Acute kidney injury(AKI)is a critical condition with limited effective therapies.Akkermansia muciniphila(A.muciniphila)is a probiotic with multiple beneficial effects,including the regulation of epithelial cell tight ...Acute kidney injury(AKI)is a critical condition with limited effective therapies.Akkermansia muciniphila(A.muciniphila)is a probiotic with multiple beneficial effects,including the regulation of epithelial cell tight junctions.Since renal pathophysiology is associated with gut barrier integrity,we hypothesized that A.muciniphila may have preventive effects on AKI.We established a lipopolysaccharide(LPS)-induced AKI mouse model to evaluate the effects of A.muciniphila.Our findings showed that pretreatment with A.muciniphila significantly attenuated kidney injury,as evidenced by reduced serum creatinine and urea nitrogen levels,alongside decreased tubular necrosis and apoptosis.A.muciniphila preserved intestinal barrier integrity and induced marked shifts in gut microbial ecology and the metabolome.A.muciniphila notably induced an increase in the relative abundance of the phylum Proteobacteria while decreasing in that of the phylum Bacteroidetes.At the genus level,Prevotella,Faecalibaculum,Moraxella,and Lactobacillus were more abundant in A.muciniphilapretreated mice.Metabolomic analysis revealed that A.muciniphila altered the gut metabolome,with changes involving pathways such as tyrosine metabolism,alanine/aspartate/glutamate homeostasis,cancer-related carbon flux,and GABAergic synaptic signaling.In conclusion,our findings indicate that A.muciniphila exerts renoprotective effects by modulating the gut-kidney axis,thereby establishing a foundation for future studies to explore the connection between gut microbiota and AKI.展开更多
Male breast cancer(MBC)is rare,representing 0.5%–1%of all breast cancers,but its incidence is increasing due to improved diagnostics and awareness.MBC typically presents in older men,is human epidermal growth factor ...Male breast cancer(MBC)is rare,representing 0.5%–1%of all breast cancers,but its incidence is increasing due to improved diagnostics and awareness.MBC typically presents in older men,is human epidermal growth factor receptor 2(HER2)-negative and estrogen receptor(ER)-positive,and lacks routine screening,leading to delayed diagnosis and advanced disease.Major risk factors include hormonal imbalance,radiation exposure,obesity,alcohol use,and Breast Cancer Gene 1 and 2(BRCA1/2)mutations.Clinically,it may resemble gynecomastia but usually appears as a unilateral,painless mass or nipple discharge.Advances in imaging and liquid biopsy have enhanced early detection.Molecular mechanisms involve hormonal signaling,HER2/epidermal growth factor receptor(EGFR)pathways,tumor suppressor gene alterations,and epigenetic changes.While standard treatments mirror those for female breast cancer,emerging options such as cyclin-dependent kinase 4 and 6(CDK4/6),and poly(ADP-ribose)polymerase(PARP)inhibitors,immunotherapy,and precision medicine are reshaping management.Incorporating artificial intelligence,molecular profiling,and male-specific clinical trials is essential to improve outcomes and bridge current diagnostic and therapeutic gaps.展开更多
Traumatic spinal cord injury result in considerable and lasting functional impairments,triggering complex inflammatory and pathological events.Spinal cord scars,often metaphorically referred to as“fire barriers,”aim...Traumatic spinal cord injury result in considerable and lasting functional impairments,triggering complex inflammatory and pathological events.Spinal cord scars,often metaphorically referred to as“fire barriers,”aim to control the spread of neuroinflammation during the acute phase but later hinder axon regeneration in later stages.Recent studies have enhanced our understanding of immunomodulation,revealing that injury-associated inflammation involves various cell types and molecules with positive and negative effects.This review employs bibliometric analysis to examine the literature on inflammatory mediators in spinal cord injury,highlighting recent research and providing a comprehensive overview of the current state of research and the latest advances in studies on neuroinflammation related to spinal cord injury.We summarize the immune and inflammatory responses at different stages of spinal cord injury,offering crucial insights for future research.Additionally,we review repair strategies based on inflammatory mediators for the injured spinal cord.Finally,this review discusses the current status and future directions of translational research focused on immune-targeting strategies,including pharmaceuticals,biomedical engineering,and gene therapy.The development of a combined,precise,and multitemporal strategy for the repair of injured spinal cords represents a promising direction for future research.展开更多
On April 14,2010,an earthquake reaching Richter scale 7.1 struck Jiegu Town of Yushu,a mountain rescue operation promptly launched. All injurers had a direct assess to take medical care,and were immediately rescued an...On April 14,2010,an earthquake reaching Richter scale 7.1 struck Jiegu Town of Yushu,a mountain rescue operation promptly launched. All injurers had a direct assess to take medical care,and were immediately rescued and rapidly evacuated by air to Xining and Golmud at lower altitudes and admitted to advanced hospitals. Almost all of the injurers have been completely recovered. Yushu Earthquake was one of the highest earthquakes in the world,with a high incidence of acute altitude illness,which was observed in about 80 % of the lowland rescuers at an altitude of 4 000 m."Rescue the rescuers"became the major task of Qinghai-Tibetan rescue teams,all the severe patients were rapidly descended to Xining and treated promptly and effectively. The outcome was excellent,all patients survived. After the earthquake,it is a long and arduous task to reconstruct what has been destroyed. Medical teams continue to work in the Yushu Earthquake area because about 30 000 workers and carders are now here for rebuilding the earthquake center. Thus the prevention and treatment of altitude illness are still critical tasks for medical teams. Although all the fights are successful,there are more experiences and lessons we have learned from the medical mountain rescue during the earthquake and the reconstruction,and reports here are to sum up our experiences from the medical mountain rescue operation in Yushu Earthquake and draw the lessons that we should learn. With the increasing of earthquake probability occurring in the Qinghai-Tibetan Plateau,we also should prepare against earthquake disasters and for further rescue training in the high mountains.展开更多
After a radiological or nuclear event, acute radiation syndrome(ARS) will present complex medical challenges that could involve the treatment of hundreds to thousands of patients. Current medical doctrine is based on ...After a radiological or nuclear event, acute radiation syndrome(ARS) will present complex medical challenges that could involve the treatment of hundreds to thousands of patients. Current medical doctrine is based on limited clinical data and remains inadequate. Efforts to develop medical innovations that address ARS complications are unlikely to be generated by the industry because of market uncertainties specific to this type of injury. A prospective strategy could be the integration of cellular therapy to meet the medical demands of ARS. The most clinically advanced cellular therapy to date is the administration of mesenchymal stem cells(MSCs). Results of currently published investigations describing MSC safety and efficacy in a variety of injury and disease models demonstrate the unique qualities of this reparative cell population in adapting to the specific requirements of the damaged tissue in which the cells integrate. This report puts forward a rationale for the further evaluation of MSC therapy to address the current unmet medical needs of ARS. We propose that the exploration of this novel therapy for the treatment of the multivariate complications of ARS could be of invaluable benefit to military medicine.展开更多
Organogenesis is regulated by a complex network of intrinsic cues, diffusible signals and cell/cell or cell/matrix interactions that drive the cells of a prospective organ to differentiate and collectively organize in...Organogenesis is regulated by a complex network of intrinsic cues, diffusible signals and cell/cell or cell/matrix interactions that drive the cells of a prospective organ to differentiate and collectively organize in three dimensions. Generating organs in vitro from embryonic stem (ES) cells may provide a simplified system to decipher how these processes are orchestrated in time and space within particular and between neighboring tissues. Recently, this field of stem cell research has also gained considerable interest for its potential applications in regenerative medicine. Among human pathologies for which stem cell-based therapy is foreseen as a promising therapeutic strategy are many retinal degenerative diseases, like retinitis pigmentosa and age-related macular degeneration. Over the last decade, progress has been made in producing ES-derived retinal cells in vitro, but engineering entire synthetic retinas was considered beyond reach. Recently however, major breakthroughs have been achieved with pioneer works describing the extraordinary self-organization of murine and human ES cells into a three dimensional structure highly resembling a retina. ES-derived retinal cells indeed assemble to form a cohesive neuroepithelial sheet that is endowed with the intrinsic capacity to recapitulate, outside an embryonic environment, the main steps of retinal morphogenesis as observed in vivo. This represents a tremendous advance that should help resolving fundamental questions related to retinogenesis. Here, we will discuss these studies, and the potential applications of such stem cell-based systems for regenerative medicine.展开更多
Objective:The aim of this article was to discuss the theory of doctor-patient co-operated evidence-based medical record and set up the preliminary frame of the doctor-patient co-operated evidence-based medical record ...Objective:The aim of this article was to discuss the theory of doctor-patient co-operated evidence-based medical record and set up the preliminary frame of the doctor-patient co-operated evidence-based medical record following the concept of narrative evidence-based medicine.Methods:The information was searched from Pubmed,Embase,CBMdisc,CNKI.A preliminary agreement was reached by referring to the principles of narrative medicine and advises given by experts of digestive system and evidence-based medicine in both Traditional Chinese Medicine and Western Medicine.Result:This research is a useful attempt to discuss the establishment of doctor-patient co-operated evidence-based medical record guided by the direction of narrative evidence-based medicine.Reflection and outlook:Doctor-patient co-operated medical record can be a key factor of the curative effect evaluation methodology system of integrated therapy of Tradition Chinese Medicine and Western Medicine on spleen and stomach diseases.展开更多
Heaven-human-earth Pattern (HHE) regarded as a crucial conception of traditional Chinese medicine (TCM) has been applied extensively in TCM diagnostics, etiology, acupuncture therapeutics, materia medica and herbal fo...Heaven-human-earth Pattern (HHE) regarded as a crucial conception of traditional Chinese medicine (TCM) has been applied extensively in TCM diagnostics, etiology, acupuncture therapeutics, materia medica and herbal formula, etc. It associates closely with Chinese classic cosmology. Since ancient time of China, many cosmic phenomena have been introduced to prove or illustrate TCM theories. Moreover, the five-element theory has been proven to be in keeping with some modern approaches of life provenance and life evolution. As a result, Chinese materia medica develops in a way of a pure natural medicine. It is of great significance that by realizing the natural features, the public nowadays can understand TCM better in its scientific connotations.展开更多
Background:Administrative database provides valuable information for large cohort studies,especially when tissue diagnosis is rather difficult such as the diagnosis for bile duct cancer(BDC).The aim of this study was ...Background:Administrative database provides valuable information for large cohort studies,especially when tissue diagnosis is rather difficult such as the diagnosis for bile duct cancer(BDC).The aim of this study was to evaluate the diagnostic accuracy of administrative database for BDC by International Classification of Diseases(ICD)-10 codes in a tertiary institute.Methods:BDC and control groups were collected from 2003 to 2016 at Seoul National University Bundang Hospital.Cases of BDC were identified in the National Health Insurance Service(NHIS)database by ICD 10-code supported by V code.The control group was selected from cases without ICD-10 codes for BDC.A definite or possible diagnosis was defined according to pathologic reports.Medical records,images,and pathology reports were analyzed to evaluate ICD-10 codes for BDC.Sensitivity,specificity,positive predictive value,and negative predictive value for BDC were analyzed according to diagnostic criteria and cancer locations.Results:A total of 1707 patients with BDC and 1707 controls were collected.Among those with BDC,1320(77.3%)were diagnosed by definite criteria.Most(99.4%)of them had adenocarcinoma.Rate of definite diagnosis was the highest for ampulla of Vater(88.9%),followed by that for extrahepatic(84.9%)and intrahepatic(68.3%)BDCs.False positive cases commonly had hepatocellular carcinomas.For overall diagnosis of BDC,sensitivity,specificity,positive predictive value,and negative predictive value were 99.94%,98.33%,98.30%,and 99.94%,respectively.Diagnostic accuracies were similar regardless of diagnostic criteria or tumor locations.Conclusions:Administrative database for BDC collected according to ICD-10 code with V code shows good accuracy.展开更多
Objectives: Different surgical techniques, with variable morbidity and recurrence rates, have been advocated for the management of chronic pilonidal sinus (PNS). This study was conducted to report the outcome of surgi...Objectives: Different surgical techniques, with variable morbidity and recurrence rates, have been advocated for the management of chronic pilonidal sinus (PNS). This study was conducted to report the outcome of surgical treatment of 634 cases of chronic PNS at a single institute between January 2001 and January 2010. Methods: Karydakis flap was performed in 244 patients (38.5%, Group 1). Excision and midline closure was performed in 371 patients (58.5%, Group 2), while the open method was used in 19 (3.0%). Data regarding patient and sinus characteristics, operative de-tails, postoperative course, complications and recurrence were recorded. Mean follow-up was 73.5 months. Results: 571 patients were male (90.1%) and 63 were female (9.9%). Their ages ranged between 16 - 44 years (mean 25.7 years). The mean body mass index was 31.2 (range 23.6 - 41.9), and 71.5% (453/634) were hirsute. Chronic PNS was the first presentation (primary) in 504 patients (79.5%) and recurrent in 130 (20.5%).Overall complication rate was 16.1% (102/ 634) and overall recurrence rate was 8.4% (53/634). Comparing both groups showed that they were similar regarding demographic characteristics, clinical presentation, hospital stay, healing time and time off work. Operative time was insignificantly longer with Karydakis technique (mean 43.2 versus 39.1 minutes, respectively). Complications were sig-nificantly more in patients with midline closure (21%, 78/371) as compared with Karydakis procedure (9%, 22/244) (P = 0.0001). Likewise, there was a significantly (P = 0.0001) higher rate of recurrence with midline closure (12.1%, 45/371) as opposed to Karydakis technique (2.5%, 6/244). Conclusions: 1) PNS affects mainly young male adults who are usually, obese and hirsute, 2) Karydakis technique for the management of chronic PNS, whether primary or recurrent, is a non-lengthy, efficient procedure that has less overall complications and a lower recurrence rate than conventional excision and midline closure.展开更多
The application of single-cell RNA sequencing(scRNA-seq)in biomedical research has advanced our understanding of the pathogenesis of disease and provided valuable insights into new diagnostic and therapeutic strategie...The application of single-cell RNA sequencing(scRNA-seq)in biomedical research has advanced our understanding of the pathogenesis of disease and provided valuable insights into new diagnostic and therapeutic strategies.With the expansion of capacity for high-throughput scRNA-seq,including clinical samples,the analysis of these huge volumes of data has become a daunting prospect for researchers entering this field.Here,we review the workflow for typical scRNA-seq data analysis,covering raw data processing and quality control,basic data analysis applicable for almost all scRNA-seq data sets,and advanced data analysis that should be tailored to specific scientific questions.While summarizing the current methods for each analysis step,we also provide an online repository of software and wrapped-up scripts to support the implementation.Recommendations and caveats are pointed out for some specific analysis tasks and approaches.We hope this resource will be helpful to researchers engaging with scRNA-seq,in particular for emerging clinical applications.展开更多
Objective:In this study,we try to establish an initial electron beam model by combining Monte Carlo simulation method with particle dynamic calculation(TRSV)for the single 6 MV X-ray accelerating waveguide of BJ-6 med...Objective:In this study,we try to establish an initial electron beam model by combining Monte Carlo simulation method with particle dynamic calculation(TRSV)for the single 6 MV X-ray accelerating waveguide of BJ-6 medical linac.Methods and Materials:1.We adapted the treatment head configuration of BJ-6 medical linac made by Beijing Medical Equipment Institute(BMEI)as the radiation system for this study.2.Use particle dynamics calculation code called TRSV to drive out the initial electron beam parameters of the energy spectrum,the spatial intensity distribution,and the beam incidence angle.3.Analyze the 6 MV X-ray beam characteristics of PDDc,OARc in a water phantom by using Monte Carlo simulation(BEAMnrc,DOSXYZnrc)for a preset of the initial electron beam parameters which have been determined by TRSV,do the comparisons of the measured results of PDDm,OARm in a real water phantom,and then use the deviations of calculated and measured results to slightly modify the initial electron beam model back and forth until the deviations meet the error less than 2%.Results:The deviations between the Monte Carlo simulation results of percentage depth doses at PDDc and off-axis ratios OARc and the measured results of PDDm and OARm in a water phantom were within 2%.Conclusion:When doing the Monte Carlo simulation to determine the parameters of an initial electron beam for a particular medical linac like BJ-6,modifying some parameters based on the particle dynamics calculation code would give some more reasonable and more acceptable results.展开更多
BACKGROUND Transplant teams often hesitate to use the right kidney(RK)in living donor(LD)transplants due to the complexities of anastomosing the short,thin-walled right renal veins,which can potentially lead to graft ...BACKGROUND Transplant teams often hesitate to use the right kidney(RK)in living donor(LD)transplants due to the complexities of anastomosing the short,thin-walled right renal veins,which can potentially lead to graft loss or graft dysfunction.Nevertheless,circumstances may arise where selecting the RK over the left kidney(LK)is unavoidable.Consequently,it is crucial to thoroughly examine the implications of such a choice on the overall transplant outcome.AIM To compare transplant outcomes between recipients of RK and LK while examining the factors that influence these outcomes.METHODS We retrospectively analyzed data from adult patients who received LD kidney transplants involving meticulous patient selection and surgical techniques at our center from January 2020 to December 2023.We included all kidney donors who were over 18,fit to donate,and had undergone diethylenetriamine pentaacetic acid split function and/or computed tomography based volumetry.The variables examined comprised donor and recipient demographics,and outcome measures included technical graft loss(TGL),delayed or slow graft function(SGF),and post-transplant serum creatinine(SC)trends.We used a logistic regression model to assess the likelihood of adverse outcomes considering the donor kidney side.RESULTS Of the 250 transplants performed during the period,56(22%)were RKs.The recipient demographics and transplant factors were comparable for the right and LKs,except that the donor warm and cold ischemia time were shorter for RKs.TGL and SGF each occurred in 2%(n=1)of RKs and 0.5%(n=1)of LKs,the difference being insignificant.These complications,however,were not related to the venous anastomosis.One RK(2%)developed delayed graft function after 48 hours,which was attributable to postoperative hypoxia rather than the surgical technique.The post-transplant SC trend and mean SC at the last follow-up were similar across both kidney sides.CONCLUSION The donor kidney side has little impact on post-transplant adverse events and graft function in LD transplants,provided that careful patient selection and precise surgical techniques are employed.展开更多
Objective Oral squamous cell carcinoma(OSCC)is an aggressive cancer with a high mortality rate.San-Zhong-Kui-Jian-Tang(SZKJT),a Chinese herbal formula,has long been used as an adjuvant therapy in cancer clinical pract...Objective Oral squamous cell carcinoma(OSCC)is an aggressive cancer with a high mortality rate.San-Zhong-Kui-Jian-Tang(SZKJT),a Chinese herbal formula,has long been used as an adjuvant therapy in cancer clinical practice.Although its therapeutic effects and molecular mechanisms in OSCC have been previously elucidated,the potential interactions and mechanisms between the active phytochemicals and their therapeutic targets are still lacking.Methods The present study employed network pharmacology and topology approaches to establish a“herbal ingredients–active phytochemicals–target interaction”network to explore the potential therapeutic targets of SZKJT-active phytochemicals in the treatment of OSCC.The role of the target proteins in oncogenesis was assessed via GO and KEGG enrichment analyses,and their interactions with the active phytochemicals of SZKJT were calculated via molecular docking and dynamic simulations.The pharmacokinetic properties and toxicity of the active phytochemicals were also predicted.Results A total of 171 active phytochemicals of SZKJT fulfilled the bioavailability and drug-likeness screening criteria,with the flavonoids quercetin,kaempferol,and naringenin having the greatest potential.The 4 crucial targets of these active phytochemicals are PTGS2,TNF,BCL2,and CASP3,which encode cyclooxygenase-2,tumor necrosis factor(TNF),BCL-2 apoptosis regulator,and caspase-3,respectively.The interactions between phytochemicals and target proteins were predicted to be thermodynamically feasible and stable via molecular docking and dynamics simulations.Finally,the results revealed that the IL-6/JAK/STAT3 pathway and TNF signaling via NF-κB are the two prominent pathways targeted by SZKJT.Conclusion In summary,this study provides computational data for in-depth exploration of the mechanism by which SZKJT activates phytochemicals to treat OSCC.展开更多
Dear Editor,Space flight(SF)is substantially increasing at present.The emergence of commercial suborbital SF,such as the Virgin Galactic with VSS Unity and VMS Eve spacecraft,is extending to civilians,being previously...Dear Editor,Space flight(SF)is substantially increasing at present.The emergence of commercial suborbital SF,such as the Virgin Galactic with VSS Unity and VMS Eve spacecraft,is extending to civilians,being previously confined to military and/or professional astronauts only.This new evidence offers additional opportunities for better characterizing the impact that the transition from Earth’s 1G to microgravity in space could have on the astronauts’health while comparing well-trained subjects such as the latt er to space newcomers[1].展开更多
N6-methyladenosine(m^(6)A), the most prevalent and conserved RNA modification in eukaryotic cells, profoundly influences virtually all aspects of mRNA metabolism. mRNA plays crucial roles in neural stem cell genesis a...N6-methyladenosine(m^(6)A), the most prevalent and conserved RNA modification in eukaryotic cells, profoundly influences virtually all aspects of mRNA metabolism. mRNA plays crucial roles in neural stem cell genesis and neural regeneration, where it is highly concentrated and actively involved in these processes. Changes in m^(6)A modification levels and the expression levels of related enzymatic proteins can lead to neurological dysfunction and contribute to the development of neurological diseases. Furthermore, the proliferation and differentiation of neural stem cells, as well as nerve regeneration, are intimately linked to memory function and neurodegenerative diseases. This paper presents a comprehensive review of the roles of m^(6)A in neural stem cell proliferation, differentiation, and self-renewal, as well as its implications in memory and neurodegenerative diseases. m^(6)A has demonstrated divergent effects on the proliferation and differentiation of neural stem cells. These observed contradictions may arise from the time-specific nature of m^(6)A and its differential impact on neural stem cells across various stages of development. Similarly, the diverse effects of m^(6)A on distinct types of memory could be attributed to the involvement of specific brain regions in memory formation and recall. Inconsistencies in m^(6)A levels across different models of neurodegenerative disease, particularly Alzheimer's disease and Parkinson's disease, suggest that these disparities are linked to variations in the affected brain regions. Notably, the opposing changes in m^(6)A levels observed in Parkinson's disease models exposed to manganese compared to normal Parkinson's disease models further underscore the complexity of m^(6)A's role in neurodegenerative processes. The roles of m^(6)A in neural stem cell proliferation, differentiation, and self-renewal, and its implications in memory and neurodegenerative diseases, appear contradictory. These inconsistencies may be attributed to the timespecific nature of m^(6)A and its varying effects on distinct brain regions and in different environments.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
Moderate to severe perinatal hypoxic-ischemic encephalopathy occurs in~1 to 3/1000 live births in high-income countries and is associated with a significant risk of death or neurodevelopmental disability.Detailed asse...Moderate to severe perinatal hypoxic-ischemic encephalopathy occurs in~1 to 3/1000 live births in high-income countries and is associated with a significant risk of death or neurodevelopmental disability.Detailed assessment is important to help identify highrisk infants,to help families,and to support appropriate interventions.A wide range of monitoring tools is available to assess changes over time,including urine and blood biomarkers,neurological examination,and electroencephalography.At present,magnetic resonance imaging is unique as although it is expensive and not suited to monitoring the early evolution of hypoxic-ischemic encephalopathy by a week of life it can provide direct insight into the anatomical changes in the brain after hypoxic-ischemic encephalopathy and so offers strong prognostic information on the long-term outcome after hypoxic-ischemic encephalopathy.This review investigated the temporal dynamics of neonatal hypoxic-ischemic encephalopathy injuries,with a particular emphasis on exploring the correlation between the prognostic implications of magnetic resonance imaging scans in the first week of life and their relationship to long-term outcome prediction,particularly for infants treated with therapeutic hypothermia.A comprehensive literature search,from 2016 to 2024,identified 20 pertinent articles.This review highlights that while the optimal timing of magnetic resonance imaging scans is not clear,overall,it suggests that magnetic resonance imaging within the first week of life provides strong prognostic accuracy.Many challenges limit the timing consistency,particularly the need for intensive care and clinical monitoring.Conversely,although most reports examined the prognostic value of scans taken between 4 and 10 days after birth,there is evidence from small numbers of cases that,at times,brain injury may continue to evolve for weeks after birth.This suggests that in the future it will be important to explore a wider range of times after hypoxic-ischemic encephalopathy to fully understand the optimal timing for predicting long-term outcomes.展开更多
BACKGROUND Restless legs syndrome(RLS)is characterized by an urge to move with an unpleasant sensation in the lower limbs.RLS typically affects the legs.However,it can also affect several other body regions,such as th...BACKGROUND Restless legs syndrome(RLS)is characterized by an urge to move with an unpleasant sensation in the lower limbs.RLS typically affects the legs.However,it can also affect several other body regions,such as the arms,abdomen,face,neck,head,and genital area.There are only a few reports of the RLS variant affecting the head.AIM To assess the epidemiological,clinical,and other aspects of the RLS variant affecting the head.METHODS We conducted a retrospective study of 17 adult patients(>18 years)who met the RLS criteria and simultaneously experienced RLS-like symptoms in the head.RESULTS The median age at which symptoms appeared was 41.6 years.Males and females were equally affected(1.1:1).All 17 patients had uncomfortable sensations in the lower legs.Insomnia or disturbed sleep was the most common comorbidity(n=16,88.2%).However,headache was the most common presenting or primary symptom(n=10,70.5%).Dizziness or an abnormal sensation in the head was the second most common presenting symptom(5 patients,29.4%).Other presenting features were leg pain,backache,and generalized body pain.All patients responded favorably to dopaminergic medications.CONCLUSION If RLS-related unpleasant sensations and pain are felt in the head,they may be misinterpreted as headache,dizziness,or psychosomatic symptoms.RLS and headaches in a subset of patients may be two phenotypic manifestations of the same disorder.展开更多
BACKGROUND Understanding a patient's clinical status and setting priorities for their care are two aspects of the constantly changing process of clinical decision-making.One analytical technique that can be helpfu...BACKGROUND Understanding a patient's clinical status and setting priorities for their care are two aspects of the constantly changing process of clinical decision-making.One analytical technique that can be helpful in uncertain situations is clinical judgment.Clinicians must deal with contradictory information,lack of time to make decisions,and long-term factors when emergencies occur.AIM To examine the ethical issues healthcare professionals faced during the coronavirus disease 2019(COVID-19)pandemic and the factors affecting clinical decision-making.METHODS This pilot study,which means it was a preliminary investigation to gather information and test the feasibility of a larger investigation was conducted over 6 months and we invited responses from clinicians worldwide who managed patients with COVID-19.The survey focused on topics related to their professional roles and personal relationships.We examined five core areas influencing critical care decision-making:Patients'personal factors,family-related factors,informed consent,communication and media,and hospital administrative policies on clinical decision-making.The collected data were analyzed using the χ^(2) test for categorical variables.RESULTS A total of 102 clinicians from 23 specialties and 17 countries responded to the survey.Age was a significant factor in treatment planning(n=88)and ventilator access(n=78).Sex had no bearing on how decisions were made.Most doctors reported maintaining patient confidentiality regarding privacy and informed consent.Approximately 50%of clinicians reported a moderate influence of clinical work,with many citing it as one of the most important factors affecting their health and relationships.Clinicians from developing countries had a significantly higher score for considering a patient's financial status when creating a treatment plan than their counterparts from developed countries.Regarding personal experiences,some respondents noted that treatment plans and preferences changed from wave to wave,and that there was a rapid turnover of studies and evidence.Hospital and government policies also played a role in critical decision-making.Rather than assessing the appropriateness of treatment,some doctors observed that hospital policies regarding medications were driven by patient demand.CONCLUSION Factors other than medical considerations frequently affect management choices.The disparity in treatment choices,became more apparent during the pandemic.We highlight the difficulties and contradictions between moral standards and the realities physicians encountered during this medical emergency.False information,large patient populations,and limited resources caused problems for clinicians.These factors impacted decision-making,which,in turn,affected patient care and healthcare staff well-being.展开更多
基金funded by the National Natural Science Foundation of China(Grant No.82470766 to H.M.)the Jiangsu Provincial Medical Key Discipline(Laboratory)Cultivation Unit(Grant No.JSDW202206 to C.X.)the First Affiliated Hospital of Nanjing Medical University Clinical Capacity Enhancement Project(Grant No.JSPH-MC-2022-18 to C.X.).
文摘Acute kidney injury(AKI)is a critical condition with limited effective therapies.Akkermansia muciniphila(A.muciniphila)is a probiotic with multiple beneficial effects,including the regulation of epithelial cell tight junctions.Since renal pathophysiology is associated with gut barrier integrity,we hypothesized that A.muciniphila may have preventive effects on AKI.We established a lipopolysaccharide(LPS)-induced AKI mouse model to evaluate the effects of A.muciniphila.Our findings showed that pretreatment with A.muciniphila significantly attenuated kidney injury,as evidenced by reduced serum creatinine and urea nitrogen levels,alongside decreased tubular necrosis and apoptosis.A.muciniphila preserved intestinal barrier integrity and induced marked shifts in gut microbial ecology and the metabolome.A.muciniphila notably induced an increase in the relative abundance of the phylum Proteobacteria while decreasing in that of the phylum Bacteroidetes.At the genus level,Prevotella,Faecalibaculum,Moraxella,and Lactobacillus were more abundant in A.muciniphilapretreated mice.Metabolomic analysis revealed that A.muciniphila altered the gut metabolome,with changes involving pathways such as tyrosine metabolism,alanine/aspartate/glutamate homeostasis,cancer-related carbon flux,and GABAergic synaptic signaling.In conclusion,our findings indicate that A.muciniphila exerts renoprotective effects by modulating the gut-kidney axis,thereby establishing a foundation for future studies to explore the connection between gut microbiota and AKI.
文摘Male breast cancer(MBC)is rare,representing 0.5%–1%of all breast cancers,but its incidence is increasing due to improved diagnostics and awareness.MBC typically presents in older men,is human epidermal growth factor receptor 2(HER2)-negative and estrogen receptor(ER)-positive,and lacks routine screening,leading to delayed diagnosis and advanced disease.Major risk factors include hormonal imbalance,radiation exposure,obesity,alcohol use,and Breast Cancer Gene 1 and 2(BRCA1/2)mutations.Clinically,it may resemble gynecomastia but usually appears as a unilateral,painless mass or nipple discharge.Advances in imaging and liquid biopsy have enhanced early detection.Molecular mechanisms involve hormonal signaling,HER2/epidermal growth factor receptor(EGFR)pathways,tumor suppressor gene alterations,and epigenetic changes.While standard treatments mirror those for female breast cancer,emerging options such as cyclin-dependent kinase 4 and 6(CDK4/6),and poly(ADP-ribose)polymerase(PARP)inhibitors,immunotherapy,and precision medicine are reshaping management.Incorporating artificial intelligence,molecular profiling,and male-specific clinical trials is essential to improve outcomes and bridge current diagnostic and therapeutic gaps.
基金supported by the National Natural Science Foundation of China,Nos.82272470 (to GN),82072439 (to GN),81930070 (to SF)the Tianjin Health Key Discipline Special Project,No.TJWJ2022XK011 (to GN)+2 种基金the Outstanding Youth Foundation of Tianjin Medical University General Hospital,No.22ZYYJQ01 (to GN)Tianjin Key Medical Disciplines,No.TJYXZDXK-027A (to SF)National Key Research and Development Program-Stem Cells and Transformation Research,No.2019YFA0112100 (to SF)
文摘Traumatic spinal cord injury result in considerable and lasting functional impairments,triggering complex inflammatory and pathological events.Spinal cord scars,often metaphorically referred to as“fire barriers,”aim to control the spread of neuroinflammation during the acute phase but later hinder axon regeneration in later stages.Recent studies have enhanced our understanding of immunomodulation,revealing that injury-associated inflammation involves various cell types and molecules with positive and negative effects.This review employs bibliometric analysis to examine the literature on inflammatory mediators in spinal cord injury,highlighting recent research and providing a comprehensive overview of the current state of research and the latest advances in studies on neuroinflammation related to spinal cord injury.We summarize the immune and inflammatory responses at different stages of spinal cord injury,offering crucial insights for future research.Additionally,we review repair strategies based on inflammatory mediators for the injured spinal cord.Finally,this review discusses the current status and future directions of translational research focused on immune-targeting strategies,including pharmaceuticals,biomedical engineering,and gene therapy.The development of a combined,precise,and multitemporal strategy for the repair of injured spinal cords represents a promising direction for future research.
基金"973"National Key Basic Research and Development Program(No.2012CB518202)Project of Qinghai Development of Science and Technology(No.2011-N-150)
文摘On April 14,2010,an earthquake reaching Richter scale 7.1 struck Jiegu Town of Yushu,a mountain rescue operation promptly launched. All injurers had a direct assess to take medical care,and were immediately rescued and rapidly evacuated by air to Xining and Golmud at lower altitudes and admitted to advanced hospitals. Almost all of the injurers have been completely recovered. Yushu Earthquake was one of the highest earthquakes in the world,with a high incidence of acute altitude illness,which was observed in about 80 % of the lowland rescuers at an altitude of 4 000 m."Rescue the rescuers"became the major task of Qinghai-Tibetan rescue teams,all the severe patients were rapidly descended to Xining and treated promptly and effectively. The outcome was excellent,all patients survived. After the earthquake,it is a long and arduous task to reconstruct what has been destroyed. Medical teams continue to work in the Yushu Earthquake area because about 30 000 workers and carders are now here for rebuilding the earthquake center. Thus the prevention and treatment of altitude illness are still critical tasks for medical teams. Although all the fights are successful,there are more experiences and lessons we have learned from the medical mountain rescue during the earthquake and the reconstruction,and reports here are to sum up our experiences from the medical mountain rescue operation in Yushu Earthquake and draw the lessons that we should learn. With the increasing of earthquake probability occurring in the Qinghai-Tibetan Plateau,we also should prepare against earthquake disasters and for further rescue training in the high mountains.
基金supported by the in-house Laboratory Independent Research (ILIR) program of the U.S. Army
文摘After a radiological or nuclear event, acute radiation syndrome(ARS) will present complex medical challenges that could involve the treatment of hundreds to thousands of patients. Current medical doctrine is based on limited clinical data and remains inadequate. Efforts to develop medical innovations that address ARS complications are unlikely to be generated by the industry because of market uncertainties specific to this type of injury. A prospective strategy could be the integration of cellular therapy to meet the medical demands of ARS. The most clinically advanced cellular therapy to date is the administration of mesenchymal stem cells(MSCs). Results of currently published investigations describing MSC safety and efficacy in a variety of injury and disease models demonstrate the unique qualities of this reparative cell population in adapting to the specific requirements of the damaged tissue in which the cells integrate. This report puts forward a rationale for the further evaluation of MSC therapy to address the current unmet medical needs of ARS. We propose that the exploration of this novel therapy for the treatment of the multivariate complications of ARS could be of invaluable benefit to military medicine.
文摘Organogenesis is regulated by a complex network of intrinsic cues, diffusible signals and cell/cell or cell/matrix interactions that drive the cells of a prospective organ to differentiate and collectively organize in three dimensions. Generating organs in vitro from embryonic stem (ES) cells may provide a simplified system to decipher how these processes are orchestrated in time and space within particular and between neighboring tissues. Recently, this field of stem cell research has also gained considerable interest for its potential applications in regenerative medicine. Among human pathologies for which stem cell-based therapy is foreseen as a promising therapeutic strategy are many retinal degenerative diseases, like retinitis pigmentosa and age-related macular degeneration. Over the last decade, progress has been made in producing ES-derived retinal cells in vitro, but engineering entire synthetic retinas was considered beyond reach. Recently however, major breakthroughs have been achieved with pioneer works describing the extraordinary self-organization of murine and human ES cells into a three dimensional structure highly resembling a retina. ES-derived retinal cells indeed assemble to form a cohesive neuroepithelial sheet that is endowed with the intrinsic capacity to recapitulate, outside an embryonic environment, the main steps of retinal morphogenesis as observed in vivo. This represents a tremendous advance that should help resolving fundamental questions related to retinogenesis. Here, we will discuss these studies, and the potential applications of such stem cell-based systems for regenerative medicine.
文摘Objective:The aim of this article was to discuss the theory of doctor-patient co-operated evidence-based medical record and set up the preliminary frame of the doctor-patient co-operated evidence-based medical record following the concept of narrative evidence-based medicine.Methods:The information was searched from Pubmed,Embase,CBMdisc,CNKI.A preliminary agreement was reached by referring to the principles of narrative medicine and advises given by experts of digestive system and evidence-based medicine in both Traditional Chinese Medicine and Western Medicine.Result:This research is a useful attempt to discuss the establishment of doctor-patient co-operated evidence-based medical record guided by the direction of narrative evidence-based medicine.Reflection and outlook:Doctor-patient co-operated medical record can be a key factor of the curative effect evaluation methodology system of integrated therapy of Tradition Chinese Medicine and Western Medicine on spleen and stomach diseases.
文摘Heaven-human-earth Pattern (HHE) regarded as a crucial conception of traditional Chinese medicine (TCM) has been applied extensively in TCM diagnostics, etiology, acupuncture therapeutics, materia medica and herbal formula, etc. It associates closely with Chinese classic cosmology. Since ancient time of China, many cosmic phenomena have been introduced to prove or illustrate TCM theories. Moreover, the five-element theory has been proven to be in keeping with some modern approaches of life provenance and life evolution. As a result, Chinese materia medica develops in a way of a pure natural medicine. It is of great significance that by realizing the natural features, the public nowadays can understand TCM better in its scientific connotations.
基金a grant from the National Research Foundation of Korea(NRF)(No.2011-0030001)the Global Core Research Center(GCRC)funded by the Korean government(MSIP).
文摘Background:Administrative database provides valuable information for large cohort studies,especially when tissue diagnosis is rather difficult such as the diagnosis for bile duct cancer(BDC).The aim of this study was to evaluate the diagnostic accuracy of administrative database for BDC by International Classification of Diseases(ICD)-10 codes in a tertiary institute.Methods:BDC and control groups were collected from 2003 to 2016 at Seoul National University Bundang Hospital.Cases of BDC were identified in the National Health Insurance Service(NHIS)database by ICD 10-code supported by V code.The control group was selected from cases without ICD-10 codes for BDC.A definite or possible diagnosis was defined according to pathologic reports.Medical records,images,and pathology reports were analyzed to evaluate ICD-10 codes for BDC.Sensitivity,specificity,positive predictive value,and negative predictive value for BDC were analyzed according to diagnostic criteria and cancer locations.Results:A total of 1707 patients with BDC and 1707 controls were collected.Among those with BDC,1320(77.3%)were diagnosed by definite criteria.Most(99.4%)of them had adenocarcinoma.Rate of definite diagnosis was the highest for ampulla of Vater(88.9%),followed by that for extrahepatic(84.9%)and intrahepatic(68.3%)BDCs.False positive cases commonly had hepatocellular carcinomas.For overall diagnosis of BDC,sensitivity,specificity,positive predictive value,and negative predictive value were 99.94%,98.33%,98.30%,and 99.94%,respectively.Diagnostic accuracies were similar regardless of diagnostic criteria or tumor locations.Conclusions:Administrative database for BDC collected according to ICD-10 code with V code shows good accuracy.
文摘Objectives: Different surgical techniques, with variable morbidity and recurrence rates, have been advocated for the management of chronic pilonidal sinus (PNS). This study was conducted to report the outcome of surgical treatment of 634 cases of chronic PNS at a single institute between January 2001 and January 2010. Methods: Karydakis flap was performed in 244 patients (38.5%, Group 1). Excision and midline closure was performed in 371 patients (58.5%, Group 2), while the open method was used in 19 (3.0%). Data regarding patient and sinus characteristics, operative de-tails, postoperative course, complications and recurrence were recorded. Mean follow-up was 73.5 months. Results: 571 patients were male (90.1%) and 63 were female (9.9%). Their ages ranged between 16 - 44 years (mean 25.7 years). The mean body mass index was 31.2 (range 23.6 - 41.9), and 71.5% (453/634) were hirsute. Chronic PNS was the first presentation (primary) in 504 patients (79.5%) and recurrent in 130 (20.5%).Overall complication rate was 16.1% (102/ 634) and overall recurrence rate was 8.4% (53/634). Comparing both groups showed that they were similar regarding demographic characteristics, clinical presentation, hospital stay, healing time and time off work. Operative time was insignificantly longer with Karydakis technique (mean 43.2 versus 39.1 minutes, respectively). Complications were sig-nificantly more in patients with midline closure (21%, 78/371) as compared with Karydakis procedure (9%, 22/244) (P = 0.0001). Likewise, there was a significantly (P = 0.0001) higher rate of recurrence with midline closure (12.1%, 45/371) as opposed to Karydakis technique (2.5%, 6/244). Conclusions: 1) PNS affects mainly young male adults who are usually, obese and hirsute, 2) Karydakis technique for the management of chronic PNS, whether primary or recurrent, is a non-lengthy, efficient procedure that has less overall complications and a lower recurrence rate than conventional excision and midline closure.
基金suppor ted by the National Key Research and Development Program of China (2022YFC2702502)the National Natural Science Foundation of China (32170742, 31970646, and 32060152)+7 种基金the Start Fund for Specially Appointed Professor of Jiangsu ProvinceHainan Province Science and Technology Special Fund (ZDYF2021SHFZ051)the Natural Science Foundation of Hainan Province (820MS053)the Start Fund for High-level Talents of Nanjing Medical University (NMUR2020009)the Marshal Initiative Funding of Hainan Medical University (JBGS202103)the Hainan Province Clinical Medical Center (QWYH202175)the Bioinformatics for Major Diseases Science Innovation Group of Hainan Medical Universitythe Shenzhen Science and Technology Program (JCYJ20210324140407021)
文摘The application of single-cell RNA sequencing(scRNA-seq)in biomedical research has advanced our understanding of the pathogenesis of disease and provided valuable insights into new diagnostic and therapeutic strategies.With the expansion of capacity for high-throughput scRNA-seq,including clinical samples,the analysis of these huge volumes of data has become a daunting prospect for researchers entering this field.Here,we review the workflow for typical scRNA-seq data analysis,covering raw data processing and quality control,basic data analysis applicable for almost all scRNA-seq data sets,and advanced data analysis that should be tailored to specific scientific questions.While summarizing the current methods for each analysis step,we also provide an online repository of software and wrapped-up scripts to support the implementation.Recommendations and caveats are pointed out for some specific analysis tasks and approaches.We hope this resource will be helpful to researchers engaging with scRNA-seq,in particular for emerging clinical applications.
文摘Objective:In this study,we try to establish an initial electron beam model by combining Monte Carlo simulation method with particle dynamic calculation(TRSV)for the single 6 MV X-ray accelerating waveguide of BJ-6 medical linac.Methods and Materials:1.We adapted the treatment head configuration of BJ-6 medical linac made by Beijing Medical Equipment Institute(BMEI)as the radiation system for this study.2.Use particle dynamics calculation code called TRSV to drive out the initial electron beam parameters of the energy spectrum,the spatial intensity distribution,and the beam incidence angle.3.Analyze the 6 MV X-ray beam characteristics of PDDc,OARc in a water phantom by using Monte Carlo simulation(BEAMnrc,DOSXYZnrc)for a preset of the initial electron beam parameters which have been determined by TRSV,do the comparisons of the measured results of PDDm,OARm in a real water phantom,and then use the deviations of calculated and measured results to slightly modify the initial electron beam model back and forth until the deviations meet the error less than 2%.Results:The deviations between the Monte Carlo simulation results of percentage depth doses at PDDc and off-axis ratios OARc and the measured results of PDDm and OARm in a water phantom were within 2%.Conclusion:When doing the Monte Carlo simulation to determine the parameters of an initial electron beam for a particular medical linac like BJ-6,modifying some parameters based on the particle dynamics calculation code would give some more reasonable and more acceptable results.
文摘BACKGROUND Transplant teams often hesitate to use the right kidney(RK)in living donor(LD)transplants due to the complexities of anastomosing the short,thin-walled right renal veins,which can potentially lead to graft loss or graft dysfunction.Nevertheless,circumstances may arise where selecting the RK over the left kidney(LK)is unavoidable.Consequently,it is crucial to thoroughly examine the implications of such a choice on the overall transplant outcome.AIM To compare transplant outcomes between recipients of RK and LK while examining the factors that influence these outcomes.METHODS We retrospectively analyzed data from adult patients who received LD kidney transplants involving meticulous patient selection and surgical techniques at our center from January 2020 to December 2023.We included all kidney donors who were over 18,fit to donate,and had undergone diethylenetriamine pentaacetic acid split function and/or computed tomography based volumetry.The variables examined comprised donor and recipient demographics,and outcome measures included technical graft loss(TGL),delayed or slow graft function(SGF),and post-transplant serum creatinine(SC)trends.We used a logistic regression model to assess the likelihood of adverse outcomes considering the donor kidney side.RESULTS Of the 250 transplants performed during the period,56(22%)were RKs.The recipient demographics and transplant factors were comparable for the right and LKs,except that the donor warm and cold ischemia time were shorter for RKs.TGL and SGF each occurred in 2%(n=1)of RKs and 0.5%(n=1)of LKs,the difference being insignificant.These complications,however,were not related to the venous anastomosis.One RK(2%)developed delayed graft function after 48 hours,which was attributable to postoperative hypoxia rather than the surgical technique.The post-transplant SC trend and mean SC at the last follow-up were similar across both kidney sides.CONCLUSION The donor kidney side has little impact on post-transplant adverse events and graft function in LD transplants,provided that careful patient selection and precise surgical techniques are employed.
文摘Objective Oral squamous cell carcinoma(OSCC)is an aggressive cancer with a high mortality rate.San-Zhong-Kui-Jian-Tang(SZKJT),a Chinese herbal formula,has long been used as an adjuvant therapy in cancer clinical practice.Although its therapeutic effects and molecular mechanisms in OSCC have been previously elucidated,the potential interactions and mechanisms between the active phytochemicals and their therapeutic targets are still lacking.Methods The present study employed network pharmacology and topology approaches to establish a“herbal ingredients–active phytochemicals–target interaction”network to explore the potential therapeutic targets of SZKJT-active phytochemicals in the treatment of OSCC.The role of the target proteins in oncogenesis was assessed via GO and KEGG enrichment analyses,and their interactions with the active phytochemicals of SZKJT were calculated via molecular docking and dynamic simulations.The pharmacokinetic properties and toxicity of the active phytochemicals were also predicted.Results A total of 171 active phytochemicals of SZKJT fulfilled the bioavailability and drug-likeness screening criteria,with the flavonoids quercetin,kaempferol,and naringenin having the greatest potential.The 4 crucial targets of these active phytochemicals are PTGS2,TNF,BCL2,and CASP3,which encode cyclooxygenase-2,tumor necrosis factor(TNF),BCL-2 apoptosis regulator,and caspase-3,respectively.The interactions between phytochemicals and target proteins were predicted to be thermodynamically feasible and stable via molecular docking and dynamics simulations.Finally,the results revealed that the IL-6/JAK/STAT3 pathway and TNF signaling via NF-κB are the two prominent pathways targeted by SZKJT.Conclusion In summary,this study provides computational data for in-depth exploration of the mechanism by which SZKJT activates phytochemicals to treat OSCC.
基金supported by the Hyperbaric Med School of the Department of Biomedical Sciences at the University of Padova,the Italian Air Force,and the Institute of Clinical Physiology(Milan)-National Research Council(IFC-CNR).
文摘Dear Editor,Space flight(SF)is substantially increasing at present.The emergence of commercial suborbital SF,such as the Virgin Galactic with VSS Unity and VMS Eve spacecraft,is extending to civilians,being previously confined to military and/or professional astronauts only.This new evidence offers additional opportunities for better characterizing the impact that the transition from Earth’s 1G to microgravity in space could have on the astronauts’health while comparing well-trained subjects such as the latt er to space newcomers[1].
基金supported by the Natural Science Foundation of Heilongjiang Province of China,Outstanding Youth Foundation,No.YQ2022H003 (to DW)。
文摘N6-methyladenosine(m^(6)A), the most prevalent and conserved RNA modification in eukaryotic cells, profoundly influences virtually all aspects of mRNA metabolism. mRNA plays crucial roles in neural stem cell genesis and neural regeneration, where it is highly concentrated and actively involved in these processes. Changes in m^(6)A modification levels and the expression levels of related enzymatic proteins can lead to neurological dysfunction and contribute to the development of neurological diseases. Furthermore, the proliferation and differentiation of neural stem cells, as well as nerve regeneration, are intimately linked to memory function and neurodegenerative diseases. This paper presents a comprehensive review of the roles of m^(6)A in neural stem cell proliferation, differentiation, and self-renewal, as well as its implications in memory and neurodegenerative diseases. m^(6)A has demonstrated divergent effects on the proliferation and differentiation of neural stem cells. These observed contradictions may arise from the time-specific nature of m^(6)A and its differential impact on neural stem cells across various stages of development. Similarly, the diverse effects of m^(6)A on distinct types of memory could be attributed to the involvement of specific brain regions in memory formation and recall. Inconsistencies in m^(6)A levels across different models of neurodegenerative disease, particularly Alzheimer's disease and Parkinson's disease, suggest that these disparities are linked to variations in the affected brain regions. Notably, the opposing changes in m^(6)A levels observed in Parkinson's disease models exposed to manganese compared to normal Parkinson's disease models further underscore the complexity of m^(6)A's role in neurodegenerative processes. The roles of m^(6)A in neural stem cell proliferation, differentiation, and self-renewal, and its implications in memory and neurodegenerative diseases, appear contradictory. These inconsistencies may be attributed to the timespecific nature of m^(6)A and its varying effects on distinct brain regions and in different environments.
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 a grant from the Health Research New Zealand(HRC)22/559(to AJG and LB)。
文摘Moderate to severe perinatal hypoxic-ischemic encephalopathy occurs in~1 to 3/1000 live births in high-income countries and is associated with a significant risk of death or neurodevelopmental disability.Detailed assessment is important to help identify highrisk infants,to help families,and to support appropriate interventions.A wide range of monitoring tools is available to assess changes over time,including urine and blood biomarkers,neurological examination,and electroencephalography.At present,magnetic resonance imaging is unique as although it is expensive and not suited to monitoring the early evolution of hypoxic-ischemic encephalopathy by a week of life it can provide direct insight into the anatomical changes in the brain after hypoxic-ischemic encephalopathy and so offers strong prognostic information on the long-term outcome after hypoxic-ischemic encephalopathy.This review investigated the temporal dynamics of neonatal hypoxic-ischemic encephalopathy injuries,with a particular emphasis on exploring the correlation between the prognostic implications of magnetic resonance imaging scans in the first week of life and their relationship to long-term outcome prediction,particularly for infants treated with therapeutic hypothermia.A comprehensive literature search,from 2016 to 2024,identified 20 pertinent articles.This review highlights that while the optimal timing of magnetic resonance imaging scans is not clear,overall,it suggests that magnetic resonance imaging within the first week of life provides strong prognostic accuracy.Many challenges limit the timing consistency,particularly the need for intensive care and clinical monitoring.Conversely,although most reports examined the prognostic value of scans taken between 4 and 10 days after birth,there is evidence from small numbers of cases that,at times,brain injury may continue to evolve for weeks after birth.This suggests that in the future it will be important to explore a wider range of times after hypoxic-ischemic encephalopathy to fully understand the optimal timing for predicting long-term outcomes.
文摘BACKGROUND Restless legs syndrome(RLS)is characterized by an urge to move with an unpleasant sensation in the lower limbs.RLS typically affects the legs.However,it can also affect several other body regions,such as the arms,abdomen,face,neck,head,and genital area.There are only a few reports of the RLS variant affecting the head.AIM To assess the epidemiological,clinical,and other aspects of the RLS variant affecting the head.METHODS We conducted a retrospective study of 17 adult patients(>18 years)who met the RLS criteria and simultaneously experienced RLS-like symptoms in the head.RESULTS The median age at which symptoms appeared was 41.6 years.Males and females were equally affected(1.1:1).All 17 patients had uncomfortable sensations in the lower legs.Insomnia or disturbed sleep was the most common comorbidity(n=16,88.2%).However,headache was the most common presenting or primary symptom(n=10,70.5%).Dizziness or an abnormal sensation in the head was the second most common presenting symptom(5 patients,29.4%).Other presenting features were leg pain,backache,and generalized body pain.All patients responded favorably to dopaminergic medications.CONCLUSION If RLS-related unpleasant sensations and pain are felt in the head,they may be misinterpreted as headache,dizziness,or psychosomatic symptoms.RLS and headaches in a subset of patients may be two phenotypic manifestations of the same disorder.
文摘BACKGROUND Understanding a patient's clinical status and setting priorities for their care are two aspects of the constantly changing process of clinical decision-making.One analytical technique that can be helpful in uncertain situations is clinical judgment.Clinicians must deal with contradictory information,lack of time to make decisions,and long-term factors when emergencies occur.AIM To examine the ethical issues healthcare professionals faced during the coronavirus disease 2019(COVID-19)pandemic and the factors affecting clinical decision-making.METHODS This pilot study,which means it was a preliminary investigation to gather information and test the feasibility of a larger investigation was conducted over 6 months and we invited responses from clinicians worldwide who managed patients with COVID-19.The survey focused on topics related to their professional roles and personal relationships.We examined five core areas influencing critical care decision-making:Patients'personal factors,family-related factors,informed consent,communication and media,and hospital administrative policies on clinical decision-making.The collected data were analyzed using the χ^(2) test for categorical variables.RESULTS A total of 102 clinicians from 23 specialties and 17 countries responded to the survey.Age was a significant factor in treatment planning(n=88)and ventilator access(n=78).Sex had no bearing on how decisions were made.Most doctors reported maintaining patient confidentiality regarding privacy and informed consent.Approximately 50%of clinicians reported a moderate influence of clinical work,with many citing it as one of the most important factors affecting their health and relationships.Clinicians from developing countries had a significantly higher score for considering a patient's financial status when creating a treatment plan than their counterparts from developed countries.Regarding personal experiences,some respondents noted that treatment plans and preferences changed from wave to wave,and that there was a rapid turnover of studies and evidence.Hospital and government policies also played a role in critical decision-making.Rather than assessing the appropriateness of treatment,some doctors observed that hospital policies regarding medications were driven by patient demand.CONCLUSION Factors other than medical considerations frequently affect management choices.The disparity in treatment choices,became more apparent during the pandemic.We highlight the difficulties and contradictions between moral standards and the realities physicians encountered during this medical emergency.False information,large patient populations,and limited resources caused problems for clinicians.These factors impacted decision-making,which,in turn,affected patient care and healthcare staff well-being.
