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Prehospital transdermal glyceryl trinitrate for ultra- acute ischaemic stroke: data from the RIGHT- 2 randomised sham- controlled ambulance trial

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Stroke & Vascular Neurology 2024年第1期9卷 38-49,I0035-I0046页

作者： jason philip appleton Lisa J Woodhouse Craig S Anderson Sandeep Ankolekar Lesley Cala Mark Dixon Timothy J England Kailash Krishnan Grant Mair Keith W Muir John Potter Christopher I Price Marc Randall Thompson G Robinson Christine Roffe Else C Sandset Jeffrey L Saver Angela Shone Aloysius Niroshan Siriwardena Joanna M Wardlaw Nikola Sprigg philip M Bath Stroke University Hospitals Birmingham NHS Foundation TrustBirminghamUK Institute of Applied HealthResearch University of Birmingham College of Medical and Dental SciencesBirminghamUK Stroke Trials Unit Mental Health and Clinical NeurosciencesUniversity of NottinghamNottinghamUK Faculty of Medicine The George Institute for Global HealthSydneyNew South WalesAustralia The George Institute China at Peking University Health Science Center BeijingChina Neurology Royal Prince Alfred HospitalSydney Health PartnersSydneyNew South WalesAustralia Department of Neurology King's College Hospital NHS Foundation TrustLondonUK Faculty of Health and Medical Sciences University of Western AustraliaCrawleyWestern AustraliaAustralia East Midlands Ambulance Service NHS Trust NottinghamUK Stroke Queen's Medical CentreNottingham University Hospitals NHS TrustNottinghamUK Centre for Clinical Brain Sciences Dementia Research InstituteUniveristy of EdinburghEdinburghUK Institute of Neurology and Psychology University of GlasgowGlasgowUK Bob Champion Research and Education Building University of East AngliaNorwichUK Institute of Neuroscience Newcastle UniversityNewcastle upon TyneUK Department of Neurology Leeds Teaching Hospitals NHS TrustLeedsUK Department of Cardiovascular Sciences and NIHR Leicester Biomedical Research Centre University of LeicesterLeicesterUK Stroke Research in Stoke Institute for Science and Technology in MedicineKeele UniversityStoke-on TrentUK Department of Neurology Oslo University HospitalOsloNorway Research and Development Norwegian Air Ambulance FoundationOsloNorway Department of Neurology and Comprehensive Stroke Center David Geffen School of MedicineUCLALos AngelesCaliforniaUSA Research and Graduate Services University of NottinghamNottinghamUK Community and Health Research Unit University of LincolnLincolnUK

Background The effect of transdermal glyceryl trinitrate(GTN,a nitrovasodilator)on clinical outcome when administered before hospital admission in suspected stroke patients is unclear.Here,we assess the safety and efficacy of GTN in the prespecified subgroup of patients who had an ischaemic stroke within the Rapid Intervention with Glyceryl trinitrate in Hypertensive stroke Trial-2(RIGHT-2).Methods RIGHT-2 was an ambulance-based multicentre sham-controlled blinded-endpoint study with patients randomised within 4hours of onset.The primary outcome was a shift in scores on the modified Rankin scale(mRS)at day 90.Secondary outcomes included death;a global analysis(Wei-Lachin test)containing Barthel Index,EuroQol-5D,mRS,telephone interview for cognitive status-modified and Zung depression scale;and neuroimaging-determined‘brain frailty’markers.Data were reported as n(%),mean(SD),median[IQR],adjusted common OR(acOR),mean difference or Mann-Whitney difference(MWD)with 95%CI.Results 597 of 1149(52%)patients had a final diagnosis of ischaemic stroke;age 75(12)years,premorbid mRS>2107(18%),Glasgow Coma Scale 14(2)and time from onset to randomisation 67[45,108]min.Neuroimaging‘brain frailty’was common:median score 2[2,3](range 0–3).At day 90,GTN did not influence the primary outcome(acOR for increased disability 1.15,95%CI 0.85 to 1.54),death or global analysis(MWD 0.00,95%CI-0.10 to 0.09).In subgroup analyses,there were non-significant interactions suggesting GTN may be associated with more death and dependency in participants randomised within 1hour of symptom onset and in those with more severe stroke.Conclusions In patients who had an ischaemic stroke,ultra-acute administration of transdermal GTN in the ambulance did not improve clinical outcomes in a population with more clinical and radiological frailty than seen in previous in-hospital trials.WHAT IS ALREADY KNOWN ON THIS TOPIC⇒Transdermal glyceryl trinitrate(GTN)was associat-ed with less death and dependency in those with acute stroke treated within 6hours of stroke

关键词： Glasgow nitrate random

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Remote platelet function testing using P-selectin expression in patients with recent cerebral ischaemia on clopidogrel

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Stroke & Vascular Neurology 2021年第1期6卷 103-108页

作者： jason philip appleton Carla Richardson Natalia Dovlatova Jane May Nikola Sprigg Stan Heptinstall philip M Bath Stroke Trials Unit Division of Clinical NeuroscienceUniversity of NottinghamNottinghamUK Stroke Division Nottingham University Hospitals NHS TrustNottinghamUK Platelet Solutions Ltd Division of Clinical NeuroscienceQueen's Medical CentreUniversity of NottinghamNottinghamUK Platelet Research Group Division of Clinical NeuroscienceQueen's Medical CentreUniversity of NottinghamNottinghamUK

Background Antiplatelet agents reduce recurrence after cerebral ischaemia but are not effective in all patients,in part because of treatment resistance.The primary aim was to assess the proportion of patients who are insensitive to clopidogrel.The secondary aim was to assess the association between insensitivity to clopidogrel and recurrent cerebrovascular events.Methods Following written informed consent,independent patients with a recent non-cardioembolic ischaemic stroke or transient ischaemic attack,and taking clopidogrel,were enrolled.Platelet function was assessed with remote measurement of surface expression of P-selectin(CD62P)using commercial kits sensitive to aspirin or clopidogrel.Participants’general practitioners provided details on recurrent vascular events at least 90 days later.Data are mean(SD)and median[IQR].Resistance was defined as:aspirin median fluorescence(MF)>500 units,clopidogrel MF>860 units.Non-parametric descriptors and tests were used.Results 63 patients were recruited:mean age 64(13.7)years,women 47%.At baseline,59(95%)patients were taking clopidogrel alone with 3(5%)on combined clopidogrel and aspirin.Assessment of platelet surface P-selectin revealed:aspirin test 528[317,834],>50054.8%;clopidogrel test 429[303,656],>86011.3%.No participants on aspirin and clopidogrel showed aspirin resistance.Thirteen(20.6%)patients had a recurrent cerebrovascular event;those with an ischaemic stroke had a non-significantly higher baseline P-selectin using the clopidogrel test as compared with those with no recurrence:626[380,801]versus 406[265,609],p=0.08.Conclusions Remote measurement of platelet function assessed using the platelet surface expression of P-selectin is feasible.11%of patients taking clopidogrel showed resistance.No significant associations were noted between clopidogrel resistance and recurrent ischaemic events.

关键词： patients cerebral function

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Blood pressure management in acute stroke

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Stroke & Vascular Neurology 2016年第2期1卷 72-82页

作者： jason P appleton Nikola Sprigg philip M Bath Stroke Trials Unit Division of Clinical NeuroscienceUniversity of NottinghamNottinghamUK

Blood pressure(BP)is elevated in 75%or more of patients with acute stroke and is associated with poor outcomes.Whether to modulate BP in acute stroke has long been debated.With the loss of normal cerebral autoregulation,theoretical concerns are twofold:high BP can lead to cerebral oedema,haematoma expansion or haemorrhagic transformation;and low BP can lead to increased cerebral infarction or perihaematomal ischaemia.Published evidence from multiple large,high-quality,randomised trials is increasing our understanding of this challenging area,such that BP lowering is recommended in acute intracerebral haemorrhage and is safe in ischaemic stroke.Here we review the evidence for BP modulation in acute stroke,discuss the issues raised and look to on-going and future research to identify patient subgroups who are most likely to benefit.

关键词： Blood acute cerebral

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Clinical management of cerebral small vessel disease:a call for a holistic approach

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Chinese Medical Journal 2021年第2期134卷 127-142页

作者： Una Clancy jason P.appleton Carmen Arteaga Fergus N.Doubal philip M.Bath Joanna M.Wardlaw Centre for Clinical Brain Sciences and UK Dementia Research InstituteUniversity of EdinburghChancellor's Building49 Little France CrescentEdinburghEH164SPUK Stroke Trials Unit Division of Clinical NeuroscienceUniversity of NottinghamNottingham NG51PBUK Stroke University Hospitals Birmingham NHS Foundation TrustMindelsohn WayEdgbastonBirmingham B152GWUK Stroke Nottingham University Hospitals NHS TrustNottingham NG51PBUK.

Cerebral small vessel disease(SVD)is a common global brain disease that causes cognitive impairment,ischemic or hemorrhagic stroke,problems with mobility,and neuropsychiatric symptoms.The brain damage,seen as focal white and deep grey matter lesions on brain magnetic resonance imaging(MRI)or computed tomography(CT),typically accumulates"covertly"and may reach an advanced state before being detected incidentally on brain scanning or causing symptoms.Patients have typically presented to different clinical services or been recruited into research focused on one clinical manifestation,perhaps explaining a lack of awareness,until recently,of the full range and complexity of SVD.In this review,we discuss the varied clinical presentations,established and emerging risk factors,relationship to SVD features on MRI or CT,and the current state of knowledge on the effectiveness of a wide range of pharmacological and lifestyle interventions.The core message is that effective assessment and clinical management of patients with SVD,as well as future advances in diagnosis,care,and treatment,will require a more"joined-up"’approach.This approach should integrate clinical expertise in stroke neurology,cognitive,and physical dysfunctions.It requires more clinical trials in order to improve pharmacological interventions,lifestyle and dietary modifications.A deeper understanding of the pathophysiology of SVD is required to steer the identification of novel interventions.An essential prerequisite to accelerating clinical trials is to improve the consistency,and standardization of clinical,cognitive and neuroimaging endpoints.

关键词： Dementia Magnetic resonance imaging Mild cognitive impairment Risk factors Small vessel disease Stroke Symptoms Treatment

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Evidence of bisphosphonate-conjugated sitafloxacin eradication of established methicillin-resistant S.aureus infection with osseointegration in murine models of implant-associated osteomyelitis

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Bone Research 2023年第4期11卷 751-763页

作者： Youliang Ren jason Weeks Thomas Xue Joshua Rainbolt Karen L.de Mesy Bentley Ye Shu Yuting Liu Elysia Masters philip Cherian Charles E.McKenna Jeffrey Neighbors Frank H.Ebetino Edward M.Schwarz Shuting Sun Chao Xie Center for Musculoskeletal Research University of Rochester Medical CenterRochesterNY 14642USA Department of Orthopaedics University of Rochester Medical CenterRochesterNY 14642USA Department of Pathology and Center for Advanced Research Technologies University of Rochester Medical CenterRochesterNY 14642USA BioVinc LLCPasadenaCA 91107USA Department of Chemistry University of Southern CaliforniaLos AngelesCA 90089USA Department of Pharmacology Pennsylvania State UniversityHersheyPA 17033USA Department of Chemistry University of RochesterRoche

Eradication of MRSA osteomyelitis requires elimination of distinct biofilms.To overcome this,we developed bisphosphonateconjugated sitafloxacin(BCS,BV600072)and hydroxybisphosphonate-conjugate sitafloxacin(HBCS,BV63072),which achieve“target-and-release”drug delivery proximal to the bone infection and have prophylactic efficacy against MRSA static biofilm in vitro and in vivo.Here we evaluated their therapeutic efficacy in a murine 1-stage exchange femoral plate model with bioluminescent MRSA(USA300LAC::lux).Osteomyelitis was confirmed by CFU on the explants and longitudinal bioluminescent imaging(BLI)after debridement and implant exchange surgery on day 7,and mice were randomized into seven groups:1)Baseline(harvested at day7,no treatment);2)HPBP(bisphosphonate control for BCS)+vancomycin;3)HPHBP(hydroxybisphosphonate control for HBCS)+vancomycin;4)vancomycin;5)sitafloxacin;6)BCS+vancomycin;and 7)HBCS+vancomycin.BLI confirmed infection persisted in all groups except for mice treated with BCS or HBCS+vancomycin.Radiology revealed catastrophic femur fractures in all groups except mice treated with BCS or HBCS+vancomycin,which also displayed decreases in peri-implant bone loss,osteoclast numbers,and biofilm.To confirm this,we assessed the efficacy of vancomycin,sitafloxacin,and HBCS monotherapy in a transtibial implant model.The results showed complete lack of vancomycin efficacy while all mice treated with HBCS had evidence of infection control,and some had evidence of osseous integrated septic implants,suggestive of biofilm eradication.Taken together these studies demonstrate that HBCS adjuvant with standard of care debridement and vancomycin therapy has the potential to eradicate MRSA osteomyelitis.

关键词： implant infection overcome

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It is safe to use transdermal glyceryl trinitrate to lower blood pressure in patients with acute ischaemic stroke with carotid stenosis

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Stroke & Vascular Neurology 2019年第5期4卷 28-35页

作者： jason P appleton Lisa J Woodhouse Andrew Belcher Daniel Bereczki Eivind Berge Valeria Caso Hui Meng Chang Hanne K Christensen Ronan Collins John Gommans Ann C Laska George Ntaios Serefnur Ozturk Gillian M Sare Szabolcs Szatmari Yongjun Wang Joanna M Wardlaw Nikola Sprigg philip M Bath for the ENOS investigators Stroke Division of Clinical NeurosciencesUniversity of NottinghamNottinghamUK Stroke Nottingham University Hospitals NHS TrustNottinghamUK Department of Neurology Semmelweis UniversityBudapestHungary Department of Internal Medicine and Cardiology Oslo University HospitalOsloNorway Stroke Unit Santa Maria della Misericordia HospitalUniversity of PerugiaPerugiaItaly Department of Neurology Singapore General HospitalSingaporeSingapore Neurology Bispebjerg and Frederiksberg HospitalCopenhagenDenmark Tallaght Hospital Trinity College DublinDublinIreland Department of Medicine Hawke's Bay District Health BoardHastingsNew Zealand Department of Clinical Science Danderyd HospitalKarolinska InstituteStockholmSweden Department of Medicine University of ThessalyLarissaGreece Neurology Selcuk University Faculty of MedicineKonyaTurkey Neurology Nottingham University Hospitals NHS TrustNottinghamUK Department of Neurology Clinical County Emergency HospitalTargu MuresRomania Neurology Beijing Tiantan HospitalBeijingChina Centre for Clinical Brain Sciences EdinburghUK

Background There is concern that blood pressure(BP)lowering in acute stroke may compromise cerebral perfusion and worsen outcome in the presence of carotid stenosis.We assessed the effect of glyceryl trinitrate(GTN)in patients with carotid stenosis using data from the Efficacy of Nitric Oxide in Stroke(ENOS)Trial.Methods ENOS randomised 4011 patients with acute stroke and raised systolic BP(140-220 mm Hg)to transdermal GTN or no GTN within 48 hours of onset.Those on prestroke antihypertensives were also randomised to stop or continue their medication for 7 days.The primary outcome was the modified Rankin Scale(mRS)at day 90.Ipsilateral carotid stenosis was split:<30%;30-<50%;50-<70%;≥70%.Data are ORs with 95%CIs adjusted for baseline prognostic factors.results 2023(60.5%)ischaemic stroke participants had carotid imaging.As compared with<30%,≥70%ipsilateral stenosis was associated with an unfavourable shift in mRS(worse outcome)at 90 days(OR 1.88,95%CI 1.44 to 2.44,p<0.001).Those with≥70%stenosis who received GTN versus no GTN had a favourable shift in mRS(OR 0.56,95%CI 0.34 to 0.93,p=0.024).In those with 50-<70%stenosis,continuing versus stopping prestroke antihypertensives was associated with worse disability,mood,quality of life and cognition at 90 days.Clinical outcomes did not differ across bilateral stenosis groups.Conclusions Following ischaemic stroke,severe ipsilateral carotid stenosis is associated with worse functional outcome at 90 days.GTN appears safe in ipsilateral or bilateral carotid stenosis,and might improve outcome in severe ipsilateral carotid stenosis.

关键词： stenosis carotid hypertensive

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Intraspecific variation in precipitation responses of a widespread C_(4) grass depends on site water limitation

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Journal of Plant Ecology 2017年第2期10卷 310-321页

作者： Michael J.Aspinwall philip A.Fay Christine V.Hawkes David B.Lowry Albina Khasanova jason Bonnette Briana K.Whitaker Nicholas Johnson Thomas E.Juenger Hawkesbury Institute for the Environment Western Sydney UniversityHawkesbury CampusLocked Bag 1797PenrithNew South Wales 2751Australia USDA-ARS Grassland Soil and Water Research Laboratory 808 East Blackland RdTempleTX 76502USA Department of Integrative Biology University of Texas at Austin1 University StationAustinTX 78712USA Department of Plant Biology Michigan State University612 Wilson RoadEast LansingMI 48824USA

Aims Variation in precipitation strongly influences plant growth,species distributions and genetic diversity.intraspecific variation in pheno-typic plasticity,the ability of a genotype to alter its growth,morphol-ogy or physiology in response to the environment,could influence species responses to changing precipitation and climate change.Despite this,the patterns and mechanisms of intraspecific varia-tion in plasticity to variable precipitation,and the degree to which genotype responses to precipitation are influenced by variation in edaphic conditions,remain poorly understood.Thus,we determined whether genotypes of a widespread C_(4) grass(Panicum virgatum L.,switchgrass)varied in aboveground productivity in response to changes in precipitation,and if site edaphic conditions modified genotype aboveground productivity responses to precipitation.We also determined if genotype productivity responses to precipitation are related to plasticity in underlying growth and phenological traits.Methods Nine P.virgatum genotypes originating from an aridity gradient were grown under four treatments spanning the 10th to the 90th percentiles of annual precipitation at two sites in central Texas:one site with deep,fine-textured soils and another site with shallow,coarse-textured soils.We measured volumetric soil water content(VWC),aboveground net primary productivity(ANPP),tiller pro-duction(tiller number),average tiller mass,canopy height,leaf area index(LAi)and flowering time on all plants at both sites and examined genotype responses to changes in precipitation.Important Findings Across precipitation treatments,VWC was 39%lower and more variable at the site with shallow,coarse-textured soils compared to the site with deep,fine-textured soils.ANPP averaged across genotypes and precipita-tion treatments was also 103%higher at the site with deep,fine-textured soils relative to the site with shallow,coarse-textured soils,indicating substantial differences in site water limitation.Where site water limi-tation was higher,ANPP of m

关键词： climate change Panicum virgatum phenology phenotypic plasticity precipitation

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Experience with Thoracic Aortic Stent-Grafting at the Royal Brisbane and Women’s Hospital: Outcomes from the First Decade

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World Journal of Cardiovascular Surgery 2012年第3期2卷 29-39页

作者： Michel R Hoenig jason Jenkins Nicholas Boyne Allan Kruger philip J Walker Department of Vascular Surgery Royal Brisbane & Women’s Hospital Herston Queensland Australia University of Queensland School of Medicine Discipline of Surgery Centre for Clinical Research Herston Queensland Australia

Objectives: To describe thoracic endovascular aortic repair (TEVAR) outcomes at the Royal Brisbane and Women’s Hospital between 2001-2010. Design: Prospective cohort study. Results: We successfully treated 95 of 97 patients for a 98% procedural success rate. Of the treated patients, 68 (72%) were males and mean age was 61 ± 17 years. Average follow up was 3.6 ± 2.0 years. Pathologies treated were: dissection (n = 35), aneurysmal disease (n = 32), traumatic disease (n = 19), coarctation (n = 5) and miscellaneous (n = 4). There was one peri-procedural myocardial infarction. Renal complications occurred in 7 patients (3 with doubling creatinine and 4 requiring temporary renal replacement therapy). Stroke occurred in 2 patients and paresis in 2 patients (permanent in one). Six patients died during index hospitalization and 17 deaths occurred during follow-up, 2 of which were confirmed secondary to aortic pathology. Age (HR 1.08 per year, p < 0.01) and ASA class (HR 2.2 per class, p = 0.02) were independently associated with mortality. There were 25 re-interventions in 22 patients. Eighteen of these re-interventions in 16 patients were related to the management of complications of TEVAR of which 13 were for endoleaks;eight type I, four type II, one type III. Conclusion: TEVAR can be used to treat thoracic aortic pathology but questions remain regarding long-term durability.

关键词： Aorta Stents Surgery

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Biopsy-free in vivo virtual histology of skin using deep learning

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Light(Science & Applications) 2021年第12期10卷 2421-2442页

作者： Jingxi Li jason Garfinkel Xiaoran Zhang Di Wu Yijie Zhang Kevin de Haan Hongda Wang Tairan Liu Bijie Bai Yair Rivenson Gennady Rubinstein philip O.Scumpia Aydogan Ozcan Electrical and Computer Engineering Department University of CaliforniaLos AngelesCA 90095USA Bioengineering Department University of CaliforniaLos AngelesCA 90095USA California NanoSystems Institute(CNSI) University of CaliforniaLos AngelesCA 90095USA Dermatology and Laser Centre Studio CityCA 91604USA Computer Science Department University of CaliforniaLos AngelesCA 90095USA Division of Dermatology University of CaliforniaLos AngelesCA 90095USA Department of Dermatology Veterans Affairs Greater Los Angeles Healthcare SystemLos AngelesCA 90073USA Department of Surgery University of CaliforniaLos AngelesCA 90095USA

An invasive biopsy followed by histological staining is the benchmark for pathological diagnosis of skin tumors.The process is cumbersome and time-consuming,often leading to unnecessary biopsies and scars.Emerging noninvasive optical technologies such as reflectance confocal microscopy(RCM)can provide label-free,cellular-level resolution,in vivo images of skin without performing a biopsy.Although RCM is a useful diagnostic tool,it requires specialized training because the acquired images are grayscale,lack nuclear features,and are difficult to correlate with tissue pathology.Here,we present a deep learning-based framework that uses a convolutional neural network to rapidly transform in vivo RCM images of unstained skin into virtually-stained hematoxylin and eosin-like images with microscopic resolution,enabling visualization of the epidermis,dermal-epidermal junction,and superficial dermis layers.The network was trained under an adversarial learning scheme,which takes ex vivo RCM images of excised unstained/label-free tissue as inputs and uses the microscopic images of the same tissue labeled with acetic acid nuclear contrast staining as the ground truth.We show that this trained neural network can be used to rapidly perform virtual histology of in vivo,label-free RCM images of normal skin structure,basal cell carcinoma,and melanocytic nevi with pigmented melanocytes,demonstrating similar histological features to traditional histology from the same excised tissue.This application of deep learning-based virtual staining to noninvasive imaging technologies may permit more rapid diagnoses of malignant skin neoplasms and reduce invasive skin biopsies.

关键词： network vivo virtual

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Utilizing Water Treatment Residuals to Reduce Phosphorus Runoff from Biosolids

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Journal of Environmental Science and Engineering(A) 2013年第7期2卷 405-417页

作者： jason Peter de Koff philip Alderson Moore Jr Rodney Dale Williams Randy Young Peter JohnAmadeus Kleinman Department of Agricultural Sciences Tennessee State University Nashville TN 37209 USA Poultry Production and Product Safety Research Unit United States Department of Agriculture~Agricultural Research ServiceFayetteville AR 72701 USA Department of Civil Engineering University of Arkansas Fayetteville AR 72701 USA Arkansas Natural Resource Commission Little Rock AR 72201 USA Pasture Systems and Watershed Management Research Unit United States Department of Agriculture~ Agricultural ResearchService University Park PA 16802 USA

Approximately 40% of biosolids (sewage sludge) produced in the U. S. are incinerated or landfilled rather than land applied due to concern over non-point source P (phosphorus) runoff. The objective of this study was to determine the impact of chemical amendments on WEP (water-extractable phosphorus) in applied treatments and DRP (dissolved reactive phosphorus) in runoff from biosolids-amended soils. Rainfall simulations were conducted in 2006 on field plots fertilized with biosolids that had been treated with alum [(Al2SO4)3·14H2O], ferric chloride (FeCl3) or an alum-based WTR (water treatment residual) at a rate of 20% (wt/wt) to reduce DRP in runoff. In 2007, rainfall simulations were conducted using WTR/biosolid blends of 15% and 30% (wt/wt) that were allowed to incubate for three weeks prior to application. Cumulative DRP runoff load observed for the 20% WTR treatment was not significantly different from other chemical treatments and resulted in a 45% reduction in DRP runoff as compared to the untreated biosolids application. Cumulative DRP runoff load in 2007 for the 15% and 30% WTR treatments resulted in significantly lower DRP loads compared to untreated biosolids and led to DRP runoff load reductions of 78% and 85% (compared to the untreated biosolids application), respectively.

关键词：生物固体用水处理活性磷残余物径流应用程序降雨模拟化学处理

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