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Abstract Tuberous sclerosis complex (TSC) is an autosomal dominant disease characterized by the development of hamartomas in the central nervous system, heart, skin, lungs, and kidneys and other manifestations including seizures, cortical tubers, radial migration lines, autism and cognitive disability. The disease is associated with pathogenic variants in the TSC1 or TSC2 genes, resulting in the hyperactivation of the mTOR pathway, a key regulator of cell growth and metabolism. Consequently, the hyperactivation of the mTOR pathway leads to abnormal tissue proliferation and the development of solid tumors. Kidney involvement in TSC is characterized by the development of cystic lesions, renal cell carcinoma and renal angiomyolipomas, which may progress and cause pain, bleeding, and loss of kidney function. Over the past years, there has been a notable shift in the therapeutic approach to TSC, particularly in addressing renal manifestations. mTOR inhibitors have emerged as the primary therapeutic option, whereas surgical interventions like nephrectomy and embolization being reserved primarily for complications unresponsive to clinical treatment, such as severe renal hemorrhage. This review focuses on the main clinical characteristics of TSC, the mechanisms underlying kidney involvement, the recent advances in therapy for kidney lesions, and the future perspectives.
Resumo O complexo da esclerose tuberosa (CET) é uma doença autossômica dominante caracterizada pelo desenvolvimento de hamartomas no sistema nervoso central, coração, pele, pulmões e rins e outras manifestações, incluindo convulsões, tubérculos corticais, linhas de migração radial, autismo e deficiência cognitiva. A doença está associada a variantes patogênicas nos genes TSC1 ou TSC2, resultando na hiperativação da via mTOR, um importante regulador do crescimento e metabolismo celular. Consequentemente, a hiperativação da via mTOR leva à proliferação anormal do tecido e ao desenvolvimento de tumores sólidos. O envolvimento renal no CET é caracterizado pelo desenvolvimento de lesões císticas, carcinoma de células renais e angiomiolipomas renais, que podem progredir e causar dor, sangramento e perda da função renal. Nos últimos anos, houve uma mudança notável na abordagem terapêutica do CET, especialmente no tratamento das manifestações renais. Os inibidores de mTOR surgiram como a principal opção terapêutica, enquanto intervenções cirúrgicas como nefrectomia e embolização são reservadas principalmente para complicações que não respondem ao tratamento clínico, como hemorragia renal grave. Esta revisão se concentra nas principais características clínicas do CET, nos mecanismos subjacentes ao envolvimento renal, nos recentes avanços na terapia para lesões renais e nas perspectivas futuras.
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Introducción: La esclerosis lateral amiotrófica (ELA) es la forma más común de enfermedad degenerativa de motoneurona en la edad adulta y es considerada una enfermedad terminal. Por lo mismo, el accionar del fonoaudiólogo debe considerar el respeto a los principios bioéticos básicos para garantizar una asistencia adecuada. Objetivo: Conocer aquellas consideraciones bioéticas relacionadas al manejo y estudio de personas con ELA para luego brindar una aproximación hacia el quehacer fonoaudiológico. Método: Se efectuó una búsqueda bibliográfica en las bases de datos PubMed, Scopus y SciELO. Se filtraron artículos publicados desde 2000 hasta junio de 2023 y fueron seleccionados aquellos que abordaban algún componente bioético en población con ELA. Resultados: Aspectos relacionados al uso del consentimiento informado y a la toma de decisiones compartidas destacaron como elementos esenciales para apoyar la autonomía de las personas. Conclusión: Una correcta comunicación y una toma de decisiones compartida son claves para respetar la autonomía de las personas. A su vez, la estandarización de procedimientos mediante la investigación clínica permitirá aportar al cumplimiento de los principios bioéticos de beneficencia y no maleficencia, indispensables para la práctica profesional.
Introduction: Amyotrophic lateral sclerosis (ALS) is the most common form of degenerative motor neuron disease in adulthood and is considered a terminal disease. For this reason, the actions of the speech therapist must consider respect for basic bioethical principles to guarantee adequate assistance. Objective: To know those bioethical considerations related to the management and study of people with ALS to then provide an approach to speech therapy. Methodology: A bibliographic search was carried out in the PubMed, Scopus, and SciELO databases. Articles published from 2000 to June 2023 were filtered and those that addressed a bioethical component in the population with ALS were selected. Results: Aspects related to the use of informed consent and shared decision-making stood out as essential elements to support people's autonomy. Conclusion: Proper communication and shared decision-making are key to respecting people's autonomy. In turn, the standardization of procedures through clinical research will contribute to compliance with the bioethical principles of beneficence and non-maleficence, essential for professional practice.
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Introduction: Multiple sclerosis significantly affects the quality of life of those suffering from this specific condition. Objective: To assess the quality of life of people with multiple sclerosis and analyse the correlation between the disease and its associated effects and different sociodemographic, clinical, and functional variables. Materials and Methods: An observational, cross-sectional, descriptive-correlational and quantitative study conducted using a non-probabilistic convenience sample composed of 70 patients suffering from multiple sclerosis registered with the Multiple Sclerosis Association of the Central Region of Portugal. The data collection protocol included sociodemographic and clinical questions, the Family Apgar Scale, and the Barthel Index. Descriptive and inferential statistics were used to process the data. Data collection took place between April and July 2021. Results: The majority of participants reported a moderate overall quality of life (M=51,78 ± 24,09). Higher scores were observed in the social relationships and environmental health domains, while lower scores were recorded for the physical domain. Better quality of life was found to be positively associated with being under 45 years old, having higher educational qualifications, living in functional families, and experiencing greater functional independence in activities of daily living. Discussion: The variables with the strongest association were those capable of influencing the physical and social domains. Those variables explained 59.00% and 53.00% of the variability. Conclusions: These results indicate that people with multiple sclerosis have a compromised quality of life, highlighting the need for new strategies focusing on early diagnosis and effective preventive interventions meant to improve quality of life across all its domains.
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Patients , Qualité de vie , Maladies démyélinisantes , Stimulants du système nerveux central , Sclérose en plaquesRésumé
Las enfermedades de Alzheimer y esclerosis múltiple son neurodegenerativas, con tratamientos complejos y de costos elevados, orientados a disminuir la progresión de la sintomatología. Sin embargo, a causa de la falta de terapias adecuadas y de los posibles efectos adversos ocasionados por tratamientos de primera línea, es necesario implementar mejores abordajes terapéuticos complementarios que no produzcan mayores efectos secundarios y mejoren la sintomatología de dichas patologías. La restricción calórica y el ayuno intermitente han demostrado ser estrategias novedosas y beneficiosas en enfermedades neurodegenerativas, a través de mecanismos inmunitarios, metabólicos y fisiológicos. Con el objetivo de determinar el uso del ayuno intermitente y la restricción calórica como tratamiento coadyuvante en esclerosis múltiple y enfermedad de Alzheimer, se realizó una revisión narrativa de artículos originales en revistas científicas, en idiomas inglés y español, de 2018 a 2022. El uso de la restricción calórica y ayuno intermitente han generado cambios positivos produciendo disminución de estados proinflamatorios, estrés oxidativo y envejecimiento. Se consideran abordajes que modulan la progresión de la enfermedad y mejoran la función cognitiva por vías de señalización de monofosfato de adenosina cinasa, factor de crecimiento similar a la insulina y la enzima sirtuina, generando un efecto neuroprotector.
Alzheimer's disease and multiple sclerosis are neurodegenerative disorders with expensive and complex treatments aimed at reducing the progression of symptoms. However, due to the lack of adequate therapies and the possible adverse effects caused by first-line treatments, it's necessary to implement better complementary therapeutic approaches that do not produce major side effects and improve symptoms. Caloric restriction and intermittent fasting have been shown to be novel and beneficial strategies in neurodegenerative diseases, through immune, metabolic, and physiological mechanisms. To determine the use of intermittent fasting and caloric restriction as a new treatment in multiple sclerosis and Alzheimer's disease, a narrative review of original articles in both national and international scientific journals, in English and Spanish languages with no greater obsolescence than five years. The use of caloric restriction and intermittent fasting have generated positive changes, producing a decrease in pro-inflammatory states, oxidative stress, and aging. Approaches that modulate disease progression and improve cognitive function of adenosine monophosphate kinase, insulin-like growth factor, and sirtuin enzyme pathways are considered, generating a neuroprotective effect.
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SalvadorRésumé
Objective To identify the causative variants in 5 Chinese families with tuberous sclerosis complex(TSC)to provide genetic counseling and prenatal diagnosis.Methods Genetic counseling and clinical diagnosis were performed in 8 patients from five unrelated TSC families by teleconsultation.With informed consent obtained from the participants,3 to 5 mL peripheral blood samples were collected from the probands and their family mem-bers for the extraction of genomic DNA.Candidate pathogenic variants were screened by panel sequencing(PS).The candidate pathogenic variants found in TSC1 and TSC2 by PS were validated by PCR-Sanger sequencing and bioinformatics analysis.Results All the pathogenic mutations were identified in the probands and their available family members.Causative variants in TSC1 or TSC2 were detected in all patients,including three reported variants and two novel variants.The two novel variants,TSC2:c.245G＞A and TSC2:c.235delG,which were predicted to cause the nonsense variant p.(Trp82?)and the frameshift variant p.(Val79Lysfs27?)respectively was believed to introduce premature stop codons.The analysis of family co-segregation and bioinformatics were identified as very positive factors for pathogenicity.Conclusions This result provides more evidences for the genetic counseling and prenatal diagnosis in these families and expand the spectrum of TSC2 pathogenic variants.
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Objective To explore the characteristics and mechanism of phase separation between TAR DNA binding protein-43(TDP-43)and ubiquitin.Methods The TARDBP gene and its truncated genes were inserted into vectors to construct recombinant plasmids for expression and protein purification.The phase separation system of ubiquitin and TDP-43 was constructed in vitro.The characteristics of the droplets formed via liquid-liquid phase separation were observed by fluorescence microscopy.The plasmids of ubiquitin and TDP-43 were co-transfected into HEK293T cells to observe aggregates containing TDP-43 and ubiquitin and find out whether TDP-43 could be ubiquitinated.Results The GFP-8Ub,TDP-43 full-length(FL)and truncated proteins were purified.TDP-43 FL and C-terminal domain(CTD)proteins were able to form droplets via phase separation with ubiquitin.The droplets changed into solid-like aggregates after prolonged incubation.Insolvable aggregates containing TDP-43 and ubiquitin were formed.TDP-43 was ubiquitinated under stress conditions in HEK293T cells after being co-transfected with ubiquitin and TDP-43 recombinant plasmids.Conclusion TDP-43 undergoes co-phase separation with ubiquitin,mainly driven by the multivalent interaction between TDP-43′s CTD structural domain and ubiquitin.The droplets finally form aggregates with solid-like properties.Under stress conditions,especially when the protein homeostasis is disrupted,TDP-43 and ubiquitin form aggregates while TDP-43 is ubiquitinated.This study reveals the basic mechanism of TDP-43 co-phase separation with ubiquitin and liquid-solid transformation.
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Objective:To retrieve, evaluate and summarize the relevant evidence for respiratory management in patients with amyotrophic lateral sclerosis (ALS), and provide reference for clinical nursing.Methods:The best practices, guidelines, expert consensus and other evidence on respiratory management in ALS patients were systematically retrieved from dometic and foreign relevant guide websites, professional associations and databases. The retrieve period was from January 1, 2016 to April 15, 2023. After the literature quality evaluation, the evidence was extracted from the literature that meets the quality standards.Results:A total of 12 references were included, including 3 guidelines, 1 expert consensus, 1 evidence summary, 4 systematic reviews, and 3 randomized controlled trails. The 25 pieces of evidence were summarized from the patients with ALS, including respiratory assessment, mechanical ventilation, secreta management, and respiratory rehabilitation.Conclusions:This study summarizes the best evidence on respiratory tract management in patients with ALS, which is convenient for clinical medical personnel to carry out more targeted and scientific respiratory assessment, intervention and guidance for patients with ALS.
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Objective To explore the risk factors of supplementary injection after foam sclerotherapy for varicose veins of lower extremities and its impact on blood coagulation function.Methods A total of 185 patients with varicose veins of lower limbs diagnosed in the First People's Hospital of Zunyi from January 2018 to December 2021 were selected.The corresponding pathological data were collected,and the D-dimer,thrombin time,and fibrinogen level of patients were detected 1 d before and 1 d after the surgery.The postoperative video phone follow-up lasted until 6 months after the surgery.The patients were divided into single treatment group and supple-mentary treatment group according to whether supplementary injection of foam sclerosing agent was needed during the follow-up.Propensity matching on the data between the two groups was conducted,and the correlation between disease course data,coagulation factors,and the occurrence of supplementary injection was analyzed.A time series model for the incidence of supplementary injection was established,and the therapeutic effect and complica-tions were observed.Results After propensity matching,there was still significant difference in the degree of lesion between the two groups(P<0.05).On the first day after surgery,there was significant difference in the D-dimer and fibrinogen groups between the two groups(P<0.05),and but no significant difference in thrombin time(P>0.05).The occurrence of supplementary injection was significantly correlated with D-dimer,fibrinogen,thrombin time,and first-time injection dose(P<0.05),and the incidence of supplementary injection was higher in patients who received first-time injection in January,August,September,and December.Both groups achieved successful treatment 6 months after surgery,and there was no significant difference in the incidence of compli-cations.Conclusion Patients with lower limb varicose veins of C3/C4 are more likely to require supplementary injection compared to patients with other levels.The level of D-dimer and fibrinogen at 1 d after surgery is positively correlated with the occurrence of supplementary injection,while the dose of the first injection is negatively corre-lated with the occurrence of supplementary injection.
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Objective To explore the relationship between peripheral blood lymphocytes and disease progression in patients with amyotrophic lateral sclerosis(ALS)in central China.Methods A total of 133 ALS patients diagnosed at Tongji Hospital,Tongji Medical College,Huazhong University of Science and Technology were evaluated for disease progression,and the includ-ed patients were divided into fast progression group and slow progression group.Peripheral blood lymphocyte subsets were de-termined and compared between the two groups.Logistic regression was used to analyze the association between the statistically different lymphocyte subgroups and the rate of disease progression.Results The proportion of CD3+CD19-T lymphocytes in the slow progression group was lower than that of the fast progression group(P＜0.05).However,the NK cell count,NK cell proportion,and the proportion of CD28+helper T cells(CD28+Th cells)were higher than those of the fast progression group(all P＜0.05).In the logistic regression analysis,an increase in NK cell count(OR=0.992,P＜0.05)and an increase in the propor-tion of CD28+Th cells(OR=0.895,P＜0.05)were protective factors for the progression of ALS.Conclusion The characteris-tics of peripheral lymphocytes differed between patients with slow and fast progression.Abnormalities in the innate immune sys-tem may be involved in the progression of ALS.
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Objective Amyotrophic lateral sclerosis(ALS)is a progressive and fatal neurodegenerative disease.Mutations in the Cu/Zn superoxide dismutase 1 gene(SOD1)have been identified as the cause of familial ALS.Sequencing the SOD1 gene may be helpful for patients with a suspected family history of ALS.This article reports for the first time a case of amyotrophic lateral sclerosis with SOD1-p.A5S mutation in Han Chinese and summarizes its clinical characteristics.Method and Results This is the first report on Chinese Han of ALS with SOD1-p.A5S mutation and review of relevant case literature to summarize its clinical characteristics.The study case is a 34-year-old male who was admitted to the Neurology Department of The First Affiliated Hospital of Xi'an Jiaotong University with a complaint of"weakness in both lower limbs for 2 years,worsening with both hands for 6 months".The main clinical manifestations were progressive limb weakness,no swallowing difficulties or cognitive impairment.Further improvement of routine examinations and electromyography after admission were made to rule out other diagnoses,and genetic testing was conducted.Based on the patient's typical clinical manifestations and evidence of involvement of lower motor neurons in the cervical,thoracic,and lumbar spinal cord areas indicated by electromyography,other diagnoses and characteristic gene testing results were reasonably excluded,and ALS was diagnosed.The genetic testing results indicated that the patient had a heterozygous mutation in SOD1 exon 1,c.13G＞T(p.A5S),and his mother had a suspicious medical history but died without genetic verification.After discharge,the follow-up period lasted until August 21,2022,with a total of 38 months and a course of 62 months.Further review of the clinical characteristics of other patients with the same site mutation reported in the literature reveals that the progress of this patient with the mutation was slower than that of other patients with the same site mutation reported in the literature.Conclusion This study shows that gene sequencing is a powerful tool for diagnosing familial ALS.The mutation of c.13G＞T(p.A5S)in exon 1 of SOD1 is a rare pathogenic variation.The progress of patients with this subtype is slow,which further indicates that gene detection has important value in the diagnosis and prognosis of ALS.
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BACKGROUND:Astrocytes are the most abundant cells in the central nervous system,and various subsets of astrocytes are heterogeneous,performing a variety of special functions.Single-cell RNA sequencing(scRNA-seq)technology developed in recent years has extended our understanding of astrocyte heterogeneity from the perspective of transcriptome profiling. OBJECTIVE:To summarize the heterogeneity of scRNA-seq technology in different time and space,and pathological states and expand our knowledge of astrocyte heterogeneity on both molecular and functional levels. METHODS:The relevant articles on astrocyte heterogeneity and scRNA-seq were searched on PubMed,Elsevier,and CNKI databases.The search terms were"astrocytes,scRNA-seq,heterogeneity,Alzheimer disease,spinal cord injury,multiple sclerosis"in Chinese and English.Finally,74 articles were selected for viewing after screening according to inclusion criteria. RESULTS AND CONCLUSION:scRNA-seq studies related to the heterogeneity of astrocytes have shown that astrocyte is significantly heterogeneous across four aspects:species,developmental stage,central nervous system region,and pathological state.(1)Unique expression of certain genes occurs in astrocytes of different species,and the discovery of species-specific genes is beneficial for the translation of clinical studies.(2)During astrocyte development,differential gene expression emerged in the cellular subtypes identified at each stage,which further refined the cellular lineage of astrocytes and laid the foundation for the study of astrocyte developmental trajectories and mechanisms.(3)The discovery of differential gene expression allows regional localization of different astrocyte subpopulations and assists in the diagnosis and treatment of neurological diseases.(4)Astrocyte heterogeneity revealed by scRNA-seq can provide specific markers at the time of disease diagnosis and identify potential therapeutic targets.(5)The heterogeneity of astrocytes exists in many aspects,interacts with each other and is complex.The mechanisms of its generation,maintenance and transformation remain unclear.At present,molecular research on the single-cell level is still lacking.Linking transcriptionally defined astrocyte subpopulations to cellular activity,behavior and disease markers in real time remains one of the great challenges in the field.
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BACKGROUND:In the initial stage of multiple sclerosis,central immune cells activate and release a large number of inflammatory factors,causing white matter demyelination and even involving gray matter neurons.The equilibrium of differentiation between different subsets of CD4+ T cells plays an important role in the progression of experimental autoimmune encephalomyelitis.The previous results of the research group showed that the active ingredient astragalus glycoprotein in astragalus can regulate the immune response in experimental autoimmune encephalomyelitis mice,and whether it has a regulatory effect on the differentiation of T cell subsets has not been determined. OBJECTIVE:To explore the therapeutic effects and immune regulatory mechanisms of astragaloside IV on experimental autoimmune encephalomyelitis mice. METHODS:Female C57BL/6 mice were divided into the normal control group,experimental autoimmune encephalomyelitis disease model group,and astragaloside IV treatment group(n=8 per group).Myelin oligodendrocyte glycoprotein peptides 35-55 were used for experimental autoimmune encephalomyelitis model induction in the last two groups.On day 10 to 28 after immunization,the astragaloside IV treatment group was treated with 40 mg/kg per day astragaloside IV intragastrically.Body weight and clinical scores of mice in each group were recorded from the immunization day to the 28th day.On the 28th day after immunization,the mouse spinal cord was taken and made into frozen sections for hematoxylin-eosin staining and Lux fast blue staining to observe pathological changes in the spinal cord.Percentage of splenic T cell subsets was detected using flow cytometry.Western blot assay was used to determine the protein expression of interferon-γ,interleukin-17 and interleukin-6 in the spinal cord.Levels of interferon-γ,interleukin-17,interleukin-6 and interleukin-4 in supernatants of cultured splenocytes were determined by ELISA. RESULTS AND CONCLUSION:(1)Compared with the experimental autoimmune encephalomyelitis disease model group,astragaloside IV could reduce the degree of weight loss in experimental autoimmune encephalomyelitis mice(P<0.05),ameliorate clinical symptoms(P<0.05),inhibit the infiltration of inflammatory cells and alleviate myelin loss(P<0.01,P<0.05).(2)Compared with the experimental autoimmune encephalomyelitis disease model group,astragaloside IV could inhibit the proportion of CD4+T cell subsets expressing interferon-γ(P<0.001)and interleukin-17(P<0.001),but increase percentages of CD4+ interleukin-10+(P<0.001)and CD4+ transforming growth factor-β+(P<0.01)T cell subsets.(3)Astragaloside IV could inhibit the expression of interferon-γ(P<0.05,P<0.01),interleukin-17(P<0.05,P<0.05),and interleukin-6(P<0.05,P<0.05)in the spinal cord and spleen,and up-regulate the expression of interleukin-4(P<0.01)in spleen.(4)These findings confirm that astragaloside IV alleviates clinical symptoms in experimental autoimmune encephalomyelitis mice,which may be related to regulating the splenic T cell subsets,therefore,inhibiting the infiltration of inflammatory cells into the center and reducing the demyelination.
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BACKGROUND:Amyotrophic lateral sclerosis is a progressive neurodegenerative disease,which often leads to the death of neurons in the brain and spinal cord.The pathogenesis of amyotrophic lateral sclerosis is extremely complex,with high refractory rate and mortality rate.There are only two kinds of drugs for its treatment,so it is urgent to develop new treatment methods to improve the prognosis of patients. OBJECTIVE:To review the mechanism of Chinese medicine and mesenchymal stem cells regulating the immune response in the treatment of amyotrophic lateral sclerosis. METHODS:"Traditional Chinese medicine,medical stem cells,ALS,immune response"were Chinese and English search terms.Articles were retrieved from WanFang,CNKI,PubMed,Web of Science and other databases from 2010 to 2023.Finally,69 articles were included for review. RESULTS AND CONCLUSION:(1)The article summarizes in detail the five mechanisms of traditional Chinese medicine regulating the immune response in the treatment of amyotrophic lateral sclerosis:mainly including the promotion of expression of closed zone protein-1 and closed protein-5 by traditional Chinese medicine such as borneol and astragaloside IV to rebuild the integrity of the blood central nervous system barrier.Fufangteng Mixture can regulate the receptor molecules on the surface of the natural killer cells to inhibit their autotoxicity.The complement system factors such as Scutellaria barbata and patchouli can inhibit their abnormal activation.Tripterygium wilfordii and Uncaria rhynchophylla inhibit the activation of microglia by mediating the production of extracellular signal-regulated kinase 1/2 attenuated inducible nitric oxide synthase.Zuogui Pill and Trichosanthes kirilowii Root promote the expression of interleukin-10 and regulate T cells to improve the immune environment.(2)Through existing research,five mechanisms of mesenchymal stem cells regulating the immune response in the treatment of amyotrophic lateral sclerosis have been summarized,mainly including reducing the expression of aquaporin 4 and reducing endothelial nitric oxide synthase signal transduction to repair the integrity of the immune barrier;releasing indoleamine 2,3-dioxygenase,prostaglandin E2 and other factors to resist natural killer cell toxicity;secretion factor H interferes with the activity of invertase and inhibits abnormal activation of the complement system;regulating the CX3CL1/CX3CR1 system axis or secreting transforming growth factors β,which can change the phenotype of microglia and inhibit its activity by other ways;increasing the expression of interleukin-10 or activating the STATS phosphorylation pathway to restore T cell function.(3)At present,there are few studies on the combination of traditional Chinese medicine and mesenchymal stem cells in the treatment of amyotrophic lateral sclerosis.Relevant research reports have shown that Jiweiling Injection can promote stem cell proliferation and differentiation and that Buyang Huanwu decoction combined with bone marrow mesenchymal stem cells can significantly improve the integrity of the blood-brain barrier.In the future,further exploration is needed to explore the synergistic treatment effect of both on refractory amyotrophic lateral sclerosis.
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BACKGROUND:Multiple sclerosis is a chronic inflammatory demyelinating disease of the central nervous system mediated by T cells.The Toll-like receptors(TLRs)/myeloid differentiation factor 88(MyD88)/nuclear factor kappa-B(NF-κB)signaling pathway plays an important role in the development of the disease.Exploring the specific mechanism of the signaling pathway is essential for further treatment of the disease and improving the prognosis of patients. OBJECTIVE:To review the TLRs/MyD88/NF-κB signaling pathway and its role in multiple sclerosis/experimental autoimmune encephalomyelitis models,which provides new ideas and strategies for the treatment of multiple sclerosis by inhibiting the TLRs/MyD88/NF-κB signaling pathway. METHODS:The literature related to the topic from January 2002 to December 2022 was searched in CNKI,WanFang and PubMed databases.A total of 61 articles were finally included for analysis. RESULTS AND CONCLUSION:The TLRs/MyD88/NF-κB signaling pathway is an important pathway that triggers a pro-inflammatory immune response.The TLRs/MyD88/NF-κB signaling pathway plays an important role in the development of multiple sclerosis by regulating the antigen presentation of dendritic cells,destroying the integrity of the blood-brain barrier,and promoting the activation of T cells,B cells and microglia.By targeting TLRs,MyD88 and NF-κB molecules,inhibiting the activation or signal transduction of TLRs,MyD88 and NF-κB,and reducing the secretion of pro-inflammatory factors,multiple sclerosis can be treated.Animal studies have shown that active ingredients of traditional Chinese medicines,such as flavonoids and glycosides,and traditional Chinese medicine compound formulas,such as Buyang Huanwu Tang,can also treat experimental autoimmune encephalomyelitis by regulating the TLRs/MyD88/NF-κB signaling pathway,which points to the direction of searching for medicines targeting the TLRs/MyD88/NF-κB signaling pathway for the treatment of multiple sclerosis.
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Purpose To evaluate the consistency and repeatability of cerebral blood flow(CBF)values measured by automatic segmentation of region of interest(ROI)and arterial spin labeling(ASL)functional image fusion in hippocampal sclerosis patients with medial temporal lobe epilepsy.Materials and Methods From January 2021 to October 2022,a total of 52 patients with medial temporal lobe epilepsy confirmed by MRI or pathology in General Hospital of Ningxia Medical University were retrospectively collected.All subjects were scanned on 3.0T MRI to obtain axial T1 weighted three-dimensional magnetization reserve gradient echo(3D-T1W1-MPGAGE)sequence and three-dimensional pseudo continuous ASL sequence.The 3D-T1W1-MPGAGE imaging were automatically segmented.Two physicians used the freeview visualization interface of freeSurfer software to fuse the ROI and ASL functional images of the hippocampal subregions and to measure the CBF values.The intra-observer and inter-observer consistency and repeatability were evaluated and analyzed.The consistency analysis and repeatability evaluation were performed via intraclass correlation coefficient(ICC),Bland-Altman diagram and Wilcoxon rank sum test.Results The ICC of CBF values measured by two physicians were all>0.750,with an average of 0.868±0.095.The ICC of left and right hippocampal subregions were as follows:subiculum(SUB):0.818/0.801,cornu ammonis(CA)1:0.920/0.907,CA2-3:0.759/0.978,CA4:0.757/0.758 and dentate gyrus(DG):0.990/0.991;The ICC delineated by the same physician's ROI were all>0.990 with an average of 0.994±0.002.The ICC of left and right hippocampal subregions were as follows:SUB:0.993/0.993,CA1:0.996/0.995,CA2-3:0.989/0.994,CA4:0.992/0.995 and DG:0.993/0.996.The Bland-Altman diagram showed the scatter distribution and consistency,and the coefficient of repeatability was obtained.The same observer had certain repeatability for the fusion measurement of automatic segmentation ROI and ASL functional images.Conclusion The CBF values measured by fusing ROI and ASL functional images of automatically segmented hippocampal subregion have higher consistency and repeatability.
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CD20 is a classic marker expressed by B cells. However, recent studies have found that CD20 is also dimly expressed on a small subset of CD3 +T cells, and the CD20 +T cells play an important proinflammatory role in multiple sclerosis (MS). Anti-CD20 monoclonal antibodies selectively deplete CD20 +T cells and effectively suppress inflammatory disease activity. Although CD20 +T cells have received increasing attention, the understanding of these cells is currently still in its infancy. This article provides an overview of the current knowledge about advanced progress of CD20 +T cells as well as their roles in MS.
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Ever since interferon-β was introduced into China more than 20 years ago and used in the disease-modifying therapies (DMT) of multiple sclerosis (MS) patients, the Chinese translations of DMT used in China are quite puzzling, even clinicians are also difficult to understand the meaning of DMT. The authors searched and traced the origins of current DMT translations, which may be mainly due to the fact that the word "modifying" in Chinese contains two meanings: correction and alleviation, obviously currently used names prefer to correct, while the exact meaning of DMT should be to alleviate disease. Considering that inaccurate translation is widely used in domestic academic conferences and academic journals, it is easy to cause misunderstanding and ambiguity. The authors believe that the meaning of DMT should be correctly and deeply understood in the specific context, and the original meaning of alleviating disease should be returned, which is also in line with the two endpoints of immunomodulatory therapy for MS and optic neuromyelitis spectrum disease, the primary endpoint being to reduce the annual recurrence rate of the diseases, the secondary one being to slow the progression of disease disability.
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Objective:To analyze the clinical phenotypes and TSC1/TSC2 gene variations in 52 children with tuberous sclerosis complex. Methods:The clinical data of 59 children with tuberous sclerosis complex hospitalized in Linyi People′s Hospital between January 2017 and October 2022 were collected. The analysis of TSC1 and TSC2 gene variations on main family members was performed, and then bioinformatics analysis followed. The positive children were divided into TSC1 gene group and TSC2 gene group, and the difference of clinical characteristics between the two groups was analyzed. Results:Among 59 children, 52 cases were detected TSC1/ TSC2 gene variations (17 cases in the TSC1 gene group and 35 cases in the TSC2 gene group). Of the 52 children, 28 (53.8%) were male, 24 were female (46.2%); 17 (32.7%) were familial cases (10 with TSC1 gene variations and 7 with TSC2 gene variations), 35 (67.3%) were sporadic cases; 46 (88.5%) had hypomelanotic macules, 13 (25.0%) had facial angiofibromas, 5 (9.6%) had shagreen patches, 49 (94.2%) had subependymal nodules/calcifications, 47 (90.4%) had cortical nodules, 2 (3.8%) had subependymal giant cell astrocytomas, 39 (75.0%) had intellectual/developmental disabilities, 49 (94.2%) had epileptic seizures, 8 (15.4%) had cardiac rhabdomyomas, 9 (17.3%) had renal angiomyolipomas, and 4 (7.7%) had retinal hamartomas. Of the 52 children, 49 variations were detected, including 4 large fragment deletion/duplication variations, and 45 point variations; 41 pathogenic variations, 7 likely pathogenic variations, and 1 variation of uncertain significance. In this study, 16 point mutations and 1 large fragment duplication mutation which had not been reported at home and abroad, and 3 high-frequency mutation sites (p.Arg692 *, p.Arg228 *, and p.Arg1200Try) were found. There was a statistically significant difference in the proportion of familial cases [10/17 vs 7/35(20%), χ2=7.838, P=0.005], median onset age of epilepsy [38.0(0.5-134.0) months vs 8.0(0.1-63.0) months, Z=3.506 , P<0.001] and the incidence of developmental retardation/intellectual impairment [8/17 vs 31/35(88.6%), χadj2=8.423, P=0.004] between the TSC1 gene and TSC2 gene groups. Conclusions:Tuberous sclerosis compiex has widespread phenotypes, can affect every body system, especially the skin and nervous system. The pathogenic gene is TSC1/ TSC2. The TSC1 gene group has more familial cases. The TSC2 gene group has an earlier onset age of epilepsy and a higher incidence of developmental retardation/intellectual impairment. In this study, 16 novel point mutations, 1 novel large fragment duplication mutation, and 3 hotspot mutations were identified, expanding the gene variation spectrum of tuberous sclerosis complex.
Résumé
Amyotrophic lateral sclerosis is a fatal neurodegenerative disease caused by the loss of motor neurons in the brain and spinal cord. Amyotrophic lateral sclerosis is currently incurable and treatment drugs are limited and can only delay the condition. The latest research shows that α-linolenic acid can prolong the survival period of patients with amyotrophic lateral sclerosis. This article reviews the neuroprotective effects of α-linolenic acid on amyotrophic lateral sclerosis through different mechanisms of action, aiming at providing some references for the treatment of amyotrophic lateral sclerosis.