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Ionic liquids as the effective technology for enhancing transdermal drug delivery: Design principles, roles, mechanisms, and future challenges

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Asian Journal of Pharmaceutical Sciences 2024年第2期19卷 38-51页

作者： Xuejun Chen Ziqing Li Chunrong Yang Degong Yang department of Pharmacy Shantou University Medical CollegeShantou 515041China Guangdong Provincial Key Laboratory of Infectious Diseases and Molecular immunopathology Shantou University Medical CollegeShantou 515041China

Ionic liquids (ILs) have been proven to be an effective technology for enhancing drug transdermal absorption. However, due to the unique structural components of ILs, the design of efficient ILs and elucidation of action mechanisms remain to be explored. In this review, basic design principles of ideal ILs for transdermal drug delivery system (TDDS) are discussed considering melting point, skin permeability, and toxicity, which depend on the molar ratios, types, functional groups of ions and inter-ionic interactions. Secondly, the contributions of ILs to the development of TDDS through different roles are described: as novel skin penetration enhancers for enhancing transdermal absorption of drugs;as novel solvents for improving the solubility of drugs in carriers;as novel active pharmaceutical ingredients (API-ILs) for regulating skin permeability, solubility, release, and pharmacokinetic behaviors of drugs;and as novel polymers for the development of smart medical materials. Moreover, diverse action mechanisms, mainly including the interactions among ILs, drugs, polymers, and skin components, are summarized. Finally, future challenges related to ILs are discussed, including underlying quantitative structure-activity relationships, complex interaction forces between anions, drugs, polymers and skin microenvironment, long-term stability, and in vivo safety issues. In summary, this article will promote the development of TDDS based on ILs.

关键词： Transdermal drug delivery system Ionic liquid Quantitative structure-activity relationship Intermolecular interaction

Transforming growth factor-beta 1 enhances discharge activity of cortical neurons

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Neural Regeneration Research 2025年第2期20卷 548-556页

作者： Zhihui Ren Tian Li Xueer Liu Zelin Zhang Xiaoxuan Chen Weiqiang Chen Kangsheng Li Jiangtao Sheng department of Microbiology and Immunology Guangdong Provincial Key Laboratory of Infectious Diseases and Molecular ImmunopathologyShantou University Medical CollegeShantouGuangdong ProvinceChina department of Neurosurgery First Affiliated Hospital of Shantou University Medical CollegeShantouGuangdong ProvinceChina

Transforming growth factor-beta 1(TGF-β1)has been extensively studied for its pleiotropic effects on central nervous system diseases.The neuroprotective or neurotoxic effects of TGF-β1 in specific brain areas may depend on the pathological process and cell types involved.Voltage-gated sodium channels(VGSCs)are essential ion channels for the generation of action potentials in neurons,and are involved in various neuroexcitation-related diseases.However,the effects of TGF-β1 on the functional properties of VGSCs and firing properties in cortical neurons remain unclear.In this study,we investigated the effects of TGF-β1 on VGSC function and firing properties in primary cortical neurons from mice.We found that TGF-β1 increased VGSC current density in a dose-and time-dependent manner,which was attributable to the upregulation of Nav1.3 expression.Increased VGSC current density and Nav1.3 expression were significantly abolished by preincubation with inhibitors of mitogen-activated protein kinase kinase(PD98059),p38 mitogen-activated protein kinase(SB203580),and Jun NH2-terminal kinase 1/2 inhibitor(SP600125).Interestingly,TGF-β1 significantly increased the firing threshold of action potentials but did not change their firing rate in cortical neurons.These findings suggest that TGF-β1 can increase Nav1.3 expression through activation of the ERK1/2-JNK-MAPK pathway,which leads to a decrease in the firing threshold of action potentials in cortical neurons under pathological conditions.Thus,this contributes to the occurrence and progression of neuroexcitatory-related diseases of the central nervous system.

关键词： central nervous system cortical neurons ERK firing properties JNK Nav1.3 p38 transforming growth factor-beta 1 traumatic brain injury voltage-gated sodium currents

RIOK1 synergizes with TRIP13 by regulating the E2F-Rb signaling pathway to promote the proliferation of esophageal cancer cells

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Genes & Diseases 2024年第3期11卷 55-58页

作者： Chengyu Li Deyuan Pan Wan Lin Danxia Deng Yingxin Zhou Hui Zhao Feng Pan Liyan Xu Enmin Li Lin Long The Key Laboratory of Molecular Biology for High Cancer Incidence Coastal Chaoshan Area Department of Biochemistry and Molecular BiologyShantou University Medical CollegeShantouGuangdong 515041China Guangdong Provincial Key Laboratory of Infectious Diseases and Molecular immunopathology Institute of Oncologic PathologyShantou University Medical CollegeShantouGuangdong 515041China Institute of Basic Medical Science Cancer Research CenterShantou University Medical CollegeShantouGuangdong 515041China Clinical Research Center Shantou Central HospitalShantouGuangdong 515041China

Esophageal cancer is one of the leading causes of cancer death in the world,with approximately half of the new cases occurring in China every year.^(1)Esophageal squamous cell carcinoma(ESCC)is the main subtype,accounting for more than 90%,and the five-year survival rate is less than 10%.Using large-scale genome analysis,many driver mutations and key pathways associated with ESCC have been identified.However,these genomic signatures have not improved the clinical management of EscC patients,or established effective targeted therapy.^(2)Esophageal cancer still lacks representative molecular markers.

关键词： cancer esophageal Esophageal

The value of the INFECTIONS scoring system in identifying bacterial infections among patients presenting at the emergency department of a middle-income country:A pilot study

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Chinese Journal of Traumatology 2024年第2期27卷 77-82页

作者： Dooshanveer C.Nuckchady department of Internal Medicine Victoria HospitalCandosMauritius

Purpose:To investigate which scoring system is the most accurate tool in predicting mortality among the infected patients who present to the emergency department in a middle-income country,and to validate a new scoring system to predict bacterial infections.Methods:This was a retrospective,single-center study among patients who were admitted via the emergency department of a public hospital.All patients who were started on antibiotics were included in the study,while patients aged0.85;however,these scoring systems failed to predict whether patients were truly infected.The INFECTIONS(short for impaired mental status,not conscious,fast heart rate,elevated creatinine,high temperature,on inotrope,low oxygen,high neutrophils and high sugar)model reached an AUROC of 0.88 to more accurately predict the infectious state of a patient.Conclusions:Middle-income countries should use the qSOFA or universal vital assessment score to identify the sickest patients in emergency department.The INFECTIONS score may help recognize patients with bacterial infections,but it should be further validated in multiple countries prior to widely use.

关键词： Prognosis Mortality Bacterial infection INFECTIONS scoring system Sequential organ failure assessment Prediction

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 fetus.The safety of psychotropic medications in the reproductive age female has not been well established.This review aimed to explore a summary of general agitation recommendations with an emphasis on ED management of agitation during pregnancy.METHODS: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 female.RESULTS:While nonpharmacological management is preferred,ED visits for agitation often require medical management.Medication should be selected based on the etiology of agitation and the clinical setting to avoid major adverse effects.Adverse effects are common in pregnant females.For mild to moderate agitation in pregnancy,diphenhydramine is an effective sedating agent with minimal adverse effects.In moderate to severe agitation,high-potency typical psychotropics are preferred due to their neutral effects on hemodynamics.Haloperidol has become the most frequently utilized psychotropic for agitation during pregnancy.Second generation psychotropics are often utilized as second-line therapy,including risperidone.Benzodiazepines and ketamine have demonstrated adverse fetal outcomes.CONCLUSION: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 utero.As 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

Quantitative assessment of the impact of a triage physician on the Accreditation Council for Graduate Medical Education resident milestones in the emergency department

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World Journal of Emergency Medicine 2024年第3期15卷 220-222页

作者： Julie Cueva Duncan Grossman Vishnu Muppala Arlene Chung Mahlaqa Butt Jefferson Drapkin Antonios Likourezos Errel Khordipour department of Emergency Medicine Maimonides Medical CenterNew York 11219USA

The “door-to-doctor” time for patients to be seen by a physician is an increasingly studied metric.Hospitals may shorten this time by implementing a triage physician (TP).The exact role of a TP may vary across departments.TPs put in preliminary orders for lab work,imaging,and treatment,and decide treatment location for further evaluation.As the prevalence of TPs grows,its effect on resident education in academic emergency departments (EDs) remains unclear.We implemented a TP in the spring of 2016 and assessed resident physicians before and after implementation.

关键词： physician doctor treatment

Phytochemical analysis, antioxidant, acetylcholinesterase, and α-amylase inhibitors from Hippeastrum hybridum extract

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Journal of Traditional Chinese Medicine 2024年第3期44卷 496-504页

作者： Naila Sher Mushtaq Ahmed Nadia Mushtaq department of Biotechnology University of Science and Technology department of Botany University of Science and Technology

OBJECTIVE:To investigate the effects of Hippeastrum hybridum（HH） as a free radical scavenger,and an inhibitor of the two enzymes i-e Alpha-amylase（α-amylase） and acetylcholinesterase（AChE）.METHODS:In this study,HH plant was preliminary analyzed for phytochemical screening and then tested for its antioxidant,anti-α-amylase,and anti-AChE efficiency via standard procedures.RESULTS:Phytochemical analysis shows the existence of different compounds;while Coumarins and quinones were absent.The total phenolic,flavonoid,and tannins content were found to be（78.52±0.69） mg GAE/g,（2.01±0.04） mg RUE/g,and（58.12±0.23） mg TAE/g of plant extract respectively.28.02%±0.02% alkaloid and 2.02%±0.05% saponins were present in the HH extract.The HH extract showed the anti-oxidant property with IC50（50%inhibition） of（151.01±0.13）(HH),（79.01±0.04）(Ascorbic acid) for ferric reducing,（91.48±0.13）(HH),（48.02±0.11）(Ascorbic acid) against Ammonium molybdenum,（156.02±0.31）(HH),（52.38±0.21）(Ascorbic acid) against DPPH,136.01±0.21（HH）,52.02±0.31（Ascorbic acid） against H2O2,and 154.12±0.03（HH）,（40.05±0.15）(Ascorbic acid)μg/mL against ABTS respectively.Statistical analysis indicated that HH caused a competitive type of inhibition of α-amylase(Vmaxremained constant and Km increases from 10.65 to84.37%) while Glucophage caused the un-competitive type of inhibition i-e both Km and Vmaxdecreased from40.49 to 69.15%and 38.86 to 69.61%respectively.The Ki,（inhibition constant）;KI,（dissociation constant）,Km,（Michaelis-Menten constant）,and IC50 were found to be62,364,68.1,and 38.08±0.22 for HH and 12,101.05,195,34.01±0.21 for Glucophage.Similarly,HH causes an anon-competitive type of inhibition of AChE i-e Km remains constant while Vmaxdecreases from 60.5%to74.1%.The calculated Ki,KI,Km,and IC50 were found to be 32,36.2,0.05,and 18.117±0.018.CONCLUSION:From the current results,it is concluded that HH extract contains bioactive compounds,and could be a good alternative to controlling oxidants,Alzheimer‘s and Type-Ⅱ diabetic diseases.

关键词： Hippeastrum hybridum acetylcholinesterase alpha-amylase antioxidant phytochemicals

Evaluation of hand infections in the emergency department using point-of-care ultrasound

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World Journal of Emergency Medicine 2024年第4期15卷 283-288页

作者： David Ahmad Haidar David Mintz Brandon M Wubben Omar Rizvi Srikar Adhikari department of Emergency Medicine Michigan MedicineAnn Arbor 48109-1382USA University of Arizona College of Medicine Tucson 85724USA department of Emergency Medicine University of IowaIowa City 52242-1009USA department of Surgery University of Arizona College of MedicineTucson 85724USA department of Emergency Medicine University of Arizona College of MedicineTucson 85724USA

BACKGROUND:We aimed to evaluate the utility of point-of-care ultrasound(POCUS)in the assessment of hand infections that present to the emergency department(ED)and its impact on medical decision making and patient management.METHODS:We conducted a retrospective review of patients who presented to two urban academic EDs with clinical presentations concerning for skin and soft tissue infections(SSTI)of the hand between December 2015 and December 2021.Two trained POCUS fellowship physicians reviewed an ED POCUS database for POCUS examinations of the hand.We then reviewed patients’electronic health records(EHR)for demographic characteristics,history,physical examination findings,ED course,additional imaging studies,consultations,impact of POCUS on patient care and final disposition.RESULTS:We included a total of 50 cases(28 male,22 female)in the final analysis.The most common presenting symptoms and exam findings were pain(100%),swelling(90%),and erythema(74%).The most common sonographic findings were edema(76%),soft tissue swelling(78%),and fluid surrounding the tendon(57%).POCUS was used in medical decision making 68%of the time(n=34),with the use of POCUS leading to changes in management 38%of the time(n=19).POCUS use led to early antibiotic use(11/19),early consultation(10/19),and led to the performance of a required procedure(8/19).The POCUS diagnosis was consistent with the discharge diagnosis of flexor tenosynovitis 8/12 times,abscess 12/16 times,and cellulitis 14/20 times.CONCLUSION:POCUS is beneficial for evaluating of hand infections that present to the ED and can be used as an important part of medical decision making to expedite patient care.

关键词： Ultrasound Point-of-care ultrasound Cellulitis Abscess Flexor tenosynovitis

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 vision.The major clinical treatments for diabetic macular edema are anti-vascular endothelial growth factor drugs and laser photocoagulation.However,although the macular thickness can be normalized with each of these two therapies used alone,the vision does not improve in many patients.This might result from the incomplete recovery of retinal ganglion cell injury.Therefore,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 recovery.In 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 combination.All patients will be followed up for 12 months.The primary outcome measure is retinal ganglion cell-inner plexiform layer thickness at 12 months after treatment.The 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 treatment.Safety measure is the incidence of adverse events at 1,3,6,9,and 12 months after treatment.The 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 period.The trial is designed to focus on clarifying the time-effect relationship between imaging measures related to the integrity of retinal ganglion cells and best-corrected visual acuity.

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