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This study aimed to investigate the relationship between the promoting effect of Zuogui Pills on ovarian and vaginal angiogenesis in early-aging rats and mobilization factors granulocyte-macrophage colony-stimulating factor(GM-CSF), stromal cell-derived factor-1(SDF-1), and their receptors of endothelial progenitor cells(EPCs) and explore the mechanism of Zuogui Pills in improving reproductive hypofunction in early-aging rats. Ultra-high performance liquid chromatography-tandem mass spectrometry(UHPLC-MS/MS) was used to analyze the chemical components of the extract of Zuogui Pills. Forty 14-month-old female early-aging rats with estrous cycle disorder were randomly divided into a blank group, a conjugated estrogen group(conjugated estrogen suspension, 65 µg·kg~(-1)), and low-(11 g·kg~(-1)) and high-dose(33 g·kg~(-1)) Zuogui Pills groups, with 10 rats in each group. In addition, 10 4-month-old female rats were assigned to the youth control group. The rats in the blank group and the youth control group were treated with 20 g·kg~(-1) distilled water by gavage, while those in the groups with drug intervention were treated with corresponding drugs by gavage, once a day for 15 days. Enzyme-linked immunosorbent assay(ELISA) was used to detect the levels of SDF-1 and GM-CSF in the mobilization of EPCs in serum. Hematoxylin-eosin(HE) staining was used to observe the changes in the number of ovarian follicles at all levels and corpus luteum, the number of vaginal epithelial layers, the number of vaginal folds, and the blood vessels of ovarian and vaginal tissues in the groups with drug intervention. Western blot was used to detect the expression of ER, GM-CSFR, CXCR4, and CXCR7 proteins in ovarian and vaginal tissues. As revealed by the results, the blank group showed decreased number of corpus luteum, gro-wing follicles at all levels, and blood vessels(P<0.05), decreased thickness of vaginal mucosa, the number of epithelial layers, the number of vaginal folds, and the number of vessels in the lamina propria(P<0.05), reduced content of SDF-1 and GM-CSF in the peripheral blood(P<0.05), and down-regulated levels of ER, CXCR4, CXCR7, and GM-CSFR proteins in ovarian and vaginal tissues(P<0.05). The groups with drug intervention showed increased number of growing follicles at all levels, corpus luteum, and blood vessels(P<0.05), decreased number of atresia follicles(P<0.05), increased thickness of vaginal mucosa, the number of epithelial layers, the number of vaginal mucosal folds, and the number of blood vessels in the lamina propria(P<0.05), increased content of SDF-1 and GM-CSF in the peripheral blood(P<0.05), and up-regulated levels of ER, CXCR4, CXCR7, and GM-CSFR proteins in ovarian and vaginal tissues(P<0.05). This experiment suggests that Zuogui Pills may promote ovarian and vaginal angiogenesis and improve the reproductive function of early-aging rats by up-regulating the levels of mobilization factors SDF-1, GM-CSF, and their receptors of EPCs.
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Estrogênios Conjugados (USP) , Fator Estimulador de Colônias de Granulócitos e Macrófagos , Ratos , Feminino , Animais , Espectrometria de Massas em Tandem , Envelhecimento , GenitáliaRESUMO
AIM: This study aimed to explore the mediating effects of adversity quotient and the moderating effect of self-efficacy on the relationship between the organizational climate and the work engagement of intensive care unit nurses. BACKGROUND: A good organizational climate can contribute to a high level of work engagement. Adversity quotient and self-efficacy are the key factors affecting nurses' work engagement, while the mechanism of these factors in the organizational climate and work engagement remains unclear. This study was conducted to contribute to the relevant field research. METHODS: The study used a cross-sectional research design and surveyed 323 intensive care unit nurses working in a public hospital in China. The data were analysed using descriptive statistical methods: Pearson correlation analysis and PROCESS macro Model 7 in the regression analysis. RESULTS: Organizational climate was positively correlated with work engagement and adversity quotient. The indirect effect of organizational climate on work engagement through adversity quotient was positive. Furthermore, self-efficacy moderated the relationship between the two factors. CONCLUSION: Cultivating organizational climate and adversity quotients is an important strategy to improve the work engagement of intensive care unit nurses, particularly for nurses with high self-efficacy. IMPLICATIONS FOR NURSING MANAGEMENT: Administrators should make efforts to create a good organizational climate and cultivate nurses' adversity quotients and self-efficacy to decrease their intent to leave.
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Enfermeiras e Enfermeiros , Recursos Humanos de Enfermagem Hospitalar , Humanos , Engajamento no Trabalho , Autoeficácia , Estudos Transversais , Inquéritos e Questionários , Unidades de Terapia Intensiva , Cultura Organizacional , Satisfação no EmpregoRESUMO
The coupling of aryl chlorides with Reformatsky reagents is a desirable strategy for the construction of α-aryl esters but has so far been substantially limited in the substrate scope due to many challenges posed by various possible side reactions. This limitation has now been overcome by the tailoring of ylide-functionalized phosphines to fit the requirements of Negishi couplings. Record-setting activities were achieved in palladium-catalyzed arylations of organozinc reagents with aryl electrophiles using a cyclohexyl-YPhos ligand bearing an ortho-tolyl-substituent in the backbone. This highly electron-rich, bulky ligand enables the use of aryl chlorides in room temperature couplings of Reformatsky reagents. The reaction scope covers diversely functionalized arylacetic and arylpropionic acid derivatives. Aryl bromides and chlorides can be converted selectively over triflate electrophiles, which permits consecutive coupling strategies.
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Nemaline myopathy (NEM) is a congenital myopathy that typically presents with proximal muscle weakness and hypotonia. To date, 13 genes have been associated with NEM. The Kelch repeat and BTB domain-containing protein 13 (KBTBD13) gene (KBTBD13)-related NEM is a rarely reported condition, and not a single case has been reported in Asia. Here, we report the case of a mother and daughter in China with NEM caused by a mutation (c.1222C>T) in KBTBD13. Their shared clinical phenotype is symmetrical muscle weakness in the arms and legs with childhood onset. Muscle magnetic resonance imaging showed the unique replacement mode of muscle with fibro-fatty tissue. Histopathological examination revealed the presence of fibers containing rod-shaped structures in the cytoplasm or under the sarcolemma. DNA sequencing analysis detected a heterozygous mutation (c.1222C>T) in KBTBD13 in this family. A founder effect for the variant may exist in the Low Countries of Belgium and the Netherlands, and the mutation may be a hotspot mutation in Europe, as it has not been reported in Asia. Our case study expands the spectrum of KBTBD13-related NEM.
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Proteínas Musculares/genética , Mutação/genética , Miopatias da Nemalina/diagnóstico por imagem , Miopatias da Nemalina/genética , China , Feminino , Humanos , Pessoa de Meia-Idade , LinhagemRESUMO
Transition-metal-catalyzed cross-coupling chemistry can be regarded as one of the most powerful protocols to construct carbon-carbon bonds. While the field is still dominated by palladium catalysis, there is an increasing interest to develop protocols that utilize cheaper and more sustainable metal sources. Herein, we report a selective, practical, and fast iron-based cross-coupling reaction that enables the formation of Csp-Csp3 and Csp2 -Csp3 bonds. In a telescoped flow process, the reaction can be combined with the Grignard reagent synthesis. Moreover, flow allows the use of a supporting ligand to be avoided without eroding the reaction selectivity.
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A continuous-flow, visible-light-promoted method has been developed to overcome the limitations of iron-catalyzed Kumada-Corriu cross-coupling reactions. A variety of strongly electron rich aryl chlorides, previously hardly reactive, could be efficiently coupled with aliphatic Grignard reagents at room temperature in high yields and within a few minutes' residence time, considerably enhancing the applicability of this iron-catalyzed reaction. The robustness of this protocol was demonstrated on a multigram scale, thus providing the potential for future pharmaceutical application.
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A convenient method for the preparation of sp3-rich heterocycles is reported. The method comprises a photocatalytic difluoroalkylation-induced 1,2-heteroarene migration of allylic alcohols. Here we describe for the first time the benefits of using flow to facilitate such migration reactions, including shorter reaction times, higher selectivities, and opportunities to scale the chemistry.
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BACKGROUND: Autosomal recessive Myotonia congenita (Becker's disease) is caused by mutations in the CLCN1 gene. The condition is characterized by muscle stiffness during sustained muscle contraction and variable degree of muscle weakness that tends to improve with repeated contractions. CASE PRESENTATION: A 21-year-old man presented with transient muscle stiffness since the last 10 years. He had difficulty in initiating movement and experienced muscle weakness after rest, which typically improved after repeated contraction (warm-up phenomenon). There was no significant family history. Medical examination showed generalized muscle hypertrophy. Serum creatine kinase level was 2-fold higher than the normal value. Electromyogram showed myotonic discharges. DNA sequence analysis identified a novel splice mutation (c.1401 + 1G > A) and a known mutation (c.1657A > T,p.Ile553Phe). He rapidly responded to treatment with mexiletine 100 mg three times a day for 6 months. CONCLUSIONS: This case report of autosomal recessive Myotonia congenita caused by a novel compound heterozygous mutation expands the genotypic spectrum of CLCN1 gene.
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Canais de Cloreto/genética , Miotonia Congênita/genética , Povo Asiático/genética , Genótipo , Humanos , Masculino , Mutação , Adulto JovemRESUMO
BACKGROUND: Filamin C-related myofibrillar myopathies (MFM) are progressive skeletal myopathies with an autosomal dominant inheritance pattern. The conditions are caused by mutations of the filamin C gene (FLNC) located in the chromosome 7q32-q35 region. Genetic variations in the FLNC gene result in various clinical phenotypes. CASE PRESENTATION: We describe a 43-year-old woman who suffered filamin C-related MFM, with symptoms first presenting in the proximal muscles of the lower limbs and eventually spreading to the upper limbs and distal muscles. The patient's serum level of creatine kinase was mildly increased. Mildy myopathic changes in the electromyographic exam and moderate lipomatous alterations in lower limb MRI were found. Histopathological examination revealed increased muscle fiber size variability, disturbances in oxidative enzyme activity, and the presence of abnormal protein aggregates and vacuoles in some muscle fibers. Ultrastructural analysis showed inclusions composed of thin filaments and interspersed granular densities. DNA sequencing analysis detected a novel 15-nucleotide deletion (c.2791_2805del, p.931_935del) in the FLNC gene. The patient's father, sister, brother, three paternal aunts, one paternal uncle, and the uncle's son also had slowly progressive muscle weakness, and thus, we detected an autosomal dominant inheritance pattern of the disorder. CONCLUSIONS: A novel heterogeneous 15-nucleotide deletion (c.2791_2805del, p.931_935del) in the Ig-like domain 7 of the FLNC gene was found to cause filamin C-related MFM. This deletion in the FLNC gene causes protein aggregation, abnormalities in muscle structure, and impairment in muscle fiber function, which leads to muscle weakness.
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Filaminas/genética , Miopatias Congênitas Estruturais/genética , Adulto , Povo Asiático/genética , Éxons/genética , Feminino , Heterozigoto , Humanos , Masculino , Mutação , Linhagem , Fenótipo , Deleção de Sequência/genéticaRESUMO
A new C-center radical-triggered bicyclization cascade of N-tethered 1,7-enynes for forming 28 examples of biologically interesting spirocyclohexadienone-containing cyclopenta[c]quinolin-4-ones with two all-carbon quaternary stereocenters has been established under mild conditions. The in situ generated diazonium salts from 4-methoxyanilines and t-BuONO are served as 4-methoxyphenyl precursors without additional oxidant, enabling 6-exo-dig cyclization/5-exo-trig ipso-cyclization to construct three new C-C bonds through metal-free dearomatization. The reaction also features broad substrate scope, annulation efficiency, and high functional group tolerance.
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A photocatalytic method for the aerobic oxidative cleavage of C=C bonds has been developed. Electron-rich aromatic disulfides were employed as photocatalyst. Upon visible-light irradiation, typical mono- and multi-substituted aromatic olefins could be converted into ketones and aldehydes at ambient temperature. Experimental and computational studies suggest that a disulfide-olefin charge-transfer complex is possibly responsible for the unconventional dissociation of S-S bond under visible light.
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We report a visible light-induced trifluoromethylation and perfluoroalkylation for cysteine conjugation using Ru(bpy)3(2+) as photocatalyst and inexpensive RFI as coupling partner. The protocol allows the introduction of a variety of perfluoro alkyl groups (C1-C10) and a CF2COOEt moiety. The reaction is high yielding (56-94% yield) and fast (2 h in batch, 12 examples). Process intensification in a photomicroreactor accelerated the reaction (5 min reaction time) and increased the yields (8 examples). Quantum yield investigations support a radical chain mechanism.
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We report an operationally simple, visible-light-driven protocol for intramolecular C-H difluoroacetamidation of arenes for the synthesis of biologically relevant 3,3-difluoro-2-oxindoles at room temperature. Using fac-Ir(ppy)3 as a photocatalyst and a 3 W blue LED as a light source, an array of difluoroxindoles was prepared from rapidly available tertiary aryl bromodifluoroacetamides in moderate to excellent yields.
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Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease characterized by motor neuron degeneration. The development of ALS involves metabolite alterations leading to tissue lesions in the nervous system. Recent advances in neuroimaging have significantly improved our understanding of the underlying pathophysiology of ALS, with findings supporting the corticoefferent axonal disease progression theory. Current studies on neuroimaging in ALS have demonstrated inconsistencies, which may be due to small sample sizes, insufficient statistical power, overinterpretation of findings, and the inherent heterogeneity of ALS. Deriving meaningful conclusions solely from individual imaging metrics in ALS studies remains challenging, and integrating multimodal imaging techniques shows promise for detecting valuable ALS biomarkers. In addition to giving an overview of the principles and techniques of different neuroimaging modalities, this review describes the potential of neuroimaging biomarkers in the diagnosis and prognostication of ALS. We provide an insight into the underlying pathology, highlighting the need for standardized protocols and multicenter collaborations to advance ALS research.
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Esclerose Lateral Amiotrófica , Biomarcadores , Neuroimagem , Esclerose Lateral Amiotrófica/diagnóstico por imagem , Esclerose Lateral Amiotrófica/metabolismo , Humanos , Neuroimagem/métodos , Neuroimagem/normas , Biomarcadores/metabolismo , Encéfalo/diagnóstico por imagem , Encéfalo/metabolismoRESUMO
OBJECTIVE: The pathological features of immune-mediated necrotizing myopathy (IMNM) are dominated by the infiltration of macrophages. We aimed to perform a histopathologic semiquantitative analysis to investigate the relationship between macrophage markers and prognosis. METHODS: Semiquantitative analysis of histologic features was performed in 62 samples of IMNM. Independent risk factors were identified through univariate and multivariate regression analysis. Cluster analysis was performed using the partitioning around the medoids (PAM) method. Decision tree modeling was utilized to efficiently determine cluster labels for IMNM patients. The validity of the developmental cohort was assessed by accuracy in comparison with the validation cohort. RESULTS: The most enriched groups in patients with IMNM were macrophages expressing CD206 and CD163. In the multivariate logistic regression model, the high density of CD163+ macrophages in perimysial connective tissue increased the risk of unfavorable prognosis (p = 0.025, OR = 1.463, 95% CI: 1.049-2.041). In cluster analysis, patients in Cluster 1, with lower CD163+ macrophage density and inflammatory burden, had a more favorable prognosis. Conversely, patients in Cluster 3, which were enriched for CD163+ macrophages in the perimysial connective tissue, had the most severe clinical features and the worst prognosis. Correlations were found between the density of CD163+ macrophages in connective tissue and symptom duration (R2 = 0.166, p < 0.001), dysphagia (p = 0.004), cardiac involvement (p = 0.021), CK (R2 = 0.067, p = 0.042), CRP (R2 = 0.117, p < 0.001), and ESR (R2 = 0.171, p < 0.001). CONCLUSION: The density of CD163+ macrophages in perimysial connective tissue may serve as a potential marker for the prediction of IMNM prognosis.
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Antígenos CD , Antígenos de Diferenciação Mielomonocítica , Tecido Conjuntivo , Macrófagos , Receptores de Superfície Celular , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Antígenos CD/metabolismo , Antígenos de Diferenciação Mielomonocítica/metabolismo , Tecido Conjuntivo/patologia , Tecido Conjuntivo/imunologia , Macrófagos/patologia , Macrófagos/imunologia , Miosite/patologia , Miosite/imunologia , Prognóstico , Receptores de Superfície Celular/metabolismoRESUMO
Brachio-cervical inflammatory myopathy (BCIM) is a rare inflammatory myopathy characterized by dysphagia, bilateral upper limb atrophy, limb-girdle muscle weakness, and myositis-specific antibody (MSA) negativity. BCIM has a low incidence and is commonly associated with autoimmune diseases. We present a case report of a 55-year-old man with progressive upper limb weakness and atrophy, diagnosed with flail arm syndrome (FAS). The initial electromyography revealed extensive spontaneous muscle activity and increased duration of motor unit potentials (MUPs). During follow-up, evidence of myogenic damage was observed, as indicated by a decreased duration of MUPs in the right biceps muscle. Laboratory and genetic testing ruled out hereditary or acquired diseases. Negative serological antibodies for myasthenia gravis. Hereditary or acquired diseases were ruled out through laboratory and genetic testing. Whole-body muscle magnetic resonance imaging (MRI) showed extensive edema and fat replacement in the bilateral upper limbs, scapular, and central axis muscles, while the lower extremities were relatively mildly affected. Muscle biopsy revealed numerous foci of inflammatory cells distributed throughout the muscle bundle, with predominant CD20, CD138, and CD68 expression, accompanied by a light infiltration of CD3 and CD4 expression. The muscle weakness improved with the combination of oral prednisone (initially 60 mg/day, tapered) and methotrexate (5 mg/week) treatment.
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Erros de Diagnóstico , Miosite , Humanos , Pessoa de Meia-Idade , Masculino , Miosite/diagnóstico , Miosite/imunologia , Braço , Músculo Esquelético/patologia , Músculo Esquelético/imunologia , Debilidade Muscular/diagnóstico , Debilidade Muscular/etiologia , Atrofia Muscular/diagnóstico , Eletromiografia , Imageamento por Ressonância MagnéticaRESUMO
Introduction: Rimmed vacuolar myopathies (RVMs) are a group of genetically heterogeneous diseases that share histopathological characteristics on muscle biopsy, including the aberrant accumulation of autophagic vacuoles. However, the presence of non-coding sequences and structural mutations, some of which remain undetectable, confound the identification of pathogenic mutations responsible for RVMs. Therefore, we assessed the clinical profiles and muscle magnetic resonance imaging (MRI) changes in 36 Chinese patients with RVMs, emphasizing the role of muscle MRI in disease identification and differential diagnosis to propose a comprehensive literature-based imaging pattern to facilitate improved diagnostic workup. Methods: All patients presented with rimmed vacuoles with varying degrees of muscular dystrophic changes and underwent a comprehensive evaluation using clinical, morphological, muscle MRI and molecular genetic analysis. We assessed muscle changes in the Chinese RVMs and provided an overview of the RVMs, focusing on the patterns of muscle involvement on MRI. Results: A total of 36 patients, including 24 with confirmed distal myopathy and 12 with limb-girdle phenotype, had autophagic vacuoles with RVMs. Hierarchical clustering of patients according to the predominant effect of the distal or proximal lower limbs revealed that most patients with RVMs could be distinguished. GNE myopathy was the most prevalent form of RVMs observed in this study. Moreover, MRI helped identify the causative genes in some diseases (e.g., desminopathy and hereditary myopathy with early respiratory failure) and confirmed the pathogenicity of a novel mutation (e.g., adult-onset proximal rimmed vacuolar titinopathy) detected using next-generation sequencing. Discussion: Collectively, our findings expand our knowledge of the genetic spectrum of RVMs in China and suggest that muscle imaging should be an integral part of assisting genetic testing and avoiding misdiagnosis in the diagnostic workup of RVM.
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BACKGROUND: Herpes zoster presents as clustered blisters on one side of the body, accompanied by nerve pain. This is caused by reactivation of the varicella zoster virus, and it occurs primarily in people with weakened immunity. Tumor and chemotherapy drugs can impair the patient's immune function, induce herpes zoster and prolong the course of disease.In these patients, skin changes can last for months and blisters can recur and cause serious complications such as postherpetic neuralgia.Acupuncture is a common alternative therapy for herpes zoster in East Asia. CASE PRESENTATION: We report a case of an elderly male patient with widespread herpes zoster in the trunk after non-Hodgkin's lymphoma chemotherapy. The patient had received conventional treatment with valaciclovir and mecobalamin within 24 hours of symptom onset. Because neither the clustered blisters nor the nerve pain were improved a week later, acupuncture and related techniques were applied. These included electro-acupuncture, surrounding acupuncture, fire acupuncture, and cupping. The patient recovered 20 days after the herpes zoster attack, and there were no adverse reactions during the treatment process. CONCLUSIONS: This case suggests that acupuncture and related techniques are effective interventions for this condition.This case report is innovative because it shows that acupuncture as an adjuvant treatment can improve the skin lesions in patients with HZ after tumour chemotherapy, relieve pain, and shorten the course of HZ.
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Terapia por Acupuntura , Herpes Zoster , Linfoma não Hodgkin , Neuralgia , Idoso , Vesícula , Herpesvirus Humano 3 , Humanos , Masculino , Recidiva Local de NeoplasiaRESUMO
OBJECTIVE: To establish a comprehensive and simple assay using denaturing high performance liquid chromatography (DHPLC) for the diagnosis of most common mutations and deletions of α-thalassemia gene in Southeast Asians and Southern Chinese. METHODS: This assay has included a duplex polymerase chain reaction (PCR) followed by DHPLC analysis. An improved PCR was also performed followed by DHPLC analysis. With this assay, a blinded study of 160 samples was screened for three common mutations and three common deletions. RESULTS: The duplex PCR-DHPLC combined with the improved PCR-DHPLC analysis has detected all mutations and the wild-type allele. The results were consistent with those by the original methods. CONCLUSION: This molecular assay may be used for the diagnosis of α-thalassemia patients from this geographical region. The method is accurate, rapid, semi-automatic and cost-effective, which makes it suitable for large-scale screening.
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Cromatografia Líquida de Alta Pressão/métodos , Análise Mutacional de DNA/métodos , Talassemia alfa/diagnóstico , Talassemia alfa/genética , Ordem dos Genes , Genótipo , Humanos , alfa-Globinas/genéticaRESUMO
Next-generation sequencing (NGS) technology has led to great advances in understanding the causes of Mendelian and complex neurological diseases. Owing to the complexity of genetic diseases, the genetic factors contributing to many rare and common neurological diseases remain poorly understood. Selecting the correct genetic test based on cost-effectiveness, coverage area, and sequencing range can improve diagnosis, treatments, and prevention. Whole-exome sequencing and whole-genome sequencing are suitable methods for finding new mutations, and gene panels are suitable for exploring the roles of specific genes in neurogenetic diseases. Here, we provide an overview of the classifications, applications, advantages, and limitations of NGS in research on neurological diseases. We further provide examples of NGS-based explorations and insights of the genetic causes of neurogenetic diseases, including Charcot-Marie-Tooth disease, spinocerebellar ataxias, epilepsy, and multiple sclerosis. In addition, we focus on issues related to NGS-based analyses, including interpretations of variants of uncertain significance, de novo mutations, congenital genetic diseases with complex phenotypes, and single-molecule real-time approaches.