Acute kidney injury:microRNAs and new therapeutic opportunities for natural products

In the past few decades,acute kidney injury(AKI),characterized by an abrupt decrease in kidney filtration rate,has become a public health issue affecting between 1%and 15%of the population,which causes high morbidity and death.There is mounting evidence that miRNAs are noncoding single-stranded RNAs with a short length of about 20 nucleotides and have been highly conserved through evolution.Through targeting mRNAs,miRNA may mediate intercellular communication during AKI’s physiological and pathological processes.It is interesting to note that natural products can improve AKI by regulating miRNA expression,which might represent a potentially innovative therapeutic strategy.This review aims at providing an overview of the new data obtained on miRNAs in the treatment and diagnosis of AKI,summarizing studies on natural products improving AKI through regulating miRNAs’expression;in the same time,it will shed new light on AKI risk biomarkers and therapeutic intervention as well.We summarized the roles of miRNAs involved in AKI progression or protection against renal injury in 32 articles;we found five natural products can improve AKI by regulating miRNA expression,which will potentially provide a reference for clinical treatment.Natural products might represent a potentially innovative therapeutic strategy;in the same time,miRNAs will shed new light on AKI risk biomarkers and therapeutic intervention.

Empirical Research on Brand Spillover Effect of Agricultural Product under the Background of Product Injury Crisis

By referring to attribution theory,influence factor and internal mechanism of crisis brand generating two kinds of spillover effects are explored. In this paper,the influence mechanism on spillover effect is explored from the angles of network and industry information. Results show that high online review dispersion is easy to cause that consumer attributes the responsibility to the outside of the enterprise,while low online review dispersion is easy to cause that consumer attributes the responsibility to the inside of the enterprise; high industry base rate information is easy to cause that consumer attributes the responsibility to the outside of the enterprise,while low industry base rate information is easy to cause that consumer attributes the responsibility to the inside of the enterprise. When consumer attributes the responsibility to the outside of the enterprise,infectious network spillover is easy to occur. When consumer attributes the responsibility to the inside of the enterprise,contrast network spillover is easy to occur. Consumer's existing brand knowledge regulates the influence of online review dispersion on responsibility attribution and the influence of industry base rate information on responsibility attribution. Research result could provide effective theoretic reference and management suggestion for crisis enterprise and even whole industry responding to product injury crisis.

Fibrinogen degradation product levels on arrival for trauma patients requiring a transfusion even without head injury

BACKGROUND: There have been few reports on the clinical significance of the fibrinogen degradation product(FDP) level in trauma patients with and without head injury. We retrospectively analyzed trauma patients with or without head injury to investigate the clinical signifi cance of the FDP level.METHODS: From April 2013 to June 2015, a medical chart review was retrospectively performed for all patients with trauma. The exclusion criteria included patients who did not receive a transfusion. The patients were divided into two groups: a FDP>100 group, which included patients who had an FDP level on arrival over 100 ng/m L, and a FDP≤100 group.RESULTS: The ratio of open fractures and the prothrombin ratio in the FDP>100 group were significantly smaller than those observed in the FDP≤100 group. The average age, ratio of blunt injury, Injury Severity Score(ISS), volume of transfusion and mortality ratio in the FDP>100 group were signifi cantly greater than those in the FDP≤100 group. There was a weakly positive correlation between the FDP level and ISS(R=0.35, P=0.002), but it was not associated with the transfusion volume. The results of an analysis excluding patients with head injury showed a similar tendency.CONCLUSION: The FDP levels may be a useful biochemical parameter for the initial evaluation of the severity of trauma and mortality even in blunt traumatized patients without head injury or with stable vital signs.

Injury of cortical neurons is caused by the advanced glycation end products-mediated pathway

Advanced glycation end products lead to cell apoptosis, and cause cell death by increasing endoplasmic reticulum stress. Advanced glycation end products alone may also directly cause damage to tissues and cells, but the precise mechanism remains unknown. This study used primary cultures of rat cerebral cortex neurons, and treated cells with different concentrations of glycation end products （50, 100, 200, 400 mg/L）, and with an antibody for the receptor of advanced glycation end products before and after treatment with advanced glycation end products. The results showed that with increasing concentrations of glycation end products, free radical content increased in neurons, and the number of apoptotic cells increased in a dose-dependent manner. Before and after treatment of advanced glycation end products, the addition of the antibody against advanced glycation end-products markedly reduced hydroxyl free radicals, malondialdehyde levels, and inhibited cell apoptosis. This result indicated that the antibody for receptor of advanced glycation end-products in neurons from the rat cerebral cortex can reduce glycation end product-induced oxidative stress damage by suppressing glycation end product receptors. Overall, our study confirms that the advanced glycation end products-advanced glycation end products receptor pathway may be the main signaling pathway leading to neuronal damage.

Real-World Safety and Performance of Saline Nasal Spray Products for Nasal Cleansing and Reducing Obstruction of the Nasal Cavity

Background and Objectives: Three post-marketing clinical follow-up studies were performed in Europe to confirm the safety and performance of four nonprescription, nasal cleansing medical devices: Otrivin Sea Water (OSW) pressurized spray, OSW with aloe vera (OSWAV), Otrisal 0.74% NaCl Metered-Dose Spray (MDS), and Prorhinel spray. Material and Methods: Observational, single-arm, retrospective studies consisting of a single online questionnaire were performed between July 2021 and December 2021. Eligible participants were adults who used the device or supervised use of the device in a participant under 18 years of age within 6 months of completing the questionnaire. Demographics, safety, and device performance were assessed. Results: Based on questionnaires submitted on OSW (n = 556), OSWAV (n = 555), Otrisal MDS (n = 555), and Prorhinel (n = 555), proportions of users who reported safety events were 1.8% for OSW, 2.3% for OSWAV, 1.4% for Otrisal MDS, and 2.0% for Prorhinel. Proportions of users who indicated they were satisfied or very satisfied with device performance ranged from 72.0% - 89.0% across all devices. Device performance for all products was also supported for additional preventative and symptomatic uses through exploratory analyses. Conclusions and Significance: These data confirm device safety and performance of OSW, OSWAV, Otrisal MDS, and Prorhinel for their intended uses.

The Role of Medical Literature, Clinical Trials and Experimental Research in Drug Product-Injury Litigation: A Primer with Two Examples

When any type of product has been ordered to be removed from the marketplace by a governmental regulatory body, that action is a powerful indicator that the product has been determined to be unsafe for further use, thereby branding the product as defective and opening up the possibility of product liability litigation. When the product is a drug or medical device, it is especially serious since the possibility of personal injury (acute and/or chronic) or death may occur. Needless to say, in these situations, product injury litigation will almost surely follow. We review the definition and requisite claims needed to establish drug product liability, and the role that the medical literature, clinical trial data, and even experimental research data can play in product (drug)-injury litigation. We show how each of these resources played a significant role in two well-known cases: Fen-Phen and thimerosal. The ultimate goal of such knowledge is to make better informed decisions about drug safety.

Intra-coronary administration of soluble receptor for advanced glycation end-products attenuates cardiac remodeling with decreased myocardial transforming growth factor-pl expression and fibrosis in minipigs with ischemia-reperfusion injury

Background The cardioprotective effects of soluble receptor for advanced glycation end-products （sRAGE） have not been evaluated in large animals and the underlying mechanisms are not fully understood. This study aimed to evaluate the effects of intra-coronary administration of sRAGE on left ventricular function and myocardial remodeling in a porcine model of ischemia-reperfusion （I/R） injury. Methods Ten male minipigs with I/R injury were randomly allocated to receive intra-coronary administration of sRAGE （sRAGE group, n=5） or saline （control group, n=5）. Echocardiography was performed before and 2 months after infarction. Myocardial expression of transforming growth factor （TGF）-β1 was determined by immunohistochemistry and fibrosis was evaluated by Sirius red staining. Results As compared with the baseline values in the control animals, left ventricular end-diastolic volume （from （19.5±5.1） to （32.3±5.6） ml, P 〈0.05） and end-systolic volume （from （8.3±3.2） to （15.2±4.1） ml, P 〈0.05） were significantly increased, whereas ejection fraction was decreased （from （61.6±13.3）% to （50.2±11.9）%, P 〈0.05）. No obvious change in these parameters was observed in the sRAGE group. Myocardial expression of TGF-β1 was significantly elevated in the infarct and non-infarct regions in the control group, as compared with sRAGE group （both P 〈0.01）. Fibrotic lesions were consistently more prominent in the infarct region of the myocardium in the control animals （P〈0.05）. Conclusion Intra-coronary sRAGE administration attenuates RAGE-mediated myocardial fibrosis and I/R injury through a TGF-β1-dependent mechanism, suggesting a clinical potential in treating RAGE/ligand-associated cardiovascular diseases.

Baicalin attenuates blood-spinal cord barrier disruption and apoptosis through PI3K/Akt signaling pathway after spinal cord injury

Baicalin is a natural active ingredient isolated from Scutellariae Radix that can cross the blood-brain barrier and exhibits neuroprotective effects on multiple central nervous system diseases.However,the mechanism behind the neuroprotective effects remains unclear.In this study,rat models of spinal cord injury were established using a modified Allen's impact method and then treated with intraperitoneal injection of Baicalin.The results revealed that Baicalin greatly increased the Basso,Beattie,Bresnahan Locomotor Rating Scale score,reduced blood-spinal cord barrier permeability,decreased the expression of Bax,Caspase-3,and nuclear factorκB,increased the expression of Bcl-2,and reduced neuronal apoptosis and pathological spinal cord injury.SH-SY5 Y cell models of excitotoxicity were established by application of 10 m M glutamate for 12 hours and then treated with 40μM Baicalin for 48 hours to investigate the mechanism of action of Baicalin.The results showed that Baicalin reversed tight junction protein expression tendencies(occludin and ZO-1)and apoptosis-related protein expression(Bax,Bcl-2,Caspase-3,and nuclear factor-κB),and also led to up-regulation of PI3 K and Akt phosphorylation.These effects on Bax,Bcl-2,and Caspase-3 were blocked by pretreatment with the PI3 K inhibitor LY294002.These findings suggest that Baicalin can inhibit bloodspinal cord barrier permeability after spinal cord injury and reduce neuronal apoptosis,possibly by activating the PI3 K/Akt signaling pathway.This study was approved by Animal Ethics Committee of Xi'an Jiaotong University on March 6,2014.

Neuroprotection mediated by natural products and their chemical derivatives

Neuronal injuries can lead to various diseases such as neurodegenerative diseases,stroke,trauma,ischemia and,more specifically,glaucoma and optic neuritis.The cellular mechanisms that regulate neuronal death include calcium influx and calcium overload,excitatory amino acid release,oxidative stress,inflammation and microglial activation.Much attention has been paid to the effective prevention and treatment of neuroprotective drugs by natural products.This review summarizes the neuroprotective aspects of natural products,extracted from Panax ginseng,Camellia sinensis,soy and some other plants,and some of their chemical derivatives.Their antioxidative and anti-inflammatory action and their inhibition of apoptosis and microglial activation are assessed.This will provide new directions for the development of novel drugs and strategies to treat neurodegenerative diseases.

Strengthening Injury Surveillance System in Iran

Objective： To strengthen the current Injury Surveillance System （IS System） in order to better monitor injury conditions, improve protection ways and promote safety. Methods： At first we carried out a study to evaluate the frameworks of IS System in the developed countries. Then all the available documents from World Health Organization, Eastern Mediterranean Regional Organization, as well as Minister of Health and Medical Education concerning Iran were reviewed. Later a national stakeholder＇s consultation was held to collect opinions and views. A national workshop was also intended for provincial representatives from 41 universities to identify the barriers and limitations of the existing program and further to strengthen injury surveillance. Results： The evaluation of the current IS System revealed many problems, mainly presented as lack of accurate pre- and post-hospital death registry, need of precise injury data registry in outpatient medical centers, incomplete injury data registry in hospitals and lack of accuracy in definition of variables in injury registry. The five main characteristics of current IS System including flexibility, acceptability, simplicity, usefulness and timeliness were evaluated as moderate by experts.Conclusions： Major revisions must be considered in the current IS System in Iran. The following elements should be added to the questionnaire： identifier, manner of arrival to the hospital, situation of the injured patient, consumption of alcohol and opioids, other involved participants in the accident, intention, severity and site of injury, side effects of surgery and medication, as well as one month follow-up results. Data should be collected from 10% of all hospitals in Iran and analyzed every 3 months. Simultaneously data should be online to be retrieved by researches.

Using modified Delphi method to propose and validate the components of a child injury surveillance system for Iran

Purpose:Child injuries are a public health concern globally.Injury surveillance systems(ISSs)have beneficial impact on child injury prevention.There is a need for evidence-based consensus on frameworks to establish child ISSs.This research aims to investigate the key components of a child ISS for Iran and to propose a framework for implementation.Methods:Data were gathered through interview with experts using unstructured questions from January 2017 to December 2018 to identify child ISS functional components.Qualitative data were analyzed using content analysis method.Then,modified Delphi method was used to validate the functional components.Based on the outcomes of the content analysis,a questionnaire with closed questions was developed and presented to a group of experts.Consensus was achieved in two rounds.Results:In round I,117 items reached consensus.In round II,5 items reached consensus and were incorporated into final framework.Consensus was reached for 122 items comprising the final framework and representing 7 key components:goals of the system,data sources,data set,coalition of stakeholders,data collection,data analysis and data distribution.Each component consisted of several subcomponents and respective elements.Conclusion:This agreed framework will assist in standardizing data collection,analysis and distribution,which help to detect child injury problems and provide evidence for preventive measures.

Modelling Visible Foliar Injury Effects on Canopy Photosynthesis and Potential Crop Yield Losses Resulting from Fluoride Exposure

Crop production models are highly developed to account for different nitrogen, light, temperature and water availability conditions and, in some species, disease or air pollutant effects. There is very limited knowledge on responses of many tropical crops, such as oil palm (Elaeis guineensis), to air pollutants although predictions of these effects are essential for industrial planning in several countries. In the absence of limitations due to water supply, the effects of leaf area loss due to necrosis and chlorosis are much more important to canopy photosynthesis than are changes in the physiological attributes that influence the efficiency of light use. Therefore, potential losses of crop production due to air pollutants such as fluoride can be inferred usefully from the extent of visible injury to foliage that may be associated with different levels of pollutant exposure.

Evaluation, treatment, and surveillance of neurogenic detrusor overactivity in spinal cord injury patients

Neurogenic detrusor overactivity is a common urodynamic finding in patients with supra-sacral spinal cord injury. Early evaluation, stepped management, and close follow-up reduce the risk of upper urinary tract deterioration, renal failure and incontinence. In this article, we aim to outline the modern pathway of the management of this complex disease. Evaluation of patients with history, physical examination, renal function assessment, cystoscopy, and urodynamic study are essential. Management of neurogenic detrusor overactivity with adequate bladder drainage, medical therapy, intradetrusor botulinum injections, and surgery can be offered in a stepwise manner. Follow-up after specific interventions should be done in a timely fashion to detect treatment response and to avoid complications of poorly managed neurogenic detrusor overactivity.

Barriers and facilitators of implementing child injury surveillance system

Purpose: Child injuries are a global public health problem and injury surveillance systems (ISS) can be beneficial by providing timely data. However, ISS implementation has challenges. Opinions of stakeholders of ISS implementation barriers and facilitators are a good source to understand this phenomenon. The aim of this study is to investigate barriers and facilitators of implementing ISS in Iran. Methods: This is a qualitative study. Data were gathered through interviews with 14 experts in the field of child injury and prevention from Iranian Ministry of Health and Medical Education (MOHME), medical univers让ies, pediatrics hospitals, general hospitals and health houses during January 2017 to September 2017. Data collection and analysis con tinued until data saturation. Data were analyzed using con tent analysis through identifying meaning units. Results: Barriers were classified in three main categories and nine subcategories including management barriers (including performance, coordination and cooperation, supervision and attitude), weakness in data capture and usage (including data collection, data recording and data dissemination) and resource limitation (including human and financial resources). Facilitators identified in three areas of policy making (including empowerment and attitude), management (including organization, function and cooperation and coordination) and data recording and usage (including data collection/distTibution and data recording). Conclusion: The most important barrier is lack of national policy in child injury prevention. The most important facil让ator is improving MOHME function through passing supportive regulations. Effective data usage and dissemination of information to those requiring data for policy making can help reduce child injuries. Coalition of stakeholders helps overcome existing barriers.

Injury surveillance information system: A review of the system requirements

Purpose: An injury surveillance information system (ISIS) collects, analyzes, and distributes data on injuries to promote health care delivery. The present study aimed to review the data elements and functional requirements of this system.Method: This study was conducted in 2019. Studies related to injury surveillance system were searched from January 2000 to September 2019 via the databases of PubMed, Web of Knowledge, ScienceDirect, and Scopus. Articles related to the epidemiology of injury, population survey, and letters to the editor were excluded, while the review and research articles related to ISISs were included in the study. Initially 324 articles were identified, and finally 22 studies were selected for review. Having reviewed the articles, the data needed were extracted and the results were synthesized narratively.Results: The results showed that most of the systems reviewed in this study used the minimum data set suggested by the World Health Organization injury surveillance guidelines along with supplementary data. The main functions considered for the system were injury track, data analysis, report, data linkage, electronic monitoring and data dissemination.Conclusion: ISISs can help to improve healthcare planning and injury prevention. Since different countries have various technical and organizational infrastructures, it is essential to identify system requirements in different settings.

Impact of chilling injury and global warming on rice yield in Heilongjiang Province

This study is focused on indexes for the rice chilling injury in Heilongjiang Province during 1960-2009. Firstly, we compared a new derived climate data weighted by rice planting density with the traditional method, and found that the new one is more reasonable to assess the impact of climate change on crop yields. Considering the frequency and intensity of rice chilling in the province, secondly, chilling indexes defined by meteorological, national and international levels were assessed. The result showed that the meteorological standards were suitable for the delayed-type injury, while the international one, so-called sum of Grow- ing Degree Day below threshold （GDDn.）, characterized best the sterile-type chilling injury for rice. The explanation ability of the rice yield time series model including both injury types as two independent variables reached approximately 92% （p 〈 0.05）. Finally, we concluded that the contribution rates of human and weather factors to rice yields are about 87.2% and 12.8% respectively, and as light increasing trend for sterile-type chilling injury was found during heading to flowing period in recent years, indicating a high chilling risk for rice planting in Heilongjiang Province in the future global warming.

Effect of fusion protein TAT and heme oxygenase-1 on liver sinusoidal endothelial cells apoptosis during preservation injury

Background Proteins or peptides can be directly transferred into cells when covalently linked to protein transduction domains （PTDs）. TAT is one of the most widely studied PTDs. The effect of fusion protein TAT and heme oxygenase-1 （HO-1） on liver sinusoidal endothelial cells （SECs） apoptosis during cold storage is unknown. The present study aimed to determine whether fusion protein TAT-HO-1 would transduce efficiently into liver during cold storage, and, if so, to determine whether TAT-HO-1 would attenuate SECs apoptosis during preservation injury in rat. Methods Livers of Sprague-Dawley rats were harvested and randomly assigned to group 1 （HTK solution） and group 2 （HTK solution containing TAT-HO-1 fusion protein） according to the type of the preservation solution. The transduction efficiency of TAT-HO-1 was examined and the impairment of SECs was assessed during the period of cold storage followed by 1 hour of reperfusion. Results TAT-HO-1 can transduce efficiently into liver during cold storage. A significantly lower apoptotic index of SECs was observed in group 2, at 6, 12 and 18 hours of cold storage after 1 hour reperfusion, when compared with group 1. TAT-HO-1 reduced HA and ET levels in liver at each time point. Both Bcl-2 and Bax protein were expressed in hepatocytes and SECs at the periphery of the sinusoidal space. Moreover, higher Bcl-2 expression and lower Bax expression were observed in group 2. Conclusions TAT-HO-1 can transduce efficiently into rat livers and shows a protective effect on SECs by attenuating apoptosis during cold ischemia/reperfusion injury. Protein transduction will be a novel therapeutic strategy to reduce the risk of preservation injury in liver transplantation.

2017至2021年河北省监测哨点医院伤害病例流行特征分析

目的了解河北省哨点医院伤害病例流行特征,为制定相应的伤害防控和干预措施提供依据。方法收集并分析2017年1月至2021年12月在河北省3个国家伤害监测点9家哨点医院门急诊首次就诊的伤害病例资料。结果2017至2021年河北省监测哨点医院报告伤害病例共248001例,男女性别比为1.49∶1,伤害发生年龄以25~64岁年龄组(58.46%)为主。伤害发生原因前5位分别是跌倒/坠落(48.52%)、机动车车祸(13.05%)、钝器伤(12.50%)、刀/锐器伤(11.33%)、非机动车车祸(6.43%)。跌倒/坠落是所有年龄组最主要的伤害原因。伤害发生时间具有一定规律性。结论跌倒/坠落、机动车车祸、钝器伤、刀/锐器伤和非机动车车祸是河北省年居民伤害主要原因,青壮年是高发人群。应针对不同人群、不同原因采取针对性的伤害防控措施,减少伤害发生。

Post-marketing safety surveillance and reevaluation of Motherwort injection：A clinical study of 10094 cases

OBJECTIVE:To investigate the safety profiles of Motherwort injection(MI).METHODS:A multi-center,prospective and drugderived hospital intensive monitoring method was conducted to assess the safety of MI in real world applications.This study was based on a very large population after the injection was approved and marketed in China.All patients using the injection in participating hospitals were monitored to determine the incidence,pattern,severity and outcome of associated adverse events.RESULTS:The post-marketing surveillance was performed in 10 094 female patients from April to December,2015.The incidence of adverse drug reactions(ADRs) was 0.79‰(8/10 094).Among the 8 patients,the reported adverse events mainly included systemic abnormalities,such as fever,chills and eyelid edema;skin and appendages disorders,such as pruritus and rash;gastrointestinal disorders,such as nausea,abdominal distension and pain;heart rate and rhythm disorders,such as palpitation and increased heart rate.All of these ADRs were mild in severity.CONCLUSION:In this study the ADRs incidence rate of MI is very low,which supports that it is generally safe for use in obstetric and gynecological diseases.However,the total number of 8 ADRs recorded over a relatively short time span seems limited,and the low number of reports could not represent an absolute guarantee of safety.

Ambulance Records as an Information Source to Document and Prevent Fall Injuries in Sweden

In Sweden, there has been only limited documentation for injuries requiring ambulance responses. The main objective of this study is, through the use of historic data, to assess the suitability of ambulance records to describe circumstances with fall injuries. Methods: The injury events data around patients were sourced from the ambulance data register. Descriptive statistics were used to describe injured patients based on age group, type of injury, place of injury, injury mechanism and consequence of an injury event. Two-group comparison was performed with Pearson’s chi-squared. Predictors of transport to hospital were identified using logistic regression analyses. Result: Ambulance provides unique data on all injury events, with direct implications for translational research, public policy and clinical practice (safety promotion). In 2002 ambulance attended 3964 injured people which represents 14% of ambulance attended workload in Värmland county, Sweden. The most common trauma location was the traffic area followed by residential area and nursing home. These three injury sites account for 2320 cases (61.6%). The most common cause of injury was falls (63.9%) followed by contact with another person (26.5%). Contact with another person is the most common site of injury in the traffic area (79.5%), and men aged 25-66 years are overrepresented. Conclusion: Logistic regression found that, age-group and place code were significant predictor for being attended by ambulance. Traffic, home and nursing homes were over-represented injury environments (61.6%) that require special attention. Most injury cases occur in the home and nursing homes among people over 67 years of age. Surprisingly, most of the injury events in the traffic environment are about hitting another person. Paramedics can provide rich and valuable data on injury events. Registration of such data is entirely possible and desirable, and can be used in preventive work.