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Importance: Ovarian torsion is a gynecological emergency caused by the twisting of the ovary and/or fallopian tube, further resulting in ischemic changes of the adnexa. Early diagnosis is likely to preserve ovarian function. Objective: The purpose of this review is to review the current findings of ovarian torsion including clinical presentations, diagnostic criteria, surgical procedures, and prognosis. Evidence Acquisition: The literature search is mainly available in PubMed and Web of Science platforms by searching "ovarian torsion" combined with one or several terms including "diagnosis" "risk factors" "surgery" and "torsion recurrence." Results: Abdominal pain, nausea, and vomiting were normal clinical presentations. In order to increase the accuracy of diagnosis, it is necessary to integrate clinical presentation and the findings of imaging and laboratory examinations. Computed tomography findings, plasma d-dimer level, and the time from pain onset play a critical role in distinguishing ovarian necrosis. The efficiency of oophoropexy on preventing recurrent ovarian torsion is controversial. Conclusion: Most patients with early diagnosis of ovarian torsion may have a better prognosis with conservative surgery. Relevance: Better understanding of ovarian torsion is critical for gynecologists to promote accuracy of diagnosis and select the optimal surgical procedure.
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Torção Ovariana , Humanos , Feminino , Torção Ovariana/diagnóstico , Prognóstico , Anormalidade Torcional/diagnósticoRESUMO
RATIONALE: Endometrial stromal sarcoma is an extremely rare mesenchymal neoplasm occurring in the extrauterine. Retroperitoneal endometrial stromal sarcoma with multiple pulmonary metastases, in particular, is extremely rare. PATIENT CONCERNS: Forty-seven-year-old woman (gravida 3, para 2), was referred to our institution with complaints of fever. DIAGNOSES: Ultrasound and computed tomographic imaging of the abdomen identified the presence of masses in the pelvic region. Additionally, computed tomographic scans and X-ray evaluations of the thorax detected dispersed masses in both the lungs and pelvic area. Histopathological analysis of the pelvic region indicated the presence of low-grade endometrial stromal sarcoma. A computed tomography-guided pneumocentesis was conducted to further characterize the pulmonary lesions, confirming the diagnosis of low-grade endometrial stromal sarcoma. INTERVENTIONS: The patient underwent tumor resection, subsequent treatment with Medroxyprogesterone acetate for 6 months, received microwave ablation for multiple lung metastases, PARP1 inhibitor for 4 courses, and has been undergoing chemotherapy (epirubicin/ifosfamide) up to the present time. OUTCOMES: Partial remission was obtained after the above treatment and this patient is now still alive maintaining for 3 years. LESSONS: The identification and management of this disease remain a significant challenge due to its low prevalence. Further research involving a larger number of cases is necessary to ensure consistency in diagnosis and to establish effective treatment guidelines.
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Neoplasias do Endométrio , Neoplasias Pulmonares , Neoplasias Retroperitoneais , Sarcoma do Estroma Endometrial , Humanos , Feminino , Neoplasias Pulmonares/secundário , Neoplasias Pulmonares/patologia , Sarcoma do Estroma Endometrial/secundário , Sarcoma do Estroma Endometrial/patologia , Sarcoma do Estroma Endometrial/terapia , Pessoa de Meia-Idade , Neoplasias Retroperitoneais/secundário , Neoplasias Retroperitoneais/patologia , Neoplasias Retroperitoneais/terapia , Neoplasias do Endométrio/patologia , Neoplasias do Endométrio/terapia , Tomografia Computadorizada por Raios XRESUMO
Background: Stickler syndrome type I (STL1) is an autosomal dominant disorder characterized by ocular, auditory, orofacial, and skeletal anomalies. The main causes of STL1 are variants in the COL2A1 gene, which encodes a type II collagen precursor protein. The specific focus of this study was on a newborn from China diagnosed with STL1, with the aim of providing novel insights into the effects of a newly identified intronic variant in the COL2A1 gene on pre-mRNA splicing. Methods: Trio whole exome sequencing was used to identify the causative variant in the family. The identified variant was validated using Sanger sequencing. Bioinformatics programs were used to predict the pathogenicity of the candidate variant. Additionally, an in vitro minigene assay was used to investigate the effects of the identified variant on RNA splicing. Results: The proband with STL1 had a novel heterozygous splicing variant in the intron nine acceptor donor site of COL2A1 (c.655-2A>G). This splice junction variant resulted in aberrant COL2A1 mRNA splicing, leading to the skipping of exon 10 and the production of a shorter protein that may lack the last 18 native amino acids. Conclusion: The c.655-2A>G variant in the COL2A1 gene leads to STL1 through abnormal splicing. By expanding the spectrum of variants in the COL2A1 gene, this finding improves the clinical understanding of STL1 and provides guidance for early diagnosis and disease counseling.
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Necroptosis is a crucial modality of programmed cell death characterized by distinct morphological and biochemical hallmarks, including cell membrane rupture, organelle swelling, cytoplasmic and nuclear disintegration, cellular contents leakage, and release of damage-associated molecular patterns (DAMPs), accompanied by the inflammatory responses. Studies have shown that necroptosis is involved in the etiology and evolution of a variety of pathologies including organ damage, inflammation disorders, and cancer. Despite its significance, the field of necroptosis research grapples with the challenge of non-standardized detection methodologies. In this review, we introduce the fundamental concepts and molecular mechanisms of necroptosis and critically appraise the principles, merits, and inherent limitations of current detection technologies. This endeavor seeks to establish a methodological framework for necroptosis detection, thereby propelling deeper insights into the research of cell necroptosis.
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BACKGROUND: Wnt/FZD-mediated signaling pathways are activated in more than 90% of hepatocellular carcinoma (HCC) cell lines. As a well-known secretory glycoprotein, Wnt3 can interact with FZD receptors on the cell surface, thereby activating the Wnt/ß-catenin signaling pathway. However, the N-glycosylation modification site of Wnt3 and the effect of this modification on the biological function of the protein are still unclear. AIM: To investigate the effect of Wnt3 N-glycosylation on the biological function of HCC cells. METHODS: Site-directed mutagenesis was used to verify the Wnt3 N-glycosylation sites, actinomycin D treatment was used to detect the stability of Wnt3 after site-directed mutation, the binding of the N-glycosylation site-directed mutant Wnt3 to FZD7 was observed by laser confocal microscopy, and the effects of the N-glycosylation site-directed mutation of Wnt3 on the Wnt/ß-catenin signaling pathway and the progression of HCC cells were detected by western blot and cell function experiments. RESULTS: Wnt3 has two N-glycosylation-modified sites (Asn90 and Asn301); when a single site at amino acid 301 is mutated, the stability of Wnt3 is weakened; the binding ability of Wnt3 to FZD7 decreases when both sites are mutated simultaneously; and the level of proteins related to the Wnt/ß-catenin signaling pathway is downregulated. Cell proliferation, migration and invasion are also weakened in the case of single 301 site and double-site mutations. CONCLUSION: These results indicate that by inhibiting the N-glycosylation of Wnt3, the proliferation, migration, invasion and colony formation abilities of liver cancer cells can be weakened, which might provide new therapeutic strategies for clinical liver cancer in the future.
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Mortality rates due to lung cancer are high worldwide. Although PD-1 and PD-L1 immune checkpoint inhibitors boost the survival of patients with non-small-cell lung cancer (NSCLC), resistance often arises. The Warburg Effect, which causes lactate build-up and potential lysine-lactylation (Kla), links immune dysfunction to tumor metabolism. The role of non-histone Kla in tumor immune microenvironment and immunotherapy remains to be clarified. Here, global lactylome profiling and metabolomic analyses of samples from patients with NSCLC is conducted. By combining multi-omics analysis with in vitro and in vivo validation, that intracellular lactate promotes extracellular lipolysis through lactyl-APOC2 is revealed. Mechanistically, lactate enhances APOC2 lactylation at K70, stabilizing it and resulting in FFA release, regulatory T cell accumulation, immunotherapy resistance, and metastasis. Moreover, the anti-APOC2K70-lac antibody that sensitized anti-PD-1 therapy in vivo is developed. This findings highlight the potential of anti lactyl-APOC2-K70 approach as a new combination therapy for sensitizing immunotherapeutic responses.
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BACKGROUND: the relationship between vitamin D deficiency and carotid intima-media thickness (CIMT) in children and adolescents with obesity is unknown. The aim of this study was to investigate the correlation between vitamin D levels and CIMT in children and adolescents with obesity. METHODS: a total of 440 children and adolescents aged 6-16 with obesity were included in the study. Anthropometric measurements, blood pressure measurements, blood lipids, blood glucose, and vitamin D levels were measured. Bilateral carotid ultrasound was performed to assess CIMT. The relationships between vitamin D levels and CIMT were assessed using multivariate linear regression with Generalized Linear Models and restricted cubic splines. Binary logistic regression analyses were conducted to explore the association between vitamin D status and the risk of abnormal CIMT. RESULTS: vitamin D levels were inversely correlated with CIMT in subjects with serum 25-hydroxyvitamin D [25(OH)D] levels less than or equal to 50 nmol/L (ß = -0.147, 95 % CI [-0.263, -0.030], p = 0.013), but this correlation was not significant in subjects with serum 25(OH)D levels above 50 nmol/L. After correcting for various confounders, the risk of abnormal CIMT was significantly higher in the vitamin D deficiency group (OR = 2.080, 95 % CI [1.112, 3.891], p = 0.022). CONCLUSIONS: vitamin D deficiency is an independent risk factor for abnormal CIMT, and vitamin D deficiency may play a promoting role in the atherosclerotic process in children and adolescents with obesity.
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BACKGROUND: There is little evidence to comprehensively summarize the adverse events (AEs) profile of intermittent fasting (IF) despite its widespread use in patients with overweight or obesity. METHODS: We searched the main electronic databases and registry websites to identify eligible randomized controlled trials (RCTs) comparing IF versus control groups. A direct meta-analysis using a fixed-effect model was conducted to pool the risk differences regarding common AEs and dropouts. Study quality was assessed by using the Jadad scale. Pre-specified subgroup and sensitivity analyses were conducted to explore potential heterogeneity. RESULTS: A total of 15 RCTs involving 1,365 adult individuals were included. Findings did not show a significant difference between IF and Control in risk rate of fatigue [0%, 95% confidence interval (CI), -1% to 2%; P = 0.61], headache [0%, 95%CI: -1% to 2%; P = 0.86] and dropout [1%, 95%CI: -2% to 4%; P = 0.51]. However, a numerically higher risk of dizziness was noted among the IF alone subgroup with non-early time restricted eating [3%, 95%CI: -0% to 6%; P = 0.08]. CONCLUSIONS: This meta-analysis suggested that IF was not associated with a greater risk of AEs in adult patients affected by overweight or obesity. Additional large-scale RCTs stratified by key confounders and designed to evaluate the long-term effects of various IF regimens are needed to ascertain these AEs profile.
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Jejum Intermitente , Obesidade , Sobrepeso , Ensaios Clínicos Controlados Aleatórios como Assunto , Adulto , Humanos , Tontura , Fadiga , Cefaleia , Jejum Intermitente/efeitos adversosRESUMO
Ovarian aging, a complex and challenging concern within the realm of reproductive medicine, is associated with reduced fertility, menopausal symptoms and long-term health risks. Our previous investigation revealed a correlation between Peroxiredoxin 4 (PRDX4) and human ovarian aging. The purpose of this research was to substantiate the protective role of PRDX4 against ovarian aging and elucidate the underlying molecular mechanism in mice. In this study, a Prdx4-/- mouse model was established and it was observed that the deficiency of PRDX4 led to only an accelerated decline of ovarian function in comparison to wild-type (WT) mice. The impaired ovarian function observed in this study can be attributed to an imbalance in protein homeostasis, an exacerbation of endoplasmic reticulum stress (ER stress), and ultimately an increase in apoptosis of granulosa cells. Furthermore, our research reveals a noteworthy decline in the expression of Follicle-stimulating hormone receptor (FSHR) in aging Prdx4-/- mice, especially the functional trimer, due to impaired disulfide bond formation. Contrarily, the overexpression of PRDX4 facilitated the maintenance of protein homeostasis, mitigated ER stress, and consequently elevated E2 levels in a simulated KGN cell aging model. Additionally, the overexpression of PRDX4 restored the expression of the correct spatial conformation of FSHR, the functional trimer. In summary, our research reveals the significant contribution of PRDX4 in delaying ovarian aging, presenting a novel and promising therapeutic target for ovarian aging from the perspective of endoplasmic reticulum protein homeostasis.
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Envelhecimento , Estresse do Retículo Endoplasmático , Células da Granulosa , Camundongos Knockout , Ovário , Peroxirredoxinas , Proteostase , Animais , Feminino , Peroxirredoxinas/metabolismo , Peroxirredoxinas/genética , Células da Granulosa/metabolismo , Células da Granulosa/patologia , Camundongos , Envelhecimento/metabolismo , Envelhecimento/patologia , Ovário/metabolismo , Ovário/patologia , Humanos , Apoptose , Receptores do FSH/metabolismo , Receptores do FSH/genéticaRESUMO
Background: Rotor syndrome (RS, OMIM#237450) is an extremely rare autosomal digenic recessive disorder characterized by mild non-hemolytic hereditary conjugated hyperbilirubinemia, caused by biallelic variation of SLCO1B1 and SLCO1B3 genes that resulted in OATP1B1/B3 dysfunction in the sinusoidal membrane leading to impaired bilirubin reuptake ability of hepatocytes. Methods: One RS pedigree was recruited and clinical features were documented. Whole genome second-generation sequencing was used to screen candidate genes and mutations, Sanger sequencing confirmed predicted mutations. Results: This study detected a homozygous nonsense variant c.1738C > T (p.R580*) in the coding region of the SLCO1B1 (NM006446) gene in a family with RS and hepatitis B virus infection by Variants analysis and Sanger sequencing, and confirmed by Copy Number Variation (CNV) analysis and Long Range PCR that there was a homozygous insertion of intron 5 of the SLCO1B3 gene into intron 5 of long-interspersed element 1 (LINE1). A few cases of such haplotypes have been reported in East Asian populations. A hepatitis B virus infection with fatty liver disease was indicated by pathology, which revealed mild-moderate lobular inflammation, moderate lobular inflammation, moderate hepatocellular steatosis, and fibrosis stage 1-2 (NAS score: 4 points/S1-2) alterations. Heterozygotes carrying p.R580* and LINE1 insertions were also detected in family members (I1, I2, III2, III3), but they did not develop conjugated hyperbilirubinemia. Conclusion: The mutations may be the molecular genetic foundation for the presence of SLCO1B1 c.1738C > T(p.R580*) and SLCO1B3 (LINE1) in this RS pedigree.
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BACKGROUND: Severe pneumonia is a common severe respiratory infection worldwide, and its treatment is challenging, especially for patients in the intensive care unit (ICU). AIM: To explore the effect of communication and collaboration between nursing teams on the treatment outcomes of patients with severe pneumonia in ICU. METHODS: We retrospectively analyzed 60 patients with severe pneumonia who were treated at the ICU of the hospital between January 1, 2021 and December 31, 2023. We compared and analyzed the respiratory mechanical indexes [airway resistance (Raw), mean airway pressure (mPaw), peak pressure (PIP)], blood gas analysis indexes (arterial oxygen saturation, arterial oxygen partial pressure, and oxygenation index), and serum inflammatory factor levels [C-reactive protein (CRP), procalcitonin (PCT), cortisol (COR), and high mobility group protein B1 (HMGB1)] of all patients before and after treatment. RESULTS: Before treatment, there was no significant difference in respiratory mechanics index and blood gas analysis index between 2 groups (P > 0.05). However, after treatment, the respiratory mechanical indexes of patients in both groups were significantly improved, and the improvement of Raw, mPaw, plateau pressure, PIP and other indexes in the combined group after communication and collaboration with the nursing team was significantly better than that in the single care group (P < 0.05). The serum CRP and PCT levels of patients were significantly decreased, and the difference was statistically significant compared with that of nursing group alone (P < 0.05). The levels of serum COR and HMGB1 before and after treatment were also significantly decreased between the two groups. CONCLUSION: The communication and collaboration of the nursing team have a significant positive impact on respiratory mechanics indicators, blood gas analysis indicators and serum inflammatory factor levels in the treatment of severe pneumonia patients in ICU.
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BACKGROUND: Primary ciliary dyskinesia (PCD) is an autosomal recessive hereditary disease characterized by recurrent respiratory infections. In clinical manifestations, DNAH5 (NM_001361.3) is one of the recessive pathogenic genes. Primary familial brain calcification (PFBC) is a neurodegenerative disease characterized by bilateral calcification in the basal ganglia and other brain regions. PFBC can be inherited in an autosomal dominant or recessive manner. A family with PCD caused by a DNAH5 compound heterozygous variant and PFBC caused by a MYORG homozygous variant was analyzed. METHODS: In this study, we recruited three generations of Han families with primary ciliary dyskinesia combined with primary familial brain calcification. Their clinical phenotype data were collected, next-generation sequencing was performed to screen suspected pathogenic mutations in the proband and segregation analysis of families was carried out by Sanger sequencing. The mutant and wild-type plasmids were constructed and transfected into HEK293T cells instantaneously, and splicing patterns were detected by Minigene splicing assay. The structure and function of mutations were analyzed by bioinformatics analysis. RESULTS: The clinical phenotypes of the proband (II10) and his sister (II8) were bronchiectasis, recurrent pulmonary infection, multiple symmetric calcifications of bilateral globus pallidus and cerebellar dentate nucleus, paranasal sinusitis in the whole group, and electron microscopy of bronchial mucosa showed that the ciliary axoneme was defective. There was also total visceral inversion in II10 but not in II8. A novel splice variant C.13,338 + 5G > C and a frameshift variant C.4314delT (p. Asn1438lysfs *10) were found in the DNAH5 gene in proband (II10) and II8. c.347_348dupCTGGCCTTCCGC homozygous insertion variation was found in the MYORG of the proband. The two pathogenic genes were co-segregated in the family. Minigene showed that DNAH5 c.13,338 + 5G > C has two abnormal splicing modes: One is that part of the intron bases where the mutation site located is translated, resulting in early translation termination of DNAH5; The other is the mutation resulting in the deletion of exon76. CONCLUSIONS: The newly identified DNAH5 splicing mutation c.13,338 + 5G > C is involved in the pathogenesis of PCD in the family, and forms a compound heterozygote with the pathogenic variant DNAH5 c.4314delT lead to the pathogenesis of PCD.
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Calcinose , Mutação , Linhagem , Humanos , Masculino , Calcinose/genética , Calcinose/patologia , Feminino , Dineínas do Axonema/genética , Adulto , Transtornos da Motilidade Ciliar/genética , Encefalopatias/genética , Fenótipo , Células HEK293 , China , Splicing de RNA/genética , Pessoa de Meia-Idade , Glicosídeo HidrolasesRESUMO
Viral diseases are becoming an important problem in Amorphophallus production due to the propagation of seed corms and their trade across regions. In this study, combined-High-Throughput Sequencing, RT-PCR, electron microscopy, and mechanical inoculation were used to analyze virus-like infected Amorphophallus samples in Yunnan province to investigate the distribution, molecular characterization, and diversity and evolution of Amorphophallus-infecting viruses including three isolates of dasheen mosaic virus and three orthotospoviruses: mulberry vein banding associated virus (MVBaV), tomato zonate spot virus (TZSV) and impatiens necrotic spot virus (INSV). The results showed that DsMV is the dominant virus infecting Amorphophallus, mixed infections with DsMV and MVBaV to Amorphophallus were quite common in Yunnan province, China. This is the first report on infection of Amorphophallus with MVBaV, TZSV, and impatiens necrotic spot virus (INSV) in China. This work will help to develop an effective integrated management strategy to control the spread of Amorphophallus viral diseases.
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Filogenia , Doenças das Plantas , China , Doenças das Plantas/virologia , Vírus de Plantas/isolamento & purificação , Vírus de Plantas/genética , Sequenciamento de Nucleotídeos em Larga Escala , RNA Viral/genéticaRESUMO
BACKGROUND: Type 2 diabetes is associated with a variety of complications, including micro- and macrovascular complications, neurological manifestations and poor wound healing. Adhering to a Mediterranean Diet (MED) is generally considered an effective intervention in individuals at risk for type 2 diabetes mellitus (T2DM). However, little is known about its effect with respect to the different specific manifestations of T2DM. This prompted us to explore the effect of MED on the three most significant microvascular complications of T2DM: diabetic retinopathy (DR), diabetic kidney disease (DKD), and vascular diabetic neuropathies (DN). METHODS: We examined the association between the MED and the incidence of these microvascular complications in a prospective cohort of 33,441 participants with hyperglycemia free of microvascular complications at baseline, identified in the UK Biobank. For each individual, we calculated the Alternate Mediterranean Diet (AMED) score, which yields a semi-continuous measure of the extent to which an individual's diet can be considered as MED. We used Cox proportional hazard models to analyze hazard ratios (HRs) and 95% confidence intervals (CIs), adjusting for demographics, lifestyle factors, medical histories and cardiovascular risk factors. RESULTS: Over a median of 12.3 years of follow-up, 3,392 cases of microvascular complications occurred, including 1,084 cases of diabetic retinopathy (DR), 2,184 cases of diabetic kidney disease (DKD), and 632 cases of diabetic neuropathies (DN), with some patients having 2 or 3 microvascular complications simultaneously. After adjusting for confounders, we observed that higher AMED scores offer protection against DKD among participants with hyperglycemia (comparing the highest AMED scores to the lowest yielded an HR of 0.79 [95% CIs: 0.67, 0.94]). Additionally, the protective effect of AMED against DKD was more evident in the hyperglycemic participants with T2DM (HR, 0.64; 95% CI: 0.50, 0.83). No such effect, however, was seen for DR or DN. CONCLUSIONS: In this prospective cohort study, we have demonstrated that higher adherence to a MED is associated with a reduced risk of DKD among individuals with hyperglycemia. Our study emphasizes the necessity for continued research focusing on the benefits of the MED. Such efforts including the ongoing clinical trial will offer further insights into the role of MED in the clinical management of DKD.
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Diabetes Mellitus Tipo 2 , Nefropatias Diabéticas , Dieta Mediterrânea , Hiperglicemia , Humanos , Estudos Prospectivos , Masculino , Feminino , Pessoa de Meia-Idade , Nefropatias Diabéticas/dietoterapia , Nefropatias Diabéticas/epidemiologia , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/epidemiologia , Diabetes Mellitus Tipo 2/dietoterapia , Idoso , Hiperglicemia/epidemiologia , Hiperglicemia/complicações , Adulto , Reino Unido/epidemiologia , Retinopatia Diabética/epidemiologia , Retinopatia Diabética/dietoterapia , Incidência , Neuropatias Diabéticas/epidemiologia , Neuropatias Diabéticas/dietoterapia , Fatores de RiscoRESUMO
Objective: We aimed to use the onset time of Alzheimer's disease (AD) as the reference time to longitudinally investigate the atrophic characteristics of brain structures prior to the onset of AD. Materials and methods: A total of 328 participants from the ADNI database with clear onset of AD and structural imaging data were included in our study. The time before the onset of AD (abbreviated as BAD) was calculated. We investigated the longitudinal brain changes in 97 regions using multivariate linear mixed effects regression models. Results: The average BAD was -28.15 months, with a range from -156 to 0 months. The 54 brain regions showed significant atrophy prior to the onset of AD, and these regions were mainly distributed in the frontal and temporal lobes. The parietal and occipital lobe exhibited relatively less atrophy than the other brain lobes. Sex, age, and magnetic field strength had greater direct impacts on structural indicators than APOE genotype and education. The analysis of interaction effects revealed that the APOE ε4 mutation carriers exhibited more severe structural changes in specific brain regions as the BAD increased. However, sex, age, and education had minimal regulatory influence on the structural changes associated with BAD. Conclusion: Longitudinal analysis, with the onset time point of AD as the reference, can accurately describe the features of structural changes preceding the onset of AD and provide a comprehensive understanding of AD development.
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Notoginseng leaf triterpenes (PNGL), derived from the dried stems and leaves of P. notoginseng, is a phytoestrogen that exerts many neuroprotective effects in vivo and in vitro of ischemic stroke. However, its impact on neurological restoration specifically in relation to angiogenesis following ischemic stroke remains unexplored. The aim of this study was to assess the effects of PNGL on angiogenesis subsequent to ischemic stroke. Male Sprague-Dawley rats were utilized in this study and were subjected to middle cerebral artery occlusion/reperfusion (MCAO/R). Post-ischemia, PNGL were administered through intraperitoneal (i.p.) injection. The high-performance liquid chromatography (HPLC) fingerprinting, triphenyltetrazolium chloride (TTC) staining, immunofluorescent staining, network pharmacology and western blot analyses were assessed to determine the therapeutical effect and molecular mechanisms of PNGL on cerebral ischemia/reperfusion injury. Our findings demonstrate that PNGL effectively reduced infarct volume, enhanced cerebral blood flow, and induced angiogenesis in rats subjected to MCAO/R. Notably, PNGL also facilitated neuronal proliferation and migration in HUMECs in vitro. The proangiogenic effects of PNGL were found to be linked to the activation of the nuclear factor erythroid 2-related factor 2 (Nrf2) pathway and the AMPK/SIRT1-mediated PGC-1/ERα axis, as well as the activation of neurological function. Our study provides evidence that PNGL hold promise as an active ingredient of inducing proangiogenic effects, potentially through the activation of the Nrf2 pathway and the AMPK/SIRT1-mediated PGC-1/ERα axis. These findings contribute to the understanding of novel mechanisms involved in the restoration of neurological function following PNGL treatment for ischemic stroke.
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AVC Isquêmico , Fator 2 Relacionado a NF-E2 , Panax notoginseng , Folhas de Planta , Ratos Sprague-Dawley , Sirtuína 1 , Triterpenos , Animais , Masculino , Fator 2 Relacionado a NF-E2/metabolismo , Ratos , Sirtuína 1/metabolismo , AVC Isquêmico/tratamento farmacológico , Triterpenos/farmacologia , Triterpenos/isolamento & purificação , Panax notoginseng/química , Folhas de Planta/química , Humanos , Fármacos Neuroprotetores/farmacologia , Proteínas Quinases Ativadas por AMP/metabolismo , Transdução de Sinais/efeitos dos fármacos , Infarto da Artéria Cerebral Média/tratamento farmacológico , Neovascularização Fisiológica/efeitos dos fármacos , China , Traumatismo por Reperfusão/tratamento farmacológico , Indutores da Angiogênese/farmacologia , AngiogêneseRESUMO
Electrocatalytic oxidation of formaldehyde (FOR) is an effective way to prevent the damage caused by formaldehyde and produce high-value products. A screening strategy of a single-layer MnO2-supported transition metal catalyst for the selective oxidation of formaldehyde to formic acid was designed by high-throughput density functional calculation. N-MnO2@Cu and MnO2@Cu are predicted to be potential FOR electrocatalysts with potential-limiting steps (PDS) of 0.008 and -0.009 eV, respectively. Electronic structure analysis of single-atom catalysts (SACs) shows that single-layer MnO2 can regulate the spin density of loaded transition metal and thus regulate the adsorption of HCHO (Ead), and Ead is volcanically distributed with the magnetic moment descriptor -|mM - mH|. In addition, the formula quantifies Ead and |mM - mH| to construct a volcano-type descriptor α describing the PDS [ΔG(*CHO)]. Other electronic and structural properties of SACs and α are used as input features for the GBR method to construct machine learning models predicting the PDS (R2 = 0.97). This study hopes to provide some insights into FOR electrocatalysts.
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BACKGROUND: Zinc finger E-box binding homEeobox 1 (ZEB1) and ZEB2 are two anoikis-related transcription factors. The mRNA expressions of these two genes are significantly increased in kidney renal clear cell carcinoma (KIRC), which are associated with poor survival. Meanwhile, the mechanisms and clinical significance of ZEB1 and ZEB2 upregulation in KIRC remain unknown. METHODS: Through the Cancer Genome Atlas (TCGA) database and Gene Expression Omnibus (GEO) database, expression profiles, prognostic value and receiver operating characteristic curves (ROCs) of ZEB1 and ZEB2 were evaluated. The correlations of ZEB1 and ZEB2 with anoikis were further assessed in TCGA-KIRC database. Next, miRTarBase, miRDB, and TargetScan were used to predict microRNAs targeting ZEB1 and ZEB2, and TCGA-KIRC database was utilized to discern differences in microRNAs and establish the association between microRNAs and ZEBs. TCGA, TIMER, TISIDB, and TISCH were used to analyze tumor immune infiltration. RESULTS: It was found that ZEB1 and ZEB2 expression were related with histologic grade in KIRC patient. Kaplan-Meier survival analyses showed that KIRC patients with low ZEB1 or ZEB2 levels had a significantly lower survival rate. Meanwhile, ZEB1 and ZEB2 are closely related to anoikis and are regulated by microRNAs. We constructed a risk model using univariate Cox and LASSO regression analyses to identify two microRNAs (hsa-miR-130b-3p and hsa-miR-138-5p). Furthermore, ZEB1 and ZEB2 regulate immune cell invasion in KIRC tumor microenvironments. CONCLUSIONS: Anoikis, cytotoxic immune cell infiltration, and patient survival outcomes were correlated with ZEB1 and ZEB2 mRNA upregulation in KIRC. ZEB1 and ZEB2 are regulated by microRNAs.
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Anoikis , Biomarcadores Tumorais , Carcinoma de Células Renais , Neoplasias Renais , MicroRNAs , Homeobox 2 de Ligação a E-box com Dedos de Zinco , Homeobox 1 de Ligação a E-box em Dedo de Zinco , Humanos , Carcinoma de Células Renais/genética , Carcinoma de Células Renais/patologia , Carcinoma de Células Renais/imunologia , Neoplasias Renais/genética , Neoplasias Renais/patologia , Neoplasias Renais/imunologia , Homeobox 1 de Ligação a E-box em Dedo de Zinco/genética , Prognóstico , Anoikis/genética , Biomarcadores Tumorais/genética , MicroRNAs/genética , Homeobox 2 de Ligação a E-box com Dedos de Zinco/genética , Homeobox 2 de Ligação a E-box com Dedos de Zinco/metabolismo , Regulação Neoplásica da Expressão Gênica , Masculino , Feminino , Estimativa de Kaplan-MeierRESUMO
BACKGROUND: Intertrochanteric fracture of the femur occurs mostly among older people, and seriously affects daily life and quality of life. At present, physical intervention, drug treatment, routine intervention and rehabilitation training are widely used for prevention of side effects, but it is still inconclusive which intervention has the best effect. AIM: To compare the effects of new intervention measures for preventing side effects of artificial joint replacement. METHODS: We searched the Chinese and English literatures for comparative studies on the prevention of side effects of new interventions for artificial joint replacement from July 2013 to June 2023 in China HowNet, PubMed, Wanfang, Weipu and other databases. Study quality was evaluated by improved Jadad scoring standard, and the effects of different interventions on preventing different complications were analyzed by meta-analysis of evidence-based medicine with Review Manager 5.0 software. RESULTS: Ten articles, including 869 cases, were finally included. The preventive effects of different interventions on the side effects of artificial joint replacement were studied, and valid data were extracted. There were two articles on the preventive effects of drug intervention, four on comparison of the preventive effects of combined and single interventions, and three on the preventive effects of physical intervention, rehabilitation training and routine intervention. Meta-analysis showed that the preventive effect of rivaroxaban was significantly better than low molecular weight heparin calcium [mean difference (MD) = -0.16, 95%CI: -0.28 to -0.04, P < 0.05]. The effect of combined intervention was significantly better than that of single intervention (MD = -0.08, 95%CI: -0.16 to -0.01, P < 0.001). Physical intervention was significantly better than routine intervention and rehabilitation training (MD = 0.26, 95%CI: 0.16-0.36, P < 0.001). CONCLUSION: Rivaroxaban combined with rehabilitation training is preferred for preventing deep vein thrombosis after artificial joint replacement. In the prevention of pulmonary embolism, rivaroxaban drug intervention is given priority. The effect of combined intervention is better than that of single intervention.
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Constructing a built-in interfacial electric field (BIEF) is an effective approach to enhance the electrocatalysts performance, but it has been rarely demonstrated for electrochemical carbon dioxide reduction reaction (CO2RR) to date. Herein, for the first time, SnO2/LaOCl nanofibers (NFs) with BIEF is created by electrospinning, exhibiting a high Faradaic efficiency (FE) of 100% C1 product (CO and HCOOH) at -0.9--1.1 V versus reversible hydrogen electrode (RHE) and a maximum FEHCOOH of 90.1% at -1.2 VRHE in H-cell, superior to the commercial SnO2 nanoparticles (NPs) and LaOCl NFs. SnO2/LaOCl NFs also exhibit outstanding stability, maintaining negligible activity degradation even after 10 h of electrolysis. Moreover, their current density and FEHCOOH are almost 400 mA cm-2 at -2.31 V and 83.4% in flow-cell. The satisfactory CO2RR performance of SnO2/LaOCl NFs with BIEF can be ascribed to tight interface of coupling SnO2 NPs and LaOCl NFs, which can induce charge redistribution, rich active sites, enhanced CO2 adsorption, as well as optimized Gibbs free energy of *OCHO. The work reveals that the BIEF will trigger interfacial accumulation and stability enhancement effects in promoting CO2RR activity and stability of SnO2-based materials, providing a novel approach to develop stable and efficient CO2RR electrocatalysts.