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Controlled release of dexamethasone from fibrin sealant for intratympanic administration in inner ear therapy

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Journal of Otology 2024年第1期19卷 55-58页

作者： Jing Zou Department of Otolaryngology-Head and Neck Surgery Changhai HospitalSecond Military Medical UniversityShanghai200433China faculty of Information Technology and Communication sciences Tampere UniversityTampereFinland

The aim of the present work was to show the sustainability of fibrin sealant in releasing dexamethasone and adjust the protocol for clinical application of the novel method in the treatment of Meniere’s disease (MD) and sudden sensorineural hearing loss (SSHL).Gelation occurred shortly after mixing dexamethasone-containing fibrinogen with thrombin.Dexamethasone was constantly released for at least 16 d at a stable level after 7d in protocol 1 (low-dose),while it was robustly released within 4 d and slowed afterward until 10 d in protocol 2(high-dose).There were significant differences among the time points in Protocol 2 (p<0.01,ANOVA),and the exponential model with the formula y=15.299*e~(-0.483*t) fits the association.The estimated concentration of dexamethasone released on 7 d in protocol 2 was slightly lower than that observed in protocol 1.The fibrin sealant is capable of constantly releasing dexamethasone with adjustable dynamics.Targeted and minimally invasive administration of the material can be achieved in the clinic by sequential injections of the fluids using a soft-tipped catheter.

关键词： Intratympanic drug delivery Controlled release Corticosteroids Meniere's disease Sudden sensorineural hearing loss

Dexamethasone does not affect endolymphatic hydrops(EH)in patients with Meniere's disease within 24 h,and intratympanic administration of gadolinium plus dexamethasone simplifies high-quality imaging of EH using a novel protocol of 7 min

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Journal of Otology 2022年第3期17卷 164-174页

作者： Jing Zou Zikai Zhao Hongbin Li Guoping Zhang Qing Zhang Jianping Lu Ilmari Pyykko Department of Otolaryngology-Head and Neck Surgery Changhai HospitalSecond Military Medical UniversityShanghaiChina Department of Radiology Changhai HospitalSecond Military Medical UniversityShanghaiChina faculty of Information Technology and Communication sciences Tampere UniversityTampereFinland Hearing and Balance Research Unit Field of OtolaryngologySchool of MedicineFaculty of Medicine and Health TechnologyTampere UniversityTampereFinland

Background:Intratympanic administration of gadolinium chelate allows for a better visualization of endolymphatic hydrops(EH)using MRI than intravenous injection and was recently further improved to facilitate high-quality imaging of EH in 7 min.The aim of the present study was to simplify the intratympanic administration protocol by mixing gadolinium chelate with therapeutic dexamethasone and to evaluate the effects of this mixture on the visualization of EH in MRI.Materials and methods:In an in vitro study,the potential impact of gadolinium-diethylenetriamine pentaacetic acid(Gd-DTPA)on the stability of dexamethasone was evaluated by analyzing dynamic changes in dexamethasone with high-performance liquid chromatography(HPLC)after mixing with GdDTPA.Ten patients with definite Meniere's disease(MD)were recruited to study the potential interference of dexamethasone on MRI visualization of EH,and 49 patients with MD were recruited to evaluate the effect of intratympanic injection of Gd-DTPA mixed with dexamethasone on MRI of EH using a 3T MR machine and a novel heavily T2-weighted 3-dimensional fluid-attenuated inversion recovery reconstructed using a magnitude plus zero-filled interpolation(hT2FLAIR-MZFI)sequence.Results:The retention times and peak area of dexamethasone in HPLC were not modified by the addition of Gd-DTPA.EH grading in the cochlea and vestibule was not influenced in any ear by intratympanic injection of dexamethasone.Excellent inner ear images were obtained from all patients,and EHs with various grades were displayed.There were significant correlations between diagnosis and cochlear EH(p<0.01,Spearman's Rho),between diagnosis and vestibular EH(p<0.01,Spearman's Rho),and between cochlear and vestibular EH(p<0.01,Spearman's Rho).The distribution of Gd-DTPA plus dexamethasone negatively correlated with the grade of vestibular EH.Injury of the endolymph-perilymph barrier was detected in one cochlea and three vestibules of 59 inner ears with MD.Conclusions:Intratympanic administration of Gd-DTPA plus d

关键词： Meniere's disease Endolymphatic hydrops MRI Contrast agent Therapeutics Topical administration

Dynamic monitoring of carcinoembryonic antigen,CA19-9 and inflammation-based indices in patients with advanced colorectal cancer undergoing chemotherapy

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World Journal of Clinical Cases 2022年第3期10卷 899-918页

作者： Nebojsa Manojlovic Goran Savic Bojan Nikolic Nemanja Rancic Clinic for Gastroenterology and Hepatology Military Medical AcademyFaculty of Medicine of the Military Medical AcademyUniversity of DefenceBelgrade 11000Serbia faculty of Medicine of the military Medical Academy University of DefenceBelgradeSerbiaMilitary Medical AcademyBelgrade 11000Serbia Institute for Radiology Military Medical AcademyBelgrade 11000Serbia Center for Clinical Pharmacology Institute for RadiologyMilitary Medical AcademyFaculty of Medicine of the Military Medical AcademyUniversity of DefenceBelgrade 11000Serbia

BACKGROUND The roles of carcinoembryonic antigen(CEA)and carbohydrate antigen(CA19-9)in monitoring the patient response to chemotherapy for metastatic colorectal cancer(mCRC)are not clearly defined,and inflammatory indices,including the neutrophil-to-lymphocyte ratio(NLR),lymphocyte-to-monocyte ratio(LMR),platelet-to-lymphocyte ratio(PLR)and systemic immune-inflammation index(SII),have been sparsely investigated for this purpose.AIM To aim of this study was to evaluate the relationship between the kinetics of CEA,CA19-9,NLR,LMR,PLR and SII in serum and patient response to chemotherapy estimated by computed tomography(CT)in patients with unresectable mCRC.METHODS Patients with mCRC treated with a 1st-line and 2nd-line chemotherapy underwent at least 3 whole-body spiral CT scans during response monitoring according to the Response Evaluation Criteria in Solid Tumour 1.1(RECIST 1.1),and simultaneous determination of CEA,CA19-9,neutrophil,lymphocyte,platelet and monocyte levels was performed.The kinetics of changes in the tumour markers and inflammatory indices were calculated as the percentage change from baseline or nadir,while receiver operating characteristic curves were drawn to select the thresholds to define patients with progressive or responsive disease with the highest sensitivity(Se)and specificity(Sp).The correlation of tumour marker kinetics with inflammatory index changes and RECIST response was determined by univariate and multivariate logistic regression analysis and the clinical utility index(CUI).RESULTS A total of 102 patients with mCRC treated with chemotherapy were included.Progressive disease(PD),defined as a CEA increase of 25.52%,resulted in an Se of 80.3%,an Sp of 84%,a good CUI negative[CUI(Ve-)]value of 0.75 and a good fraction correct(FC)value of 81.2;at a CEA cut-off of-60.85%with an Se of 100%and an Sp of 35.7%for PD,CT could be avoided in 25.49%of patients.The 21.49%CA19-9 cut-off for PD had an Se of 66.5%,an Sp of 87.4%,an acceptable CUI(Ve-)value of 0.65 and an acceptable FC value of

关键词： Tumour markers Carcinoembryonic antigen Carbohydrate antigen Inflammatory-based indices Chemotherapy response Metastatic colorectal cancer

A high‐voltage solid‐state Marx generator with adjustable pulse edges

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High Voltage 2023年第5期8卷 878-888页

作者： Junfeng Rao Rui Zhang Fukun Shi Longyu Zhuang Zhenyu Ji Jie Zhuang Chinese Academy of sciences Suzhou Institute of Biomedical Engineering and TechnologySuzhouChina University of Shanghai for Science and Technology School of Mechanical EngineeringShanghaiChina Air Force military Medical University Faculty of Biomedical EngineeringXi'anChina

Most reactors for non‐thermal plasma excitation are capacitive to pulse generators.The density and temperature of electrons in plasma are dominated by the discharging currents which are proportional to the pulse edges.However,adjusting the pulse edges is quite challenging since the switching speed and the inductance and capacitance in the discharging loops dominate them.This study proposes a drive circuit for solid‐state Marx generators with adjustable edges.The drive circuit controls the Miller plateau by adjusting the gate voltage amplitude to adjust both the rise time and fall time of pulses continuously and independently.The influence of the gate voltage on the Miller plateau and the rise time is studied.The feasibility is verified by both simulating and experimental results.An 8‐stage solid‐state Marx generator prototype was built,and 4.8‐kV pulses with a rise time in the range of 79 ns‐22.21μs were obtained over capacitive loads.Adjusting pulse edges can control the current amplitudes in dielectric barrier discharge loads.

关键词： pulse generator state

Time-dependent force of infection and effective reproduction ratio in an age-structure dengue transmission model in Bandung City,Indonesia

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Infectious Disease Modelling 2022年第3期7卷 430-447页

作者： Juni Wijayanti Puspita Muhammad Fakhruddin Nuning Nuraini Edy Soewono Doctoral Program of Mathematics Faculty of Mathematics and Natural SciencesInstitut Teknologi BandungJl.Ganesha10Bandung40132Jawa BaratIndonesia Department of Mathematics Faculty of Military Mathematics and Natural SciencesThe Republic of Indonesia Defense UniversityIPSC AreaSentulBogor16810Indonesia Department of Mathematics Faculty of Mathematics and Natural SciencesInstitut Teknologi BandungJl.Ganesha10Bandung40132Jawa BaratIndonesia

Dengue virus infection is a leading health problem in many endemic countries,including Indonesia,characterized by high morbidity and wide spread.It is known that the risk factors that influence the transmission intensity vary among different age groups,which can have implications for dengue control strategies.A time-dependent four−age structure model of dengue transmission was constructed in this study.A vaccination scenario as control strategy was also applied to one of the age groups.Daily incidence data of dengue cases from Santo Borromeus Hospital,Bandung,Indonesia,from 2014 to 2016 was used to estimate the infection rate.We used two indicators to identify the changes in dengue transmission intensity for this period in each age group:the annual force of infection(FoI)and the effective reproduction ratio based on a time-dependent transmission rate.The results showed that the yearly FoI of children(age 0–4 years)increased significantly from 2014 to 2015,at 10.08%.Overall,the highest FoI before and after vaccination occurred in youngsters(age 5–14 years),with a FoI of about 6%per year.In addition,based on the daily effective reproduction ratio,it was found that vaccination of youngsters could reduce the number of dengue cases in Bandung city faster than vaccination of children.

关键词： age structure model dengue transmission effective reproduction ratio force of infection

Effect of selective laser treatment on initiation of fatigue crack in the main part of an undercarriage drag strut

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Chinese Journal of Aeronautics 2019年第3期32卷 701-714页

作者： Anna BIE? Marek SZKODO Jerzy DOBERSKI Bart?omiej KARPI?SKI Technical sciences faculty University of Warmia and Mazury in Olsztyn Mechanical Engineering faculty Gdansk University of Technology military Aircraft Factory No.2 Joint Stock Company Szubińska 107 85-915 Bydgoszcz Poland

This paper presents the results of material characterization and a fatigue test conducted for a laser-re-melted drag strut used in an aircraft landing gear. The drag strut was re-melted with a CO_2 laser beam. Eight re-melted paths were made in the form of spiral lines along the axis of the drag strut. Next, the drag strut was subjected to variable loads on a testing machine simulating loads occurring when an aircraft lands. The fatigue test showed that the laser-treated drag strut was able to withstand 1700 simulated cycles of landing. This result was 70% better than that obtained for a drag strut with no laser treatment. In order to find the reason for the increase in the number of cycles of simulated landings, tests were carried out using transmission and scanning electron microscopes, a computer microtomograph, an X-ray diffractometer, and a nanoindenter,respectively. Results of the conducted research indicated that the reasons for the increased fatigue life of the laser-treated undercarriage drag strut were both an ultra-fine cellular martensitic microstructure and compressing residual stresses generated during the laser re-melting of the surface layer of the material.

关键词： Fatigue wear Laser re-melting Nanoindentation testing Residual stresses Steel alloy

Thermodynamic analysis for a third grade fluid through a vertical channel with internal heat generation

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Journal of Hydrodynamics 2015年第2期27卷 264-272页

作者： ADESANYA Samuel O. MAKINDE Oluwole D. Department of Mathematical sciences Redeemer's University faculty of military Science Stellenbosch University

This paper makes the thermodynamic analysis in forced convective flow of a third grade fluid through a vertical channel. Due to the reactive nature of the fluid, the effect of internal heat generation is considered and assumed to be a linear function of temperature. The coupled nonlinear dimensionless ordinary differential equations governing the fluid flow are solved by using the Adomian decomposition method(ADM). The effects of various physical parameters such as third grade material parameter, buoyancy parameter and heat generation parameter on the thermal structure of flow are presented and discussed.

关键词：热力学分析通道垂直 Adomian分解法流体流动方程热量液体强制对流

MEFV,IRF8,ADA,PEPD,and NBAS gene variants and elevated serum cytokines in a patient with unilateral sporadic Meniere's disease and vascular congestion over the endolymphatic sac

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Journal of Otology 2022年第3期17卷 175-181页

作者： Jing Zou Zikai Zhao Guoping Zhang Qing Zhang Ilmari Pyykko Department of Otolaryngology-Head and Neck Surgery Changhai HospitalSecond Military Medical UniversityShanghaiChina faculty of Information Technology and Communication sciences Tampere UniversityTampereFinland Hearing and Balance Research Unit Field of OtolaryngologySchool of MedicineFaculty of Medicine and Health TechnologyTampere UniversityTampereFinland

The etiology and underlying mechanism of Meniere's disease(MD)development are still unknown,although inflammation and autoimmunity have been implicated as underlying mechanisms.The human endolymphatic sac(ES)has been reported to have innate and adaptive immune capacity in local immune reactions.In vivo demonstration of inflammation of the ES in patients with MD is missing in the literature.We report the case of a 47-year-old female patient diagnosed with unilateral MD with genetic variants and cytokine markers indicating inflammation and vascular congestion of the ES.Endolymphatic hydrops in the right cochlea(grade 2)and vestibulum(grade 3)were detected using MRI.She carried heterozygous variants in MEFV(c.442G>C),IRF8(c.1157G>T),ADA(c.445C>T),PEPD(c.151G>A),NBAS(c.4049T>C),CSF2RB(c.2222C>T),HPS6(c.277G>T),IL2RB(c.1109C>T),IL12RB1(c.1384G>T),IL17RC(c.260_271del GCAAGAGC TGGG),LIG1(c.746G>A),RAG1(c.650C>A),and SLX4(c.1258G>C,c.5072A>G).In the serum,the levels of granulocyte colony-stimulating factor(G-CSF),macrophage inflammatory protein 1a,and IL7 were significantly elevated,and the level of IL2Ra was reduced.Intratympanic administration of dexamethasone temporarily alleviated her hearing loss.Her vertigo was significantly relieved but remained slight after ES administration of corticosteroids.

关键词： Meniere's disease Autoinflammation Autoimmune Immune organ Endolymphatic sac

20-Hydroxyecdysone Improves Neuronal Differentiation of Adult Hippocampal Neural Stem Cells in High Power Microwave Radiation-Exposed Rats

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Biomedical and Environmental sciences 2022年第6期35卷 504-517页

作者： LIU Jing Jing ZHANG Hong Yan CHEN Xin ZHANG Guang Bin LIN Jiang Kai FENG Hua CHU Wei Hua Department of Neurosurgery and Key Laboratory of Neurotrauma Southwest HospitalThird Military Medical University(Army Medical University)Chongqing 400038China Department of Occupational Health Faculty of Preventive MedicineThird Military Medical University(Army Medical University)Chongqing 400038China

Objective The hippocampus is thought to be a vulnerable target of microwave exposure.The aim of the present study was to investigate whether 20-hydroxyecdysone(20E)acted as a fate regulator of adult rat hippocampal neural stem cells(NSCs).Furthermore,we investigated if 20E attenuated high power microwave(HMP)radiation-induced learning and memory deficits.Methods Sixty male Sprague-Dawley rats were randomly divided into three groups:normal controls,radiation treated,and radiation+20E treated.Rats in the radiation and radiation+20E treatment groups were exposed to HPM radiation from a microwave emission system.The learning and memory abilities of the rats were assessed using the Morris water maze test.Primary adult rat hippocampal NSCs were isolated in vitro and cultured to evaluate their proliferation and differentiation.In addition,hematoxylin&eosin staining,western blotting,and immunofluorescence were used to detect changes in the rat brain and the proliferation and differentiation of the adult rat hippocampal NSCs after HPM radiation exposure.Results The results showed that 20E induced neuronal differentiation of adult hippocampal NSCs from HPM radiation-exposed rats via the Wnt3a/β-catenin signaling pathway in vitro.Furthermore,20E facilitated neurogenesis in the subgranular zone of the rat brain following HPM radiation exposure.Administration of 20E attenuated learning and memory deficits in HPM radiation-exposed rats and frizzled-related protein(FRZB)reduced the 20E-induced nuclear translocation ofβ-catenin,while FRZB treatment also reversed 20E-induced neuronal differentiation of NSCs in vitro.Conclusion These results suggested that 20E was a fate regulator of adult rat hippocampal NSCs,where it played a role in attenuating HPM radiation-induced learning and memory deficits.

关键词： High power microwave Hippocampus 20-hydroxyecdysone Learning and memory