Objective The associations of serum trace element levels with disease progression and survival duration were assessed in individuals diagnosed with sporadic amyotrophic lateral sclerosis(sALS)in China.Methods Clinical...Objective The associations of serum trace element levels with disease progression and survival duration were assessed in individuals diagnosed with sporadic amyotrophic lateral sclerosis(sALS)in China.Methods Clinical data,including diagnostic indicators,clinical characteristics,Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised(ALSFRS-R)scores,and serum concentrations of calcium(Ca),magnesium(Mg),iron(Fe),copper(Cu),and zinc(Zn),were collected for hospitalized patients with sALS between 2018 and 2021.Correlation analysis,random forest analysis,and the Gehan-Breslow-Wilcoxon test were used to evaluate the relations between serum trace element levels,disease progression,and survival duration.Results Lower serum Ca levels and higher Mg levels were observed in patients with ALSFRS-R scores<39.Serum Mg was significantly negatively correlated with ALSFRS-R,trunk,and respiratory scores.Serum Cu and Zn also showed significant negative correlations with the respiratory score,whereas Ca and Fe were not significantly correlated with the ALSFRS-R score.The serum levels of Ca,Mg,Cu,Zn,and Fe remained consistent regardless of the site of disease onset.ALSFRS-R analysis revealed that serum Ca and Mg had a substantial effect on the total ALSFRS-R score,with serum Mg significantly influencing the course of the disease.Notably,low serum Mg levels were associated with extended survival times in patients with sALS.Conclusion Serum levels of Ca and Mg play critical roles in the progression of sALS,and a reduced serum Mg level is related to an extended survival time.展开更多
Detecting biomarkers in body fluids by optical lateral flow immune assay(LFIA) technology provides rapid access to disease information for early diagnosis.LFIA is based on an antigen-antibody reaction and is rapidly b...Detecting biomarkers in body fluids by optical lateral flow immune assay(LFIA) technology provides rapid access to disease information for early diagnosis.LFIA is based on an antigen-antibody reaction and is rapidly becoming the preferred choice of physicians and patients for point-of-care testing due to its simplicity,cost-effectiveness,and rapid detection.Observing the optical signal change from the colloidal gold of the traditional LFIA strip has been widely applied for various biomarkers detection in body fluids.Despite the significant progress,rapid real-time detection of color changes in the colloidal gold by the naked eye still faces many limitations,such as large errors and the inability to quantify and accurately detect.New optical LFIA strip technology has emerged in recent years to extend its application scenarios for achieving quantitative detection such as fluorescence,afterglow,and chemiluminescence.Herein,we summarized the development of optical LFIA technology from single to hyphenated optical signals for biomarkers detection in body fluids from invasive and non-invasive sources.Moreover,the challenge and outlook of optical LFIA strip technology are highlighted to inspire the designing of next-generation diagnostic platforms.展开更多
Lateral movement represents the most covert and critical phase of Advanced Persistent Threats(APTs),and its detection still faces two primary challenges:sample scarcity and“cold start”of new entities.To address thes...Lateral movement represents the most covert and critical phase of Advanced Persistent Threats(APTs),and its detection still faces two primary challenges:sample scarcity and“cold start”of new entities.To address these challenges,we propose an Uncertainty-Driven Graph Embedding-Enhanced Lateral Movement Detection framework(UGEA-LMD).First,the framework employs event-level incremental encoding on a continuous-time graph to capture fine-grained behavioral evolution,enabling newly appearing nodes to retain temporal contextual awareness even in the absence of historical interactions and thereby fundamentally mitigating the cold-start problem.Second,in the embedding space,we model the dependency structure among feature dimensions using a Gaussian copula to quantify the uncertainty distribution,and generate augmented samples with consistent structural and semantic properties through adaptive sampling,thus expanding the representation space of sparse samples and enhancing the model’s generalization under sparse sample conditions.Unlike static graph methods that cannot model temporal dependencies or data augmentation techniques that depend on predefined structures,UGEA-LMD offers both superior temporaldynamic modeling and structural generalization.Experimental results on the large-scale LANL log dataset demonstrate that,under the transductive setting,UGEA-LMD achieves an AUC of 0.9254;even when 10%of nodes or edges are withheld during training,UGEA-LMD significantly outperforms baseline methods on metrics such as recall and AUC,confirming its robustness and generalization capability in sparse-sample and cold-start scenarios.展开更多
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder characterized by the progressive degeneration of upper and lower motor neurons in the brainstem and spinal cord,leading to muscle weakness,para...Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder characterized by the progressive degeneration of upper and lower motor neurons in the brainstem and spinal cord,leading to muscle weakness,paralysis,and respiratory failure (Morgan and Orrell,2016).展开更多
The growing recognition of the role of genetics in the development of amyotrophic lateral sclerosis is evident.However,there has yet to be a comprehensive analysis of the clinical characteristics and genetics of famil...The growing recognition of the role of genetics in the development of amyotrophic lateral sclerosis is evident.However,there has yet to be a comprehensive analysis of the clinical characteristics and genetics of familial amyotrophic lateral sclerosis in an Asian population.This study aimed to provide an in-depth analysis of the clinical features and genetic spectrum of familial amyotrophic lateral sclerosis over 15 years in a clinic-based cohort of patients from the Chinese mainland.Enrollment of 302 amyotrophic lateral sclerosis families from 28 provinces was undertaken from January 2008 to September 2023.A group-based trajectory model for disease progression based on amyotrophic lateral sclerosis Functional Rating Scale-Revised(ALSFRS-R)scores was validated using bootstrap internal validation in patients with familial amyotrophic lateral sclerosis,as well as patients with sporadic amyotrophic lateral sclerosis(matched at a 1:4 ratio,with replacement).DNA samples from 244 index patients were screened for variants in the pathogenic genes SOD1,FUS,TDP43,and C9ORF72,of which 146 were also subjected to genome-wide next-generation sequencing.Gene-level burden analysis was used to evaluate the distribution of rare variants in the cohort.We found that rapid dynamic disease progression was associated with an older age at onset,shorter diagnostic delay,lower body mass index,bulbar onset,and≥1 affected first-degree relative.Certain attributes,such as age at onset and time from onset to diagnosis,had comparable impacts on the clinical progression trajectories of both familial amyotrophic lateral sclerosis and sporadic amyotrophic lateral sclerosis.Harboring pathogenic/likely pathogenic variants in amyotrophic lateral sclerosis-causative genes reduced the age of onset of familial amyotrophic lateral sclerosis.Among the patients with familial amyotrophic lateral sclerosis,17.8%possessed≥2 pathogenic/likely pathogenic variants.Sequencing kernel association test analysis showed that the SOD1 rare variant burden(P=1.3e-15)was associated with a significant risk of familial amyotrophic lateral sclerosis.Our findings conclusively confirmed the clinical features and genetic spectrum of familial amyotrophic lateral sclerosis over 15 years in a clinical cohort from China,contributing to a deeper understanding of genotype-phenotype relationships in familial amyotrophic lateral sclerosis.This comprehensive evaluation of specific clinical characteristics,clinical prognosis,and genetic variants of amyotrophic lateral sclerosis based on detailed clinical and genetic information may lead to the development of genotype-specific treatment approaches.展开更多
AIM: To evaluate the long-term results of radiofrequency ablation (RFA) compared to left lateral sectionectomy (LLS) in patients with Child-Pugh class A disease for the treatment of single and small hepatocellular car...AIM: To evaluate the long-term results of radiofrequency ablation (RFA) compared to left lateral sectionectomy (LLS) in patients with Child-Pugh class A disease for the treatment of single and small hepatocellular carcinoma (HCC) in the left lateral segments.展开更多
Amyotrophic lateral sclerosis is a devastating neurodegenerative disease for which the current treatment approaches remain severely limited.The principal pathological alterations of the disease include the selective d...Amyotrophic lateral sclerosis is a devastating neurodegenerative disease for which the current treatment approaches remain severely limited.The principal pathological alterations of the disease include the selective degeneration of motor neurons in the brain,brainstem,and spinal cord,as well as abnormal protein deposition in the cytoplasm of neurons and glial cells.The biological markers under extensive scrutiny are predominantly located in the cerebrospinal fluid,blood,and even urine.Among these biomarke rs,neurofilament proteins and glial fibrillary acidic protein most accurately reflect the pathologic changes in the central nervous system,while creatinine and creatine kinase mainly indicate pathological alterations in the peripheral nerves and muscles.Neurofilament light chain levels serve as an indicator of neuronal axonal injury that remain stable throughout disease progression and are a promising diagnostic and prognostic biomarker with high specificity and sensitivity.However,there are challenges in using neurofilament light chain to diffe rentiate amyotrophic lateral sclerosis from other central nervous system diseases with axonal injury.Glial fibrillary acidic protein predominantly reflects the degree of neuronal demyelination and is linked to non-motor symptoms of amyotrophic lateral sclerosis such as cognitive impairment,oxygen saturation,and the glomerular filtration rate.TAR DNA-binding protein 43,a pathological protein associated with amyotrophic lateral sclerosis,is emerging as a promising biomarker,particularly with advancements in exosome-related research.Evidence is currently lacking for the value of creatinine and creatine kinase as diagnostic markers;however,they show potential in predicting disease prognosis.Despite the vigorous progress made in the identification of amyotrophic lateral sclerosis biomarkers in recent years,the quest for definitive diagnostic and prognostic biomarke rs remains a formidable challenge.This review summarizes the latest research achievements concerning blood biomarkers in amyotrophic lateral sclerosis that can provide a more direct basis for the differential diagnosis and prognostic assessment of the disease beyond a reliance on clinical manifestations and electromyography findings.展开更多
We are reporting a long-time magnetic resonance imaging(MRI) follow-up in a rare case of cardiac left lateral wall hypertrophy. Hypertrophic cardiomyopathy(HCM) is the most common genetic cardiovascular disorder and a...We are reporting a long-time magnetic resonance imaging(MRI) follow-up in a rare case of cardiac left lateral wall hypertrophy. Hypertrophic cardiomyopathy(HCM) is the most common genetic cardiovascular disorder and a significant cause of sudden cardiac death. Cardiac magnetic resonance(CMR) imaging can be a valuable tool for assessment of detailed information on size,localization,and tissue characteristics of hypertrophied myocardium. However,there is still little knowledge of long-term evolution of HCM as visualized by magnetic resonance imaging. Recently,our group reported a case of left lateral wall HCM as a rare variant of the more common forms,such as septal HCM,or apical HCM. As we now retrieved an old cardiac MRI acquired in this patient more than 20 years ago,we are able to provide the thrilling experience of an ultra-long MRI followup presentation in this rare case of left lateral wall hypertrophy. Furthermore,this case outlines the tremendous improvements in imaging quality within the last two decades of CMR imaging.展开更多
BACKGROUND A limited number of studies have demonstrated that sleeping in the left lateral decubitus(LLD)decreases nocturnal reflux in patients with gastroesophageal reflux disease(GERD)compared to right lateral decub...BACKGROUND A limited number of studies have demonstrated that sleeping in the left lateral decubitus(LLD)decreases nocturnal reflux in patients with gastroesophageal reflux disease(GERD)compared to right lateral decubitus(RLD)and supine.AIM This systematic review summarizes the association between sleeping in the LLD position and nocturnal reflux in patients with GERD.METHODS Studies published up to July 17,2023,in MEDLINE,EMBASE,and CENTRAL were searched.Eligible studies were randomized and nonrandomized studies assessing the effect of sleeping in LLD compared to RLD and supine in reducing nocturnal reflux in GERD patients.Outcomes include the acid exposure time(AET)(%time in pH<4),acid clearance time(ACT)(in sec/episode),number of reflux episodes,and improvement in N-GSSIQ scores.RESULTS Two nonrandomized studies showed decreased AET and ACT in LLD sleep position in comparison to RLD(mean difference[MD]-2.03[95%CI:-3.62 to-0.45];-81.84[95%CI:-127.48 to-36.20],respectively)and supine position(MD-2.71[95%CI:-4.34 to-1.09];-74.47[95%CI:-116.26 to-32.69],respectively).There was no difference in AET and ACT between RLD sleep position and supine.Furthermore,one randomized controlled trial investigating the use of electronic sleep positional therapy,which increased the duration of LLD sleep and decreased the duration of RLD sleep compared to sham,showed nocturnal symptoms improvement(improved N-GSSIQ score,increased reflux-free nights,and resolution of nocturnal reflux symptoms).CONCLUSION Current evidence suggests that sleeping on the left side could reduce nocturnal reflux and improve GERD-related quality of life,therefore warranting interventions that promote LLD sleep position.展开更多
BACKGROUND:Tracheal intubation(TI)is a fundamental procedure for securing the airway or assisting ventilation in emergency medicine.Tracheal intubation in the lateral position(TILP)has been utilized in clinical practi...BACKGROUND:Tracheal intubation(TI)is a fundamental procedure for securing the airway or assisting ventilation in emergency medicine.Tracheal intubation in the lateral position(TILP)has been utilized in clinical practice,demonstrating potential advantages in specific scenarios,including emergency settings.However,there is a lack of comprehensive reviews and practical protocols on TILP application.To address this gap,we performed a narrative review,and provided evidence-based recommendations to formulate a practice protocol,to assist clinicians to effectively apply TILP.METHODS:We conducted a narrative review of TILP applications and developed recommendations based on clinical research evidence and clinical experience.Delphi method was used among the TILP consortium to grade the strength of the recommendations and to help reach consensus.The practice protocols were formulated as warranted by advancements in medical knowledge,technology,and practice.RESULTS:This narrative review summarized the current evidence on TILP application,highlighting its safety,efficacy,challenges,and potential complications.In total,24 recommendations and a clinical protocol for TILP application in emergency patients were established.CONCLUSION:TILP is a valuable technique in emergency medicine.We reviewed its application in emergency settings and formulated recommendations along with a clinical practice protocol.Future studies are needed to evaluate the safety and efficacy of TILP,broaden its scope of application,and explore effective training protocols.展开更多
Objectives: This study aimed to evaluate operative benefits of artificial pnuemothorax in thoracoscopic esophagectomy in the left lateral decubitus position. Methods: We retrospectively analyzed short-term surgical ou...Objectives: This study aimed to evaluate operative benefits of artificial pnuemothorax in thoracoscopic esophagectomy in the left lateral decubitus position. Methods: We retrospectively analyzed short-term surgical outcomes including learning curve of 60 consecutive patients who underwent thoracoscopic esophagectomy with artificial pnuemothorax in the left lateral decubitus position between April 2010 and November 2012 in our department. Results: The median operation time and intraoperative blood loss were 443 min and 220 ml, respectively, and these values were 174 min and 95 ml, respectively, in the thoracic phase of surgery. The median number of harvested lymph node was 37. Only 1 patient required conversion to open esophagectomy. The postoperative 30-day mortality rate was 1.7%. The thoracic operation time significantly decreased after an experience of 10 cases and intraoperative blood loss during thoracic phasesignificantly decreased after an experience of 20 cases (p < 0.05), and operation time remained constant for the following cases. The number of harvested lymph nodes did not exhibit significant changes with an increase in the number of case experienced. Conclusions: Artificial pneumothorax provided the shorting of learning curve at the thoracoscopic esophagectomy in the left lateral decubitus position.展开更多
BACKGROUND In laparoscopic proximal gastrectomy(LPG),the prolapse of the hepatic left lateral lobe near the lesser curvature and esophageal hiatus can obstruct the field of vision and operation.Therefore,it is necessa...BACKGROUND In laparoscopic proximal gastrectomy(LPG),the prolapse of the hepatic left lateral lobe near the lesser curvature and esophageal hiatus can obstruct the field of vision and operation.Therefore,it is necessary to retract or obstruct the hepatic left lateral lobe to ensure a clear field of vision.AIM To investigate the safety and clinical efficacy of the modified hepatic left lateral lobe inversion technique for LPG.METHODS A retrospective analysis was conducted on the clinical data of 13 consecutive patients with early-stage upper gastric adenocarcinoma or adenocarcinoma of the esophagogastric junction treated with LPG from January to December 2023 at the Department of Gastrointestinal Surgery,Second Affiliated Hospital of Fujian Medical University.The modified hepatic left lateral lobe inversion technique was used to expose the surgical field in all patients,and short-term outcomes were observed.RESULTS In all 13 patients,the modified hepatic left lateral lobe inversion technique was successful during surgery without the need for re-retraction or alteration of the liver traction method.There were no instances of esophageal hiatus occlusion,eliminating the need for forceps to assist in exposure.There was no occurrence of intraoperative hepatic hemorrhage,hepatic vein injury,or hepatic congestion.No postoperative digestive complications of Clavien-Dindo grade≥II occurred wi-thin 30 days after surgery,except for a single case of pulmonary infection.Some patients experienced increases in alanine aminotransferase and aspartate aminotransferase levels on the first day after surgery,which significantly decreased by the third day and returned to normal by the seventh day after surgery.CONCLUSION The modified hepatic left lateral lobe inversion technique has demonstrated satisfactory results,offering ad-vantages in terms of facilitating surgical procedures,reducing surgical trauma,and protecting the liver.展开更多
This paper presents the design of an asymmetrically variable wingtip anhedral angles morphing aircraft,inspired by biomimetic mechanisms,to enhance lateral maneuver capability.Firstly,we establish a lateral dynamic mo...This paper presents the design of an asymmetrically variable wingtip anhedral angles morphing aircraft,inspired by biomimetic mechanisms,to enhance lateral maneuver capability.Firstly,we establish a lateral dynamic model considering additional forces and moments resulting during the morphing process,and convert it into a Multiple Input Multiple Output(MIMO)virtual control system by importing virtual inputs.Secondly,a classical dynamics inversion controller is designed for the outer-loop system.A new Global Fast Terminal Incremental Sliding Mode Controller(NDO-GFTISMC)is proposed for the inner-loop system,in which an adaptive law is implemented to weaken control surface chattering,and a Nonlinear Disturbance Observer(NDO)is integrated to compensate for unknown disturbances.The whole control system is proven semiglobally uniformly ultimately bounded based on the multi-Lyapunov function method.Furthermore,we consider tracking errors and self-characteristics of actuators,a quadratic programmingbased dynamic control allocation law is designed,which allocates virtual control inputs to the asymmetrically deformed wingtip and rudder.Actuator dynamic models are incorporated to ensure physical realizability of designed allocation law.Finally,comparative experimental results validate the effectiveness of the designed control system and control allocation law.The NDO-GFTISMC features faster convergence,stronger robustness,and 81.25%and 75.0%reduction in maximum state tracking error under uncertainty compared to the Incremental Nonlinear Dynamic Inversion Controller based on NDO(NDO-INDI)and Incremental Sliding Mode Controller based on NDO(NDO-ISMC),respectively.The design of the morphing aircraft significantly enhances lateral maneuver capability,maintaining a substantial control margin during lateral maneuvering,reducing the burden of the rudder surface,and effectively solving the actuator saturation problem of traditional aircraft during lateral maneuvering.展开更多
Schwann cells are essential for the maintenance and function of motor neurons,axonal networks,and the neuromuscular junction.In amyotrophic lateral sclerosis,where motor neuron function is progressively lost,Schwann c...Schwann cells are essential for the maintenance and function of motor neurons,axonal networks,and the neuromuscular junction.In amyotrophic lateral sclerosis,where motor neuron function is progressively lost,Schwann cell function may also be impaired.Recently,important signaling and potential trophic activities of Schwann cell-derived exosomal vesicles have been reported.This case report describes the treatment of a patient with advanced amyotrophic lateral sclerosis using serial intravenous infusions of allogeneic Schwann cell-derived exosomal vesicles,marking,to our knowledge,the first instance of such treatment.An 81-year-old male patient presented with a 1.5-year history of rapidly progressive amyotrophic lateral sclerosis.After initial diagnosis,the patient underwent a combination of generic riluzole,sodium phenylbutyrate for the treatment of amyotrophic lateral sclerosis,and taurursodiol.The patient volunteered to participate in an FDA-approved single-patient expanded access treatment and received weekly intravenous infusions of allogeneic Schwann cell-derived exosomal vesicles to potentially restore impaired Schwann cell and motor neuron function.We confirmed that cultured Schwann cells obtained from the amyotrophic lateral sclerosis patient via sural nerve biopsy appeared impaired(senescent)and that exposure of the patient’s Schwann cells to allogeneic Schwann cell-derived exosomal vesicles,cultured expanded from a cadaver donor improved their growth capacity in vitro.After a period of observation lasting 10 weeks,during which amyotrophic lateral sclerosis Functional Rating Scale-Revised and pulmonary function were regularly monitored,the patient received weekly consecutive infusions of 1.54×1012(×2),and then consecutive infusions of 7.5×1012(×6)allogeneic Schwann cell-derived exosomal vesicles diluted in 40 mL of Dulbecco’s phosphate-buffered saline.None of the infusions were associated with adverse events such as infusion reactions(allergic or otherwise)or changes in vital signs.Clinical lab serum neurofilament and cytokine levels measured prior to each infusion varied somewhat without a clear trend.A more sensitive in-house assay suggested possible inflammasome activation during the disease course.A trend for clinical stabilization was observed during the infusion period.Our study provides a novel approach to address impaired Schwann cells and possibly motor neuron function in patients with amyotrophic lateral sclerosis using allogeneic Schwann cell-derived exosomal vesicles.Initial findings suggest that this approach is safe.展开更多
Objective To investigate therelationships between serum concentration of insulin -like growth factor - I (IGF-I) and left ventricular function as well as coronary collateral circulation in patients with coronary arter...Objective To investigate therelationships between serum concentration of insulin -like growth factor - I (IGF-I) and left ventricular function as well as coronary collateral circulation in patients with coronary artery disease (CAD) . Methods In 41 patients with CAD and 15 control subjects without CAD, the concentrations of serum IGF - I were measured using radioimmunoassay. The relationships between the concentration of serum IGF - I and Leaman coronary artery score, Rentrop grade of coronary collateral circulation, left ventricular ejection fraction (LVEF) as well as left ventricular wall motion Cortina score were assessed. Results 1. There was no significant difference in the mean level of serum IGF -I between the CAD group and the control group (107. 92±44.74 ng/ml vs 113.05 ±33. 65 ng/ml, P> 0. 05), but the IGF - I concentrations in the subgroup with collateral circulation were significantly greater than that in the control group (147. 33 ±29. 92 ng/ml vs 113. 05±33. 65 ng/ml, P < 0. 01) or in the subgroup without collateral circulation (147. 33 ±29. 92 ng/ml vs 80. 01±29. 75 ng/ml , P < 0. 01). 2. The serum concentration of IGF -I had no significant correlation to the Leaman coronary artery score. 3. The serum level of IGF -I had significantly positive correlation to both LVEF ( r = 0. 45, P < 0. 001) and the Rentrop grade of coronary collateral circulation ( r = 0. 74, P < 0. 001), and was negatively related to the left ventricular wall motion Cortina score (r = -0. 53, P < 0. 001). 4. The Leaman coronary artery score had no significant correlation to the Rentrop grade of coronary collateral circulation. 5. The Leaman coronary artery score was related to neither the LVEF nor the Cortina score in the whole CAD group. In the subgroup without coronary collateral circulation, however, the Leaman score had significantly negative correlation to LVEF ( r = - 0. 46, P < 0. 05) and positive correlation to the Cortina score (r = 0. 47, P < 0. 05) . Conclusions The serum concentration of IGF -I was associated with both left ventricular function and coronary collateral circulation in patients with CAD. IGF -I may play a role in promoting coronary collateral circulation and in protecting left ventricular function in patients with coronary artery disease.展开更多
BACKGROUND Lateral facial clefts are atypical with a low incidence in the facial cleft spectrum.With the development of ultrasonography(US)prenatal screening,such facial malformations can be detected and diagnosed pre...BACKGROUND Lateral facial clefts are atypical with a low incidence in the facial cleft spectrum.With the development of ultrasonography(US)prenatal screening,such facial malformations can be detected and diagnosed prenatally rather than at birth.Although three-dimensional US(3DUS)can render the fetus'face via 3D reconstruction,the 3D images are displayed on two-dimensional screens without field depth,which impedes the understanding of untrained individuals.In contrast,a 3D-printed model of the fetus'face helps both parents and doctors develop a more comprehensive understanding of the facial malformation by creating more interactive aspects.Herein,we present an isolated lateral facial cleft case that was diagnosed via US combined with a 3D-printed model.CASE SUMMARY A 31-year-old G2P1 patient presented for routine prenatal screening at the 22nd wk of gestation.The coronal nostril-lip section of two-dimensional US(2DUS)demonstrated that the fetus'bilateral oral commissures were asymmetrical,and left oral commissure was abnormally wide.The left oblique-coronal section showed a cleft at the left oral commissure which extended to the left cheek.The results of 3DUS confirmed the cleft.Furthermore,we created a model of the fetal face using 3D printing technology,which clearly presented facial malformations.The fetus was diagnosed with a left lateral facial cleft,which was categorized as a No.7 facial cleft according to the Tessier facial cleft classification.The parents terminated the pregnancy at the 24th wk of gestation after parental counseling.CONCLUSION In the diagnostic course of the current case,in addition to the traditional application of 2D and 3DUS,we created a 3D-printed model of the fetus,which enhanced diagnostic evidence,benefited the education of junior doctors,improved parental counseling,and had the potential to guide surgical planning.展开更多
Amyotrophic lateral sclerosis(ALS)is a neuromuscular condition resulting from the progressive degeneration of motor neurons in the cortex,brainstem,and spinal cord.While the typical clinical phenotype of ALS involves ...Amyotrophic lateral sclerosis(ALS)is a neuromuscular condition resulting from the progressive degeneration of motor neurons in the cortex,brainstem,and spinal cord.While the typical clinical phenotype of ALS involves both upper and lower motor neurons,human and animal studies over the years have highlighted the potential spread to other motor and non-motor regions,expanding the phenotype of ALS.Although superoxide dismutase 1(SOD1)mutations represent a minority of ALS cases,the SOD1 gene remains a milestone in ALS research as it represents the first genetic target for personalized therapies.Despite numerous single case reports or case series exhibiting extramotor symptoms in patients with ALS mutations in SOD1(SOD1-ALS),no studies have comprehensively explored the full spectrum of extramotor neurological manifestations in this subpopulation.In this narrative review,we analyze and discuss the available literature on extrapyramidal and non-motor features during SOD1-ALS.The multifaceted expression of SOD1 could deepen our understanding of the pathogenic mechanisms,pointing towards a multidisciplinary approach for affected patients in light of new therapeutic strategies for SOD1-ALS.展开更多
Amyotrophic lateral sclerosis is a rare neurodegenerative disease characterized by the involvement of both upper and lower motor neurons.Early bilateral limb involvement significantly affects patients'daily lives ...Amyotrophic lateral sclerosis is a rare neurodegenerative disease characterized by the involvement of both upper and lower motor neurons.Early bilateral limb involvement significantly affects patients'daily lives and may lead them to be confined to bed.However,the effect of upper and lower motor neuron impairment and other risk factors on bilateral limb involvement is unclear.To address this issue,we retrospectively collected data from 586 amyotrophic lateral sclerosis patients with limb onset diagnosed at Peking University Third Hospital between January 2020 and May 2022.A univariate analysis revealed no significant differences in the time intervals of spread in different directions between individuals with upper motor neuron-dominant amyotrophic lateral sclerosis and those with classic amyotrophic lateral sclerosis.We used causal directed acyclic graphs for risk factor determination and Cox proportional hazards models to investigate the association between the duration of bilateral limb involvement and clinical baseline characteristics in amyotrophic lateral sclerosis patients.Multiple factor analyses revealed that higher upper motor neuron scores(hazard ratio[HR]=1.05,95%confidence interval[CI]=1.01–1.09,P=0.018),onset in the left limb(HR=0.72,95%CI=0.58–0.89,P=0.002),and a horizontal pattern of progression(HR=0.46,95%CI=0.37–0.58,P<0.001)were risk factors for a shorter interval until bilateral limb involvement.The results demonstrated that a greater degree of upper motor neuron involvement might cause contralateral limb involvement to progress more quickly in limb-onset amyotrophic lateral sclerosis patients.These findings may improve the management of amyotrophic lateral sclerosis patients with limb onset and the prediction of patient prognosis.展开更多
Behavioural lateralization,which reflects the functional specializations of the two brain hemispheres,is assumed to play an important role in cooperative intraspecific interactions.However,there are few studies focuse...Behavioural lateralization,which reflects the functional specializations of the two brain hemispheres,is assumed to play an important role in cooperative intraspecific interactions.However,there are few studies focused on the lateralization in cooperative behaviours of individuals,especially in a natural setting.In the present study,we investigated Iateralized spatial interactions between the partners in life-long monogamous pairs.The male-female pairs of two geese species(barnacle,Branta leucopsis,and white-fronted,Anser albifrons geese),were observed during different stages of the annual cycle in a variety of conditions.In geese flocks,we recorded which visual hemifield(left/right)the following partner used to monitor the leading partner relevant to the type of behaviour and the disturbance factors.In a significant majority of pairs,the following bird viewed the leading partner with the left eye during routine behaviours such as resting and feeding in undisturbed conditions.This behavioural lateralization,implicating the right hemisphere processing,was consistent across the different aggregation sites and years of the study.In contrast,no significant bias was found in a variety of geese behaviours associated with enhanced disturbance(when alert on water,flying or fleeing away when disturbed,feeding during the hunting period,in urban area feeding and during moulting).We hypothesize that the increased demands for right hemisphere processing to deal with stressful and emergency situations may interfere with the manifestation of lateralization in social interactions.展开更多
Soft robots,as a modern gateway to unlocking the mysteries of underwater realms,present new complexities.Modeling their behavior when in contact with external forces,whether point-based or distributed,is a primary cha...Soft robots,as a modern gateway to unlocking the mysteries of underwater realms,present new complexities.Modeling their behavior when in contact with external forces,whether point-based or distributed,is a primary challenge due to the nature of soft bodies.To obtain a holistic view of the system’s behavior determining the governing dynamics is deemed necessary.This paper proposes a new technique to simulate the dynamic lateral undulation of a soft robotic fish with a cable-driven soft tail.By integrating the rigid finite element method with rigid-body robotics,the model represents the undulation of a finite number of rigid elements connected through a set of torsional spring and damper.Instead of directly modeling external forces,we substitute equivalent joint torques into the system dynamics,allowing us to consider external effects without complicating the model.The resulting model yields valuable insights into the system’s behavior,including propulsive and lateral forces.A comparison with experimental results shows strong agreement,with a tip amplitude error of 10% at 0.8 Hz,5.25% at 1.6 Hz and 2.54%at 2.2 Hz flapping frequency.These findings illuminate the influence of lateral undulation on the overall dynamics,paving the way for fully autonomous robotic fish.展开更多
文摘Objective The associations of serum trace element levels with disease progression and survival duration were assessed in individuals diagnosed with sporadic amyotrophic lateral sclerosis(sALS)in China.Methods Clinical data,including diagnostic indicators,clinical characteristics,Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised(ALSFRS-R)scores,and serum concentrations of calcium(Ca),magnesium(Mg),iron(Fe),copper(Cu),and zinc(Zn),were collected for hospitalized patients with sALS between 2018 and 2021.Correlation analysis,random forest analysis,and the Gehan-Breslow-Wilcoxon test were used to evaluate the relations between serum trace element levels,disease progression,and survival duration.Results Lower serum Ca levels and higher Mg levels were observed in patients with ALSFRS-R scores<39.Serum Mg was significantly negatively correlated with ALSFRS-R,trunk,and respiratory scores.Serum Cu and Zn also showed significant negative correlations with the respiratory score,whereas Ca and Fe were not significantly correlated with the ALSFRS-R score.The serum levels of Ca,Mg,Cu,Zn,and Fe remained consistent regardless of the site of disease onset.ALSFRS-R analysis revealed that serum Ca and Mg had a substantial effect on the total ALSFRS-R score,with serum Mg significantly influencing the course of the disease.Notably,low serum Mg levels were associated with extended survival times in patients with sALS.Conclusion Serum levels of Ca and Mg play critical roles in the progression of sALS,and a reduced serum Mg level is related to an extended survival time.
基金supported by the National Natural Science Foundation of China (Nos.22234005,22494632,22404081)the Natural Science Foundation of Jiangsu Province (Nos.BK20222015,BK20240534)。
文摘Detecting biomarkers in body fluids by optical lateral flow immune assay(LFIA) technology provides rapid access to disease information for early diagnosis.LFIA is based on an antigen-antibody reaction and is rapidly becoming the preferred choice of physicians and patients for point-of-care testing due to its simplicity,cost-effectiveness,and rapid detection.Observing the optical signal change from the colloidal gold of the traditional LFIA strip has been widely applied for various biomarkers detection in body fluids.Despite the significant progress,rapid real-time detection of color changes in the colloidal gold by the naked eye still faces many limitations,such as large errors and the inability to quantify and accurately detect.New optical LFIA strip technology has emerged in recent years to extend its application scenarios for achieving quantitative detection such as fluorescence,afterglow,and chemiluminescence.Herein,we summarized the development of optical LFIA technology from single to hyphenated optical signals for biomarkers detection in body fluids from invasive and non-invasive sources.Moreover,the challenge and outlook of optical LFIA strip technology are highlighted to inspire the designing of next-generation diagnostic platforms.
基金supported by the Zhongyuan University of Technology Discipline Backbone Teacher Support Program Project(No.GG202417)the Key Research and Development Program of Henan under Grant 251111212000.
文摘Lateral movement represents the most covert and critical phase of Advanced Persistent Threats(APTs),and its detection still faces two primary challenges:sample scarcity and“cold start”of new entities.To address these challenges,we propose an Uncertainty-Driven Graph Embedding-Enhanced Lateral Movement Detection framework(UGEA-LMD).First,the framework employs event-level incremental encoding on a continuous-time graph to capture fine-grained behavioral evolution,enabling newly appearing nodes to retain temporal contextual awareness even in the absence of historical interactions and thereby fundamentally mitigating the cold-start problem.Second,in the embedding space,we model the dependency structure among feature dimensions using a Gaussian copula to quantify the uncertainty distribution,and generate augmented samples with consistent structural and semantic properties through adaptive sampling,thus expanding the representation space of sparse samples and enhancing the model’s generalization under sparse sample conditions.Unlike static graph methods that cannot model temporal dependencies or data augmentation techniques that depend on predefined structures,UGEA-LMD offers both superior temporaldynamic modeling and structural generalization.Experimental results on the large-scale LANL log dataset demonstrate that,under the transductive setting,UGEA-LMD achieves an AUC of 0.9254;even when 10%of nodes or edges are withheld during training,UGEA-LMD significantly outperforms baseline methods on metrics such as recall and AUC,confirming its robustness and generalization capability in sparse-sample and cold-start scenarios.
文摘Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder characterized by the progressive degeneration of upper and lower motor neurons in the brainstem and spinal cord,leading to muscle weakness,paralysis,and respiratory failure (Morgan and Orrell,2016).
基金supported by the Natural Science Foundation of Beijing,Nos.7244428(to WZ)and 7222215(to JH)the Peking University Medicine Sailing Program forYoung Scholars’Scientific and Technological Innovation,No.BMU2023YFJHPY034(to WZ)+4 种基金the National Natural Science Foundation of China,Nos.81873784,82071426(to DF),and81974197(to JH)the Clinical Cohort Construction Program of Peking University Third Hospital,No.BYSYDL2019002(to DF)Beijing Physician-Scientist TrainingProgram,No.BJPSTP-2024-03(to JH)the China Postdoctoral Science Foundation,Nos.2022TQ0014(to LX),2022M720284(to LX)the E-Town Cooperation&Development Foundation,No.YCXJ-JZ-2023-017(to LX).
文摘The growing recognition of the role of genetics in the development of amyotrophic lateral sclerosis is evident.However,there has yet to be a comprehensive analysis of the clinical characteristics and genetics of familial amyotrophic lateral sclerosis in an Asian population.This study aimed to provide an in-depth analysis of the clinical features and genetic spectrum of familial amyotrophic lateral sclerosis over 15 years in a clinic-based cohort of patients from the Chinese mainland.Enrollment of 302 amyotrophic lateral sclerosis families from 28 provinces was undertaken from January 2008 to September 2023.A group-based trajectory model for disease progression based on amyotrophic lateral sclerosis Functional Rating Scale-Revised(ALSFRS-R)scores was validated using bootstrap internal validation in patients with familial amyotrophic lateral sclerosis,as well as patients with sporadic amyotrophic lateral sclerosis(matched at a 1:4 ratio,with replacement).DNA samples from 244 index patients were screened for variants in the pathogenic genes SOD1,FUS,TDP43,and C9ORF72,of which 146 were also subjected to genome-wide next-generation sequencing.Gene-level burden analysis was used to evaluate the distribution of rare variants in the cohort.We found that rapid dynamic disease progression was associated with an older age at onset,shorter diagnostic delay,lower body mass index,bulbar onset,and≥1 affected first-degree relative.Certain attributes,such as age at onset and time from onset to diagnosis,had comparable impacts on the clinical progression trajectories of both familial amyotrophic lateral sclerosis and sporadic amyotrophic lateral sclerosis.Harboring pathogenic/likely pathogenic variants in amyotrophic lateral sclerosis-causative genes reduced the age of onset of familial amyotrophic lateral sclerosis.Among the patients with familial amyotrophic lateral sclerosis,17.8%possessed≥2 pathogenic/likely pathogenic variants.Sequencing kernel association test analysis showed that the SOD1 rare variant burden(P=1.3e-15)was associated with a significant risk of familial amyotrophic lateral sclerosis.Our findings conclusively confirmed the clinical features and genetic spectrum of familial amyotrophic lateral sclerosis over 15 years in a clinical cohort from China,contributing to a deeper understanding of genotype-phenotype relationships in familial amyotrophic lateral sclerosis.This comprehensive evaluation of specific clinical characteristics,clinical prognosis,and genetic variants of amyotrophic lateral sclerosis based on detailed clinical and genetic information may lead to the development of genotype-specific treatment approaches.
文摘AIM: To evaluate the long-term results of radiofrequency ablation (RFA) compared to left lateral sectionectomy (LLS) in patients with Child-Pugh class A disease for the treatment of single and small hepatocellular carcinoma (HCC) in the left lateral segments.
文摘Amyotrophic lateral sclerosis is a devastating neurodegenerative disease for which the current treatment approaches remain severely limited.The principal pathological alterations of the disease include the selective degeneration of motor neurons in the brain,brainstem,and spinal cord,as well as abnormal protein deposition in the cytoplasm of neurons and glial cells.The biological markers under extensive scrutiny are predominantly located in the cerebrospinal fluid,blood,and even urine.Among these biomarke rs,neurofilament proteins and glial fibrillary acidic protein most accurately reflect the pathologic changes in the central nervous system,while creatinine and creatine kinase mainly indicate pathological alterations in the peripheral nerves and muscles.Neurofilament light chain levels serve as an indicator of neuronal axonal injury that remain stable throughout disease progression and are a promising diagnostic and prognostic biomarker with high specificity and sensitivity.However,there are challenges in using neurofilament light chain to diffe rentiate amyotrophic lateral sclerosis from other central nervous system diseases with axonal injury.Glial fibrillary acidic protein predominantly reflects the degree of neuronal demyelination and is linked to non-motor symptoms of amyotrophic lateral sclerosis such as cognitive impairment,oxygen saturation,and the glomerular filtration rate.TAR DNA-binding protein 43,a pathological protein associated with amyotrophic lateral sclerosis,is emerging as a promising biomarker,particularly with advancements in exosome-related research.Evidence is currently lacking for the value of creatinine and creatine kinase as diagnostic markers;however,they show potential in predicting disease prognosis.Despite the vigorous progress made in the identification of amyotrophic lateral sclerosis biomarkers in recent years,the quest for definitive diagnostic and prognostic biomarke rs remains a formidable challenge.This review summarizes the latest research achievements concerning blood biomarkers in amyotrophic lateral sclerosis that can provide a more direct basis for the differential diagnosis and prognostic assessment of the disease beyond a reliance on clinical manifestations and electromyography findings.
基金Supported by The German Research Foundation(DFG)the University of Wuerzburg in the funding programme Open Access Publishing
文摘We are reporting a long-time magnetic resonance imaging(MRI) follow-up in a rare case of cardiac left lateral wall hypertrophy. Hypertrophic cardiomyopathy(HCM) is the most common genetic cardiovascular disorder and a significant cause of sudden cardiac death. Cardiac magnetic resonance(CMR) imaging can be a valuable tool for assessment of detailed information on size,localization,and tissue characteristics of hypertrophied myocardium. However,there is still little knowledge of long-term evolution of HCM as visualized by magnetic resonance imaging. Recently,our group reported a case of left lateral wall HCM as a rare variant of the more common forms,such as septal HCM,or apical HCM. As we now retrieved an old cardiac MRI acquired in this patient more than 20 years ago,we are able to provide the thrilling experience of an ultra-long MRI followup presentation in this rare case of left lateral wall hypertrophy. Furthermore,this case outlines the tremendous improvements in imaging quality within the last two decades of CMR imaging.
文摘BACKGROUND A limited number of studies have demonstrated that sleeping in the left lateral decubitus(LLD)decreases nocturnal reflux in patients with gastroesophageal reflux disease(GERD)compared to right lateral decubitus(RLD)and supine.AIM This systematic review summarizes the association between sleeping in the LLD position and nocturnal reflux in patients with GERD.METHODS Studies published up to July 17,2023,in MEDLINE,EMBASE,and CENTRAL were searched.Eligible studies were randomized and nonrandomized studies assessing the effect of sleeping in LLD compared to RLD and supine in reducing nocturnal reflux in GERD patients.Outcomes include the acid exposure time(AET)(%time in pH<4),acid clearance time(ACT)(in sec/episode),number of reflux episodes,and improvement in N-GSSIQ scores.RESULTS Two nonrandomized studies showed decreased AET and ACT in LLD sleep position in comparison to RLD(mean difference[MD]-2.03[95%CI:-3.62 to-0.45];-81.84[95%CI:-127.48 to-36.20],respectively)and supine position(MD-2.71[95%CI:-4.34 to-1.09];-74.47[95%CI:-116.26 to-32.69],respectively).There was no difference in AET and ACT between RLD sleep position and supine.Furthermore,one randomized controlled trial investigating the use of electronic sleep positional therapy,which increased the duration of LLD sleep and decreased the duration of RLD sleep compared to sham,showed nocturnal symptoms improvement(improved N-GSSIQ score,increased reflux-free nights,and resolution of nocturnal reflux symptoms).CONCLUSION Current evidence suggests that sleeping on the left side could reduce nocturnal reflux and improve GERD-related quality of life,therefore warranting interventions that promote LLD sleep position.
基金National Natural Science Foundation of China(U24A20714 to XMF and 82102238 to PC)。
文摘BACKGROUND:Tracheal intubation(TI)is a fundamental procedure for securing the airway or assisting ventilation in emergency medicine.Tracheal intubation in the lateral position(TILP)has been utilized in clinical practice,demonstrating potential advantages in specific scenarios,including emergency settings.However,there is a lack of comprehensive reviews and practical protocols on TILP application.To address this gap,we performed a narrative review,and provided evidence-based recommendations to formulate a practice protocol,to assist clinicians to effectively apply TILP.METHODS:We conducted a narrative review of TILP applications and developed recommendations based on clinical research evidence and clinical experience.Delphi method was used among the TILP consortium to grade the strength of the recommendations and to help reach consensus.The practice protocols were formulated as warranted by advancements in medical knowledge,technology,and practice.RESULTS:This narrative review summarized the current evidence on TILP application,highlighting its safety,efficacy,challenges,and potential complications.In total,24 recommendations and a clinical protocol for TILP application in emergency patients were established.CONCLUSION:TILP is a valuable technique in emergency medicine.We reviewed its application in emergency settings and formulated recommendations along with a clinical practice protocol.Future studies are needed to evaluate the safety and efficacy of TILP,broaden its scope of application,and explore effective training protocols.
文摘Objectives: This study aimed to evaluate operative benefits of artificial pnuemothorax in thoracoscopic esophagectomy in the left lateral decubitus position. Methods: We retrospectively analyzed short-term surgical outcomes including learning curve of 60 consecutive patients who underwent thoracoscopic esophagectomy with artificial pnuemothorax in the left lateral decubitus position between April 2010 and November 2012 in our department. Results: The median operation time and intraoperative blood loss were 443 min and 220 ml, respectively, and these values were 174 min and 95 ml, respectively, in the thoracic phase of surgery. The median number of harvested lymph node was 37. Only 1 patient required conversion to open esophagectomy. The postoperative 30-day mortality rate was 1.7%. The thoracic operation time significantly decreased after an experience of 10 cases and intraoperative blood loss during thoracic phasesignificantly decreased after an experience of 20 cases (p < 0.05), and operation time remained constant for the following cases. The number of harvested lymph nodes did not exhibit significant changes with an increase in the number of case experienced. Conclusions: Artificial pneumothorax provided the shorting of learning curve at the thoracoscopic esophagectomy in the left lateral decubitus position.
基金Key Clinical Specialty Discipline Construction Program of Fujian,Fujian Health Medicine and Politics,No.[2022]884.
文摘BACKGROUND In laparoscopic proximal gastrectomy(LPG),the prolapse of the hepatic left lateral lobe near the lesser curvature and esophageal hiatus can obstruct the field of vision and operation.Therefore,it is necessary to retract or obstruct the hepatic left lateral lobe to ensure a clear field of vision.AIM To investigate the safety and clinical efficacy of the modified hepatic left lateral lobe inversion technique for LPG.METHODS A retrospective analysis was conducted on the clinical data of 13 consecutive patients with early-stage upper gastric adenocarcinoma or adenocarcinoma of the esophagogastric junction treated with LPG from January to December 2023 at the Department of Gastrointestinal Surgery,Second Affiliated Hospital of Fujian Medical University.The modified hepatic left lateral lobe inversion technique was used to expose the surgical field in all patients,and short-term outcomes were observed.RESULTS In all 13 patients,the modified hepatic left lateral lobe inversion technique was successful during surgery without the need for re-retraction or alteration of the liver traction method.There were no instances of esophageal hiatus occlusion,eliminating the need for forceps to assist in exposure.There was no occurrence of intraoperative hepatic hemorrhage,hepatic vein injury,or hepatic congestion.No postoperative digestive complications of Clavien-Dindo grade≥II occurred wi-thin 30 days after surgery,except for a single case of pulmonary infection.Some patients experienced increases in alanine aminotransferase and aspartate aminotransferase levels on the first day after surgery,which significantly decreased by the third day and returned to normal by the seventh day after surgery.CONCLUSION The modified hepatic left lateral lobe inversion technique has demonstrated satisfactory results,offering ad-vantages in terms of facilitating surgical procedures,reducing surgical trauma,and protecting the liver.
基金supported by the National Natural Science Foundation of China(Nos.62103052 and No.52175214)。
文摘This paper presents the design of an asymmetrically variable wingtip anhedral angles morphing aircraft,inspired by biomimetic mechanisms,to enhance lateral maneuver capability.Firstly,we establish a lateral dynamic model considering additional forces and moments resulting during the morphing process,and convert it into a Multiple Input Multiple Output(MIMO)virtual control system by importing virtual inputs.Secondly,a classical dynamics inversion controller is designed for the outer-loop system.A new Global Fast Terminal Incremental Sliding Mode Controller(NDO-GFTISMC)is proposed for the inner-loop system,in which an adaptive law is implemented to weaken control surface chattering,and a Nonlinear Disturbance Observer(NDO)is integrated to compensate for unknown disturbances.The whole control system is proven semiglobally uniformly ultimately bounded based on the multi-Lyapunov function method.Furthermore,we consider tracking errors and self-characteristics of actuators,a quadratic programmingbased dynamic control allocation law is designed,which allocates virtual control inputs to the asymmetrically deformed wingtip and rudder.Actuator dynamic models are incorporated to ensure physical realizability of designed allocation law.Finally,comparative experimental results validate the effectiveness of the designed control system and control allocation law.The NDO-GFTISMC features faster convergence,stronger robustness,and 81.25%and 75.0%reduction in maximum state tracking error under uncertainty compared to the Incremental Nonlinear Dynamic Inversion Controller based on NDO(NDO-INDI)and Incremental Sliding Mode Controller based on NDO(NDO-ISMC),respectively.The design of the morphing aircraft significantly enhances lateral maneuver capability,maintaining a substantial control margin during lateral maneuvering,reducing the burden of the rudder surface,and effectively solving the actuator saturation problem of traditional aircraft during lateral maneuvering.
基金support from the Miami Project to Cure Paralysis,the Buoniconti Fund,and the Interdisciplinary Stem Cell Institute(to AK,WDD,JDG,and ADL)the unconditional support of Dean Henri Ford of the Leonard M.Miller School of Medicine at the University of Miami.
文摘Schwann cells are essential for the maintenance and function of motor neurons,axonal networks,and the neuromuscular junction.In amyotrophic lateral sclerosis,where motor neuron function is progressively lost,Schwann cell function may also be impaired.Recently,important signaling and potential trophic activities of Schwann cell-derived exosomal vesicles have been reported.This case report describes the treatment of a patient with advanced amyotrophic lateral sclerosis using serial intravenous infusions of allogeneic Schwann cell-derived exosomal vesicles,marking,to our knowledge,the first instance of such treatment.An 81-year-old male patient presented with a 1.5-year history of rapidly progressive amyotrophic lateral sclerosis.After initial diagnosis,the patient underwent a combination of generic riluzole,sodium phenylbutyrate for the treatment of amyotrophic lateral sclerosis,and taurursodiol.The patient volunteered to participate in an FDA-approved single-patient expanded access treatment and received weekly intravenous infusions of allogeneic Schwann cell-derived exosomal vesicles to potentially restore impaired Schwann cell and motor neuron function.We confirmed that cultured Schwann cells obtained from the amyotrophic lateral sclerosis patient via sural nerve biopsy appeared impaired(senescent)and that exposure of the patient’s Schwann cells to allogeneic Schwann cell-derived exosomal vesicles,cultured expanded from a cadaver donor improved their growth capacity in vitro.After a period of observation lasting 10 weeks,during which amyotrophic lateral sclerosis Functional Rating Scale-Revised and pulmonary function were regularly monitored,the patient received weekly consecutive infusions of 1.54×1012(×2),and then consecutive infusions of 7.5×1012(×6)allogeneic Schwann cell-derived exosomal vesicles diluted in 40 mL of Dulbecco’s phosphate-buffered saline.None of the infusions were associated with adverse events such as infusion reactions(allergic or otherwise)or changes in vital signs.Clinical lab serum neurofilament and cytokine levels measured prior to each infusion varied somewhat without a clear trend.A more sensitive in-house assay suggested possible inflammasome activation during the disease course.A trend for clinical stabilization was observed during the infusion period.Our study provides a novel approach to address impaired Schwann cells and possibly motor neuron function in patients with amyotrophic lateral sclerosis using allogeneic Schwann cell-derived exosomal vesicles.Initial findings suggest that this approach is safe.
文摘Objective To investigate therelationships between serum concentration of insulin -like growth factor - I (IGF-I) and left ventricular function as well as coronary collateral circulation in patients with coronary artery disease (CAD) . Methods In 41 patients with CAD and 15 control subjects without CAD, the concentrations of serum IGF - I were measured using radioimmunoassay. The relationships between the concentration of serum IGF - I and Leaman coronary artery score, Rentrop grade of coronary collateral circulation, left ventricular ejection fraction (LVEF) as well as left ventricular wall motion Cortina score were assessed. Results 1. There was no significant difference in the mean level of serum IGF -I between the CAD group and the control group (107. 92±44.74 ng/ml vs 113.05 ±33. 65 ng/ml, P> 0. 05), but the IGF - I concentrations in the subgroup with collateral circulation were significantly greater than that in the control group (147. 33 ±29. 92 ng/ml vs 113. 05±33. 65 ng/ml, P < 0. 01) or in the subgroup without collateral circulation (147. 33 ±29. 92 ng/ml vs 80. 01±29. 75 ng/ml , P < 0. 01). 2. The serum concentration of IGF -I had no significant correlation to the Leaman coronary artery score. 3. The serum level of IGF -I had significantly positive correlation to both LVEF ( r = 0. 45, P < 0. 001) and the Rentrop grade of coronary collateral circulation ( r = 0. 74, P < 0. 001), and was negatively related to the left ventricular wall motion Cortina score (r = -0. 53, P < 0. 001). 4. The Leaman coronary artery score had no significant correlation to the Rentrop grade of coronary collateral circulation. 5. The Leaman coronary artery score was related to neither the LVEF nor the Cortina score in the whole CAD group. In the subgroup without coronary collateral circulation, however, the Leaman score had significantly negative correlation to LVEF ( r = - 0. 46, P < 0. 05) and positive correlation to the Cortina score (r = 0. 47, P < 0. 05) . Conclusions The serum concentration of IGF -I was associated with both left ventricular function and coronary collateral circulation in patients with CAD. IGF -I may play a role in promoting coronary collateral circulation and in protecting left ventricular function in patients with coronary artery disease.
文摘BACKGROUND Lateral facial clefts are atypical with a low incidence in the facial cleft spectrum.With the development of ultrasonography(US)prenatal screening,such facial malformations can be detected and diagnosed prenatally rather than at birth.Although three-dimensional US(3DUS)can render the fetus'face via 3D reconstruction,the 3D images are displayed on two-dimensional screens without field depth,which impedes the understanding of untrained individuals.In contrast,a 3D-printed model of the fetus'face helps both parents and doctors develop a more comprehensive understanding of the facial malformation by creating more interactive aspects.Herein,we present an isolated lateral facial cleft case that was diagnosed via US combined with a 3D-printed model.CASE SUMMARY A 31-year-old G2P1 patient presented for routine prenatal screening at the 22nd wk of gestation.The coronal nostril-lip section of two-dimensional US(2DUS)demonstrated that the fetus'bilateral oral commissures were asymmetrical,and left oral commissure was abnormally wide.The left oblique-coronal section showed a cleft at the left oral commissure which extended to the left cheek.The results of 3DUS confirmed the cleft.Furthermore,we created a model of the fetal face using 3D printing technology,which clearly presented facial malformations.The fetus was diagnosed with a left lateral facial cleft,which was categorized as a No.7 facial cleft according to the Tessier facial cleft classification.The parents terminated the pregnancy at the 24th wk of gestation after parental counseling.CONCLUSION In the diagnostic course of the current case,in addition to the traditional application of 2D and 3DUS,we created a 3D-printed model of the fetus,which enhanced diagnostic evidence,benefited the education of junior doctors,improved parental counseling,and had the potential to guide surgical planning.
文摘Amyotrophic lateral sclerosis(ALS)is a neuromuscular condition resulting from the progressive degeneration of motor neurons in the cortex,brainstem,and spinal cord.While the typical clinical phenotype of ALS involves both upper and lower motor neurons,human and animal studies over the years have highlighted the potential spread to other motor and non-motor regions,expanding the phenotype of ALS.Although superoxide dismutase 1(SOD1)mutations represent a minority of ALS cases,the SOD1 gene remains a milestone in ALS research as it represents the first genetic target for personalized therapies.Despite numerous single case reports or case series exhibiting extramotor symptoms in patients with ALS mutations in SOD1(SOD1-ALS),no studies have comprehensively explored the full spectrum of extramotor neurological manifestations in this subpopulation.In this narrative review,we analyze and discuss the available literature on extrapyramidal and non-motor features during SOD1-ALS.The multifaceted expression of SOD1 could deepen our understanding of the pathogenic mechanisms,pointing towards a multidisciplinary approach for affected patients in light of new therapeutic strategies for SOD1-ALS.
基金supported by the National Natural Science Foundation of China,Nos.82071426,81873784Clinical Cohort Construction Program of Peking University Third Hospital,No.BYSYDL2019002(all to DF)。
文摘Amyotrophic lateral sclerosis is a rare neurodegenerative disease characterized by the involvement of both upper and lower motor neurons.Early bilateral limb involvement significantly affects patients'daily lives and may lead them to be confined to bed.However,the effect of upper and lower motor neuron impairment and other risk factors on bilateral limb involvement is unclear.To address this issue,we retrospectively collected data from 586 amyotrophic lateral sclerosis patients with limb onset diagnosed at Peking University Third Hospital between January 2020 and May 2022.A univariate analysis revealed no significant differences in the time intervals of spread in different directions between individuals with upper motor neuron-dominant amyotrophic lateral sclerosis and those with classic amyotrophic lateral sclerosis.We used causal directed acyclic graphs for risk factor determination and Cox proportional hazards models to investigate the association between the duration of bilateral limb involvement and clinical baseline characteristics in amyotrophic lateral sclerosis patients.Multiple factor analyses revealed that higher upper motor neuron scores(hazard ratio[HR]=1.05,95%confidence interval[CI]=1.01–1.09,P=0.018),onset in the left limb(HR=0.72,95%CI=0.58–0.89,P=0.002),and a horizontal pattern of progression(HR=0.46,95%CI=0.37–0.58,P<0.001)were risk factors for a shorter interval until bilateral limb involvement.The results demonstrated that a greater degree of upper motor neuron involvement might cause contralateral limb involvement to progress more quickly in limb-onset amyotrophic lateral sclerosis patients.These findings may improve the management of amyotrophic lateral sclerosis patients with limb onset and the prediction of patient prognosis.
基金supported by the Russian Science Foundation(grant no.19-14-00119)The complex expeditions on Kolguev Island for wildfowl population monitoring were supported by Vogelschutz-Komitee and Conservation Bundesamt fur Naturschutz,BfN,(MEERESENTEN grant 3516821500).
文摘Behavioural lateralization,which reflects the functional specializations of the two brain hemispheres,is assumed to play an important role in cooperative intraspecific interactions.However,there are few studies focused on the lateralization in cooperative behaviours of individuals,especially in a natural setting.In the present study,we investigated Iateralized spatial interactions between the partners in life-long monogamous pairs.The male-female pairs of two geese species(barnacle,Branta leucopsis,and white-fronted,Anser albifrons geese),were observed during different stages of the annual cycle in a variety of conditions.In geese flocks,we recorded which visual hemifield(left/right)the following partner used to monitor the leading partner relevant to the type of behaviour and the disturbance factors.In a significant majority of pairs,the following bird viewed the leading partner with the left eye during routine behaviours such as resting and feeding in undisturbed conditions.This behavioural lateralization,implicating the right hemisphere processing,was consistent across the different aggregation sites and years of the study.In contrast,no significant bias was found in a variety of geese behaviours associated with enhanced disturbance(when alert on water,flying or fleeing away when disturbed,feeding during the hunting period,in urban area feeding and during moulting).We hypothesize that the increased demands for right hemisphere processing to deal with stressful and emergency situations may interfere with the manifestation of lateralization in social interactions.
文摘Soft robots,as a modern gateway to unlocking the mysteries of underwater realms,present new complexities.Modeling their behavior when in contact with external forces,whether point-based or distributed,is a primary challenge due to the nature of soft bodies.To obtain a holistic view of the system’s behavior determining the governing dynamics is deemed necessary.This paper proposes a new technique to simulate the dynamic lateral undulation of a soft robotic fish with a cable-driven soft tail.By integrating the rigid finite element method with rigid-body robotics,the model represents the undulation of a finite number of rigid elements connected through a set of torsional spring and damper.Instead of directly modeling external forces,we substitute equivalent joint torques into the system dynamics,allowing us to consider external effects without complicating the model.The resulting model yields valuable insights into the system’s behavior,including propulsive and lateral forces.A comparison with experimental results shows strong agreement,with a tip amplitude error of 10% at 0.8 Hz,5.25% at 1.6 Hz and 2.54%at 2.2 Hz flapping frequency.These findings illuminate the influence of lateral undulation on the overall dynamics,paving the way for fully autonomous robotic fish.
