PANoptosis is a newly identified type of regulated cell death that consists of pyroptosis,apoptosis,and nec roptosis,which simultaneously occur during the pathophysiological process of infectious and inflammatory dise...PANoptosis is a newly identified type of regulated cell death that consists of pyroptosis,apoptosis,and nec roptosis,which simultaneously occur during the pathophysiological process of infectious and inflammatory diseases.Although our previous lite rature mining study suggested that PANoptosis might occur in neuronal ischemia/repe rfusion injury,little experimental research has been reported on the existence of PANoptosis.In this study,we used in vivo and in vitro retinal neuronal models of ischemia/repe rfusion injury to investigate whether PAN optosis-like cell death(simultaneous occurrence of pyroptosis,apo ptosis,and necroptosis)exists in retinal neuronal ischemia/repe rfusion injury.Our results showed that ischemia/repe rfusion injury induced changes in morphological features and protein levels that indicate PANoptosis-like cell death in retinal neurons both in vitro and in vivo.Ischemia/repe rfusion inju ry also significantly upregulated caspase-1,caspase-8,and NLRP3 expression,which are important components of the PANoptosome.These results indicate the existence of PANoptosis-like cell death in ischemia/reperfusion injury of retinal neurons and provide preliminary experimental evidence for future study of this new type of regulated cell death.展开更多
BACKGROUND:The high morbidity,high mortality and low survival rate of cardiac arrest(CA)cause a heavy global burden.We aimed to analyze the changes in scientific output related to CA over the past two decades.METHODS:...BACKGROUND:The high morbidity,high mortality and low survival rate of cardiac arrest(CA)cause a heavy global burden.We aimed to analyze the changes in scientific output related to CA over the past two decades.METHODS:We analyzed the scientific output related to CA from 2000 to 2020 via the Web of Science.The data were analyzed using CiteSpace software.RESULTS:In total,28,312 articles relating to CA were identified in the Web of Science.The volume of scientific research output in the field of global CA research was mainly distributed in the Americas,Europe and Asia,covering a wide range.Of the 28,312 articles,the research content of the highly cited literature mainly focused on CA,mild hypothermia treatment,and prognosis of CA patients.CONCLUSION:Various scientific methods were applied to reveal scientific productivity,collaboration,and research hotspots in the CA research field.Cardiopulmonary resuscitation(CPR),extracorporeal membrane oxygenation(ECMO),survival and target temperature management are research hotspots.Future research on CA will continue to focus on its treatment and prognosis to improve the survival rate of CA patients.展开更多
Sepsis is currently a major problem and challenge facing the medical community.With rapid development and progress of modern medicine,researchers have put more and more attention on sepsis;meanwhile,the morbidity and ...Sepsis is currently a major problem and challenge facing the medical community.With rapid development and progress of modern medicine,researchers have put more and more attention on sepsis;meanwhile,the morbidity and mortality of sepsis remains high despite great efforts from experts in various fields.According to updated guidelines,sepsis is defined as life-threatening organ dysfunction caused by a dysregulated host response to infection.Infection is the initial step of sepsis progression,and development from infection to sepsis is a complex pathophysiological process,including pathogen invasion,cytokine release,capillary leakage,microcirculation dysfunction,etc.which finally leads to organ metabolic disorders and functional failure.According to the latest recommended international guidelines of Sepsis 3.0,the presence of infection and SOFA score≥2 are considered as the diagnostic criteria for sepsis,and the"rescue"measures mainly focus on reversal of organ dysfunction.However,despite nearly two decades of efforts,the"Save Sepsis Campaign"has not achieved satisfactory results.Emergency medicine is the frontier subject of acute and severe illness which treats patients with acute infections at the earliest.If at this stage,physicians can predict the possibility of sepsis progression from demographic characteristics,localize the pathogen and infection,detect the inflammatory storms by tests of cytokines and evaluate the severity of the infection with more effective clinical scoring system,and then take effective measures to prevent infection from developing into sepsis in high-risk patients,the morbidity and mortality of sepsis in patients with acute infection will be greatly reduced.Based on this situation,Chinese emergency medicine experts proposed the concept of"preventing and blocking"sepsis,and launched the nationwide"Preventing Sepsis Campaign in China(PSCC)"nationwide.The main concept is summarized as"three early and two reduces"which includes early detection,early diagnosis and early intervention during t展开更多
Wounds in diabetic patients,especially diabetic foot ulcers,are more difficult to heal compared with normal wounds and can easily deteriorate,leading to amputation.Common treatments cannot heal diabetic wounds or cont...Wounds in diabetic patients,especially diabetic foot ulcers,are more difficult to heal compared with normal wounds and can easily deteriorate,leading to amputation.Common treatments cannot heal diabetic wounds or control their many complications.Growth factors are found to play important roles in regulating complex diabetic wound healing.Different growth factors such as transforming growth factor beta 1,insulin-like growth factor,and vascular endothelial growth factor play different roles in diabetic wound healing.This implies that a therapeutic modality modulating different growth factors to suit wound healing can significantly improve the treatment of diabetic wounds.Further,some current treatments have been shown to promote the healing of diabetic wounds by modulating specific growth factors.The purpose of this study was to discuss the role played by each growth factor in therapeutic approaches so as to stimulate further therapeutic thinking.展开更多
Nasopharyngeal carcinoma(NPC),a malignant tumor originating from the nasopharynx,is one of the common malignant tumors of the head and neck.There are significant geographical differences in the incidence of nasopharyn...Nasopharyngeal carcinoma(NPC),a malignant tumor originating from the nasopharynx,is one of the common malignant tumors of the head and neck.There are significant geographical differences in the incidence of nasopharyngeal carcinoma,with a high incidence in China and Southeast Asian countries.Herein,we designed and synthesized a novel near-infrared fluorescent(NIRF)probe to detect glutathione(GSH)in cellular and tumor environments using semi-naphthofluorescein(SNAFL)as the fluorescent molecular backbone and 2-fluoro-4-nitrobenzenesulfonate as the recognition moiety.Upon reaction with GSH,SNAFL-GSH emitted a fluorescence signal,and its emission wavelength at 650 nm was remarkably enhanced.The results of selectivity experiments indicated that SNAFL-GSH was able to discriminate GSH from Cys,Hcy,and H_(2) S.Moreover,SNAFL-GSH could image both endogenous and exogenous GSH and distinguish normal and cancer cells by fluorescence signal difference.At the cellular level,cisplatin(DDP)-induced ferroptosis and inhibition of proliferation of various NPC cell lines(CNE2,CNE1,5-8F cells)by erastin combined with DDP were visualized with the help of SNAFL-GSH.In a mouse tumor xenograft model,we successfully employed SNAFL-GSH for the evaluation of the efficacy of erastin combined with DDP in the treatment of NPC.More importantly,the probe could image cancerous tissue sections from NPC patients with an imaging depth of approximately 80µm.It was foreseen that SNAFL-GSH offered great potential for application in the diagnosis and evaluation of the therapeutic efficacy of NPC,and these results would also provide new ideas for the clinical treatment of NPC.展开更多
Monomethyl auristatin E(MMAE)is a derivative of the marine peptide Dolastatin 10,which has therapeutic effects against various cancers according to its antimitotic activity in multiple clinical trials.The antibody dru...Monomethyl auristatin E(MMAE)is a derivative of the marine peptide Dolastatin 10,which has therapeutic effects against various cancers according to its antimitotic activity in multiple clinical trials.The antibody drug conjugate(ADC)of MMAE is currently used in clinical practice.However,the safety issues of MMAE-based ADC,such as high drug toxicity and poor bioavailability,still exist when using it for anticancer therapy.A sustained release of drug delivery approach should be used to reduce toxicity and achieve sufficient anticancer effects.Herein,PLGA-b-PEG 2000 with excellent biocompatibility and slow degradation ability was adopted to construct MMAE-loaded nanoparticles for safe and effective chemotherapy.The sustained release effect and the immunogenic cell death(ICD)effect of PLGA-MMAE nanoparticles were assessed by in vitro experiments.The PLGA-MMAE nanoparticles effectively accumulated in the tumor through the enhanced permeability and retention(EPR)effect,inducing cell apoptosis and causing a certain degree of immune response.The sustained drug release of PLGA-MMAE improved the bioavailability and effectively reduced the toxicity and development of the tumor compared to the effect of free MMAE or ADC.Overall,this study provides a safe and effective chemotherapeutic approach,as well as a simple and effective synthetic process for MMAE-based nanoparticles,improving their therapeutic efficacy and safety.展开更多
Triphenylamine(TPA)-based aggregation-induced emission luminogens(TPA-AIEgens),a type of photoactive material utilizing the typical TPA moiety,has recently attracted increasing attention for the diagnostics and treatm...Triphenylamine(TPA)-based aggregation-induced emission luminogens(TPA-AIEgens),a type of photoactive material utilizing the typical TPA moiety,has recently attracted increasing attention for the diagnostics and treatment of tumors due to their remarkable chemo-physical performance in optoelectronic research.TPA-AIEgens are distinguished from other photoactive agents by their strong fluorescence,good sensitivity,high signal-to-noise ratio,resistance to photobleaching,and lack of high concentration or aggregation-caused fluoresce quenching effects.In this review,we summarize the current advancements and the biomedical progress of TPA-AIEgens in tumor theranostics.First,the design principles of TPAAIEgens photoactive agents as well as the advanced targeting strategies for nuclei,cell membranes,cell organelle and tumors were introduced,respectively.Next,the applications of TPA-AIEgens in tumor diagnosis and therapeutic techniques were reviewed.Last,the challenges and prospects of TPA-AIEgens for cancer therapy were performed.The given landscape of the TPA-AIEgens hereby is meaningful for the further design and utilization of the novel photoactive material,which could be beneficial for the development of clinic applications.展开更多
BACKGROUND:Several observational studies have shown an association between homocysteine(Hcy)levels and chronic obstructive pulmonary disease(COPD),but causal relationships are not clear.Our study aimed to explore the ...BACKGROUND:Several observational studies have shown an association between homocysteine(Hcy)levels and chronic obstructive pulmonary disease(COPD),but causal relationships are not clear.Our study aimed to explore the causal relationship between plasma Hcy and COPD by two-sample Mendelian randomization(MR).METHODS:A two-sample MR study was performed to infer the causal link.Genetically predicted plasma Hcy was selected as an instrumental variable(Ⅳ)from published genome-wide association study(GWAS)meta-analyses.COPD with different etiologies was extracted as outcome variables from other GWAS meta-analyses.The main MR analysis was performed using the inversevariance weighted(IVW)method.Additional analyses were further performed using Cochran’s Q-test and MR-Egger regression to evaluate the heterogeneity or horizontal pleiotropy of our findings.RESULTS:MR analysis showed no significant association between plasma Hcy and COPD.The results of the groups were consistent with the sensitivity analysis and repeated analysis,without heterogeneity or horizontal pleiotropy.The IVW results showed COPD hospital admissions(odds ratio[OR]1.06,95%confidence interval[CI]0.91-1.24,P=0.42),asthma/COPD(OR 0.97,95%CI0.89-1.06,P=0.55),COPD-related chronic infection(OR 1.50,95%CI 0.57-3.99,P=0.41),COPDI asthma/interstitial lung disease(ILD)-related pneumonia or pneumonia-derived septicemia(OR 0.93,95%CI 0.86-1.02,P=0.13),and COPD-related respiratory insufficiency(OR 1.00,95%CI 0.7-1.44,P=0.99).CONCLUSION:There is no direct causal relationship between plasma Hcy and COPD in our study.As Hcy is known to have deleterious effects on endothelial function and vascular homeostasis,further studies are needed to investigate whether additional factors mediate the association between Hcy and COPD.展开更多
BACKGROUND:The ion shift index(ISI) as a prognostic indicator that can show the severity of hypoxic-ischemic injury.We aimed to evaluate the performance of the ISI in predicting unfavorable neurological outcomes at ho...BACKGROUND:The ion shift index(ISI) as a prognostic indicator that can show the severity of hypoxic-ischemic injury.We aimed to evaluate the performance of the ISI in predicting unfavorable neurological outcomes at hospital discharge in cardiac arrest(CA) patients following extracorporeal cardiopulmonary resuscitation(ECPR) and to compare its performance to other prognostic predictors.METHODS:This was a retrospective observational study including adult CA patients treated with ECPR between January 2018 and December 2022 in a tertiary hospital.Data regarding clinical characteristics and laboratory parameters were collected from medical records.The ISI was determined based on the first available serum electrolyte levels after ECPR.The primary outcome was unfavorable neurological status at hospital discharge,defined as Cerebral Performance Categories 3–5.Comparisons of the characteristics between the two groups were made using the χ2 test for categorical variables and the t-test or non-parametric Mann-Whitney U-test for continuous variables,as appropriate.Correlation analysis was performed using Spearman’s rank correlation coeficient.A two-tailed P-value <0.05 was considered statistically significant.RESULTS:Among the 122 patients involved,46(37.7%) had out-of-hospital CA,and 88 had unfavorable neurological outcomes.The ISI was significantly higher in the unfavorable outcome group than in the favorable outcome group(3.74 [3.15–4.57] vs.2.69 [2.51–3.07],P<0.001).A higher ISI level was independently related to unfavorable outcome(odds ratio=6.529,95% confidence interval 2.239–19.044,P=0.001).An ISI level >3.12 predicted unfavorable outcomes with a sensitivity and specificity of 74.6% and 85.2%,respectively(P<0.001).The prognostic performance of ISI(area under the curve [AUC]=0.887) was similar to that of other predictors,such as gray-to-white matter ratio(AUC=0.850,P=0.433) and neuronspecific enolase(AUC=0.925,P=0.394).CONCLUSION:ISI may be used as a prognostic biomarker to predict neurological outcomes in 展开更多
Ischemic stroke is a serious cerebrovascular disease with high morbidity and mortality.As a result of ischemia-reperfusion,a cascade of pathophysiological responses is triggered by the imbalance in metabolic supply an...Ischemic stroke is a serious cerebrovascular disease with high morbidity and mortality.As a result of ischemia-reperfusion,a cascade of pathophysiological responses is triggered by the imbalance in metabolic supply and demand,resulting in cell loss.These cellular injuries follow various molecular mechanisms solely or in combination with this disorder.Mitochondria play a driving role in the pathophysiological processes of ischemic stroke.Once ischemic stroke occurs,damaged cells would respond to such stress through mitophagy.Mitophagy is known as a conservatively selective autophagy,contributing to the removal of excessive protein aggregates and damaged intracellular components,as well as aging mitochondria.Moderate mitophagy may exert neuroprotection against stroke.Several pathways associated with the mitochondrial network collectively contribute to recovering the homeostasis of the neurovascular unit.However,excessive mitophagy would also promote ischemia-reperfusion injury.Therefore,mitophagy is a double-edged sword,which suggests that maximizing the benefits of mitophagy is one of the direction of future efforts.This review emphasized the role of mitophagy in ischemic stroke,and highlighted the crosstalk between mitophagy and apoptosis/necroptosis.展开更多
Acute lung injury is featured as diffuse pulmonary edema and persistent hypoxemia caused by lung or systemic injury.It is believed that these pathological changes are associated with damage to the alveolar epithelium ...Acute lung injury is featured as diffuse pulmonary edema and persistent hypoxemia caused by lung or systemic injury.It is believed that these pathological changes are associated with damage to the alveolar epithelium and vascular endothelium,recruitment of inflammatory cells,and inflammatory factor storms.In recent years,the metabolic reprogramming of lung parenchymal cells and immune cells,particularly alterations in glycolysis,has been found to occur in acute lung injury.Inhibition of glycolysis can reduce the severity of acute lung injury.Thus,this review focuses on the interconnection between acute lung injury and glycolysis and the mechanisms of interaction,which may bring hope for the treatment of acute lung injury.展开更多
Objective:To explore the possible mechanism of neutrophil exosomes regulating macrophage apoptosis.Methods:neutrophils were induced by lipopolysaccharide,inflammatory factors were detected by ELISA,the morphology of e...Objective:To explore the possible mechanism of neutrophil exosomes regulating macrophage apoptosis.Methods:neutrophils were induced by lipopolysaccharide,inflammatory factors were detected by ELISA,the morphology of exosomes was identified by electron microscope,and the expression of mir-15a-5p in exosomes was detected by RT-PCR;Raw267.4 macrophages was treated with neutrophil exosomes and mir-15a-5p mimic respectively,CCK8 to detect cell viability,flow cytometry to detect apoptosis;The binding sites of mir-15a-5p and BCL2L2 were predicted and verified by double luciferase experiment;RT-PCR and Western blot verified that mir-15a-5p regulate the expression of BCL2L2.Results:lipopolysaccharide induced neutrophil inflammatory factors IL-2,IL-6,IL-10 and TNF-α.The morphological characteristics of exosomes were observed by electron microscope.Mir-15a-5p was significantly overexpressed in neutrophil exosomes induced by lipopolysaccharide;Lipopolysaccharide-induced neutrophil exosomes and mir-15a-5p simulants can promote raw267.4 macrophage apoptosis and inhibit its cell viability;Targetscan database predicted that mir-15a-5p and BCL2L2 had binding sites.Double-luciferase experiment verified that mir-15a-5p and BCL2L2 bound through binding sites;Mir-15a-5p mimic was transfected into raw267.4 macrophages which inhibit the expression of BCL2L2 mRNA and protein.Conclusion:inflammatory neutrophils may promote raw267.4 by secreting exosomes containing mir-15a-5p and inhibiting BCL2L2 by targeting macrophage apoptosis.This may provide a theoretical basis for further understanding the molecular mechanism of inflammatory regulation of neutrophils and macrophages.展开更多
Objective:To explore effect of calcium citrate on bone integration in a rabbit femur defect model, and to compare the bone formation with different sizes by radiological and histological study. Methods:Twenty-four mal...Objective:To explore effect of calcium citrate on bone integration in a rabbit femur defect model, and to compare the bone formation with different sizes by radiological and histological study. Methods:Twenty-four male Japanese white rabbits were randomly divided into three groups (Group A.B.C)in this study.Under anesthesia,defects of four sizes(1.2,1.5,2.0 and 2.5 mm) were created in each of the rabbits.Commercially pure calcium citrate powder was placed inside the medullary compartment of the femur(Experimental),while in the contralateral femur(Control) nothing was implanted.The defects were analyzed using radiography and histological analysis by using Imagepro-Plus 6.0 software after animal was sacrificed at 4th(Group A),6th(Group B) and 8th(Group C) weeks postoperatively.Four samples were analyzed for each size of defect and each healing period.Results:The histological and the radiologic evaluation were performed after sacrification of all rabbits on postoperative 4th and 6th weeks,It showed significant difference between the experimental group and the control group when these defects were less than or equal to 2.0 mm.No statistical difference was observed when these defects were larger than 2.0 mm at all healing periods except at the 4th week.Conclusions:Calcium citrate affects the early periods of hone defects healing mechanism in Japanese white rabbits positively,especially when the defect is not too large,We suggest further studies on calcium citrate to determine the effects of various dosages,administration ways and the experimental time on the bone defects.展开更多
BACKGROUND:We aimed to examine prospective associations between diff erent intensities and diff erent types of physical activity(PA)in early pregnancy and hypertensive disorders of pregnancy(HDP)among Chinese women.ME...BACKGROUND:We aimed to examine prospective associations between diff erent intensities and diff erent types of physical activity(PA)in early pregnancy and hypertensive disorders of pregnancy(HDP)among Chinese women.METHODS:A total of 6,820 pregnant women from the Tongji-Shuangliu Birth Cohort were included in this study.The pregnancy physical activity questionnaire(PPAQ)was used to assess PA,including household/caregiving,occupational,sports/exercise,and transportation activities in the first trimester of pregnancy.The diagnosis of HDP was collected,including gestational hypertension(GH)and preeclampsia(PE).Data were analyzed by unconditional multivariate logistic regression,and the odds ratio(OR)and 95%confi dence interval(CI)were calculated.RESULTS:A total of 178(2.6%)of the 6,820 women were diagnosed with HDP,of which 126(1.8%)were GH and 52(0.8%)were PE.Overall,we found no association between PA in early pregnancy and PE.A trend toward lower risk was found only among women with GH and among those with higher levels of moderate-to-vigorous intensity physical activity(MVPA)(adjusted OR 0.54,95%CI 0.31–0.96).No association was observed between PA and HDP in early pregnancy,regardless of diff erent intensities or types of PA.CONCLUSION:MVPA in the first trimester is an influencing factor of HDP.Encouraging pregnant women to engage in MVPA in the fi rst trimester may help to prevent GH.展开更多
Objective:The integration of training in theory and practice across the medical education spectrum is being encouraged to increase student understanding and skills in the sciences.This study aimed to determine the dec...Objective:The integration of training in theory and practice across the medical education spectrum is being encouraged to increase student understanding and skills in the sciences.This study aimed to determine the deciding factors that drive students'perceived advantages in class to improve precision education and the teaching model.Methods:A mixed strategy of an existing flipped classroom(FC)and a case-based learning(CBL)model was conducted in a medical morphology curriculum for 575 postgraduate students.The subjective learning evaluation of the individuals(learning time,engagement,study interest and concentration,and professional integration)was collected and analyzed after FC-CBL model learning.Results:The results from the general evaluation showed promising results of the medical morphology in the FC-CBL model.Students felt more engaged by instructors in person and benefited in terms of time-saving,flexible arrangements,and professional improvement.Our study contributed to the FC-CBL model in Research Design in postgraduate training in 4 categories:1)advancing a guideline of precision teaching according to individual characteristics;2)revealing whether a learning background is needed for a Research Design course to guide setting up a preliminary course;3)understanding the perceived advantages and their interfaces;and 4)barriers and/or improvement to implement the FC-CBL model in the Research Design class,such as a richer description of e-learning and hands-on practice.Conclusion:Undertaking a FC-CBL combined model could be a useful addition to pedagogy for medical morphology learning in postgraduate training.展开更多
BACKGROUND: Less attention is directed toward gaining a better understanding of the burden and prevention of injuries, in low and middle income countries(LMICs). We report the establishment of a trauma registry at the...BACKGROUND: Less attention is directed toward gaining a better understanding of the burden and prevention of injuries, in low and middle income countries(LMICs). We report the establishment of a trauma registry at the Adult Emergency and Trauma Centre(AETC) at Queen Elizabeth Central Hospital(QECH) in Blantyre, Malawi and identify high risk geographic areas. METHODS: We devised a paper based two-page trauma registry form. Ten data clerks and all AETC clinicians were trained to complete demographic and clinical details respectively. Descriptive data, regression and hotspot analyses were done using STATA 15 statistical package and ArcGIS(16) software respectively.RESULTS: There were 3,747 patients from May 2013 to May 2015. The most common mechanisms of injury were assault(38.2%), and road traffi c injuries(31.6%). The majority had soft tissue injury(53.1%), while 23.8% had no diagnosis indicated. Fractures(OR 19.94 [15.34–25.93]), head injury and internal organ injury(OR 29.5 [16.29–53.4]), and use of ambulance(OR 1.57 [1.06–2.33]) were found to be predictive of increased odds of being admitted to hospital while assault(OR 0.69 [0.52–0.91]) was found to be associated with less odds of being admitted to hospital. Hot spot analysis showed that at 99% confidence interval, Ndirande, Mbayani and Limbe were the top hot spots for injury occurrence. CONCLUSION: We have described the process of establishing an integrated and potentially sustainable trauma registry. Signifi cant data were captured to provide details on the epidemiology of trauma and insight on how care could be improved at AETC and surrounding health facilities. This approach may be relevant in similar poor resource settings.展开更多
Sepsis is an infection-induced systemic inflammatory syndrome.The immune response in sepsis is characterized by the activation of both proinflammatory and anti-inflammatory pathways.When sepsis occurs,the expression a...Sepsis is an infection-induced systemic inflammatory syndrome.The immune response in sepsis is characterized by the activation of both proinflammatory and anti-inflammatory pathways.When sepsis occurs,the expression and activity of many inflammatory cytokines are markedly affected.Xenobiotic receptors are chemical-sensing transcription factors that play essential roles in the transcriptional regulation of drug-metabolizing enzymes(DMEs).Xenobiotic receptors mediate the functional crosstalk between sepsis and drug metabolism because the inflammatory cytokines released during sepsis can affect the expression and activity of xenobiotic receptors and thus impact the expression and activity of DMEs.Xenobiotic receptors in turn may affect the clinical outcomes of sepsis.Thisreview focuses on the sepsis-induced inflammatory response and xenobiotic receptors such as pregnane X receptor(PXR),aryl hydrocarbon receptor(AHR),glucocorticoid receptor(GR),and constitutive androstane receptor(CAR),DMEs such as CYP1A,CYP2B6,CYP2C9,and CYP3A4,and drug transporters such as p-glycoprotein(P-gp),and multidrug resistance-associated protein(MRPs)that are affected by sepsis.Understanding the xenobiotic receptor-mediated effect of sepsis on drug metabolism will help to improve the safe use of drugs in sepsis patients and the development of new xenobiotic receptor-based therapeutic strategies for sepsis.展开更多
With the influence of many factors such as the aging of the population,the younger smokers,and the serious air pollution,the incidence of chronic respiratory diseases is increasing year by year.In the treatment of res...With the influence of many factors such as the aging of the population,the younger smokers,and the serious air pollution,the incidence of chronic respiratory diseases is increasing year by year.In the treatment of respiratory diseases,clinical intervention is still mainly based on drug control of pulmonary symptoms.However,systemic drugs have disadvantages such as many adverse reactions and severe systemic side effects.In recent years,the research and development of local drug delivery systems for the respiratory tract has brought new changes to the treatment of respiratory diseases.Locally delivered drugs can directly act on the airways and have the characteristics of fast onset,good curative effect and small side effects.It is a simple,efficient and safe treatment method,which has a very significant effect,and has become a hot topic of current research and promotion.This paper briefly reviews the development track and latest research progress of respiratory local drug delivery systems at home and abroad,in order to provide reference for clinical workers in drug selection and application.展开更多
1.Introduction Sudden cardiac death(SCD)refers to sudden death due to a variety of cardiac causes.It is manifested as a sudden loss of consciousness,cardiac arrest,and respiratory arrest and generally shows early symp...1.Introduction Sudden cardiac death(SCD)refers to sudden death due to a variety of cardiac causes.It is manifested as a sudden loss of consciousness,cardiac arrest,and respiratory arrest and generally shows early symptoms that are atypical and not easily detected[1].According to a recent study,nearly 544?000 patients suffer from SCD every year in China[2].Rescue of SCD patients in the shortest time is important as the survival rate will decrease by 7%-10%if the rescue is delayed for one minute[3].However,SCD mostly occurs in public places outside the hospital,including public sports places,transportation hubs(such as airports,railway stations,and subway stations),shopping centers,factories,and so on.Therefore,out-of-hospital cardiac arrest(OHCA)is a huge threat to people's lives."Chain of survival"proposed by the American Heart Association in 2015 emphasized the importance of early call for help,rapid implementation of high-quality cardiopulmonary resuscitation(CPR),and immediate use of an automated external defibrillator(AED)in improving the survival rate of OHCA patients.Studies have shown that conducting CPR within 1 min and AEDs defibrillation within 3 to 5 min can achieve a 50%to 70%survival rate for cardiac arrest patients[4].Therefore,early defibrillation of OHCA patients will markedly increase the survival rate.展开更多
Human cytosolic sulfotransferase 2 A1(SULT2A1) is an important phase II metabolic enzyme. The detection of SULT2A1 is helpful for the functional characterization of SULT2A1 and diagnosis of its related diseases. Howev...Human cytosolic sulfotransferase 2 A1(SULT2A1) is an important phase II metabolic enzyme. The detection of SULT2A1 is helpful for the functional characterization of SULT2A1 and diagnosis of its related diseases. However, due to the overlapping substrate specificity among members of the sulfotransferase family, it is difficult to develop a probe substrate for selective detection of SULT2A1. In the present study, through characterization of the sulfation of series of bufadienolides, arenobufagin(AB) was proved as a potential probe substrate for SULT2A1 with high sensitivity and specificity. Subsequently, the sulfation of AB was characterized by experimental and molecular docking studies. The sulfate-conjugated metabolite was identified as AB-3-sulfate.The sulfation of AB displayed a high selectivity for SULT2A1 which was confirmed by in vitro reaction phenotyping assays. The sulfation of AB by human liver cytosols and recombinant SULT2A1 both obeyed Michaelis-Menten kinetics, with similar kinetic parameters. Molecular docking was performed to understand the interaction between AB and SULT2A1, in which the lack of interaction with Met-137 and Tyr-238 of SULT2A1 made it possible to eliminate substrate inhibition of AB sulfation. Finally, the probe was successfully used to determine the activity of SULT2A1 and its isoenzymes in tissue preparations of human and laboratory animals.展开更多
基金supported by the National Natural Science Foundation of China,Nos.81772134,81971891,82172196,81571939(ail to KX)the Key Laboratory of Emergency and Trauma(Hainan Medical University)of Ministry of Education,No.KLET-202108(to KX)+1 种基金the Fundamental Research Funds for the Central Universities of Central South University of China,No.2020zzts218(to WTY)Hunan Provincial Innovation Foundation for Postgraduate of China,No.CX20200116(to WTY)。
文摘PANoptosis is a newly identified type of regulated cell death that consists of pyroptosis,apoptosis,and nec roptosis,which simultaneously occur during the pathophysiological process of infectious and inflammatory diseases.Although our previous lite rature mining study suggested that PANoptosis might occur in neuronal ischemia/repe rfusion injury,little experimental research has been reported on the existence of PANoptosis.In this study,we used in vivo and in vitro retinal neuronal models of ischemia/repe rfusion injury to investigate whether PAN optosis-like cell death(simultaneous occurrence of pyroptosis,apo ptosis,and necroptosis)exists in retinal neuronal ischemia/repe rfusion injury.Our results showed that ischemia/repe rfusion injury induced changes in morphological features and protein levels that indicate PANoptosis-like cell death in retinal neurons both in vitro and in vivo.Ischemia/repe rfusion inju ry also significantly upregulated caspase-1,caspase-8,and NLRP3 expression,which are important components of the PANoptosome.These results indicate the existence of PANoptosis-like cell death in ischemia/reperfusion injury of retinal neurons and provide preliminary experimental evidence for future study of this new type of regulated cell death.
基金This study was supported by the National Natural Science Foundation of China(8216120150)Hainan Provincial Key Research and Development Project(ZDYF2020112)+2 种基金Hainan Provincial Science and Technology Major Project(ZDKJ202004)Key Laboratory of Emergency and Trauma(Hainan Medical University)Ministry of Education(Grant.KLET-202002).
文摘BACKGROUND:The high morbidity,high mortality and low survival rate of cardiac arrest(CA)cause a heavy global burden.We aimed to analyze the changes in scientific output related to CA over the past two decades.METHODS:We analyzed the scientific output related to CA from 2000 to 2020 via the Web of Science.The data were analyzed using CiteSpace software.RESULTS:In total,28,312 articles relating to CA were identified in the Web of Science.The volume of scientific research output in the field of global CA research was mainly distributed in the Americas,Europe and Asia,covering a wide range.Of the 28,312 articles,the research content of the highly cited literature mainly focused on CA,mild hypothermia treatment,and prognosis of CA patients.CONCLUSION:Various scientific methods were applied to reveal scientific productivity,collaboration,and research hotspots in the CA research field.Cardiopulmonary resuscitation(CPR),extracorporeal membrane oxygenation(ECMO),survival and target temperature management are research hotspots.Future research on CA will continue to focus on its treatment and prognosis to improve the survival rate of CA patients.
基金supported by CAMS Innovation Fund for Medical Sciences(2019-I2M-5-023)
文摘Sepsis is currently a major problem and challenge facing the medical community.With rapid development and progress of modern medicine,researchers have put more and more attention on sepsis;meanwhile,the morbidity and mortality of sepsis remains high despite great efforts from experts in various fields.According to updated guidelines,sepsis is defined as life-threatening organ dysfunction caused by a dysregulated host response to infection.Infection is the initial step of sepsis progression,and development from infection to sepsis is a complex pathophysiological process,including pathogen invasion,cytokine release,capillary leakage,microcirculation dysfunction,etc.which finally leads to organ metabolic disorders and functional failure.According to the latest recommended international guidelines of Sepsis 3.0,the presence of infection and SOFA score≥2 are considered as the diagnostic criteria for sepsis,and the"rescue"measures mainly focus on reversal of organ dysfunction.However,despite nearly two decades of efforts,the"Save Sepsis Campaign"has not achieved satisfactory results.Emergency medicine is the frontier subject of acute and severe illness which treats patients with acute infections at the earliest.If at this stage,physicians can predict the possibility of sepsis progression from demographic characteristics,localize the pathogen and infection,detect the inflammatory storms by tests of cytokines and evaluate the severity of the infection with more effective clinical scoring system,and then take effective measures to prevent infection from developing into sepsis in high-risk patients,the morbidity and mortality of sepsis in patients with acute infection will be greatly reduced.Based on this situation,Chinese emergency medicine experts proposed the concept of"preventing and blocking"sepsis,and launched the nationwide"Preventing Sepsis Campaign in China(PSCC)"nationwide.The main concept is summarized as"three early and two reduces"which includes early detection,early diagnosis and early intervention during t
基金Supported by the National Natural Science Foundation of China,No.81971891 and No.82172196Key Laboratory of Emergency and Trauma(Hainan Medical University)of Ministry of Education,No.KLET-202108the College Students’Innovation and Entrepreneurship Project,No.S20210026020013.
文摘Wounds in diabetic patients,especially diabetic foot ulcers,are more difficult to heal compared with normal wounds and can easily deteriorate,leading to amputation.Common treatments cannot heal diabetic wounds or control their many complications.Growth factors are found to play important roles in regulating complex diabetic wound healing.Different growth factors such as transforming growth factor beta 1,insulin-like growth factor,and vascular endothelial growth factor play different roles in diabetic wound healing.This implies that a therapeutic modality modulating different growth factors to suit wound healing can significantly improve the treatment of diabetic wounds.Further,some current treatments have been shown to promote the healing of diabetic wounds by modulating specific growth factors.The purpose of this study was to discuss the role played by each growth factor in therapeutic approaches so as to stimulate further therapeutic thinking.
基金supported by the Hainan Province Science and Technology Special Fund(Nos.ZDYF2021SHFZ219,ZDYF2022SHFZ288)National Natural Science Foundation of China(Nos.21961010,22264013,22204037)+3 种基金Hainan Provincial Natural Science Foundation of China(No.822RC831)Natural Science Research Talent Project of Hainan Medical University(No.JBGS202101)Project for Functional Materials and Molecular Imaging Science Innovation Group of Hainan Medical UniversityHainan Province Clinical Medical Center(2021).
文摘Nasopharyngeal carcinoma(NPC),a malignant tumor originating from the nasopharynx,is one of the common malignant tumors of the head and neck.There are significant geographical differences in the incidence of nasopharyngeal carcinoma,with a high incidence in China and Southeast Asian countries.Herein,we designed and synthesized a novel near-infrared fluorescent(NIRF)probe to detect glutathione(GSH)in cellular and tumor environments using semi-naphthofluorescein(SNAFL)as the fluorescent molecular backbone and 2-fluoro-4-nitrobenzenesulfonate as the recognition moiety.Upon reaction with GSH,SNAFL-GSH emitted a fluorescence signal,and its emission wavelength at 650 nm was remarkably enhanced.The results of selectivity experiments indicated that SNAFL-GSH was able to discriminate GSH from Cys,Hcy,and H_(2) S.Moreover,SNAFL-GSH could image both endogenous and exogenous GSH and distinguish normal and cancer cells by fluorescence signal difference.At the cellular level,cisplatin(DDP)-induced ferroptosis and inhibition of proliferation of various NPC cell lines(CNE2,CNE1,5-8F cells)by erastin combined with DDP were visualized with the help of SNAFL-GSH.In a mouse tumor xenograft model,we successfully employed SNAFL-GSH for the evaluation of the efficacy of erastin combined with DDP in the treatment of NPC.More importantly,the probe could image cancerous tissue sections from NPC patients with an imaging depth of approximately 80µm.It was foreseen that SNAFL-GSH offered great potential for application in the diagnosis and evaluation of the therapeutic efficacy of NPC,and these results would also provide new ideas for the clinical treatment of NPC.
基金funded by the Hainan Provincial Joint Project of Sanya Yazhou Bay Science and Technology City(No.820LH027)the Hainan Provincial Natural Science Foundation of China(No.823RC472)+1 种基金the Open Project Program of Wuhan National Laboratory for Optoelectronics(No.2021WNLOKF008)the Hainan University Scientific Research Foundation(KYQD(ZR)19107).
文摘Monomethyl auristatin E(MMAE)is a derivative of the marine peptide Dolastatin 10,which has therapeutic effects against various cancers according to its antimitotic activity in multiple clinical trials.The antibody drug conjugate(ADC)of MMAE is currently used in clinical practice.However,the safety issues of MMAE-based ADC,such as high drug toxicity and poor bioavailability,still exist when using it for anticancer therapy.A sustained release of drug delivery approach should be used to reduce toxicity and achieve sufficient anticancer effects.Herein,PLGA-b-PEG 2000 with excellent biocompatibility and slow degradation ability was adopted to construct MMAE-loaded nanoparticles for safe and effective chemotherapy.The sustained release effect and the immunogenic cell death(ICD)effect of PLGA-MMAE nanoparticles were assessed by in vitro experiments.The PLGA-MMAE nanoparticles effectively accumulated in the tumor through the enhanced permeability and retention(EPR)effect,inducing cell apoptosis and causing a certain degree of immune response.The sustained drug release of PLGA-MMAE improved the bioavailability and effectively reduced the toxicity and development of the tumor compared to the effect of free MMAE or ADC.Overall,this study provides a safe and effective chemotherapeutic approach,as well as a simple and effective synthetic process for MMAE-based nanoparticles,improving their therapeutic efficacy and safety.
基金funded by the Hainan Provincial Joint Project of Sanya Yazhou Bay Science and Technology City(No.820LH027)the Hainan Provincial Natural Science Foundation of China(No.823RC472)+4 种基金the Open Project Program of Wuhan National Laboratory for Optoelectronics(No.2021WNLOKF008)the Hainan University Scientific Research Foundation(No.KYQD(ZR)19107)Natural Science Research Talent Project of Hainan Medical University(No.JBGS202101)Hainan Province Clinical Medical Center(2021)Project for Functional Materials and Molecular Imaging Science Innovation Group of Hainan Medical University。
文摘Triphenylamine(TPA)-based aggregation-induced emission luminogens(TPA-AIEgens),a type of photoactive material utilizing the typical TPA moiety,has recently attracted increasing attention for the diagnostics and treatment of tumors due to their remarkable chemo-physical performance in optoelectronic research.TPA-AIEgens are distinguished from other photoactive agents by their strong fluorescence,good sensitivity,high signal-to-noise ratio,resistance to photobleaching,and lack of high concentration or aggregation-caused fluoresce quenching effects.In this review,we summarize the current advancements and the biomedical progress of TPA-AIEgens in tumor theranostics.First,the design principles of TPAAIEgens photoactive agents as well as the advanced targeting strategies for nuclei,cell membranes,cell organelle and tumors were introduced,respectively.Next,the applications of TPA-AIEgens in tumor diagnosis and therapeutic techniques were reviewed.Last,the challenges and prospects of TPA-AIEgens for cancer therapy were performed.The given landscape of the TPA-AIEgens hereby is meaningful for the further design and utilization of the novel photoactive material,which could be beneficial for the development of clinic applications.
基金supported by grants from Hainan Provincial Natural Science Foundation of China(821RC557,2019RC232)National Natural Science Foundation of China(81871611,82160647)+1 种基金Finance Science and Technology Program of Sichuan Province(2022YFS0602)Hainan Clinical Medical Research Center Project(LCYX202310)。
文摘BACKGROUND:Several observational studies have shown an association between homocysteine(Hcy)levels and chronic obstructive pulmonary disease(COPD),but causal relationships are not clear.Our study aimed to explore the causal relationship between plasma Hcy and COPD by two-sample Mendelian randomization(MR).METHODS:A two-sample MR study was performed to infer the causal link.Genetically predicted plasma Hcy was selected as an instrumental variable(Ⅳ)from published genome-wide association study(GWAS)meta-analyses.COPD with different etiologies was extracted as outcome variables from other GWAS meta-analyses.The main MR analysis was performed using the inversevariance weighted(IVW)method.Additional analyses were further performed using Cochran’s Q-test and MR-Egger regression to evaluate the heterogeneity or horizontal pleiotropy of our findings.RESULTS:MR analysis showed no significant association between plasma Hcy and COPD.The results of the groups were consistent with the sensitivity analysis and repeated analysis,without heterogeneity or horizontal pleiotropy.The IVW results showed COPD hospital admissions(odds ratio[OR]1.06,95%confidence interval[CI]0.91-1.24,P=0.42),asthma/COPD(OR 0.97,95%CI0.89-1.06,P=0.55),COPD-related chronic infection(OR 1.50,95%CI 0.57-3.99,P=0.41),COPDI asthma/interstitial lung disease(ILD)-related pneumonia or pneumonia-derived septicemia(OR 0.93,95%CI 0.86-1.02,P=0.13),and COPD-related respiratory insufficiency(OR 1.00,95%CI 0.7-1.44,P=0.99).CONCLUSION:There is no direct causal relationship between plasma Hcy and COPD in our study.As Hcy is known to have deleterious effects on endothelial function and vascular homeostasis,further studies are needed to investigate whether additional factors mediate the association between Hcy and COPD.
基金supported by the Key Laboratory of Emergency and Trauma (Hainan Medical University),Ministry of Education (KLET-202202)。
文摘BACKGROUND:The ion shift index(ISI) as a prognostic indicator that can show the severity of hypoxic-ischemic injury.We aimed to evaluate the performance of the ISI in predicting unfavorable neurological outcomes at hospital discharge in cardiac arrest(CA) patients following extracorporeal cardiopulmonary resuscitation(ECPR) and to compare its performance to other prognostic predictors.METHODS:This was a retrospective observational study including adult CA patients treated with ECPR between January 2018 and December 2022 in a tertiary hospital.Data regarding clinical characteristics and laboratory parameters were collected from medical records.The ISI was determined based on the first available serum electrolyte levels after ECPR.The primary outcome was unfavorable neurological status at hospital discharge,defined as Cerebral Performance Categories 3–5.Comparisons of the characteristics between the two groups were made using the χ2 test for categorical variables and the t-test or non-parametric Mann-Whitney U-test for continuous variables,as appropriate.Correlation analysis was performed using Spearman’s rank correlation coeficient.A two-tailed P-value <0.05 was considered statistically significant.RESULTS:Among the 122 patients involved,46(37.7%) had out-of-hospital CA,and 88 had unfavorable neurological outcomes.The ISI was significantly higher in the unfavorable outcome group than in the favorable outcome group(3.74 [3.15–4.57] vs.2.69 [2.51–3.07],P<0.001).A higher ISI level was independently related to unfavorable outcome(odds ratio=6.529,95% confidence interval 2.239–19.044,P=0.001).An ISI level >3.12 predicted unfavorable outcomes with a sensitivity and specificity of 74.6% and 85.2%,respectively(P<0.001).The prognostic performance of ISI(area under the curve [AUC]=0.887) was similar to that of other predictors,such as gray-to-white matter ratio(AUC=0.850,P=0.433) and neuronspecific enolase(AUC=0.925,P=0.394).CONCLUSION:ISI may be used as a prognostic biomarker to predict neurological outcomes in
基金This work was supported by grants from the National Natural Science Foundation of China(No.81971891,No.82172196,No.81772134 and No.81571939)Key Laboratory of Emergency and Trauma(Hainan Medical University)of Ministry of Education(No.KLET-202108)the College Students’Innovation and Entrepreneurship Project(No.S20210026020013).
文摘Ischemic stroke is a serious cerebrovascular disease with high morbidity and mortality.As a result of ischemia-reperfusion,a cascade of pathophysiological responses is triggered by the imbalance in metabolic supply and demand,resulting in cell loss.These cellular injuries follow various molecular mechanisms solely or in combination with this disorder.Mitochondria play a driving role in the pathophysiological processes of ischemic stroke.Once ischemic stroke occurs,damaged cells would respond to such stress through mitophagy.Mitophagy is known as a conservatively selective autophagy,contributing to the removal of excessive protein aggregates and damaged intracellular components,as well as aging mitochondria.Moderate mitophagy may exert neuroprotection against stroke.Several pathways associated with the mitochondrial network collectively contribute to recovering the homeostasis of the neurovascular unit.However,excessive mitophagy would also promote ischemia-reperfusion injury.Therefore,mitophagy is a double-edged sword,which suggests that maximizing the benefits of mitophagy is one of the direction of future efforts.This review emphasized the role of mitophagy in ischemic stroke,and highlighted the crosstalk between mitophagy and apoptosis/necroptosis.
基金supported by National Natural Science Foundation of China(No.81960351)High-level Talent Fund of Hainan Province(No.822RC835).
文摘Acute lung injury is featured as diffuse pulmonary edema and persistent hypoxemia caused by lung or systemic injury.It is believed that these pathological changes are associated with damage to the alveolar epithelium and vascular endothelium,recruitment of inflammatory cells,and inflammatory factor storms.In recent years,the metabolic reprogramming of lung parenchymal cells and immune cells,particularly alterations in glycolysis,has been found to occur in acute lung injury.Inhibition of glycolysis can reduce the severity of acute lung injury.Thus,this review focuses on the interconnection between acute lung injury and glycolysis and the mechanisms of interaction,which may bring hope for the treatment of acute lung injury.
基金National Natural Science Foundation of China (No.82060357)Hainan Natural Science Foundation (No.2019RC370,820RC757)Research Project of Hainan Provincial Health Commission (No.20A200021)。
文摘Objective:To explore the possible mechanism of neutrophil exosomes regulating macrophage apoptosis.Methods:neutrophils were induced by lipopolysaccharide,inflammatory factors were detected by ELISA,the morphology of exosomes was identified by electron microscope,and the expression of mir-15a-5p in exosomes was detected by RT-PCR;Raw267.4 macrophages was treated with neutrophil exosomes and mir-15a-5p mimic respectively,CCK8 to detect cell viability,flow cytometry to detect apoptosis;The binding sites of mir-15a-5p and BCL2L2 were predicted and verified by double luciferase experiment;RT-PCR and Western blot verified that mir-15a-5p regulate the expression of BCL2L2.Results:lipopolysaccharide induced neutrophil inflammatory factors IL-2,IL-6,IL-10 and TNF-α.The morphological characteristics of exosomes were observed by electron microscope.Mir-15a-5p was significantly overexpressed in neutrophil exosomes induced by lipopolysaccharide;Lipopolysaccharide-induced neutrophil exosomes and mir-15a-5p simulants can promote raw267.4 macrophage apoptosis and inhibit its cell viability;Targetscan database predicted that mir-15a-5p and BCL2L2 had binding sites.Double-luciferase experiment verified that mir-15a-5p and BCL2L2 bound through binding sites;Mir-15a-5p mimic was transfected into raw267.4 macrophages which inhibit the expression of BCL2L2 mRNA and protein.Conclusion:inflammatory neutrophils may promote raw267.4 by secreting exosomes containing mir-15a-5p and inhibiting BCL2L2 by targeting macrophage apoptosis.This may provide a theoretical basis for further understanding the molecular mechanism of inflammatory regulation of neutrophils and macrophages.
基金supported by grants-in-Aid for Scientifc research. No.30800220/C100201.from the National Natural Science Foundation of ChinaKey Project of Scientce and Technology Planning of Hainan Province(ZDXM20110051)
文摘Objective:To explore effect of calcium citrate on bone integration in a rabbit femur defect model, and to compare the bone formation with different sizes by radiological and histological study. Methods:Twenty-four male Japanese white rabbits were randomly divided into three groups (Group A.B.C)in this study.Under anesthesia,defects of four sizes(1.2,1.5,2.0 and 2.5 mm) were created in each of the rabbits.Commercially pure calcium citrate powder was placed inside the medullary compartment of the femur(Experimental),while in the contralateral femur(Control) nothing was implanted.The defects were analyzed using radiography and histological analysis by using Imagepro-Plus 6.0 software after animal was sacrificed at 4th(Group A),6th(Group B) and 8th(Group C) weeks postoperatively.Four samples were analyzed for each size of defect and each healing period.Results:The histological and the radiologic evaluation were performed after sacrification of all rabbits on postoperative 4th and 6th weeks,It showed significant difference between the experimental group and the control group when these defects were less than or equal to 2.0 mm.No statistical difference was observed when these defects were larger than 2.0 mm at all healing periods except at the 4th week.Conclusions:Calcium citrate affects the early periods of hone defects healing mechanism in Japanese white rabbits positively,especially when the defect is not too large,We suggest further studies on calcium citrate to determine the effects of various dosages,administration ways and the experimental time on the bone defects.
基金supported by Hainan Provincial Natural Science Foundation of China(821QN414,822RC845,821RC557)the Central Guidance on Local Science and Technology Development Fund of Hainan Province(ZY2021HN19)Hainan Clinical Medical Research Center Project(LCYX202205).
文摘BACKGROUND:We aimed to examine prospective associations between diff erent intensities and diff erent types of physical activity(PA)in early pregnancy and hypertensive disorders of pregnancy(HDP)among Chinese women.METHODS:A total of 6,820 pregnant women from the Tongji-Shuangliu Birth Cohort were included in this study.The pregnancy physical activity questionnaire(PPAQ)was used to assess PA,including household/caregiving,occupational,sports/exercise,and transportation activities in the first trimester of pregnancy.The diagnosis of HDP was collected,including gestational hypertension(GH)and preeclampsia(PE).Data were analyzed by unconditional multivariate logistic regression,and the odds ratio(OR)and 95%confi dence interval(CI)were calculated.RESULTS:A total of 178(2.6%)of the 6,820 women were diagnosed with HDP,of which 126(1.8%)were GH and 52(0.8%)were PE.Overall,we found no association between PA in early pregnancy and PE.A trend toward lower risk was found only among women with GH and among those with higher levels of moderate-to-vigorous intensity physical activity(MVPA)(adjusted OR 0.54,95%CI 0.31–0.96).No association was observed between PA and HDP in early pregnancy,regardless of diff erent intensities or types of PA.CONCLUSION:MVPA in the first trimester is an influencing factor of HDP.Encouraging pregnant women to engage in MVPA in the fi rst trimester may help to prevent GH.
基金supported by grants from the Hunan Province Academic Degree and Graduate Education Reform Project(No.2020JGYB028)the National Natural Science Foundation of China(No.81971891,No.82172196,No.81772134)+1 种基金the Key Laboratory of Emergency and Trauma(Hainan Medical University)of the Ministry of Education(No.KLET-202108)the College Students'Innovation and Entrepreneurship Project(No.S20210026020013).
文摘Objective:The integration of training in theory and practice across the medical education spectrum is being encouraged to increase student understanding and skills in the sciences.This study aimed to determine the deciding factors that drive students'perceived advantages in class to improve precision education and the teaching model.Methods:A mixed strategy of an existing flipped classroom(FC)and a case-based learning(CBL)model was conducted in a medical morphology curriculum for 575 postgraduate students.The subjective learning evaluation of the individuals(learning time,engagement,study interest and concentration,and professional integration)was collected and analyzed after FC-CBL model learning.Results:The results from the general evaluation showed promising results of the medical morphology in the FC-CBL model.Students felt more engaged by instructors in person and benefited in terms of time-saving,flexible arrangements,and professional improvement.Our study contributed to the FC-CBL model in Research Design in postgraduate training in 4 categories:1)advancing a guideline of precision teaching according to individual characteristics;2)revealing whether a learning background is needed for a Research Design course to guide setting up a preliminary course;3)understanding the perceived advantages and their interfaces;and 4)barriers and/or improvement to implement the FC-CBL model in the Research Design class,such as a richer description of e-learning and hands-on practice.Conclusion:Undertaking a FC-CBL combined model could be a useful addition to pedagogy for medical morphology learning in postgraduate training.
基金The trauma registry project was supported financially by the Health Partnership Scheme funded by the Tropical Health and Education Trust(THET)funded by the UK Department for International Development(DFID)
文摘BACKGROUND: Less attention is directed toward gaining a better understanding of the burden and prevention of injuries, in low and middle income countries(LMICs). We report the establishment of a trauma registry at the Adult Emergency and Trauma Centre(AETC) at Queen Elizabeth Central Hospital(QECH) in Blantyre, Malawi and identify high risk geographic areas. METHODS: We devised a paper based two-page trauma registry form. Ten data clerks and all AETC clinicians were trained to complete demographic and clinical details respectively. Descriptive data, regression and hotspot analyses were done using STATA 15 statistical package and ArcGIS(16) software respectively.RESULTS: There were 3,747 patients from May 2013 to May 2015. The most common mechanisms of injury were assault(38.2%), and road traffi c injuries(31.6%). The majority had soft tissue injury(53.1%), while 23.8% had no diagnosis indicated. Fractures(OR 19.94 [15.34–25.93]), head injury and internal organ injury(OR 29.5 [16.29–53.4]), and use of ambulance(OR 1.57 [1.06–2.33]) were found to be predictive of increased odds of being admitted to hospital while assault(OR 0.69 [0.52–0.91]) was found to be associated with less odds of being admitted to hospital. Hot spot analysis showed that at 99% confidence interval, Ndirande, Mbayani and Limbe were the top hot spots for injury occurrence. CONCLUSION: We have described the process of establishing an integrated and potentially sustainable trauma registry. Signifi cant data were captured to provide details on the epidemiology of trauma and insight on how care could be improved at AETC and surrounding health facilities. This approach may be relevant in similar poor resource settings.
基金supported by grants from the National Natural Science Foundation of China(8140130969and 8176130232)Hainan Provincial Science and Technology Major Project(ZDKJ201804,China).
文摘Sepsis is an infection-induced systemic inflammatory syndrome.The immune response in sepsis is characterized by the activation of both proinflammatory and anti-inflammatory pathways.When sepsis occurs,the expression and activity of many inflammatory cytokines are markedly affected.Xenobiotic receptors are chemical-sensing transcription factors that play essential roles in the transcriptional regulation of drug-metabolizing enzymes(DMEs).Xenobiotic receptors mediate the functional crosstalk between sepsis and drug metabolism because the inflammatory cytokines released during sepsis can affect the expression and activity of xenobiotic receptors and thus impact the expression and activity of DMEs.Xenobiotic receptors in turn may affect the clinical outcomes of sepsis.Thisreview focuses on the sepsis-induced inflammatory response and xenobiotic receptors such as pregnane X receptor(PXR),aryl hydrocarbon receptor(AHR),glucocorticoid receptor(GR),and constitutive androstane receptor(CAR),DMEs such as CYP1A,CYP2B6,CYP2C9,and CYP3A4,and drug transporters such as p-glycoprotein(P-gp),and multidrug resistance-associated protein(MRPs)that are affected by sepsis.Understanding the xenobiotic receptor-mediated effect of sepsis on drug metabolism will help to improve the safe use of drugs in sepsis patients and the development of new xenobiotic receptor-based therapeutic strategies for sepsis.
基金Hainan Innovation Team Project of Hainan(820CXTD448)Hainan Province Key R&D Program International Science and Technology Cooperation Project(GHYF2022011)+8 种基金Key R&D Projects in Hainan ProvincZDYF2020223Hainan Provincial Major Science and Technology Project(ZDKJ2021036)Hainan Provincial Natural Science Foundation of High-level Talent Project 2019RC212Chinese Academy of Medical Sciences Medical and Health Science and Technology Innovation Engineering Project(2019-12M-5-023)Major Science and Technology Project of Hainan Province(ZDKJ2021039,ZDKJ202004)Key Topics of Hainan Medical College's Educational and Scientific Research Projects(HYZD202111)National Natural Science Foundation of China(81860001,82011530049 and 82160012)Open Project of the Key Laboratory of Tropical Disease Prevention and Control of the NHC(2021NHCTDCKFKT21008)Hainan Provincial Clinical Medical Center Construction Project Fund。
文摘With the influence of many factors such as the aging of the population,the younger smokers,and the serious air pollution,the incidence of chronic respiratory diseases is increasing year by year.In the treatment of respiratory diseases,clinical intervention is still mainly based on drug control of pulmonary symptoms.However,systemic drugs have disadvantages such as many adverse reactions and severe systemic side effects.In recent years,the research and development of local drug delivery systems for the respiratory tract has brought new changes to the treatment of respiratory diseases.Locally delivered drugs can directly act on the airways and have the characteristics of fast onset,good curative effect and small side effects.It is a simple,efficient and safe treatment method,which has a very significant effect,and has become a hot topic of current research and promotion.This paper briefly reviews the development track and latest research progress of respiratory local drug delivery systems at home and abroad,in order to provide reference for clinical workers in drug selection and application.
基金This study was supported by Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences(2019-I2M-5-023)Hainan Provincial Science and Technology Major Project(ZDKJ201804)+2 种基金National Natural Science Foundation of China(81871611)National Natural Science Foundation of China(81760352)Project of Hainan Provincial Department of Education(Hnjg2019ZD-16).
文摘1.Introduction Sudden cardiac death(SCD)refers to sudden death due to a variety of cardiac causes.It is manifested as a sudden loss of consciousness,cardiac arrest,and respiratory arrest and generally shows early symptoms that are atypical and not easily detected[1].According to a recent study,nearly 544?000 patients suffer from SCD every year in China[2].Rescue of SCD patients in the shortest time is important as the survival rate will decrease by 7%-10%if the rescue is delayed for one minute[3].However,SCD mostly occurs in public places outside the hospital,including public sports places,transportation hubs(such as airports,railway stations,and subway stations),shopping centers,factories,and so on.Therefore,out-of-hospital cardiac arrest(OHCA)is a huge threat to people's lives."Chain of survival"proposed by the American Heart Association in 2015 emphasized the importance of early call for help,rapid implementation of high-quality cardiopulmonary resuscitation(CPR),and immediate use of an automated external defibrillator(AED)in improving the survival rate of OHCA patients.Studies have shown that conducting CPR within 1 min and AEDs defibrillation within 3 to 5 min can achieve a 50%to 70%survival rate for cardiac arrest patients[4].Therefore,early defibrillation of OHCA patients will markedly increase the survival rate.
基金the NSFC (81503152,81622047,81473334 and 81503201),distinguished professor of Liaoning Provincesponsored by Liaoning BaiQianWan Talents Program Innovationthe National Key Research and Development Program of China (2017YFC1700200) for financial support
文摘Human cytosolic sulfotransferase 2 A1(SULT2A1) is an important phase II metabolic enzyme. The detection of SULT2A1 is helpful for the functional characterization of SULT2A1 and diagnosis of its related diseases. However, due to the overlapping substrate specificity among members of the sulfotransferase family, it is difficult to develop a probe substrate for selective detection of SULT2A1. In the present study, through characterization of the sulfation of series of bufadienolides, arenobufagin(AB) was proved as a potential probe substrate for SULT2A1 with high sensitivity and specificity. Subsequently, the sulfation of AB was characterized by experimental and molecular docking studies. The sulfate-conjugated metabolite was identified as AB-3-sulfate.The sulfation of AB displayed a high selectivity for SULT2A1 which was confirmed by in vitro reaction phenotyping assays. The sulfation of AB by human liver cytosols and recombinant SULT2A1 both obeyed Michaelis-Menten kinetics, with similar kinetic parameters. Molecular docking was performed to understand the interaction between AB and SULT2A1, in which the lack of interaction with Met-137 and Tyr-238 of SULT2A1 made it possible to eliminate substrate inhibition of AB sulfation. Finally, the probe was successfully used to determine the activity of SULT2A1 and its isoenzymes in tissue preparations of human and laboratory animals.
