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Liver as a new target organ in Alzheimer's disease:insight from cholesterol metabolism and its role in amyloid-beta clearance

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Neural Regeneration Research 2025年第3期20卷 695-714页

作者： Beibei Wu Yuqing Liu Hongli Li Lemei Zhu Lingfeng Zeng Zhen Zhang Weijun Peng Department of Integrated traditional chinese&Western medicine The Second Xiangya HospitalCentral South UniversityChangshaHunan ProvinceChina Academician Workstation Changsha Medical UniversityChangshaHunan ProvinceChina Yangsheng college of traditional chinese medicine Guizhou University of Traditional Chinese MedicineGuiyangGuizhou ProvinceChina Qinhuangdao Shanhaiguan Pharmaceutical Co. LtdQinhuangdaoHebei ProvinceChina National Clinical Research Center for Mental Disorder The Second Xiangya HospitalCentral South UniversityChangshaHunan ProvinceChina

Alzheimer's disease,the primary cause of dementia,is characterized by neuropathologies,such as amyloid plaques,synaptic and neuronal degeneration,and neurofibrillary *** amyloid plaques are the primary characteristic of Alzheimer's disease in the central nervous system and peripheral organs,targeting amyloid-beta clearance in the central nervous system has shown limited clinical efficacy in Alzheimer's disease *** abnormalities are commonly observed in patients with Alzheimer's *** liver is the primary peripheral organ involved in amyloid-beta metabolism,playing a crucial role in the pathophysiology of Alzheimer's ***,impaired cholesterol metabolism in the liver may exacerbate the development of Alzheimer's *** this review,we explore the underlying causes of Alzheimer's disease and elucidate the role of the liver in amyloid-beta clearance and cholesterol ***,we propose that restoring normal cholesterol metabolism in the liver could represent a promising therapeutic strategy for addressing Alzheimer's disease.

关键词： ABCA1 Alzheimer's disease amyloid-beta apolipoprotein E cholesterol metabolism liver liver X receptor low-density lipoprotein receptor-related protein 1 peripheral clearance tauroursodeoxycholic acid

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Neuroprotective potential for mitigating ischemia-reperfusion-induced damage

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Neural Regeneration Research 2025年第8期20卷 2199-2217页

作者： Zi Ye Runqing Liu Hangxing Wang Aizhen Zuo Cen Jin Nan Wang Huiqi Sun Luqian Feng Hua Yang The Clinical Medical college Guizhou Medical UniversityGuiyangGuizhou ProvinceChina Division of Infectious Diseases Department of Internal MedicinePeking Union Medical College HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina School of Medical Imaging Guizhou Medical UniversityGuiyangGuizhou ProvinceChina Division of Gastroenterology First Affiliated Hospital of Zhengzhou UniversityZhengzhouHenan ProvinceChina The second Clinical Medical college Lanzhou UniversityLanzhouGansu ProvinceChina Department of Neurosurgery Affiliated Hospital of Guizhou Medical UniversityGuiyangGuizhou ProvinceChina

Reperfusion following cerebral ischemia causes both structural and functional damage to brain tissue and could aggravate a patient's condition;this phenomenon is known as cerebral ischemia-reperfusion *** studies have elucidated the neuroprotective role of the sirtuin protein family(Sirtuins)in modulating cerebral ischemia-reperfusion ***,the potential of utilizing it as a novel intervention target to influence the prognosis of cerebral ischemia-reperfusion injury requires additional *** this review,the origin and research progress of Sirtuins are summarized,suggesting the involvement of Sirtuins in diverse mechanisms that affect cerebral ischemia-reperfusion injury,including inflammation,oxidative stress,blood-brain barrier damage,apoptosis,pyroptosis,and *** therapeutic avenues related to Sirtuins that may improve the prognosis of cerebral ischemia-reperfusion injury were also investigated by modulating Sirtuins expression and affecting representative pathways,such as nuclear factor-kappa B signaling,oxidative stress mediated by adenosine monophosphate-activated protein kinase,and the forkhead box *** review also summarizes the potential of endogenous substances,such as RNA and hormones,drugs,dietary supplements,and emerging therapies that regulate Sirtuins *** review also reveals that regulating Sirtuins mitigates cerebral ischemia-reperfusion injury when combined with other risk *** Sirtuins show promise as a potential target for the treatment of cerebral ischemiareperfusion injury,most recent studies are based on rodent models with circadian rhythms that are distinct from those of humans,potentially influencing the efficacy of Sirtuinstargeting drug ***,this review provides new insights into the role of Sirtuins in the pathology and treatment of cerebral ischemia-reperfusion injury.

关键词： apoptosis autophagy blood-brain barrier dietary supplements drug hormones inflammation neuroprotection oxidative stress prognosis pyroptosis reperfusion injury risk factors RNA therapeutics

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FSD1 inhibits glioblastoma diffuse infiltration through restriction of HDAC6-mediated microtubule deacetylation

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Science China Life Sciences 2025年

作者： Dake Xiao Haowen Ran Lishu Chen Yuanyuan Li Yan Cai Songyang Zhang Qinghui Qi Huiran Wu Cheng Zhang Shuailiang Cao Lanjuan Mi Haohao Huang Ji Qi Qiuying Han Haiqing Tu Huiyan Li Tao Zhou Fangye Li Ailing Li Jianghong Man Nanhu Laboratory National Center of Biomedical Analysis School of traditional chinese medicine Capital Medical University Department of Neurosurgery General Hospital of Central Theater Command of Chinese PLA School of Life and Health Sciences Huzhou College Department of Neurosurgery Beijing Fengtai Hospital Department of Neurosurgery First Medical Center of PLA General Hospital

The infiltration of glioblastoma multiforme(GBM) is predominantly characterized by diffuse spread, contributing significantly to therapy resistance and recurrence of GBM. In this study, we reveal that microtubule deacetylation, mediated through the downregulation of fibronectin type III and SPRY domain-containing 1(FSD1), plays a pivotal role in promoting GBM diffuse infiltration. FSD1 directly interacts with histone deacetylase 6(HDAC6) at its second catalytic domain, thereby impeding its deacetylase activity on α-tubulin and preventing microtubule deacetylation and depolymerization. This inhibitory interaction is disrupted upon phosphorylation of FSD1 at its Ser317 and Ser324 residues by activated CDK5, leading to FSD1 dissociation from microtubules and facilitating HDAC6-mediated α-tubulin deacetylation. Furthermore, increased expression of FSD1 or interference with FSD1 phosphorylation reduces microtubule deacetylation, suppresses invasion of GBM stem cells, and ultimately mitigates tumor infiltration in orthotopic GBM xenografts. Importantly, GBM tissues exhibit diminished levels of FSD1 expression, correlating with microtubule deacetylation and unfavorable clinical outcomes in GBM patients. These findings elucidate the mechanistic involvement of microtubule deacetylation in driving GBM cell invasion and offer potential avenues for managing GBM infiltration.

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Efficacy of self-made Gengnian decoction on phosphatidylinositol 3-kinases/protein kinase B/mammalian target of rapamycin signaling pathway in perimenopausal rats

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Journal of traditional chinese medicine 2019年第6期39卷 861-866页

作者： Zhang Fan Cao Junyan Zhang Xin Wang Jing Yi Xu the second affiliated hospital of guiyang University of traditional chinese medicine

OBJECTIVE:To investigate the efficacy of self-made Gengnian decoction on expressions of phosphatidylinositol 3-kinase(PI3 K),protein kinase B(Akt)and mammalian target of rapamycin(m TOR)in ovarian tissues of perimenopausal *** were identified with symptom pattern of kidney-Yang deficiency in terms of traditional chinese ***:Female Sprague-Dawley rats aged10-12 months were *** cycle was observed by vaginal smears of keratinocytes to screen the perimenopausal model *** chosen rats were randomly divided into five groups,including perimenopausal model of kidney-Yang deficiency group(24 rats),self-made Gengnian decoction of high-dose group(24 rats),self-made Gengnian decoction of middle-dose group(24 rats),self-made Gengnian decoction of low dose group(24 rats)and tibolone control group(24 rats).In addition,rats aged 4-6 months were selected as young control *** perimenopausal model rats of kidney-Yang deficiency were prepared by alternative intramuscular injection of hydrocortisone 5 mg·kg^-1·d^-1The successfully prepared models in self-made Gengnian decoction of high-dose,middle-dose and low-dose groups and tibolone control group were given self-made Gengnian decoction 26.4,13.2 and 6.6 mg·kg^-1·d^-1,and tibolone tablets solvent 0.22 mg·kg^-1·d^-1,respectively,through intragastric *** group and young control group were given the same dose of normal saline,1 time a day for 15 consecutive days.24 h after the last administration,blood and ovarian tissues were collected after anesthesia with 20%ethyl *** follicles of different levels in ovarian tissue were observed and counted by histopathological hematoxylin-eosin *** linked immunosorbent assay was applied to test insulin-like growth factor-1(IGF-1)level in the serum of experimental *** expression levels of PI3 K,phosphorylated-Akt(p-Akt)and phosphorylated-m TOR(p-m TOR)m RNA in ovarian tissue were detected by quantitative real-time po

关键词： Premenopause Insulin-like growth factor-1 Phosphatidylinositol 3-kinase Protein-serine-threonine kinases TOR serine-threonine kinases Gengnian decoction

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Mechanism of action of Linggui Zhugan Decoction in treating non-alcoholic fatty liver disease using untargeted metabolomics approach

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traditional medicine Research 2025年第2期10卷 65-76页

作者： Huan Pei Ren-Lin Li Xin-Ran Song Qian-Qian Wan Yu-Ming Wang Han-Zhou Li Wei-Quan Xu Jia-Bao Liao Wei-Bo Wen Jing Miao Huan-Tian Cui School of Basic medicine Yunnan University of Chinese MedicineKunming 650599China School Clinical Medical college Yunnan University of Chinese MedicineKunming 650599China First School of Clinical medicine Yunnan University of Chinese MedicineKunming 650599China School of Integrative chinese and Western medicine Tianjin University of Traditional Chinese MedicineTianjin 301617China Department of Pharmacy Tianjin Second People's HospitalTianjin 300192China

Background:Non-alcoholic fatty liver disease(NAFLD)is a liver disorder characterized by the accumulation and degeneration of fat in the liver cells,a condition that may further deteriorate and lead to cirrhosis and liver *** studies showed that metabolic dysfunction can promote NAFLD *** Zhugan Decoction(LGZGD)has therapeutic effects on *** mechanism of LGZGD still remains *** study was to examine the impact of LGZGD on the metabolic processes involved in the development of ***:A mice model of NAFLD was treated with *** therapeutic potential of LGZGD was evaluated by assessing the activity of transaminases,lipids levels of blood,and pathological changes in the liver of the mice model of ***,this study also evaluated the influence of LGZGD on liver inflammation and oxidative ***:The results of untargeted metabolomics analysis showed that LGZGD reduced the disordered lipid metabolism in NAFLD *** improved the oxidative stress and also reduced the levels of pro-inflammatory cytokines in the *** metabolomics analysis of liver samples revealed that LGZGD treatment improved metabolic disorders,including alanine,aspartate,glutamate,glycerophospholipid metabolism,and citrate *** RT-qPCR and Western blot results showed that LGZGD could regulate the expression of key enzymes in the metabolic pathway of the citrate cycle,including ATP-citrate lyase(ACLY),alanine-glyoxylate aminotransferase-2(AGXT2),phosphatidylethanolamine N-methyltransferase(PEMT),and succinate dehydrogenase(SDH).Conclusion:We found that LGZGD can treat NAFLD by reducing inflammatory responses,inhibiting oxidative stress,regulating alanine,aspartate,glutamate,and glycerophospholipid metabolism,and citrate cycle pathways.

关键词： NAFLD LGZGD untargeted metabolomics glycerophospholipid metabolism citrate cycle

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Effect of Astragalus polysaccharide in treatment of diabetes mellitus: a narrative review

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Journal of traditional chinese medicine 2019年第1期39卷 133-138页

作者： Zhang Zexi Zhang Lei Xu Hansong Department of endocrinology Guiyang College of Traditional Chinese MedicineGuiyang 550000China First Teaching hospital of Tianjin University of traditional chinese medicine Tianjin 300100China NO.2 hospital affiliated to traditional chinese medicine college of guiyang Guiyang 550000China

Diabetes mellitus is a chronic endocrine/metabolism disease characterized by hyperglycemia arising from defects in insulin action, insulin secretion,or both. Diabetes mellitus is often complicated by visceral lesions, which can lead to serious complications and death. A variety of new agents are in development for the treatment of the disease. Astragalus polysaccharides are monomer components extracted from the traditional chinese medicine,Huangqi(Radix Astragali Mongolici), which have been studied widely for treating diabetes mellitus with promising effects in recent years. This paper reviews recent advances in experimental studies on the effects of Astragalus polysaccharides in treating diabetes mellitus. The effects of Astragalus polysaccharides on the etiology and complication of diabetes mellitus including insulin resistance and secretion, diabetic neuropathy, diabetic retinopathy, diabetic cardiomyopathy, diabetic foot, and infection complicated by diabetes mellitus are discussed.

关键词： Diabetes mellitus Astragalus polysaccharide Review

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Electroacupuncture Attenuates Immune-Inflammatory Response in Hippocampus of Rats with Vascular Dementia by Inhibiting TLR4/MyD88 Signaling Pathway

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chinese Journal of Integrative medicine 2022年第2期28卷 153-161页

作者： BU Yu LI Wen-shuang LIN Ji WEI Yu-wei SUN Qiu-ying ZHU Shi-jie TANG Zhong-sheng School of Basic medicine Guizhou University of Traditional Chinese MedicineGuiyang(550025)China Department of Hematology the Second Affiliated Hospital of Guizhou University of Traditional Chinese MedicineGuiyang(550025)China

Objective:To investigate whether electroacupuncture(EA)alleviates cognitive impairment by suppressing the toll-like receptor 4(TLR4)/myeloid differentiation factor 88(MyD88)signaling pathway,which triggers immune-inflammatory responses in the hippocampus of rats with vascular dementia(VaD).Methods:The experiments were conducted in 3 parts and in total the Sprague-Dawley rats were randomly divided into 8 groups by a random number table,including sham,four-vessel occlusion(4-VO),4-VO+EA,4-VO+non-EA,sham+EA,4-VO+lipopolysaccharide(LPS),4-VO+LPS+EA,and 4-VO+TAK-242 *** VaD model was established by the 4-VO *** days later,rats were treated with EA at 5 acupoints of Baihui(DV 20),Danzhong(RN 17),Geshu(BL 17),Qihai(RN 6)and Sanyinjiao(SP 6),once per day for 3 consecutive *** subsets,lymphocyte transformation rates,and inflammatory cytokines interleukin-6(IL-6)and tumor necrosis factorα(TNF-α)were measured to assess immune function and inflammation in VaD *** electron microscopy was used to observe the ultrastructure of nerve cells in the *** levels of TLR4,MyD88,IL-6,and TNF-αwere detected after EA ***4/MyD88 signaling and cognitive function were also assessed after intracerebroventricular injection of TLR4 antagonist TAK-242 or TLR4 agonist LPS with or without ***:Compared with the 4-VO group,EA notably improved immune function of rats in the 4-VO+EA group,inhibited the protein and mRNA expressions of TLR4 and MyD88 in the hippocampus of rats,reduced the expressions of serum IL-6 and TNF-α(all P0.05).Conclusions:EA attenuated cognitive impairment associated with immune inflammation by inhibition of the TLR4/MyD88 signaling ***,EA may be a promising alternative therapy for the treatment of VaD.

关键词： electroacupuncture vascular dementia immune-inflammation toll-like receptor 4/myeloid differentiation factor 88 signaling pathway

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A comparative study of electroacupuncture at Zhongliao （BL33） and other acupoints for overactive bladder symptoms

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Frontiers of medicine 2017年第1期11卷 129-136页

作者： Likun Yang Yang Wang Qian Mo Zhishun Liu Department of Acupuncture Guang'anmen Hospital China Academy of Chinese Medical Sciences Beijing 100053 China Graduate college of Tianjin University of traditional chinese medicine Tianjin 300193 China School of Acupuncture-Moxibustion and Tuina Guiyang College of Traditional Chinese Medicine Guiyang 550025 China Department of Acupuncture the Second Affiliated Hospital of Guiyang College of Traditional Chinese Medicine Guiyang 550003 China

Electroacupuncture （EA） at Zhongliao （BL33） can improve the symptoms of overactive bladder （OAB）, such as urinary frequency, urgency, and incontinence. However, its performance compared with other acupoints remains unclear. This study investigated the effects of EA at BL33 with deep needling on rats with OAB by detecting urodynamics in eight groups： no intervention group, D-BL33 group （deep needling at BL33）, S-BL33 group （shallow needling at BL33）, non-acupoint group （needling at the non-acupoint next to BL33）, Weizhong （BL40） group, Sanyinjiao （SP6） group, Tongtian （BL7） group, and Hegu （LI4） group. Results revealed that EA at BL33 with deep needling, BL40, and SP6 prolonged the intercontraction interval （ICI） of rats with OAB （P= 0.001, P = 0.005, P = 0.046, respectively, post-treatment vs. post-modeling）. Furthermore, the change in ICI from post-modeling in the D-BL33 group was significantly greater than those of the no intervention and other EA groups （all P 〈 0.01）. Significantly shortened vesical micturition time （VMT） and elevated maximum detrusor pressure （MDP） were also observed in the D-BL33 group （P = 0.017 and P = 0.024, respectively, post-treatment vs. post-modeling）. However, no statistically significant differences in the changes of VMT and MDP from post- modeling were observed between D-BL33 and the other EA groups. In conclusion, EA at BL33 with deep needling may inhibit acetic-acid-induced OAB more effectively.

关键词： overactive bladder electroacupuncture acupuncture points

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Treatment of nutcracker syndrome with spermatic vein ligation and iliac vein anastomosis:Case report of three cases

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Asian Pacific Journal of Tropical medicine 2012年第11期5卷 923-924页

作者： Xiao-Yong Gong Wei Zheng Hong Du Yi Lei Ya-Hui Xue Chao-Hui Xue Xian-Chao An Gang Zheng Department of Urology Surgery Second Affiliated HospitalShaanxi College of Traditional Chinese Medicine B Ultrasonic Rooms Second Affiliated HospitalShaanxi College of Traditional Chinese Medicine Department of Vascular Surgery Second Affiliated HospitalShaanxi College of Traditional Chinese Medicine

Three patients with nutcracker syndrome(NCS) were enrolled in the *** clinical symptoms mainly included proteinuria and serious *** Doppler ultrasound and computed tomography showed that the patients had constricted abdominal aortas,reduced superior mesenteric artery angles,and thinned left renal *** then underwent left spermatic vein ligation and iliac vein *** were checked tliree months after their operation,and results showed that their sperms were improved and their proteinuria disappeared. The color Doppler ultrasound showed new cycle *** clinical manifestations are complicated,and need combination diagnosis of symptoms and auxiliary examination to detennine surgical *** of spermatic vein and vein anastomosis can be used to treat NCS.

关键词： Diagnosis Nutcracker syndrome Spermatic vein Treatment Vein anastomosis

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Radix Scrophulariae Extracts Exert Effect on Hyperthyroidism via MST1/Hippo Signaling Pathway

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chinese Journal of Integrative medicine 2023年第11期29卷 998-1006页

作者： ZHANG Ning YE Tao LU Xu LI Zi-hui LI Ling Department of Pharmacy The First Affiliated Hospital of Guizhou University of Traditional Chinese MedicineGuiyang(50001)China Department of chinese medicine Rehabilitation The First Affiliated Hospital of Guizhou University of Traditional Chinese MedicineGuiyang(50001)China college of Pharmacy Guizhou University of Traditional Chinese MedicineGuiyang(550025)China college of Life and Health Dalian UniversityDalianLiaoning Province(116622)China

Objective:To explore the mechanism of Radix Scrophulariae(RS)extracts in the treatment of hyperthyroidism rats by regulating proliferation,apoptosis,and autophagy of thyroid cell through the mammalian sterile 20-like kinase 1(MST1)/Hippo ***:Twenty-four rats were randomly divided into 4 groups according to a random number table:control,model group,RS,and RS+Hippo inhibitor(XMU-MP-1)groups(n=6 per group).Rats were gavaged with levothyroxine sodium tablet suspension(LST,8μg/kg)for 21 days except for the control ***,rats in the RS group were gavaged with RS extracts at the dose of 1,350 mg/kg,and rats in the RS+XMU-MP-1 group were gavaged with 1,350 mg/kg RS extracts and 1 mg/kg *** 15 days of administration,thyroid gland was taken for gross observation,and histopathological changes were observed by hematoxylin-eosin *** structure of Golgi secretory vesicles in thyroid tissues was observed by transmission electron *** expression of thyrotropin receptor(TSH-R)was observed by ***-deoxynucleoitidyl transferase mediated nick end labeling assay was used to detect cell apoptosis in thyroid ***-time quantity primer chain reaction and Western blot were used to detect the expressions of MST1,p-large tumor suppressor gene 1(LATS1),p-Yes1 associated transcriptional regulator(YAP),proliferating cell nuclear antigen(PCNA),G_(1)/S-specific cyclin-D1(Cyclin D1),B-cell lymphoma-2(Bcl-2),Caspase-3,microtubule-associated proeins light chain 3Ⅱ/Ⅰ(LC3-Ⅱ/Ⅰ),and recombinant human autophagy related 5(ATG5).Thyroxine(T4)level was detected by enzyme-linked immunosorbent ***:The thyroid volume of rats in the model group was significantly increased compared to the normal control group(P<0.01),and pathological changes such as uneven size of follicular epithelial cells,disorderly arrangement,and irregular morphology *** secretion of small vesicles by Golgi apparatus was reduced,and the exp

关键词： Radix inhibited Scr

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