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Disease tolerance is an essential defense strategy against pathogens, alleviating tissue damage regardless of pathogen multiplication. However, its genetic and molecular basis remains largely unknown. Here, we discovered that protein condensation at the endoplasmic reticulum (ER) regulates disease tolerance in Arabidopsis against Pseudomonas syringae. During infection, Hematopoietic protein-1 (HEM1) and Bax-inhibitor 1 (BI-1) coalesce into ER-associated condensates facilitated by their phase-separation behaviors. While BI-1 aids in clearing these condensates via autophagy, it also sequesters lipid-metabolic enzymes within condensates, likely disturbing lipid homeostasis. Consequently, mutations in hem1, which hinder condensate formation, or in bi-1, which prevent enzyme entrapment, enhance tissue-damage resilience, and preserve overall plant health during infection. These findings suggest that the ER is a crucial hub for maintaining cellular homeostasis and establishing disease tolerance. They also highlight the potential of engineering disease tolerance as a defense strategy to complement established resistance mechanisms in combating plant diseases.
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BACKGROUND: Lower eyelid suspension, a common therapeutic procedure for facial paralysis-induced eyelid retraction, faces challenges due to high recurrence in patients lacking facial muscle function and impedes wider adoption. This research aims to explore the potential effects of restoring orbicularis oculi muscle tension through facial nerve reanimation prior to lower eyelid suspension and to define the indications for lower eyelid suspension. METHODS: The study encompassed 32 individuals with complete facial paralysis, segmented into group A (reanimation group) and group B (non-reanimation group), based on whether the orbicularis oculi muscle's tension was restored through facial nerve reconstruction prior to lower eyelid suspension. Subjective assessments of eyelid closure (the inter-eyelid gap upon gentle closure) and objective methods measures of scleral show (the distance from the pupil's center to the lower eyelid margin, MRD2) were used to provide a comprehensive analysis of long-term effectiveness. RESULTS: The group A exhibited significantly greater long-term improvement in lagophthalmos and lower eyelid ectropion. The alterations in MRD2 measured 2.66 ± 0.27 mm in the group A versus 2.08 ± 0.53 mm in the group B, denoting a statistically significant variance (p < 0.001). Moreover, while the ratio of MRD2 preoperative 6 months postoperative revealed no significant difference between groups, a significant difference emerged in 12 months postoperative (group A: 1.02 ± 0.21; group B: 1.18 ± 0.24; p < 0.05), with the values in group A closer to 1, indicative of enhanced symmetry. CONCLUSIONS: Restoring the tension in the orbicularis oculi muscle through facial nerve reconstruction prior to palmaris longus tendon sling could effectively sustain long-term outcomes of lower eyelid retraction correction and reduce the recurrence rate. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .
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OBJECTIVE: Facial paralysis (FP), which resulted from head and neck cancer resection, significantly impacts patients' quality of life. Traditional assessments rely on subjective evaluations and electromyography, whereas functional magnetic resonance imaging offers a noninvasive alternative for enhanced rehabilitation. Acupuncture has shown promise in promoting cerebral cortex reorganization, yet the precise relationship between acupuncture-induced structural and functional changes remains unclear, necessitating further investigation into therapeutic mechanisms. METHODS: Fifty-five patients afflicted with FP underwent evaluations using voxel-mirrored homotopic connectivity (VMHC) and tract-based spatial statistics and were divided into the acupuncture intervention group (n = 35) and pseudo intervention group (n = 20). Comparative analyses of metrics pre and postintervention were conducted to delineate therapy-induced modifications in acupuncture intervention. The postacupuncture effect between groups to verify the necessity of accurate positioning for the rehabilitation of FP. RESULTS: Patients with FP showed deficits in VMHC in regions of the postcentral, precentral, and parietal areas. Corpus callosum and internal capsule showed significantly increased fractional anisotropy of the white matter skeleton in tract-based spatial statistics after treatment. Comparison postintervention results between groups exhibited deficits in VMHC and increased fractional anisotropy in regions of the corpus callosum in the acupuncture intervention group. CONCLUSIONS: Early acupuncture intervention may suppress cortical hyperactivation and restore interhemispheric inhibition across the corpus callosum to inhibit maladaptive structural plasticity. Precise acupoint localization is crucial for effective therapy, highlighting the potential of postacupuncture cortical space data for refining therapeutic strategies.
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5-endo-trig radical cyclization has long been recognized as one of the most straightforward ways for the construction of densely functionalized five-membered rings. Nevertheless, according to Baldwin's rules, the 5-endo-trig radical cyclization is kinetically disfavored due to stereoelectronic effects and thus usually proceeds via a slow rate, which renders its application a challenging task. In recent years, with the emergence of efficient radical generation methods and effective cyclization strategies, 5-endo-trig radical cyclization has been successfully accelerated to a synthetically useful rate and has been utilized in the access of diverse five-membered carbo- and heterocyclic compounds. This review comprehensively summarizes the methodologies involving the 5-endo-trig radical cyclization process, with particular emphasis on the elucidation of the promoting strategies, which include the polar effect, geometrical constraints, spin delocalization effect, and persistent radical effect. Each of these strategies is discussed in detail, with illustrative examples from recent literature studies to highlight their practical applications and effectiveness. It is anticipated that the in-depth understanding of the 5-endo-trig radical cyclization provided by this review would inspire further innovation of this privileged reaction mode and expand its applications. Moreover, the potent ring-closure-promoting strategies revealed herein would also contribute to achieving other challenges of cyclizations with particular significance for organic synthesis.
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Goose astroviruses (GAstVs) are important pathogens which can cause gout in goslings leading to huge economic losses for the goose farming industry in China. In 2023, an infectious disease characterized by visceral gout broke out in commercial goose farms in Guangxi and Guangdong provinces of China. In this study, two GAstV strains of GXNN and GDCS were successfully isolated from these two disease-ridden goose farms. The complete genomic lengths of these two strains were 7166 bp, and phylogenetic analysis showed that they were both GAstV-2 subtypes. The 3-dimensional structures of the capsid protein were predicted and six characteristic mutation sites at amino acid positions 60, 61, 228, 229, 456 and 523 were found within the strong antigenic regions. A recombination event occurred at 6833-7070 nt between the GAstV TZ03 and Turkey astrovirus CA/00 and this was detected in both the GXNN and GDCS strains. Another recombinant event occurred at 63-2747 nt between the GAstV XT1 and GAstV SDPY and this was detected in the GDCS strain. When 1-day-old goslings were infected with the novel GXNN and GDCS strains, they showed severe visceral gout. This was accompanied by enlarged spleens, liver hemorrhages and urate deposits in the kidneys and ureters and their blood urea nitrogen levels were significantly elevated. The mortality rates of the GXNN- and GDCS-infected groups were pathogenically high at 80 % and 60 %, respectively. These results will promote our understanding of the evolution and epidemic potential of GAstVs in China.
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Plant immune homeostasis is achieved through a balanced immune activation and suppression, enabling effective defense while averting autoimmunity. In Arabidopsis, disrupting a mitogen-activated protein (MAP) kinase cascade triggers nucleotide-binding leucine-rich-repeat (NLR) SUPPRESSOR OF mkk1/2 2 (SUMM2)-mediated autoimmunity. Through an RNAi screen, we identify PUB5, a putative plant U-box E3 ligase, as a critical regulator of SUMM2-mediated autoimmunity. In contrast to typical E3 ligases, PUB5 stabilizes CRCK3, a calmodulin-binding receptor-like cytoplasmic kinase involved in SUMM2 activation. A closely related E3 ligase, PUB44, functions oppositely with PUB5 to degrade CRCK3 through monoubiquitylation and internalization. Furthermore, CRCK3, highly expressed in roots and conserved across plant species, confers resistance to Fusarium oxysporum, a devastating soil-borne fungal pathogen, in both Arabidopsis and cotton. These findings demonstrate the antagonistic role of an E3 ligase pair in fine-tuning kinase proteostasis for the regulation of NLR-mediated autoimmunity and highlight the function of autoimmune activators in governing plant root immunity against fungal pathogens.
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Proteínas de Arabidopsis , Arabidopsis , Autoimunidade , Resistência à Doença , Fusarium , Doenças das Plantas , Imunidade Vegetal , Ubiquitina-Proteína Ligases , Arabidopsis/imunologia , Arabidopsis/microbiologia , Arabidopsis/genética , Ubiquitina-Proteína Ligases/metabolismo , Ubiquitina-Proteína Ligases/genética , Proteínas de Arabidopsis/metabolismo , Proteínas de Arabidopsis/genética , Doenças das Plantas/microbiologia , Doenças das Plantas/imunologia , Fusarium/imunologia , Proteínas NLR/metabolismo , Proteínas NLR/genética , Regulação da Expressão Gênica de Plantas , Ubiquitinação , Proteínas de TransporteRESUMO
Transcription factors (TFs) tightly control plant development by regulating gene expression. The phase separation of TFs plays a vital role in gene regulation. Many plant TFs have the potential to form phase-separated protein condensates; however, little is known about which TFs are regulated by phase separation and how it affects their roles in plant development. Here, we report that the rice (Oryza sativa) single Myb TF TELOMERE REPEAT-BINDING FACTOR 2 (TRBF2) is highly expressed in fast-growing tissues at the seedling stage. TRBF2 is a transcriptional repressor that binds to the transcriptional start site of thousands of genes. Mutation of TRBF2 leads to pleiotropic developmental defects and misexpression of many genes. TRBF2 displays characteristics consistent with phase separation in vivo and forms phase-separated condensates in vitro. The H1/H5 domain of TRBF2 plays a crucial role in phase separation, chromatin targeting and gene repression. Replacing the H1/H5 domain by a phase-separated intrinsically disordered region from Arabidopsis (Arabidopsis thaliana) AtSERRATE partially recovers the function of TRBF2 in gene repression in vitro and in transgenic plants. We also found that TRBF2 is required for trimethylation of histone H3 Lys27 (H3K27me3) deposition at specific genes and genome-wide. Our findings reveal that phase separation of TRBF2 facilitates gene repression in rice development.
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BACKGROUND: Although the correlation between liver toxicity and vancomycin is generally considered low, it has been observed that the use of vancomycin can lead to abnormal liver function indicators, such as elevated aspartate aminotransferase, alanine aminotransferase, alpha fetoprotein, and jaundice. To further understand the clinical features associated with vancomycin-induced liver toxicity and to provide clinical guidance, we conducted an analysis of the characteristics and clinical manifestations of vancomycin-induced liver injury. METHODS: Patients with liver function injury who received vancomycin treatment at the Third Xiangya Hospital of Central South University and Hunan Maternal and Child Health Hospital between 2016 and 2021 were selected for retrospective analysis of their general characteristics, vancomycin course, dose, liver function index, severity of liver injury, and concomitant medications. RESULTS: Of the 4562 patients who received vancomycin, 17 patients were finally included, with an incidence rate of 0.37%. Of these patients, 12 were male (70.6%) and 5 were female (29.4%), ranging in age from 17 to 84 years with a mean average age of 45.41 ± 20.405 years. All patients were evaluated using Naranjo's score, with score ≥ 3. The dosage, time, and plasma concentration of vancomycin were analyzed and it was found that nine patients (52.94%) had abnormal liver function when initially given a dose of 1 g every 12 hours. In total, 14 patients (82.35%) with liver injury were taking vancomycin in combination with two to four drugs, and severe liver injury occurred in patients taking vancomycin in combination with two drugs. The occurrence time of liver injury was 2-12 days after starting vancomycin, with a mean of 4.53 ± 2.401 days. Of these patients, 16 patients (94.1%) showed liver function abnormalities within 7 days of taking the drug, and 2 patients with grade 3-4 liver injury both showed liver function abnormalities within 3 days of taking the drug. Only 4 of the 17 patients (23.53%) had vancomycin blood concentrations within the normal range, and there was no correlation found between blood concentration and severity of liver injury. Analysis of the correlation between the severity of liver injury and vancomycin showed that none of the patients had allergies such as rash, two patients (11.76%) had jaundice, and fatigue occurred in five patients (29.41%). The remaining ten patients (58.82%) had no symptoms related to liver injury. All 17 patients had abnormal aspartate aminotransferase/alanine aminotransferase levels and 9 patients also had abnormal bilirubin levels. In 15 patients (88.24%), the severity of liver injury was grade 1, indicating mild liver injury, and no correlation was observed between the severity of liver injury and creatinine. Of the 17 patients, 1 patient received no intervention, 4 patients stopped taking vancomycin after developing liver injury, 1 patient reduced the dose, and 11 patients (64.7%) were treated with hepatic protectant. CONCLUSION: Although the study concluded that the incidence of liver injury was not high, the liver toxicity of vancomycin should still be considered and liver function indicators should be monitored during the clinical use of vancomycin.
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Antibacterianos , Doença Hepática Induzida por Substâncias e Drogas , Vancomicina , Humanos , Vancomicina/efeitos adversos , Feminino , Masculino , Pessoa de Meia-Idade , Adulto , Estudos Retrospectivos , Antibacterianos/efeitos adversos , Adolescente , Idoso , Adulto Jovem , Idoso de 80 Anos ou mais , Testes de Função HepáticaRESUMO
Cyclobutanes are popular structural units in bioactive compounds and versatile intermediates in synthetic chemistry, but their synthesis is challenging owing to high ring strain. In this study, a novel method for highly regio- and diastereoselective synthesis of fluoroalkylcyclobutanes bearing vicinal quaternary and tertiary stereocenters is realized by a photocatalytic 4-exo-trig cyclization cascade of thioalkynes or trifluoromethylalkenes. Density functional theory calculations reveal that a unique fluorine effect, arising from hyperconjugative πâσ*C-F interactions, accounts for the regio-reversed radical addition at the sterically hindered alkene carbon, which facilitates an unprecedented 4-exo-trig ring closure. This chemistry enables the direct and controllable construction of medicinally valuable quaternary-carbon-containing cyclobutanes from readily available raw materials, nicely complementing the existing methods.
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A de novo method for direct construction of cyclopenta[b]indolines via a photocatalytic fluoroalkylative radical cyclization cascade of ynamides has been established, which proceeds via a sequence of radical addition, 1,5-HAT, 5-endo-trig cyclization, intramolecular arylation, and oxidative deprotonation. This protocol allows for the controllable assembly of a tricyclic architecture with three contiguous stereocenters, showcasing its high efficiency, compatibility, and regio- and diastereoselectivity for accessing pharmacologically significant fluoroalkylated cyclopenta[b]indolines. It represents one of the very few examples of tetrafunctionalization of alkynes.
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Oreocharisleveilleana Fedde was collected in Ta-pin in 1910 and published in 1911. The collected location was verified within western Luodian County, Guizhou Province, China. However, there have been no records of the species' collection for more than 100 years since then. After extensive investigations by our research team on the type locality and its surrounding areas, we found that it is widely distributed in western Luodian County and eastern Wangmo County, Guizhou Province, China. During further research on the original literature, type specimens and type locality of O.leveilleana, the taxonomic position of O.leveilleana, which was once treated as a synonym of O.auricula (S.Moore) C.B.Clarke, was found to have a taxonomic problem. Through morphological research combined with geographical distribution analysis, it has been determined that it should belong to the genus Petrocodon Hance and it is the same species as P.coccineus (C.Y.Wu ex H.W.Li) Yin Z.Wang. According to the regulations and suggestions of the 2018 "International Code of Nomenclature for Algae, Fungi, and Plants (Shenzhen Code)", we propose and confirm a new combination - Petrocodonleveilleanus (Fedde) X.X.Bai & F.Wen and treat P.coccineus as a synonym of the new combination. Due to its unique bright red flowers within Petrocodon, its original Chinese name has been retained.
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Recently, the FeOCl-type two-dimensional materials have attracted significant attention owing to their versatile applications in fields such as thermoelectricity and photocatalysis. This study aims to systematically investigate the thermoelectric properties of ScSX (X = Cl, Br, and I) monolayers by a combination of the first-principles calculations and the machine-learning interatomic potential approach. These monolayers are indirect semiconductors with band gaps of 3.22 (ScSCl), 3.27 (ScSBr), and 2.87 eV (ScSI), respectively. The lattice thermal conductivity is decreased by 25.72% (20.90%), 44.05% (40.00%), and 30.96% (34.76%) for ScSCl, ScSBr, and ScSI along the x-axis (y-axis) when the four-phonon scattering is introduced, indicating its important role in phonon transport. Anharmonic phonon scattering yields high Grüneisen parameter and scattering rate values, hence causing these low lattice thermal conductivities. Additionally, the large Seebeck coefficients and electrical conductivities of n-type doped ScSX monolayers contribute to their excellent power factors (24.69, 25.66, and 24.99 mW/K2·m for ScSCl, ScSBr and ScSI at 300 K, respectively). Based on the excellent power factor and low thermal conductivity, the maximum values of the figure of merit are calculated to be 2.68, 3.39, and 3.21 for ScSCl, ScSBr, and ScSI monolayers at 700 K, respectively. Our research provides valuable insights into the phonon thermal transport of ScSX monolayers and suggests a promising approach to address high-order anharmonicity.
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Engineering disease-resistant plants can be a powerful solution to the issue of food security. However, it requires addressing two fundamental questions: what genes to express and how to control their expressions. To find a solution, we screen CRISPR-edited upstream open reading frame (uORF) variants in rice, aiming to optimize translational control of disease-related genes. By switching uORF types of the 5'-leader from Arabidopsis TBF1, we modulate the ribosome accessibility to the downstream firefly luciferase. We assume that by switching uORF types using CRISPR, we could generate uORF variants with alternative translation efficiency (CRISPR-aTrE-uORF). These variants, capable of boosting translation for resistance-associated genes and dampening it for susceptible ones, can help pinpoint previously unidentified genes with optimal expression levels. To test the assumption, we screened edited uORF variants and found that enhanced translational suppression of the plastic glutamine synthetase 2 can provide broad-spectrum disease resistance in rice with minimal fitness costs. This strategy, which involves modifying uORFs from none to some, or from some to none or different ones, demonstrates how translational agriculture can speed up the development of disease-resistant crops. This is vital for tackling the food security challenges we face due to growing populations and changing climates.
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Sistemas CRISPR-Cas , Resistência à Doença , Fases de Leitura Aberta , Oryza , Oryza/genética , Resistência à Doença/genética , Fases de Leitura Aberta/genética , Sistemas CRISPR-Cas/genética , Edição de Genes/métodos , Doenças das Plantas/genética , Arabidopsis/genética , Plantas Geneticamente Modificadas/genética , Biossíntese de Proteínas/genética , Regulação da Expressão Gênica de Plantas , Produtos Agrícolas/genética , Traduções , Repetições Palindrômicas Curtas Agrupadas e Regularmente Espaçadas/genéticaRESUMO
A 5'-leader, known initially as the 5'-untranslated region, contains multiple isoforms due to alternative splicing (aS) and alternative transcription start site (aTSS). Therefore, a representative 5'-leader is demanded to examine the embedded RNA regulatory elements in controlling translation efficiency. Here, we develop a ranking algorithm and a deep-learning model to annotate representative 5'-leaders for five plant species. We rank the intra-sample and inter-sample frequency of aS-mediated transcript isoforms using the Kruskal-Wallis test-based algorithm and identify the representative aS-5'-leader. To further assign a representative 5'-end, we train the deep-learning model 5'leaderP to learn aTSS-mediated 5'-end distribution patterns from cap-analysis gene expression data. The model accurately predicts the 5'-end, confirmed experimentally in Arabidopsis and rice. The representative 5'-leader-contained gene models and 5'leaderP can be accessed at RNAirport (http://www.rnairport.com/leader5P/). The Stage 1 annotation of 5'-leader records 5'-leader diversity and will pave the way to Ribo-Seq open-reading frame annotation, identical to the project recently initiated by human GENCODE.
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Regiões 5' não Traduzidas , Regiões 5' não Traduzidas/genética , Processamento Alternativo/genética , Oryza/genética , Bases de Dados Genéticas , Sítio de Iniciação de Transcrição , Arabidopsis/genética , Redes Neurais de Computação , Modelos Genéticos , Algoritmos , Aprendizado Profundo , Regulação da Expressão Gênica de Plantas/genética , Plantas/genética , RNA de Plantas/genéticaRESUMO
With over 600 valid species, the wrasses (family Labridae) are among the largest and most successful families of the marine teleosts. They feature prominently on coral reefs where they are known not only for their impressive diversity in colouration and form but also for their functional specialisation and ability to occupy a wide variety of trophic guilds. Among the wrasses, the parrotfishes (tribe Scarini) display some of the most dramatic examples of trophic specialisation. Using abrasion-resistant biomineralized teeth, parrotfishes are able to mechanically extract protein-rich micro-photoautotrophs growing in and among reef carbonate material, a dietary niche that is inaccessible to most other teleost fishes. This ability to exploit an otherwise untapped trophic resource is thought to have played a role in the diversification and evolutionary success of the parrotfishes. In order to better understand the key evolutionary innovations leading to the success of these dietary specialists, we sequenced and analysed the genome of a representative species, the spotted parrotfish (Cetoscarus ocellatus). We find significant expansion, selection and duplications within several detoxification gene families and a novel poly-glutamine expansion in the enamel protein ameloblastin, and we consider their evolutionary implications. Our genome provides a useful resource for comparative genomic studies investigating the evolutionary history of this highly specialised teleostean radiation.
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Background: Neurotoxicity is a rare adverse event for ertapenem. Given the limited evidence, large patient data are needed to aid in the identification and management of this fatal complication. Aim of the review, we summarize the characteristics, risk factors, and treatment of ertapenem-induced neurotoxicity. Methods: Pubmed, Web of Science, Embase, Cochrane library, Wanfang, CNKI, China VIP database were searched up from 31 October 2001 to 31 December 2022. All articles concerning neurotoxicity induced by ertapenem were included. The retrieved articles were screened by two experienced clinicians by reading the titles, abstracts, and full texts. Results: A total of 66 patients were included, with a median age of 71.5 years (range 40-92), of whom 45 (68.2%) were male. Twelve patients (18.2%) received irrational doses (exceeding the recommended dose), and 30 patients (45.5%) had chronic renal insufficiency. The median time to symptom onset was 5 (range 1-14). Epileptiform seizures (42.4%), visual hallucinations (36.4%), altered mental status (25.8%), and confusion (22.7%) were the most common symptoms of ertapenem-induced neurotoxicity. Of the 29 patients with reported albumin levels, 25 had serum albumin <3.5 g/dl. Ertapenem was discontinued in 95.5% of patients, and 90.9% recovered completely. Median time to symptom recovery was 7 days (range 1-42) after intervention including antiepileptic administration, or hemodialysis. Conclusion: Neurotoxicity is a rare adverse event for ertapenem, especially in patients with advanced age, renal insufficiency, pre-existing neurological disease, and hypoalbuminemia. This adverse reaction usually resolves with medication interruption, or antiepileptic administration and hemodialysis.
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Mounting an efficient defense against pathogens requires RNA binding proteins (RBPs) to regulate immune mRNAs transcription, splicing, export, translation, storage, and degradation. RBPs often have multiple family members, raising the question of how they coordinate to carry out diverse cellular functions. In this study, we demonstrate that EVOLUTIONARILY CONSERVED C-TERMINAL REGION 9 (ECT9), a member of the YTH protein family in Arabidopsis, can condensate with its homolog ECT1 to control immune responses. Among the 13 YTH family members screened, only ECT9 can form condensates that decrease after salicylic acid (SA) treatment. While ECT1 alone cannot form condensates, it can be recruited to ECT9 condensates in vivo and in vitro. Notably, the ect1/9 double mutant, but not the single mutant, exhibits heightened immune responses to the avirulent pathogen. Our findings suggest that co-condensation is a mechanism by which RBP family members confer redundant functions.
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Translational reprogramming is a fundamental layer of immune regulation, but how such a global regulatory mechanism operates remains largely unknown. Here we perform a genetic screen and identify Arabidopsis HEM1 as a global translational regulator of plant immunity. The loss of HEM1 causes exaggerated cell death to restrict bacterial growth during effector-triggered immunity (ETI). By improving ribosome footprinting, we reveal that the hem1 mutant increases the translation efficiency of pro-death immune genes. We show that HEM1 contains a plant-specific low-complexity domain (LCD) absent from animal homologues. This LCD endows HEM1 with the capability of phase separation in vitro and in vivo. During ETI, HEM1 interacts and condensates with the translation machinery; this activity is promoted by the LCD. CRISPR removal of this LCD causes more ETI cell death. Our results suggest that HEM1 condensation constitutes a brake mechanism of immune activation by controlling the tissue health and disease resistance trade-off during ETI.
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Proteínas de Arabidopsis , Arabidopsis , Animais , Regulação da Expressão Gênica de Plantas , Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Resistência à Doença , Imunidade Vegetal/genética , Doenças das Plantas/microbiologiaRESUMO
Myasthenia gravis (MG) is a rare but life-threatening adverse event with pembrolizumab. What is known about pembrolizumab-induced MG is largely based on case reports. This analysis collected pembrolizumab-induced MG cases from Chinese and English databases published from September 1, 2014, to June 30, 2022. Demographic and clinical information of the patients, management, and outcome data were collected and analyzed. Sixty-five patients with a median age of 73 years (range 30-86), including 43 male patients (66.2%), were included. Eight patients (12.3%) with prior MG experienced worsening symptoms after receiving pembrolizumab. The median time to the onset of MG was four weeks (range 0.7-27). The most common symptoms were ptosis (81.5%, 53 patients), diplopia (50.8%, 33 patients), dyspnea (44.6%, 29 patients), trunk or peripheral weakness (43.1%, 28 patients), and dysphagia (30.8%, 20 patients). Concurrent myositis and myocarditis occurred in 13 (20.0%) and 17 patients (26.2%). Pembrolizumab was discontinued in 63 patients (96.9%). Forty-four patients (67.7%) received combination therapies based on steroids (intravenous immune globulin, plasmapheresis, or immunosuppressants). Twenty-seven patients (41.5%) had symptoms completely recovered. Fourteen patients (21.5%) died from immunotoxicity or primary cancers. Clinicians should consider the possibility of pembrolizumab-induced MG, especially during the first eight weeks of therapy. Patients should be treated as early as possible, regardless of the severity of the initial symptoms.
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Miastenia Gravis , Humanos , Masculino , Adulto , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Miastenia Gravis/induzido quimicamente , Miastenia Gravis/diagnóstico , Miastenia Gravis/tratamento farmacológico , Anticorpos Monoclonais Humanizados/efeitos adversos , Imunoglobulinas Intravenosas/uso terapêutico , Terapia CombinadaRESUMO
OBJECTIVES: Dabigatran-induced oesophagitis has emerged in recent years. However, the incidence and clinical characteristics of patients with dabigatran-induced oesophagitis have not yet been clarified. The aim of this study was to examine the clinical characteristics of the disease. METHODS: A retrospective analysis was undertaken of the literature on dabigatran-induced oesophagitis in Chinese and English from 2008 onwards. RESULTS: There were 20 men (74.07%) and seven women (25.93%) in the study; their median age was 75 years (range 37-90). The main clinical symptoms were dysphagia (42.31%), odynophagia (26.92%), retrosternal pain (23.08%) and heartburn (23.08%). Endoscopy mainly showed sloughing mucosal casts (14 cases, 56%), ulcers (8 cases, 32%) and erosion (6 cases, 24%). The main injury sites were the mid to lower oesophagus (32%) and the mid oesophagus (32%). Withdrawal of dabigatran or giving the correct medication regimen resulted in rapid recovery of clinical symptoms from 1 day in some patients and up to 4 weeks, and mucosal recovery (2-5 weeks) in a median time of 3 weeks (range 0.29-48) in all patients. CONCLUSIONS: Oesophagitis is a rare complication of dabigatran with a good prognosis. Patients should be given proper medication instructions to prevent the occurrence of dabigatran-induced oesophagitis.