<span style="font-family:Verdana;">Enzalutamide is a hormonal therapy that blocks the action of androgens, such as testosterone in the treatment of metastatic castration-resistant prostate cancer. <...<span style="font-family:Verdana;">Enzalutamide is a hormonal therapy that blocks the action of androgens, such as testosterone in the treatment of metastatic castration-resistant prostate cancer. </span><span style="font-family:Verdana;">Stevens-Johnson syndrome and toxic epidermal necrolysis (SJS/TEN) overlap and are part of an adverse drug reaction continuum of disease, in which there is a 10% - 30% involvement of the skin surface with mucositis, blisters, skin slough, and a macular rash. A 66-year-old male was treated with enzalutamide for metastatic prostate cancer and developed SJS/TEN overlap with 25% total body surface area skin involvement. The patient received a </span><span style="font-family:Verdana;">seven-day course of cyclosporine to which he responded by re-epithelialization </span><span style="font-family:Verdana;">but succumbed to multi-organ failure. While SJS/TEN has been reported with apalutamide, to our knowledge, this is the first case of SJS/TEN overlap with enzalutamide.</span>展开更多
Johns Hopkins University School of Medicine (JHUSOM) has been a leader in medical education since its inception in 1893. The influence of John Dewey on the founders of the school is evident in the design of the curri...Johns Hopkins University School of Medicine (JHUSOM) has been a leader in medical education since its inception in 1893. The influence of John Dewey on the founders of the school is evident in the design of the curriculum,which included serious study of basic science for two years,followed by 'learning by doing' in the 3d and 4th clinical years. After the Flexner report in 1910 which lauded the school as an exemplary model,this became the standard curricular structure of undergraduate medical education in the US. Since its founding Hopkins,like other medical schools,has struggled with burgeoning biomedical knowledge and the tension between time and content. The last curricular revision was implemented in 1992,and had several themes,including:(1) decreased lecture time and increased small group learning; (2) early clinical experience and more ambulatory clinical experience; (3) integration of the basic sciences to improve learning and reduce redundancy; (4) development of a longitudinal course for the social sciences,(named 'The Physician and Society' course); (5) a required thesis project for graduation. All but the last were implemented. Our students have done well in this curriculum. 98-100% pass the licensing board exams,and over 90% obtain their first choice for residency positions,often in highly competitive programs such as Dermatology,Neurosurgery and Ophthalmology. Approximately 30% of graduates are listed in the AAMC faculty roster-one of the highest percentages of graduates going to academic medicine in the country.展开更多
The Retrovirus Epidemiology Donor Study (REDS) was established in 1989 with funding from the National Heart,Lung,and Blood Institute ( NHLBI ) of the National Institutes of Health in the United States.The initial prog...The Retrovirus Epidemiology Donor Study (REDS) was established in 1989 with funding from the National Heart,Lung,and Blood Institute ( NHLBI ) of the National Institutes of Health in the United States.The initial program coordinated activities in five large US blood centers in San Francisco,Los Angeles,Oklahoma City,Detroit,and Baltimore with a coordinating center Westat in Rockville MD.展开更多
Glaucoma service of Johns Hopkins University is currently involved in a range of research projects.This overview will cover the major clinical activities currently underway.
Narrative medicine is a multidisciplinary field of inquiry and practice based on the premise that medical care takes place in the context of stories.Research on narrative medicine training suggests that it conveys ben...Narrative medicine is a multidisciplinary field of inquiry and practice based on the premise that medical care takes place in the context of stories.Research on narrative medicine training suggests that it conveys benefits such as improved communication skills and personal and professional growth to physicians,medical students,and other health care providers.Narrative medicine can promote empathy and trust between patients and physicians and foster self-care.In 2014,the author and a colleague started an ongoing inter-disciplinary narrative medicine program in the Children’s Center of the Johns Hopkins Hospital called AfterWards.The program,which meets monthly,is open to all on a volunteer basis.Through literature,art,and writing,AfterWards nurtures empathy,encourages reflective practice,and builds community among a diverse group of health care providers.Through a series of lectures and workshops at Johns Hopkins Medicine,Peking Union Medical College,and Fudan Hospital in Shanghai,the author has introduced AfterWards to Chinese medical educators and clinicians.Working with Dr.Marta Hanson,she created an AfterWards Facilitator’s Guide for the use of Chinese practitioners.A recent White Paper on Chinese health care indicates that an infusion of humanities-based education,of which narrative medicine forms a part,can help rebuild patient-physician trust.Recently,there has been an increase in interest in narrative medicine in the United States and China.However,more research is needed to demonstrate the impact of programs like AfterWards.Challenges to the implementation of narrative medicine programs remain,most significantly in terms of expertise,resources,and time.展开更多
Neurons are highly polarized,morphologically asymmetric,and functionally compartmentalized cells that contain long axons extending from the cell body.For this reason,their maintenance relies on spatiotemporal regulati...Neurons are highly polarized,morphologically asymmetric,and functionally compartmentalized cells that contain long axons extending from the cell body.For this reason,their maintenance relies on spatiotemporal regulation of organelle distribution between the somatodendritic and axonal domains.Although some organelles,such as mitochondria and smooth endoplasmic reticulum,are widely distributed throughout the neuron,others are segregated to either the somatodendritic or axonal compartment.For example,Golgi outposts and acidified lysosomes are predominantly present in the somatodendritic domain and rarely distributed along the axon,whereas newly formed autophagosomes and synaptic vesicles are mainly distributed in the distal axon(Britt et al.,2016).展开更多
Human dental pulp stem cell transplantation has been shown to be an effective therapeutic strategy for spinal cord injury.However,whether the human dental pulp stem cell secretome can contribute to functional recovery...Human dental pulp stem cell transplantation has been shown to be an effective therapeutic strategy for spinal cord injury.However,whether the human dental pulp stem cell secretome can contribute to functional recovery after spinal cord injury remains unclear.In the present study,we established a rat model of spinal cord injury based on impact injury from a dropped weight and then intraperitoneally injected the rats with conditioned medium from human dental pulp stem cells.We found that the conditioned medium effectively promoted the recovery of sensory and motor functions in rats with spinal cord injury,decreased expression of the microglial pyroptosis markers NLRP3,GSDMD,caspase-1,and interleukin-1β,promoted axonal and myelin regeneration,and inhibited the formation of glial scars.In addition,in a lipopolysaccharide-induced BV2 microglia model,conditioned medium from human dental pulp stem cells protected cells from pyroptosis by inhibiting the NLRP3/caspase-1/interleukin-1βpathway.These results indicate that conditioned medium from human dental pulp stem cells can reduce microglial pyroptosis by inhibiting the NLRP3/caspase-1/interleukin-1βpathway,thereby promoting the recovery of neurological function after spinal cord injury.Therefore,conditioned medium from human dental pulp stem cells may become an alternative therapy for spinal cord injury.展开更多
Brain tissue requires high amounts of copper(Cu)for its key physiological processes,such as energy production,neurotransmitter synthesis,maturation of neuropeptides,myelination,synaptic plasticity,and radical scavengi...Brain tissue requires high amounts of copper(Cu)for its key physiological processes,such as energy production,neurotransmitter synthesis,maturation of neuropeptides,myelination,synaptic plasticity,and radical scavenging.The requirements for Cu in the brain vary depending on specific brain regions,cell types,organism age,and nutritional status.Cu imbalances cause or contribute to several life-threatening neurologic disorders including Menkes disease,Wilson disease,Alzheimer’s disease,Parkinson’s disease,and others.Despite the well-established role of Cu homeostasis in brain development and function,the mechanisms that govern Cu delivery to the brain are not well defined.This review summarizes available information on Cu transfer through the brain barriers and discusses issues that require further research.展开更多
Neuroinflammation exacerbates secondary damage after spinal cord injury,while microglia/macrophage pyroptosis is important to neuroinflammation.Circular RNAs(circRNAs)play a role in the central nervous system.However,...Neuroinflammation exacerbates secondary damage after spinal cord injury,while microglia/macrophage pyroptosis is important to neuroinflammation.Circular RNAs(circRNAs)play a role in the central nervous system.However,the functional role and mechanism of circRNAs in regulating microglia/macrophage pyroptosis after spinal cord injury are still poorly studied.In the present study,we detected microglia/macrophage pyroptosis in a female rat model of spinal cord injury,along with upregulated levels of circ0000381 in the spinal cord.Our further experimental results suggest that circ0000381 may function as a sponge to sequester endogenous microRNA423-3p(miR-423-3p),which can increase the expression of NOD-like receptor 3(NLRP3),a pyroptosis marker.Therefore,upregulation of circ0000381 may be a compensatory change after spinal cord injury to attenuate microglia/macrophage pyroptosis.Indeed,knockdown of circ0000381 expression exacerbated microglia/macrophage pyroptosis.Collectively,our findings provide novel evidence for the upregulation of circ0000381,which may serve as a neuroprotective mechanism to attenuate microglia/macrophage pyroptosis after spinal cord injury.Accordingly,circ0000381 may be a novel therapeutic target for the treatment of spinal cord injury.展开更多
Bone is a mechanosensitive tissue and undergoes constant remodeling to adapt to the mechanical loading environment.However,it is unclear whether the signals of bone cells in response to mechanical stress are processed...Bone is a mechanosensitive tissue and undergoes constant remodeling to adapt to the mechanical loading environment.However,it is unclear whether the signals of bone cells in response to mechanical stress are processed and interpreted in the brain.In this study,we found that the hypothalamus of the brain regulates bone remodeling and structure by perceiving bone prostaglandin E2(PGE2)concentration in response to mechanical loading.Bone PGE2 levels are in proportion to their weight bearing.When weight bearing changes in the tail-suspension mice,the PGE2 concentrations in bones change in line with their weight bearing changes.Deletion of cyclooxygenase-2(COX2)in the osteoblast lineage cells or knockout of receptor 4(EP4)in sensory nerve blunts bone formation in response to mechanical loading.Moreover,knockout of TrkA in sensory nerve also significantly reduces mechanical load-induced bone formation.Moreover,mechanical loading induces cAMP-response element binding protein(CREB)phosphorylation in the hypothalamic arcuate nucleus(ARC)to inhibit sympathetic tyrosine hydroxylase(TH)expression in the paraventricular nucleus(PVN)for osteogenesis.Finally,we show that elevated PGE2 is associated with ankle osteoarthritis(AOA)and pain.Together,our data demonstrate that in response to mechanical loading,skeletal interoception occurs in the form of hypothalamic processing of PGE2-driven peripheral signaling to maintain physiologic bone homeostasis,while chronically elevated PGE2 can be sensed as pain during AOA and implication of potential treatment.展开更多
Neurological disorders are a diverse group of conditions that affect the nervous system and include neurodegenerative diseases(Alzheimer’s disease,multiple sclerosis,Parkinson’s disease,Huntington’s disease),cerebr...Neurological disorders are a diverse group of conditions that affect the nervous system and include neurodegenerative diseases(Alzheimer’s disease,multiple sclerosis,Parkinson’s disease,Huntington’s disease),cerebrovascular conditions(stroke),and neurodevelopmental disorders(autism spectrum disorder).Although they affect millions of individuals around the world,only a limited number of effective treatment options are available today.Since most neurological disorders express mitochondria-related metabolic perturbations,metformin,a biguanide type II antidiabetic drug,has attracted a lot of attention to be repurposed to treat neurological disorders by correcting their perturbed energy metabolism.However,controversial research emerges regarding the beneficial/detrimental effects of metformin on these neurological disorders.Given that most neurological disorders have complex etiology in their pathophysiology and are influenced by various risk factors such as aging,lifestyle,genetics,and environment,it is important to identify perturbed molecular functions that can be targeted by metformin in these neurological disorders.These molecules can then be used as biomarkers to stratify subpopulations of patients who show distinct molecular/pathological properties and can respond to metformin treatment,ultimately developing targeted therapy.In this review,we will discuss mitochondria-related metabolic perturbations and impaired molecular pathways in these neurological disorders and how these can be used as biomarkers to guide metformin-responsive treatment for the targeted therapy to treat neurological disorders.展开更多
Over the past decade,medical researchers in China have debated whether the Pi(脾)corresponds to the biomedical spleen or pancreas.This debate exemplifies a broader phenomenon of“anatomical retrofitting”,or the anach...Over the past decade,medical researchers in China have debated whether the Pi(脾)corresponds to the biomedical spleen or pancreas.This debate exemplifies a broader phenomenon of“anatomical retrofitting”,or the anachronistic imposition of contemporary categories onto living historical objects.“Anatomical retrofitting”as a means of rectifying cases of mistranslation further positions the biomedical spleen and pancreas as representing ahistorical,universal truths.This framework gives rise to a conceptual binary:while the biomedical spleen is universalized as what philosophers may describe as“logical”ontology,the Pi connects to a different nature of reality,or“metaphysical”ontology.Far from being an object of imprecision,the Pi was a dynamic vessel that also shared characteristics with the humoral spleen.Given that scholars in China have already subjected Pi to historical scrutiny,this paper urges scholars to do the same with biomedical anatomy.For instance,historically situating the humoral spleen demonstrates that it became less known and less articulated as it transformed into the biomedical spleen.Meanwhile,the pancreas remained an unstable epistemic object that took on the dynamic functions of the humoral spleen in nineteenth-century organotherapy.Through primary source analysis and literature review,this paper contends that the apparent ontological incommensurability between Pi and spleen is neither mutually exclusive nor irreconcilable.Instead,the dynamic nature of internal viscera,their many functions,and their participation in epistemic practices contribute to an ongoing ontological ambivalence that persists despite the forced certainty of anatomical retrofitting.展开更多
To determine the cause(s)of perturbations seen in dayside equatorial ground magnetograms,we conducted a systematic survey of simultaneous ground-based and geosynchronous satellite-based observations during the 90-day ...To determine the cause(s)of perturbations seen in dayside equatorial ground magnetograms,we conducted a systematic survey of simultaneous ground-based and geosynchronous satellite-based observations during the 90-day period from December 1,2020 to February 28,2021.We examined Huancayo ground magnetometer observations from 14:00:00 to 20:00:00 UT each day,during which Huancayo passed through local noon.From those data we chose perturbation events selected on the basis of large(>20 nT)event amplitude and classified the selected events as responding primarily to solar wind pressure,or to variations in the north/south component of the interplanetary magnetic field(IMF Bz),or perhaps in part to both.The results show that an equivalent number of events were identified for each model during this 90-day period.Variations in the lagged solar wind dynamic pressure routinely correspond to nearly simultaneous sudden impulses recorded at both geosynchronous orbit and on the ground.Variations in IMF Bz produce erosion signatures at geosynchronous orbit and can correspond to ground events if lag times for reconnection to enhance convection in the magnetosphere are taken into account.展开更多
Background:Acute improvement in range of motion(ROM)is a widely reported effect of stretching and foam rolling,which is commonly explained by changes in pain threshold and/or musculotendinous stiffness.Interestingly,t...Background:Acute improvement in range of motion(ROM)is a widely reported effect of stretching and foam rolling,which is commonly explained by changes in pain threshold and/or musculotendinous stiffness.Interestingly,these effects were also reported in response to various other active and passive interventions that induce responses such as enhanced muscle temperature.Therefore,we hypothesized that acute ROM enhancements could be induced by a wide variety of interventions other than stretching or foam rolling that promote an increase in muscle temperature.Methods:After a systematic search in PubMed,Web of Science,and SPORTDiscus databases,38 studies comparing the effects of stretching and foam rolling with several other interventions on ROM and passive properties were included.These studies had 1134 participants in total,and the data analysis resulted in 140 effect sizes(ESs).ES calculations were performed using robust variance estimation model with R-package.Results:Study quality of the included studies was classified as fair(PEDro score=4.58)with low to moderate certainty of evidence.Results showed no significant differences in ROM(ES=0.01,p=0.88),stiffness(ES=0.09,p=0.67),or passive peak torque(ES=-0.30,p=0.14)between stretching or foam rolling and the other identified activities.Funnel plots revealed no publication bias.Conclusion:Based on current literature,our results challenge the established view on stretching and foam rolling as a recommended component of warm-up programs.The lack of significant difference between interventions suggests there is no need to emphasize stretching or foam rolling to induce acute ROM,passive peak torque increases,or stiffness reductions.展开更多
Prostate cancer poses a significant health challenge globally,demanding proactive prevention strategies.This editorial explores the emerging role of vitamin D in prostate cancer prevention.While traditionally associat...Prostate cancer poses a significant health challenge globally,demanding proactive prevention strategies.This editorial explores the emerging role of vitamin D in prostate cancer prevention.While traditionally associated with bone health,vitamin D is increasingly recognized for its broader impact on immune function,cellular signaling,and cancer prevention.Epidemiological studies suggest an intriguing link between vitamin D deficiency and elevated prostate cancer risk,particularly in regions with limited sunlight exposure.Mechanistically,vitamin D regulates cellular processes,inhibiting unchecked cancer cell growth and bols-tering immune surveillance.Personalized prevention strategies,considering individual factors,are deemed essential for harnessing the full potential of vitamin D.To unlock this potential,the future calls for robust research,public awareness campaigns,dietary improvements,and vigilant medical guidance.Collaborative efforts are poised to pave the way toward a future where vitamin D stands as a sentinel in prostate cancer prevention,ushering in hope and improved health for men worldwide.展开更多
The Lunar Environment heliospheric X-ray Imager(LEXI)and Solar wind Magnetosphere Ionosphere Link Explorer(SMILE)missions will image the Earth’s dayside magneto pause and cusps in soft X-rays after their respective l...The Lunar Environment heliospheric X-ray Imager(LEXI)and Solar wind Magnetosphere Ionosphere Link Explorer(SMILE)missions will image the Earth’s dayside magneto pause and cusps in soft X-rays after their respective launches in the near future,to specify glo bal magnetic reconnection modes for varying solar wind conditions.To suppo rt the success of these scientific missions,it is critical to develop techniques that extract the magnetopause locations from the observed soft X-ray images.In this research,we introduce a new geometric equation that calculates the subsolar magnetopause position(RS)from a satellite position,the look direction of the instrument,and the angle at which the X-ray emission is maximized.Two assumptions are used in this method:(1)The look direction where soft X-ray emissions are maximized lies tangent to the magnetopause,and(2)the magnetopause surface near the subsolar point is almost spherical and thus RSis nea rly equal to the radius of the magneto pause curvature.We create synthetic soft X-ray images by using the Open Geospace General Circulation Model(OpenGGCM)global magnetohydrodynamic model,the galactic background,the instrument point spread function,and Poisson noise.We then apply the fast Fourier transform and Gaussian low-pass filte rs to the synthetic images to re move noise and obtain accurate look angles for the soft X-ray pea ks.From the filte red images,we calculate RS and its accuracy for different LEXI locations,look directions,and solar wind densities by using the OpenGGCM subsolar magnetopause location as ground truth.Our method estimates RS with an accuracy of<0.3 RE when the solar wind density exceeds>10 cm-3.The accuracy improves for greater solar wind densities and during southward interplanetary magnetic fields.The method ca ptures the magnetopause motion during southwa rd interplaneta ry magnetic field turnings.Consequently,the technique will enable quantitative analysis of the magnetopause motion and help reveal the dayside reconnection modes for dynamic solar wind conditions.This technique will suppo rt the LEXI and SMILE missions in achieving their scientific o bjectives.展开更多
AIM:To explore the usage of choroidal thickness measured by swept-source optical coherence tomography(SS-OCT)to detect myopic macular degeneration(MMD)in high myopic participants.METHODS:Participants with bilateral hi...AIM:To explore the usage of choroidal thickness measured by swept-source optical coherence tomography(SS-OCT)to detect myopic macular degeneration(MMD)in high myopic participants.METHODS:Participants with bilateral high myopia(≤−6 diopters)were recruited from a subset of the Guangzhou Zhongshan Ophthalmic Center-Brien Holden Vision Institute High Myopia Cohort Study.SS-OCT was performed to determine the choroidal thickness,and myopic maculopathy was graded by the International Meta-Analysis for Pathologic Myopia(META-PM)Classification.Presence of MMD was defined as META-PM category 2 or above.RESULTS:A total of 568 right eyes were included for analysis.Eyes with MMD(n=106,18.7%)were found to have older age,longer axial lengths(AL),higher myopic spherical equivalents(SE),and reduced choroidal thickness in each Early Treatment Diabetic Retinopathy Study(ETDRS)grid sector(P<0.001).The area under the receiver operating characteristic(ROC)curves(AUC)for subfoveal choroidal thickness(0.907)was greater than that of the model,including age,AL,and SE at 0.6249,0.8208,and 0.8205,respectively.The choroidal thickness of the inner and outer nasal sectors was the most accurate indicator of MMD(AUC of 0.928 and 0.923,respectively).An outer nasal sector choroidal thickness of less than 74μm demonstrated the highest odds of predicting MMD(OR=33.8).CONCLUSION:Choroidal thickness detects the presence of MMD with high agreement,particularly of the inner and outer nasal sectors of the posterior pole,which appears to be a biometric parameter more precise than age,AL,or SE.展开更多
Accurately predicting fluid forces acting on the sur-face of a structure is crucial in engineering design.However,this task becomes particularly challenging in turbulent flow,due to the complex and irregular changes i...Accurately predicting fluid forces acting on the sur-face of a structure is crucial in engineering design.However,this task becomes particularly challenging in turbulent flow,due to the complex and irregular changes in the flow field.In this study,we propose a novel deep learning method,named mapping net-work-coordinated stacked gated recurrent units(MSU),for pre-dicting pressure on a circular cylinder from velocity data.Specifi-cally,our coordinated learning strategy is designed to extract the most critical velocity point for prediction,a process that has not been explored before.In our experiments,MSU extracts one point from a velocity field containing 121 points and utilizes this point to accurately predict 100 pressure points on the cylinder.This method significantly reduces the workload of data measure-ment in practical engineering applications.Our experimental results demonstrate that MSU predictions are highly similar to the real turbulent data in both spatio-temporal and individual aspects.Furthermore,the comparison results show that MSU predicts more precise results,even outperforming models that use all velocity field points.Compared with state-of-the-art methods,MSU has an average improvement of more than 45%in various indicators such as root mean square error(RMSE).Through comprehensive and authoritative physical verification,we estab-lished that MSU’s prediction results closely align with pressure field data obtained in real turbulence fields.This confirmation underscores the considerable potential of MSU for practical applications in real engineering scenarios.The code is available at https://github.com/zhangzm0128/MSU.展开更多
文摘<span style="font-family:Verdana;">Enzalutamide is a hormonal therapy that blocks the action of androgens, such as testosterone in the treatment of metastatic castration-resistant prostate cancer. </span><span style="font-family:Verdana;">Stevens-Johnson syndrome and toxic epidermal necrolysis (SJS/TEN) overlap and are part of an adverse drug reaction continuum of disease, in which there is a 10% - 30% involvement of the skin surface with mucositis, blisters, skin slough, and a macular rash. A 66-year-old male was treated with enzalutamide for metastatic prostate cancer and developed SJS/TEN overlap with 25% total body surface area skin involvement. The patient received a </span><span style="font-family:Verdana;">seven-day course of cyclosporine to which he responded by re-epithelialization </span><span style="font-family:Verdana;">but succumbed to multi-organ failure. While SJS/TEN has been reported with apalutamide, to our knowledge, this is the first case of SJS/TEN overlap with enzalutamide.</span>
文摘Johns Hopkins University School of Medicine (JHUSOM) has been a leader in medical education since its inception in 1893. The influence of John Dewey on the founders of the school is evident in the design of the curriculum,which included serious study of basic science for two years,followed by 'learning by doing' in the 3d and 4th clinical years. After the Flexner report in 1910 which lauded the school as an exemplary model,this became the standard curricular structure of undergraduate medical education in the US. Since its founding Hopkins,like other medical schools,has struggled with burgeoning biomedical knowledge and the tension between time and content. The last curricular revision was implemented in 1992,and had several themes,including:(1) decreased lecture time and increased small group learning; (2) early clinical experience and more ambulatory clinical experience; (3) integration of the basic sciences to improve learning and reduce redundancy; (4) development of a longitudinal course for the social sciences,(named 'The Physician and Society' course); (5) a required thesis project for graduation. All but the last were implemented. Our students have done well in this curriculum. 98-100% pass the licensing board exams,and over 90% obtain their first choice for residency positions,often in highly competitive programs such as Dermatology,Neurosurgery and Ophthalmology. Approximately 30% of graduates are listed in the AAMC faculty roster-one of the highest percentages of graduates going to academic medicine in the country.
文摘The Retrovirus Epidemiology Donor Study (REDS) was established in 1989 with funding from the National Heart,Lung,and Blood Institute ( NHLBI ) of the National Institutes of Health in the United States.The initial program coordinated activities in five large US blood centers in San Francisco,Los Angeles,Oklahoma City,Detroit,and Baltimore with a coordinating center Westat in Rockville MD.
文摘Glaucoma service of Johns Hopkins University is currently involved in a range of research projects.This overview will cover the major clinical activities currently underway.
基金The study is financed by the grant of Johns Hopkins University School of Medicine,Baltimore,Maryland,USA.
文摘Narrative medicine is a multidisciplinary field of inquiry and practice based on the premise that medical care takes place in the context of stories.Research on narrative medicine training suggests that it conveys benefits such as improved communication skills and personal and professional growth to physicians,medical students,and other health care providers.Narrative medicine can promote empathy and trust between patients and physicians and foster self-care.In 2014,the author and a colleague started an ongoing inter-disciplinary narrative medicine program in the Children’s Center of the Johns Hopkins Hospital called AfterWards.The program,which meets monthly,is open to all on a volunteer basis.Through literature,art,and writing,AfterWards nurtures empathy,encourages reflective practice,and builds community among a diverse group of health care providers.Through a series of lectures and workshops at Johns Hopkins Medicine,Peking Union Medical College,and Fudan Hospital in Shanghai,the author has introduced AfterWards to Chinese medical educators and clinicians.Working with Dr.Marta Hanson,she created an AfterWards Facilitator’s Guide for the use of Chinese practitioners.A recent White Paper on Chinese health care indicates that an infusion of humanities-based education,of which narrative medicine forms a part,can help rebuild patient-physician trust.Recently,there has been an increase in interest in narrative medicine in the United States and China.However,more research is needed to demonstrate the impact of programs like AfterWards.Challenges to the implementation of narrative medicine programs remain,most significantly in terms of expertise,resources,and time.
基金supported by the Merkin PNNR Center(23-DF/C2/261)(to HS).
文摘Neurons are highly polarized,morphologically asymmetric,and functionally compartmentalized cells that contain long axons extending from the cell body.For this reason,their maintenance relies on spatiotemporal regulation of organelle distribution between the somatodendritic and axonal domains.Although some organelles,such as mitochondria and smooth endoplasmic reticulum,are widely distributed throughout the neuron,others are segregated to either the somatodendritic or axonal compartment.For example,Golgi outposts and acidified lysosomes are predominantly present in the somatodendritic domain and rarely distributed along the axon,whereas newly formed autophagosomes and synaptic vesicles are mainly distributed in the distal axon(Britt et al.,2016).
基金supported by the Research Foundation of Technology Committee of Tongzhou District,No.KJ2019CX001(to SX).
文摘Human dental pulp stem cell transplantation has been shown to be an effective therapeutic strategy for spinal cord injury.However,whether the human dental pulp stem cell secretome can contribute to functional recovery after spinal cord injury remains unclear.In the present study,we established a rat model of spinal cord injury based on impact injury from a dropped weight and then intraperitoneally injected the rats with conditioned medium from human dental pulp stem cells.We found that the conditioned medium effectively promoted the recovery of sensory and motor functions in rats with spinal cord injury,decreased expression of the microglial pyroptosis markers NLRP3,GSDMD,caspase-1,and interleukin-1β,promoted axonal and myelin regeneration,and inhibited the formation of glial scars.In addition,in a lipopolysaccharide-induced BV2 microglia model,conditioned medium from human dental pulp stem cells protected cells from pyroptosis by inhibiting the NLRP3/caspase-1/interleukin-1βpathway.These results indicate that conditioned medium from human dental pulp stem cells can reduce microglial pyroptosis by inhibiting the NLRP3/caspase-1/interleukin-1βpathway,thereby promoting the recovery of neurological function after spinal cord injury.Therefore,conditioned medium from human dental pulp stem cells may become an alternative therapy for spinal cord injury.
基金supported by the National Institute of Health grant R01 GM101502(to SL).
文摘Brain tissue requires high amounts of copper(Cu)for its key physiological processes,such as energy production,neurotransmitter synthesis,maturation of neuropeptides,myelination,synaptic plasticity,and radical scavenging.The requirements for Cu in the brain vary depending on specific brain regions,cell types,organism age,and nutritional status.Cu imbalances cause or contribute to several life-threatening neurologic disorders including Menkes disease,Wilson disease,Alzheimer’s disease,Parkinson’s disease,and others.Despite the well-established role of Cu homeostasis in brain development and function,the mechanisms that govern Cu delivery to the brain are not well defined.This review summarizes available information on Cu transfer through the brain barriers and discusses issues that require further research.
基金supported by the National Natural Science Foundation of China,No.81901241(to YZ)。
文摘Neuroinflammation exacerbates secondary damage after spinal cord injury,while microglia/macrophage pyroptosis is important to neuroinflammation.Circular RNAs(circRNAs)play a role in the central nervous system.However,the functional role and mechanism of circRNAs in regulating microglia/macrophage pyroptosis after spinal cord injury are still poorly studied.In the present study,we detected microglia/macrophage pyroptosis in a female rat model of spinal cord injury,along with upregulated levels of circ0000381 in the spinal cord.Our further experimental results suggest that circ0000381 may function as a sponge to sequester endogenous microRNA423-3p(miR-423-3p),which can increase the expression of NOD-like receptor 3(NLRP3),a pyroptosis marker.Therefore,upregulation of circ0000381 may be a compensatory change after spinal cord injury to attenuate microglia/macrophage pyroptosis.Indeed,knockdown of circ0000381 expression exacerbated microglia/macrophage pyroptosis.Collectively,our findings provide novel evidence for the upregulation of circ0000381,which may serve as a neuroprotective mechanism to attenuate microglia/macrophage pyroptosis after spinal cord injury.Accordingly,circ0000381 may be a novel therapeutic target for the treatment of spinal cord injury.
基金This research was supported by NIH National Institute on Aging under Award Number R01 AG076783,R01 AG068997 and P01 AG066603(to X.C.).
文摘Bone is a mechanosensitive tissue and undergoes constant remodeling to adapt to the mechanical loading environment.However,it is unclear whether the signals of bone cells in response to mechanical stress are processed and interpreted in the brain.In this study,we found that the hypothalamus of the brain regulates bone remodeling and structure by perceiving bone prostaglandin E2(PGE2)concentration in response to mechanical loading.Bone PGE2 levels are in proportion to their weight bearing.When weight bearing changes in the tail-suspension mice,the PGE2 concentrations in bones change in line with their weight bearing changes.Deletion of cyclooxygenase-2(COX2)in the osteoblast lineage cells or knockout of receptor 4(EP4)in sensory nerve blunts bone formation in response to mechanical loading.Moreover,knockout of TrkA in sensory nerve also significantly reduces mechanical load-induced bone formation.Moreover,mechanical loading induces cAMP-response element binding protein(CREB)phosphorylation in the hypothalamic arcuate nucleus(ARC)to inhibit sympathetic tyrosine hydroxylase(TH)expression in the paraventricular nucleus(PVN)for osteogenesis.Finally,we show that elevated PGE2 is associated with ankle osteoarthritis(AOA)and pain.Together,our data demonstrate that in response to mechanical loading,skeletal interoception occurs in the form of hypothalamic processing of PGE2-driven peripheral signaling to maintain physiologic bone homeostasis,while chronically elevated PGE2 can be sensed as pain during AOA and implication of potential treatment.
文摘Neurological disorders are a diverse group of conditions that affect the nervous system and include neurodegenerative diseases(Alzheimer’s disease,multiple sclerosis,Parkinson’s disease,Huntington’s disease),cerebrovascular conditions(stroke),and neurodevelopmental disorders(autism spectrum disorder).Although they affect millions of individuals around the world,only a limited number of effective treatment options are available today.Since most neurological disorders express mitochondria-related metabolic perturbations,metformin,a biguanide type II antidiabetic drug,has attracted a lot of attention to be repurposed to treat neurological disorders by correcting their perturbed energy metabolism.However,controversial research emerges regarding the beneficial/detrimental effects of metformin on these neurological disorders.Given that most neurological disorders have complex etiology in their pathophysiology and are influenced by various risk factors such as aging,lifestyle,genetics,and environment,it is important to identify perturbed molecular functions that can be targeted by metformin in these neurological disorders.These molecules can then be used as biomarkers to stratify subpopulations of patients who show distinct molecular/pathological properties and can respond to metformin treatment,ultimately developing targeted therapy.In this review,we will discuss mitochondria-related metabolic perturbations and impaired molecular pathways in these neurological disorders and how these can be used as biomarkers to guide metformin-responsive treatment for the targeted therapy to treat neurological disorders.
文摘Over the past decade,medical researchers in China have debated whether the Pi(脾)corresponds to the biomedical spleen or pancreas.This debate exemplifies a broader phenomenon of“anatomical retrofitting”,or the anachronistic imposition of contemporary categories onto living historical objects.“Anatomical retrofitting”as a means of rectifying cases of mistranslation further positions the biomedical spleen and pancreas as representing ahistorical,universal truths.This framework gives rise to a conceptual binary:while the biomedical spleen is universalized as what philosophers may describe as“logical”ontology,the Pi connects to a different nature of reality,or“metaphysical”ontology.Far from being an object of imprecision,the Pi was a dynamic vessel that also shared characteristics with the humoral spleen.Given that scholars in China have already subjected Pi to historical scrutiny,this paper urges scholars to do the same with biomedical anatomy.For instance,historically situating the humoral spleen demonstrates that it became less known and less articulated as it transformed into the biomedical spleen.Meanwhile,the pancreas remained an unstable epistemic object that took on the dynamic functions of the humoral spleen in nineteenth-century organotherapy.Through primary source analysis and literature review,this paper contends that the apparent ontological incommensurability between Pi and spleen is neither mutually exclusive nor irreconcilable.Instead,the dynamic nature of internal viscera,their many functions,and their participation in epistemic practices contribute to an ongoing ontological ambivalence that persists despite the forced certainty of anatomical retrofitting.
文摘To determine the cause(s)of perturbations seen in dayside equatorial ground magnetograms,we conducted a systematic survey of simultaneous ground-based and geosynchronous satellite-based observations during the 90-day period from December 1,2020 to February 28,2021.We examined Huancayo ground magnetometer observations from 14:00:00 to 20:00:00 UT each day,during which Huancayo passed through local noon.From those data we chose perturbation events selected on the basis of large(>20 nT)event amplitude and classified the selected events as responding primarily to solar wind pressure,or to variations in the north/south component of the interplanetary magnetic field(IMF Bz),or perhaps in part to both.The results show that an equivalent number of events were identified for each model during this 90-day period.Variations in the lagged solar wind dynamic pressure routinely correspond to nearly simultaneous sudden impulses recorded at both geosynchronous orbit and on the ground.Variations in IMF Bz produce erosion signatures at geosynchronous orbit and can correspond to ground events if lag times for reconnection to enhance convection in the magnetosphere are taken into account.
文摘Background:Acute improvement in range of motion(ROM)is a widely reported effect of stretching and foam rolling,which is commonly explained by changes in pain threshold and/or musculotendinous stiffness.Interestingly,these effects were also reported in response to various other active and passive interventions that induce responses such as enhanced muscle temperature.Therefore,we hypothesized that acute ROM enhancements could be induced by a wide variety of interventions other than stretching or foam rolling that promote an increase in muscle temperature.Methods:After a systematic search in PubMed,Web of Science,and SPORTDiscus databases,38 studies comparing the effects of stretching and foam rolling with several other interventions on ROM and passive properties were included.These studies had 1134 participants in total,and the data analysis resulted in 140 effect sizes(ESs).ES calculations were performed using robust variance estimation model with R-package.Results:Study quality of the included studies was classified as fair(PEDro score=4.58)with low to moderate certainty of evidence.Results showed no significant differences in ROM(ES=0.01,p=0.88),stiffness(ES=0.09,p=0.67),or passive peak torque(ES=-0.30,p=0.14)between stretching or foam rolling and the other identified activities.Funnel plots revealed no publication bias.Conclusion:Based on current literature,our results challenge the established view on stretching and foam rolling as a recommended component of warm-up programs.The lack of significant difference between interventions suggests there is no need to emphasize stretching or foam rolling to induce acute ROM,passive peak torque increases,or stiffness reductions.
文摘Prostate cancer poses a significant health challenge globally,demanding proactive prevention strategies.This editorial explores the emerging role of vitamin D in prostate cancer prevention.While traditionally associated with bone health,vitamin D is increasingly recognized for its broader impact on immune function,cellular signaling,and cancer prevention.Epidemiological studies suggest an intriguing link between vitamin D deficiency and elevated prostate cancer risk,particularly in regions with limited sunlight exposure.Mechanistically,vitamin D regulates cellular processes,inhibiting unchecked cancer cell growth and bols-tering immune surveillance.Personalized prevention strategies,considering individual factors,are deemed essential for harnessing the full potential of vitamin D.To unlock this potential,the future calls for robust research,public awareness campaigns,dietary improvements,and vigilant medical guidance.Collaborative efforts are poised to pave the way toward a future where vitamin D stands as a sentinel in prostate cancer prevention,ushering in hope and improved health for men worldwide.
基金supported by NASA(Grant Nos.80NSSC19K0844,80NSSC20K1670,80MSFC20C0019,and 80GSFC21M0002)support from NASA Goddard Space Flight Center internal funding programs(HIF,Internal Scientist Funding Model,and Internal Research and Development)。
文摘The Lunar Environment heliospheric X-ray Imager(LEXI)and Solar wind Magnetosphere Ionosphere Link Explorer(SMILE)missions will image the Earth’s dayside magneto pause and cusps in soft X-rays after their respective launches in the near future,to specify glo bal magnetic reconnection modes for varying solar wind conditions.To suppo rt the success of these scientific missions,it is critical to develop techniques that extract the magnetopause locations from the observed soft X-ray images.In this research,we introduce a new geometric equation that calculates the subsolar magnetopause position(RS)from a satellite position,the look direction of the instrument,and the angle at which the X-ray emission is maximized.Two assumptions are used in this method:(1)The look direction where soft X-ray emissions are maximized lies tangent to the magnetopause,and(2)the magnetopause surface near the subsolar point is almost spherical and thus RSis nea rly equal to the radius of the magneto pause curvature.We create synthetic soft X-ray images by using the Open Geospace General Circulation Model(OpenGGCM)global magnetohydrodynamic model,the galactic background,the instrument point spread function,and Poisson noise.We then apply the fast Fourier transform and Gaussian low-pass filte rs to the synthetic images to re move noise and obtain accurate look angles for the soft X-ray pea ks.From the filte red images,we calculate RS and its accuracy for different LEXI locations,look directions,and solar wind densities by using the OpenGGCM subsolar magnetopause location as ground truth.Our method estimates RS with an accuracy of<0.3 RE when the solar wind density exceeds>10 cm-3.The accuracy improves for greater solar wind densities and during southward interplanetary magnetic fields.The method ca ptures the magnetopause motion during southwa rd interplaneta ry magnetic field turnings.Consequently,the technique will enable quantitative analysis of the magnetopause motion and help reveal the dayside reconnection modes for dynamic solar wind conditions.This technique will suppo rt the LEXI and SMILE missions in achieving their scientific o bjectives.
基金Supported by the National Natural Science Foundation of China(No.82301249,No.82371086)the Science and Technology Projects in Guangzhou(No.SL2024A04J01756)the Fundamental Research Funds of the State Key Laboratory of Ophthalmology(No.83000-32030003).
文摘AIM:To explore the usage of choroidal thickness measured by swept-source optical coherence tomography(SS-OCT)to detect myopic macular degeneration(MMD)in high myopic participants.METHODS:Participants with bilateral high myopia(≤−6 diopters)were recruited from a subset of the Guangzhou Zhongshan Ophthalmic Center-Brien Holden Vision Institute High Myopia Cohort Study.SS-OCT was performed to determine the choroidal thickness,and myopic maculopathy was graded by the International Meta-Analysis for Pathologic Myopia(META-PM)Classification.Presence of MMD was defined as META-PM category 2 or above.RESULTS:A total of 568 right eyes were included for analysis.Eyes with MMD(n=106,18.7%)were found to have older age,longer axial lengths(AL),higher myopic spherical equivalents(SE),and reduced choroidal thickness in each Early Treatment Diabetic Retinopathy Study(ETDRS)grid sector(P<0.001).The area under the receiver operating characteristic(ROC)curves(AUC)for subfoveal choroidal thickness(0.907)was greater than that of the model,including age,AL,and SE at 0.6249,0.8208,and 0.8205,respectively.The choroidal thickness of the inner and outer nasal sectors was the most accurate indicator of MMD(AUC of 0.928 and 0.923,respectively).An outer nasal sector choroidal thickness of less than 74μm demonstrated the highest odds of predicting MMD(OR=33.8).CONCLUSION:Choroidal thickness detects the presence of MMD with high agreement,particularly of the inner and outer nasal sectors of the posterior pole,which appears to be a biometric parameter more precise than age,AL,or SE.
基金supported by the Japan Society for the Promotion of Science(JSPS)KAKENHI(JP22H03643)Japan Science and Technology Agency(JST)Support for Pioneering Research Initiated by the Next Generation(SPRING)(JPMJSP2145)+2 种基金JST Through the Establishment of University Fellowships Towards the Creation of Science Technology Innovation(JPMJFS2115)the National Natural Science Foundation of China(52078382)the State Key Laboratory of Disaster Reduction in Civil Engineering(CE19-A-01)。
文摘Accurately predicting fluid forces acting on the sur-face of a structure is crucial in engineering design.However,this task becomes particularly challenging in turbulent flow,due to the complex and irregular changes in the flow field.In this study,we propose a novel deep learning method,named mapping net-work-coordinated stacked gated recurrent units(MSU),for pre-dicting pressure on a circular cylinder from velocity data.Specifi-cally,our coordinated learning strategy is designed to extract the most critical velocity point for prediction,a process that has not been explored before.In our experiments,MSU extracts one point from a velocity field containing 121 points and utilizes this point to accurately predict 100 pressure points on the cylinder.This method significantly reduces the workload of data measure-ment in practical engineering applications.Our experimental results demonstrate that MSU predictions are highly similar to the real turbulent data in both spatio-temporal and individual aspects.Furthermore,the comparison results show that MSU predicts more precise results,even outperforming models that use all velocity field points.Compared with state-of-the-art methods,MSU has an average improvement of more than 45%in various indicators such as root mean square error(RMSE).Through comprehensive and authoritative physical verification,we estab-lished that MSU’s prediction results closely align with pressure field data obtained in real turbulence fields.This confirmation underscores the considerable potential of MSU for practical applications in real engineering scenarios.The code is available at https://github.com/zhangzm0128/MSU.