1.Effect Analysis of Different Interventions to Improve Neuroinflammation in The Treatment of Alzheimer’s Disease
Jiang-Hui SHAN ; Chao-Yang CHU ; Shi-Yu CHEN ; Zhi-Cheng LIN ; Yu-Yu ZHOU ; Tian-Yuan FANG ; Chu-Xia ZHANG ; Biao XIAO ; Kai XIE ; Qing-Juan WANG ; Zhi-Tao LIU ; Li-Ping LI
Progress in Biochemistry and Biophysics 2025;52(2):310-333
Alzheimer’s disease (AD) is a central neurodegenerative disease characterized by progressive cognitive decline and memory impairment in clinical. Currently, there are no effective treatments for AD. In recent years, a variety of therapeutic approaches from different perspectives have been explored to treat AD. Although the drug therapies targeted at the clearance of amyloid β-protein (Aβ) had made a breakthrough in clinical trials, there were associated with adverse events. Neuroinflammation plays a crucial role in the onset and progression of AD. Continuous neuroinflammatory was considered to be the third major pathological feature of AD, which could promote the formation of extracellular amyloid plaques and intracellular neurofibrillary tangles. At the same time, these toxic substances could accelerate the development of neuroinflammation, form a vicious cycle, and exacerbate disease progression. Reducing neuroinflammation could break the feedback loop pattern between neuroinflammation, Aβ plaque deposition and Tau tangles, which might be an effective therapeutic strategy for treating AD. Traditional Chinese herbs such as Polygonum multiflorum and Curcuma were utilized in the treatment of AD due to their ability to mitigate neuroinflammation. Non-steroidal anti-inflammatory drugs such as ibuprofen and indomethacin had been shown to reduce the level of inflammasomes in the body, and taking these drugs was associated with a low incidence of AD. Biosynthetic nanomaterials loaded with oxytocin were demonstrated to have the capability to anti-inflammatory and penetrate the blood-brain barrier effectively, and they played an anti-inflammatory role via sustained-releasing oxytocin in the brain. Transplantation of mesenchymal stem cells could reduce neuroinflammation and inhibit the activation of microglia. The secretion of mesenchymal stem cells could not only improve neuroinflammation, but also exert a multi-target comprehensive therapeutic effect, making it potentially more suitable for the treatment of AD. Enhancing the level of TREM2 in microglial cells using gene editing technologies, or application of TREM2 antibodies such as Ab-T1, hT2AB could improve microglial cell function and reduce the level of neuroinflammation, which might be a potential treatment for AD. Probiotic therapy, fecal flora transplantation, antibiotic therapy, and dietary intervention could reshape the composition of the gut microbiota and alleviate neuroinflammation through the gut-brain axis. However, the drugs of sodium oligomannose remain controversial. Both exercise intervention and electromagnetic intervention had the potential to attenuate neuroinflammation, thereby delaying AD process. This article focuses on the role of drug therapy, gene therapy, stem cell therapy, gut microbiota therapy, exercise intervention, and brain stimulation in improving neuroinflammation in recent years, aiming to provide a novel insight for the treatment of AD by intervening neuroinflammation in the future.
2.Comparison of small-sample multi-class machine learning models for plasma concentration prediction of valproic acid
Xi CHEN ; Shen’ao YUAN ; Hailing YUAN ; Jie ZHAO ; Peng CHEN ; Chunyan TIAN ; Yi SU ; Yunsong ZHANG ; Yu ZHANG
China Pharmacy 2025;36(11):1399-1404
OBJECTIVE To construct three-class (insufficient, normal, excessive) and two-class (insufficient, normal) models for predicting plasma concentration of valproic acid (VPA), and compare the performance of these two models, with the aim of providing a reference for formulating clinical medication strategies. METHODS The clinical data of 480 patients who received VPA treatment and underwent blood concentration test at the Xi’an International Medical Center Hospital were collected from November 2022 to September 2024 (a total of 695 sets of data). In this study, predictive models were constructed for target variables of three-class and two-class models. Feature ranking and selection were carried out using XGBoost scores. Twelve different machine learning algorithms were used for training and validation, and the performance of the models was evaluated using three indexes: accuracy, F1 score, and the area under the working characteristic curve of the subject (AUC). RESULTS XGBoost feature importance scores revealed that in the three-class model, the importance ranking of kidney disease and electrolyte disorders was higher. However, in the two-class model, the importance ranking of these features significantly decreased, suggesting a close association with the excessive blood concentration of VPA. In the three-class model, Random Forest method performed best, with F1 score of 0.704 0 and AUC of 0.519 3 on the test set; while in the two-class model, CatBoost method performed optimally, with F1 score of 0.785 7 and AUC of 0.819 5 on the test set. CONCLUSIONS The constructed three-class model has the ability to predict excessive VPA blood concentration, but its prediction and model generalization abilities are poor; the constructed two-class model can only perform classification prediction for insufficient and normal blood concentration cases, but its model performance is stronger.
3.Somatic CDKN2A copy number variations are associated with the prognosis of esophageal squamous cell dysplasia
Zhiyuan FAN ; Jing ZHOU ; Yuan TIAN ; Yu QIN ; Zhaojun LIU ; Liankun GU ; M. Sanford DAWSEY ; Wenqiang WEI ; Dajun DENG
Chinese Medical Journal 2024;137(8):980-989
Background::Somatic copy number variations (SCNVs) in the CDKN2A gene are among the most frequent events in the dysplasia-carcinoma sequence of esophageal squamous cell carcinoma. However, whether CDKN2A SCNVs are useful biomarkers for the risk stratification and management of patients with esophageal squamous cell dysplasia (ESCdys) is unknown. This study aimed to investigate the characteristics and prognostic value of CDKN2A SCNVs in patients with mild or moderate (m/M) ESCdys. Methods::This study conducted a prospective multicenter study of 205 patients with a baseline diagnosis of m/M ESCdys in five high-risk regions of China (Ci County, Hebei Province; Yanting, Sichuan Province; Linzhou, Henan Province; Yangzhong, Jiangsu Province; and Feicheng, Shandong Province) from 2005 to 2019. Genomic DNA was extracted from paraffin biopsy samples and paired peripheral white blood cells from patients, and a quantitative polymerase chain reaction assay, P16-Light, was used to detect CDKN2A copy number. The cumulative regression and progression rates of ESCdys were evaluated using competing risk models. Results::A total of 205 patients with baseline m/M ESCdys were enrolled. The proportion of ESCdys regression was significantly lower in the CDKN2A deletion cohort than in the diploid and amplification cohorts (18.8% [13/69] vs. 35.0% [28/80] vs. 51.8% [29/56], P <0.001). In the univariable competing risk analysis, the cumulative regression rate was statistically significantly lower ( P = 0.008), while the cumulative progression rate was higher ( P = 0.017) in ESCdys patients with CDKN2A deletion than in those without CDKN2A deletion. CDKN2A deletion was also an independent predictor of prognosis in ESCdys ( P = 0.004) in the multivariable analysis. Conclusion::The results indicated that CDKN2A SCNVs are associated with the prognosis of ESCdys and may serve as potential biomarkers for risk stratification.
4.Research progress in regulatory mechanism and traditional Chinese medicine intervention of circular RNA for coronary atherosclerotic heart disease
Lan-Tian HU ; Xue-Na XIE ; Yu-Ying WANG ; Mei LIU ; Hong-Ai GUO ; Rong YUAN ; Qi-Qi XIN ; Yu MIAO ; Wei-Hong CONG
Chinese Pharmacological Bulletin 2024;40(11):2014-2019
Coronary atherosclerotic heart disease(CHD)is an ischemic cardiovascular condition caused by the narrowing or blockage of the vascular lumen due to coronary atherosclerosis.Clinically,it presents as angina pectoris,heart failure,or sud-den cardiac death,and stands as one of the primary causes of mortality among both urban and rural populations in China.Cir-cRNA,classified as non-coding RNAs,can function as upstream regulatory molecules for miRNA or RNA-binding proteins.They actively participate in various pathological processes associated with CHD,including endothelial cell dysfunction,smooth mus-cle cell migration,macrophage-derived foam cell formation,an-giogenesis,myocardial injury,and repair,as well as post-in-farction heart failure.The expression pattern of these molecules is highly specific to the illness and tissue,indicating their poten-tial as therapeutic targets for disease management and as biomar-kers.Furthermore,they also open up new avenues for drug tar-get development in the field of traditional Chinese medicine.This article aims to provide an overview of the recent research progress on circRNA in the regulation of coronary heart disease,as well as the mechanisms involved in traditional Chinese medi-cine.It serves as a valuable reference for future research on cor-onary heart disease.
5.Three-dimensional finite element analysis of lumbar disc herniation under different body positions
Ben-Jing YIN ; Yu LU ; Fu-Tao JI ; Rong-Neng QIU ; Yuan-Yang XIE ; Ge CHEN ; Tian-Li XU ; Chao-Yu BAO ; Ju-Bao LI
China Journal of Orthopaedics and Traumatology 2024;37(6):599-604
Objective To campare biomechanical effects of different postural compression techniques on three-dimensional model of lumbar disc herniation(LDH)by finite element analysis.Methods Lumbar CT image of a 48-year-old female patient with LDH(heighted 163 cm,weighted 53 kg)was collected.Mimics 20.0,Geomagic Studio,Solidwords and other software were used to establish three-dimensional finite element model of LDH on L4,5 segments.Compression techniques under horizon-tal position,30° forward bending and 10° backward extension were simulated respectively.After applying the pressure,the ef-fects of compression techniques under different positions on stress,strain and displacement of various tissues of intervertebral disc and nerve root were observed.Results L4,5 segment finite element model was successfully established,and the model was validated.When compression manipulation was performed on the horizontal position,30° flexion and 10° extension,the annular stress were 0.732,5.929,1.286 MPa,the nucleus pulposus stress were 0.190,1.527,0.295 MPa,and the annular strain were 0.097,0.922 and 0.424,the strain sizes of nucleus pulposus were 0.153,1.222 and 0.282,respectively.The overall displace-ment distance of intervertebral disc on Y direction were-3.707,-18.990,-4.171 mm,and displacement distance of nerve root on Y direction were+7.836,+5.341,+3.859 mm,respectively.The relative displacement distances of nerve root and interverte-bral disc on Y direction were 11.543,24.331 and 8.030 mm,respectively.Conclusion Compression manipulation could make herniated intervertebral disc produce contraction and retraction trend,by increasing the distance between herniated interverte-bral disc and nerve root,to reduce symptoms of nerve compression,to achieve purpose of treatment for patients with LDH,in which the compression manipulation is more effective when the forward flexion is 30°.
6.Progress of tricuspid regurgitation interventional treatment
Chinese Journal of Interventional Cardiology 2024;32(10):588-595
Tricuspid regurgitation(TR)is a common heart valve disease.The increasing morbidity with age and the high mortality in the later stage of TR make more and more people pay attention to tricuspid valve(TV)and TR.For patients with severe TR,medicine management with diuretic as the core is not effective enough,and surgical management is faced with the problem of old patients,high surgical mortality.Transcatheter tricuspid valve interventions(TTVI)has made rapid progress in recent years.Currently,devices for TR can be divided into 2 categories:valve repair and valve replace.Both of them have demonstrated safety and efficacy,and are supported by preliminary clinical trials.In this review,the progress of relevant devices for tricuspid valve regurgitation and their clinical trials are introduced.
7.Thin corpus callosum and"lynx ear sign":A report of a family of hereditary spastic paraplegia type 11
Zongyong YU ; Ziyang WU ; Feifei TIAN ; Jing LI ; Wei YUAN ; Xin LI ; Haiping WEI ; Guode WU ; Jun LIU
Chinese Journal of Nervous and Mental Diseases 2024;50(10):632-635
To report a case with hereditary spastic paraplegia type 11(SPG11)in association with typical thin corpus callosum(TCC)and"Ears-of-the-lynx sign"on MRI imaging.The patient was a 13-year-old boy.The main symptoms are walking instability and falling easily.Over the period of one year,the symptoms gradually progressed when accompanied by poor handwriting and a decrease in learning ability.The parents are not related.Brain MRI shows a thin corpus callosum,and high symmetric signals in the anterior horn of the lateral ventricles on T2 and Flair sequence.WES detected two heterozygous mutations in the SPG11 gene,NM_025137:c.2073delT and c.257+5G>A,respectively from the parents.The proband was finally diagnosed with SPG11.Brain MRI found that TCC and"lynx ear sign"are highly sensitive and specific for the diagnosis of SPG11.The patients with spastic paraplegia should be considered the possibility of SPG11.
8.Expert consensus on limb management of patients with transvenous temporary cardiac pacing
Radioactive Interventional Nursing Professional Committee of Chinese Nursing Association ; Huafen LIU ; Jiali ZHOU ; Zheng HUANG ; Zhixia ZHANG ; Jingyu LIANG ; Zhongxiang CAI ; Fuhong CHEN ; Yunying ZHOU ; Yunyan XIANYU ; Lin YAN ; Huidan YU ; Huizhen PENG ; Jian ZHU ; Yuan TIAN ; Yan ZHANG ; Hejun JIANG ; Su ZHANG
Chinese Journal of Nursing 2024;59(13):1581-1583
Objective To form the expert consensus on the limb management of patients with transvenous temporary cardiac pacing,standardize the limb management of patients with transvenous temporary cardiac pacing,and reduce complications related to the limb.Methods Using evidence-based methods,the evidence in this field was searched,evaluated and summarized,and relevant recommendations and research conclusions were extracted and classified by the level of evidence quality,and then the first draft of the consensus was formed.From December 2023 to January 2024,through 2 rounds of expert consultation and 4 rounds of expert meetings,the content was adjusted and the consensus was reached.Results Totally 16 experts participated in the consultation.The positive coefficient is 100%;the authoritative coefficient is 0.847 and 0.836;the average value of each index is more than>3.8;the coefficient of variation is less than 0.21.The Kendall's harmony coefficient of the 2 rounds of expert consultation is 0.372 and 0.314,respectively,which were statistically significant.The consensus covers the preoperative,intraoperative and postoperative on limb management of patients with transvenous temporary cardiac pacing.Totally 11 themes were involved,including the preoperative preparation,position and catheter fixation in operation,position and catheter fixation in postoperative,activity,turn and transfer,duty shift on limb,nursing care after withdrawal of the catheter,prevention of deep vein thrombosis of the operative limb and prevent infection.Conclusion The consensus is highly scientific,and it is helpful to standardize the limb management of patients with transvenous temporary cardiac pacing.
9.Effects of different processes on the overall quality of Yanggan Jiangcao Mixture
Yu-Xin LIU ; Ya-Ping ZHU ; Li-Yuan TIAN ; Lei WU
Chinese Traditional Patent Medicine 2024;46(7):2157-2163
AIM To investigate the effects of extraction,concentration,centrifugation,sterilization processes on overall quality of Yanggan Jiangcao Mixture.METHODS The analysis was performed on a 20℃ thermostatic Phenomenex Luna C18column(250 mm×4.6 mm,5 μm),with the mobile phase comprising of acetonitrile-0.1% phosphoric acid flowing at 1 mL/min in a gradient elution manner.The HPLC fingerprints were established,after which the contents of salidroside,geniposide,forsythoside A,specnuezhenide,glycyrrhizic acid and atractylenolideⅢ,along with the calculation of their transfer rates.RESULTS There were twenty common peaks in the fingerprints for fifteen batches of samples under different processes with the similarities of more than 0.950.Six constituents showed good linear relationships within their own ranges(r≥0.999 0),whose average recoveries were 96.96%-106.69% with the RSDs of 0.97%-2.87%,and the transfer rates and total transfer rates were more than 80% and more than 90%,respectively.CONCLUSION Yanggan Jiangcao Mixture demonstrates good stability under different processes.
10.Analysis of DRG policy implementation dilemma and countermeasures of China based on Smith policy implementation process model
Manchen LYU ; Dian ZHOU ; Di TIAN ; Yuan ZHOU ; Yu ZHANG ; Tongbin XUE ; Xuezhen LIU ; Ye WU
Chinese Journal of Hospital Administration 2024;40(9):662-665
DRG payment reform is an important means to control the unreasonable growth of medical expenses, improve the quality of medical services and achieve a win-win situation among three sides of hospitals, medical insurance and patients. This study adopted the Smith policy implementation process model to analyze the difficulties in the DRG policy implementation process from four aspects(idealized policies, policy implementation institutions, target groups, and policy environment), including the deviation between policy connotations and actual needs; the interest objectives of all parties were not completely aligned, the target group lacked a sense of identity, and the social impact and technological support needed to be improved. It was suggested that optimization should be carried out from four dimensions: policy supply coordination and precision, performance evaluation and personnel literacy, target group cognitive level and participation willingness, and policy implementation environment and atmosphere, in order to synergistically promote the effective implementation of DRG policies.

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