RESUMO
BACKGROUND: Focused ultrasound ablation surgery (FUAS) has been widely employed to treat patients with uterine fibroid (UF). This study aimed to estimate myometrial stiffness changes in patients who received FUAS for UFs or myomectomy (ME) and compare the recovery of surrounding myometrium between FUAS and ME groups. Our results may provide more evidence for guiding the proper conception timing in patients with UF. METHODS: This study enrolled 173 patients from May 2022 to August 2023. Shear wave elastography (SWE) was used to dynamically monitor myometrial elasticity changes in patients before and after surgery. Moreover, our study monitored and analyzed the stiffness changes in the targeted fibroid after FUAS, as well as in the myometrium around after FUAS or ME. RESULTS: The stiffness of the myometrium around the resected fibroid was significantly higher than at the preoperative level until 6 months. Conversely, the stiffness of the surrounding myometrium was only temporarily increased 1 day after FUAS. The comparison between FUAS and ME groups regarding the stiffness of the surrounding myometrium showed that nonsignificant differences were detected between the two groups before the treatment. The stiffness of the surrounding myometrium in the ME group was statistically significantly higher than that of the FUAS group 1 day as well as 1, 3, and 6 months after the treatment, respectively. CONCLUSION: The FUAS had less impact on the surrounding myometrium than the ME, which may be more conducive to the recovery of myometrial elasticity in patients with UF.
Assuntos
Elasticidade , Leiomioma , Miométrio , Miomectomia Uterina , Humanos , Feminino , Leiomioma/cirurgia , Leiomioma/diagnóstico por imagem , Miométrio/cirurgia , Miométrio/diagnóstico por imagem , Adulto , Miomectomia Uterina/métodos , Ablação por Ultrassom Focalizado de Alta Intensidade/métodos , Pessoa de Meia-Idade , Neoplasias Uterinas/cirurgia , Técnicas de Imagem por Elasticidade/métodosRESUMO
OBJECTIVE: The purpose of this systematic review and meta-analysis was to assess the clinical efficacy and safety of ultrasound (US)-guided high intensity focused ultrasound (HIFU) in the treatment of breast fibroadenoma in different studies. METHODS: Studies evaluating the efficacy and safety of US-guided HIFU in the treatment of histologically-proven FA with follow-up outcomes of more than 3 months were searched through MEDLINE/PubMed databases. Volume reduction rate (VRR) and side effects were extracted and compared for further analysis. RESULTS: Of 29 identified articles, 10 studies involving 385 women and more than 545 FAs met the inclusion criteria. The mean VRR at 6 months and 12 months after HIFU was 52.00% and 72.00%. In terms of intraoperative safety, nine studies reported mild to moderate pain, with an average visual analogue scale (VAS) score ranging from 1.60 to 7.10. The most common postoperative side effect associated with HIFU was subcutaneous ecchymosis and less frequent were pain, erythema, and skin pigmentation, most of which disappeared within weeks. No serious side effects were observed. CONCLUSION: S-guided HIFU is an effective and safe noninvasive treatment for breast FA that does not cause serious side effects. Further studies are needed to explore crucial influencing factors of VRR.
Assuntos
Neoplasias da Mama , Fibroadenoma , Ablação por Ultrassom Focalizado de Alta Intensidade , Humanos , Fibroadenoma/terapia , Fibroadenoma/diagnóstico por imagem , Ablação por Ultrassom Focalizado de Alta Intensidade/métodos , Feminino , Neoplasias da Mama/terapia , Neoplasias da Mama/cirurgia , Resultado do TratamentoRESUMO
Despite the high mortality rate associated with sepsis, no specific drugs are available. Decoy receptor 3 (DcR3) is now considered a valuable biomarker and therapeutic target for managing inflammatory conditions. DcR3-SUMO, an analog of DcR3, has a simple production process and high yield. However, its precise underlying mechanisms in sepsis remain unclear. This study investigated the protective effects of DcR3-SUMO on lipopolysaccharide (LPS)-induced inflammatory cells and septic mice. We evaluated the effects of DcR3 intervention and overexpression on intracellular inflammatory cytokine levels in vitro. DcR3-SUMO significantly reduced cytokine levels within inflammatory cells, and notably increased DcR3 protein and mRNA levels in LPS-induced septic mice, confirming its anti-inflammatory efficacy. Our in vitro and in vivo results demonstrated comparable anti-inflammatory effects between DcR3-SUMO and native DcR3. DcR3-SUMO protein administration in septic mice notably enhanced tissue morphology, decreased sepsis scores, and elevated survival rates. Furthermore, DcR3-SUMO treatment effectively lowered inflammatory cytokine levels in the serum, liver, and lung tissues, and mitigated the extent of tissue damage. AlphaFold3 structural predictions indicated that DcR3-SUMO, similar to DcR3, effectively interacts with the three pro-apoptotic ligands, namely TL1A, LIGHT, and FasL. Collectively, DcR3-SUMO and DcR3 exhibit comparable anti-inflammatory effects, making DcR3-SUMO a promising therapeutic agent for sepsis.
Assuntos
Citocinas , Lipopolissacarídeos , Membro 6b de Receptores do Fator de Necrose Tumoral , Sepse , Animais , Sepse/metabolismo , Sepse/tratamento farmacológico , Membro 6b de Receptores do Fator de Necrose Tumoral/metabolismo , Membro 6b de Receptores do Fator de Necrose Tumoral/genética , Camundongos , Citocinas/metabolismo , Inflamação/metabolismo , Masculino , Humanos , Proteínas Recombinantes de Fusão/farmacologia , Anti-Inflamatórios/farmacologia , Membro 15 da Superfamília de Ligantes de Fatores de Necrose Tumoral/metabolismo , Camundongos Endogâmicos C57BLRESUMO
Despite its high mortality, specific and effective drugs for sepsis are lacking. Decoy receptor 3 (DcR3) is a potential biomarker for the progression of inflammatory diseases. The recombinant human DcR3-Fc chimera protein (DcR3.Fc) suppresses inflammatory responses in mice with sepsis, which is critical for improving survival. The Fc region can exert detrimental effects on the patient, and endogenous peptides are highly conducive to clinical application. However, the mechanisms underlying the effects of DcR3 on sepsis are unknown. Herein, we aimed to demonstrate that DcR3 may be beneficial in treating sepsis and investigated its mechanism of action. Recombinant DcR3 was obtained in vitro. Postoperative DcR3 treatment was performed in mouse models of lipopolysaccharide- and cecal ligation and puncture (CLP)-induced sepsis, and their underlying molecular mechanisms were explored. DcR3 inhibited sustained excessive inflammation in vitro, increased the survival rate, reduced the proinflammatory cytokine levels, changed the circulating immune cell composition, regulated the gut microbiota, and induced short-chain fatty acid synthesis in vivo. Thus, DcR3 protects against CLP-induced sepsis by inhibiting the inflammatory response and apoptosis. Our study provides valuable insights into the molecular mechanisms associated with the protective effects of DcR3 against sepsis, paving the way for future clinical studies. IMPORTANCE: Sepsis affects millions of hospitalized patients worldwide each year, but there are no sepsis-specific drugs, which makes sepsis therapies urgently needed. Suppression of excessive inflammatory responses is important for improving the survival of patients with sepsis. Our results demonstrate that DcR3 ameliorates sepsis in mice by attenuating systematic inflammation and modulating gut microbiota, and unveil the molecular mechanism underlying its anti-inflammatory effect.
Assuntos
Ceco , Modelos Animais de Doenças , Membro 6b de Receptores do Fator de Necrose Tumoral , Sepse , Animais , Sepse/tratamento farmacológico , Sepse/microbiologia , Camundongos , Membro 6b de Receptores do Fator de Necrose Tumoral/genética , Membro 6b de Receptores do Fator de Necrose Tumoral/metabolismo , Ceco/cirurgia , Humanos , Ligadura , Punções , Masculino , Camundongos Endogâmicos C57BL , Microbioma Gastrointestinal , Citocinas/metabolismo , Lipopolissacarídeos , Apoptose/efeitos dos fármacos , InflamaçãoRESUMO
BACKGROUND: Colon cancer is one of the most common digestive tract malignancies. Although immunotherapy has brought new hope to colon cancer patients, there is still a large proportion of patients who do not benefit from immunotherapy. Studies have shown that neutrophils can interact with immune cells and immune factors to affect the prognosis of patients. METHODS: We first determined the infiltration level of neutrophils in tumors using the CIBERSORT algorithm and identified key genes in the final risk model by Spearman correlation analysis and subsequent Cox analysis. The risk score of each patient was obtained by multiplying the Cox regression coefficient and the gene expression level, and patients were divided into two groups based on the median of risk score. Differences in overall survival (OS) and progression-free survival (PFS) were assessed by Kaplan-Meier survival analysis, and model accuracy was validated in independent dataset. Differences in immune infiltration and immunotherapy were evaluated by immunoassay. Finally, immunohistochemistry and western blotting were performed to verify the expression of the three genes in the colon normal and tumor tissues. RESULTS: We established and validated a risk scoring model based on neutrophil-related genes in two independent datasets, The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) database, with SLC11A1 and SLC2A3 as risk factors and MMP3 as a protective factor. A new nomogram was constructed and validated by combining clinical characteristics and the risk score model to better predict patients OS and PFS. Immune analysis showed that patients in the high-risk group had immune cell infiltration level, immune checkpoint level and tumor mutational burden, and were more likely to benefit from immunotherapy. CONCLUSIONS: The low-risk group showed better OS and PFS than the high-risk group in the neutrophil-related gene-based risk model. Patients in the high-risk group presented higher immune infiltration levels and tumor mutational burden and thus may be more responsive to immunotherapy.
Assuntos
Neoplasias do Colo , Neutrófilos , Humanos , Neoplasias do Colo/genética , Neoplasias do Colo/terapia , Fatores de Risco , Algoritmos , ImunoterapiaRESUMO
JOURNAL/nrgr/04.03/01300535-202419110-00031/figure1/v/2024-03-08T184507Z/r/image-tiff Amyotrophic lateral sclerosis is a neurodegenerative disease, and the molecular mechanism underlying its pathology remains poorly understood. However, inflammation is known to play an important role in the development of this condition. To identify driver genes that affect the inflammatory response in amyotrophic lateral sclerosis, as well as potential treatment targets, it is crucial to analyze brain tissue samples from patients with both sporadic amyotrophic lateral sclerosis and C9orf72-related amyotrophic lateral sclerosis. Therefore, in this study we used a network-driven gene analysis tool, NetBID2.0, which is based on SJARACNe, a scalable algorithm for the reconstruction of accurate cellular networks, to experimentally analyze sequencing data from patients with sporadic amyotrophic lateral sclerosis. The results showed that the OSMR gene is pathogenic in amyotrophic lateral sclerosis and participates in the progression of amyotrophic lateral sclerosis by mediating the neuroinflammatory response. Furthermore, there were differences in OSMR activity and expression between patients with sporadic amyotrophic lateral sclerosis and those with C9orf72-related amyotrophic lateral sclerosis. These findings suggest that OSMR may be a diagnostic and prognostic marker for amyotrophic lateral sclerosis.
RESUMO
Amyotrophic lateral sclerosis (ALS) is a rare neurodegenerative disease which damages upper and lower motor neurons (UMN and LMN) innervating the muscles of the trunk, extremities, head, neck and face in cerebrum, brain stem and spinal cord, which results in the progressive weakness, atrophy and fasciculation of muscle innervated by the related UMN and LMN, accompanying with the pathological signs leaded by the cortical spinal lateral tract lesion. The pathogenesis about ALS is not fully understood, and no specific drugs are available to cure and prevent the progression of this disease at present. In this review, we reviewed the structure and associated functions of copper-zinc superoxide dismutase 1 (SOD1), discuss why SOD1 is crucial to the pathogenesis of ALS, and outline the pathogenic mechanisms of SOD1 in ALS that have been identified at recent years, including glutamate-related excitotoxicity, mitochondrial dysfunction, endoplasmic reticulum stress, oxidative stress, axonal transport disruption, prion-like propagation, and the non-cytologic toxicity of glial cells. This review will help us to deeply understand the current progression in this field of SOD1 pathogenic mechanisms in ALS.
Assuntos
Esclerose Lateral Amiotrófica , Superóxido Dismutase-1 , Esclerose Lateral Amiotrófica/metabolismo , Esclerose Lateral Amiotrófica/patologia , Esclerose Lateral Amiotrófica/genética , Humanos , Superóxido Dismutase-1/metabolismo , Superóxido Dismutase-1/genética , Animais , Neurônios Motores/metabolismo , Neurônios Motores/patologia , Estresse Oxidativo/fisiologiaRESUMO
Tumor immunotherapy is booming around the world. However, strategies to activate the immune system and alleviate the immunosuppression still need to be refined. Here, we demonstrate for the first time that low-intensity pulsed ultrasound (LIPUS, spatial average time average intensity (Isata) is 200 mW/cm2, frequency is 0.3 MHz, repetition frequency is 1 kHz, and duty cycle is 20%) triggers the immune system and further reverses the immunosuppressive state in the mouse models of breast cancer by irradiating the spleen of mice. LIPUS inhibited tumor growth and extended survival in mice with 4 T-1 tumors. Further studies had previously shown that LIPUS enhanced the activation of CD4+ and CD8+ T cells in the spleen and led to significant changes in cytokines, as well as induced upregulation of mRNA levels involved in multiple immune regulatory pathways in the spleen. In addition, LIPUS promoted tumor-infiltrating lymphocyte accumulation and CD8+ T cell activation and improved the dynamics of cytokines/chemokines in the tumor microenvironment, resulting in a reversal of the immunosuppressive state of the tumor microenvironment. These results suggest a novel approach to activate the immune response by irradiating the spleen with LIPUS.
Assuntos
Neoplasias , Baço , Animais , Camundongos , Linfócitos T CD8-Positivos , Ondas Ultrassônicas , Terapia de Imunossupressão , Citocinas , ImunossupressoresRESUMO
Amyotrophic lateral sclerosis refers to a neurodegenerative disease involving the motor system, the cause of which remains unexplained despite several years of research. Thus, the journey to understanding or treating amyotrophic lateral sclerosis is still a long one. According to current research, amyotrophic lateral sclerosis is likely not due to a single factor but rather to a combination of mechanisms mediated by complex interactions between molecular and genetic pathways. The progression of the disease involves multiple cellular processes and the interaction between different complex mechanisms makes it difficult to identify the causative factors of amyotrophic lateral sclerosis. Here, we review the most common amyotrophic lateral sclerosis-associated pathogenic genes and the pathways involved in amyotrophic lateral sclerosis, as well as summarize currently proposed potential mechanisms responsible for amyotrophic lateral sclerosis disease and their evidence for involvement in amyotrophic lateral sclerosis. In addition, we discuss current emerging strategies for the treatment of amyotrophic lateral sclerosis. Studying the emergence of these new therapies may help to further our understanding of the pathogenic mechanisms of the disease.
RESUMO
Introduction: This study aimed to compare the efficacy and safety of docetaxel + trastuzumab + pertuzumab and docetaxel + carboplatin + trastuzumab + pertuzumab for treating HER2-positive breast cancer. Method: HER2-positive breast cancer from patients diagnosed between January 2020 and September 2022 were included in this retrospective study. Docetaxel + trastuzumab + pertuzumab or docetaxel + carboplatin + trastuzumab + pertuzumab was selected as the neoadjuvant regimen. The primary endpoint was a complete pathological remission rate. Secondary endpoints were toxicity during neoadjuvant treatment, adjustment of the neoadjuvant therapy scheme, and adjuvant medication. Result: A total of 81 patients were included in this study (38 in the docetaxel + carboplatin + trastuzumab + pertuzumab treatment group and 43 in the docetaxel + trastuzumab + pertuzumab group). The complete pathological remission rates in the docetaxel + carboplatin + trastuzumab + pertuzumab and docetaxel + trastuzumab + pertuzumab groups were 44.7% (95% confidence interval: 30.2%-60.3%) and 51.2% (95% confidence interval: 36.8%-65.4%), respectively. The incidence of grade 3 or higher toxicity in the docetaxel + carboplatin + trastuzumab + pertuzumab group was significantly higher than that in the docetaxel + trastuzumab + pertuzumab group (68.4% vs 39.5%, P = .009). Neutropenia and asthenia were the most common grade 3 or higher toxicities. The incidence of neoadjuvant scheme adjustment was significantly higher in the docetaxel + carboplatin + trastuzumab + pertuzumab group than in the docetaxel + trastuzumab + pertuzumab group (26.3% vs 7.0%, P = .039). The proportion of patients who received <6 cycles of neoadjuvant therapy was significantly higher in the docetaxel + carboplatin + trastuzumab + pertuzumab group than in the docetaxel + trastuzumab + pertuzumab group (31.6% vs 4.7%, P = .004). Patients in the docetaxel + carboplatin + trastuzumab + pertuzumab group received higher doses of granulocyte-macrophage colony-stimulating factor. Conclusion: In the neoadjuvant treatment of HER2-positive breast cancer, the docetaxel + trastuzumab + pertuzumab regimen might be more tolerated than the docetaxel + carboplatin + trastuzumab + pertuzumab regimen and did not show a lower complete pathological remission rate. However, our findings require further validation through prospective studies.
Assuntos
Neoplasias da Mama , Humanos , Feminino , Neoplasias da Mama/patologia , Docetaxel , Terapia Neoadjuvante/efeitos adversos , Carboplatina , Estudos Retrospectivos , Estudos Prospectivos , Receptor ErbB-2 , Resultado do Tratamento , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Trastuzumab/uso terapêuticoRESUMO
Amyotrophic Lateral Sclerosis (ALS) is one of the commonest neurodegenerative diseases of adult-onset, which is characterized by the progressive death of motor neurons in the cerebral cortex, brain stem and spinal cord. The dysfunction and death of motor neurons lead to the progressive muscle weakness, atrophy, fasciculations, spasticity and ultimately the whole paralysis of body. Despite the identification of several genetic mutations associated with the pathogenesis of ALS, including mutations in chromosome 9 open reading frame 72 leading to the abnormal expansion of GGGGCC repeat sequence, TAR DNA-binding protein 43, fused in sarcoma/translocated in liposarcoma, copper/zinc superoxide dismutase 1 (SOD1) and TANK-binding kinase 1, the exact mechanisms underlying the specific degeneration of motor neurons that causes ALS remain incompletely understood. At present, since the transgenic model expressed SOD1 mutants was established, multiple in vitro models of ALS have been developed for studying the pathology, pathophysiology and pathogenesis of ALS as well as searching the effective neurotherapeutics. This review reviewed the details of present established in vitro models used in studying the pathology, pathophysiology and pathogenesis of ALS. Meanwhile, we also discussed the advantages, disadvantages, cost and availability of each models.
Assuntos
Esclerose Lateral Amiotrófica , Animais , Humanos , Camundongos , Esclerose Lateral Amiotrófica/metabolismo , Superóxido Dismutase-1/genética , Superóxido Dismutase-1/metabolismo , Modelos Animais de Doenças , Neurônios Motores/metabolismo , Mutação/genética , Superóxido Dismutase/metabolismo , Camundongos TransgênicosRESUMO
To analyze the influencing factors of energy efficiency factors (EEF) in focused ultrasound ablation surgery (FUAS) for unresectable pancreatic cancer and build a dosimetry model. The patients with unresectable pancreatic cancer that underwent FUAS were enrolled from 3 clinical centers between June 2015 and June 2022 for retrospective analysis. The significance of the factors with the potential to affect the EEF was assessed, correlations among the factors were analyzed, and the accuracy of the prediction models established by the factors containing different imaging features was compared. From a total of 236 cases, 215 cases were screened for study, EEF was significantly correlated with mode of anesthesia, grayscale change, tumor volume, tumor location, the distance from the tumor center to skin, contrast-enhanced computer tomography enhancement type, T2-weighted imaging fat suppression signal intensity and contrast-enhanced T1-weighted imaging enhancement type on magnetic resonance imaging. The resultant multiple regression models of EEF achieved significance, contains predictors of Tumor volume, the distance from tumor center to skin, T2-weighted imaging fat suppression signal intensity, and contrast-enhanced T1-weighted imaging enhancement type had better goodness of fit. Compared with CT, the EEF prediction model established by adding magnetic resonance imaging features showed better prediction in FUAS treatment of unresectable pancreatic cancer.
Assuntos
Anestesia , Anestesiologia , Neoplasias Pancreáticas , Humanos , Estudos Retrospectivos , Neoplasias Pancreáticas/diagnóstico por imagem , Neoplasias Pancreáticas/cirurgia , Neoplasias PancreáticasRESUMO
Suppression of excessive inflammatory responses improves the survival of patients with sepsis. We previously illustrated the anti-inflammatory effects of fucoxanthin (FX), a natural carotenoid isolated from brown algae; nevertheless, the underlying mechanism remains unknown. In this study, we examine the mechanism of the action of FX by targeting interferon regulatory factor 3 (IRF3) to inhibit inflammatory response. We observed that FX regulated innate immunity by inhibiting IRF3 phosphorylation in vitro. The in silico approach demonstrated a good binding mode between FX and IRF3. To examine the in vivo effects of FX, a mouse model of sepsis induced by cecal ligation and puncture (CLP) was created using both wild-type (WT) and Irf3-/- mice. FX significantly reduced pro-inflammatory cytokine levels and reactive oxygen species production, changed the circulating immune cell composition, and increased the survival rate of the CLP-induced sepsis model. Overall, FX ameliorated sepsis by targeting IRF3 activation, providing novel insights into the therapeutic potential and molecular mechanism of action of FX in the treatment of sepsis and suggesting that it may be used clinically to improve the survival rate in mice undergoing sepsis.
Assuntos
Fator Regulador 3 de Interferon , Sepse , Camundongos , Animais , Fator Regulador 3 de Interferon/genética , Fator Regulador 3 de Interferon/metabolismo , Inflamação/tratamento farmacológico , Inflamação/genética , Sepse/tratamento farmacológico , Sepse/genética , Xantofilas/metabolismoRESUMO
Current studies suggest that the abnormal alteration of brain lipid binding protein (BLBP) might participate in the pathogenesis of amyotrophic lateral sclerosis (ALS). However, the detailed understanding of ALS pathogenesis been yet to be elucidated. Therefore, this research intended to explore the potential effects of BLBP in ALS. The observation and analysis of BLBP-altered features in various anatomical areas and different spinal segments was conducted at the pre-onset, onset, and progression stages of Tg(SOD1*G93A)1Gur (TG) mice and the same periods of age-matched SOD1 wild-type (WT) mice by fluorescence immunohistochemistry and western blotting. BLBP-positive cells were comprehensively distributed in various spinal anatomical areas, especially in both the anterior and posterior horn, around the central canal and in anterior, lateral, and posterior funiculi. Overall, BLBP expression tended to increase from the pre-onset to the onset to the progression stages of the same periods of age-matched WT mice. Furthermore, in TG mice, BLBP expression in the entire spinal cord significantly increased from onset to the progression stage. BLBP was expressed in neurons, astrocytes, and radial glial cells, and at the early and late stages of neural precursor cells (NPCs) and was predominantly distributed outside the cell nucleus. The increase of BLBP-positive cells was closely related to neural cell reduction in TG mice. The distribution and increased expression of BLBP among the cervical, thoracic, and lumbar segments of the spinal cord might participate in the development of ALS and exert potential effects in the pathogenesis of ALS by regulating NPCs.
Assuntos
Esclerose Lateral Amiotrófica , Proteína 7 de Ligação a Ácidos Graxos , Células-Tronco Neurais , Animais , Camundongos , Esclerose Lateral Amiotrófica/genética , Proteína 7 de Ligação a Ácidos Graxos/genética , Superóxido Dismutase-1RESUMO
OBJECTIVES: To investigate changes in vaginal microecology in women with high-risk human papillomavirus (HR-HPV) infection after focused ultrasound (FU) treatment. MATERIALS AND METHODS: We collected vaginal secretions at the time of admission and 3 months after FU treatment from 169 women who received FU treatment for cervical HR-HPV infection between July 2020 and September 2022. Among them, there were 101 patients with cute vaginitis, we also collected their vaginal secretions after one week of drug treatment. These samples were evaluated for vaginal microecology and HPV-DNA examination. RESULTS: Of the 169 patients, 101 (59.7%) suffered from acute vaginitis at the time of admission. After one week of targeted antibiotics drug treatment, there were no pathogens or pus cells on the field of microscopic vision, but there was no significant difference(p > 0.05) in the diversity and density of vaginal flora, the proportion and function of Lactobacillus (H2O2 negative rate) between one week after treatment and at the time of admission. At the time of admission of the 169 patients, the normal flora rate was 40.3%, which increased to 93.5% three months after FU treatment. The differences in vaginal secretion parameters at the time of admission and 3 months after FU treatment were as follows: H2O2 negative rate (37.3% vs. 3.6%), leukocyte esterase positive rate (54.4% vs. 5.9%), sialidase positive rate (38.5% vs. 4.1%), bacterial vaginitis positive rate (55% vs. 4.7%), fungal vaginitis positive rate (44.4% vs. 5.9%), and trichomonal vaginitis positive rate (7.1% vs. 0). The difference was statistically significant (p < 0.01). The pH value and Nagent score at the time of admission were significantly higher than those three months after FU. Three months after FU, the positive rate of HPV was 5.8% in the group of patients with normal vaginal microecology at the time of admission and post-FU; it was 6.7% in the group of patients with abnormal vaginal microecology at the time of admission and normal vaginal microecology post-FU; and it was 100% in the group patients with abnormal vaginal microecology at the time of admission and post-FU. A significant difference was observed among the three groups (p < 0.01). CONCLUSION: FU is an effective treatment for patients with cervical HR-HPV infection. FU does not interfere with the vaginal microecology of HR-HPV positive patients with normal vaginal microecology.FU followed by antibiotic drug therapy for pathogens is beneficial to restore the function of Lactobacillus vaginalis in HR-HPV positive patients with acute vaginitis,so as to improve the vaginal microecology of HR-HPV positive patients with abnormal vaginal microecology.
Assuntos
Infecções por Papillomavirus , Neoplasias do Colo do Útero , Vaginite , Humanos , Feminino , Infecções por Papillomavirus/tratamento farmacológico , Peróxido de Hidrogênio , Papillomaviridae/genética , Vagina/diagnóstico por imagem , Vaginite/tratamento farmacológico , Vaginite/microbiologiaRESUMO
A high-quality domain-oriented dataset is crucial for the domain-specific named entity recognition (NER) task. In this study, we introduce a novel education-oriented Chinese NER dataset (EduNER). To provide representative and diverse training data, we collect data from multiple sources, including textbooks, academic papers, and education-related web pages. The collected documents span ten years (2012-2021). A team of domain experts is invited to accomplish the education NER schema definition, and a group of trained annotators is hired to complete the annotation. A collaborative labeling platform is built for accelerating human annotation. The constructed EduNER dataset includes 16 entity types, 11k+ sentences, and 35,731 entities. We conduct a thorough statistical analysis of EduNER and summarize its distinctive characteristics by comparing it with eight open-domain or domain-specific NER datasets. Sixteen state-of-the-art models are further utilized for NER tasks validation. The experimental results can enlighten further exploration. To the best of our knowledge, EduNER is the first publicly available dataset for NER task in the education domain, which may promote the development of education-oriented NER models.
RESUMO
Previous studies have indicated that the pathogenesis of amyotrophic lateral sclerosis (ALS) is closely linked to 5-hydroxytryptamine (5-HT). To investigate this further, we administered 5-HT receptor antagonists to SOD1*G93A transgenic (ALS mouse model) and wide-type mice. This involved intraperitoneal injections of either granisetron, piboserod, or ritanserin, which inhibit the 5-HT3, 5-HT4, and 5-HT2 receptors, respectively. The transgenic mice were found to have fewer 5-HT-positive cells in the spinal cord compared with wide-type mice. We found that the administration of granisetron reduced the body weight of the transgenic mice, while piboserod and ritanserin worsened the motor functioning, as assessed using a hanging wire test. However, none of the 5-HT receptor antagonists affected the disease progression. We analyzed the distribution and/or expression of TAR DNA binding protein 43 (TDP-43) and superoxide dismutase 1 G93A (SOD1-G93A), which form abnormal aggregates in ALS. We found that the expression of these proteins increased following the administration of all three 5-HT receptor antagonists. In addition, the disease-related mislocalization of TDP-43 to the cytoplasm increased markedly for all three drugs. In certain anatomical regions, the 5-HT receptor antagonists also led to a marked increase in the number of astrocytes and microglia and a decrease in the number of neurons. These results indicate that 5-HT deficiency may play a role in the pathogenesis of amyotrophic lateral sclerosis by inducing the abnormal expression and/or distribution of TDP-43 and SOD1-G93A and by activating glial cells. 5-HT could therefore be a potential therapeutic target for amyotrophic lateral sclerosis.
RESUMO
PURPOSE: To explore the potential of AVPR2 in the immunotherapy of head and neck squamous cell carcinoma (HNSCC), thus providing insights into a novel antitumour strategy. METHODS: In this study, we performed a comprehensive analysis of the AVPR2 gene in HNSCC using public datasets from The Cancer Genome Atlas and Gene Expression Omnibus. We explored the potential molecular mechanism of HNSCC in clinical prognosis and tumour immunity from the aspects of gene expression, prognosis, immune subtypes, and immune infiltration. RESULTS: AVPR2 expression was significantly downregulated in primary HNSCC tissue compared with normal tissue. HNSCC patients with high AVPR2 expression had a better prognosis. Moreover, the results of GSEA showed that immune subtype surface AVPR2 is involved in immune modulation. Furthermore, significant strong correlations between AVPR2 expression and infiltrating immune cells existed in HNSCC, and marker genes of infiltrating immune cells were also significantly related to AVPR2 expression in HNSCC. These results suggest that AVPR2 expression can influence the infiltration of tumour immune cells. Finally, we found that only high levels of B-cell infiltration, rather than those of other immune cells, can predict a longer overall survival in patients with HNSCC. Future studies are needed to explore the role of AVPR2 and tumour-infiltrating B cells in HNSCC. CONCLUSIONS: The AVPR2 gene may be a prognostic biomarker of HNSCC. Moreover, AVPR2 may play a role in HNSCC immune modulation, and the regulation of tumour-infiltrating B cells by AVPR2 may be a key link.
Assuntos
Linfócitos B , Neoplasias de Cabeça e Pescoço , Receptores de Vasopressinas , Carcinoma de Células Escamosas de Cabeça e Pescoço , Humanos , Biomarcadores Tumorais/genética , Regulação Neoplásica da Expressão Gênica , Neoplasias de Cabeça e Pescoço/genética , Prognóstico , Carcinoma de Células Escamosas de Cabeça e Pescoço/genética , Receptores de Vasopressinas/genéticaRESUMO
BACKGROUND: Cesarean scar pregnancy (CSP) treated with either high-intensity focused ultrasound ablation (HIFU-a) or uterine artery embolization (UAE) combined with ultrasound-guided dilation and curettage (USg-D&C) was effective. However, there is insufficient comparative research evidence on clinical efficacy and subsequent pregnancy outcomes after previous CSP treatment. This study aims to investigate the efficacy, safety, and subsequent pregnancy outcomes of HIFU-a compared to UAE before USg-D&C for the treatment of CSP. METHODS: Between January 2016 and July 2020, a total of 272 patients received the pretreatment with HIFU-a or UAE(HIFU-a group: n = 118; UAE group: n = 154). The clinical characteristics, treatment success rate, postoperative pregnancy rate and outcome of the two groups were compared and analyzed. RESULTS: The demographic characteristics of the two groups were similar. After pretreatment, the adverse events rate of HIFU-a group was lower than that of UAE group (10.40% (16/154) vs. 40.70% (48/118), P = 0.00). All patients received the USg-D&C. The HIFU-a group was of less intraoperative blood loss (10.00 (5.00-20.00) vs. 12.50 (5.00-30.00) ml, P = 0.03). There was no statistically significant difference between the two groups in success rates. However, the HIFU-a group was of a shorter duration of postoperative vaginal bleeding (12.00 (9.00-13.00) vs. 14.00 (12.00-15.00) days, P = 0.00). There was no significant difference between the two groups in terms of subsequent pregnancy rates (P = 0.317). However, the recurrent CSP (rCSP) rate in the HIFU-a group was lower than that in the UAE group (7.70% (6/78) vs. 19.70%(13/66), P = 0.03). CONCLUSIONS: CSP treated with either HIFU-a or UAE combined with USg-D&C was safe and effective. Although no significant difference was found in the subsequent pregnancy outcomes of the two groups, the rCSP was more common in the UAE group. So, we recommend HIFU-a combined with USg-D&C treatment modality.
Assuntos
Gravidez Ectópica , Embolização da Artéria Uterina , Gravidez , Feminino , Humanos , Resultado da Gravidez , Embolização da Artéria Uterina/efeitos adversos , Estudos Retrospectivos , Cicatriz/etiologia , Gravidez Ectópica/diagnóstico por imagem , Gravidez Ectópica/etiologia , Gravidez Ectópica/cirurgia , Dilatação e Curetagem , Resultado do Tratamento , Hemorragia Pós-Operatória/etiologia , Ultrassonografia de IntervençãoRESUMO
Heterogenous nuclear ribonucleoprotein G is down-regulated in the spinal cord of the Tg(SOD1*G93A)1Gur (TG) amyotrophic lateral sclerosis mouse model. However, most studies have only examined heterogenous nuclear ribonucleoprotein G expression in the amyotrophic lateral sclerosis model and heterogenous nuclear ribonucleoprotein G effects in amyotrophic lateral sclerosis pathogenesis such as in apoptosis are unknown. In this study, we studied the potential mechanism of heterogenous nuclear ribonucleoprotein G in neuronal death in the spinal cord of TG and wild-type mice and examined the mechanism by which heterogenous nuclear ribonucleoprotein G induces apoptosis. Heterogenous nuclear ribonucleoprotein G in spinal cord was analyzed using immunohistochemistry and western blotting, and cell proliferation and proteins (TAR DNA binding protein 43, superoxide dismutase 1, and Bax) were detected by the Cell Counting Kit-8 and western blot analysis in heterogenous nuclear ribonucleoprotein G siRNA-transfected PC12 cells. We analyzed heterogenous nuclear ribonucleoprotein G distribution in spinal cord in the amyotrophic lateral sclerosis model at various time points and the expressions of apoptosis and proliferation-related proteins. Heterogenous nuclear ribonucleoprotein G was mainly localized in neurons. Amyotrophic lateral sclerosis mice were examined at three stages: preonset (60-70 days), onset (90-100 days) and progression (120-130 days). The number of heterogenous nuclear ribonucleoprotein G-positive cells was significantly higher in the anterior horn of the lumbar spinal cord segment of TG mice at the preonset stage than that of control group but lower than that of the control group at the onset stage. The number of heterogenous nuclear ribonucleoprotein G-positive cells in both central canal and surrounding gray matter of the whole spinal cord of TG mice at the onset stage was significantly lower than that in the control group, whereas that of the lumbar spinal cord segment of TG mice was significantly higher than that in the control group at preonset stage and significantly lower than that in the control group at the progression stage. The numbers of heterogenous nuclear ribonucleoprotein G-positive cells in the posterior horn of cervical and thoracic segments of TG mice at preonset and progression stages were significantly lower than those in the control group. The expression of heterogenous nuclear ribonucleoprotein G in the cervical spinal cord segment of TG mice was significantly higher than that in the control group at the preonset stage but significantly lower at the progression stage. The expression of heterogenous nuclear ribonucleoprotein G in the thoracic spinal cord segment of TG mice was significantly increased at the preonset stage, significantly decreased at the onset stage, and significantly increased at the progression stage compared with the control group. heterogenous nuclear ribonucleoprotein G expression in the lumbar spinal cord segment of TG mice was significantly lower than that of the control group at the progression stage. After heterogenous nuclear ribonucleoprotein G gene silencing, PC12 cell survival was lower than that of control cells. Both TAR DNA binding protein 43 and Bax expressions were significantly increased in heterogenous nuclear ribonucleoprotein G-silenced cells compared with control cells. Our study suggests that abnormal distribution and expression of heterogenous nuclear ribonucleoprotein G might play a protective effect in amyotrophic lateral sclerosis development via preventing neuronal death by reducing abnormal TAR DNA binding protein 43 generation in the spinal cord.