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To elucidate the deregulated functional modules that drive clear cell renal cell carcinoma (ccRCC), we performed comprehensive genomic, epigenomic, transcriptomic, proteomic, and phosphoproteomic characterization of treatment-naive ccRCC and paired normal adjacent tissue samples. Genomic analyses identified a distinct molecular subgroup associated with genomic instability. Integration of proteogenomic measurements uniquely identified protein dysregulation of cellular mechanisms impacted by genomic alterations, including oxidative phosphorylation-related metabolism, protein translation processes, and phospho-signaling modules. To assess the degree of immune infiltration in individual tumors, we identified microenvironment cell signatures that delineated four immune-based ccRCC subtypes characterized by distinct cellular pathways. This study reports a large-scale proteogenomic analysis of ccRCC to discern the functional impact of genomic alterations and provides evidence for rational treatment selection stemming from ccRCC pathobiology.
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Carcinoma de Células Renais/genética , Proteínas de Neoplasias/genética , Proteogenômica , Transcriptoma/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/imunologia , Carcinoma de Células Renais/imunologia , Carcinoma de Células Renais/patologia , Intervalo Livre de Doença , Exoma/genética , Feminino , Regulação Neoplásica da Expressão Gênica/genética , Genoma Humano/genética , Humanos , Masculino , Pessoa de Meia-Idade , Proteínas de Neoplasias/imunologia , Fosforilação Oxidativa , Fosforilação/genética , Transdução de Sinais/genética , Transcriptoma/imunologia , Microambiente Tumoral/genética , Microambiente Tumoral/imunologia , Sequenciamento do ExomaRESUMO
Whether synthetic genomes can power life has attracted broad interest in the synthetic biology field. Here, we report de novo synthesis of the largest eukaryotic chromosome thus far, synIV, a 1,454,621-bp yeast chromosome resulting from extensive genome streamlining and modification. We developed megachunk assembly combined with a hierarchical integration strategy, which significantly increased the accuracy and flexibility of synthetic chromosome construction. Besides the drastic sequence changes, we further manipulated the 3D structure of synIV to explore spatial gene regulation. Surprisingly, we found few gene expression changes, suggesting that positioning inside the yeast nucleoplasm plays a minor role in gene regulation. Lastly, we tethered synIV to the inner nuclear membrane via its hundreds of loxPsym sites and observed transcriptional repression of the entire chromosome, demonstrating chromosome-wide transcription manipulation without changing the DNA sequences. Our manipulation of the spatial structure of synIV sheds light on higher-order architectural design of the synthetic genomes.
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Núcleo Celular , Saccharomyces cerevisiae , Saccharomyces cerevisiae/genética , Cromossomos/genética , Genoma Fúngico , Biologia Sintética/métodosRESUMO
Mendelian randomization (MR) provides valuable assessments of the causal effect of exposure on outcome, yet the application of conventional MR methods for mapping risk genes encounters new challenges. One of the issues is the limited availability of expression quantitative trait loci (eQTLs) as instrumental variables (IVs), hampering the estimation of sparse causal effects. Additionally, the often context- or tissue-specific eQTL effects challenge the MR assumption of consistent IV effects across eQTL and GWAS data. To address these challenges, we propose a multi-context multivariable integrative MR framework, mintMR, for mapping expression and molecular traits as joint exposures. It models the effects of molecular exposures across multiple tissues in each gene region, while simultaneously estimating across multiple gene regions. It uses eQTLs with consistent effects across more than one tissue type as IVs, improving IV consistency. A major innovation of mintMR involves employing multi-view learning methods to collectively model latent indicators of disease relevance across multiple tissues, molecular traits, and gene regions. The multi-view learning captures the major patterns of disease relevance and uses these patterns to update the estimated tissue relevance probabilities. The proposed mintMR iterates between performing a multi-tissue MR for each gene region and joint learning the disease-relevant tissue probabilities across gene regions, improving the estimation of sparse effects across genes. We apply mintMR to evaluate the causal effects of gene expression and DNA methylation for 35 complex traits using multi-tissue QTLs as IVs. The proposed mintMR controls genome-wide inflation and offers insights into disease mechanisms.
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Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Análise da Randomização Mendeliana , Locos de Características Quantitativas , Humanos , Análise da Randomização Mendeliana/métodos , Estudo de Associação Genômica Ampla/métodos , Especificidade de Órgãos/genética , Modelos Genéticos , Polimorfismo de Nucleotídeo ÚnicoRESUMO
Cigarette smoking adversely affects many aspects of human health, and epigenetic responses to smoking may reflect mechanisms that mediate or defend against these effects. Prior studies of smoking and DNA methylation (DNAm), typically measured in leukocytes, have identified numerous smoking-associated regions (e.g., AHRR). To identify smoking-associated DNAm features in typically inaccessible tissues, we generated array-based DNAm data for 916 tissue samples from the GTEx (Genotype-Tissue Expression) project representing 9 tissue types (lung, colon, ovary, prostate, blood, breast, testis, kidney, and muscle). We identified 6,350 smoking-associated CpGs in lung tissue (n = 212) and 2,735 in colon tissue (n = 210), most not reported previously. For all 7 other tissue types (sample sizes 38-153), no clear associations were observed (false discovery rate 0.05), but some tissues showed enrichment for smoking-associated CpGs reported previously. For 1,646 loci (in lung) and 22 (in colon), smoking was associated with both DNAm and local gene expression. For loci detected in both lung and colon (e.g., AHRR, CYP1B1, CYP1A1), top CpGs often differed between tissues, but similar clusters of hyper- or hypomethylated CpGs were observed, with hypomethylation at regulatory elements corresponding to increased expression. For lung tissue, 17 hallmark gene sets were enriched for smoking-associated CpGs, including xenobiotic- and cancer-related gene sets. At least four smoking-associated regions in lung were impacted by lung methylation quantitative trait loci (QTLs) that co-localize with genome-wide association study (GWAS) signals for lung function (FEV1/FVC), suggesting epigenetic alterations can mediate the effects of smoking on lung health. Our multi-tissue approach has identified smoking-associated regions in disease-relevant tissues, including effects that are shared across tissue types.
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Fumar Cigarros , Metilação de DNA , Masculino , Feminino , Humanos , Metilação de DNA/genética , Epigênese Genética , Estudo de Associação Genômica Ampla , Fumar/efeitos adversos , Fumar/genética , Expressão GênicaRESUMO
Recently a dark matter-electron (DM-electron) paradigm has drawn much attention. Models beyond the standard halo model describing DM accelerated by high energy celestial bodies are under intense examination as well. In this Letter, a velocity components analysis (VCA) method dedicated to swift analysis of accelerated DM-electron interactions via semiconductor detectors is proposed and the first HPGe detector-based accelerated DM-electron analysis is realized. Utilizing the method, the first germanium based constraint on sub-GeV solar reflected DM-electron interaction is presented with the 205.4 kg·day dataset from the CDEX-10 experiment. In the heavy mediator scenario, our result excels in the mass range of 5-15 keV/c^{2}, achieving a 3 orders of magnitude improvement comparing with previous semiconductor experiments. In the light mediator scenario, the strongest laboratory constraint for DM lighter than 0.1 MeV/c^{2} is presented. The result proves the feasibility and demonstrates the vast potential of the VCA technique in future accelerated DM-electron analyses with semiconductor detectors.
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OBJECTIVE: Small-for-gestational-age (SGA) neonates are at increased risk of perinatal mortality and morbidity. We aimed to investigate the performance of uterine artery pulsatility index (UtA-PI) at 19-24 weeks' gestation to predict the delivery of a SGA neonate in a Chinese population. METHODS: This was a retrospective cohort study using data obtained between January 2010 and June 2018. Doppler ultrasonography was performed at 19-24 weeks' gestation. SGA was defined as birth weight below the 10th centile according to the INTERGROWTH-21st fetal growth standards. The performance of UtA-PI to predict the delivery of a SGA neonate was assessed using receiver-operating-characteristics (ROC)-curve analysis. RESULTS: We included 6964 singleton pregnancies, of which 748 (11%) delivered a SGA neonate, including 115 (15%) women with preterm delivery. Increased UtA-PI was associated with an elevated risk of SGA, both in neonates delivered at or after 37 weeks' gestation (term SGA) and those delivered before 37 weeks (preterm SGA). The areas under the ROC curve (AUCs) for UtA-PI were 64.4% (95% CI, 61.5-67.3%) and 75.8% (95% CI, 69.3-82.3%) for term and preterm SGA, respectively. The performance of combined screening by maternal demographic/clinical characteristics and estimated fetal weight in the detection of term and preterm SGA was improved significantly by the addition of UtA-PI, although the increase in AUC was modest (2.4% for term SGA and 4.9% for preterm SGA). CONCLUSIONS: This is the first Chinese study to evaluate the role of UtA-PI at 19-24 weeks' gestation in the prediction of the delivery of a neonate with SGA. The addition of UtA-PI to traditional risk factors improved the screening performance for SGA, and this improvement was greater in predicting preterm SGA compared with term SGA. © 2023 International Society of Ultrasound in Obstetrics and Gynecology.
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Ultrassonografia Pré-Natal , Artéria Uterina , Gravidez , Recém-Nascido , Feminino , Humanos , Lactente , Masculino , Terceiro Trimestre da Gravidez , Artéria Uterina/diagnóstico por imagem , Estudos Retrospectivos , Estudos Prospectivos , Recém-Nascido Pequeno para a Idade Gestacional , Retardo do Crescimento Fetal/diagnóstico por imagem , Idade Gestacional , Ultrassonografia Doppler , Fluxo PulsátilRESUMO
Objective: To examine the efficacy and experience of staged and segmented two hybrid surgeries for total repair of Debakey type â aortic dissection (TIAD). Methods: This study was a retrospective case series. The clinic data of 10 patients with acute TIAD who were admitted to the Department of Cardiac Surgery, Second Hospital of Lanzhou University or the First People's Hospital of Lanzhou, between January 2016 and August 2022, were retrospectively studied. Ten patients underwent hybrid surgeries in two hospitalizations (stages), including 7 males and 3 females with an age of (60±7) years (range: 49 to 71 years). In stage 1, the first type â ¡ hybrid arch repair was performed to treat the ascending, total arch, and descending thoracic aorta for acute TIAD without circulatory arrest. In stage 2, the second hybrid surgery including infrarenal abdominal aorta replacement, visceral arteries bypass and endovascular thoracoabdominal aortic repair was performed to treat residual thoracoabdominal aortic dissection after the first hybrid operation (segmented). Basic data, preoperative concomitant diseases, high-risk factors, surgical approaches and postoperative complications of all important organs, as well as CT imaging were analyzed. Results: There was no death in the 20 hybrid surgical procedures. In stage 1 type â ¡ hybrid surgery, 4 cases underwent reconstruction of the aortic sinutubular junction, while Bentall and David surgery was performed for 3 cases, respectively. A patient received coronary artery bypass grafting. Then all patients were sequentially treated with arch debranching and thoracic aortic endovascular repair. Postoperative complications included renal insufficiency (4/10), hemofiltration (1/10), hypoxemia (4/10), neurologic event (1/10) and type â ¡ endoleak (1/10). Complete false lumen thrombosis occurred in 9/10 of the patients. All complications recovered successfully at discharge and the average hospital stay was (21±4) days (range: 16 to 28 days) in the first hospitalization. At stage 2, the second hybrid surgery was successfully performed in all patients. No paraplegia, hepatic or renal insufficiency, or endoleak occurred. However, branch graft embolism of the left renal artery was found in one patient 3 days after laparotomy, as well as of superior mesenteric artery in another. Superior mesenteric artery occlusion was successfully treated by endovascular recanalization. Complete false lumen thrombosis occurred in all patients. Although all patients had different degrees of intestinal dysfunction, they were gradually relieved at discharge, and the average hospital stay was (19±2)days (range:16 to 21 days) in the second hospitalization. During follow-up, CT angiography showed aortic remodeling in all patients. Conclusion: Staged and segmented two hybrid surgeries are safe and feasible for total repair of Debakey type â aortic dissection and are associated with acceptable early and midterm outcomes.
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Dissecção Aórtica , Implante de Prótese Vascular , Humanos , Masculino , Pessoa de Meia-Idade , Feminino , Dissecção Aórtica/cirurgia , Estudos Retrospectivos , Idoso , Implante de Prótese Vascular/métodos , Resultado do Tratamento , Aneurisma da Aorta Torácica/cirurgia , Aorta Torácica/cirurgia , StentsRESUMO
Objective: The aim of this paper is to compare the refractive correction effects of rigid gas permeable contact lenses (RGPCL) and spectacle correction in children with aphakia after congenital cataract surgery. Methods: This was a prospective non-randomized controlled trial. Children with aphakic eyes after congenital cataract surgery, who underwent vision correction in the Strabismus and Pediatric Ophthalmology Clinic of Beijing Tongren Hospital affiliated with Capital Medical University from April 2012 to November 2019, were continuously collected. Those who voluntarily chose to wear RGPCL for refractive correction were included in the experimental group. Patients with monocular disease were in trial group 1, and patients with binocular disease were in trial group 2. Patients who chose to wear frame glasses for refractive correction were included in the control group. Patients with monocular disease were in control group 1, and patients with binocular disease were in control group 2. Regional origin, medical history, and family information were collected at the first diagnosis. During the follow-up, adverse reactions occurring during the process of wearing glasses were recorded. The Teller acuity card was used for visual examination to obtain the best-corrected visual acuity and convert it into the logarithm of the minimum resolution angle. The degree of nystagmus was determined according to the amplitude and frequency of nystagmus. Treatment cost, treatment compliance, and the reasons for adopting or not adopting RGPCL were analyzed through a questionnaire completed by the parents of children with RGPCL. Results: A total of 203 children (344 eyes) who underwent congenital cataract surgery were included, including 124 males (210 eyes) and 79 females (134 eyes). The age range was 3 to 36 months. There were 28 cases in the experimental group, including 19 cases in trial group 1 and 9 cases in trial group 2. There were 175 cases in the control group, including 43 cases in control group 1 and 132 cases in control group 2. Except for 6 months of age, the visual acuity of the experimental group was better than that of the control group, and the differences were statistically significant (P<0.05). The visual acuity of children in trial group 1 was better than that of children in control group 1 at the same age. Among them, at 12 months of age [1.54 (1.27, 1.97), 1.84 (0.97, 2.12)], 18 months of age [1.27 (0.97, 1.84), 1.84 (0.97, 2.12)], 24 months of age [1.54 (1.27, 1.84), 1.84 (0.97, 2.12)], and 30 months old [0.97 (0.66, 1.27), 1.54 (0.66, 2.12)], the difference was statistically significant (P<0.001). The visual acuity of children in trial group 2 was better than that in control group 2 at the same age. Among them, at 18 months old [1.27 (0.97, 1.54), 1.27 (0.66, 2.12)], 24 months old [0.97 (0.66, 1.27), 1.27 (0.66, 2.12)], and 30 months old [1.27 (0.66, 2.12)], the difference was statistically significant (P<0.05). The remission rate of nystagmus in the experimental group was 8/9 (8 cases), the remission rate of nystagmus in the control group was 34.40% (32 cases), and the exacerbation rate was 29.03% (27 cases). The average annual cost of the experimental group was 25 125 yuan, and that of the control group was 2 511 yuan. Conclusions: RGPCL is a well-tolerated, safe, and effective treatment for infants and young children. The visual acuity and degree of nystagmus were significantly improved in children who wore RGPCL for aphakia refractive correction after congenital cataract surgery compared with spectacle correction.
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Afacia , Extração de Catarata , Catarata , Lentes de Contato , Nistagmo Patológico , Oftalmologia , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Catarata/terapia , Catarata/congênito , Óculos , Estudos ProspectivosRESUMO
A high-peak-power sub-500-fs mode-locked optically pumped semiconductor laser is innovatively developed with only three components of a semiconductor gain chip, a semiconductor saturable absorber, and a focusing lens. The developed laser near the threshold pump power of 3.9 W can be operated with stable fundamental mode locking. The laser output can be naturally turned into the stable harmonic mode locking (HML) with the order gradually changing from 2nd to 8th by increasing the pump power from 4.0 W to 5.0 W. Due to the onset of the high-order transverse modes, the order of HML is fixed at 8th for a pump power greater than 5.0 W. For the HML with order less than 8th, the overall peak power and pulse width in the HML are approximately 0.36â kW and 550 fs, respectively. In the operation of 8th-order HML, the minimum pulse width and maximum peak power can reach 480 fs and 0.95â kW, respectively.
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Spin-triplet superconductors play central roles in Majorana physics and quantum computing but are difficult to identify. We show the methods of kink-point upper critical field and flux quantization in superconducting rings can unequivocally identify spin-singlet, spin-triplet in centrosymmetric superconductors, and singlet-triplet admixture in noncentrosymmetric superconductors, as realized in γ-BiPd, ß-Bi_{2}Pd, and α-BiPd, respectively. Our findings are essential for identifying triplet superconductors and exploring their quantum properties.
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OBJECTIVE: Hysterectomy is the most common gynaecological surgery, performed mainly for benign uterine pathologies in women. Studies have suggested that hysterectomy is associated with osteoarthritis (OA); however, the association remains controversial. This study aimed to investigate the association between hysterectomy and the risk of OA. METHOD: We performed a population-based nested case-control study using the National Health Insurance programme database from 2000 to 2016 in Taiwan. All medical conditions for each case and control were categorized using the International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) and ICD-10. A multiple conditional logistic regression model was applied to analyse the adjusted odds ratio (aOR) and 95% confidence interval (CI) for the association between hysterectomy and OA. RESULTS: Our analyses included 16 592 patients with OA and 66 368 matched controls. After adjustment for possible confounders, hysterectomy had a significant association with OA (aOR = 1.19, 95% CI = 1.09-1.30), especially knee OA (aOR = 1.25, 95% CI = 1.13-1.38). Furthermore, women who received oestrogen therapy (ET) alone and patients who underwent hysterectomy without ET showed a greater risk of OA development compared to women who did not receive ET (aOR = 1.14, 95% CI = 1.07-1.23, and aOR = 1.19, 95% CI = 1.08-1.31, respectively). CONCLUSION: Our findings indicate that hysterectomy is associated with OA, especially knee OA. We also found that women who received ET alone and patients who underwent hysterectomy without ET had an increased risk of OA.
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Histerectomia , Osteoartrite do Joelho , Humanos , Feminino , Estudos de Casos e Controles , Histerectomia/efeitos adversos , Osteoartrite do Joelho/epidemiologia , Osteoartrite do Joelho/cirurgia , Osteoartrite do Joelho/etiologia , Modelos Logísticos , Taiwan/epidemiologia , Fatores de Risco , Estudos RetrospectivosRESUMO
Objective: To investigate the clinical characteristics of patients with rheumatic diseases and abnormal liver function, as well as determine the proportion and severity of liver function abnormalities. Methods: Cross-sectional study. Data were collected from patients registered in the Chinese Rheumatism Date Center from 2011 to 2021. The rheumatic diseases analyzed in this study were rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), Sjogren syndrome (SS), ankylosing spondylitis (AS), and gout. Patient data, including demographic characteristics [ such as age, sex, body mass index,(BMI), and smoking history], liver function test results [including alanine aminotransferase (ALT), aspartate aminotransferase, alkaline phosphatase(ALP), and total bilirubin], and use of anti-rheumatic immune drugs and liver-protective drugs, were collected and compared between groups with normal and abnormal liver functions. In addition, the proportions of abnormal liver function were compared between sex and age groups. Results: A total of 116 308 patients were included in this study, including 49 659 with RA, 17 597 with SLE, 9 039 with SS, 11 321 with AS, and 28 692 with gout. The lowest proportion of liver function abnormalities was observed in patients with RA[11.02% (5 470/49 659)], followed by those with SS[17.97% (1 624/9 039)] and AS [18.22% (2 063/11 321) ], whereas patients with SLE [21.14% (3 720/17 597) ] and gout [28.73% (8 242/28 692)] exhibited the highest proportion of these abnormalities. Elevated ALT, mostly classified as grade 1, was the most commonly noted liver function abnormality, whereas elevated ALP was the least common. Some patients who took liver-protective drugs had normal liver function, with the lowest percentage observed in patients with gout [7.45% (36/483) ] and ranging from 21.7% to 30.34% in patients with RA, SLE, SS, and AS. The proportion of liver function abnormalities was higher in males than in females for all disease types [RA: 13.8%(1 368/9 906) vs. 10.3%(4 102/39 753); SLE: 33.6% (479/1 424) vs. 20.0% (3 241/16 173); SS: 25.4%(111/437) vs. 17.6%(1 513/8 602); AS: 20.1%(1 629/8 119) vs. 13.6% (434/3 202); and gout: 29.3% (8 033/27 394) vs. 16.1% (209/1 298)]. In RA, SLE, and AS, the proportions of liver function abnormalities were similar across all age groups. In SS, the proportion of liver function abnormalities increased with age [<40 years: 14.9%(294/1 979); 40-59 years: 18.1%(858/4 741); ≥60 years: 20.4%(472/2 319)], whereas a reversal of this trend was observed in gout [<40 years: 34.9%(4 294/12 320); 40-59 years: 25.5%(2 905/11 398);≥60 years: 21.0%(1 042/4 971)]. Conclusions: The proportions of combined liver function abnormalities in patients with rheumatologic diseases were high, and the utilization rates of liver-protective drugs were low. It is necessary to pay more attention to monitoring patients' liver function, timely administer liver-protective drugs, and optimize liver-protective regimens during the treatment of rheumatic diseases.
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Antirreumáticos , Artrite Reumatoide , Gota , Lúpus Eritematoso Sistêmico , Doenças Reumáticas , Síndrome de Sjogren , Espondilite Anquilosante , Feminino , Masculino , Humanos , Adulto , Estudos Transversais , Fígado , Fosfatase AlcalinaRESUMO
The data of 1 268 newly diagnosed gliomas from the Fourth Ward of Neurosurgery Department of Beijing Tiantan Hospital between April 2013 and March 2022 were retrospectively analyzed. Based on postoperative pathology, the gliomas were divided into groups: oligodendrogliomas (n=308), astrocytomas (n=337) and glioblastomas (n=623). According to the O6-methylguanine-DNA methyl transferase (MGMT) promoter status defined by the 12% of best cut-off value in previous research results, patients were divided into methylation group (n=763) and non-methylation group (n=505). Methylation level [M (Q1, Q3)] in patients with glioblastoma, astrocytoma and oligodendroglioma was 6% (2%, 24%), 17% (10%, 28%) and 29% (19%, 40%), respectively (P<0.001). Compared with non-methylation patients, the progression-free survival (PFS) and overall survival (OS) of glioblastomas patients with methylation of MGMT promoter demonstrated more favorable prognosis [M (Q1, Q3)]) of PFS: 14.0 (6.0, 36.0) months vs 8.0 (4.0, 15.0) months, P<0.001; M (Q1, Q3) of OS: 29.0 (17.0, 60.5) months vs 16.0 (11.0, 26.5) months, P<0.001]. In astrocytomas patients, the PFS was much longer for those with methylation [the median PFS of patients with methylation was not observed at the end of follow-up, but those without methylation showed a median PFS of 46.0 (29.0, 52.0) months] (P=0.001). However, no statistically significant difference was observed in OS [the median OS of patients with methylation was not observed at the end of follow-up, but those without methylation had a median OS of 62.0 (46.0, 98.0) months] (P=0.085). In oligodendrogliomas patients, no statistically significant differences of PFS and OS were observed between patients with methylation and those without methylation. MGMT promoter status was a related factor affecting PFS and OS in glioblastomas (PFS: HR=0.534,95%CI: 0.426-0.668, P<0.001; OS: HR=0.451, 95%CI: 0.353-0.576, P<0.001). Moreover, MGMT promoter status was also a related factor affecting PFS in astrocytomas (HR=0.462, 95%CI: 0.221-0.966, P=0.040), but not for OS (HR=0.664, 95%CI: 0.259-1.690, P=0.389). The methylation level of MGMT promoter differed substantially in different types of gliomas, and the status of MGMT promoter profoundly affected the prognosis of glioblastomas.
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Astrocitoma , Glioblastoma , Glioma , Oligodendroglioma , Humanos , Estudos Retrospectivos , Glioma/genética , Prognóstico , Metilases de Modificação do DNA/genética , Proteínas Supressoras de Tumor/genética , Enzimas Reparadoras do DNA/genéticaRESUMO
Thirteen consecutive patients with entrapped temporal horn syndrome in the Department of Neurosurgery of Beijing Tiantan Hospital from February 2018 to September 2022 were retrospectively analyzed, and there were 5 males and 8 females, with a mean age of (43±21) years. Increased intracranial pressure caused by hydrocephalus was the main clinical symptom. All the patients underwent refined temporal-to-frontal horn shunt, and all the symptoms were improved after surgery. Postoperative Karnofsky performance score (KPS) [90 (90, 100)] was higher than preoperative KPS [57 (40, 70)] (P=0.001). However, postoperative entrapped temporal horn volume [13.85 (8.90, 15.25) cm3] decreased, compared with preoperative volume [66.52 (38.65, 88.65) cm3] (P=0.001). Likewise, postoperative midline shift [0.77 (0, 1.50) mm] was longer than preoperative midline shift [6.69 (2.50, 10.00) mm] (P=0.002). No surgery-related complications were observed after the operation. Therefore, the refined temporal-to-frontal horn shunt is safe and effective treatment for entrapped temporal horn syndrome, with favorable outcomes.
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Hidrocefalia , Masculino , Feminino , Humanos , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Estudos Retrospectivos , Lobo Temporal/cirurgia , Resultado do Tratamento , Procedimentos Neurocirúrgicos/efeitos adversos , Síndrome , Derivação Ventriculoperitoneal/efeitos adversosRESUMO
It has attracted much attention worldwide that the application of artificial intelligence (AI) in primary screening and clinical diagnosis and treatment of eye diseases. In recent years, this technology has also been widely used in various grass-roots eye disease management, effectively improving the current situation of weak eye disease diagnosis ability and shortage of human resources in primary medical institutions. At present, there is no reference standard or guideline for the management mode, implementation content and management method of vision health management based on this technology, which are in urgent need of standardization. The article described the work mode exploration of AI-assisted grass-roots visual health management in Shanghai and shared practical experience. The aim is to provide reference for other provinces in China to carry out relevant work.
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Inteligência Artificial , Humanos , China , Padrões de Referência , Recursos HumanosRESUMO
Objective: To obtain the diversity and abundance of fast-growing bacteria in the surface water of the northeast coast of Hainan Island in China, different cultivation methods were employed. This study also aims to provide a reference for isolating bacterial samples from seawater sources and preventing marine-derived pathogens. Methods: Based on the principles of taxonomic design, surface seawater samples were collected from six locations along the northeast coast of Hainan Island in China in March, June, October, and December 2021. Then, bacterial enrichment was performed based on traditional cultivation methods for Salmonella, Vibrio, Burkholderia pseudomallei, Actinomycetes, and general marine bacteria. After that, bacterial species identification was conducted by 16S rDNA amplicon sequencing and metagenomic sequencing. Results: A total of 1 151 fast-growing cultivable bacteria belonging to 66 genera and 213 species were identified using five different culture protocols. In different cultivation protocols, Bacillus and Klebsiella demonstrated extensive discriminatory advantages and ranked among the top genera in terms of abundance. Protocol 1 had Escherichia, Klebsiella, and Citrobacter as dominant genera. Pathogenic bacteria detected by protocol 1 included Klebsiella pneumoniae and Escherichia coli, with 37 and 29 strains respectively, while Salmonella enterica was uniquely detected with seven isolates. Proteus, Enterococcus, and Providencia were the dominant genera in protocol 2, and Proteus mirabilis was the most abundant pathogenic bacteria detected with 66 isolates. Vibrio cholerae was uniquely detected with six isolates at a higher abundance. Klebsiella, Escherichia, and Acinetobacter were the dominant genera in protocol 3, and Klebsiella pneumoniae was the most abundant pathogenic bacteria detected with 53 isolates, while Acinetobacter nosocomialis was uniquely detected with seven isolates. Vibrio and Pseudoalteromonas were the dominant genera in protocol 4, and they showed advantages in isolating and cultivating Marine-derived Vibrio. Exiguobacterium, Staphylococcus, and Bacillus were the dominant genera in protocol 5. Bacillus cereus and Lactococcus lactis were the most abundant pathogenic bacteria detected with 20 and 15 isolates, respectively, while Lactococcus lactis was uniquely detected at higher abundance. Metagenomic sequencing showed that Klebsiella pneumoniae was significantly dominant with a gene abundance of 51.11%, followed by Alcanivorax sp. at 12.57%. Conclusion: The surface water of the northeast coast of Hainan Island in China exhibits a rich diversity of bacteria, with Klebsiella pneumoniae being highly abundant in the studied area. Different cultivation methods demonstrate distinct selective advantages in culturing bacterial genera and pathogens. Therefore, it is necessary to optimize cultivation conditions for specific marine bacteria.
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Bactérias , Água , Humanos , Bactérias/genética , Água do Mar/microbiologia , Escherichia coli , Enterococcus , Klebsiella pneumoniae , ChinaRESUMO
Due to the unique anatomical structure and physiological barriers of the eye, drug delivery for ocular diseases presents a formidable challenge. Conventional methods of ocular drug administration often suffer from limitations such as low drug bioavailability and a lack of tissue targeting, necessitating multiple administrations to achieve the desired therapeutic drug concentrations. In recent years, microneedles, known for their attributes of safety, minimally invasive application, and high efficiency, have found widespread application in ocular drug delivery research. Among the various types of microneedles, dissolving polymer microneedles have emerged as a prominent focus in the field of ocular drug delivery due to their distinct advantages over other microneedle types. This article provides a comprehensive summary and outlook on the progress in the application of dissolving polymer microneedles for drug delivery in ocular diseases.
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Sistemas de Liberação de Medicamentos , Polímeros , Humanos , Preparações Farmacêuticas , Olho , FaceRESUMO
Objective: To analyze the disease composition and primary surgical procedures in pediatric inpatients with secondary glaucoma. Methods: A retrospective case series study was conducted. Clinical data of children aged≤16 years with secondary glaucoma who were admitted to the Zhongshan Ophthalmic Center, Sun Yat-sen University, between January 1, 2017, and December 31, 2021, were included. The patients were classified according to the Childhood Glaucoma Research Network (CGRN) classification system, and their diagnoses, underlying factors, gender, age of onset, affected eye(s), age and type of initial surgery, and ophthalmic examination data were analyzed. Statistical analysis was performed using Kruskal-Wallis rank sum test and χ2 test. Results: A total of 540 patients (744 eyes) were included in this study, comprising 319 males (59.1%) and 221 females (40.9%). Unilateral disease was observed in 336 cases (62.2%), while bilateral involvement was present in 204 cases (37.8%). The age of onset was 4.0 (0.0, 9.0) years, and the median age of the first anti-glaucoma surgery was 5.0 (0.7, 10.0) years. Among them, there were 195 cases (36.1%) of secondary glaucoma associated with non-acquired ocular anomalies (SCG-O), with a median age of onset of 0.0 (0.0, 4.0) years, and 97 of these cases (49.7%) were male. secondary glaucoma associated with non-acquired systemic disease or syndrome (SCG-S) were observed in 68 cases (12.6%), with a median age of glaucoma onset of 0.1 (0.0, 4.0) years, and 47 of these cases (69.1%) were male. Secondary glaucoma associated with acquired conditions (SCG-A) accounted for 192 cases (35.6%), with a median age of onset of 9.0 (5.0, 13.0) years, and 125 of these cases (65.1%) were male. There were 85 cases (15.7%) of secondary glaucoma following cataract surgery (SCG-C), with a median age of onset of 3.0 (0.8, 7.0) years, and 50 of these cases (58.8%) were male. Male patients were predominant in SCG-S and SCG-A, with 47 cases (69.1%) and 125 cases (65.1%), respectively (χ2=9.94, 17.52; P=0.002,<0.001). Except for SCG-O, all other types of pediatric secondary glaucoma predominantly affected only one eye: SCG-S in 52 cases (76.5%), SCG-A in 128 cases (66.7%), and SCG-C in 54 cases (63.5%) (χ2=19.06, 21.33, 6.22; all P<0.05). The highest proportion of SCG-O was attributed to congenital ectropion uveae (46 cases, 23.6%). Sturge-Weber syndrome was the most common SCG-S (45 cases, 66.3%), while SCG-A mostly resulted from trauma (59 cases, 30.8%) and corticosteroid use (56 cases, 29.2%). Trabeculectomy (211 eyes, 30.8%) and glaucoma drainage device implantation (197 eyes, 28.7%) were the most frequently performed primary surgical procedures. Conclusions: SCG-O and SCG-A were found to be common types of pediatric secondary glaucoma. The age of onset and the choice of primary anti-glaucoma surgical procedures varied among different types of pediatric secondary glaucoma. However, overall, trabeculectomy and glaucoma drainage device implantation were the primary surgical procedures predominantly employed.
Assuntos
Glaucoma , Trabeculectomia , Criança , Feminino , Humanos , Masculino , Olho , Glaucoma/patologia , Glaucoma/cirurgia , Estudos Retrospectivos , Pré-Escolar , Implantes para Drenagem de Glaucoma , Corticosteroides/uso terapêuticoRESUMO
Objectives: To analyze the reasons of missed diagnosis or misdiagnosis on anomalous origin of left coronary artery from pulmonary artery (ALCAPA) by echocardiography. Methods: This is a retrospective study. Patients with ALCAPA who underwent surgical treatment in Union Hospital, Tongji Medical College, Huazhong University of Science and Technology from August 2008 to December 2021 were included. According to the results of preoperative echocardiography and surgical diagnosis, the patients were divided into confirmed group or missed diagnosis/misdiagnosis group. The results of preoperative echocardiography were collected, and the specific echocardiographic signs were analyzed. According to the experience of the doctors, the echocardiographic signs were divided into four types, namely clear displayed, vague/doubtful displayed, no display and no notice, and the display rate of each sign was calculated (display rate=number of clearly displayed cases/total number of cases×100%). By referring the surgical data, we analyzed and recorded the pathological anatomy and pathophysiological characteristics of the patients, and the rate of missed diagnosis/misdiagnosis of echocardiography in patients with different characteristics was compared. Results: A total of 21 patients were enrolled, including 11 males, aged 1.8 (0.8, 12.3) years (range 1 month to 47 years). Except for one patient with anomalous origin of left anterior descending artery, the others were all originated from the main left coronary artery (LCA). There were 13 cases of ALCAPA in infant and children, and 8 cases of adult ALCAPA. There were 15 cases in the confirmed group (diagnostic accuracy was 71.4% (15/21)), and 6 cases in the missed diagnosis/misdiagnosis group (three cases were misdiagnosed as primary endocardial fibroelastosis, two cases were misdiagnosed as coronary-pulmonary artery fistula; and one case was missed diagnosis). The working years of the physicians in the confirmed group were longer than those in the missed diagnosis/misdiagnosed group ((12.8±5.6) years vs. (8.3±4.7) years, P=0.045). In infants with ALCAPA, the detection rate of LCA-pulmonary shunt (8/10 vs. 0, P=0.035) and coronary collateral circulation (7/10 vs. 0, P=0.042) in confirmed group was higher than that in missed diagnosis/misdiagnosed group. In adult ALCAPA patients, the detection rate of LCA-pulmonary artery shunt was higher in confirmed group than that in missed diagnosis/misdiagnosed group (4/5 vs. 0, P=0.021). The missed diagnosis/misdiagnosis rate of adult type was higher than that of infant type (3/8 vs. 3/13, P=0.410). The rate of missed diagnosis/misdiagnosis was higher in patients with abnormal origin of branches than that of abnormal origin of main trunk (1/1 vs. 5/21, P=0.028). The rate of missed diagnosis/misdiagnosis in patients with LCA running between the main and pulmonary arteries was higher than that distant from the main pulmonary artery septum (4/7 vs. 2/14, P=0.064). The rate of missed diagnosis/misdiagnosis in patients with severe pulmonary hypertension was higher than that in patients without severe pulmonary hypertension (2/3 vs. 4/18, P=0.184). The reasons with an echocardiography missed diagnosis/misdiagnosis rate of≥50% included that (1) the proximal segment of LCA ran between the main and pulmonary arteries; (2) abnormal opening of LCA at the right posterior part of the pulmonary artery; (3) abnormal origin of LCA branches; (4) complicated with severe pulmonary hypertension. Conclusions: Echocardiography physicians' knowledge of ALCAPA and diagnostic vigilance are critical to the accuracy of diagnosis. Attention should be paid to the pediatric cases with no obvious precipitating factors of left ventricular enlargement, regardless of whether the left ventricular function is normal or not, the origin of coronary artery should be routinely explored.