%CI:0.821-0.973,P=0.010)showed a direct negative causal association with the risk of cervical disc degeneration.The results of the inverse analysis showed that when cervical disc degeneration was used as exposure data,there was no significant causal relationship with any of the 91 inflammatory proteins.The results of the sensitivity analysis showed that the Cochran's Q test for the two-way Mendelian randomization,the MR-Egger regression method,and the MR-PRESSO results had P values greater than 0.05,indicating that there was no significant heterogeneity or multiplicity in the analysis of the causal effect between inflammatory proteins and cervical disc degeneration.To conclude,there may be a relatively significant potential causal relationship between glial cell line-derived neurotrophic factor,interleukin 4,monocyte chemotactic protein-1,interleukin 17C levels,interleukin 18,and interleukin 2 levels and cervical disc degeneration,which provides valuable clues for research on the potential mechanisms of cervical disc degeneration as well as early prevention and drug treatment of cervical disc degeneration.

BACKGROUND:Electrical stimulation is an effective treatment plan for peripheral nerve injuries,but different frequencies of electrical stimulation have different mechanisms and applications for promoting peripheral nerve recovery.OBJECTIVE:To systematically sort out and summarize the roles and applications of different frequencies of electrical stimulation in the treatment of peripheral nerve injuries,and to deeply analyze the advantages and disadvantages of various methods in order to find the most beneficial treatment strategy for patients'nerve recovery.METHODS:Computer-based searches were conducted in the China National Knowledge Infrastructure(CNKI)and PubMed databases from the inception of the databases to May 2024.The search terms included"peripheral nerve injury,electrical stimulation,low frequency electrical stimulation,medium frequency electrical stimulation,high frequency electrical stimulation,TENS,interfering electricity,short wave,ultrashort wave,frequency"in both English and Chinese.Ultimately,74 relevant documents were included for analysis.RESULTS AND CONCLUSION:Peripheral nerve injury,a common clinical disease,can cause sensory and motor dysfunction in patients.Low-frequency electrical stimulation can promote cell proliferation and accelerate the expression of nerve growth factor within the cell after electrical stimulation,promote macrophage recruitment and infiltration,accelerate the clearance of myelin debris,and promote myelin regeneration of damaged axons.Medium-frequency electrical stimulation can act on deeper tissues and is better for relieving neuropathic pain.High-frequency electrical stimulation can promote the proliferation of Schwann cells and macrophages,inhibit inflammatory factors,and rapidly recruit cells to the site of nerve injury,accelerating the speed of nerve repair.Different frequencies of electrical stimulation have their own advantages in promoting the recovery of peripheral nerve injuries,but there are still some issues,such as differences in the site of electrical stimulation and the treatment plans for various disease types.

BACKGROUND:Electromyographic biofeedback therapy has demonstrated unique advantages of non-invasive,real-time feedback,personalized treatment and promotion of neuroplasticity,and can promote the recovery of motor function in patients with spinal cord injury.OBJECTIVE:To review the current application status and therapeutic effects of electromyographic biofeedback combined with exercise therapy,robotic exoskeletons,and virtual reality technology in the recovery of motor function after spinal cord injury.METHODS:Relevant literature was retrieved from CNKI and PubMed databases up to May 2024.The search terms included"spinal cord injury,EMG biofeedback,physical therapy,robotic exoskeleton,VR,motor function,exercise"in both English and Chinese.Finally,71 articles were included for review.RESULTS AND CONCLUSION:Mechanisms by which electromyographic biofeedback therapy promotes spinal cord injury rehabilitation include promoting neural plasticity changes,strengthening neuromuscular connections and improving movement patterns.Electromyographic biofeedback,as an emerging tool for treating spinal cord injury,is often used in conjunction with other therapeutic methods,including exercise therapy,robotic exoskeletons,and VR,to promote the recovery of motor function after spinal cord injury.The effectiveness of combination therapy has been significantly improved.However,there are still some problems and challenges,such as the lack of detailed analysis of the mechanism,the lack of large-scale trials that provide strong evidence for combined efficacy,and the limited adaptability of the technology.Future research can focus on these aspects:to improve the personalization and accuracy of electromyographic biofeedback;to develop new rehabilitation equipment and expand the application areas of electromyographic biofeedback combined with more advanced technologies or engineering equipment;to apply electromyographic biofeedback to gait training systems,respiratory training systems,and limb-linkage rehabilitation systems,so as to improve the accuracy of the feedback and the effect of personalized treatment plans.At the same time,the ease of use and comfort of the equipment will be improved.

BACKGROUND:Cervical disc degeneration is a common degenerative disease,and inflammatory proteins play an important role in cervical disc degeneration,but the specific mechanisms involved remain to be thoroughly investigated.OBJECTIVE:Using the Mendelian randomization method to assess the potential causal relationship between 91 inflammatory proteins and cervical disc degeneration.METHODS:Genome-wide association analysis statistics for 91 inflammatory proteins(from GCST90274758 to GCST90274848)were obtained from the Genome-Wide Association Analysis Catalog of publicly available genome-wide association analysis data and genome-wide association analysis data for cervical disc degeneration from the Finngen database(finngen_R10_M13_CERVICDISCV).Inverse variance weighting,MR-Egger regression,weighted median,weighted modeling,and simple modeling were used to investigate the causal relationship between inflammatory proteins and cervical disc degeneration.Sensitivity analyses were performed to test whether the results of the Mendelian randomization analysis were reliable,and then the inverse Mendelian randomization analysis was performed in the same way.RESULTS AND CONCLUSION:The results of the forward analysis showed that a total of six inflammatory proteins were significantly and causally associated with cervical disc degeneration,of which glial cell lineage-derived neurotrophic factor(odds ratio(OR)=1.095,95%confidence interval(CI):1.012-1.184,P=0.023),interleukin 4(OR=1.094,95%CI:1.002-1.194,P=0.045)and monocyte chemotactic protein-1 levels(OR=1.062,95%CI:1.001-1.127,P=0.048)showed a direct positive causal association with the risk of cervical disc degeneration;interleukin 17C(OR=0.906,95%CI:0.839-0.979,P=0.013),interleukin 18(OR=0.924,95%CI:0.866-0.986,P=0.017)and interleukin 2 levels(OR=0.894,95%CI:0.821-0.973,P=0.010)showed a direct negative causal association with the risk of cervical disc degeneration.The results of the inverse analysis showed that when cervical disc degeneration was used as exposure data,there was no significant causal relationship with any of the 91 inflammatory proteins.The results of the sensitivity analysis showed that the Cochran's Q test for the two-way Mendelian randomization,the MR-Egger regression method,and the MR-PRESSO results had P values greater than 0.05,indicating that there was no significant heterogeneity or multiplicity in the analysis of the causal effect between inflammatory proteins and cervical disc degeneration.To conclude,there may be a relatively significant potential causal relationship between glial cell line-derived neurotrophic factor,interleukin 4,monocyte chemotactic protein-1,interleukin 17C levels,interleukin 18,and interleukin 2 levels and cervical disc degeneration,which provides valuable clues for research on the potential mechanisms of cervical disc degeneration as well as early prevention and drug treatment of cervical disc degeneration.