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BACKGROUND: Growth Differentiation Factor 15 (GDF15), a divergent member of the TGF-ß superfamily, signals via the hindbrain glial-derived neurotrophic factor receptor alpha-like and rearranged during transfection receptor co-receptor (GFRAL-RET) complex. In nonclinical species, GDF15 is a potent anorexigen leading to substantial weight loss. MBL949 is a half-life extended recombinant human GDF15 dimer. METHODS: MBL949 was evaluated in multiple nonclinical species and then in humans in two randomized and placebo-controlled clinical trials. In the Phase 1 first-in-human, single ascending dose trial MBL949 or placebo was injected subcutaneously to overweight and obese healthy volunteers (n=65) at doses ranging from 0.03 to 20 mg. In Phase 2, MBL949 or placebo was administered subcutaneously every other week for a total of 8 doses to obese participants (n=126) in five different dose regimens predicted to be efficacious based on data from the Phase 1 trial. RESULTS: In nonclinical species, MBL949 was generally safe and effective with reduced food intake and body weight in mice, rats, dogs, and monkeys. Weight loss was primarily from reduced fat, and metabolic endpoints improved. A single ascending dose study in overweight or obese healthy adults demonstrated mean terminal half-life of 18-22 days, and evidence of weight loss at the higher doses. In the Phase 2, weight loss was minimal following biweekly dosing of MBL949 for 14 weeks. MBL949 was safe and generally tolerated in humans over the dose range tested, adverse events of the gastrointestinal system were the most frequent observed. CONCLUSION: The prolonged half-life of MBL949 supports biweekly dosing in patients. MBL949 had an acceptable safety profile. The robust weight loss observed in nonclinical species did not translate to weight loss efficacy in humans. TRIAL REGISTRATION: ClinicalTrials.gov NCT05199090.
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Cardiovascular diseases (CVDs) are one of the most significant diseases that pose a threat to human health. The innovative traditional Chinese medicine Tongxinluo Capsule, developed under the guidance of the theory of traditional Chinese medicine, has good clinical efficacy in various cardiovascular diseases, this medicine has effects such as blood protection, vascular protection, myocardial protection, stabilizing vulnerable plaques, and vasodilation. However, CVDs are a multifactorial disease, and their underlying mechanisms are not fully understood. Therefore, exploring the mechanism of action and clinical application of Tongxinluo Capsule in the treatment of various cardiovascular diseases is beneficial for exerting its therapeutic effect from multiple components, targets, and pathways. At the same time, it provides broader treatment ideas for other difficult to treat diseases in the cardiovascular event chain, and has significant theoretical and clinical significance for improving the treatment of cardiovascular diseases with traditional Chinese medicine.
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Psoriasis is a global health concern, and biological therapies have proven to be highly effective in treating psoriatic patients in many countries. We performed a bibliometric analysis of current research on biological agents for the treatments of psoriasis, investigating research patterns and public interest in this area. We conducted a thorough review of articles on biological agents for psoriasis in the Web of Science Core Collection spanning from 2000 to 2022. Our study involved examining the distribution of these articles based on publication year, affiliations, countries, authors, and journals. To visualize this data effectively, we employed bibliometric tools like CiteSpace and the R package bibliometrix. Our analysis encompassed 8,047 publications. The number of papers published sharply increased from 2009, either reaching its peak in 2022 or not yet reaching it. The United States (n = 2,292), Kristian Reich (n = 166), and British Journal of Dermatology (n = 368) emerged as the top countries, author, and journal, respectively, in terms of publication productivity. The burst references predominantly focused on evaluating the safety and efficacy of biological treatments. The keyword citation network identified 11 clusters, with research themes revolving around "double blind", "efficacy", "therapy", "safety", and "psoriatic arthritis" were the research focuses. Additionally, potential future research areas such as "multicenter," "drug survival," and "severity" were emphasized. This study sheds light on the evolving research landscape and public interest in biological agents for psoriasis. The results suggest rapid expansion in this field, with the United States at the forefront. Enhanced international collaboration is recommended, and forthcoming research endeavors may concentrate on predicting treatment outcomes and adverse effects. Researching new biological agents, broadening the indications for biological agent treatment, and creating personalized treatment plans may pave the way for further research.
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Two Enterobacter strains 170198T and 170250T were isolated from clinical blood samples from distinct patients in a hospital in Chengdu, China, in 2022. These isolates were subjected to whole-genome sequencing. A phylogenomic tree based on 2,096 concatenated core genes showed that the two strains were clustered within the genus Enterobacter. The average nucleotide identity (ANI) and in silico DNA-DNA hybridization (isDDH) values between each of the two strains and type strains of all currently known Enterobacter species were determined. The two strains belonged to two novel species as the highest ANI and isDDH values with type strains of all currently known Enterobacter species below the cutoff for species demarcation (96% for ANI and 70% for isDDH). Then the physiological and biochemical studies demonstrated that biochemical features and the profile of whole fatty acids of strains 170198T and 170250T were largely consistent with those known Enterobacter species. Nevertheless, the two novel species can be differentiated from all other Enterobacter species by certain biochemical characteristics. In conclusion, 170198T and 170250T represent two novel species of the genus Enterobacter, for which we propose Enterobacter chinensis sp. nov. and Enterobacter rongchengensis sp. nov., as the species names. The type strains of Enterobacter chinensis sp. nov., and Enterobacter rongchengensis sp. nov. are 170198T (=GDMCC 1.3549T=JCM 35826T) and 170250T (=GDMCC 1.3670T=JCM 36189T), respectively. The two novel species have clinical significance with the ability to cause bloodstream infections.IMPORTANCEEnterobacter is a group of bacteria comprising several common opportunistic pathogens and has a complicated taxonomy. Here, we reported two novel Enterobacter species. We demonstrated that the two novel species can be differentiated from other Enterobacter species by certain phenotypic characteristics and therefore provide information for designing tests for identification. We also showed that strains of the two novel species are able to cause human bloodstream infections and carry multiple virulence factors and therefore are of clinical significance. We highlight that the virulence of Enterobacter is less studied and warrants further exploration. We believe that the findings here are valuable for enhancing the appreciation toward Enterobacter, an important pathogen.
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Enterobacter , Infecções por Enterobacteriaceae , Filogenia , Fatores de Virulência , Enterobacter/genética , Enterobacter/isolamento & purificação , Enterobacter/classificação , Enterobacter/patogenicidade , Humanos , Infecções por Enterobacteriaceae/microbiologia , Fatores de Virulência/genética , China , Ácidos Graxos/análise , DNA Bacteriano/genética , Técnicas de Tipagem Bacteriana , Antibacterianos/farmacologia , Sequenciamento Completo do Genoma , Testes de Sensibilidade Microbiana , Hibridização de Ácido Nucleico , RNA Ribossômico 16S/genética , Genoma Bacteriano/genética , Feminino , MasculinoRESUMO
Psoriasis is a chronic systemic inflammatory cutaneous disease. Where the immune system plays an important role in its pathogenesis, with key inflammatory intercellular signalling peptides and proteins including IL-17 and IL-23. The psychoneurological system also figures prominently in development of psoriasis. There is a high prevalence of comorbidity between psoriasis and mental health disorders such as depression, anxiety and mania. Patients with psoriasis often suffer from pathological pain in the lesions, and their neurological accidents could improve the lesions in innervated areas. The immune system and the psychoneurological system interact closely in the pathogenesis of psoriasis. Patients with psoriasis exhibit abnormal levels of neuropeptides both in circulating and localized lesion, acting as immunomodulators involved in the inflammatory response. Moreover, receptors for inflammatory factors are expressed in both peripheral and central nervous systems (CNSs), suggesting that nervous system can receive and be influenced by signals from immune system. Key inflammatory intercellular signalling peptides and proteins in psoriasis, such as IL-17 and IL-23, can be involved in sensory signalling and may affect synaptic plasticity and the blood-brain barrier of CNS through the circulation. This review provides an overview of the multiple effects on the peripheral and CNS under conditions of systemic inflammation in psoriasis, providing a framework and inspiration for in-depth studies of neuroimmunomodulation in psoriasis.
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Sistema Nervoso Central , Interleucina-17 , Interleucina-23 , Psoríase , Psoríase/metabolismo , Psoríase/imunologia , Humanos , Sistema Nervoso Central/metabolismo , Interleucina-23/metabolismo , Interleucina-17/metabolismo , Neuroimunomodulação , Neuropeptídeos/metabolismo , Inflamação/metabolismo , Sistema Nervoso Periférico/metabolismo , Animais , Transdução de SinaisRESUMO
Glaesserella parasuis (G. parasuis) is the causative agent of porcine Glässer's disease, resulting in high mortality rates in pigs due to excessive inflammation-induced tissue damage. Previous studies investigating the protective effects of G. parasuis vaccination indicated a possible role of ApoA1 in reflecting disease progression following G. parasuis infection. However, the mechanisms of ApoA1 expression and its role in these infections are not well understood. In this investigation, newborn porcine tracheal (NPTr) epithelial cells infected with G. parasuis were used to elucidate the molecular mechanism and role of ApoA1. The study revealed that the AMPK pathway activation inhibited ApoA1 expression in NPTr cells infected with G. parasuis for the first time. Furthermore, Egr1 was identified as a core transcription factor regulating ApoA1 expression using a CRISPR/Cas9-based system. Importantly, it was discovered that APOA1 protein significantly reduced apoptosis, pyroptosis, necroptosis, and inflammatory factors induced by G. parasuis in vivo. These findings not only enhance our understanding of ApoA1 in response to bacterial infections but also highlight its potential in mitigating tissue damage caused by G. parasuis infection.
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Proteínas Quinases Ativadas por AMP , Apolipoproteína A-I , Proteína 1 de Resposta de Crescimento Precoce , Haemophilus parasuis , Transdução de Sinais , Doenças dos Suínos , Animais , Suínos , Apolipoproteína A-I/genética , Apolipoproteína A-I/metabolismo , Proteína 1 de Resposta de Crescimento Precoce/genética , Proteína 1 de Resposta de Crescimento Precoce/metabolismo , Haemophilus parasuis/genética , Doenças dos Suínos/microbiologia , Doenças dos Suínos/genética , Proteínas Quinases Ativadas por AMP/metabolismo , Proteínas Quinases Ativadas por AMP/genética , Infecções por Haemophilus/veterinária , Infecções por Haemophilus/microbiologia , Células Epiteliais/microbiologia , Regulação da Expressão Gênica , Traqueia/microbiologia , Traqueia/metabolismo , Apoptose , Animais Recém-NascidosRESUMO
Ciliogenesis-associated kinase 1 (CILK1) plays a key role in the ciliogenesis and ciliopathies. It remains totally unclear whether CILK1 is involved in tumor progression and therapy resistance. Here, we report that the aberrant high-expression of CILK1 in breast cancer is required for tumor cell proliferation and chemoresistance. Two compounds, CILK1-C30 and CILK1-C28, were identified with selective inhibitory effects towards the Tyr-159/Thr-157 dual-phosphorylation of CILK1, pharmacological inhibition of CILK1 significantly suppressed tumor cell proliferation and overcame chemoresistance in multiple experimental models. Large-scale screen of CILK1 substrates confirmed that the kinase directly phosphorylates ERK1, which is responsible for CILK1-mediated oncogenic function. CILK1 is also indicated to be responsible for the chemoresistance of small-cell lung cancer cells. Our data highlight the importance of CILK1 in cancer, implicating that targeting CILK1/ERK1 might offer therapeutic benefit to cancer patients.
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Neoplasias da Mama , Resistencia a Medicamentos Antineoplásicos , Animais , Feminino , Humanos , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Linhagem Celular Tumoral , Proliferação de Células , Resistencia a Medicamentos Antineoplásicos/genética , MAP Quinase Quinase Quinases , Proteína Quinase 3 Ativada por Mitógeno/metabolismo , Fosforilação , Proteínas Proto-OncogênicasRESUMO
Toad venom, a traditional Chinese medicine, exhibits remarkable medicinal properties of significant therapeutic value. The peptides present within toad venom possess a wide range of biological functions, yet the neuropeptide B (NPB) and it modification requires further exploration to comprehensively understand its mechanisms of action and potential applications. In this study, a fusion peptide, ANTP-BgNPB, was designed to possess better analgesic properties through the transdermal modification of BgNPB. After optimizing the conditions, the expression of ANTP-BgNPB was successfully induced. The molecular dynamics simulations suggested that the modified protein exhibited improved stability and receptor binding affinity compared to its unmodified form. The analysis of the active site of ANTP-BgNPB and the verification of mutants revealed that GLN3, SER38, and ARG42 were crucial for the protein's recognition and binding with G protein-coupled receptor 7 (GPR7). Moreover, experiments conducted on mice using the hot plate and acetic acid twist body models demonstrated that ANTP-BgNPB was effective in transdermal analgesia. These findings represent significant progress in the development of transdermal delivery medications and could have a significant impact on pain management.
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Analgésicos , Desenho de Fármacos , Animais , Analgésicos/química , Analgésicos/farmacologia , Camundongos , Peptídeos/química , Peptídeos/farmacologia , Administração Cutânea , Masculino , Relação Estrutura-Atividade , Simulação de Dinâmica Molecular , Estrutura Molecular , Relação Dose-Resposta a Droga , Dor/tratamento farmacológico , HumanosRESUMO
BACKGROUND: Hospice care professionals often experience trauma patient deaths and multiple patient deaths in a short period of time (more so than other nurses). This repeated exposure to the death process and the death of patients leads to greater psychological pressure on hospice care professionals. But at present, people pay more attention to the feelings and care burden of the family members of dying patients but pay less attention to medical staff. Thus, this study aimed to develop a scale on the burden of care for hospice care providers and assess the coping capacity of hospice professionals. Raising awareness of the psychological burden of hospice professionals. METHODS: Through a literature review, research group discussion, Delphi method and a pre-survey of professional coping skills among nurses, 200 hospice professionals who had received training in hospice care from pilot institutions engaged in or providing hospice care were selected for investigation. Cronbach's α coefficient and split-half reliability were used to test the internal consistency of the scale, and content validity and explore factor analysis (EFA) were used to test the construct validity of the scale. RESULTS: Two rounds of Delphi methods were carried out, and the effective recovery rate was 100%. The expert authority coefficients of the two rounds were 0.838 and 0.833, respectively. The Kendall's W coefficient of experts in the first round was 0.121 ~ 0.200 (P < 0.05), and the Kendall's W coefficient of the second round was 0.115-0.136 (P < 0.05), indicating a good level of expert coordination. The final survey scale for the care burden of hospice professionals included four dimensions-working environment (9 items), professional roles (8 items), clinical nursing (9 items) and psychological burden (7 items)-with a total of 33 items. The total Cronbach's α coefficient of the scale was 0.963, and the Cronbach's α coefficients of the working environment, professional roles, clinical nursing and psychological burden dimensions were 0.920, 0.889, 0.936 and 0.910, respectively. The total split-half reliability of the scale was 0.927, and the split-half reliability of each dimension was 0.846, 0.817, 0.891, and 0.832. The content validity of the scale items ranged from 0.90 to 1.00. Exploratory factor analysis revealed 5 common factors, with a total cumulative contribution rate of 68.878%. The common degree of each item in the scale was > 0.4, and the factor loading of each item was also > 0.4. CONCLUSION: The scale is an open-access, short, easy-to-administer scale. And which for assessing hospice care burden among hospice professionals developed in this study demonstrated strong reliability and validity. This tool can serve as a dependable instrument for evaluating the burden of hospice care for terminally ill patients by professionals in the hospice setting.
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Cuidados Paliativos na Terminalidade da Vida , Hospitais para Doentes Terminais , Humanos , Adaptação Psicológica , China , Psicometria , Reprodutibilidade dos Testes , Inquéritos e QuestionáriosRESUMO
BACKGROUND: Lupus erythematosus (LE) is a spectrum of autoimmune diseases. Due to the complexity of cutaneous LE (CLE), clinical skin image-based artificial intelligence is still experiencing difficulties in distinguishing subtypes of LE. OBJECTIVES: We aim to develop a multimodal deep learning system (MMDLS) for human-AI collaboration in diagnosis of LE subtypes. METHODS: This is a multi-centre study based on 25 institutions across China to assist in diagnosis of LE subtypes, other eight similar skin diseases and healthy subjects. In total, 446 cases with 800 clinical skin images, 3786 multicolor-immunohistochemistry (multi-IHC) images and clinical data were collected, and EfficientNet-B3 and ResNet-18 were utilized in this study. RESULTS: In the multi-classification task, the overall performance of MMDLS on 13 skin conditions is much higher than single or dual modals (Sen = 0.8288, Spe = 0.9852, Pre = 0.8518, AUC = 0.9844). Further, the MMDLS-based diagnostic-support help improves the accuracy of dermatologists from 66.88% ± 6.94% to 81.25% ± 4.23% (p = 0.0004). CONCLUSIONS: These results highlight the benefit of human-MMDLS collaborated framework in telemedicine by assisting dermatologists and rheumatologists in the differential diagnosis of LE subtypes and similar skin diseases.
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Tibetan pig is a geographically isolated pig breed that inhabits high-altitude areas of the Qinghai-Tibetan plateau. At present, there is limited research on viral diseases in Tibetan pigs. This study provides a novel metagenomic exploration of the gut virome in Tibetan pigs (altitude ≈ 3000 m) across three critical developmental stages, including lactation, nursery, and fattening. The composition of viral communities in the Tibetan pig intestine, with a dominant presence of Microviridae phages observed across all stages of development, in combination with the previous literature, suggest that it may be associated with geographical locations with high altitude. Functional annotation of viral operational taxonomic units (vOTUs) highlights that, among the constantly increasing vOTUs groups, the adaptability of viruses to environmental stressors such as salt and heat indicates an evolutionary response to high-altitude conditions. It shows that the lactation group has more abundant viral auxiliary metabolic genes (vAMGs) than the nursery and fattening groups. During the nursery and fattening stages, this leaves only DNMT1 at a high level. which may be a contributing factor in promoting gut health. The study found that viruses preferentially adopt lytic lifestyles at all three developmental stages. These findings not only elucidate the dynamic interplay between the gut virome and host development, offering novel insights into the virome ecology of Tibetan pigs and their adaptation to high-altitude environments, but also provide a theoretical basis for further studies on pig production and epidemic prevention under extreme environmental conditions.
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Altitude , Microbioma Gastrointestinal , Metagenômica , Viroma , Animais , Suínos , Viroma/genética , Microbioma Gastrointestinal/genética , Tibet , Vírus/genética , Vírus/classificação , Metagenoma , Feminino , Genoma ViralRESUMO
BACKGROUND: Our aim was to target the unsatisfied need for early detection of the at-risk population and determine the subgroup of patients whose psoriasis (PsO) could transform into psoriatic arthritis (PsA). METHODS: A retrospective and longitudinal case-control study was conducted at Beijing Chao-yang Hospital. It included 75 patients who were clinically diagnosed with PsA in the case group and 345 who solely suffered from PsO without PsA in the control group. A variety of baseline covariates were gathered from every patient with PsO. Univariate and multivariate analyses and receiver operating characteristic (ROC) curves were used to identify underlying risk factors and determine whether it was necessary to examine the imaging of PsO patients. RESULTS: In multivariate logistic regression analysis, age ≥40 (odds ratio (OR): 1.04, 95% confidence interval (CI): 1.02-1.06, P < 0.01), nail involvement (OR: 1.17, 95% CI: 1.09-1.32, P < 0.01), erythrocyte sedimentation rate (ESR) (OR: 1.03, 95% CI: 1.01-1.06, P < 0.05) and elevated high-sensitivity C-reactive protein (hs-CRP) (OR: 1.31, 95% CI: 1.13-1.53, P < 0.01) were perceived to be risk factors for the transformation from PsO into clinical PsA. By combining magnetic resonance imaging (MRI)-detected enthesitis with tenosynovitis, combined predictors demonstrated better diagnostic efficacy, with an improvement in specificity (94.3% vs. 69%) and similarities in sensitivity (89% vs. 84.6%). The areas under the ROC curve (AUCs) amounted to 0.925 (95% CI: 0.882-0.967, P < 0.01) and 0.858 (95% CI: 0.814-0.903, P < 0.01). CONCLUSIONS: It was identified that age ≥40, nail involvement, as well as an elevated ESR, and hs-CRP served as independent risk factors for PsO transforming into PsA. Additionally, MRI provides additional value for the early recognition of PsA.
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ETHNOPHARMACOLOGICAL RELEVANCE: As reported in the Ancient Chinese Medicinal Books, Ginkgo biloba L. fruit has been used as a traditional Chinese medicine for the treatment asthma and cough or as a disinfectant. Our previous study demonstrated that G. biloba exocarp extract (GBEE), an extract of a traditional Chinese herb, inhibits the formation of methicillin-resistant Staphylococcus aureus (MRSA) biofilms. However, GBEE is a crude extract that contains many components, and the underlying mechanisms of purified GBEE fractions extracted with solvents of different polarities are unknown. AIM OF THE STUDY: This study aimed to investigate the different components in GBEE fractions extracted with solvents of different polarities and their antibacterial effects and mechanisms against MRSA and Staphylococcus haemolyticus biofilms both in vitro and in vivo. METHODS: The components in different fractions were detected by high-performance liquid chromatography-high resolution mass spectrometry (HPLC-HRMS). Microbroth dilution assays and time growth curves were used to determine the antibacterial effects of the fractions on 15 clinical bacterial isolates. Crystal violet staining, scanning electron microscopy (SEM) and transmission electron microscopy (TEM) were utilized to identify the fractions that affected bacterial biofilm formation. The potential MRSA targets of the GBEE fraction obtained with petroleum ether (PE), denoted GBEE-PE, were screened by transcriptome sequencing, and the gene expression profile was verified by quantitative polymerase chain reaction (qPCR). RESULTS: HPLC-HRMS analysis revealed that the four GBEE fractions (extracted with petroleum ether, ethyl acetate, n-butanol, and water) contained different ginkgo components, and the antibacterial effects decreased as the polarity of the extraction solvent increased. The antibacterial activity of GBEE-PE was greater than that of the GBEE fraction extracted with ethyl acetate (EA). GBEE-PE improved H. illucens survival and reduced MRSA colonization in model mouse organs. Crystal violet staining and SEM and TEM analyses revealed that GBEE-PE inhibited MRSA and S. haemolyticus biofilm formation. Transcriptional analysis revealed that GBEE-PE inhibits MRSA biofilms by altering ion transport, cell wall metabolism and virulence-related gene expression. In addition, the LO2 cell viability and H. illucens toxicity assay data showed that GBEE-PE at 20 mg/kg was nontoxic. CONCLUSION: The GBEE fractions contained different components, and their antibacterial effects decreased with increases in the polarity of the extraction solvent. GBEE-PE limited MRSA growth and biofilm formation by affecting ion transport, cell wall synthesis, and virulence-related pathways. This research provides a more detailed overview of the mechanism by which GBEE-PE inhibits MRSA both in vitro and in vivo and suggests that GBEE-PE is a new prospective antimicrobial with the potential to be used in MRSA therapeutics in the future.
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Acetatos , Alcanos , Staphylococcus aureus Resistente à Meticilina , Animais , Camundongos , Ginkgo biloba/química , Virulência , Violeta Genciana/farmacologia , Estudos Prospectivos , Extratos Vegetais/farmacologia , Solventes/química , Antibacterianos/farmacologia , Biofilmes , Testes de Sensibilidade MicrobianaRESUMO
Colonisation by bacterial pathogens typically precedes invasive infection and seeds transmission. Thus, effective decolonisation strategies are urgently needed. The literature reports attempts to use phages for decolonisation. To assess the in-vivo efficacy and safety of phages for bacterial decolonisation, we performed a systematic review by identifying relevant studies to assess the in-vivo efficacy and safety of phages for bacterial decolonisation. We searched PubMed, Embase (Ovid), MEDLINE (Ovid), Web of Science, and the Cochrane Library to identify relevant articles published between Jan 1, 1990, and May 12, 2023, without language restrictions. We included studies that assessed the efficacy of phage for bacterial decolonisation in humans or vertebrate animal models. This systematic review is registered with PROSPERO, CRD42023457637. We identified 6694 articles, of which 56 (51 animal studies and five clinical reports) met the predetermined selection criteria and were included in the final analysis. The gastrointestinal tract (n=49, 88%) was the most studied bacterial colonisation site, and other sites were central venous catheters, lung, nose, skin, and urinary tract. Of the 56 included studies, the bacterial load at the colonisation site was reported to decrease significantly in 45 (80%) studies, but only five described eradication of the target bacteria. 15 studies reported the safety of phages for decolonisation. No obvious adverse events were reported in both the short-term and long-term observation period. Given the increasing life-threatening risks posed by bacteria that are difficult to treat, phages could be an alternative option for bacterial decolonisation, although further optimisation is required before their application to meet clinical needs.
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Infecções Bacterianas , Bacteriófagos , Humanos , Infecções Bacterianas/terapia , Animais , Bactérias/virologia , Terapia por Fagos/métodosRESUMO
RATIONALE: Uterine perforation is a serious complication of intrauterine contraceptive device (IUD) placement. However, as complete uterine perforation and extrauterine migration may remain asymptomatic, thorough localization of the IUD is important prior to reinsertion. PATIENT CONCERNS: A 33-year-old patient who has had 4 IUD insertions, wherein the location of the first IUD (inserted 14 years ago) was not identified prior to reinsertion and replacement of the subsequent three. She presented to hospital with a 6-month history of abdominal pain. Pelvic ultrasonography (US), radiography, hysteroscopy and laparoscopy examinations confirmed that a retained migrated IUD in the right broad ligament. DIAGNOSIS: Uterine perforation, IUD migration to the broad ligament. INTERVENTIONS: The patient underwent hysteroscopy and laparoscopy. OUTCOMES: Both IUDs were successfully removed without any complications.
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Ligamento Largo , Migração de Dispositivo Intrauterino , Dispositivos Intrauterinos , Perfuração Uterina , Feminino , Humanos , Adulto , Perfuração Uterina/diagnóstico por imagem , Perfuração Uterina/etiologia , Migração de Dispositivo Intrauterino/efeitos adversos , Dispositivos Intrauterinos/efeitos adversos , RadiografiaRESUMO
A facile method was developed for the selective thioetherification of uracils using sulfonyl hydrazide as the thioetherification reagent. This method offers advantages such as avoiding the use of additives and expensive metal catalysts, and providing good to excellent yields of various uracil thioethers. Experimental studies have demonstrated that the reaction follows a free radical pathway. Notably, the reaction can be carried out without solvent.