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Mitochondria-targeted nanoparticles overcome chemoresistance via downregulating BACH1/CD47 axis in ovarian carcinoma

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Chinese Chemical Letters 2024年第5期35卷 344-350页

作者： Ke Gong Jinghan Liao Jiangtao Lin Quan Wang Zhihua Wu Liting Wang Jiali Zhang Yi Dong Yourong Duan Jianhua Chen State Key Laboratory of Systems Medicine for Cancer Shanghai Cancer InstituteRenji HospitalSchool of MedicineShanghai Jiao Tong UniversityShanghai 200032China department of Ultrasound Xinhua HospitalSchool of MedicineShanghai Jiao Tong UniversityShanghai 200092China department of Oncology Shanghai General HospitalShanghai Jiao Tong University School of MedicineShanghai 200080China

The platinum-based chemotherapy is a routine strategy for the treatment of ovarian cancer,while it is prone to chemoresistance in clinical,which hinders the ***,it is urgently needed to elucidate the underlying mechanism of drug resistance and form the appropriate *** sequencing results showed that cisplatin(DDP)resistant ovarian cancer overexpressed BTB and CNC homology 1(BACH1),and up-regulated the“don’t eat me”signal *** identified that hemin,a BACH1 inhibitor,could effectively down-regulate BACH1 and simultaneously inhibit ***,hemin has a synergistic effect with *** designed a pH-responsive nanoparticle(H/D@FA-CaP-NPs)in which folic acid(FA)ensured targeting of ovarian cancer cells,while hemin inhibited BACH1 as well as down-regulated CD47,achieving the promotion of apoptosis of tumor cells and inducing phagocytosis of tumors by ***,hemin has a synergistic effect with DDP to promote apoptosis of tumor ***,hemin and DDP was encapsulated within hydrophobic 1,2-distearoyl-sn-glycero-3-phosphoethanolamine(DSPE)to form a tight core,and hydrophilic polyethylene glycol 2000(PEG2000)and calcium phosphate(CaP)formed the outside shell,and FA was modified on the surface of *** terms of function,(a)FA enhanced the active targeting of nanoparticles to tumors;(b)NPs targeted mitochondria to induce reactive oxygen species(ROS)production;(c)hemin encapsulated in nanoparticles could specifically target BACH1,thereby down regulating CD47;(d)hemin had a synergistic effect with DDP,thus augmenting the ***,mitochondria-targeted nanoparticles H/D@FA-CaP-NPs promoted tumor apoptosis and mobilized phagocytosis to treat tumor,providing a novel scheme for clinical treatment of cisplatin-resistant ovarian carcinoma.

关键词： Cisplatin-resistant Hemin BACH1 CD47 Phagocytosis ROS Synergistic effect

Molecular mechanism of Xuebijing in treating pyogenic liver abscess complicated with sepsis

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World Journal of emergency Medicine 2024年第1期15卷 35-40页

作者： Wei Zhou Maiying Fan Xiang Li Fang Yu En Zhou Xiaotong Han department of emergency Medicine the First Affi liated Hospital of Hunan Normal University/Hunan Provincial People’s HospitalChangsha 410005China department of Otolaryngology-head and Neck Surgery the First Affi liated Hospital of Hunan Normal University/Hunan Provincial People’s HospitalChangsha 410005China

BACKGROUND:Xuebijing(XBJ)can alleviate the inflammatory response,improve organ function,and shorten the intensive care unit(ICU)stay in patients with pyogenic liver abscess(PLA)complicated with sepsis,but the molecular mechanisms have not been *** study aimed to explore the molecular mechanism of XBJ in treating PLA complicated with sepsis using a network pharmacology ***:The active ingredients and targets of XBJ were retrieved from the ETCM *** targets related to PLA and sepsis were retrieved from the GeneCards,PharmGKB,DisGeNet,Online Mendelian Inheritance in Man(OMIM),Therapeutic Targets Database(TTD),and DrugBank *** targets of PLA complicated with sepsis were mapped to the targets of XBJ to identify potential treatment ***-protein interaction networks were analyzed using the STRING *** treatment targets were imported into the Metascape platform for Gene Ontology(GO)functional enrichment and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment *** docking was performed to validate the interactions between active ingredients and core ***:XBJ was found to have 54 potential treatment targets for PLA complicated with ***-1β(IL-1β),interleukin-6(IL-6),and tumor necrosis factor(TNF)were identifi ed as core *** enrichment analysis revealed important pathways,including the interleukin-17(IL-17)signaling pathway,the TNF signaling pathway,the nuclear factor-kappa B(NF-κB)signaling pathway,and the Toll-like receptor(TLR)signaling *** docking experiments indicated stable binding between XBJ active ingredients and core ***:XBJ may exert therapeutic eff ects on PLA complicated with sepsis by modulating signaling pathways,such as the IL-17,TNF,NF-κB,and TLR pathways,and targeting IL-1β,IL-6,and TNF.

关键词： Xuebijing injection Pyogenic liver abscess Sepsis

Lipid nanovehicles overcome barriers to systemic RNA delivery: Lipid components, fabrication methods, and rational design

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Acta Pharmaceutica Sinica B 2024年第2期14卷 579-601页

作者： Jing Yan Hao Zhang Guangfeng Li Jiacan Su Yan Wei Can Xu Institute of Translational Medicine Shanghai UniversityShanghai 200444China Institute of Medicine Shanghai UniversityShanghai 200444China department of Orthopedics Xinhua HospitalShanghai Jiao Tong University School of MedicineShanghai 200092China department of Orthopedics Shanghai Zhongye HospitalShanghai 200941China Organoid Research Center Shanghai UniversityShanghai 200444China department of Gastroenterology Changhai HospitalShanghai 200433China

Lipid nanovehicles are currently the most advanced vehicles used for RNA delivery,as demonstrated by the approval of patisiran for amyloidosis therapy in *** illuminate the unique superiority of lipid nanovehicles in RNA delivery,in this review,we first introduce various RNA therapeutics,describe systemic delivery barriers,and explain the lipid components and methods used for lipid nanovehicle ***,we emphasize crucial advances in lipid nanovehicle design for overcoming barriers to systemic RNA ***,the current status and challenges of lipid nanovehicle-based RNA therapeutics in clinical applications are also *** objective is to provide a comprehensive overview showing how to utilize lipid nanovehicles to overcome multiple barriers to systemic RNA delivery,inspiring the development of more high-performance RNA lipid nanovesicles in the future.

关键词： Lipid nanovehicles RNAtherapeutics Barriers to systemicRNA delivery Lipid components Fabricationmethods Lipid nanovehicledesign Extrahepatictissue targeting Organ tropism

Neuroprotective Effect and Mechanism of Tanreqing Injection on Ischemic Stroke:Insights from Network Pharmacology and in vivo Experiments

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Chinese Journal of Integrative Medicine 2024年第8期30卷 713-720页

作者： LI Zhong-hao PU Xiao-qi LI Sha-sha DONG Xiao-ke ZHANG Guo-qiang WANG Yu LIU Jin-min department of emergency China-Japan Friendship HospitalBeijing100029China department of Neurology Beijing University of Chinese Medicine Dongfang HospitalBeijing100078China department of Radiology China-Japan Friendship HospitalBeijing100029China Graduate School Beijing University of Chinese MedicineBeijing100029China

Objective To explore the neuroprotective effects and mechanism of Tanreqing Injection(TRQ)on treating ischemic stroke based on network pharmacology and in vivo experimental *** The chemical compounds of TRQ were retrieved based on published data,with targets retrieved from PubChem,Therapeutic Target Database and *** visualization and analysis were performed using Cytoscape,with protein-protein interaction networks derived from the STRING *** analysis was performed using Kyoto Encyclopedia of Genes Genomes pathway and Gene Ontology *** in vivo experiments,the middle cerebral artery occlusion(MCAO)model was *** volume was determined by 2,3,5-triphenyltetrazolium hydrochloride staining and protein expressions were analyzed by Western *** docking was performed to predict ligand-receptor *** We screened 81 chemical compounds in TRQ and retrieved their therapeutic *** the targets,116 were therapeutic targets for *** enrichment analysis showed that the apelin signaling pathway was a key pathway for ischemic ***,in in vivo experiment we found that administering with intraperitoneal injection of 2.5 mL/kg TRQ every 6 h could significantly reduce the infarct volume of MCAO rats(P<0.05).In addition,protein levels of the apelin receptor(APJ)/phosphatidylinositol 3-kinase(PI3K)/protein kinase B(AKT)pathway were increased by TRQ(P<0.05).In addition,41 chemical compounds in TRQ could bind to *** The neuroprotective effect of TRQ may be related to the APJ/PI3K/AKT signaling ***,further studies are needed to confirm the findings.

关键词： Tanreqing Injection Chinese medicine ischemic stroke middle cerebral artery occlusion quantitative estimate of drug-likeness

emergency department management of acute agitation in the reproductive age female and pregnancy

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World Journal of emergency Medicine 2024年第2期15卷 83-90页

作者： Ariella Gartenberg Kayla Levine Alexander Petrie department of emergency Medicine Jacobi Medical Center and Montefiore Medical CenterNY 10461USA department of Psychiatry and Behavioral Sciences Albert Einstein College of Medicine and Montefiore Medical CenterNY 10461USA department of emergency Medicine Jacobi Medical Center and North Central Bronx HospitalNY 10461USA

BACKGROUND:Agitation is a common presentation within emergent departments(EDs).Agitation during pregnancy should be treated as an obstetric emergency,as the distress may jeopardize both the patient and *** safety of psychotropic medications in the reproductive age female has not been well *** review aimed to explore a summary of general agitation recommendations with an emphasis on ED management of agitation during ***:A literature review was conducted to explore the pathophysiology of acute agitation and devise a preferred treatment plan for ED management of acute agitation in the reproductive age or pregnant ***:While nonpharmacological management is preferred,ED visits for agitation often require medical *** should be selected based on the etiology of agitation and the clinical setting to avoid major adverse *** effects are common in pregnant *** mild to moderate agitation in pregnancy,diphenhydramine is an effective sedating agent with minimal adverse *** moderate to severe agitation,high-potency typical psychotropics are preferred due to their neutral effects on *** has become the most frequently utilized psychotropic for agitation during *** generation psychotropics are often utilized as second-line therapy,including *** and ketamine have demonstrated adverse fetal ***:While randomized control studies cannot be ethically conducted on pregnant patients requiring sedation,animal models and epidemiologic studies have demonstrated the effects of psychotropic medication exposure in *** the fetal risk associated with multiple doses of psychotropic medications remains unknown,weighing the risks and benefits of each agent,while utilizing the lowest effective dose remains critical in the treatment of acute agitation within the EDs.

关键词： Agitation Pregnancy Haloperidol Ketamine Benzodiazepines

Phrenic nerve block: the key to managing acute biliary pain?

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World Journal of emergency Medicine 2024年第1期15卷 62-63页

作者： Michael Shalaby Joshua Luftig department of emergency Medicine and Critical Care Herbert Wertheim College of Medicine at Florida International UniversityMiami 33199USA Advanced emergency Ultrasound Mount Sinai Medical CenterMiami Beach 33140USA department of emergency Medicine Highland HospitalAlameda Health SystemOakland 94602USA

Over the past two decades,the USA has witnessed a steep rise in the incidence of acute cholecystitis(AC),[1]even among children,[2]with over 200,000 cases annually.[3]Patients with AC often present to the emergency department(ED)experiencing severe distress,with most describing their pain level as“intolerable.”[4]Furthermore,there is usually a considerable delay before surgery,with a median time from diagnosis of AC to surgery of 28.5 h,[5]and a substantial percentage of patients wait as long as 10 d.[6]Prolonged delays before surgery lead to increased opioid use,which is associated with extended hospital stays and higher rates of readmission after cholecystectomy.[7]Furthermore,opioids can lead to vomiting,respiratory depression,delirium,and ultimately addiction.[8]We propose a novel regional anesthesia technique for managing AC:right phrenic nerve *** method could offer improved pain control and a more favorable risk profile in selected patients when compared to current ED practices.

关键词： pain anesthesia diagnosis

Risk factors for postpartum posttraumatic stress disorder after emergency admission

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World Journal of emergency Medicine 2024年第2期15卷 121-125页

作者： Fengxia Du Jun Zha Yan Li Lichao Fang Shuyu Xia Youjia Yu department of Obstetrics Suzhou Xiangcheng People’s HospitalSuzhou 215131China department of Anesthesiology the Second Affiliated Hospital of Wannan Medical CollegeWuhu 241000China department of Anesthesiology Suzhou Xiangcheng People’s HospitalSuzhou 215131China department of emergency and Intensive Care Unit Suzhou Xiangcheng People’s HospitalSuzhou 215131China

BACKGROUND:Postpartum posttraumatic stress disorder(PTSD)can occur in women who give birth after emergency *** identification of risk factors for this condition is crucial for developing effective preventive *** retrospective study aimed to explore the incidence and risk factors for postpartum PTSD in women who give birth after emergency ***:Medical records of women who gave birth after emergency admission were collected between March 2021 and April *** patients’general conditions and perinatal clinical indicators were *** puerperae were divided into PTSD group and control group based on symptom occurrence at six weeks *** logistic regression analysis was performed to identify risk ***:A total of 276 puerperae were included,with a PTSD incidence of 20.3% at six weeks *** logistic regression analysis identified emergency cesarean section(odds ratio[OR]=2.102;95%confidence interval[CI]:1.114-3.966,P=0.022),admission to the emergency department after midnight(12:00 AM)(OR=2.245;95%CI:1.170-4.305,Pemergency cesarean section,admission to the emergency department after midnight,and cervical dilation were identified as independent risk factors for postpartum PTSD,while analgesic pump use was a protective *** findings provide insights for developing more effective preventive measures for women who give birth after emergency admission.

关键词： Risk factors Posttraumatic stress disorder emergency Delivery

Comparison of the pathological characteristics of uninjured skin tissues of diabetic rodents and diabetic patients

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中华内分泌外科杂志（中英文） 2024年第3期18卷 339-345页

作者： Du Juan Liu Ying Zhu Anfeng Song Dongming Qu Shiguang Yuan Zhixin emergency Critical and Translational Medicine LaboratoryJilin Province People’s HospitalChangchun 130021China emergency Medicine department of General hospital of Northern Theater Command Laboratory of Rescue Center of Severe Wound and Trauma PLAShenyang 110016China department of Pathology the Centre Hospital of ChangchunChangchun 130021China department of emergency Surgery Jilin Province People’s HospitalChangchun 130021China

Objective To study uninjured diabetic skin structure and compare the pathological characteristics of skin tissue from mouse and rat models of diabetes mellitus(DM)and humans with *** Establishing the DM C57BL/6J mice skin tissue models and db/db mice skin tissue models,as well as DM rat skin tissue *** tissues were collected from the animal models and DM *** biopsy specimens were stained with hematoxylin and eosin(HE)staining,Masson trichrome staining and periodic acid-Schiff(PAS)***(1)Skin from mice with streptozotocin(STZ)-induced DM was thinner and had less hair than skin from control *** epidermis had abnormal keratinization and dermal collagen and elastin fibers were dense and significantly atrophied.(2)Compared with the control group,skin tissue from db/db mice was thinner and had less *** was no aberrant keratinization in the epidermis,and dermal collagen and elastin fibres were loose.(3)Skin tissue from rats with STZ-induced DM was significantly thinner than control *** epidermis had mildly abnormal keratinization,and the dermis layer was atrophied and partly *** focal lipofuscin was deposited.(4)Whole skin tissue from patients with diabetes was significantly thinner than skin from subjects without *** epidermis had mild hyper keratinization,and the dermal elastin fibers were atrophied,loose,irregular,and showed focal mucoid *** Uninjured DM skin tissues were thinner and more irregular than normal *** changes in rat DM skin were most like those seen in the skin of patients with DM.

关键词： Diabetes mellitus Skin Human Mouse Rat

mTORC2:The“Ace in the Hole”for a Broader Control of Epileptic Seizures?

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Neuroscience Bulletin 2024年第5期40卷 677-679页

作者： Shuo Zhang Xiongfeng Guo Wei Huang Cenglin Xu department of Pharmacy The First Affiliated Hospital of Zhejiang Chinese Medical University(Zhejiang Provincial Hospital of Chinese Medicine)Hangzhou310006China The Second Affiliated hospital of Zhejiang Chinese Medical University(Zhejiang xinhua hospital) Key Laboratory of Neuropharmacology and Translational Medicine of Zhejiang ProvinceSchool of Pharmaceutical SciencesZhejiang Chinese Medical UniversityHangzhou310053China

Over 70 million people worldwide suffer from epilepsy-one of the most prevalent chronic neurological disorders[1].Despite the availability of over thirty anti-seizure drugs(ASDs)that mainly act on voltage-gated ion channels or inhibitory GABAergic receptors,the effectiveness of these drugs in achieving seizure freedom remains unsatisfactory due to pharmacoresistance and the inevitable occurrence of side-effects.

关键词： drugs spite epilepsy