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Fanlian Huazhuo Formula alleviates high-fat diet-induced nonalcoholic fatty liver disease by modulating autophagy and lipid synthesis signaling pathway

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World Journal of Gastroenterology 2024年第30期30卷 3584-3608页

作者： Meng-Yuan Niu Geng-Ting Dong Yi Li Qing Luo Liu Cao Xi-Min Wang Qi-Wen Wang Yi-Ting Wang Zhe Zhang Xi-Wen Zhong Wei-Bo Dai Le-Yu Li Pharmacology Laboratory Zhongshan Hospital of Traditional Chinese Medicine Affiliated to Guangzhou University of Traditional Chinese MedicineZhongshan 528400Guangdong ProvinceChina Department of Endocrinology Zhongshan Hospital of Traditional Chinese Medicine Affiliated to Guangzhou University of Traditional Chinese MedicineZhongshan 528400Guangdong ProvinceChina

BACKGROUND Fanlian Huazhuo Formula(FLHZF)has the functions of invigorating spleen and resolving phlegm,clearing heat and purging *** has been identified to have therapeutic effects on type 2 diabetes mellitus(T2DM)in clinical ***-alcoholic fatty liver disease(NAFLD)is frequently diagnosed in patients with ***,the therapeutic potential of FLHZF on NAFLD and the underlying mechanisms need further *** To elucidate the effects of FLHZF on NAFLD and explore the underlying hepatoprotective mechanisms in vivo and in *** HepG2 cells were treated with free fatty acid for 24 hours to induce lipid accumulation cell ***,experiments were conducted with the different concentrations of freeze-dried powder of FLHZF for 24 hours.C57BL/6 mice were fed a high-fat diet for 8-week to establish a mouse model of NAFLD,and then treated with the different concentrations of FLHZF for 10 *** FLHZF had therapeutic potential against lipid accumulation and abnormal changes in biochemical indicators in vivo and in *** experiments verified that FLHZF alleviated abnormal lipid metabolism might by reducing oxidative stress,regulating the AMPKα/SREBP-1C signaling pathway,activating autophagy,and inhibiting hepatocyte *** FLHZF alleviates abnormal lipid metabolism in NAFLD models by regulating reactive oxygen species,autophagy,apoptosis,and lipid synthesis signaling pathways,indicating its potential for clinical application in NAFLD.

关键词： Fanlian Huazhuo Formula Nonalcoholic fatty liver disease Autophagy Apoptosis AMPKα/SREBP-1C signal pathway Oxidative stress

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Ultra-conservative noncoding RNA uc.243 confers chemo-resistance by facilitating the efflux of the chemotherapeutic drug in ovarian cancer

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BIOCELL 2024年第8期48卷 1265-1273页

作者： SHAN JIANG XIUFENG LIN YANFEI CHEN XINNING LI JIALI KANG Department of Gynecology and Obstetrics The First Affiliated Hospital of Jinan UniversityGuangzhou510180China Reproductive Medical Center Boai Hospital of Zhongshan Affiliated to Southern Medical UniversityZhongshan528400China Department of Gynecology and Obstetrics Boai Hospital of Zhongshan Affiliated to Southern Medical UniversityZhongshan528400China Department of Gynecology and Obstetrics Guangzhou First People’s HospitalGuangzhou Medical UniversityGuangzhou510180China

Background:Despite improvements in objective response rates to cisplatin-based combination chemotherapy,the majority of advanced ovarian cancer remains suboptimal,resulting in poor *** has been found that non-coding RNAs(ncRNAs)not only participate in the transmission of signals between various cells but also participate in tumor immunity and anti-tumor immune responses,thereby regulating tumor occurrence and ***,the function and detailed mechanism of ultraconserved RNA(ucRNA)in ovarian cancer chemoresistance is still ***:Western blotting assay,Quantitative real-time PCR analysis(qPCR),and Kaplan-Meier Plotter analysis were performed to analyze the expression and prognosis of uc.243 in ovarian *** assay and Annexin V assay were performed to analyze the function of uc.243 in cisplatin resistance in ovarian cancer *** pull-down and qPCR experiments were performed to explore the molecular mechanism of uc.243 enhancing cisplatin resistance in ovarian cancer ***:Herein,we found that uc.243 was remarkably upregulated and correlated with patient survival in chemoresistance ovarian cancer patients compared with chemo-sensitive ovarian *** experiment displayed that uc.243 induced cisplatin resistance on ovarian cancer cells by facilitating the efflux of cisplatin(CDDP);but inhibiting the expression of uc.243 significantly reverses this ***,uc.243 can inhibit the binding of RNA binding protein DGCR8 microprocessor complex subunit to pri-miR-155,thereby inhibiting the cleavage of pri-miR-155 and decrease in mature miR-155,subsequently upregulates the expression of ATP binding cassette subfamily B member(ABCB1,ABCC2).Conclusion:Our research findings indicate that uc.243 can induce chemotherapy resistance in ovarian cancer,suggesting that it may become a new prognostic biomarker for malignant ovarian cancer.

关键词： Ultra-conserved non-coding RNA uc.243 Drug efflux Drug transporters Chemoresistance Ovarian cancer

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Extracellular vesicles derived from mesenchymal stem cells mediate extracellular matrix remodeling in osteoarthritis through the transport of microRNA-29a

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World Journal of Stem Cells 2024年第2期16卷 191-206页

作者： Fan Yang Wan-Qi Xiong Chen-Zhi Li Ming-Jian Wu Xiu-Zhi Zhang Chun-Xiao Ran Zhen-Hao Li Yan Cui Bao-Yi Liu De-Wei Zhao Department of Orthopedics Affiliated Zhongshan Hospital of Dalian UniversityDalian 116001Liaoning ProvinceChina

BACKGROUND Knee osteoarthritis(KOA)is a common orthopedic condition with an uncertain etiology,possibly involving genetics and *** like changes in chondrocyte microenvironment,oxidative stress,inflammation,and immune responses affect KOA ***-stage treatment options primarily target symptom *** stem cells(MSCs)show promise for treatment,despite *** research highlights microRNAs(miRNAs)within MSC-released extracellular vesicles that can potentially promote cartilage regeneration and hinder KOA *** suggests exosomes(Exos)as a promising avenue for future *** these findings emphasize the need for effective KOA progression management,further safety and efficacy validation for Exos is *** To explore miR-29a’s role in KOA,we’ll create miR-29a-loaded vesicles,testing for early treatment in rat *** Extraction of bone marrow MSC-derived extracellular vesicles,preparation of engineered vesicles loaded with miR-29a using ultrasonication,and identification using quantitative reverse transcription polymerase chain reaction;after establi-shing a rat model of KOA,rats were randomly divided into three groups:Blank control group injected with saline,normal extracellular vesicle group injected with normal extracellular vesicle suspension,and engineered extrace-llular vesicle group injected with engineered extracellular vesicle *** three groups evaluation,histological detection,and immunohistochemical detection to compare and evaluate the progress of various forms of *** General behavioral observation results showed that the extracellular vesicle group and engineered extracellular vesicle group had better performance in all four indicators of pain,gait,joint mobility,and swelling compared to the blank control ***,the engineered extracellular vesicle group had better pain relief at 4 wk and better knee joint mobility at 8 wk compared to the nor

关键词： Exosomes Osteoarthritis Mesenchymal stem cells MicroRNA-29a Intra-articular injection

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Chinese expert consensus on the clinical application of drugcoated balloon(2^(nd) Edition)

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Journal of Geriatric Cardiology 2024年第2期21卷 135-152页

作者： The Expert Writing Committee of the Chinese Expert Consensus on Clinical Applications of Drug-Coated Balloon(2^(nd)Edition) Jun-Bo GE Yun-Dai CHEN 不详 zhongshan hospital Fudan University Chinese PLA General hospital

Percutaneous coronary interventions have progressed through the era of plain balloon dilation, bare-metal stent insertion to drug-eluting stent treatment, which has significantly reduced the acute occlusion and restenosis rates of target vessels and improved patient prognosis, making drug-eluting stents the mainstream interventional treatment for coronary artery disease. In recent years, drug-coated balloons(DCBs) have become a new treatment strategy for coronary artery disease, and the drugs used in the coating and the coating technology have progressed in the past years. Without permanent implant, a DCB delivers antiproliferative drugs rapidly and uniformly into the vessel wall via the excipient during a single balloon dilation. Many evidence suggests that DCB angioplasty is an effective measure for dealing with in-stent restenosis and de novo lesions in small coronary *** more clinical studies are published, new evidence is emerging for the use of DCB angioplasty in a wide range of coronary diseases, and the indications are expanding internationally. Based on the latest research from China and elsewhere, the Expert Writing Committee of the Chinese Expert Consensus on Clinical Applications of Drug-Coated Balloon has updated the previous DCB consensus after evidence-based discussions and meetings in terms of adequate preparation of in-stent restenosis lesions, expansion of the indications for coronary de novo lesions, and precise guidance of DCB treatment by intravascular imaging and functional evaluation.

关键词： balloon drugs dealing

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Calcineurin inhibitors-related posterior reversible encephalopathy syndrome in liver transplant recipients: Three case reports and review of literature

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World Journal of Hepatology 2024年第9期16卷 1297-1307页

作者： Yu Gong Department of Intensive Care Unit Fudan University Affiliated Zhongshan HospitalShanghai 200032China

BACKGROUND Posterior reversible encephalopathy syndrome(PRES),characterized by acute neurological deterioration and extensive white matter lesions on T2-fluid attenuated inversion recovery magnetic resonance imaging(MRI),is increasingly associated with calcineurin inhibitors(CNI)-related *** diagnosis is crucial,as early intervention,including the modification or discontinuation of CNI therapy,strict blood pressure management,corticosteroid treatment,and supportive care can significantly improve patient outcomes and *** growing clinical recognition of CNI-related PRES underscores the importance of identifying and managing this condition in patients presenting with acute neurological *** SUMMARY This report describes three cases of liver transplant recipients who developed *** first case involves a 60-year-old woman who experienced seizures,aphasia,and hemiplegia on postoperative day(POD)9,with MRI revealing ischemic foci followed by extensive white matter *** replacing tacrolimus,her symptoms improved,and no significant MRI abnormalities were observed after three years of *** second case concerns a 54-year-old woman with autoimmune hepatitis who developed headaches,seizures,and extensive white matter demyelination on MRI on *** the switch to rapamycin and the initiation of corticosteroids,her symptoms resolved,and she was discharged on *** third case details a 60-year-old woman with hepatocellular carcinoma who developed PRES,evidenced by brain MRI abnormal-ities on *** to rapamycin and corticosteroid therapy led to her full recovery,and she was discharged on *** cases highlight the critical importance of early diagnosis,CNI modification,and stringent management in improving outcomes for liver transplant recipients with CNI related *** Clinical manifestations,combined with characteristic MRI findings,are crucial in diagnosing PRES among organ transplan

关键词： Posterior reversible encephalopathy syndrome Calcineurin inhibitors Liver transplantation Prognosis Case report

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Efficacy and safety of targeted therapy plus immunotherapy combined with hepatic artery infusion chemotherapy (FOLFOX) for unresectable hepatocarcinoma

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World Journal of Gastroenterology 2024年第17期30卷 2321-2331页

作者： Zhi-Peng Lin Xiao-Long Hu Du Chen Da-Bei Huang Xu-Gong Zou Hai Zhong Sheng-Xiang Xu Yuan Chen Xiao-Qun Li Jian Zhang Department of Interventional Medicine Zhongshan People’s HospitalZhongshan 528400Guangdong ProvinceChina

BACKGROUND The advent of cutting-edge systemic therapies has driven advances in the treatment of hepatocellular carcinoma(HCC),and therapeutic strategies with multiple modes of delivery have been shown to be more efficacious than ***,the mechanisms underlying this innovative treatment modality have not been *** To evaluate the clinical efficacy of targeted therapy plus immunotherapy combined with hepatic arterial infusion chemotherapy(HAIC)of FOLFOX in patients with unresectable *** We enrolled 53 patients with unresectable HCC who received a combination of targeted therapy,immunotherapy,and HAIC of FOLFOX between December 2020 and June 2021 and assessed the efficacy and safety of the treatment *** The objective response rate was 60.4%(32/53),complete response was 24.5%(13/53),partial response was 35.9%(19/53),and stable disease was 39.6%(21/53).The median duration of response and median progression-free survival were 9.1 and 13.9 months,*** surgical conversion rate was 34.0%(18/53),and 1-year overall survival was 83.0%without critical complicating diseases or adverse events(AEs).CONCLUSION The regimen of HAIC of FOLFOX,targeted therapy,and immunotherapy was curative for patients with unresectable HCC,with no serious AEs and a high rate of surgical conversion.

关键词： Hepatocellular carcinoma Hepatic arterial infusion chemotherapy Targeted therapy Immunotherapy Adverse events

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Pharmacokinetic enhancement of oncolytic virus M1 by inhibiting JAK-STAT pathway

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Acta Pharmaceutica Sinica B 2024年第6期14卷 2554-2566页

作者： Jingyi Tan Jiayu Zhang Cheng Hu Gongwei Wang Qianyao Ren Chaoqun Wang Jia Dan Zexin Zeng Jun Hu Wenbo Zhu Jiankai Liang Jing Cai Ying Liu Guangmei Yan Yuan Lin Department of Pharmacology Zhongshan School of MedicineSun Yat-sen UniversityGuangzhou 510080China The Sixth affiliated hospital Sun Yat-sen UniversityGuangzhou 510655China Department of Urology the Third Affiliated Hospital of Sun Yat-sen UniversityGuangzhou 510630China Advanced Medical Technology Center the First Affiliated Hospital-Zhongshan School of MedicineSun Yat-sen UniversityGuangzhou 510080China Key Laboratory of Human Microbiome and Elderly Chronic Diseases Ministry of EducationGuangzhou 510655China Department of Infectious Diseases the Third Affiliated Hospital of Sun Yat-sen UniversityGuangzhou 510630China

Oncolytic viruses(OVs),a group of replication-competent viruses that can selectively infect and kill cancer cells while leaving healthy cells intact,are emerging as promising living anticancer *** traditional drugs composed of non-replicating compounds or biomolecules,the replicative nature of viruses confer unique pharmacokinetic properties that require further *** some pharmacokinetics studies of OVs,mechanistic insights into the connection between OV pharmacokinetics and antitumor efficacy remain ***,we characterized the pharmacokinetic profile of oncolytic virus M1(OVM)in immunocompetent mouse tumor models and identified the JAK-STAT pathway as a key modulator of OVM *** suppressing the JAK-STAT pathway,early OVM pharmacokinetics are ameliorated,leading to enhanced tumor-specific viral accumulation,increased AUC and Cmax,and improved antitumor *** than compromising antitumor immunity after JAK-STAT inhibition,the improved pharmacokinetics of OVM promotes T cell recruitment and activation in the tumor microenvironment,providing an optimal opportunity for the therapeutic outcome of immune checkpoint blockade,such as *** together,this study advances our understanding of the pharmacokinetic-pharmacodynamic relationship in OV therapy.

关键词： Pharmacokinetics Oncolytic virus JAK-STAT Anticancer

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Senegenin suppresses hepatocellular carcinoma by regulating OGlcNAcylation

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World Journal of Gastrointestinal Oncology 2024年第9期16卷 3994-4005页

作者： Xiang Zhang Li-Qiong Wang Zhi-Yong Liu Department of Traditional Chinese Medicine Qingpu Branch of Zhongshan Hospital Affiliated to Fudan UniversityShanghai 201700China Department of Hepatology Longhua Hospital Affiliated to Shanghai University of Traditional Chinese MedicineShanghai 200032China

BACKGROUND Based on current knowledge,hepatocellular carcinoma(HCC)is a condition with numerous etiologies and risk ***,the pathogenesis of HCC remains *** To investigate the roles of senegenin and O-GlcNAcylation in the growth and metastasis of *** The levels of O-linked N-acetylglucosamine transferase(OGT)and O-GlcNAcylation in HCC cells and tissues were detected using western blot *** effects of senegenin and O-GlcNAcylation on the proliferation of HCC cells were investigated in vitro using cell counting kit-8 and clonogenic *** potential effects of senegenin and O-GlcNAcylation on HCC metastasis were examined using the transwell migration assay.O-GlcNAcylation levels were altered via drug treatment and lentiviral infection,and western blot analysis was used to detect proteins involved in various *** Western blot analysis revealed that OGT and O-GlcNAcylation levels were significantly elevated in HCC tissues and cells.O-GlcNAcylation levels in HCC cells were significantly altered by drug treatment and lentiviral *** increase in the glycosylation level was linked to enhanced proliferation,invasiveness,clonogenicity,and metastatic potential of cancer cells.O-GlcNAcylation induced by senegenin was found to slow the proliferation and migration of HCC *** levels of proteins involved in nuclear factor-kappa B(NF-κB)and c-Jun N-terminal kinase(JNK)pathways,which are associated with endoplasmic reticulum stress,were *** Senegenin lowers O-GlcNAcylation levels,decreases OGT expression,and inhibits cancer cell growth and metastasis by regulating proteins involved in NF-κB and JNK pathways.

关键词： Senegenin O-GlcNAcylation Liver cancer Pathogenesis Metastasis

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Anti-vascular endothelial growth factor drugs combined with laser photocoagulation maintain retinal ganglion cell integrity in patients with diabetic macular edema: study protocol for a prospective, non-randomized, controlled clinical trial

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Neural Regeneration Research 2024年第4期19卷 923-928页

作者： Xiangjun Li Chunyan Li Hai Huang Dan Bai Jingyi Wang Anqi Chen Yu Gong Ying Leng Department of Ophthalmology Affiliated Hospital of Beihua University Department of Endocrinology Affiliated Hospital of Beihua University

The integrity of retinal ganglion cells is tightly associated with diabetic macular degeneration that leads to damage and death of retinal ganglion cells,affecting *** major clinical treatments for diabetic macular edema are anti-vascular endothelial growth factor drugs and laser ***,although the macular thickness can be normalized with each of these two therapies used alone,the vision does not improve in many *** might result from the incomplete recovery of retinal ganglion cell ***,a prospective,non-randomized,controlled clinical trial was designed to investigate the effect of anti-vascular endothelial growth factor drugs combined with laser photocoagulation on the integrity of retinal ganglion cells in patients with diabetic macular edema and its relationship with vision *** this trial,150 patients with diabetic macular edema will be equally divided into three groups according to therapeutic methods,followed by treatment with anti-vascular endothelial growth factor drugs,laser photocoagulation therapy,and their *** patients will be followed up for 12 *** primary outcome measure is retinal ganglion cell-inner plexiform layer thickness at 12 months after *** secondary outcome measures include retinal ganglion cell-inner plexiform layer thickness before and 1,3,6,and 9 months after treatment,retinal nerve fiber layer thickness,best-corrected visual acuity,macular area thickness,and choroidal thickness before and 1,3,6,9,and 12 months after *** measure is the incidence of adverse events at 1,3,6,9,and 12 months after *** study protocol hopes to validate the better efficacy and safety of the combined treatment in patients with diabetic macula compared with the other two monotherapies alone during the 12-month follow-up *** trial is designed to focus on clarifying the time-effect relationship between imaging measures related to the integrity of retinal

关键词： choroidal thickness diabetic macular edema laser photocoagulation retinal ganglion cell-inner plexiform layer thickness retinal ganglion cells retinal nerve fiber layer thickness thickness of the macular area vascular endothelial growth factor visual acuity

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Exosome-biomimetic nanocarriers for oral drug delivery

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Chinese Chemical Letters 2024年第9期35卷 65-71页

作者： Fengjie Liu Fansu Meng Zhenjiang Yang Huan Wang Yuehong Ren Yu Cai Xingwang Zhang Department of Pharmaceutics College of PharmacyJinan UniversityGuangzhou 511443China zhongshan hospital of Traditional Chinese Medicine affiliated to Guangzhou University of TCM Zhongshan 528400China Shenzhen Traditional Chinese Medicine hospital Shenzhen 518033China State Key Laboratory of Bioactive Molecules and Druggability Assessment Jinan UniversityGuangzhou 511443China

Exosomes as authigenous nanovesicles secreted by living cells represent a significant class of *** virtue of their unique roles in intercellular communication,exosomes can mediate intercellular information/cargoes exchange as messenger and facilitate drug delivery as smart *** medication is the most clinically relied upon route of administration and can achieve both topical and systemic therapeutic effects after *** and exosome-derived vectors have shown to be of high value in oral drug delivery,since they enable efficient oral delivery of therapeutic molecules by targeting intestinal epithelial *** recent years,exosome-biomimetic nanocarriers have emerged as an important catalyzer in innovating oral drug delivery *** this work,we roundly reviewed the biogenesis and functions of exosomes,their extraction and characterization methods,resources available for exosomes harvest,and design philosophy of exosome-derived vehicles,particularly highlighting the oral delivery application of exosome-biomimetic nanocarriers for diverse *** evidence suggests that exosome-biomimetic nanocarriers hold great promise for oral delivery of intractable drugs with potential biopharmaceutic issues.

关键词： Exosomes Oral delivery Biomimetic nanocarriers Targeting Bioavailability

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