1.Neuromolecular Mechanisms of Transcranial Electrical Stimulation for The Improvement of Alzheimer’s Disease
Yuan YUAN ; Zhuang-Fei CHEN ; Yu FU
Progress in Biochemistry and Biophysics 2025;52(5):1179-1195
Alzheimer’s disease (AD) is one of the most common and severe dementias, severely affecting the physical and mental health and quality of life of patients and imposing a heavy burden on society. Recently, transcranial electrical stimulation (tES) has shown great potential for improving cognitive function in AD. Transcranial direct current stimulation (tDCS) and transcranial alternating current stimulation (tACS) are the two main forms of tES. The present review mainly summarizes the neuromolecular mechanisms of tDCS and tACS for the improvement of AD. Both techniques show similarities in exerting neuroprotective effects, improving cerebral blood flow to alleviate cerebrovascular dysfunction, affecting the state and function of astrocytes, affecting the levels of amyloid β‑protein (Aβ) and phosphorylated tau (p-tau) proteins, and affecting neuroplasticity. Specifically, tDCS improves neuronal status, inhibits neuronal apoptosis, improves cholinergic neurons and reduces oxidative stress, etc., and further exerts neuroprotective effects, but tACS mainly maintains the normal function of cholinergic neurons to exert the effects. For the alleviation of cerebrovascular dysfunction, tDCS has particular advantages in optimizing the neural vascular unit and improving the blood-brain barrier. For astrocytes, tDCS attenuates inflammatory responses by inhibiting their activation. In contrast, the effect of tACS on the activation state of microglial cells is still controversial for enhancement in AD mice and inhibition in patients. For Aβ levels, the effects of tDCS in AD patients are also inconclusive, but in AD rodents, tDCS may regulate molecular pathways related to Aβ production and degradation, thereby removing Aβ. In addition, tACS reduces p-tau levels in AD patients, but tDCS shows a trend toward reduction. In short, the effect of tES on Aβ and p-tau needs further investigation. Regarding neuroplasticity, tDCS improves cortical and synaptic plasticity, but tACS improves only synaptic plasticity. However, both techniques do not affect the molecular level associated with plasticity. On the other hand, this review has summarized some interesting findings of tES in non-AD rodents that may be relevant to the pathological mechanisms of AD. For neuroprotection, tDCS can promote neurogenesis, GABAergic and glutamatergic neurotransmission, modulate neuroprotection-related signaling pathways, reduce oxidative stress, and protect hippocampal neurons. In addition, tDCS inhibits conversion of microglia to the M1 phenotype and promotes conversion to the M2 phenotype, thereby reducing neuroinflammation. Importantly, tDCS induces changes in molecular indices associated with synaptic plasticity. These findings in non-AD rodents provide a reference for understanding the potential effect and possible mechanism of tES in AD and for exploring new approaches to treat other diseases with similar pathological features. In addition, tES has shown some effects in AD rodents, such as tACS improving plasticity, that have not been studied in non-AD rodents. These effects suggest the particular complexity of the pathological mechanisms of AD, which should be considered when applying the results of tES studies in non-AD rodents to AD rodents. In conclusion, this review provides a comprehensive overview of the neuromolecular mechanisms of tES in AD research and highlights its promise as a non-invasive brain stimulation technique in the treatment of AD. Furthermore, tES will play an indispensable role in the treatment of neuropsychiatric disorders and in the study of brain function.
2.Study on component analysis,fingerprint establishment and anti-inflammatory spectrum-effect relationship of Yao ethnic medicine Pittosporum pauciflorum
Dan QIN ; Peng FU ; Jiajie CAO ; Qingchen TANG ; Jie GAO
China Pharmacy 2025;36(18):2244-2249
OBJECTIVE To analyze chemical components of Yao ethnic medicine Pittosporum pauciflorum, establish its fingerprint and investigate the spectrum-effect relationship of its anti-inflammatory effect. METHODS UHPLC-Q-Orbitrap-MS technology was used to analyze the chemical components of P. pauciflorum (batch S6). The fingerprints for 10 batches of P. pauciflorum from different producing areas in Guangxi Province (batches S1-S10) were established by HPLC, and similarity assessment and chemometric pattern recognition analysis were conducted. RAW264.7 inflammatory cell model was induced by lipopolysaccharide, and the anti-inflammatory activity of P. pauciflorum was investigated. Using inhibition rates of nitric oxide (NO), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and IL-1β as efficacy indicators, grey relational analysis and partial least squares regression analysis were adopted to evaluate the spectrum-effect relationship of the anti-inflammatory effect of P. pauciflorum. RESULTS There were 60 chemical components, including flavonoids, phenolic acids, lipids, etc., identified in P. pauciflorum. The fingerprints for 10 batches of P. pauciflorum showed 14 common peaks,with similarity values ranging from 0.883 to 0.991. Three common peaks were assigned neochlorogenic acid (peak 5), chlorogenic acid (peak 7), and syringaldehyde (peak 10). The classification results of the systematic clustering analysis and the principal component analysis were basically consistent. Batches S1 to S10 of P. pauciflorum significantly reduced the levels of NO, TNF-α, IL-6 (except for batch S5) and IL-1β in the cell supernatant (P<0.05 or P<0.01). Inhibition rates of above inflammatory indexes were 10.26%-39.96%, 14.96%-31.36%, 1.38%-21.27%, 18.54%-28.00%, respectively. The contents of neochlorogenic acid, syringaldehyde, as well as the components corresponding to peaks 1, 3, 9, 12 and 14,exhibited a strong correlation with the anti-inflammatory effects of P. pauciflorum. CONCLUSIONS The present study has analyzed the chemical components of P. pauciflorum and established HPLC fingerprints for 10 batches of P. pauciflorum. Each batch of medicinal herbs demonstrates certain anti- inflammatory activities, among which neochlorogenic acid, syringaldehyde, and the components corresponding to peaks 1, 3, 9, 12 and 14 are likely to be the active anti-inflammatory components.
3.Discussion on common problems after introducing "reduction factor" into different working hour systems in occupational exposure assessment in GBZ 2.1—2019
Ji HUANG ; Pingning DUAN ; Lifeng MAI ; Songwen FU
Journal of Environmental and Occupational Medicine 2024;41(3):330-334
Occupational exposure limits for hazardous agents in the workplace—Part 1: Chemical hazardous agents (GBZ 2.1—2019) has been implemented since April 1, 2020. The document redefines the evaluation of occupational exposure by introducing a "reduction factor" to adjust the occupational exposure limits of chemical hazardous agents for long working hour systems to ensure a protection level reasonable for the workers and equivalent to conventional occupational exposure limits. This paper discussed common problems encountered in the context of using this adjustment strategy, such as the adjustment being unable to cover all working hours, and the adjustment of values of terms associated with occupational exposure limits. Corresponding solutions were proposed. Working cycle and average exposure time of each working cycle were introduced to evaluate the actual working hours of workers. Regarding involved terms, adjustments of their corresponding values were clarified according to their definitions and application scenarios. Examples were provided for occupational health service providers so that their occupational health practices could be carried out in a more scientific and reasonable manner.
4.Early clinical outcomes of the domestic KokaclipTM transcatheter edge-to-edge mitral valve repair system for severe degenerative mitral regurgitation: A single-arm, prospective, single-group target value clinical trial
Tong TAN ; Bingqi FU ; Peijian WEI ; Nianjin XIE ; Haozhong LIU ; Xiaoyi LI ; Shengwen WANG ; Haijiang GUO ; Jian LIU ; Jimei CHEN ; Jian ZHUANG ; Huiming GUO
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2024;31(02):269-275
Objective To summarize and analyze the preliminary clinical outcomes of the KokaclipTM transcatheter edge-to-edge mitral valve repair system for severe degenerative mitral regurgitation (DMR). Methods This study was a single-arm, prospective, single-group target value clinical trial that enrolled patients who underwent the KokaclipTM transcatheter edge-to-edge repair (TEER) system for DMR in the Department of Heart Surgery of Guangdong Provincial People's Hospital, Guangdong Cardiovascular Institute from June 2022 to January 2023. Differences in the grade of mitral regurgitation (MR) during the perioperative and follow-up periods were compared, and the incidences of adverse events such as all-cause death, thoracotomy conversion, reoperation, and severe recurrence of MR during the study period were investigated. Results The enrolled patient population consisted of 14 (50.0%) females with a mean age of 70.9±5.4 years. Twenty-eight (100.0%) patients were preoperatively diagnosed with typeⅡ DMR, with a prolapse width of 12.5 (11.0, 16.1) mm, a degree of regurgitation 4+ leading to pulmonary venous reflux, and a New York Heart Association cardiac function class≥Ⅲ. All patients completed the TEER procedure successfully, with immediate postoperative improvement of MR to 0, 1+, and 2+ grade in 2 (7.1%), 21 (75.0%), and 5 (17.9%) patients, respectively. Mitral valve gradient was 2.5 (2.0, 3.0) mm Hg. Deaths, thoracotomy conversion, or device complications such as unileaflet clamping, clip dislodgement, or leaflet injury were negative. Twenty-eight (100.0%) patients completed at least 3-month postoperative follow-up with a median follow-up time of 5.9 (3.6, 6.8) months, during which patients had a mean MR grade of 1.0+ (1.0+, 2.0+) grade and a significant improvement from preoperative values (P<0.001). There was no recurrence of ≥3+ regurgitation, pulmonary venous reflux, reoperation, new-onset mitral stenosis, or major adverse cardiovascular events. Twenty-two (78.6%) patients’ cardiac function improved to classⅠorⅡ. Conclusion The domestic KokaclipTM TEER system has shown excellent preliminary clinical results in selected DMR patients with a high safety profile and significant improvement in MR. Additional large sample volume, prospective, multicenter studies, and long-term follow-up are expected to validate the effectiveness of this system in the future.
5.Prenatal diagnostic value of MRI in fetal Chiari malformation
Yan ZHUANG ; Chang-An CHEN ; He ZHANG ; Xiao-Wei HUANG ; Guo-Fu ZHANG
Fudan University Journal of Medical Sciences 2024;51(2):191-197,217
Objective To evaluate the value of magnetic resonance imaging(MRI)in prenatal diagnosis of fetal Chiari malformation.Methods The prenatal MRI findings of 27 cases of Chiari malformation confirmed by follow-up in Obstetrics and Gynecology Hospital,Fudan University from Feb 2010 to Feb 2022 were retrospectively analyzed and compared with ultrasound findings.Results Twenty-seven pregnant women,aged from 16-36 years(average 28.0 years)and 27 fetuses with gestation from 15.3-38.4 weeks(average 24.3 weeks)were studied.There were 18 cases of Chiari Ⅱ(Chiari malformation type Ⅱ,CMⅡ),3 cases of Chiari Ⅲ(CMⅢ),6 cases of Chiari Ⅳ(CMⅣ).CMⅡ and CMⅢ images showed brain herniation,descending pons,narrowing or disappearance of the posterior fossa cistern and the fourth ventricle,the subarachnoid space disappears.There were 17 cases of hydrocephalus,2 cases of cerebrospinal fluid loss,17 cases of"lemon head"and"banana cerebellar"signs,4 cases of encephalocele,15 cases of spinal bifida,3 cases of lower spinal cord and 2 cases of spinal cavity,4 cases of spinal angular deformity and 6 cases of other malformations.In CMⅣ,there were 2 cases of undeveloped cerebellum and 4 cases of cerebellum and brainstem dysplasia,hydrocephalus in 5 cases,posterior fossa cistern widening in 4 cases,and other malformations in 4 cases.MRI showed the posterior fossa structure and spinal cord more clearly than ultrasound,and could find lesions not detected by ultrasound.Conclusion Prenatal MRI can be used as a complementary examination of ultrasound,which can improve the accuracy of diagnosis of Chiari malformation,reduce the rate of missed diagnosis,and clarify the classification of Chiari malformation.
6.Practices on"Center-Multidisciplinary Team"Structure for Rare Disease Management in General Hospitals
Yu ZHUANG ; Yuan ZHONG ; Xinxia WU ; Xuedong XU ; Rong MU ; Xiaohui ZHU ; Rong LI ; Wei FU
Chinese Hospital Management 2024;44(9):37-40
Objectives It was a preliminary exploration on rare disease management of comprehensive hospital based on the"Center-Multidisciplinary Team"structure.Methods By applying interrupted time series analysis,the characteristics and related medical service of rare disease patients discharged from sample hospitals from 2021 to 2023 were measured.Results The results showed that the hospital served 19 825 rare disease patients from 2021 to 2023.The proportion of patients whose main diagnosis were rare diseases was approximately 27%.The interrupted time series technique indicated that the expected proportion of rare disease patients increased instantly by 1.89 thousand points.The capability to diagnose has significantly improved,with a growing trend on volume of bioinformatics analysis services for rare diseases patients.Conclusion The rare disease management based on the"Center-Team"structure can increase the attention of medical staff to rare diseases,strengthen the diagnostic capacity of rare diseases,and make patient management more continuous and disciplinary co-operation more efficient without significantly increasing the input burden on hospitals.
7.Practices on"Center-Multidisciplinary Team"Structure for Rare Disease Management in General Hospitals
Yu ZHUANG ; Yuan ZHONG ; Xinxia WU ; Xuedong XU ; Rong MU ; Xiaohui ZHU ; Rong LI ; Wei FU
Chinese Hospital Management 2024;44(9):37-40
Objectives It was a preliminary exploration on rare disease management of comprehensive hospital based on the"Center-Multidisciplinary Team"structure.Methods By applying interrupted time series analysis,the characteristics and related medical service of rare disease patients discharged from sample hospitals from 2021 to 2023 were measured.Results The results showed that the hospital served 19 825 rare disease patients from 2021 to 2023.The proportion of patients whose main diagnosis were rare diseases was approximately 27%.The interrupted time series technique indicated that the expected proportion of rare disease patients increased instantly by 1.89 thousand points.The capability to diagnose has significantly improved,with a growing trend on volume of bioinformatics analysis services for rare diseases patients.Conclusion The rare disease management based on the"Center-Team"structure can increase the attention of medical staff to rare diseases,strengthen the diagnostic capacity of rare diseases,and make patient management more continuous and disciplinary co-operation more efficient without significantly increasing the input burden on hospitals.
8.Study on the effect of control scan method in precise CT localization scan on patients with head and neck tumors
Jieying ZHUANG ; Min WANG ; Feiyue SHI ; Lin FU ; Lili CHEN ; Fei CHEN ; Xiaowei WEI
China Medical Equipment 2024;21(3):8-11,18
Objective:To study the position of computed tomography(CT)slice of marker points of radiotherapy,which was determined by control scan(CS)method,on the application effect of patients with head and neck tumors who received radiotherapy.Methods:Based on Control Scan(CS)method,a calculator program of mark-point slice position was made,which was an enterprise WeChat program that could be used in calculating position and CT position scan of patients with head and neck tumor(slice thickness was 3mm).A total of 60 patients with head and neck tumor were selected,and the patients who underwent CT positioning scan by using CS method were divided into observation group,and patients who underwent CT position scan by using conventional method were divided into control group,with 30 cases in each group.The number of cases with three metal marker points displayed at the same slice,and the number of slices containing the CT images of marker point between the located CT scan were compared.Results:The number of patients in the observation group and the control group who showed three markers at the same level at the same time were respectively 26 cases and 13 cases,and observation group increased by 13 cases(43.4%)than control group,and the difference was significant(x2=12.382,P<0.05).The number of CT images with only 1 slice of observation group and control group were respectively 4 cases and 0 cases,which increased by 4 cases(13.3%)than the control group,and the difference was significant(x2=2.411,P<0.05).Conclusions:The CT localization scan of radiotherapy,which uses CS to assist patients with head and neck tumor,can precisely calculate and obtain the primary position of target of CT localization scan.It can take the images of 3 mental marker points of patient who receives radiotherapy to occur at the same CT slice as soon as possible,which has better application effect.It can effectively improve the convenience and work effectiveness of radiotherapy.
9.Study on the mechanism of Yifei xuanfei jiangzhuo formula against vascular dementia
Guifeng ZHUO ; Wei CHEN ; Jinzhi ZHANG ; Deqing HUANG ; Bingmao YUAN ; Shanshan PU ; Xiaomin ZHU ; Naibin LIAO ; Mingyang SU ; Xiangyi CHEN ; Yulan FU ; Lin WU
China Pharmacy 2024;35(18):2207-2212
OBJECTIVE To investigate the mechanism of Yifei xuanfei jiangzhuo formula (YFXF) against vascular dementia (VD). METHODS The differentially expressed genes of YFXF (YDEGs) were obtained by network pharmacology. High-risk genes were screened from YDEGs by using the nomogram model. The optimal machine learning models in generalized linear, support vector machine, extreme gradient boosting and random forest models were screened based on high-risk genes. VD model rats were established by bilateral common carotid artery occlusion, and were randomly divided into model group and YFXF group (12.18 g/kg, by the total amount of crude drugs), and sham operation group was established additionally, with 6 rats in each group. The effects of YFXF on behavior (using escape latency and times of crossing platform as indexes), histopathologic changes of cerebral cortex, and the expression of proteins related to the secreted phosphoprotein 1 (SPP1)/phosphoinositide 3-kinase (PI3K)/protein kinase B (aka Akt) signaling pathway and the mRNA expression of SPP1 in cerebral cortex of VD rats were evaluated. RESULTS A total of 6 YDEGs were obtained, among which SPP1, CCL2, HMOX1 and HSPB1 may be high-risk genes of VD. The generalized linear model based on high-risk genes had the highest prediction accuracy (area under the curve of 0.954). Compared with the model group, YFXF could significantly shorten the escape latency of VD rats, significantly increase the times of crossing platform (P<0.05); improve the pathological damage of cerebral cortex, such as neuronal shrinkage and neuronal necrosis; significantly reduce the expressions of SPP1 protein and mRNA (P<0.05), while significantly increase the phosphorylation levels of PI3K and Akt (P<0.05). CONCLUSIONS VD high-risk genes SPP1, CCL2, HMOX1 and HSPB1 may be the important targets of YFXF. YFXF may play an anti-VD role by down-regulating the protein and mRNA expressions of SPP1 and activating PI3K/Akt signaling pathway.
10.Treatment of Tile type C pelvic ring fracture using orthopedic robot combined with Starr pelvis reduction frame
Gang-Qiang JIANG ; Fu-De JIAO ; Ji-Chong YING ; Tian-Ming YU ; Jian-Lei LIU ; Yun-Qiang ZHUANG
China Journal of Orthopaedics and Traumatology 2024;37(5):445-450
Objective To investigate the clinical effect of orthopedic robot combined with Starr pelvic reduction frame in the treatment of Tile type C pelvic ring fracture.Methods From October 2019 to May 2021,14 patients with type C pelvic ring fracture were treated with robotic combined with Starr pelvic reduction frame,including 9 males and 5 females.The age ranged from 33 to 69 years.All the 14 patients had fresh closed fractures without femur,tibia and fibula fracture.Surgery was complet-ed from 4 to 7 d after hospital admission.During the operation,the X-ray carbon bed was used,the pelvic ring was reduced by Starr pelvis reduction frame,and pelvic ring fracture was treated by orthopedic robot.Operation time,bleeding volume,fluo-roscopy times of single screw placement,fracture reduction quality,affected limb function and complications were observed.Radiological reduction was evaluated using Matta scoring standard,and clinical efficacy was evaluated by Majeed pelvic func-tion scoring system at the final follow-up.Results All of 14 patients successfully completed the operation,the operation time was 84 to 141 min,the bleeding volume was 20 to 50 ml,and the fluoroscopy times of single screw insertion was 4 to 9 times.All of 14 patients were followed up for 12 to 24 months.The healing time was 3 to 7 months.No complications such as fracture of internal fixation,screw loosening,infection and nerve injury were found.According to the evaluation criteria of Matta imag-ing reduction,9 cases were excellent,4 cases were good,and 1 case was fair.At the final follow-up,Majeed pelvic function scoring system was used:10 cases were excellent,4 cases were good.Conclusion The treatment of type C pelvic ring fracture with robotic combined Starr pelvis reduction frame is simple,time-saving,less trauma,less complications and effective.

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