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.Electrical stimulation induces miR-741-3p to regulate Radil and promote Schwann cell migration
Qing LIU ; Bo GAO ; Xiao YANG ; Yu JIANG ; Pei WANG
Chinese Journal of Tissue Engineering Research 2025;29(19):4038-4043
BACKGROUND:More and more animal experiments and clinical studies have confirmed that electrical stimulation can promote the repair of peripheral nerve injury,but the specific mechanism is not yet fully understood. OBJECTIVE:To investigate the effect of electrical stimulation-induced miR-741-3p regulating Radil on Schwann cell migration. METHODS:(1)Twelve male SD rats were randomly divided into electrical stimulation group and control group.The electrical stimulation group received continuous electrical stimulation for 7 days after sciatic nerve compression injury,while the control group was not treated after sciatic nerve compression.The injured nerves were taken on day 7 after operation.The expression difference of miR-741-3p between the two groups was verified by fluorescence in situ hybridization.(2)The target genes of miR-741-3p were predicted by miRDB,TargetScan,and miRWalk databases.(3)Schwann cells were transfected with miR-741-3p mimetic and its control,miR-741-3p inhibitor and its control,Radil siRNA and its control,miR-741-3p inhibitor+Radil siRNA and miR-741-3p inhibitor+siRNA control.The transfection efficiency was detected by RT-PCR.The migration ability of Schwann cells was detected by Transwell chamber. RESULTS AND CONCLUSION:(1)The fluorescence intensity of miR-741-3p in the electrical stimulation group was lower than that in the control group.(2)The results of database prediction showed that 69 genes might be the target genes of miR-741-3p.Radil was one of the predicted target genes,which was mainly involved in cell adhesion and migration.(3)Compared with the miR-741-3p inhibitor control group,the number of Schwann cell migration increased in the miR-741-3p inhibitor group(P<0.05).Compared with the miR-741-3p mimic control group,the number of Schwann cell migration in the miR-741-3p mimic group decreased(P<0.05).Compared with the siRNA control group,the number of Schwann cell migration was decreased in the Radil siRNA group(P<0.05).(4)Compared with miR-741-3p inhibitor control group,the expression level of Radil was increased in miR-741-3p inhibitor group.Compared with miR-741-3p mimic control group,the expression level of Radil was decreased in miR-741-3p mimic group.(5)Compared with miR-741-3p inhibitor+siRNA control group,the number of Schwann cell migration was reduced in miR-741-3p inhibitor+Radil siRNA group(P<0.05).The results showed that electrical stimulation promoted the migration of Schwann cells by down-regulating miR-741-3p and targeting Radil gene.
3.Consensus statement on research and application of Chinese herbal medicine derived extracellular vesicles-like particles (2023 edition).
Qing ZHAO ; Tong WANG ; Hongbin WANG ; Peng CAO ; Chengyu JIANG ; Hongzhi QIAO ; Lihua PENG ; Xingdong LIN ; Yunyao JIANG ; Honglei JIN ; Huantian ZHANG ; Shengpeng WANG ; Yang WANG ; Ying WANG ; Xi CHEN ; Junbing FAN ; Bo LI ; Geng LI ; Bifeng LIU ; Zhiyang LI ; Suhua QI ; Mingzhen ZHANG ; Jianjian ZHENG ; Jiuyao ZHOU ; Lei ZHENG ; Kewei ZHAO
Chinese Herbal Medicines 2024;16(1):3-12
To promote the development of extracellular vesicles of herbal medicine especially the establishment of standardization, led by the National Expert Committee on Research and Application of Chinese Herbal Vesicles, research experts in the field of herbal medicine and extracellular vesicles were invited nationwide with the support of the Expert Committee on Research and Application of Chinese Herbal Vesicles, Professional Committee on Extracellular Vesicle Research and Application, Chinese Society of Research Hospitals and the Guangdong Engineering Research Center of Chinese Herbal Vesicles. Based on the collation of relevant literature, we have adopted the Delphi method, the consensus meeting method combined with the nominal group method to form a discussion draft of "Consensus statement on research and application of Chinese herbal medicine derived extracellular vesicles-like particles (2023)". The first draft was discussed in online and offline meetings on October 12, 14, November 2, 2022 and April and May 2023 on the current status of research, nomenclature, isolation methods, quality standards and research applications of extracellular vesicles of Chinese herbal medicines, and 13 consensus opinions were finally formed. At the Third Academic Conference on Research and Application of Chinese Herbal Vesicles, held on May 26, 2023, Kewei Zhao, convenor of the consensus, presented and read the consensus to the experts of the Expert Committee on Research and Application of Chinese Herbal Vesicles. The consensus highlights the characteristics and advantages of Chinese medicine, inherits the essence, and keeps the righteousness and innovation, aiming to provide a reference for colleagues engaged in research and application of Chinese herbal vesicles at home and abroad, decode the mystery behind Chinese herbal vesicles together, establish a safe, effective and controllable accurate Chinese herbal vesicle prevention and treatment system, and build a bridge for Chinese medicine to the world.
4. Mechanism of EGFR inhibitor AG1478 combined with oxaliplatin in inhibiting PI3K/AKT pathway and promoting autophagy in HI 975 cells
Jin-Qing HUANG ; Yang LI ; Dong-Xue WEI ; Shan JIANG ; Shao-Feng JIANG
Chinese Pharmacological Bulletin 2024;40(2):242-278
Aim To explore the effect of oxaliplatin combined with epidermal growth factor receptor tyrosine kinase inhibitor AG1478 on autophagy in non-small cell lung cancer H1975 cells. Methods H1975 cells were cultured in vitro using gradient concentrations of AG1478 (0, 5, 10, 15, 20, 25, 30, 35, 40 jjimol • IT
5.Epidemiological trends and disease burden of lower gastrointestinal bleeding in children within 10 years
Guoying TANG ; Qing LIU ; Mingyue ZHU ; Yongping ZHAO ; Pingying JIANG ; Linyun YANG
Journal of Public Health and Preventive Medicine 2024;35(1):100-103
Objective To retrospectively analyze the epidemiological trend of children with lower gastrointestinal bleeding in recent 10 years,and investigate the change of their disease burden,so as to provide a theoretical basis for the accurate prevention and control of children's lower gastrointestinal bleeding. Methods A total of 671 children with "lower gastrointestinal bleeding" who were diagnosed in our hospital from 2012 to 2021 were collected as research subjects. To analyze the microscopic examination rate and common etiology of lower gastrointestinal bleeding in children in the past 10 years,as well as the epidemiological characteristics of different age groups, different regions and different basic diseases; Calculate and compare the rate of disability life lost (YLD), early death life lost (YLL) and disability adjusted life year (DALY) of children with lower gastrointestinal bleeding within 10 years, and calculate the annual change percentage (AAPC) to analyze the change trend of disease burden. Results The microscopic examination rate of children with lower gastrointestinal bleeding showed a trend of increasing in the past 10 years (P<0.001). Among them, the most common causes are Crohn's disease, ulcerative colitis and chronic colitis. The proportion of children with lower gastrointestinal bleeding was higher in boys, >18 years old, hypertension and gastroenteritis. The DALY rate, YLL rate and YLD rate caused by lower gastrointestinal bleeding in the past 10 years showed an upward trend (P<0.05). Conclusion The microscopic examination rate of lower gastrointestinal bleeding in children was graduallyincreasing,and the prevalence rate of basic diseases such as boys,hypertension and gastroenteritis was increasing;in addition,the disease burden caused by children's lower gastrointestinal bleeding was also increasing year by year and should be protected.
6.Bionic design,preparation and clinical translation of oral hard tissue restorative materials
Han ZHAO ; Yan WEI ; Xuehui ZHANG ; Xiaoping YANG ; Qing CAI ; Chengyun NING ; Mingming XU ; Wenwen LIU ; Ying HUANG ; Ying HE ; Yaru GUO ; Shengjie JIANG ; Yunyang BAI ; Yujia WU ; Yusi GUO ; Xiaona ZHENG ; Wenjing LI ; Xuliang DENG
Journal of Peking University(Health Sciences) 2024;56(1):4-8
Oral diseases concern almost every individual and are a serious health risk to the popula-tion.The restorative treatment of tooth and jaw defects is an important means to achieve oral function and support the appearance of the contour.Based on the principle of"learning from the nature",Deng Xu-liang's group of Peking University School and Hospital of Stomatology has proposed a new concept of"microstructural biomimetic design and tissue adaptation of tooth/jaw materials"to address the worldwide problems of difficulty in treating dentine hypersensitivity,poor prognosis of restoration of tooth defects,and vertical bone augmentation of alveolar bone after tooth loss.The group has broken through the bottle-neck of multi-stage biomimetic technology from the design of microscopic features to the enhancement of macroscopic effects,and invented key technologies such as crystalline/amorphous multi-level assembly,ion-transportation blocking,and multi-physical properties of the micro-environment reconstruction,etc.The group also pioneered the cationic-hydrogel desensitizer,digital stump and core integrated restora-tions,and developed new crown and bridge restorative materials,gradient functionalisation guided tissue regeneration membrane,and electrically responsive alveolar bone augmentation restorative membranes,etc.These products have established new clinical strategies for tooth/jaw defect repair and achieved inno-vative results.In conclusion,the research results of our group have strongly supported the theoretical im-provement of stomatology,developed the technical system of oral hard tissue restoration,innovated the clinical treatment strategy,and led the progress of the stomatology industry.
7.A Bibliometric and Visual Analysis of the Current Status and Trends of Foren-sic Mixed Stain Research
Qing-Wei FAN ; Ling LI ; Hui-Ling YANG ; Ting-Ting DENG ; Dong-Dong XU ; Yun WANG ; Bing DU ; Jiang-Wei YAN
Journal of Forensic Medicine 2024;40(1):20-29
Objective To explore the context and hotspot changes of forensic mixed stain research through bibliometric approach.Methods The literature of forensic mixed stain included in the core col-lection of Web of Science database from 2011 to 2022 were collected as the study object,and the an-nual publication number,countrie(region),institution,journal,keywords,etc.were bibliometrically and visually analyzed using the R-based Bibliometrix 1.1.6 package and VOSviewer 1.6.18 software.Re-sults A total of 732 articles on forensic mixed stain were included from 2011 to 2022,with the an-nual number of articles published and the annual citation frequency showing a steady increase year by year.Among the 59 countries(regions)with the most published articles,the United States ranked first with 246 articles,followed by China with 153 articles.The literature came from 104 journals,and the total number of articles published in the top 10 journals was 633.FORENSIC SCI INT GENET ranked first with 307 articles.Visual analysis using VOSviewer software showed that keywords could be divided into four research clusters,namely the genetic marker development group(blue),the mixed stain typing analysis theory group(red),the sequencing analysis group(yellow),and the case sample research group(green).It can be divided into four development stages in terms of different time peri-ods:early development(2011-2013),middle development(2014-2016),rapid development(2017-2020)and latest development(2021-2022).Conclusion The number of publications by domestic and foreign scholars in the study of mixed stain in forensic science is showing a relatively stable trend.Machine learning,next generation sequencing and other research have been the hottest topics that have attracted the most attention in recent years,which is expected to further develop the theory of mixed stain typing and sequencing analysis in forensic mixed stain research.
8.Effect of "Internet plus" exercise prescription intervention on upper limb function and quality of life of breast cancer patients at home after surgery
Yang JIANG ; Weiting ZHAO ; Qing CHU ; Ziyu LU ; Yujie GAO ; Wenxia YAN ; Yaoyao JIANG
Chinese Journal of Practical Nursing 2024;40(11):809-816
Objective:To explore the effect of "Internet plus" exercise prescription intervention on upper limb dysfunction and quality of life of breast cancer patients at home after surgery, so as to provide reference for health management of breast cancer patients after surgery.Methods:Adopting a prospective randomized controlled trial research method. From November 2021 to January 2023, 124 breast cancer patients in the breast and thyroid surgery department of Xiang′an Hospital Affiliated to Xiamen University were selected for the study. According to the random number table method, they were randomly divided into an intervention group (62 cases) and a control group (62 cases). The control group patients were given routine training, and the intervention group patients received routine training in the first four weeks after operation, and "Internet plus" exercise prescription intervention in the fifth week after operation. The upper limb dysfunction, quality of life before and after the intervention and motor compliance after the intervention between the two groups were compared.Results:A total of 117 patients were ultimately included, and they were all female, with 58 patients in the intervention group aged (51.01 ± 9.77) years old and 59 patients in the control group aged (51.47 ± 9.85) years old. There was no statistically significant difference in upper limb dysfunction and quality of life between the two groups of patients before intervention ( P>0.05). After the intervention, the degree of upper limb dysfunction in the intervention group was (63.55 ± 7.02) points, which were lower than that in the control group (67.13 ± 7.25) points, and the difference was statistically significant ( t = 2.71, P<0.01). After the intervention, the total score of quality of life and the scores of physiological status, social/family status, emotional status, functional status and additional attention of breast cancer patients in the intervention group were (115.27 ± 17.35), (22.65 ± 4.53), (22.79 ± 4.36), (20.96 ± 3.95), (19.56 ± 4.22), (29.31 ± 5.24) points, which were higher than those in the control group (104.28 ± 17.04), (20.57 ± 4.48), (20.85 ± 4.23), (18.75 ± 4.04), (17.18 ± 4.06), (26.93 ± 5.21) points, the differences were statistically significant ( t values were 2.44-3.46, all P<0.05). In terms of exercise compliance of breast cancer patients in the intervention group, the aerobic exercise completion rate was 91.38% (53/58), muscle strength training completion rate was 77.59% (45/58), stretching exercise completion rate was 86.21% (50/58), exercise frequency was (3.96 ± 1.13) times/week, exercise duration was (29.51 ± 7.64) min/time, which was superior to 77.97% (46/59), 57.63% (34/59), 69.49% (41/59), (3.38 ± 0.94) times/week, (23.96 ± 7.33) min/time in the control group, the differences were statistically significant ( χ2 = 4.04, 5.31, 4.73, t = 3.02, 4.01, all P<0.05). Conclusions:"Internet plus" exercise prescription intervention has the characteristics of convenience, intuition and strong operability, which is conducive to improving the upper limb dysfunction, quality of life and exercise compliance of breast cancer patients at home after surgery. It is recommended to be popularized and applied clinically.
9.Clinical trial of brexpiprazole in the treatment of adults with acute schizophrenia
Shu-Zhe ZHOU ; Liang LI ; Dong YANG ; Jin-Guo ZHAI ; Tao JIANG ; Yu-Zhong SHI ; Bin WU ; Xiang-Ping WU ; Ke-Qing LI ; Tie-Bang LIU ; Jie LI ; Shi-You TANG ; Li-Li WANG ; Xue-Yi WANG ; Yun-Long TAN ; Qi LIU ; Uki MOTOMICHI ; Ming-Ji XIAN ; Hong-Yan ZHANG
The Chinese Journal of Clinical Pharmacology 2024;40(5):654-658
Objective To evaluate the efficacy and safety of brexpiprazole in treating acute schizophrenia.Methods Patients with schizophrenia were randomly divided into treatment group and control group.The treatment group was given brexpiprozole 2-4 mg·d-1 orally and the control group was given aripiprazole 10-20 mg·d-1orally,both were treated for 6 weeks.Clinical efficacy of the two groups,the response rate at endpoint,the changes from baseline to endpoint of Positive and Negative Syndrome Scale(PANSS),Clinical Global Impression-Improvement(CGI-S),Personal and Social Performance scale(PSP),PANSS Positive syndrome subscale,PANSS negative syndrome subscale were compared.The incidence of treatment-related adverse events in two groups were compared.Results There were 184 patients in treatment group and 186 patients in control group.After treatment,the response rates of treatment group and control group were 79.50%(140 cases/184 cases)and 82.40%(150 cases/186 cases),the scores of CGI-I of treatment group and control group were(2.00±1.20)and(1.90±1.01),with no significant difference(all P>0.05).From baseline to Week 6,the mean change of PANSS total score wese(-30.70±16.96)points in treatment group and(-32.20±17.00)points in control group,with no significant difference(P>0.05).The changes of CGI-S scores in treatment group and control group were(-2.00±1.27)and(-1.90±1.22)points,PSP scores were(18.80±14.77)and(19.20±14.55)points,PANSS positive syndrome scores were(-10.30±5.93)and(-10.80±5.81)points,PANSS negative syndrome scores were(-6.80±5.98)and(-7.30±5.15)points,with no significant difference(P>0.05).There was no significant difference in the incidence of treatment-related adverse events between the two group(69.00%vs.64.50%,P>0.05).Conclusion The non-inferiority of Brexpiprazole to aripiprazole was established,with comparable efficacy and acceptability.
10.Effect of oxaliplatin combined with AG1478 on lung cancer by regulating reactive oxygen species and inhibiting PI3K/AKT pathway
Dong-Xue WEI ; Shao-Feng JIANG ; Shan CUI ; Yang LI ; Jin-Qing HUANG
The Chinese Journal of Clinical Pharmacology 2024;40(12):1754-1758
Objective To investigate the effect of epidermal growth factor tyrosine kinase inhibitor AG1478 combined with oxaliplatin(OXA)on non-small cell lung cancer cells H1299.Methods H1299 cells were divided into control group(conventional culture,without drug),OXA-25,-50,-100 groups(25,50 and 100 μmol·L-1 OXA),AG-20 group(20 μmol·L-1AG1478)and OXA+AG group(25 μmol·L-1 OXA and 20 μmol·L-1AG1478).Detection of cell survival rate by MTT assay and calculation of half inhibitory concentration(IC50).Reactive oxygen species(ROS)probe H2DCFDA was used to detect ROS levels.Autophagy of H1299 cells was detected by MDC method.Western blot was used to detect the expression levels of phosphorylated-phosphoinositide 3-kinase(p-PI3 K),phosphorylated-protein kinase B(p-AKT),autophagy protein(Beclin-1)and microtubule associated protein light chain 3-Ⅱ(LC3-Ⅱ).Results The IC50 of OXA on H1299 cells was 91.09 μmol·L-1.The IC50 of AG1478 on H1299 cells was 31.83 μmol·L-1.The relative ROS level were 1.00±0.03,1.15±0.02,1.76±0.04,2.89±0.02,1.05±0.01 and 3.20±0.03,respectively;the relative MDC levels were 1.00±0.04,1.10±0.02,1.16±0.02,1.46±0.04,1.04±0.01 and 1.31±0.02,respectively;the relative expression levels of p-PI3K protein were 1.12±0.05,0.88±0.06,0.72±0.07,0.60±0.05,0.91±0.07 and 0.64±0.09,respectively;the relative expression levels of p-AKT protein were 1.09±0.04,0.87±0.08,0.77±0.07,0.63±0.05,0.76±0.05 and 0.46±0.03,respectively;the relative expression levels of Beclin-1 protein were 0.82±0.03,0.91±0.04,1.06±0.28,1.11±0.03,0.87±0.04 and 1.27±0.10,respectively;the relative expression levels of LC3-Ⅱ protein were 0.65±0.08,0.82±0.11,1.08±0.12,1.38±0.09,0.72±0.11 and 1.38±0.15,respectively.Compared the OXA+AG group and the OXA single group with the control group,compared the OXA+AG group with the OXA single group,there were statistically significant differences in the above indicators(P<0.05,P<0.01).Conclusion AG1478 combined with OXA can increase ROS levels in non-small cell lung cancer cells H1299 and inhibit the activation of PI3K signaling pathway,thus inducing autophagy.


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