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Mitochondrial transplantation confers protection against the effects of ischemic stroke by repressing microglial pyroptosis and promoting neurogenesis

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Neural Regeneration Research 2024年第6期19卷 1325-1335页

作者： Li Sun Zhaoyan Zhao Jing Guo Yuan Qin Qian Yu Xiaolong Shi Fei Guo Haiqin Zhang Xude Sun Changjun Gao Qian Yang Department of Experimental Surgery The Second Affiliated Hospital of Air Force Medical University Department of Anesthesiology The Second Affiliated Hospital of Air Force Medical University

Transferring healthy and functional mitochondria to the lateral ventricles confers neuroprotection in a rat model of ischemia-reperfusion injury. Autologous mitochondrial transplantation is also beneficial in pediatric patients with cardiac ischemia-reperfusion injury. Thus, transplantation of functional exogenous mitochondria may be a promising therapeutic approach for ischemic disease. To explore the neuroprotective effect of mitochondria transplantation and determine the underlying mechanism in ischemic stroke, in this study we established a photo-thrombosis-induced mouse model of focal ischemia and administered freshly isolated mitochondria via the tail vein or to the injury site(in situ). Animal behavior tests, immunofluorescence staining, 2,3,5-triphenyltetrazolium chloride(TTC) staining, mRNA-seq, and western blotting were used to assess mouse anxiety and memory, cortical infarct area, pyroptosis, and neurogenesis, respectively. Using bioinformatics analysis, western blotting, co-immunoprecipitation, and mass spectroscopy, we identified S100 calcium binding protein A9(S100A9) as a potential regulator of mitochondrial function and determined its possible interacting proteins. Interactions between exogenous and endogenous mitochondria, as well as the effect of exogenous mitochondria on recipient microglia, were assessed in vitro. Our data showed that:(1) mitochondrial transplantation markedly reduced mortality and improved emotional and cognitive function, as well as reducing infarct area, inhibiting pyroptosis, and promoting cortical neurogenesis;(2) microglial expression of S100A9 was markedly increased by ischemic injury and regulated mitochondrial function;(3) in vitro, exogenous mitochondria enhanced mitochondrial function, reduced redox stress, and regulated microglial polarization and pyroptosis by fusing with endogenous mitochondria; and(4) S100A9 promoted internalization of exogenous mitochondria by the microglia, thereby amplifying their pro-proliferation and anti-inflammatory effects. Taken togeth

关键词： ischemic stroke microglia mitochondria transplantation neurogenesis pyroptosis

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Magnesium-L-threonate treats Alzheimer's disease by modulating the microbiota-gut-brain axis

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Neural Regeneration Research 2024年第10期19卷 2281-2289页

作者： Wang Liao Jiana Wei Chongxu Liu Haoyu Luo Yuting Ruan Yingren Mai Qun Yu Zhiyu Cao Jiaxin Xu Dong Zheng Zonghai Sheng Xianju Zhou Jun Liu Department of Neurology The Second Affiliated Hospital of Guangzhou Medical UniversityGuangzhouGuangdong ProvinceChina Special medical Service Center Neuroscience CenterIntegrated Hospital of Traditional Chinese MedicineSouthern Medical UniversityGuangdongGuangdong ProvinceChina Department of Rehabilitation The Second Affiliated HospitalGuangzhou Medical UniversityGuangzhouGuangdong ProvinceChina Department of Neurology Sun Yat-sen Memorial HospitalSun Yat-sen UniversityGuangzhouGuangdong ProvinceChina Department of Neurology The Affiliated Brain Hospital of Guangzhou Medical UniversityGuangzhouGuangdong ProvinceChina Institute of Biomedical and Health Engineering Shenzhen Institute of Advanced TechnologyChinese Academy of SciencesShenzhenGuangdong ProvinceChina

Disturbances in the microbiota-gut-brain axis may contribute to the development of Alzheimer's disease. Magnesium-L-threonate has recently been found to have protective effects on learning and memory in aged and Alzheimer's disease model mice. However, the effects of magnesium-L-threonate on the gut microbiota in Alzheimer's disease remain unknown. Previously, we reported that magnesium-L-threonate treatment improved cognition and reduced oxidative stress and inflammation in a double-transgenic line of Alzheimer's disease model mice expressing the amyloid-β precursor protein and mutant human presenilin 1(APP/PS1). Here, we performed 16S r RNA amplicon sequencing and liquid chromatography-mass spectrometry to analyze changes in the microbiome and serum metabolome following magnesium-Lthreonate exposure in a similar mouse model. Magnesium-L-threonate modulated the abundance of three genera in the gut microbiota, decreasing Allobaculum and increasing Bifidobacterium and Turicibacter. We also found that differential metabolites in the magnesiumL-threonate-regulated serum were enriched in various pathways associated with neurodegenerative diseases. The western blotting detection on intestinal tight junction proteins(zona occludens 1, occludin, and claudin-5) showed that magnesium-L-threonate repaired the intestinal barrier dysfunction of APP/PS1 mice. These findings suggest that magnesium-L-threonate may reduce the clinical manifestations of Alzheimer's disease through the microbiota-gut-brain axis in model mice, providing an experimental basis for the clinical treatment of Alzheimer's disease.

关键词： Alzheimer's disease APP/PS1 double-transgenic Alzheimer's disease mouse model inflammation intestinal barrier dysfunction magnesium-L-threonate microbiome microbiota-gut-brain axis oxidative stress serum metabolites

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Effect of pediatric Tuina on children's recurrent acute respiratory tract infections: a retrospective cohort study in Southern China

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Journal of Traditional Chinese Medicine 2024年第3期44卷 586-594页

作者： YIN Lingjia ST?LSBY LUNDBORG Cecilia WU Darong YANG Jinghua ALVESSON Helle M?lsted CAI Jianxiong LU Taoying XIE Qianwen MARRONE Gaetano Department of Global Public Health Karolinska Institutet State Key Laboratory of Dampness Syndrome of Chinese Medicine the Second Affiliated Hospital of Guangzhou University of Chinese Medicine Outcome Assessment Research Team in Chinese Medicine the Second Affiliated Hospital of Guangzhou University of Chinese Medicine Health Construction Administration Centre Guangdong Provincial Hospital of Chinese Medicine Guangdong Provincial Key Laboratory of Clinical Research on Traditional Chinese Medicine Syndrome the Second Affiliated Hospital of Guangzhou University of Chinese Medicine Department of Pediatrics the Second Affiliated Hospital of Guangzhou University of Chinese Medicine

OBJECTIVE: To determine the effectiveness of pediatric Tuina(PT) in preventing recurrent acute respiratory tract infections(ARTIs) in children. METHODS: This is a retrospective cohort study based on the electronic medical records of children with recurrent ARTIs in 2016. Children were divided into a PT group or a non-PT group, according to whether they had received PT or not in 2016. The primary outcome was the number of ARTI episodes in 2017 and 2018. The secondary outcomes were the number of ARTIs leading to outpatient department visits and outpatient antibiotic prescriptions due to ARTIs in the same time period. Negative binomial regressions were used to detect the association between PT and the outcomes. RESULTS: A total of 2303 children were included in the analysis, including 94 in the PT group and 2209 in the non-PT group. Children who received PT six or more times in 2016 had fewer episodes of ARTIs in 2017 [incidence rate ratio(IRR): 0.59, 95% confidence interval(CI)(0.42-0.84)] and 2018 [IRR: 0.58, 95% CI(0.36-0.94)] and fewer outpatient department visits due to ARTIs in 2017 [IRR: 0.56, 95% CI(0.38-0.83)] than children who had not received PT in 2016. There was no significant difference in the number of outpatient antibiotic prescriptions between the two groups. CONCLUSIONS: Receiving PT six or more times within one year is associated with a decrease in recurrent ARTIs in children in the following two years. Randomized controlled trials are needed for effect evaluation prior to establishing PT as a method for preventing recurrent ARTIs among children.

关键词： child massage pediatric Tuina respiratory tract infections

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Metadherin promotes stem cell phenotypes and correlated with immune infiltration in hepatocellular carcinoma

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World Journal of Gastroenterology 2024年第8期30卷 901-918页

作者： Yi-Ying Wang Mei-Mei Shen Jian Gao Department of Gastroenterology The Second Affiliated Hospital of Chongqing Medical UniversityChongqing 400010China Department of Gastroenterology and Hepatology The Second Affiliated Hospital of Chongqing Medical UniversityChongqing 400010China

BACKGROUND Metadherin(MTDH)is a key oncogene in most cancer types,including hepato-cellular carcinoma(HCC).Notably,MTDH does not affect the stemness pheno-type or immune infiltration of HCC.AIM To explore the role of MTDH on stemness and immune infiltration in HCC.METHODS MTDH expression in HCC tissues was detected using TCGA and GEO databases.Immunohistochemistry was used to analyze the tissue samples.MTDH was stably knocked down or overexpressed by lentiviral transfection in the two HCC cell lines.The invasion and migration abilities of HCC cells were evaluated using Matrigel invasion and wound healing assays.Next,we obtained liver cancer stem cells from the spheroids by culturing them in a serum-free medium.Gene expression was determined by western blotting and quantitative reverse transcri-ption PCR.Flow cytometry,immunofluorescence,and tumor sphere formation assays were used to characterize stem-like cells.The effects of MTDH inhibition on tumor growth were evaluated in vivo.The correlation of MTDH with immune cells,immunomodulators,and chemokines was analyzed using ssGSEA and TISIDB databases.RESULTS HCC tissues expressed higher levels of MTDH than normal liver tissues.High MTDH expression was associated with a poor prognosis.HCC cells overex-pressing MTDH exhibited stronger invasion and migration abilities,exhibited a stem cell-like phenotype,and formed spheres;however,MTDH inhibition attenuated these effects.MTDH inhibition suppressed HCC progression and CD133 expression in vivo.MTDH was positively correlated with immature dendritic,T helper 2 cells,central memory CD8^(+)T,memory B,activated dendritic,natural killer(NK)T,NK,activated CD4^(+)T,and central memory CD4^(+)T cells.MTDH was negatively correlated with activated CD8^(+)T cells,eosinophils,activated B cells,monocytes,macrophages,and mast cells.A positive correlation was observed between the MTDH level and CXCL2 expression,whereas a negative correlation was observed between the MTDH level and CX3CL1 and CXCL12 expression.CONCLUSION High levels of M

关键词： Metadherin Hepatocellular carcinoma Cancer stem cells Immune infiltration

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Design,synthesis,and biological evaluation of novel chrysin derivatives as poly(ADP-ribose)polymerase 1(PARP1)inhibitors for the treatment of breast cancer

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Chinese Journal of Natural Medicines 2024年第5期22卷 455-465页

作者： YANG Yao TONG Jing XIE Xianshun CAO Hong FU Yong LUO Yong LIU Shan CHEN Wen YANG Ning Hengyang medical School University of South ChinaHengyang 421200China Emergency Department Hengyang Medical SchoolThe Second Affiliated HospitalUniversity of South ChinaHengyang 421200China Hengyang medical School The Second Affiliated HospitalUniversity of South ChinaHengyang 421200China Hemato-oncology Department Hengyang Medical SchoolThe Second Affiliated HospitalUniversity of South ChinaHengyang 421200China Department of Breast and Thyroid Surgery Hengyang Medical SchoolThe Second Affiliated HospitalUniversity of South ChinaHengyang 421200China

In this study,we reported the discovery and structure-activity relationship analysis of chrysin derivatives as a new class of inhibitors targeting poly(ADP-ribose)polymerase 1(PARP1).Among these derivatives,compound 5d emerged as the most effective chrysin-based inhibitor of PARP1,with an IC50 value of 108 nmol·L^(-1).This compound significantly inhibited the proliferation and migration of breast cancer cell lines HCC-1937 and MDA-MB-436 by inducing DNA damage.Furthermore,5d induced apoptosis and caused an extended G1/S-phase in these cell lines.Molecular docking studies revealed that 5d possesses a strong binding affinity toward PARP1.In vivo,in a xenograft model,5d effectively reduced tumor growth by downregulating PARP1 expression.Overall,compound 5d shows promise as a potential therapeutic agent for the treatment of BRCA wild-type breast cancer.

关键词： Chrysin derivatives PARP1 Antitumor DNA damage Small molecules

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Berberine Enhances Intestinal Mucosal Barrier Function by Promoting Vitamin D Receptor Activity

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Chinese Journal of Integrative Medicine 2024年第2期30卷 143-151页

作者： HUANG Yong-quan LIU Jia-lin CHEN Geng-xin SHEN Dan-ting ZHU Wang CHEN Xin-lin LIU Feng-bin HOU Qiu-ke Graduate School Guangzhou University of Chinese MedicineGuangzhou(510405)China Department of Orthopedics the Second Affiliated Hospital of Guangzhou University of Chinese MedicineGuangzhou(510006)China Department of Preventive Medicine and Health Statistics Guangzhou University of Chinese MedicineGuangzhou(510006)China Department of Gastroenterology the First Affiliated Hospital of Guangzhou University of Chinese MedicineGuangzhou(510405)China

Objective:To evaluate if berberine can act on vitamin D receptors(VDR)and thereby regulate the expression of tight junction proteins(TJPs)in irritable bowel syndrome-diarrhea-predominant(IBS-D)rats.Methods:The newborn rats were induced into IBS-D rat model via neonatal maternal separation combined with acetic acid chemical stimulation.After modeling,the model was evaluated and rats were divided into the control group and berberine treatment groups(0.85,1.7 and 3.4 mg/kg,once a day for 2 weeks).The distal colon was obtained and colonic epithelial cells(CECs)were isolated and cultured after IBS-D model evaluation.The vitamin D receptor response element(VDRE)reporter gene was determined in the CECs of IBS-D rats to analyze the effect of berberine on the VDRE promoter.VDR overexpression or silencing technology was used to analyze whether VDR plays a role in promoting intestinal barrier repair,and to determine which region of VDR plays a role in berberine-regulated intestinal TJPs.Results:The IBS-D rat model was successfully constructed and the symptoms were improved by berberine in a dose-dependent manner(P<0.05).The activity of VDRE promoter was also effectively promoted by berberine(P<0.05).Berberine increased the expression of TJPs in IBS-D CECs(P<0.05).VDR expression was significantly increased after transfection of different domains of VDR when compared to normal control and basic plasmid groups(all P<0.05).RT-qPCR and Western blot results showed that compared with the blank group,expressions of occludin and zonula occludens-1 were significantly higher in VDR containing groups(all P<0.05).Berberine plus pCMV-Myc-VDR-N group exerted the highest expression levels of occludin and zonula occludens-1(P<0.05).Conclusion:Berberine enhances intestinal mucosal barrier function of IBS-D rats by promoting VDR activity,and the main site of action is the N-terminal region of VDR.

关键词： berberine Chinese medicine irritable bowel syndrome-diarrhea-predominant vitamin D receptors intestinal mucosal barrier tight junction proteins

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Can NogoA Be a Suitable Target to Treat Ischemic Stroke?

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Neuroscience Bulletin 2024年第4期40卷 557-560页

作者： Suliman Khan Abdul Nasir medical Research Center The Second Affiliated Hospital of Zhengzhou UniversityZhengzhou540014China

Treating stroke or restoring brain function after stroke remains challenging for clinicians[1,2].Researchers have largely focused on developing neuroprotective strategies and translating these discoveries from rodent experiments to the clinical setting;however,these have been typified by several failures[2].It is known that astrocytes play a crucial role in the pathogenesis of ischemic stroke[3,4].They are activated in response to stimuli arising from injury,characterized by drastic changes to their morphology and function-associated gene expression.Reactive astrocytes exacerbate secondary neurodegeneration(repair of nervous tissue by the generation of new neurons,glial cells,axons,myelin,or synapses)[5]as well as provide neuroprotection during CNS pathologies[6].It is worth noting that myelin-related neurite growth inhibitors induce the suppression of axon regeneration after stroke[7].

关键词： protective NogoA clinical

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Intermittent sliding-lock-knot suture for limbal conjunctival autograft fixation in pterygium surgery:a technique note

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International Journal of Ophthalmology(English edition) 2024年第5期17卷 838-844页

作者： Ling Zhang Run-Hua Lyu Jing-Ru Wang Wen-Jian Shi Feng Zheng Ying-Ying Gao Department of Ophthalmology the Second Affiliated HospitalFujian Medical UniversityQuanzhou 362000Fujian ProvinceChina Department of Neurosurgery the Second Affiliated HospitalFujian Medical UniversityQuanzhou 362000Fujian ProvinceChina

AIM:To report a technique used with intermittent slidinglock-knot(ISLK)fixation for limbal conjunctival autografts in pterygium surgery and compared with those of routine intermittent(RI)fixation.METHODS:Consecutive patients with primary pterygium who had undergone pterygium excision combined with limbal conjunctival autograft transplantation between March 2021 and March 2022 at our institute were retrospectively analyzed.Primary outcome measures were mean duration of surgery and suture removal,degree of conjunctival hyperemia on postoperative day 1,pain score at suture removal,postoperative symptoms at 6mo,including conjunctival hyperemia,foreign body sensation,and graft stability.RESULTS:Ninety-eight patients underwent monocular surgery and were divided into ISLK(51 eyes)and RI(47 eyes)groups according to the type of conjunctiva autograft fixation method planned.There was no significant difference in mean duration of surgery between the two groups(18.59±2.39min vs 18.15±2.20min,P=0.417);however,compared to the RI group,shorter suture removal times were observed in the ISLK group[0.58min(0.42-0.87)vs 3.00min(2.21-4.15),P<0.001].The degree of conjunctival hyperemia on postoperative day 1 was milder in the ISLK group(P<0.001).Pain scores at suture removal were lower in the ISLK group than in RI group[1(0-3)vs 2(1-4),P<0.001].Postoperative symptoms at 6mo were comparable between the groups(P=0.487),with no recurrence.CONCLUSION:ISLK is an innovative method for limbal conjunctival autograft fixation after pterygium excision.Compared to RI fixation,ISLK facilitates suture removal and reduces discomfort,with comparable surgery duration and less conjunctival hyperemia.

关键词： intermittent sliding-lock-knot fixation pterygium suture removal

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Global and regional trends in the incidence and mortality burden of endometrial cancer,1990–2019:Updated results from the Global Burden of Disease Study,2019

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Chinese medical Journal 2024年第3期137卷 294-302页

作者： Jianyang Feng Rongjin Lin Haoxian Li Jiayan Wang Hong He Department of Obstetrics and Gynecology Guangdong Provincial Key Laboratory of Major Obstetric Diseasethe Third Affiliated Hospital of Guangzhou Medical UniversityGuangzhouGuangdong 510000China Department of Fetal Medicine and Prenatal Diagnosis the Third Affiliated Hospital of Guangzhou Medical UniversityGuangzhouGuangdong 510000China

Background:The disease burdens for endometrial cancer(EC)vary across different countries and geographical regions and change every year.Herein,we reported the updated results of the Global Burden of Disease Study 2019 on EC with respect to age-standardized incidence and mortality from 1990 to 2019.Methods:The annual percentage change(APC)of incidence and mortality was evaluated using joinpoint regression analysis to examine the temporal trends during the same timeframe in terms of the global landscape,different sociodemographic indices(SDI),and geographic regions.The relationship between Human Development Index(HDI)and incidence and mortality was additionally explored.Results:The age-standardized incidence rates(ASIRs)revealed a significant average global elevation by 0.5%per year(95%confidence interval[CI],0.3–0.7;P<0.001).The age-standardized mortality rates(ASMRs),in contrast,fell by an average of 0.8%per year(95%CI,−1.0 to−0.7;P<0.001)worldwide.The ASIRs and ASMRs for EC varied across different SDIs and geographical regions.We noted four temporal trends and a significant reduction by 0.5%per year since 2010 in the ASIR,whereas we detected six consecutively decreasing temporal trends in ASMR during the entire period.Notably,the estimated APCs were significantly positively correlated with HDIs(ρ=0.22;95%CI,0.07–0.35;P=0.003)with regard to incident cases in 2019.Conclusions:Incidence rates for EC reflected a significant increase overall(although we observed a decline since 2010),and the death rates declined consecutively from 1990 to 2019.We posit that more precise strategies can be tailored and then implemented based on the distinct age-standardized incidence and mortality burden in different geographical areas.

关键词： Endometrial cancer Global Burden of Disease Incidence Mortality Trends

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Analysis of the causes of primary revision after unicompartmental knee arthroplasty: A case series

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World Journal of Clinical Cases 2024年第9期12卷 1560-1568页

作者： Jin-Long Zhao Xiao Jin He-Tao Huang Wei-Yi Yang Jia-Hui Li Ming-Hui Luo Jun Liu Jian-Ke Pan The second Clinical medical College Guangzhou University of Chinese MedicineGuangzhou 510405Guangdong ProvinceChina Department of Chinese Medicine The First Affiliated HospitalJinan UniversityGuangzhou 510630Guangdong ProvinceChina The second School of Clinical medical Sciences Guangzhou University of Chinese MedicineGuangdong Academy of Traditional Chinese MedicineGuangzhou 510405Guangdong ProvinceChina The second affiliated hospital Guangzhou University of Chinese Medicine(Guangdong Provincial Hospital of Chinese Medicine)Guangzhou 510120Guangdong ProvinceChina The affiliated TCM hospital Guangzhou Medical UniversityGuangzhou 510405Guangdong ProvinceChina The Research Team on Bone and Joint Degeneration and Injury Guangdong Provincial Academy of Chinese Medical SciencesGuangzhou 510405Guangdong ProvinceChina

BACKGROUND Unicompartmental knee arthroplasty(UKA)has great advantages in the treatment of unicompartmental knee osteoarthritis,but its revision rate is higher than that of total knee arthroplasty.AIM To summarize and analyse the causes of revision after UKA.METHODS This is a retrospective case series study in which the reasons for the first revision after UKA are summarized.We analysed the clinical symptoms,medical histories,laboratory test results,imaging examination results and treatment processes of the patients who underwent revision and summarized the reasons for primary revision after UKA.RESULTS A total of 13 patients,including 3 males and 10 females,underwent revision surgery after UKA.The average age of the included patients was 67.62 years.The prosthesis was used for 3 d to 72 months.The main reasons for revision after UKA were improper suturing of the surgical opening(1 patient),osteophytes(2 patients),intra-articular loose bodies(2 patients),tibial prosthesis loosening(2 patients),rheumatoid arthritis(1 patient),gasket dislocation(3 patients),anterior cruciate ligament injury(1 patient),and medial collateral ligament injury with residual bone cement(1 patient).CONCLUSION The causes of primary revision after UKA were gasket dislocation,osteophytes,intra-articular loose bodies and tibial prosthesis loosening.Avoidance of these factors may greatly reduce the rate of revision after UKA,improve patient satisfaction and reduce medical burden.

关键词： Unicompartmental knee arthroplasty Total knee arthroplasty Causes Revision Case series

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