To:Chinese Association for International Understanding (CAFIU)CONGRATULATIONS LETTER Dear friends,I was glad to receive the news that your institution,our long-term partner,is celebrating its 40th anniversary since th...To:Chinese Association for International Understanding (CAFIU)CONGRATULATIONS LETTER Dear friends,I was glad to receive the news that your institution,our long-term partner,is celebrating its 40th anniversary since the founding of the Association.In the past few years,our two institutions as part of the non-govemmental sector.have jointly done several projects aimed at getting to know each other and especially on the promotion and construction of President Xi Jinping’s big Initiative,"One Belt and One Road".展开更多
Spinal cord injuries lead to significant loss of motor, sensory, and autonomic functions, presenting major challenges in neural regeneration. Achieving effective therapeutic concentrations at injury sites has been a s...Spinal cord injuries lead to significant loss of motor, sensory, and autonomic functions, presenting major challenges in neural regeneration. Achieving effective therapeutic concentrations at injury sites has been a slow process, partly due to the difficulty of delivering drugs effectively. Nanoparticles, with their targeted delivery capabilities, biocompatibility, and enhanced bioavailability over conventional drugs, are garnering attention for spinal cord injury treatment. This review explores the current mechanisms and shortcomings of existing treatments, highlighting the benefits and progress of nanoparticle-based approaches. We detail nanoparticle delivery methods for spinal cord injury, including local and intravenous injections, oral delivery, and biomaterial-assisted implantation, alongside strategies such as drug loading and surface modification. The discussion extends to how nanoparticles aid in reducing oxidative stress, dampening inflammation, fostering neural regeneration, and promoting angiogenesis. We summarize the use of various types of nanoparticles for treating spinal cord injuries, including metallic, polymeric, protein-based, inorganic non-metallic, and lipid nanoparticles. We also discuss the challenges faced, such as biosafety, effectiveness in humans, precise dosage control, standardization of production and characterization, immune responses, and targeted delivery in vivo. Additionally, we explore future directions, such as improving biosafety, standardizing manufacturing and characterization processes, and advancing human trials. Nanoparticles have shown considerable progress in targeted delivery and enhancing treatment efficacy for spinal cord injuries, presenting significant potential for clinical use and drug development.展开更多
Current therapeutic strategies for ischemic stroke fall short of the desired objective of neurological functional recovery.Therefore,there is an urgent need to develop new methods for the treatment of this condition.E...Current therapeutic strategies for ischemic stroke fall short of the desired objective of neurological functional recovery.Therefore,there is an urgent need to develop new methods for the treatment of this condition.Exosomes are natural cell-derived vesicles that mediate signal transduction between cells under physiological and pathological conditions.They have low immunogenicity,good stability,high delivery efficiency,and the ability to cross the blood–brain barrier.These physiological properties of exosomes have the potential to lead to new breakthroughs in the treatment of ischemic stroke.The rapid development of nanotechnology has advanced the application of engineered exosomes,which can effectively improve targeting ability,enhance therapeutic efficacy,and minimize the dosages needed.Advances in technology have also driven clinical translational research on exosomes.In this review,we describe the therapeutic effects of exosomes and their positive roles in current treatment strategies for ischemic stroke,including their antiinflammation,anti-apoptosis,autophagy-regulation,angiogenesis,neurogenesis,and glial scar formation reduction effects.However,it is worth noting that,despite their significant therapeutic potential,there remains a dearth of standardized characterization methods and efficient isolation techniques capable of producing highly purified exosomes.Future optimization strategies should prioritize the exploration of suitable isolation techniques and the establishment of unified workflows to effectively harness exosomes for diagnostic or therapeutic applications in ischemic stroke.Ultimately,our review aims to summarize our understanding of exosome-based treatment prospects in ischemic stroke and foster innovative ideas for the development of exosome-based therapies.展开更多
Parkinson’s disease is a common neurodegenerative disease with movement disorders associated with the intracytoplasmic deposition of aggregate proteins such asα-synuclein in neurons.As one of the major intracellular...Parkinson’s disease is a common neurodegenerative disease with movement disorders associated with the intracytoplasmic deposition of aggregate proteins such asα-synuclein in neurons.As one of the major intracellular degradation pathways,the autophagy-lysosome pathway plays an important role in eliminating these proteins.Accumulating evidence has shown that upregulation of the autophagy-lysosome pathway may contribute to the clearance ofα-synuclein aggregates and protect against degeneration of dopaminergic neurons in Parkinson’s disease.Moreover,multiple genes associated with the pathogenesis of Parkinson’s disease are intimately linked to alterations in the autophagy-lysosome pathway.Thus,this pathway appears to be a promising therapeutic target for treatment of Parkinson’s disease.In this review,we briefly introduce the machinery of autophagy.Then,we provide a description of the effects of Parkinson’s disease–related genes on the autophagy-lysosome pathway.Finally,we highlight the potential chemical and genetic therapeutic strategies targeting the autophagy–lysosome pathway and their applications in Parkinson’s disease.展开更多
Spinal muscular atrophy(SMA)is a genetic condition that results in selective lower motor neuron loss with concomitant muscle weakness and atrophy.The genetic cause of SMA was understood in 1995 when loss or impairment...Spinal muscular atrophy(SMA)is a genetic condition that results in selective lower motor neuron loss with concomitant muscle weakness and atrophy.The genetic cause of SMA was understood in 1995 when loss or impairment of the survival motor neuron 1(SMN1)gene was identified as the main contributing factor(Lefebvre et al.,1995).This,in combination with the discovery that humans have a“back-up”gene,SMN2,which can produce low levels(approximately 10%)of the full-length functional SMN protein,has led to the generation of SMA-specific gene therapies.SMA was traditionally classified according to age of symptom onset and developmental milestones achieved,with life expectancy and severity varying between individuals.Now,SMN2 copy number is used as a proxy for the prediction of disease severity,with higher SMN2 copy number typically being associated with reduced severity of SMA,although this relationship is not absolute:some individuals with low SMN2 copy number have less severe SMA phenotypes and vice versa.Additionally,the etiology of SMA is further complicated by other factors,such as non-typical nucleotide variants and SMN2-independent modifiers of disease severity.展开更多
Development of the telencephalon relies upon several signaling centers-localized cellular populations that supply secreted factors to pattern the cortical neuroepithelium.One such signaling center is the cortical hem,...Development of the telencephalon relies upon several signaling centers-localized cellular populations that supply secreted factors to pattern the cortical neuroepithelium.One such signaling center is the cortical hem,which arises during embryonic development at the telencephalic dorsal midline,adjacent to the choroid plexus and hippocampal primordium(Figure 1A).While the cortical hem has also been described in reptiles and birds,most of our knowledge about the developmental roles of the cortical hem is derived from the analysis in mice.The cortical hem produces several types of secreted molecules,including wingless-related integration site(Wnt)and bone morphogenetic(Bmp)proteins.The cortical hem is particularly important for the development of the hippocampus,which is involved in learning and memory,and the neocortex,which is the most complex brain region that mediates multiple types of behavior and higher cognitive functions(Mangale et al.,2008;Dal-Valle-Anton and Borrell,2022).展开更多
Several promising plasma biomarker proteins,such as amyloid-β(Aβ),tau,neurofilament light chain,and glial fibrillary acidic protein,are widely used for the diagnosis of neurodegenerative diseases.However,little is k...Several promising plasma biomarker proteins,such as amyloid-β(Aβ),tau,neurofilament light chain,and glial fibrillary acidic protein,are widely used for the diagnosis of neurodegenerative diseases.However,little is known about the long-term stability of these biomarker proteins in plasma samples stored at-80°C.We aimed to explore how storage time would affect the diagnostic accuracy of these biomarkers using a large cohort.Plasma samples from 229 cognitively unimpaired individuals,encompassing healthy controls and those experiencing subjective cognitive decline,as well as 99 patients with cognitive impairment,comprising those with mild cognitive impairment and dementia,were acquired from the Sino Longitudinal Study on Cognitive Decline project.These samples were stored at-80°C for up to 6 years before being used in this study.Our results showed that plasma levels of Aβ42,Aβ40,neurofilament light chain,and glial fibrillary acidic protein were not significantly correlated with sample storage time.However,the level of total tau showed a negative correlation with sample storage time.Notably,in individuals without cognitive impairment,plasma levels of total protein and tau phosphorylated protein threonine 181(p-tau181)also showed a negative correlation with sample storage time.This was not observed in individuals with cognitive impairment.Consequently,we speculate that the diagnostic accuracy of plasma p-tau181 and the p-tau181 to total tau ratio may be influenced by sample storage time.Therefore,caution is advised when using these plasma biomarkers for the identification of neurodegenerative diseases,such as Alzheimer's disease.Furthermore,in cohort studies,it is important to consider the impact of storage time on the overall results.展开更多
Alzheimer’s disease is a common neurodegenerative disorder defined by decreased reasoning abilities,memory loss,and cognitive deterioration.The presence of the blood-brain barrier presents a major obstacle to the dev...Alzheimer’s disease is a common neurodegenerative disorder defined by decreased reasoning abilities,memory loss,and cognitive deterioration.The presence of the blood-brain barrier presents a major obstacle to the development of effective drug therapies for Alzheimer’s disease.The use of ultrasound as a novel physical modulation approach has garnered widespread attention in recent years.As a safe and feasible therapeutic and drug-delivery method,ultrasound has shown promise in improving cognitive deficits.This article provides a summary of the application of ultrasound technology for treating Alzheimer’s disease over the past 5 years,including standalone ultrasound treatment,ultrasound combined with microbubbles or drug therapy,and magnetic resonance imaging-guided focused ultrasound therapy.Emphasis is placed on the benefits of introducing these treatment methods and their potential mechanisms.We found that several ultrasound methods can open the blood-brain barrier and effectively alleviate amyloid-βplaque deposition.We believe that ultrasound is an effective therapy for Alzheimer’s disease,and this review provides a theoretical basis for future ultrasound treatment methods.展开更多
BACKGROUND Malignant transformation(MT)of mature cystic teratoma(MCT)has a poor prognosis,especially in advanced cases.Concurrent chemoradiotherapy(CCRT)has an inhibitory effect on MT.CASE SUMMARY Herein,we present a ...BACKGROUND Malignant transformation(MT)of mature cystic teratoma(MCT)has a poor prognosis,especially in advanced cases.Concurrent chemoradiotherapy(CCRT)has an inhibitory effect on MT.CASE SUMMARY Herein,we present a case in which CCRT had a reduction effect preoperatively.A 73-year-old woman with pyelonephritis was referred to our hospital.Computed tomography revealed right hydronephrosis and a 6-cm pelvic mass.Endoscopic ultrasound-guided fine-needle biopsy(EUS-FNB)revealed squamous cell carci-noma.The patient was diagnosed with MT of MCT.Due to her poor general con-dition and renal malfunction,we selected CCRT,expecting fewer adverse effects.After CCRT,her performance status improved,and the tumor size was reduced;surgery was performed.Five months postoperatively,the patient developed dis-semination and lymph node metastases.Palliative chemotherapy was ineffective.She died 18 months after treatment initiation.CONCLUSION EUS-FNB was useful in the diagnosis of MT of MCT;CCRT suppressed the disea-se and improved quality of life.展开更多
The Janus fabrics designed for personal moisture/thermal regulation have garnered significant attention for their potential to enhance human comfort.However,the development of smart and dynamic fabrics capable of mana...The Janus fabrics designed for personal moisture/thermal regulation have garnered significant attention for their potential to enhance human comfort.However,the development of smart and dynamic fabrics capable of managing personal moisture/thermal comfort in response to changing external environments remains a challenge.Herein,a smart cellulose-based Janus fabric was designed to dynamically manage personal moisture/heat.The cotton fabric was grafted with N-isopropylacrylamide to construct a temperature-stimulated transport channel.Subsequently,hydrophobic ethyl cellulose and hydrophilic cellulose nanofiber were sprayed on the bottom and top sides of the fabric to obtain wettability gradient.The fabric exhibits anti-gravity directional liquid transportation from hydrophobic side to hydrophilic side,and can dynamically and continuously control the transportation time in a wide range of 3–66 s as the temperature increases from 10 to 40℃.This smart fabric can quickly dissipate heat at high temperatures,while at low temperatures,it can slow down the heat dissipation rate and prevent the human from becoming too cold.In addition,the fabric has UV shielding and photodynamic antibacterial properties through depositing graphitic carbon nitride nanosheets on the hydrophilic side.This smart fabric offers an innovative approach to maximizing personal comfort in environments with significant temperature variations.展开更多
Spinal cord injuries impose a notably economic burden on society,mainly because of the severe after-effects they cause.Despite the ongoing development of various therapies for spinal cord injuries,their effectiveness ...Spinal cord injuries impose a notably economic burden on society,mainly because of the severe after-effects they cause.Despite the ongoing development of various therapies for spinal cord injuries,their effectiveness remains unsatisfactory.However,a deeper understanding of metabolism has opened up a new therapeutic opportunity in the form of metabolic reprogramming.In this review,we explore the metabolic changes that occur during spinal cord injuries,their consequences,and the therapeutic tools available for metabolic reprogramming.Normal spinal cord metabolism is characterized by independent cellular metabolism and intercellular metabolic coupling.However,spinal cord injury results in metabolic disorders that include disturbances in glucose metabolism,lipid metabolism,and mitochondrial dysfunction.These metabolic disturbances lead to corresponding pathological changes,including the failure of axonal regeneration,the accumulation of scarring,and the activation of microglia.To rescue spinal cord injury at the metabolic level,potential metabolic reprogramming approaches have emerged,including replenishing metabolic substrates,reconstituting metabolic couplings,and targeting mitochondrial therapies to alter cell fate.The available evidence suggests that metabolic reprogramming holds great promise as a next-generation approach for the treatment of spinal cord injury.To further advance the metabolic treatment of the spinal cord injury,future efforts should focus on a deeper understanding of neurometabolism,the development of more advanced metabolomics technologies,and the design of highly effective metabolic interventions.展开更多
BACKGROUND Liver stiffness(LS)measurement with two-dimensional shear wave elastography(2D-SWE)correlates with the degree of liver fibrosis and thus indirectly reflects liver function reserve.The size of the spleen inc...BACKGROUND Liver stiffness(LS)measurement with two-dimensional shear wave elastography(2D-SWE)correlates with the degree of liver fibrosis and thus indirectly reflects liver function reserve.The size of the spleen increases due to tissue proliferation,fibrosis,and portal vein congestion,which can indirectly reflect the situation of liver fibrosis/cirrhosis.It was reported that the size of the spleen was related to posthepatectomy liver failure(PHLF).So far,there has been no study combining 2D-SWE measurements of LS with spleen size to predict PHLF.This prospective study aimed to investigate the utility of 2D-SWE assessing LS and spleen area(SPA)for the prediction of PHLF in hepatocellular carcinoma(HCC)patients and to develop a risk prediction model.AIM To investigate the utility of 2D-SWE assessing LS and SPA for the prediction of PHLF in HCC patients and to develop a risk prediction model.METHODS This was a multicenter observational study prospectively analyzing patients who underwent hepatectomy from October 2020 to March 2022.Within 1 wk before partial hepatectomy,ultrasound examination was performed to measure LS and SPA,and blood was drawn to evaluate the patient’s liver function and other conditions.Least absolute shrinkage and selection operator logistic regression and multivariate logistic regression analysis was applied to identify independent predictors of PHLF and develop a nomogram.Nomogram performance was validated further.The diagnostic performance of the nomogram was evaluated with receiver operating charac-teristic curve compared with the conventional models,including the model for end-stage liver disease(MELD)score and the albumin-bilirubin(ALBI)score.RESULTS A total of 562 HCC patients undergoing hepatectomy(500 in the training cohort and 62 in the validation cohort)were enrolled in this study.The independent predictors of PHLF were LS,SPA,range of resection,blood loss,international normalized ratio,and total bilirubin.Better diagnostic performance of the nomogram was obtained in the training[area under receiver operating characteristic curve(AUC):0.833;95%confidence interval(95%CI):0.792-0.873;sensitivity:83.1%;specificity:73.5%]and validation(AUC:0.802;95%CI:0.684-0.920;sensitivity:95.5%;specificity:52.5%)cohorts compared with the MELD score and the ALBI score.CONCLUSION This PHLF nomogram,mainly based on LS by 2D-SWE and SPA,was useful in predicting PHLF in HCC patients and presented better than MELD score and ALBI score.展开更多
Spinal cord injury involves non-reversible damage to the central nervous system that is characterized by limited regenerative capacity and secondary inflammatory damage.The expression of the C-C motif chemokine ligand...Spinal cord injury involves non-reversible damage to the central nervous system that is characterized by limited regenerative capacity and secondary inflammatory damage.The expression of the C-C motif chemokine ligand 2/C-C motif chemokine receptor 2 axis exhibits significant differences before and after injury.Recent studies have revealed that the C-C motif chemokine ligand 2/C-C motif chemokine receptor 2 axis is closely associated with secondary inflammatory responses and the recruitment of immune cells following spinal cord injury,suggesting that this axis is a novel target and regulatory control point for treatment.This review comprehensively examines the therapeutic strategies targeting the C-C motif chemokine ligand 2/C-C motif chemokine receptor 2 axis,along with the regenerative and repair mechanisms linking the axis to spinal cord injury.Additionally,we summarize the upstream and downstream inflammatory signaling pathways associated with spinal cord injury and the C-C motif chemokine ligand 2/C-C motif chemokine receptor 2 axis.This review primarily elaborates on therapeutic strategies that target the C-C motif chemokine ligand 2/C-C motif chemokine receptor 2 axis and the latest progress of research on antagonistic drugs,along with the approaches used to exploit new therapeutic targets within the C-C motif chemokine ligand 2/C-C motif chemokine receptor 2 axis and the development of targeted drugs.Nevertheless,there are presently no clinical studies relating to spinal cord injury that are focusing on the C-C motif chemokine ligand 2/C-C motif chemokine receptor 2 axis.This review aims to provide new ideas and therapeutic strategies for the future treatment of spinal cord injury.展开更多
Precision medicine is a growing field worldwide.Despite its potential benefit to many patients,several major obstacles must be overcome before precision medicine can be more widely used in clinical practice.The main o...Precision medicine is a growing field worldwide.Despite its potential benefit to many patients,several major obstacles must be overcome before precision medicine can be more widely used in clinical practice.The main obstacles are associated with the quality of samples used for genomic analysis。展开更多
Traumatic brain injury and Alzheimer's disease share pathological similarities,including neuronal loss,amyloid-βdeposition,tau hyperphosphorylation,blood-brain barrier dysfunction,neuroinflammation,and cognitive ...Traumatic brain injury and Alzheimer's disease share pathological similarities,including neuronal loss,amyloid-βdeposition,tau hyperphosphorylation,blood-brain barrier dysfunction,neuroinflammation,and cognitive deficits.Furthermore,traumatic brain injury can exacerbate Alzheimer's disease-like pathologies,potentially leading to the development of Alzheimer's disease.Nanocarriers offer a potential solution by facilitating the delive ry of small interfering RNAs across the blood-brain barrier for the targeted silencing of key pathological genes implicated in traumatic brain injury and Alzheimer's disease.U nlike traditional approaches to neuro regeneration,this is a molecula r-targeted strategy,thus avoiding non-specific drug actions.This review focuses on the use of nanocarrier systems for the efficient and precise delive ry of siRNAs,discussing the advantages,challenges,and future directions.In principle,siRNAs have the potential to target all genes and non-targetable protein s,holding significant promise for treating various diseases.Among the various therapeutic approaches currently available for neurological diseases,siRNA gene silencing can precisely"turn off"the expression of any gene at the genetic level,thus radically inhibiting disease progression;however,a significant challenge lies in delivering siRNAs across the blood-brain barrier.Nanoparticles have received increasing attention as an innovative drug delive ry tool fo r the treatment of brain diseases.They are considered a potential therapeutic strategy with the advantages of being able to cross the blood-brain barrier,targeted drug delivery,enhanced drug stability,and multifunctional therapy.The use of nanoparticles to deliver specific modified siRNAs to the injured brain is gradually being recognized as a feasible and effective approach.Although this strategy is still in the preclinical exploration stage,it is expected to achieve clinical translation in the future,creating a new field of molecular targeted therapy and precision medicine for the treatment of Alzheimer's disease associated with traumatic brain injury.展开更多
Tuning the coordination atoms of central metal is an effective means to improve the electrocatalytic activity of atomic catalysts.Herein,iridium(Ir) is proposed to be asymmetrically anchored by sp-N and pyridinic N of...Tuning the coordination atoms of central metal is an effective means to improve the electrocatalytic activity of atomic catalysts.Herein,iridium(Ir) is proposed to be asymmetrically anchored by sp-N and pyridinic N of hydrogen-substituted graphdiyne(HsGDY),and coordinated with OH as an Ir atomic catalyst(Ir_(1)-N-HsGDY).The electron structures,especially the d-band center of Ir atom,are optimized by these specific coordination atoms.Thus,the as-synthesized Ir_(1)-N-HsGDY exhibits excellent electrocatalytic performances for oxygen reduction and hydrogen evolution reactions in both acidic and alkaline media.Benefiting from the unique structure of HsGDY,IrN_(2)(OH)_(3) has been developed and demonstrated to act as the active site in these electrochemical reactions.All those indicate the fresh role of the sp-N in graphdiyne in producing a new anchor way and contributing to promote the electrocatalytic activity,showing a new strategy to design novel electrochemical catalysts.展开更多
Introduction: Sickle cell disease is a public health problem in sub-Saharan Africa. A national referral center for the management of infants and pregnant women with sickle cell disease (CPMI-NFED) was created three de...Introduction: Sickle cell disease is a public health problem in sub-Saharan Africa. A national referral center for the management of infants and pregnant women with sickle cell disease (CPMI-NFED) was created three decades ago in Cotonou, in the south of Benin with two regional branches including that of Parakou in the North for better access of patients to specialized care. This work is a review of five years of activities in order to describe the epidemiological, clinical, hematological and evolutionary profiles of the children followed up in the said branch. Method: This was a descriptive and retrospective cross-sectional study on the medical records of children with sickle cell disease, followed up at the regional branch of CPMI-NFED in Borgou/Alibori from June 1, 2017 to May 31, 2022. The variables studied were epidemiological, clinical, biological and evolutionary. Results: A total of 101 children with sickle cell disease were included in the study, including 78 homozygous SS (77.2%) and 23 heterozygous SC (22.8%). Their mean age at inclusion was 51.2 ± 37.6 months [6 - 204]. The sex ratio was 1.4. Vaso-occlusive crises were the main diagnostic circumstances in 42.3% of homozygotes. More than half of the children (51.5%) had a regular follow-up. The average baseline level of hemoglobin (Hb) in homozygous children was 8.8 ± 1.4 g/dl [5.8 - 11.5];and the rate of Hb S varied between 61.9 and 94.7%. In heterozygous SC children, the mean baseline level of Hb was 10.7 ± 0.6 g/dl [9.7 - 11.5]. Acute complications observed during follow-up were dominated by pneumonia and vaso-occlusive crises in both phenotypes. The overall mortality was 3% and only affected homozygous patients. Conclusion: On average, three out of four children were homozygous in our cohort. The main acute complications were infectious and vaso-occlusive. The mortality only affected homozygous carriers. Specialized follow-up has contributed to improving the quality of life of children with sickle cell disease. This could be implemented on a large scale for better survival of children with sickle cell disease.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
Background: Pacemaker implantation is a very old activity which has revolutionized the cardiology practice throughout the world. This activity is effective at the Haute Correze Hospital Center since more than 20 years...Background: Pacemaker implantation is a very old activity which has revolutionized the cardiology practice throughout the world. This activity is effective at the Haute Correze Hospital Center since more than 20 years. Due to progress in this area, and the increasing request within this center located at the outskirts of town, we set out to evaluate our pacemaker activity in general and more specifically to assess the post-procedural complications in our series patients. Methodology: This was a retrospective longitudinal study. Data were recorded for period of 90 months from 27/05/2016 to 19/11/2023. This data collection was possible via a specific register completed by computerized patient data from the SillageTM software. All files of patients implanted with single or dual chamber pacemakers were included, generator replacements, upgrading procedures and addition of leads were excluded. The sampling was non-probabilistic, consecutive and non-exhaustive. Statistical analysis was carried out using the Excel 2019 spreadsheet and SPSS version 23 software. The quantitative variables were presented as mean ± standard deviation, the qualitative data as proportions. Results: A total of 303 first-time pacemaker’s implantations were carried out during the study period (rate of 40 per year). The average age in the population was 79.7 ± 9.4 years (44 - 99 years) with a male predominance of 63.7% (n = 193). Atrioventricular block (2nd and 3rd degree) was the main indication for pacemaker implantation in 42.9% of cases (n = 130). Patients were most often implanted with a dual-chamber pacemaker (57.7%, n = 175). The approach was most often cephalic in 72.6% of cases (n = 220), followed by the subclavian access in 27.4% of cases (n = 84). The average fluoroscopy time was 7.9 min ± 2.4 (1 - 43). The average irradiation dose in gray/cm2 was 12.4 ± 9.3 (0.22 - 117.5). The average length of hospitalization was 7 ± 4 (2 - 26) days. The overall complication rate at one year was 12.9% (n = 39). These complications are distributed as follows: Leads dislodgement in 8.2% (n = 25), hematoma 3.6% (n = 11) all without clinical consequences, pneumothorax 0.7% (n = 2), both cases of pneumothorax did not require specific care, infection (superficial) in 0.3% (n = 1). Leads dislodgement occurred after a median time of 18 days (IQR: 3 - 36). The earliest dislodgement was observed on D0 and the latest on D207. No serious complications were recorded. The average atrial threshold at implantation/first control/last follow-up was 0.7/1.3/0.8 V, respectively. The average ventricular threshold at implantation/first control/last follow-up was 0.5/1.08/0.87 V, respectively. The average atrial detection at implantation/first control/last follow-up was 3.2/2.3/ 2.05 mv, respectively. The average ventricular detection at implantation/first control/last follow-up was 10.3/11.03/10.8 mv. The average atrial impedance at implantation/first control/last follow-up was 610/457/457 ohms. The average ventricular impedance at implantation/first control/last follow-up was 754/547/563 ohms. Conclusion: Pacemaker implantation is safe at the Haute Correze Hospital Center with a relatively low rate of complications, in this case an almost zero major infection and no serious hematoma. The peripheral hospital should remain a focal point of this activity in order to respond more quickly to the needs of the populations.展开更多
Objective:Accurate prognosis prediction is critical for individualized-therapy making of gastric cancer patients.We aimed to develop and test 6-month,1-,2-,3-,5-,and 10-year overall survival(OS)and cancer-specific sur...Objective:Accurate prognosis prediction is critical for individualized-therapy making of gastric cancer patients.We aimed to develop and test 6-month,1-,2-,3-,5-,and 10-year overall survival(OS)and cancer-specific survival(CSS)prediction models for gastric cancer patients following gastrectomy.Methods:We derived and tested Survival Quilts,a machine learning-based model,to develop 6-month,1-,2-,3-,5-,and 10-year OS and CSS prediction models.Gastrectomy patients in the development set(n=20,583)and the internal validation set(n=5,106)were recruited from the Surveillance,Epidemiology,and End Re-sults(SEER)database,while those in the external validation set(n=6,352)were recruited from the China National Cancer Center Gastric Cancer(NCCGC)database.Furthermore,we selected gastrectomy patients with-out neoadjuvant therapy as a subgroup to train and test the prognostic models in order to keep the accuracy of tumor-node-metastasis(TNM)stage.Prognostic performances of these OS and CSS models were assessed using the Concordance Index(C-index)and area under the curve(AUC)values.Results:The machine learning model had a consistently high accuracy in predicting 6-month,1-,2-,3-,5-,and 10-year OS in the SEER development set(C-index=0.861,0.832,0.789,0.766,0.740,and 0.709;AUC=0.784,0.828,0.840,0.849,0.869,and 0.902,respectively),SEER validation set(C-index=0.782,0.739,0.712,0.698,0.681,and 0.660;AUC=0.751,0.772,0.767,0.762,0.766,and 0.787,respectively),and NCCGC set(C-index=0.691,0.756,0.751,0.737,0.722,and 0.701;AUC=0.769,0.788,0.790,0.790,0.787,and 0.788,respectively).The model was able to predict 6-month,1-,2-,3-,5-,and 10-year CSS in the SEER development set(C-index=0.879,0.858,0.820,0.802,0.784,and 0.774;AUC=0.756,0.827,0.852,0.863,0.874,and 0.884,respectively)and SEER validation set(C-index=0.790,0.763,0.741,0.729,0.718,and 0.708;AUC=0.706,0.758,0.767,0.766,0.766,and 0.764,respectively).In multivariate analysis,the high-risk group with risk score output by 5-year OS model was proved to be a strong survival predictor both in the SEER development set(hazard ratio[HR]=14.59,95%confidence interval[CI]:1.872-2.774,P<0.001),SEER validation set(HR=2.28,95%CI:13.089-16.293,P<0.001),and NCCGC set(HR=1.98,95%CI:1.617-2.437,P<0.001).We further explored the prognostic value of risk score resulted 5-year CSS model of gastrectomy patients,and found that high-risk group remained as an independent CSS factor in the SEER development set(HR=12.81,95%CI:11.568-14.194,P<0.001)and SEER validation set(HR=1.61,95%CI:1.338-1.935,P<0.001).Conclusion:Survival Quilts could allow accurate prediction of 6-month,1-,2-,3-,5-,and 10-year OS and CSS in gastric cancer patients following gastrectomy.展开更多
文摘To:Chinese Association for International Understanding (CAFIU)CONGRATULATIONS LETTER Dear friends,I was glad to receive the news that your institution,our long-term partner,is celebrating its 40th anniversary since the founding of the Association.In the past few years,our two institutions as part of the non-govemmental sector.have jointly done several projects aimed at getting to know each other and especially on the promotion and construction of President Xi Jinping’s big Initiative,"One Belt and One Road".
基金supported by the Key Research Projects of Universities of Henan Province,No.21A320064 (to XS)the National Key Research and Development Program of China,No.2021YFA1201504 (to LZ)+1 种基金the Strategic Priority Research Program of the Chinese Academy of Science,No.XDB36000000 (to CW)the National Natural Science Foundation of China,Nos.31971295,12374406 (both to LZ)。
文摘Spinal cord injuries lead to significant loss of motor, sensory, and autonomic functions, presenting major challenges in neural regeneration. Achieving effective therapeutic concentrations at injury sites has been a slow process, partly due to the difficulty of delivering drugs effectively. Nanoparticles, with their targeted delivery capabilities, biocompatibility, and enhanced bioavailability over conventional drugs, are garnering attention for spinal cord injury treatment. This review explores the current mechanisms and shortcomings of existing treatments, highlighting the benefits and progress of nanoparticle-based approaches. We detail nanoparticle delivery methods for spinal cord injury, including local and intravenous injections, oral delivery, and biomaterial-assisted implantation, alongside strategies such as drug loading and surface modification. The discussion extends to how nanoparticles aid in reducing oxidative stress, dampening inflammation, fostering neural regeneration, and promoting angiogenesis. We summarize the use of various types of nanoparticles for treating spinal cord injuries, including metallic, polymeric, protein-based, inorganic non-metallic, and lipid nanoparticles. We also discuss the challenges faced, such as biosafety, effectiveness in humans, precise dosage control, standardization of production and characterization, immune responses, and targeted delivery in vivo. Additionally, we explore future directions, such as improving biosafety, standardizing manufacturing and characterization processes, and advancing human trials. Nanoparticles have shown considerable progress in targeted delivery and enhancing treatment efficacy for spinal cord injuries, presenting significant potential for clinical use and drug development.
基金supported by the National Natural Science Foundation of China,Nos.82071291(to YY),82301464(to HM)the Norman Bethune Health Science Center of Jilin University,No.2022JBGS03(to YY)+2 种基金a grant from Department of Science and Technology of Jilin Province,Nos.YDZJ202302CXJD061(to YY),20220303002SF(to YY)a grant from Jilin Provincial Key Laboratory,No.YDZJ202302CXJD017(to YY)Talent Reserve Program of First Hospital of Jilin University,No.JDYYCB-2023002(to ZNG)。
文摘Current therapeutic strategies for ischemic stroke fall short of the desired objective of neurological functional recovery.Therefore,there is an urgent need to develop new methods for the treatment of this condition.Exosomes are natural cell-derived vesicles that mediate signal transduction between cells under physiological and pathological conditions.They have low immunogenicity,good stability,high delivery efficiency,and the ability to cross the blood–brain barrier.These physiological properties of exosomes have the potential to lead to new breakthroughs in the treatment of ischemic stroke.The rapid development of nanotechnology has advanced the application of engineered exosomes,which can effectively improve targeting ability,enhance therapeutic efficacy,and minimize the dosages needed.Advances in technology have also driven clinical translational research on exosomes.In this review,we describe the therapeutic effects of exosomes and their positive roles in current treatment strategies for ischemic stroke,including their antiinflammation,anti-apoptosis,autophagy-regulation,angiogenesis,neurogenesis,and glial scar formation reduction effects.However,it is worth noting that,despite their significant therapeutic potential,there remains a dearth of standardized characterization methods and efficient isolation techniques capable of producing highly purified exosomes.Future optimization strategies should prioritize the exploration of suitable isolation techniques and the establishment of unified workflows to effectively harness exosomes for diagnostic or therapeutic applications in ischemic stroke.Ultimately,our review aims to summarize our understanding of exosome-based treatment prospects in ischemic stroke and foster innovative ideas for the development of exosome-based therapies.
基金supported by the National Natural Science Foundation of China,No.82101340(to FJ).
文摘Parkinson’s disease is a common neurodegenerative disease with movement disorders associated with the intracytoplasmic deposition of aggregate proteins such asα-synuclein in neurons.As one of the major intracellular degradation pathways,the autophagy-lysosome pathway plays an important role in eliminating these proteins.Accumulating evidence has shown that upregulation of the autophagy-lysosome pathway may contribute to the clearance ofα-synuclein aggregates and protect against degeneration of dopaminergic neurons in Parkinson’s disease.Moreover,multiple genes associated with the pathogenesis of Parkinson’s disease are intimately linked to alterations in the autophagy-lysosome pathway.Thus,this pathway appears to be a promising therapeutic target for treatment of Parkinson’s disease.In this review,we briefly introduce the machinery of autophagy.Then,we provide a description of the effects of Parkinson’s disease–related genes on the autophagy-lysosome pathway.Finally,we highlight the potential chemical and genetic therapeutic strategies targeting the autophagy–lysosome pathway and their applications in Parkinson’s disease.
基金supported by the Faculty Research Fund(Faculty of Medicine&Health Science,Keele University)Career Development Award–(April 2022)(to SJB)。
文摘Spinal muscular atrophy(SMA)is a genetic condition that results in selective lower motor neuron loss with concomitant muscle weakness and atrophy.The genetic cause of SMA was understood in 1995 when loss or impairment of the survival motor neuron 1(SMN1)gene was identified as the main contributing factor(Lefebvre et al.,1995).This,in combination with the discovery that humans have a“back-up”gene,SMN2,which can produce low levels(approximately 10%)of the full-length functional SMN protein,has led to the generation of SMA-specific gene therapies.SMA was traditionally classified according to age of symptom onset and developmental milestones achieved,with life expectancy and severity varying between individuals.Now,SMN2 copy number is used as a proxy for the prediction of disease severity,with higher SMN2 copy number typically being associated with reduced severity of SMA,although this relationship is not absolute:some individuals with low SMN2 copy number have less severe SMA phenotypes and vice versa.Additionally,the etiology of SMA is further complicated by other factors,such as non-typical nucleotide variants and SMN2-independent modifiers of disease severity.
基金supported by R01 NS093009 grant from NIH(to VVC).
文摘Development of the telencephalon relies upon several signaling centers-localized cellular populations that supply secreted factors to pattern the cortical neuroepithelium.One such signaling center is the cortical hem,which arises during embryonic development at the telencephalic dorsal midline,adjacent to the choroid plexus and hippocampal primordium(Figure 1A).While the cortical hem has also been described in reptiles and birds,most of our knowledge about the developmental roles of the cortical hem is derived from the analysis in mice.The cortical hem produces several types of secreted molecules,including wingless-related integration site(Wnt)and bone morphogenetic(Bmp)proteins.The cortical hem is particularly important for the development of the hippocampus,which is involved in learning and memory,and the neocortex,which is the most complex brain region that mediates multiple types of behavior and higher cognitive functions(Mangale et al.,2008;Dal-Valle-Anton and Borrell,2022).
基金supported by the National Key Research&Development Program of China,Nos.2021YFC2501205(to YC),2022YFC24069004(to JL)the STI2030-Major Project,Nos.2021ZD0201101(to YC),2022ZD0211800(to YH)+2 种基金the National Natural Science Foundation of China(Major International Joint Research Project),No.82020108013(to YH)the Sino-German Center for Research Promotion,No.M-0759(to YH)a grant from Beijing Municipal Science&Technology Commission(Beijing Brain Initiative),No.Z201100005520018(to JL)。
文摘Several promising plasma biomarker proteins,such as amyloid-β(Aβ),tau,neurofilament light chain,and glial fibrillary acidic protein,are widely used for the diagnosis of neurodegenerative diseases.However,little is known about the long-term stability of these biomarker proteins in plasma samples stored at-80°C.We aimed to explore how storage time would affect the diagnostic accuracy of these biomarkers using a large cohort.Plasma samples from 229 cognitively unimpaired individuals,encompassing healthy controls and those experiencing subjective cognitive decline,as well as 99 patients with cognitive impairment,comprising those with mild cognitive impairment and dementia,were acquired from the Sino Longitudinal Study on Cognitive Decline project.These samples were stored at-80°C for up to 6 years before being used in this study.Our results showed that plasma levels of Aβ42,Aβ40,neurofilament light chain,and glial fibrillary acidic protein were not significantly correlated with sample storage time.However,the level of total tau showed a negative correlation with sample storage time.Notably,in individuals without cognitive impairment,plasma levels of total protein and tau phosphorylated protein threonine 181(p-tau181)also showed a negative correlation with sample storage time.This was not observed in individuals with cognitive impairment.Consequently,we speculate that the diagnostic accuracy of plasma p-tau181 and the p-tau181 to total tau ratio may be influenced by sample storage time.Therefore,caution is advised when using these plasma biomarkers for the identification of neurodegenerative diseases,such as Alzheimer's disease.Furthermore,in cohort studies,it is important to consider the impact of storage time on the overall results.
基金supported by the National Natural Science Foundation of China,Nos.82371886(to JY),81925020(to DM),82202797(to LW),and 82271218(to CZ).
文摘Alzheimer’s disease is a common neurodegenerative disorder defined by decreased reasoning abilities,memory loss,and cognitive deterioration.The presence of the blood-brain barrier presents a major obstacle to the development of effective drug therapies for Alzheimer’s disease.The use of ultrasound as a novel physical modulation approach has garnered widespread attention in recent years.As a safe and feasible therapeutic and drug-delivery method,ultrasound has shown promise in improving cognitive deficits.This article provides a summary of the application of ultrasound technology for treating Alzheimer’s disease over the past 5 years,including standalone ultrasound treatment,ultrasound combined with microbubbles or drug therapy,and magnetic resonance imaging-guided focused ultrasound therapy.Emphasis is placed on the benefits of introducing these treatment methods and their potential mechanisms.We found that several ultrasound methods can open the blood-brain barrier and effectively alleviate amyloid-βplaque deposition.We believe that ultrasound is an effective therapy for Alzheimer’s disease,and this review provides a theoretical basis for future ultrasound treatment methods.
文摘BACKGROUND Malignant transformation(MT)of mature cystic teratoma(MCT)has a poor prognosis,especially in advanced cases.Concurrent chemoradiotherapy(CCRT)has an inhibitory effect on MT.CASE SUMMARY Herein,we present a case in which CCRT had a reduction effect preoperatively.A 73-year-old woman with pyelonephritis was referred to our hospital.Computed tomography revealed right hydronephrosis and a 6-cm pelvic mass.Endoscopic ultrasound-guided fine-needle biopsy(EUS-FNB)revealed squamous cell carci-noma.The patient was diagnosed with MT of MCT.Due to her poor general con-dition and renal malfunction,we selected CCRT,expecting fewer adverse effects.After CCRT,her performance status improved,and the tumor size was reduced;surgery was performed.Five months postoperatively,the patient developed dis-semination and lymph node metastases.Palliative chemotherapy was ineffective.She died 18 months after treatment initiation.CONCLUSION EUS-FNB was useful in the diagnosis of MT of MCT;CCRT suppressed the disea-se and improved quality of life.
基金support of this work by National Key Research and Development Program of China(2019YFC19059003)the Natural Science Foundation of the Jiangsu Higher Education Institutions of China(23KJB430024)+1 种基金Jiangsu Funding Program for Excellent Postdoctoral Talent(2023ZB680)Priority Academic Program Development of Jiangsu Higher Education Institutions(PAPD)are gratefully acknowledged.
文摘The Janus fabrics designed for personal moisture/thermal regulation have garnered significant attention for their potential to enhance human comfort.However,the development of smart and dynamic fabrics capable of managing personal moisture/thermal comfort in response to changing external environments remains a challenge.Herein,a smart cellulose-based Janus fabric was designed to dynamically manage personal moisture/heat.The cotton fabric was grafted with N-isopropylacrylamide to construct a temperature-stimulated transport channel.Subsequently,hydrophobic ethyl cellulose and hydrophilic cellulose nanofiber were sprayed on the bottom and top sides of the fabric to obtain wettability gradient.The fabric exhibits anti-gravity directional liquid transportation from hydrophobic side to hydrophilic side,and can dynamically and continuously control the transportation time in a wide range of 3–66 s as the temperature increases from 10 to 40℃.This smart fabric can quickly dissipate heat at high temperatures,while at low temperatures,it can slow down the heat dissipation rate and prevent the human from becoming too cold.In addition,the fabric has UV shielding and photodynamic antibacterial properties through depositing graphitic carbon nitride nanosheets on the hydrophilic side.This smart fabric offers an innovative approach to maximizing personal comfort in environments with significant temperature variations.
基金supported by the National Natural Science Foundation of China,No.82202681(to JW)the Natural Science Foundation of Zhejiang Province,Nos.LZ22H090003(to QC),LR23H060001(to CL).
文摘Spinal cord injuries impose a notably economic burden on society,mainly because of the severe after-effects they cause.Despite the ongoing development of various therapies for spinal cord injuries,their effectiveness remains unsatisfactory.However,a deeper understanding of metabolism has opened up a new therapeutic opportunity in the form of metabolic reprogramming.In this review,we explore the metabolic changes that occur during spinal cord injuries,their consequences,and the therapeutic tools available for metabolic reprogramming.Normal spinal cord metabolism is characterized by independent cellular metabolism and intercellular metabolic coupling.However,spinal cord injury results in metabolic disorders that include disturbances in glucose metabolism,lipid metabolism,and mitochondrial dysfunction.These metabolic disturbances lead to corresponding pathological changes,including the failure of axonal regeneration,the accumulation of scarring,and the activation of microglia.To rescue spinal cord injury at the metabolic level,potential metabolic reprogramming approaches have emerged,including replenishing metabolic substrates,reconstituting metabolic couplings,and targeting mitochondrial therapies to alter cell fate.The available evidence suggests that metabolic reprogramming holds great promise as a next-generation approach for the treatment of spinal cord injury.To further advance the metabolic treatment of the spinal cord injury,future efforts should focus on a deeper understanding of neurometabolism,the development of more advanced metabolomics technologies,and the design of highly effective metabolic interventions.
基金Supported by the National Natural Science Foundations of China,No.81873897 and No.82102050Shanghai Science and Technology Development Foundation,No.22Y11911500Shanghai Municipal Health Commission of Science and Research Fund,No.202140378.
文摘BACKGROUND Liver stiffness(LS)measurement with two-dimensional shear wave elastography(2D-SWE)correlates with the degree of liver fibrosis and thus indirectly reflects liver function reserve.The size of the spleen increases due to tissue proliferation,fibrosis,and portal vein congestion,which can indirectly reflect the situation of liver fibrosis/cirrhosis.It was reported that the size of the spleen was related to posthepatectomy liver failure(PHLF).So far,there has been no study combining 2D-SWE measurements of LS with spleen size to predict PHLF.This prospective study aimed to investigate the utility of 2D-SWE assessing LS and spleen area(SPA)for the prediction of PHLF in hepatocellular carcinoma(HCC)patients and to develop a risk prediction model.AIM To investigate the utility of 2D-SWE assessing LS and SPA for the prediction of PHLF in HCC patients and to develop a risk prediction model.METHODS This was a multicenter observational study prospectively analyzing patients who underwent hepatectomy from October 2020 to March 2022.Within 1 wk before partial hepatectomy,ultrasound examination was performed to measure LS and SPA,and blood was drawn to evaluate the patient’s liver function and other conditions.Least absolute shrinkage and selection operator logistic regression and multivariate logistic regression analysis was applied to identify independent predictors of PHLF and develop a nomogram.Nomogram performance was validated further.The diagnostic performance of the nomogram was evaluated with receiver operating charac-teristic curve compared with the conventional models,including the model for end-stage liver disease(MELD)score and the albumin-bilirubin(ALBI)score.RESULTS A total of 562 HCC patients undergoing hepatectomy(500 in the training cohort and 62 in the validation cohort)were enrolled in this study.The independent predictors of PHLF were LS,SPA,range of resection,blood loss,international normalized ratio,and total bilirubin.Better diagnostic performance of the nomogram was obtained in the training[area under receiver operating characteristic curve(AUC):0.833;95%confidence interval(95%CI):0.792-0.873;sensitivity:83.1%;specificity:73.5%]and validation(AUC:0.802;95%CI:0.684-0.920;sensitivity:95.5%;specificity:52.5%)cohorts compared with the MELD score and the ALBI score.CONCLUSION This PHLF nomogram,mainly based on LS by 2D-SWE and SPA,was useful in predicting PHLF in HCC patients and presented better than MELD score and ALBI score.
基金supported by the National Natural Science Foundation of China(Key Program),No.11932013the National Natural Science Foundation of China(General Program),No.82272255+2 种基金Armed Police Force High-Level Science and Technology Personnel ProjectThe Armed Police Force Focuses on Supporting Scientific and Technological Innovation TeamsKey Project of Tianjin Science and Technology Plan,No.20JCZDJC00570(all to XC)。
文摘Spinal cord injury involves non-reversible damage to the central nervous system that is characterized by limited regenerative capacity and secondary inflammatory damage.The expression of the C-C motif chemokine ligand 2/C-C motif chemokine receptor 2 axis exhibits significant differences before and after injury.Recent studies have revealed that the C-C motif chemokine ligand 2/C-C motif chemokine receptor 2 axis is closely associated with secondary inflammatory responses and the recruitment of immune cells following spinal cord injury,suggesting that this axis is a novel target and regulatory control point for treatment.This review comprehensively examines the therapeutic strategies targeting the C-C motif chemokine ligand 2/C-C motif chemokine receptor 2 axis,along with the regenerative and repair mechanisms linking the axis to spinal cord injury.Additionally,we summarize the upstream and downstream inflammatory signaling pathways associated with spinal cord injury and the C-C motif chemokine ligand 2/C-C motif chemokine receptor 2 axis.This review primarily elaborates on therapeutic strategies that target the C-C motif chemokine ligand 2/C-C motif chemokine receptor 2 axis and the latest progress of research on antagonistic drugs,along with the approaches used to exploit new therapeutic targets within the C-C motif chemokine ligand 2/C-C motif chemokine receptor 2 axis and the development of targeted drugs.Nevertheless,there are presently no clinical studies relating to spinal cord injury that are focusing on the C-C motif chemokine ligand 2/C-C motif chemokine receptor 2 axis.This review aims to provide new ideas and therapeutic strategies for the future treatment of spinal cord injury.
基金the Japan Agency for Medical Research and Development(Grant Nos.20lk0201002j0001,21lk0201005j0001,and 22lk0201007j0001)。
文摘Precision medicine is a growing field worldwide.Despite its potential benefit to many patients,several major obstacles must be overcome before precision medicine can be more widely used in clinical practice.The main obstacles are associated with the quality of samples used for genomic analysis。
基金supported by Open Project of the Key Laboratory of Trauma and Orthopedics Research Medicine in Henan Province,No.HZKFKT20220504(to YZ)the National Natural Science Foundation of China,No.32000877(to YZ)and Open Scientific Research Program of Military Logistics,No.BLB20J009(to YZ)。
文摘Traumatic brain injury and Alzheimer's disease share pathological similarities,including neuronal loss,amyloid-βdeposition,tau hyperphosphorylation,blood-brain barrier dysfunction,neuroinflammation,and cognitive deficits.Furthermore,traumatic brain injury can exacerbate Alzheimer's disease-like pathologies,potentially leading to the development of Alzheimer's disease.Nanocarriers offer a potential solution by facilitating the delive ry of small interfering RNAs across the blood-brain barrier for the targeted silencing of key pathological genes implicated in traumatic brain injury and Alzheimer's disease.U nlike traditional approaches to neuro regeneration,this is a molecula r-targeted strategy,thus avoiding non-specific drug actions.This review focuses on the use of nanocarrier systems for the efficient and precise delive ry of siRNAs,discussing the advantages,challenges,and future directions.In principle,siRNAs have the potential to target all genes and non-targetable protein s,holding significant promise for treating various diseases.Among the various therapeutic approaches currently available for neurological diseases,siRNA gene silencing can precisely"turn off"the expression of any gene at the genetic level,thus radically inhibiting disease progression;however,a significant challenge lies in delivering siRNAs across the blood-brain barrier.Nanoparticles have received increasing attention as an innovative drug delive ry tool fo r the treatment of brain diseases.They are considered a potential therapeutic strategy with the advantages of being able to cross the blood-brain barrier,targeted drug delivery,enhanced drug stability,and multifunctional therapy.The use of nanoparticles to deliver specific modified siRNAs to the injured brain is gradually being recognized as a feasible and effective approach.Although this strategy is still in the preclinical exploration stage,it is expected to achieve clinical translation in the future,creating a new field of molecular targeted therapy and precision medicine for the treatment of Alzheimer's disease associated with traumatic brain injury.
基金supported by the National Natural Science Foundation of China(22172090,21790051)the National Key Research and Development Project of China(2022YFA1204500,2022YFA1204501)+2 种基金the Natural Science Foundation of Shan-dong Province(ZR2021MB015)the Open Funds of the State Key Laboratory of Electroanalytical Chemistry(SKLEAC202202)the Young Scholars Program of Shandong University。
文摘Tuning the coordination atoms of central metal is an effective means to improve the electrocatalytic activity of atomic catalysts.Herein,iridium(Ir) is proposed to be asymmetrically anchored by sp-N and pyridinic N of hydrogen-substituted graphdiyne(HsGDY),and coordinated with OH as an Ir atomic catalyst(Ir_(1)-N-HsGDY).The electron structures,especially the d-band center of Ir atom,are optimized by these specific coordination atoms.Thus,the as-synthesized Ir_(1)-N-HsGDY exhibits excellent electrocatalytic performances for oxygen reduction and hydrogen evolution reactions in both acidic and alkaline media.Benefiting from the unique structure of HsGDY,IrN_(2)(OH)_(3) has been developed and demonstrated to act as the active site in these electrochemical reactions.All those indicate the fresh role of the sp-N in graphdiyne in producing a new anchor way and contributing to promote the electrocatalytic activity,showing a new strategy to design novel electrochemical catalysts.
文摘Introduction: Sickle cell disease is a public health problem in sub-Saharan Africa. A national referral center for the management of infants and pregnant women with sickle cell disease (CPMI-NFED) was created three decades ago in Cotonou, in the south of Benin with two regional branches including that of Parakou in the North for better access of patients to specialized care. This work is a review of five years of activities in order to describe the epidemiological, clinical, hematological and evolutionary profiles of the children followed up in the said branch. Method: This was a descriptive and retrospective cross-sectional study on the medical records of children with sickle cell disease, followed up at the regional branch of CPMI-NFED in Borgou/Alibori from June 1, 2017 to May 31, 2022. The variables studied were epidemiological, clinical, biological and evolutionary. Results: A total of 101 children with sickle cell disease were included in the study, including 78 homozygous SS (77.2%) and 23 heterozygous SC (22.8%). Their mean age at inclusion was 51.2 ± 37.6 months [6 - 204]. The sex ratio was 1.4. Vaso-occlusive crises were the main diagnostic circumstances in 42.3% of homozygotes. More than half of the children (51.5%) had a regular follow-up. The average baseline level of hemoglobin (Hb) in homozygous children was 8.8 ± 1.4 g/dl [5.8 - 11.5];and the rate of Hb S varied between 61.9 and 94.7%. In heterozygous SC children, the mean baseline level of Hb was 10.7 ± 0.6 g/dl [9.7 - 11.5]. Acute complications observed during follow-up were dominated by pneumonia and vaso-occlusive crises in both phenotypes. The overall mortality was 3% and only affected homozygous patients. Conclusion: On average, three out of four children were homozygous in our cohort. The main acute complications were infectious and vaso-occlusive. The mortality only affected homozygous carriers. Specialized follow-up has contributed to improving the quality of life of children with sickle cell disease. This could be implemented on a large scale for better survival of children with sickle cell disease.
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.
文摘Background: Pacemaker implantation is a very old activity which has revolutionized the cardiology practice throughout the world. This activity is effective at the Haute Correze Hospital Center since more than 20 years. Due to progress in this area, and the increasing request within this center located at the outskirts of town, we set out to evaluate our pacemaker activity in general and more specifically to assess the post-procedural complications in our series patients. Methodology: This was a retrospective longitudinal study. Data were recorded for period of 90 months from 27/05/2016 to 19/11/2023. This data collection was possible via a specific register completed by computerized patient data from the SillageTM software. All files of patients implanted with single or dual chamber pacemakers were included, generator replacements, upgrading procedures and addition of leads were excluded. The sampling was non-probabilistic, consecutive and non-exhaustive. Statistical analysis was carried out using the Excel 2019 spreadsheet and SPSS version 23 software. The quantitative variables were presented as mean ± standard deviation, the qualitative data as proportions. Results: A total of 303 first-time pacemaker’s implantations were carried out during the study period (rate of 40 per year). The average age in the population was 79.7 ± 9.4 years (44 - 99 years) with a male predominance of 63.7% (n = 193). Atrioventricular block (2nd and 3rd degree) was the main indication for pacemaker implantation in 42.9% of cases (n = 130). Patients were most often implanted with a dual-chamber pacemaker (57.7%, n = 175). The approach was most often cephalic in 72.6% of cases (n = 220), followed by the subclavian access in 27.4% of cases (n = 84). The average fluoroscopy time was 7.9 min ± 2.4 (1 - 43). The average irradiation dose in gray/cm2 was 12.4 ± 9.3 (0.22 - 117.5). The average length of hospitalization was 7 ± 4 (2 - 26) days. The overall complication rate at one year was 12.9% (n = 39). These complications are distributed as follows: Leads dislodgement in 8.2% (n = 25), hematoma 3.6% (n = 11) all without clinical consequences, pneumothorax 0.7% (n = 2), both cases of pneumothorax did not require specific care, infection (superficial) in 0.3% (n = 1). Leads dislodgement occurred after a median time of 18 days (IQR: 3 - 36). The earliest dislodgement was observed on D0 and the latest on D207. No serious complications were recorded. The average atrial threshold at implantation/first control/last follow-up was 0.7/1.3/0.8 V, respectively. The average ventricular threshold at implantation/first control/last follow-up was 0.5/1.08/0.87 V, respectively. The average atrial detection at implantation/first control/last follow-up was 3.2/2.3/ 2.05 mv, respectively. The average ventricular detection at implantation/first control/last follow-up was 10.3/11.03/10.8 mv. The average atrial impedance at implantation/first control/last follow-up was 610/457/457 ohms. The average ventricular impedance at implantation/first control/last follow-up was 754/547/563 ohms. Conclusion: Pacemaker implantation is safe at the Haute Correze Hospital Center with a relatively low rate of complications, in this case an almost zero major infection and no serious hematoma. The peripheral hospital should remain a focal point of this activity in order to respond more quickly to the needs of the populations.
基金supported by grant from the National Key R&D Program of China(grant number:2017YFC0908300)the Fun-damental Research Funds for the Central Universities(grant number:3332023136).
文摘Objective:Accurate prognosis prediction is critical for individualized-therapy making of gastric cancer patients.We aimed to develop and test 6-month,1-,2-,3-,5-,and 10-year overall survival(OS)and cancer-specific survival(CSS)prediction models for gastric cancer patients following gastrectomy.Methods:We derived and tested Survival Quilts,a machine learning-based model,to develop 6-month,1-,2-,3-,5-,and 10-year OS and CSS prediction models.Gastrectomy patients in the development set(n=20,583)and the internal validation set(n=5,106)were recruited from the Surveillance,Epidemiology,and End Re-sults(SEER)database,while those in the external validation set(n=6,352)were recruited from the China National Cancer Center Gastric Cancer(NCCGC)database.Furthermore,we selected gastrectomy patients with-out neoadjuvant therapy as a subgroup to train and test the prognostic models in order to keep the accuracy of tumor-node-metastasis(TNM)stage.Prognostic performances of these OS and CSS models were assessed using the Concordance Index(C-index)and area under the curve(AUC)values.Results:The machine learning model had a consistently high accuracy in predicting 6-month,1-,2-,3-,5-,and 10-year OS in the SEER development set(C-index=0.861,0.832,0.789,0.766,0.740,and 0.709;AUC=0.784,0.828,0.840,0.849,0.869,and 0.902,respectively),SEER validation set(C-index=0.782,0.739,0.712,0.698,0.681,and 0.660;AUC=0.751,0.772,0.767,0.762,0.766,and 0.787,respectively),and NCCGC set(C-index=0.691,0.756,0.751,0.737,0.722,and 0.701;AUC=0.769,0.788,0.790,0.790,0.787,and 0.788,respectively).The model was able to predict 6-month,1-,2-,3-,5-,and 10-year CSS in the SEER development set(C-index=0.879,0.858,0.820,0.802,0.784,and 0.774;AUC=0.756,0.827,0.852,0.863,0.874,and 0.884,respectively)and SEER validation set(C-index=0.790,0.763,0.741,0.729,0.718,and 0.708;AUC=0.706,0.758,0.767,0.766,0.766,and 0.764,respectively).In multivariate analysis,the high-risk group with risk score output by 5-year OS model was proved to be a strong survival predictor both in the SEER development set(hazard ratio[HR]=14.59,95%confidence interval[CI]:1.872-2.774,P<0.001),SEER validation set(HR=2.28,95%CI:13.089-16.293,P<0.001),and NCCGC set(HR=1.98,95%CI:1.617-2.437,P<0.001).We further explored the prognostic value of risk score resulted 5-year CSS model of gastrectomy patients,and found that high-risk group remained as an independent CSS factor in the SEER development set(HR=12.81,95%CI:11.568-14.194,P<0.001)and SEER validation set(HR=1.61,95%CI:1.338-1.935,P<0.001).Conclusion:Survival Quilts could allow accurate prediction of 6-month,1-,2-,3-,5-,and 10-year OS and CSS in gastric cancer patients following gastrectomy.