1.Application of Non-invasive Deep Brain Stimulation in Parkinson’s Disease Treatment
Yu-Feng ZHANG ; Wei WANG ; Zi-Jun LU ; Jiao-Jiao LÜ ; Yu LIU
Progress in Biochemistry and Biophysics 2025;52(5):1196-1205
Parkinson’s disease (PD) is a common neurodegenerative disorder that significantly impacts patients’ independence and quality of life, imposing a substantial burden on both individuals and society. Although dopaminergic replacement therapies provide temporary relief from various symptoms, their long-term use often leads to motor complications, limiting overall effectiveness. In recent years, non-invasive deep brain stimulation (DBS) techniques have emerged as promising therapeutic alternatives for PD, offering a means to modulate deep brain regions with high precision without invasive procedures. These techniques include temporal interference stimulation (TIs), low-intensity transcranial focused ultrasound stimulation (LITFUS), transcranial magneto-acoustic stimulation (TMAS), non-invasive optogenetic modulation, and non-invasive magnetoelectric stimulation. They have demonstrated significant potential in alleviating various PD symptoms by modulating neural activity within specific deep brain structures affected by the disease. Among these approaches, TIs and LITFUS have received considerable attention. TIs generate low-frequency interference by applying two slightly different high-frequency electric fields, targeting specific brain areas to alleviate symptoms such as tremors and bradykinesia. LITFUS, on the other hand, uses low-intensity focused ultrasound to non-invasively stimulate deep brain structures, showing promise in improving both motor function and cognition in PD patients. The other three techniques, while still in early research stages, also hold significant promise for deep brain modulation and broader clinical applications, potentially complementing existing treatment strategies. Despite these promising findings, significant challenges remain in translating these techniques into clinical practice. The heterogeneous nature of PD, characterized by variable disease progression and individualized treatment responses, necessitates flexible protocols tailored to each patient’s unique needs. Additionally, a comprehensive understanding of the mechanisms underlying these treatments is crucial for refining protocols and maximizing their therapeutic potential. Personalized medicine approaches, such as the integration of neuroimaging and biomarkers, will be pivotal in customizing stimulation parameters to optimize efficacy. Furthermore, while early-stage clinical trials have reported improvements in certain symptoms, long-term efficacy and safety data are limited. To validate these techniques, large-scale, multi-center, randomized controlled trials are essential. Parallel advancements in device design, including the development of portable and cost-effective systems, will improve patient access and adherence to treatment protocols. Combining non-invasive DBS with other interventions, such as pharmacological treatments and physical therapy, could also provide a more comprehensive and synergistic approach to managing PD. In conclusion, non-invasive deep brain stimulation techniques represent a promising frontier in the treatment of Parkinson’s disease. While they have demonstrated considerable potential in improving symptoms and restoring neural function, further research is needed to refine protocols, validate long-term outcomes, and optimize clinical applications. With ongoing technological and scientific advancements, these methods could offer PD patients safer, more effective, and personalized treatment options, ultimately improving their quality of life and reducing the societal burden of the disease.
2.Identification, expression and protein interaction analysis of Aux/IAA and ARF gene family in Senna tora L.
Zhao FENG ; Shi-peng LIU ; Rui-hua LÜ ; Rui-hua LÜ ; Xiao-chen HU ; Ming-ying ZHANG ; Ren-jun MAO ; Gang ZHANG
Acta Pharmaceutica Sinica 2024;59(3):751-763
The early response of plant auxin gene family
3.C-X3-C motif chemokine ligand 1/C-X3-C motif chemokine receptor 1 pathway in the recovery of memory function in hemorrhagic shock/resuscitation rats
Xiao-Jun WU ; Ri-Xing WANG ; Fang-Chong LIN ; You-Kai LÜ ; Qi-Tao FENG ; Tian-Qi YUN
Acta Anatomica Sinica 2024;55(2):158-166
Objective To investigate the effect of microglia activation regulated by C-X3-C motif chemokine ligand 1(CX3CL1)-C-X3-C motif chemokine receptor 1(CX3CR1)pathway on memory function in hemorrhagic shock/resuscitation rats.Methods The experiment was divided into two parts.In the first part,the rats were randomly divided into sham group,model-0.5 hour group,model-1.5 hour group,model-3 hour group,10 rats in each group.There were differences in the time of hemorrhagic shock among each group.In the second part,rats were randomly divided into control group and CX3CL1 group,10 rats in each group.The rats in CX3CL1 group were treated with CX3CL1 protein factor(intraventricular injection),and the rats in control group were treated with saline.All rats were trained in Morris water maze experiments before model construction,and tests of Morris water maze experiments were carried out after 4 days of model construction.After completion,the whole brains were taken for HE staining and immunohistochemical staining.Cerebrospinal fluid was taken for detection of inflammatory cytokines,and hippocampus tissues were taken for Real-time PCR detection and Western blotting detection.Results Compared with the sham group,the escape latency of rats in model group increased,the number of platform crossings and the resident time in the third quadrant decreased.The neuronal state was impaired in HE staining in model group.In addition,compared with the sham group,the expression of ionized calcium binding adaptor molecule-1(Iba1)in the brain of the rats in model group increased,the contents of tumor necrosis factor-α(TNF-α)and interleukin(IL)-6 in the cerebrospinal fluid increased,and the M1-type microglia markers CD16,TNF-α,IL-1β and inducible nitric oxide synthase(iNOS)mRNA content increased.At the same time,compared with the sham group,the expressions of CX3CL1 and CX3CR1 in the brain of model group decreased,and the expressions of phosphorylated nuclear factor-κB(p-NF-κB)and nucleotide binding oligomerization domain(NOD)-like receptor protein 3(NLRP3)increased.However,compared with the control group,rats in CX3CL1 group had reduced escape latency,increased platform crossing times and quadrantⅢresident time,and recovered neuronal states.In addition,the expression of Iba1 in the brain of CX3CL1 group decreased,the contents of TNF-α and IL-6 in the cerebrospinal fluid decreased,the mRNA contents of M1-type microglia markers like CD16,TNF-α,IL-1β and iNOS decreased,and the mRNA contents of markers of M2-type microglia glial like CD206,transforming growth factor-β(TGF-β),arginase-1(Arg1),Chitinase 3-like protein 1(Ym 1)increased.Conclusion CX3CL1 can help inhibit the excessive activation of microglia,induce the polarization of microglia to M2 type,inhibit the polarization of M1 type,reduce the release of inflammatory cytokines,and alleviate the memory function damage induced by hemorrhagic shock/resuscitation.
4.Analysis of work-related injury medical expenses and influencing factors in Kunshan City from 2016 to 2021
Yun HAN ; Jun LÜ ; Yuanjing CHEN ; Gang CHEN
China Occupational Medicine 2024;51(2):219-222
ObjectiveTo understand the influencing factors of work-related injury medical expenses in Kunshan City. Methods The work-related injury data of Kunshan City from 2016 to 2021 were collected from the “Jiangsu Human Resources and Social Security Integration Handling Platform” of Kunshan Municipal Human Resources and Social Security Bureau, and the influencing factors of work-related injury medical expenses were analyzed using quantile regression. Results The median (interquartile range) of per capita work-related injury medical expenses in Kunshan City from 2016 to 2021 was 1 025.6(7 199.1) yuan. The result of 0.50 quantile regression analysis showed that the work-related injury medical expenses of male workers were higher than that of female workers (P<0.01), the work-related injury medical expenses of workers aged 46 and above were higher than those aged 16-<26 (P<0.01), the work-related injury medical expenses of veteran workers were lower than those of new workers (P<0.01), the work-related injury medical expenses of workers in the third, fourth, fifth, and sixth major risk industries were higher than that in the first major risk industry (all P<0.05), the work-related injury medical expenses on lower limb, head and neck, trunk, and multiple injured areas were lower than upper limb injuries (all P<0.01), the work-related injury medical expenses of workers with death, grades 5 to 6, grades 7 to 10, failure to reach grade, and ungraded injuries were lower than those of workers with grades 1 to 4 injuries (all P<0.01), the medical expenses for work-related injuries such as scalds, burns, and scorch were higher than cuts, abrasions, and stabs injuries (P<0.01). Conclusion The influencing factors of the workers' medical expenses for work-related injuries are age, gender, and injured body part. It is necessary to further strengthen the prevention of work-related injuries for males, new workers, workers in the third to sixth major risk industries, and those aged 46 and above. Meanwhile, it is needed to prevent workers from suffering scalds, burns, scorch injuries, upper limb injuries, and high disability grades injuries, to reduce the economic burden on workers and the society.
5.Competency and professional activities for Chinese pediatric rehabilitation therapists based on World Health Or-ganization rehabilitation competency framework
Lei FENG ; Jun LÜ ; Xiaoqian WANG ; Hongying ZHENG ; Ping SHAO ; Anni WANG ; Mei SUN ; Gang CHEN
Chinese Journal of Rehabilitation Theory and Practice 2024;30(7):752-759
Objective To construct the competency and professional activities of pediatric rehabilitation therapists in China based on World Health Organization rehabilitation competency framework(RCF). Methods Competencies,activities,and tasks in the field of pediatric rehabilitation were collected through literature,offi-cial websites and interviews with key informants using RCF.Competency requirements suitable for pediatric re-habilitation therapists were selected,competency dimensions and activities were adjusted based on the context of pediatric rehabilitation therapy.Similar content was integrated through thematic framework analysis and content analysis.Competencies were matched with typical professional activities.A competency framework and profes-sional activities for Chinese pediatric rehabilitation therapists were developed,and the Delphi method was used to survey 22 experts,ultimately confirming competency dimensions and activity content. Results The enthusiasm coefficient of experts was 88.00%,the authority coefficient was 0.84,and the expert opinions were more focused on importance.The CV values of all competency dimensions and activities were≤0.25,and the W test was statistically significant(P<0.05),indicating a high degree of coordination among experts.A com-petency framework for pediatric rehabilitation therapists in China,included 17 competency dimensions and 17 professional activities. Conclusion To explore the competency of typical professions through RCF may enhance the application of research re-sults in the field of rehabilitation,which provides a reference for clarifying the job content and cultivating the competency of Chinese pediatric rehabilitation therapists.
6.Competency and professional activities of pediatric rehabilitation therapists in three provinces/cities of East China
Lanqing CHEN ; Jun LÜ ; Xiaoqian WANG ; Hongying ZHENG ; Ping SHAO ; Anni WANG ; Mei SUN ; Gang CHEN
Chinese Journal of Rehabilitation Theory and Practice 2024;30(7):760-767
Objective To investigate the current situation of competency and professional activities of pediatric rehabilitation thera-pists in Jiangsu,Shanghai and Zhejiang. Methods A questionnaire survey was conducted on 168 pediatric rehabilitation therapists in Jiangsu,Shanghai and Zheji-ang,from December,2022 to February,2023,and the general information and the competency were obtained.A total of 35 pediatric rehabilitation therapists were interviewed one-on-one,from October,2022 to January,2023,using thematic framework. Results A total of 162 effective questionnaires were collected.The level of competency of pediatric rehabilitation thera-pists was(3.44±0.87);and it was higher in professional literacy(3.90±0.77)and practice(3.83±0.77),and lower in management and leadership(2.92±1.44),and research(2.14±1.64).Latent class analysis showed that the thera-pists could be divided into four categories,of which the"medium competency"accounted for the most proportion(34.57%),and"low learning and research"was the least(8.64%).The interviews identified problems of compe-tency such as maintaining communication with children's families and managing self-professional development. Conclusion Self-reported rehabilitation competency levels of pediatric rehabilitation therapists in three provinces and cit-ies are above three points in all four dimensions,except for the management and leadership dimension,where the score is below three points.
7.Quercetin inhibits the activity of neuroendocrine tumor cells by regulating the GAS5/miR-18b-5p axis
Wen-Juan WU ; Bo LI ; Hai-Hong LÜ ; Jun CHEN ; Wen KOU
The Chinese Journal of Clinical Pharmacology 2024;40(10):1429-1433
Objective To investigate the inhibitory effect of quercetin on Gastro entero pancreatic NEN(GEP-NEN).Methods Human pancreatic neuroendocrine tumor BON-1 cells were randomly divided into control group,quercetin group(80 μmol·L-1 quercetin),quercetin+si-NC group(transfected with si-NC+80 μmol·L-1 quercetin),quercetin+si-growth arrest-specific+ranscript 5(GAS5)group(transfected with si-GAS5+80 μmol·L-1 quercetin).Dual luciferase reporter gene assay was used to verify the targeted binding of GASS5 to miR-18b-5p;real-time quantitative fluorescent PCR(qRT-PCR)was used to detect the mRNA expression levels of B-cell lymphoma-2(Bcl-2)and Bel-2 associated X protein(Bax);positive expression of GAS5 and miR-18b-5p in cells was detected by fluorescence in situ hybridization(FISH)assay.Results Dual luciferase reporter gene results showed that GAS5 was targeted to miR-18b-5p.The GAS5 expression levels of control group,quercetin group,quercetin+si-NC group and quercetin+si-GAS5 group were 1.00±0.13,1.72±0.19,1.78±0.14 and 1.16±0.11,respectively;the expression levels of miR-18b-5p were 1.00±0.15,0.67±0.08,0.72±0.06 and 0.95±0.11 respectively;Bax mRNA expression levels were 1.00±0.12,2.17±0.25,2.32±0.28 and 1.37±0.15,respectively;Bcl-2 mRNA expression levels were 1.00±0.15,0.41±0.05,0.37±0.06 and 1.21±0.13,respectively.The above indexes were significantly different between quercetin group and control group(all P<0.05);the above indexes were significantly different between quercetin+si-NC group and quercetin+si-GAS5 group(all P<0.05).Conclusion Quercetin may slow down the development of GEP-NEN by targeting GAS5/miR-18b-5p molecular axis to inhibit cell growth.
8.Analysis of the mechanisms of Guanxinning Tablet for antithrombotic and microthrombotic effects caused by COVID-19 based on network pharmacology
Pei-yu GONG ; Guang-xu XIAO ; Wen-jun LI ; Guan-wei FAN ; Ming LÜ ; Jin-qiang ZHU
Acta Pharmaceutica Sinica 2024;59(9):2545-2555
Thrombosis is a key factor that increases the mortality rate of COVID-19 patients and causes long COVID sequelae. Guanxinning Tablet (GXNT), which is composed of
9.Discovery of the targets and lead compounds of traditional Chinese medicine based on the molecular trajectory of diabetes evolution
Yu ZHANG ; Jiang-lan LONG ; Ai-ting WANG ; Hao LÜ ; Ke-jun DENG ; Hao LIN ; Dan YAN
Acta Pharmaceutica Sinica 2024;59(8):2199-2204
Exploring the action targets (groups) of traditional Chinese medicine (TCM) is an important proposition to promote the innovation and development of TCM, but it has attracted a lot of attention as to whether it is related to the efficacy or the disease. Our team found that the metabolomic signature molecules in the development of diabetes mellitus (DM) were significantly associated with the clinical efficacy of Yuquan Pill through a large clinical sample study. Taking this as a clue, our team intends to expand the information on the omics features of DM development, and discover the key targets (groups) and their lead compounds for the hypoglycemic effect of Yuquan Pill. The project includes: ① Based on the retrospective clinical trials, using omics technology integrated with generative artificial intelligence, mining the characteristic information of proteome and microbiome, forming driving factors together with metabolome characteristic molecules, and characterizing the molecular trajectories of diabetes evolution and their interference by Yuquan Pill; ② Taking the evolving molecular trajectories as a link and pointer, using anthropomorphic modeling and molecular biology techniques such as chemical proteomics to discover the key targets (groups) of Yuquan Pill's hypoglycemic effect, with the prospective clinical samples for validation; ③ Evaluate the overall response of key targets (groups) using graph neural network technology, and search for drug-derived/endogenous lead compounds with proven clinical pathologies and clear mechanisms of action, so as to provide a new paradigm and technology for the discovery of complex active ingredient targets (groups) of TCM that are related to their clinical efficacy, as well as for the discovery of innovative medicines.
10.Molecular mechanism of young Sca-1 bone marrow stem cell on old cardiac fibroblast cell apoptosis in aging mice
Rao LÜ ; Jiadi YU ; Liuzhen LI ; Chulan ZHAN ; Liyue ZHAO ; Yueliang LI ; Jun DONG ; Jiao LI
The Journal of Practical Medicine 2024;40(17):2369-2374
Objective To investigate the impact of Sca-1 bone marrow derived stem cells on apoptosis in murine cardiac fibroblasts and the molecular mechanisms of young(Y)Sca-1 bone marrow stem cell(BMSC)on old(O)cardiac fibroblast cell(CFC)apoptosis.Methods The apoptosis and survival of Y and O CFC were assessed under hypoxic conditions.Co-cultures of Y and O Sca-1 bone marrow-derived mesenchymal stem cells(BMSC)with O CFC were established to investigate the impact of Sca-1 BMSC on the apoptotic response and viability of O CFC,employing TUNEL staining,qRT-PCR,Western Blot,and CCK8 assays.Furthermore,differential secretion profiles of growth factors by Y and O Sca-1 BMSC were compared using qRT-PCR and ELISA analysis.Results Compared to Y CFC,O CFC exhibited an increased rate of apoptosis and a decreased rate of cell survival.However,when compared to O cells,Y Sca-1 BMC significantly reduced apoptosis in O CFC and enhanced cell survival.Moreover,Y Sca-1 BMSC demonstrated a higher secretion of GDF5(Growth Differentiation Factor 5)than O cells(P<0.05).Importantly,the protective effects of Y Sca-1 BMSC on apoptosis and survival in O CFC were abolished upon neutral-ization of GDF5 expression.Conclusion Y Sca-1 BMSC decreases O CFC apoptosis through GDF5.

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