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Amyotrophic lateral sclerosis (ALS) is a rare neurodegenerative disease with a challenging treatment landscape, due to its complex pathogenesis and limited availability of clinical drugs. Ferroptosis, an iron-dependent form of programmed cell death (PCD), stands distinct from apoptosis, necrosis, autophagy, and other cell death mechanisms. Recent studies have increasingly highlighted the role of iron deposition, reactive oxygen species (ROS) accumulation, oxidative stress, as well as systemic Xc- and glutamate accumulation in the antioxidant system in the pathogenesis of amyotrophic lateral sclerosis. Therefore, targeting ferroptosis emerges as a promising strategy for amyotrophic lateral sclerosis treatment. This review introduces the regulatory mechanism of ferroptosis, the relationship between amyotrophic lateral sclerosis and ferroptosis, and the drugs used in the clinic, then discusses the current status of amyotrophic lateral sclerosis treatment, hoping to provide new directions and targets for its treatment.
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Sclérose latérale amyotrophique , Ferroptose , Ferroptose/effets des médicaments et des substances chimiques , Ferroptose/physiologie , Sclérose latérale amyotrophique/métabolisme , Sclérose latérale amyotrophique/traitement médicamenteux , Sclérose latérale amyotrophique/anatomopathologie , Humains , Animaux , Stress oxydatif/physiologie , Espèces réactives de l'oxygène/métabolisme , Fer/métabolisme , Antioxydants/usage thérapeutiqueRÉSUMÉ
Ferroptosis is a non-apoptotic mode of programmed cell death characterized by iron dependence and lipid peroxidation. Since the ferroptosis was proposed, researchers have revealed the mechanisms of its formation and continue to explore effective inhibitors of ferroptosis in disease. Recent studies have shown a correlation between ferroptosis and the pathological mechanisms of neurodegenerative diseases, as well as diseases involving tissue or organ damage. Acting on ferroptosis-related targets may provide new strategies for the treatment of ferroptosis-mediated diseases. This article specifically describes the metabolic pathways of ferroptosis and summarizes the reported mechanisms of action of natural and synthetic small molecule inhibitors of ferroptosis and their efficacy in disease. The paper also describes ferroptosis treatments such as gene therapy, cell therapy, and nanotechnology, and summarises the challenges encountered in the clinical translation of ferroptosis inhibitors. Finally, the relationship between ferroptosis and other modes of cell death is discussed, hopefully paving the way for future drug design and discovery.
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Alzheimer's disease (AD) is a neurodegenerative disorder characterized by a complex pathogenesis, which involves the formation of amyloid plaques and neurofibrillary tangles. Many recent studies have revealed a close association between ferroptosis and the pathogenesis of AD. Factors such as ferroptosis-associated iron overload, lipid peroxidation, disturbances in redox homeostasis, and accumulation of reactive oxygen species have been found to contribute to the pathological progression of AD. In this review, we explore the mechanisms underlying ferroptosis, describe the link between ferroptosis and AD, and examine the reported efficacy of ferroptosis inhibitors in treating AD. Finally, we discuss the potential challenges to ferroptosis inhibitors use in the clinic, enabling their faster use in clinical treatment.
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Maladie d'Alzheimer , Ferroptose , Ferroptose/physiologie , Ferroptose/effets des médicaments et des substances chimiques , Humains , Maladie d'Alzheimer/métabolisme , Maladie d'Alzheimer/traitement médicamenteux , Maladie d'Alzheimer/anatomopathologie , Animaux , Espèces réactives de l'oxygène/métabolisme , Peroxydation lipidique/effets des médicaments et des substances chimiques , Peroxydation lipidique/physiologieRÉSUMÉ
Spondylocostal dysostosis (SCDO) encompasses a group of skeletal disorders characterized by multiple segmentation defects in the vertebrae and ribs. SCDO has a complex genetic etiology. This study aimed to analyze and identify pathogenic variants in a fetus with SCDO. Copy number variant sequencing and whole exome sequencing were performed on a Chinese fetus with SCDO, followed by bioinformatics analyses, in vitro functional assays and a systematic review on the reported SCDO cases with LFNG pathogenic variants. Ultrasound examinations in utero exhibited that the fetus had vertebral malformation, scoliosis and tethered cord, but rib malformation was not evident. We found a novel homozygous variant (c.1078 C > T, p.R360C) within the last exon of LFNG. The variant was predicted to cause loss of function of LFNG by in silico prediction tools, which was confirmed by an in vitro assay of LFNG enzyme activity. The systematic review listed a total of 20 variants of LFNG in SCDO. The mutational spectrum spans across all exons of LFNG except the last one. This study reported the first Chinese case of LFNG-related SCDO, revealing the prenatal phenotypes and expanding the mutational spectrum of the disorder.
Sujet(s)
, Femelle , Humains , Grossesse , Malformations multiples/génétique , Malformations multiples/anatomopathologie , Asiatiques/génétique , Variations de nombre de copies de segment d'ADN , Peuples d'Asie de l'Est , Foetus/malformations , Hernie diaphragmatique , Myéloméningocèle/génétique , Myéloméningocèle/imagerie diagnostique , Mutation , Glycosyltransferase/génétiqueRÉSUMÉ
Congenital adrenal hyperplasia (CAH) is a group of autosomal recessive disorders predominantly characterized by impaired corticosteroid synthesis. Clinical phenotypes include hypoadrenocorticism, electrolyte disturbances, abnormal gonadal development, and short stature, of which severe hyponadrenocorticism and salt wasting can be life-threatening. Genetic analysis can help in the clinical diagnosis of CAH. However, the 21-OHD-causing gene CYP21A2 is arranged in tandem with the highly homologous CYP21A1P pseudogene, making it difficult to determine the exact genotypes using the traditional method of multiplex ligation-dependent probe amplification (MLPA) plus Sanger sequencing or next-generation sequencing (NGS). We applied a long-read sequencing-based approach termed comprehensive analysis of CAH (CACAH) to 48 newborns with CAH that were diagnosed by clinical features and the traditional MLPA plus Sanger sequencing method for retrospective analysis, to evaluate its efficacy in the clinical diagnosis of neonatal CAH. Compared with the MLPA plus Sanger sequencing method, CACAH showed 100 % consistency in detecting SNV/indel variants located in exons and exon-intron boundary regions of CAH-related genes. It can directly determine the cis-trans relationship without the need to analyze parental genotypes, which reduces the time to diagnosis. Moreover, CACAH was able to distinguish different CYP21A1P/CYP21A2 and TNXA/TNXB chimeras, and detect additional variants (CYP21A2 variants c.-121C > T, c.*13G > A, c.*52C > T, c.*440C > T, c.*443 T > C, and TNXB variants c.12463 + 2 T > C, c.12204 + 5G > A). We also identified the TNXB variant c.11435_11524 + 30del alone instead of as a part of the TNXA/TNXB-CH-1 chimera in two newborns, which might be introduced by gene conversion. All of these characteristics enabled clinicians to better explain the phenotype of subjects and manage them more effectively. CACAH has a great advantage over the traditional MLPA and Sanger sequencing methods, showing substantial potential in the genetic diagnosis and screening of neonatal CAH.
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Hyperplasie congénitale des surrénales , Nanisme , Nouveau-né , Humains , Hyperplasie , Études rétrospectives , Hyperplasie congénitale des surrénales/diagnostic , Hyperplasie congénitale des surrénales/génétique , Séquençage nucléotidique à haut débit , Ténascine , Steroid 21-hydroxylase/génétiqueRÉSUMÉ
BACKGROUND: Newborn screening (NBS) aims to detect congenital anomalies, and next-generation sequencing (NGS) has shown promise in this aspect. However, the NBS strategy for monogenic inherited diseases in China remains insufficient. METHODS: We developed a NeoEXOME panel comprising 601 genes that are relevant to the Chinese population found through extensive research on available databases. An interpretation system to grade the results into positive (high-risk, moderate-risk, and low-risk genotypes), negative, and carrier according to the American College of Medical Genetics (ACMG) guidelines was also developed. We validated the panel to evaluate its efficacy by using data from the "1000 Genomes Project" and conducted a pilot multicenter study involving 3423 neonates. RESULTS: The NGS positive rate in the 1000 Genomes Project was 7.6% (23/301), whereas the rate was 12.0% in the multicenter study, including 3249 recruited neonates. Notably, in 200 neonates, positive per conventional NBS, 58.5% (69/118) showed results consistent with NGS. In the remaining 3049 neonates showing negative results in conventional NBS, 271 (8.9%) were positive per NGS, and nine of them were clinically diagnosed with diseases in the follow-up. CONCLUSION: We successfully designed a NeoEXOME panel for targeted sequencing of monogenic inherited diseases in NBS. The panel demonstrated high performance in the Chinese population, particularly for the early detection of diseases with no biochemical markers.
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Séquençage nucléotidique à haut débit , Dépistage néonatal , Humains , Nouveau-né , Projets pilotes , , Dépistage néonatal/méthodes , Génotype , Séquençage nucléotidique à haut débit/méthodesRÉSUMÉ
The demand of microwave absorption materials (MAMs) with unique morphologies and electromagnetic (EM) balance has become necessary in recent years. Due to the ease of synthesis and tunable structure, metal-organic frameworks (MOFs) are widely used for this special MAMs. In this study, a new three-dimensional hybrid MOF is proposed that is co-doped with six equally branched star morphologies. The Co-C composite has the same six-branched morphology as that of the precursor. When the EM wave is incident, this special structure makes it easier for the EM wave to enter the material vertically due to the expansion of the incident surface, which is effective in adjusting the transmission path of the electron and the reflection and distribution of the EM wave. Because of the special morphology and magneto-dielectric synergy, the Co-C composite shows a minimum reflection loss (RLmin) of -48.5 dB at 11.0 GHz at an absorption thickness of 3.0 mm, with a microwave absorption bandwidth (EAB) of 6.1 GHz. This research provides a practical guidance for preparing the MAMs of special star structure.
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Hepatoid adenocarcinoma (HAC) is a rare, malignant, extrahepatic tumor with histologic features similar to those of hepatocellular carcinoma. HAC is most often associated with elevated alpha-fetoprotein (AFP). HAC can occur in multiple organs, including the stomach, esophagus, colon, pancreas, lungs, and ovaries. HAC differs greatly from typical adenocarcinoma in terms of its biological aggression, poor prognosis, and clinicopathological characteristics. However, the mechanisms underlying its development and invasive metastasis remain unclear. The purpose of this review was to summarize the clinicopathological features, molecular traits, and molecular mechanisms driving the malignant phenotype of HAC, in order to support the clinical diagnosis and treatment of HAC.
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Adénocarcinome , Carcinome hépatocellulaire , Tumeurs du foie , Tumeurs de l'estomac , Humains , Tumeurs du foie/anatomopathologie , Tumeurs de l'estomac/anatomopathologie , Adénocarcinome/traitement médicamenteux , Carcinome hépatocellulaire/anatomopathologie , AlphafoetoprotéinesRÉSUMÉ
Purpose: The study aimed to quantify the global trends of the incidence rates of multidrug-resistant (MDR) tuberculosis (MDR-TB) and extensively drug-resistant (XDR) tuberculosis (XDR-TB). Methods: Cases, age-standardized rates (ASRs), and incidence rates of MDR-TB and XDR-TB during 2010-2019 were obtained from the Global Burden of Disease Study 2019. The incidence trends of MDR-TB and XDR-TB were evaluated using the estimated annual percentage changes (EAPCs) in ASRs. The relationships among the ASRs of MDR-TB and XDR-TB, the MDR rate, the XDR rate, and socio-demographic index (SDI) were assessed using locally weighted regression and Pearson's correlation coefficient. Results: The global ASR of MDR-TB on average decreased by 1.36% (EAPC = -1.36, 95% confidence interval [CI] = -2.19 to -0.52) per year whereas that of XDR-TB was stable (EAPC = 0.69, 95% CI = -0.15-1.54) during 2010-2019. The incidence trends of MDR-TB in most regions and countries were decreasing, but those of XDR-TB were increasing. People aged 35-44 and 55-64 years had the highest incidence rates for MDR-TB and XDR-TB. The MDR and XDR rates both peaked in those aged 35-44 years. Areas with higher SDI tended to have lower ASRs of MDR-TB (p < 0.001, ρ = -0.43). Conclusion: The current achievements for the incidence trends of MDR-TB and XDR-TB are insufficient. More strategies and tools need to be developed to further curb MDR-TB and XDR-TB, especially in high-risk areas and age groups, and in low SDI regions.
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Increasing evidence shows that human papillomavirus (HPV) E6/E7 deletion in cervical cancer cells may be related to the immunosuppressive tumor microenvironment and adverse reactions or resistance to immune checkpoint blockade. Here, we demonstrate that liposome delivery of CRISPR/cas9 can effectively knock out HPV, which, in turn, induces autophagy and triggers cell death-related immune activation by releasing damage-related molecular patterns. The results of in vivo experiments showed that HPV-targeting guide RNA-liposomes could promote CD8+ T cell infiltration in tumor tissues; enhance the expression of proinflammatory cytokines, such as interleukin-12, tumor necrosis factor-α, and interferon-γ, and reduce regulatory T cells and myeloid suppressor cells. The combination of HPV-targeting guide RNA-liposomes with immune checkpoint inhibitors and antiprogrammed death-1 antibodies produced highly effective antitumor effects. In addition, combination therapy induced immune memory in the cervical cancer model.
Sujet(s)
Protéines des oncogènes viraux , Infections à papillomavirus , Tumeurs du col de l'utérus , Femelle , Humains , Tumeurs du col de l'utérus/thérapie , Tumeurs du col de l'utérus/anatomopathologie , Liposomes , Protéines des oncogènes viraux/génétique , Infections à papillomavirus/complications , Infections à papillomavirus/thérapie , Systèmes CRISPR-Cas , Protéines de répression/génétique , ARN , Protéines E7 de papillomavirus/génétique , Microenvironnement tumoralRÉSUMÉ
BACKGROUND: A low survival rate in patients with cardiac arrest is associated with failure to recognize the condition in its initial stage. Therefore, recognizing the warning symptoms of cardiac arrest in the early stage may play an important role in survival. AIM: To investigate the warning symptoms of cardiac arrest and to determine the correlation between the symptoms and outcomes. METHODS: We included all adult patients with all-cause cardiac arrest who visited Peking University Third Hospital or Beijing Friendship Hospital between January 2012 and December 2014. Data on population, symptoms, resuscitation parameters, and outcomes were analysed. RESULTS: Of the 1021 patients in the study, 65.9% had symptoms that presented before cardiac arrest, 25.2% achieved restoration of spontaneous circulation (ROSC), and 7.2% survived to discharge. The patients with symptoms had higher rates of an initial shockable rhythm (12.2% vs 7.5%, P = 0.020), ROSC (29.1% vs 17.5%, P = 0.001) and survival (9.2% vs 2.6%, P = 0.001) than patients without symptoms. Compared with the out-of-hospital cardiac arrest (OHCA) without symptoms subgroup, the OHCA with symptoms subgroup had a higher rate of calls before arrest (81.6% vs 0.0%, P < 0.001), health care provider-witnessed arrest (13.0% vs 1.4%, P = 0.001) and bystander cardiopulmonary resuscitation (15.5% vs 4.9%, P = 0.002); a shorter no flow time (11.7% vs 2.8%, P = 0.002); and a higher ROSC rate (23.8% vs 13.2%, P = 0.011). Compared to the in-hospital cardiac arrest (IHCA) without symptoms subgroup, the IHCA with symptoms subgroup had a higher mean age (66.2 ± 15.2 vs 62.5 ± 16.3 years, P = 0.005), ROSC (32.0% vs 20.6%, P = 0.003), and survival rates (10.6% vs 2.5%, P < 0.001). The top five warning symptoms were dyspnea (48.7%), chest pain (18.3%), unconsciousness (15.2%), paralysis (4.3%), and vomiting (4.0%). Chest pain (20.9% vs 12.7%, P = 0.011), cardiac etiology (44.3% vs 1.5%, P < 0.001) and survival (33.9% vs 16.7%, P = 0.001) were more common in males, whereas dyspnea (54.9% vs 45.9%, P = 0.029) and a non-cardiac etiology (53.3% vs 41.7%, P = 0.003) were more common in females. CONCLUSION: Most patients had warning symptoms before cardiac arrest. Dyspnea, chest pain, and unconsciousness were the most common symptoms. Immediately recognizing these symptoms and activating the emergency medical system prevents resuscitation delay and improves the survival rate of OHCA patients in China.
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Purpose: This study aimed to determine Down syndrome (DS) burden using years lived with disability (YLDs), years of life lost (YLLs), disability-adjusted life years (DALYs), and the trends in these parameters. Methods: We obtained the annual YLDs, YLLs, DALYs, and age-standardized rates (ASRs) of DS from 2010 to 2019 using the Global Health Data Exchange tool. The estimated annual percentage changes (EAPCs) in ASR were used to quantify and evaluate DS burden trends. Gaussian-process regression and Pearson's correlation coefficient were used to assess the relationship between DS burden and socio-demographic index (SDI). Results: Global DALYs decreased by 2.68% from 2010 to 2019 but the ASR was stable, which was mostly explained by the stability in the ASR for YLLs. The ASR of YLDs showed an increasing trend (EAPC = 1.07, 95% CI = 0.45 to 1.69). There was notable regional imbalance, with most of the DALYs or ASRs in areas with relatively low SDI. The DALY rates of DS were mostly from the YLLs of children younger than 1 year. Lower SDI areas tended to have higher DS burdens (ρ = -0.3, p < 0.001). Conclusion: This systematic analysis of the global disease burden of DS from 2010 to 2019 revealed that although the global DS DALY and YLL rate is stable, the YLD rate is increasing. And the DS burden varies significantly differences among regions or countries. The present results suggest that future strategies should focus on DS-related deaths in children younger than 1 year and the DS burden in low-SDI regions or countries, since this may be effective in further reducing DS burden.
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OBJECTIVES: Phenylketonuria (PKU) is an inherited autosomal recessive disorder of phenylalanine metabolism. It is mainly caused by a deficiency in phenylalanine hydroxylase (PAH) and frequently diagnosed with Sanger sequencing. To some extent, allelic dropout can explain the inconsistency in genotype and phenotype. METHODS: Three families were evaluated through DNA sequence analysis, multiplex ligation-dependent probe amplification (MLPA) and prenatal diagnosis technologies. The possibility of inconsistency in phenotype and genotype with c.331C>T variant was analysed. RESULTS: Through pedigree analysis, three mothers carried a homozygous c.331C>T variant, which was a false-positive result. New primers were used, and this error was caused by allelic dropout. In this case, c.158G>A was likely a benign variant. CONCLUSIONS: Sequence variants in primer-binding regions could cause allelic dropout, creating unpredictable errors in genotyping. Our results emphasised the need for careful measures to treat genotype-phenotype inconsistencies.
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Phenylalanine 4-monooxygenase , Phénylcétonuries , Allèles , Femelle , Génotype , Humains , Mutation , Phénotype , Phenylalanine 4-monooxygenase/génétique , Phenylalanine 4-monooxygenase/métabolisme , Phénylcétonuries/diagnostic , Phénylcétonuries/génétique , GrossesseRÉSUMÉ
BACKGROUND: Radiation-induced lung injury (RILI) is lacking effective therapeutic strategies. In this study, we conducted TGF-ß1-based CRISPR/Cas9 gene therapy for RILI. OBJECTIVE: Mouse lungs were irradiated with a single-dose of 20-Gy gamma rays followed by intravenous administration of Ad-CRISPR-TGF-ß1 or Ad- CRISPR-Null. METHODS: Haematoxylin and eosin staining, as well as Masson staining, were performed to observe lung morphology. Albumin and IgM concentrations in bronchoalveolar lavage fluid were measured by ELISA. Cytokine levels were measured using ELISA and/or real-time PCR with terminal deoxynucleotidyl transferase-mediated nick-end labelling. RESULTS: Ad-CRISPR-TTGF-ß1 improved histopathological and biochemical markers of lung injury, reduced secretion and expression of inflammatory cytokines, and inhibited progression of fibrosis. Importantly, the SK1/S1P axis, which is known to play a key role via S1P1 in TGF-ß1-dependent S1PR pattern remodelling, is responsible for promoting fibrosis. CONCLUSION: Our results indicate novel insights for RILI therapy.
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Lésion pulmonaire , Animaux , Systèmes CRISPR-Cas/génétique , Cytokines/génétique , Cytokines/métabolisme , Fibrose , Thérapie génétique , Poumon/métabolisme , Lésion pulmonaire/génétique , Lésion pulmonaire/thérapie , Souris , Souris de lignée C57BL , Facteur de croissance transformant bêta-1/génétique , Facteur de croissance transformant bêta-1/métabolismeRÉSUMÉ
Carbonaceous microwave absorbing materials are in vital demand due to the extensive electromagnetic pollution in 5G network era and urgent requirements for stealth technology in national defense domain. Rather than the complicated vapor deposition method, a simple biomass-derived approach sheds light on the mass production of carbon materials for its ubiquitous, environmental-friendly, cost-off, and sustainable advantages. Herein, a concise review of recent advances in designing carbonaceous materials for EM attention is provided with particular stress on the biomass categories and the synthetic method. The three dimensional (3D) interconnected network of carbon materials are highlighted in analysis regarding the biomass selection, functional process, pore-forming strategy and the microwave absorption performance of the corresponding composites. Nature fiber-derived carbon materials, possessing high-aspect ratio fiber structure, are also discussed due to their potential in weaving manufacture and diverse application for flexible cloaking fabric. In the end, the current challenge and the directional perspective for utilizing biomass-derived carbon absorbing materials with effective EM properties are outlined.
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Carbone , Micro-ondes , BiomasseRÉSUMÉ
This study describes a successful case of preimplantation genetic testing for the monogenic disease (PGT-M) of methylmalonic acidemia (MMA). To avoid the transmission of pathogenic mutations and unnecessary pregnancy termination we applied next-generation sequencing (NGS)-based haplotyping on a couple with a previously deceased MMA offspring. After embryo preparation, all samples were amplified successfully by whole genome amplification. We performed preimplantation genetic testing for aneuploidy (PGT-A) to determine the copy number of embryos' chromosomes. PGT-A results showed five blastocysts (2, 11, 14, 15 and 16) with balanced chromosomes (46, XN). Two techniques were used for PGT-M. Sanger sequencing was used to detect the mutations of MMUT gene directly, and NGS-based single nucleotide polymorphism (SNP) haplotyping was used to distinguish the chromosomes that carried the mutation. Sanger sequencing and NGS-based SNP haplotyping confirmed that samples 2 and 15 carried c.730insTT, samples 11 and 15 carried c.1105 C > T and samples 14 and 16 did not carry any mutation. Thus, blastocyst 14 was transferred into the mother's uterus. After prenatal diagnosis at 18 weeks of gestation, a healthy infant without MMUT mutation was born at full term. This study highlights the efficiency of NGS-based SNP haplotyping for PGT-M of MMA.Abbreviations: MMA: methylmalonic acidemia; MMUT: methylmalonyl-CoA mutase; PGT-M: preimplantation genetic testing for monogenic disease; PGD: preimplantation genetic diagnosis; IVF: in vitro fertilization; ADO: allele dropout; WGA: whole genome amplification; SNP: single nucleotide polymorphism; NGS: next-generation sequencing; PND: prenatal diagnosis; ICSI: intracytoplasmic sperm injection; TE: trophectoderm; DOP-PCR: degenerate oligonucleotide primed polymerase chain reaction; PGT-A: preimplantation genetic testing for aneuploidy; PCR: polymerase chain reaction.
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Aminoacidopathies congénitales , Diagnostic préimplantatoire , Aneuploïdie , Blastocyste , Femelle , Fécondation in vitro , Dépistage génétique , Séquençage nucléotidique à haut débit , Humains , Polymorphisme de nucléotide simple , GrossesseRÉSUMÉ
Toxic epidermal necrolysis (TEN) and Stevens-Johnson syndrome (SJS) are potentially fatal mucocutaneous diseases characterized by extensive necrosis and exfoliation of the epidermis. TEN and SJS are most often caused by various kinds of drugs. Other risk factors for SJS/TEN include pneumonia infection, HIV infection, genetic factors, underlying immune diseases, and tumors. SJS and TEN were first identified in 1922, but at present, a widely recognized view is that SJS and TEN represent phases in the continuous progress of the same disease. SJS/TEN has a very high mortality, but is rare, and cases of SJS/TEN combined with systemic lupus erythematosus (SLE) are even less common. Occasionally, acute cutaneous manifestations of SLE and SJS/TEN can be phenotypically similar, both causing extensive epidermal necrosis. In this paper, we present a recent case of a 32-year-old female SLE patient with a drug-induced (the health product, astaxanthin) TEN/SJS. To provide context to this case, we have reviewed relevant case studies published in English, accessed via PubMed databases. The search covers all published case studies from 1988 to 2019. We collected a total of 30 cases in the literature, and analyzed their characteristics from the aspects of gender, suspicious medication history, and treatment in order to expand clinicians' approach to diagnosis and treatment.
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Infections à VIH , Lupus érythémateux disséminé , Syndrome de Stevens-Johnson , Adulte , Femelle , Infections à VIH/complications , Humains , Lupus érythémateux disséminé/complications , Nécrose , Syndrome de Stevens-Johnson/diagnostic , Syndrome de Stevens-Johnson/étiologie , Syndrome de Stevens-Johnson/anatomopathologieRÉSUMÉ
BACKGROUND: The aim of this study is to investigate a new mechanism that may affect spontaneous abortions (SA): Can long interspersed nuclear element-1 (LINE-1) insertions in embryo cells lead to early SA? METHODS: The method involves prospective study on new mechanism of human early SA. Twenty SA tissues and 10 induced abortion (IA) tissues were utilized for this experiment. Western Blot, Immunohistochemistry (IHC), and reverse transcription-polymerase chain reaction were used to analyze different LINE-1 proteins and mRNA expression between early SA tissues and early IA tissues. SPSS software version 21.0 was used for statistical analysis. RESULTS: Western Blot demonstrated that the LINE-1 protein expression in SA tissues (Mean: 60.2%) is higher than in IA tissues (Mean: 30.3%) in 91% of the compared samples. reverse transcription-polymerase chain reaction showed that LINE-1 mRNA expression in SA tissues (Mean: 64.2%) is higher than in IA tissues (Mean: 29.2%) in 6 primer pairs in 89% of the compared samples. IHC showed that the LINE-1 protein expression in SA tissues (Mean: 59.2%) is higher than in IA tissues (Mean: 28.8%) in 83% of the compared samples. CONCLUSIONS: Expression of LINE-1 in early SA tissues is higher than in IA tissues, LINE-1 may lead to early SA and LINE-1 plays a role in early SA, this shows that a new mechanism may be involved in SA.
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Avortement provoqué , Avortement spontané , Grossesse , Femelle , Humains , Avortement spontané/génétique , Rétroéléments/génétique , Études prospectives , ARN messager/génétiqueRÉSUMÉ
OBJECTIVE: To explore the clinical features, treatment and prognosis of ductal adenocarcinoma of the prostate (DAP) and get a deeper insight into the malignancy. METHODS: We retrospectively studied the clinical data on 45 cases of confirmed DAP, 26 in the high-risk group and 19 in the medium-risk group, treated from January 2013 to September 2020. We compared the time and rate of biochemical recurrence and the rate of imaging progression between the two groups of patients, and evaluated the effect of palliative transurethral bipolar plasma resection of the prostate (pTU-PKRP) on the lower urinary tract symptoms (LUTS). RESULTS: Of the 45 cases of DAP, 4 (8.9%) were of the simple type, and 41 (91.1%) complicated by prostatic acinar carcinoma (PAA). And of the latter 41 cases, 9 (21.9%) were complicated by neuroendocrine differentiation and another 4 (9.8%) by intraductal carcinoma. The time to biochemical recurrence was longer in the medium-risk than in the high-risk group (P < 0.05). No statistically significant differences were observed in the rates of biochemical recurrence and imaging progression between the two groups (P > 0.05). The maximum urinary flow rate (Qmax), postvoid residual urine volume (PVR), IPSS and QOL of the patients were significantly improved at 6 months after pTU-PKRP compared with the baseline (P < 0.05). CONCLUSION: Radical prostatectomy can improve the prognosis of early DAP, while for advanced DAP with serious LUTS, pTU-PKRP can improve the quality of life of the patients.