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OBJECTIVE: The aim of this study is to systematically examine and compare the characteristics distinguishing colorectal adenomatous polyps from normal mucosal intestinal microbiota. METHODS: A total of 30 specimens were obtained from patients diagnosed with colorectal adenomatous polyps (adenoma group) who underwent endoscopic removal at Wenzhou People's Hospital between September 2021 and November 2021. Concurrently, 30 normal mucosal specimens were collected from patients without adenomatous polyps (control group). Subsequently, microbiome total DNA extraction was carried out, followed by PCR amplification targeting the V3-V4 region of the 16S rDNA. High-throughput sequencing was conducted using the Illumina MiSeq platform. Subsequent to sequencing, bioinformatics analysis was used to assess the diversity, composition, and functional aspects of the intestinal microbiota in both study groups. RESULTS: A notable dissimilarity in the microbiota structure was identified, specifically within the transverse colon, between these two groups (Pâ <â 0.05). Species composition analysis revealed that Escherichia, Fusobacterium, and Bacteroides were predominant bacteria in both groups, with Escherichia and Enterobacter displaying significant differences at the genera level between the control group and the adenoma group (Pâ <â 0.05). Correlation analysis and functional prediction demonstrated substantial disparities in interactions among dominant intestinal microbial genera within patients from both groups. Additionally, it was discovered that the intestinal microbiomes in patients in the adenoma group exhibited a significantly higher pathogenic potential. CONCLUSION: Upon conducting a comprehensive analysis, it was discerned that the microbiota present in the transverse colon of the control group exhibited distinctive characteristics that may contribute to the maintenance of intestinal health.
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BACKGROUND: Benign recurrent intrahepatic cholestasis (BRIC) is a rare autosomal recessive disorder, characterized by episodes of intense pruritus, elevated serum levels of alkaline phosphatase and bilirubin, and near-normal -glutamyl transferase. These episodes may persist for weeks to months before spontaneously resolving, with patients typically remaining asymptomatic between occurrences. Diagnosis entails the evaluation of clinical symptoms and targeted genetic testing. Although BRIC is recognized as a benign genetic disorder, the triggers, particularly psychosocial factors, remain poorly understood. CASE SUMMARY: An 18-year-old Chinese man presented with recurrent jaundice and pruritus after a cold, which was exacerbated by self-medication involving vitamin B and paracetamol. Clinical and laboratory evaluations revealed elevated levels of bilirubin and liver enzymes, in the absence of viral or autoimmune liver disease. Imaging excluded biliary and pancreatic abnormalities, and liver biopsy demonstrated centrilobular cholestasis, culminating in a BRIC diagnosis confirmed by the identification of a novel ATP8B1 gene mutation. Psychological assessment of the patient unveiled stress attributable to academic and familial pressures, regarded as potential triggers for BRIC. Initial relief was observed with ursodeoxycholic acid and cetirizine, followed by an adjustment of the treatment regimen in response to elevated liver enzymes. The patient's condition significantly improved following a stress-related episode, thanks to a comprehensive management approach that included psychosocial support and medical treatment. CONCLUSION: Our research highlights genetic and psychosocial influences on BRIC, emphasizing integrated diagnostic and management strategies.
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Introduction: Secondary hyperparathyroidism (SHPT) is a common and serious complication of chronic kidney disease (CKD). Elucidating the metabolic characteristics of SHPT may provide a new theoretical basis for its prevention and treatment. This study aimed to perform a metabolomic analysis of SHPT in patients with CKD stages 3-5 not receiving dialysis. Methods: A total of 76 patients with CKD, 85 patients with CKD-SHPT, and 67 healthy controls were enrolled in this study. CKD was diagnosed according to the criteria specified in the Kidney Disease Improving Global Outcomes 2012 guidelines. SHPT was diagnosed by experienced clinicians according to the Renal Disease Outcomes Quality Initiative Clinical Practice Guidelines. Serum renal function markers and the lipid profile were analyzed. Untargeted ultra performance liquid chromatography-tandem mass spectrometry was used to analyze the serum metabolites of patients with CKD and SHPT. Multivariate analysis of the data was performed using principal component analysis and partial least square discriminant analysis. Serum differential metabolites were identified and further characterized using databases. Pathway enrichment analysis was performed using the Kyoto Encyclopedia of Genes and Genomes database. Correlations between differential metabolites and clinical parameters were determined using the Spearman correlation. Results: The serum metabolomic profiles of patients with CKD with and without SHPT differed significantly. Differential metabolites were mainly enriched in the top four Kyoto Encyclopedia of Genes and Genomes pathways: phenylalanine, tyrosine, and tryptophan biosynthesis; sphingolipid metabolism; glycerophospholipid metabolism; and phenylalanine metabolism. In total, 31 differential metabolites were identified; of these, L-tryptophan and (R)-(+)-1-phenylethylamine were decreased, while other amino acids and their derivatives, uremia toxins, carnitine, and lipids, were increased significantly in patients with SHPT compared to those without. The 14 lipid metabolites were positively correlated with levels of Urea, serum creatinine, cystatin C, and triglycerides and negatively correlated with the estimated glomerular filtration rate and levels of total and high- and low-density lipoprotein cholesterol. Discussion: Disturbed amino acid and lipid metabolism were more apparent in patients with SHPT than in those without. This metabolomic profile of SHPT may provide a therapeutic foundation for its future clinical management.
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Hiperparatireoidismo Secundário , Metabolômica , Insuficiência Renal Crônica , Humanos , Feminino , Masculino , Hiperparatireoidismo Secundário/sangue , Hiperparatireoidismo Secundário/etiologia , Pessoa de Meia-Idade , Insuficiência Renal Crônica/sangue , Insuficiência Renal Crônica/terapia , Insuficiência Renal Crônica/complicações , Metabolômica/métodos , Idoso , Adulto , Diálise Renal , Biomarcadores/sangue , Metaboloma , Estudos de Casos e ControlesRESUMO
STUDY QUESTION: Can pregnancy outcomes following fresh elective single embryo transfer (eSET) in gonadotropin-releasing hormone (GnRH) antagonist protocols increase using a gonadotropin (Gn) step-down approach with cessation of GnRH antagonist on the day of hCG administration (hCG day) in patients with normal ovarian response? SUMMARY ANSWER: The modified GnRH antagonist protocol using the Gn step-down approach and cessation of GnRH antagonist on the hCG day is effective in improving live birth rates (LBRs) per fresh eSET cycle. WHAT IS KNOWN ALREADY: Currently, there is no consensus on optimal GnRH antagonist regimens. Studies have shown that fresh GnRH antagonist cycles result in poorer pregnancy outcomes than the long GnRH agonist (GnRHa) protocol. Endometrial receptivity is a key factor that contributes to this phenomenon. STUDY DESIGN, SIZE, DURATION: An open label randomized controlled trial (RCT) was performed between November 2021 and August 2022. There were 546 patients allocated to either the modified GnRH antagonist or the conventional antagonist protocol at a 1:1 ratio. PARTICIPANTS/MATERIALS, SETTING, METHODS: Both IVF and ICSI cycles were included, and the sperm samples used were either fresh or frozen from the partner, or from frozen donor ejaculates. The primary outcome was the LBRs per fresh SET cycle. Secondary outcomes included rates of implantation, clinical and ongoing pregnancy, miscarriage, and ovarian hyperstimulation syndrome (OHSS), as well as clinical outcomes of ovarian stimulation. MAIN RESULTS AND THE ROLE OF CHANCE: Baseline demographic features were not significantly different between the two ovarian stimulation groups. However, in the intention-to-treat (ITT) population, the LBRs in the modified antagonist group were significantly higher than in the conventional group (38.1% [104/273] vs. 27.5% [75/273], relative risk 1.39 [95% CI, 1.09-1.77], P = 0.008). Using a per-protocol (PP) analysis which included all the patients who received an embryo transfer, the LBRs in the modified antagonist group were also significantly higher than in the conventional group (48.6% [103/212] vs. 36.8% [74/201], relative risk 1.32 [95% CI, 1.05-1.66], P = 0.016). The modified antagonist group achieved significantly higher implantation rates, and clinical and ongoing pregnancy rates than the conventional group in both the ITT and PP analyses (P < 0.05). The two groups did not show significant differences between the number of oocytes retrieved or mature oocytes, two-pronuclear zygote (2PN) rates, the number of embryos obtained, blastocyst progression and good-quality embryo rates, early miscarriage rates, or OHSS incidence rates (P > 0.05). LIMITATIONS, REASONS FOR CAUTION: A limitation of our study was that the subjects were not blinded to the treatment allocation in the RCT trial. Only women under 40 years of age who had a good prognosis were included in the analysis. Therefore, use of the modified antagonist protocol in older patients with a low ovarian reserve remains to be investigated. In addition, the sample size for Day 5 elective SET was small, so larger trials will be required to strengthen these findings. WIDER IMPLICATIONS OF THE FINDINGS: The modified GnRH antagonist protocol using the Gn step-down approach and cessation of GnRH antagonist on hCG day improved the LBRs per fresh eSET cycle in normal responders. STUDY FUNDING/COMPETING INTEREST(S): This project was funded by grant 2022YFC2702503 from the National Key Research & Development Program of China and grant 2021140 from the Beijing Health Promotion Association. The authors declare no conflicts of interest. TRIAL REGISTRATION NUMBER: The RCT was registered in the Chinese Clinical Trial Registry; Study Number: ChiCTR2100053453. TRIAL REGISTRATION DATE: 21 November 2021. DATE OF FIRST PATIENT'S ENROLLMENT: 23 November 2021.
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OBJECTIVE: To investigate the safety and efficacy of endovascular treatment for totally occlusive lesions of the subclavian artery (SCA). METHODS: A retrospective study was performed on 57 patients treated with angioplasty and stenting, including 42 males and 15 females, with an average age of 61.8 years (range: 49 to 81 years). Efficacy, safety, and complications were evaluated. RESULTS: Procedural success was achieved for 47/57 patients and symptoms were relieved. Rat-tail occlusion is the most common type, and all cases were successfully recanalized. Plain type occlusion is less common with a recanalization rate of 55.6%. Hilly and plain occlusions are the main types of stent implantation failure. Through univariate analysis and trend matching analysis, the type of SCA occlusion and surgical approach had statistical significance on the success rate of surgery. The mean follow-up time was 34.6 ± 16.2 months. The cumulative stent patency rates at 1, 3, and 5 years were 95.5%, 86.4%, and 77.3% in the calcified plaque group and 92.0%, 76.0%, and 68.0% in the non-calcified plaque group, respectively. The 3-year and 5-year patency rates in the calcified plaque group were higher than those in the non-calcified plaque group (p < .05). CONCLUSION: Different occlusion types and surgical approaches can affect the surgical success rate. The combined femoral and brachial approach can improve the rate of recanalization of SCA occlusions. The patency rates at 3 and 5 years in the calcified plaque group were higher than those in the non-calcified plaque group.
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Immunotherapy had shown good antitumor activity in a variety of solid tumors, but low benefit in CRC, so there was an urgent need to explore new biomarkers. We evaluated the role of KMT2C using publicly available data from the Cancer Genome Atlas (TCGA) and Memorial Sloan Kettering Cancer Center (MSKCC). In addition, further analysis was performed in an internal cohort. Moreover, the mutant profiles of KMT2C was analyzed in a large CRC cohort. The relationship between clinical pathologic features and KMT2C were analyzed with using the two-sided chi-squared test or the Fisher exact test. Clinicopathologic characteristics associated with overall survival using Cox regression and the Kaplan-Meier method. We found that KMT2C-mutated CRC patients in the immunotherapy cohort had significantly improved OS compared with KMT2C WT patients (P = 0.013). However, this phenomenon did not exist in non-immunotherapy cohort. Our cohort validated the value of KMT2C mutations in predicting better clinical outcomes, including ORR (P < 0.0001) and OS (P = 0.010). Meanwhile, KMT2C mutation was associated with higher tumor mutation burden, MSI score, higher levels of immune-associated T cells, neutrophil, and M1-type macrophages. Our study suggested that KMT2C mutation might be a potential positive predictor for CRC immunotherapy.
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Neoplasias Colorretais , Humanos , Mutação , Biomarcadores , Neoplasias Colorretais/genética , Neoplasias Colorretais/terapia , Imunoterapia , Biomarcadores Tumorais/genéticaRESUMO
The management and comprehension of relapsed or refractory multiple myeloma (RRMM) continues to pose a significant challenge. By integrating single-cell RNA sequencing (scRNA-seq) data of 15 patients with plasma cell disorders (PCDs) and proteomic data obtained from mass spectrometry-based analysis of CD138+ plasma cells (PCs) from 144 PCDs patients, we identified a state of malignant PCs characterized by high stemness score and increased proliferation originating from RRMM. This state has been designated as proliferating stem-like plasma cells (PSPCs). NUCKS1 was identified as the gene marker representing the stemness of PSPCs. Comparison of differentially expressed genes among various PC states revealed a significant elevation in LGALS1 expression in PSPCs. Survival analysis on the MMRF CoMMpass dataset and GSE24080 dataset established LGALS1 as a gene associated with unfavourable prognostic implications for multiple myeloma. Ultimately, we discovered three specific ligand-receptor pairs within the midkine (MDK) signalling pathway network that play distinct roles in facilitating efficient cellular communication between PSPCs and the surrounding microenvironment cells. These insights have the potential to contribute to the understanding of molecular mechanism and the development of therapeutic strategies involving the application of stem-like cells in RRMM treatment.
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Amino acids are the building blocks of proteins and are widely used as important ingredients for other nitrogen-containing molecules. Here, we report the sustainable production of amino acids from biomass-derived hydroxy acids with high activity under visible-light irradiation and mild conditions, using atomic ruthenium-promoted cadmium sulfide (Ru1/CdS). On a metal basis, the optimized Ru1/CdS exhibits a maximal alanine formation rate of 26.0â molAla â gRu -1 â h-1, which is 1.7â times and more than two orders of magnitude higher than that of its nanoparticle counterpart and the conventional thermocatalytic process, respectively. Integrated spectroscopic analysis and density functional theory calculations attribute the high performance of Ru1/CdS to the facilitated charge separation and O-H bond dissociation of the α-hydroxy group, here of lactic acid. The operando nuclear magnetic resonance further infers a unique "double activation" mechanism of both the CH-OH and CH3-CH-OH structures in lactic acid, which significantly accelerates its photocatalytic amination toward alanine.
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Aminoácidos , Biomassa , Compostos de Cádmio , Rutênio , Sulfetos , Sulfetos/química , Rutênio/química , Compostos de Cádmio/química , Catálise , Aminoácidos/química , Processos Fotoquímicos , Teoria da Densidade Funcional , LuzRESUMO
Myocardial ischemia/reperfusion (I/R) decreases cardiac function and efficiency. Accumulating evidence suggests that long noncoding RNAs (lncRNAs) have been linked to the cellular processes of myocardial I/R injury. The present investigation elucidated the function of lncRNA colon cancer-associated transcript 2 (CCAT2) in myocardial I/R injury and the related mechanisms.AC16 cardiomyocytes were exposed to hypoxia (16 hours) /reoxygenation (6 hours) (H/R) to mimic myocardial I/R models in vitro. CCAT2 and microRNA (miR) -539-3p expressions in AC16 cardiomyocytes were measured using real-time quantitative polymerase chain reaction. B-cell-specific Moloney murine leukemia virus insertion region 1 (BMI1) protein levels in AC16 cardiomyocytes were determined by western blotting. Cell viability, lactate dehydrogenase (LDH) leakage, reactive oxygen species (ROS) levels, mitochondrial membrane potential, and apoptosis were detected using Counting Kit-8, LDH Assay Kit, dihydroethidium assay, 5,5',6,6'-tetrachloro1,1',3,3'-tetramethylbenzimidazolylcarbocyanine iodide staining, flow cytometry, and western blotting, respectively. The interactions between the molecules were confirmed using the dual-luciferase gene reporter. The wingless/integrated/beta-catenin (Wnt/ß-catenin) pathway under the H/R condition was detected by western blotting.CCAT2 and BMI1 mRNA expressions were reduced in H/R-exposed AC16 cardiomyocytes. CCAT2 overexpression exerted protective effects against H/R-induced cardiomyocyte injury, as demonstrated by increased cell viability and mitochondrial membrane potential and decreased LDH leakage, ROS levels, and apoptosis. In addition, CCAT2 positively regulated BMI1 expression by binding to miR-539-3p. CCAT2 knockdown or miR-539-3p overexpression restrained the protective effects of BMI1 against H/R-induced cardiomyocyte injury. In addition, miR-539-3p overexpression reversed the protective effects of CCAT2. Furthermore, CCAT2 activated the Wnt/ß-catenin pathway under the H/R condition via the miR-539-3p/BMI1 axis.Overall, this investigation showed the protective effects of the CCAT2/miR-539-3p/BMI1/Wnt/ß-catenin regulatory axis against cardiomyocyte injury induced by H/R.
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Neoplasias do Colo , Doença da Artéria Coronariana , MicroRNAs , Isquemia Miocárdica , Traumatismo por Reperfusão Miocárdica , RNA Longo não Codificante , Animais , Humanos , Camundongos , Apoptose/fisiologia , beta Catenina/metabolismo , Neoplasias do Colo/metabolismo , Doença da Artéria Coronariana/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , Isquemia Miocárdica/metabolismo , Traumatismo por Reperfusão Miocárdica/genética , Traumatismo por Reperfusão Miocárdica/prevenção & controle , Traumatismo por Reperfusão Miocárdica/metabolismo , Miócitos Cardíacos/metabolismo , Complexo Repressor Polycomb 1/genética , Espécies Reativas de Oxigênio/metabolismo , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismoRESUMO
BACKGROUND: Optical coherence tomography (OCT) or OCT angiography (OCTA) has been investigated in few research studies of psychiatric disorders. No research has been done using OCT or OCTA in patients with borderline personality disorder (BPD). METHODS: OCTA measured foveal avascular zone (FAZ), macular vessel density (MVD), and peripapillary vessel density (PVD). OCT measured the peripapillary retinal fiber layer (RNFL) and central retinal thickness (CRT). The study utilized the Ottawa Self-Injury Inventory, Hamilton Anxiety Rating Scale (HAMA), and Global Assessment of Functioning (GAF) to assess the symptom characteristics of individuals with BPD. RESULTS: Fifty-nine eyes of BPD patients and 58 eyes of normal subjects were analyzed, MVD of the superficial retinal capillary plexus declined noticeably in most subfields (p < 0.05). Significant differences were observed in the whole inner ring and outer ring index between BPD and HC groups (p < 0.05). The patients with BPD exhibited lower RNFL and CRT, the difference was significant (p < 0.05). CRT indicated a significant negative correlation with the Ottawa Self-Injury Inventory (p < 0.05). In addition, we observed that there was a negative correlation identified between the MVD of the inner ring and HAMA (p < 0.05). Meanwhile, the MVD of the outer ring was positively correlated with GAF (p < 0.05). The areas under the receiver operating characteristic curves (AUROCs) for distinguishing BPD and HC eyes in OCTA were the highest for fovea MVD (0.679), followed by outer ring MVD (0.669), inner ring MVD (0.641), FAZ (0.579). In OCT, CRT was highest for BPD (0.711), followed by RNFL (0.625). CONCLUSION: The OCT and OCTA can non-invasively detect microvascular and morphology changes of the retina in BPD patients compared to healthy control subjects.
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Transtorno da Personalidade Borderline , Macula Lutea , Humanos , Angiofluoresceinografia/métodos , Vasos Retinianos/diagnóstico por imagem , Tomografia de Coerência Óptica/métodos , Transtorno da Personalidade Borderline/diagnóstico por imagem , Macula Lutea/irrigação sanguíneaRESUMO
Purpose: To reveal the clinical significance, pathological involvement and molecular mechanism of imprinted in Prader-Willi syndrome (IPW) in RPE anomalies that contribute to AMD. Methods: IPW expression under pathological conditions were detected by microarrays and qPCR assays. In vitro cultured fetal RPE cells were used to study the pathogenicity induced by IPW overexpression and to analyze its upstream and downstream regulatory networks. Results: We showed that IPW is upregulated in the macular RPE-choroid tissue of dry AMD patients and in fetal RPE cells under oxidative stress, inflammation and dedifferentiation. IPW overexpression in fetal RPE cells induced aberrant apical-basal polarization as shown by dysregulated polarized markers, disrupted tight and adherens junctions, and inhibited phagocytosis. IPW upregulation was also associated with RPE oxidative damages, as demonstrated by intracellular accumulation of reactive oxygen species, reduced cell proliferation, and accelerated cell apoptosis. Mechanically, N6-methyladenosine level of the IPW transcript regulated its stability with YTHDC1 as the reader. IPW mediated RPE features by suppressing MEG3 expression to sequester its inhibition on the AKT serine-threonine kinase (AKT)/mammalian target of rapamycin (mTOR) pathway. We also noticed that the mTOR inhibitor rapamycin suppresses the AKT/mTOR pathway to alleviate the IPW-induced RPE anomalies. Conclusions: We revealed that IPW overexpression in RPE induces aberrant apical-basal polarization and oxidative damages, thus contributing to AMD progression. We also annotated the upstream and downstream regulatory networks of IPW in RPE. Our findings shed new light on the molecular mechanisms of RPE dysfunctions, and indicate that IPW blockers may be a promising option to treat RPE abnormalities in AMD.
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Adenina/análogos & derivados , Degeneração Macular , Síndrome de Prader-Willi , Humanos , Epitélio Pigmentado da Retina/patologia , Síndrome de Prader-Willi/genética , Síndrome de Prader-Willi/metabolismo , Síndrome de Prader-Willi/patologia , Proteínas Proto-Oncogênicas c-akt/metabolismo , Regulação para Cima , Degeneração Macular/metabolismo , Estresse Oxidativo , Serina-Treonina Quinases TOR/metabolismoRESUMO
Dragon's Blood (DB) serves as a precious Chinese medicine facilitating blood circulation and stasis dispersion. Daemonorops draco (D. draco; Qi-Lin-Jie) and Dracaena cochinchinensis (D. cochinchinenesis; Long-Xue-Jie) are two reputable plant sources for preparing DB. This work was designed to comprehensively characterize and compare the metabolome differences between D. draco and D. cochinchinenesis, by integrating liquid chromatography/mass spectrometry and untargeted metabolomics analysis. Offline two-dimensional liquid chromatography/ion mobility-quadrupole time-of-flight mass spectrometry (2D-LC/IM-QTOF-MS), by utilizing a powerful hybrid scan approach, was elaborated for multicomponent characterization. Configuration of an XBridge Amide column and an HSS T3 column in offline mode exhibited high orthogonality (A0 0.80) in separating the complex components in DB. Particularly, the hybrid high-definition MSE-high definition data-dependent acquisition (HDMSE-HDDDA) in both positive and negative ion modes was applied for data acquisition. Streamlined intelligent data processing facilitated by the UNIFI™ (Waters) bioinformatics platform and searching against an in-house chemical library (recording 223 known compounds) enabled efficient structural elucidation. We could characterize 285 components, including 143 from D. draco and 174 from D. cochinchinensis. Holistic comparison of the metabolomes among 21 batches of DB samples by the untargeted metabolomics workflows unveiled 43 significantly differential components. Separately, four and three components were considered as the marker compounds for identifying D. draco and D. cochinchinenesis, respectively. Conclusively, the chemical composition and metabolomic differences of two DB resources were investigated by a dimension-enhanced analytical approach, with the results being beneficial to quality control and the differentiated clinical application of DB.
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Quimiometria , Metaboloma , Extratos Vegetais , Espectrometria de Massas , Cromatografia Líquida , Cromatografia Líquida de Alta Pressão/métodosRESUMO
OBJECTIVE: To explore the changes in the health-related quality of life (HRQoL) in patients with primary aldosteronism (PA) after standardized treatment and determine the effects of different variables on the change in the HRQoL of patients. METHODS: A total of 116 patients with PA were prospectively included from November 2020 to March 2022. Data were collected at their initial diagnosis and the follow-up after 12 months of treatment, including demographic and clinical data and the scores of the Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36). The scores of each dimension of SF-36 of patients before and after treatment were compared, and the factors affecting their change in the quality of life were analyzed using multiple linear regression. RESULTS: After standardized treatment, the aldosterone-to-renin ratio (Z = -4.967, P < .001), systolic blood pressure (t = 8.985, P < .001), and diastolic blood pressure (t = 7.233, P < .001) of patients with PA decreased compared with baseline, and hypokalemia was effectively corrected (χ2 = 69.014, P < .001). In terms of quality of life, 6 of 8 dimensions of SF-36 and the total score of SF-36 significantly improved at 1-year follow-up compared with baseline (all P < .05). The results of multiple linear regression showed that the improvement in the HRQoL in patients with PA after standardized treatment was correlated with the change in the blood potassium level (P = .007) and systolic blood pressure (P = .003). CONCLUSION: Correction of hypokalemia and control of diastolic blood pressure are essential factors contributing to the improvement in the HRQoL in patients with PA regardless of the standardized treatment received.
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Hiperaldosteronismo , Hipopotassemia , Humanos , Qualidade de Vida , Hiperaldosteronismo/terapia , Hipopotassemia/etiologia , Pressão Sanguínea , Estudos Prospectivos , AldosteronaRESUMO
BACKGROUND: Research has shown the diagnostic potential of optical coherence tomography (OCT) and OCT angiography (OCTA) in various psychiatric disorders. However, there is few research focusing on changes specific to Major Depressive Disorder (MDD), and the diagnostic value of OCT combined with OCTA parameters for MDD remains unclear. METHODS: In this study, we investigated microvascular and morphology changes in the retina of MDD patients using a combination of OCTA and OCT parameters, and to examine their correlation with MDD mood and cognitive function in order to assess their diagnostic capability. RESULTS: Our findings revealed a significant decline in macular vessel density (MVD) in the superficial retinal capillary plexus (SRCP) across all subfields, except the NO area. We also observed a significant positive correlation between fovea and Stroop-1, as well as between temporal inner (TI) and Stroop-3 in MDD patients. Furthermore, we identified a negative correlation between fovea and Self-Rating Depression Scale, as well as between Superior outer (SO) and Difficulties in Emotion Regulation Scale-C in MDD patients. LIMITATIONS: The sample size was small. Anatomical variables in blood flow may contribute to variability between subjects and outcomes. CONCLUSIONS: The diagnostic value of OCTA suggests their potential as valuable tools for monitoring and diagnosing MDD.
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Transtorno Depressivo Maior , Vasos Retinianos , Humanos , Vasos Retinianos/diagnóstico por imagem , Angiofluoresceinografia/métodos , Transtorno Depressivo Maior/diagnóstico por imagem , Tomografia de Coerência Óptica/métodos , RetinaRESUMO
STUDY OBJECTIVES: This study aimed to evaluate the safety and short-term effect of contemporaneous surgeries (bariatric surgery plus uvulopalatopharyngoplasty [UPPP]) in the treatment of morbid obesity comorbid with severe obstructive sleep apnea (OSA). METHODS: A retrospective cohort study was performed to identify patients with obesity and severe OSA who underwent laparoscopic sleeve gastrectomy (LSG) with or without UPPP surgeries between December 2019 and December 2021 in our center. Patients were divided into 2 groups according to different surgical methods (contemporaneous group [LSG with UPPP] vs LSG-only group). Data about surgical safety, OSA remission, and effectiveness of weight loss were collected and analyzed between the 2 groups before and 12 months after surgery. RESULTS: A total of 101 patients were included in this study (contemporaneous group [LSG with UPPP], n = 42 vs LSG only group, n = 59). There was no significant difference in surgical safety between the 2 groups, and both OSA and obesity were significantly improved at 12.5 ± 2.1 months postoperative follow-up. The apnea-hypopnea index decreased from 68.7 ± 30.4 events/h to 10.2 ± 7.0 events/h in the contemporaneous group (P < .001) and from 64.7 ± 26.2 events/h to 18.9 ± 9.8 events/h in the LSG group (P < .001). Moreover, the apnea-hypopnea index decreased to below 5 events/h in 50% of patients (21/42) in the contemporaneous group but only in 13.5% of patients in the LSG group (P < .001). In the LSG group 20 (34%) patients achieved a reduction in apnea-hypopnea index < 15 events/h and resolution of daytime sleepiness. CONCLUSIONS: Contemporaneous surgery (concurrent bariatric and UPPP surgeries) is feasible and an effective option for patients with obesity and severe OSA. However, our finding suggests that approximately a third of patients undergoing LSG with UPPP may not derive significant benefit from the UPPP portion of the contemporaneous surgical approach. CITATION: Yang C, Yu W, Yao K, et al. Concurrent laparoscopic sleeve gastrectomy with uvulopalatopharyngoplasty in the treatment of morbid obesity comorbid with severe obstructive sleep apnea: a retrospective cohort study. J Clin Sleep Med. 2024;20(4):555-564.
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Laparoscopia , Obesidade Mórbida , Apneia Obstrutiva do Sono , Humanos , Obesidade Mórbida/complicações , Obesidade Mórbida/cirurgia , Estudos Retrospectivos , Resultado do Tratamento , Apneia Obstrutiva do Sono/complicações , Apneia Obstrutiva do Sono/epidemiologia , Apneia Obstrutiva do Sono/cirurgia , Gastrectomia/métodos , Laparoscopia/métodosRESUMO
Purpose: The efficacy of adjunctive ambrisentan treatment in patients with systemic sclerosis (SSc) suffering from digital ulcers (DUs) was investigated.Material and methods: Patients (4 males, 7 females) diagnosed with SSc at our hospital between 2017 and 2022 were enrolled. Ten of them had diffuse SSc, while one had limited SSc. These patients received daily 5 mg doses of ambrisentan in addition to their regular SSc treatment for 16 weeks. Parameters including the total number and size of existing and new DUs, Visual Analog Score (VAS), frequency of Raynaud's phenomenon (RP) attacks, and any adverse effects were assessed.Results: At baseline, the median number and size of DUs was 3.0 (interquartile range (IQR): 2.0-4.0 cm) and 0.4 cm (IQR: 0.3-0.5 cm), respectively. Following the intervention, seven patients with a median of 2.0 DUs and a size of 0.35 cm (IQR: 0.15-0.45 cm) at baseline achieved complete healing. Significant improvements were also observed in other patients. VAS scores decreased from a baseline median of 5.0-0.0 (IQR: 0.0-1.0), and both the frequency and duration of RP attacks notably reduced.Conclusion: Adjunctive ambrisentan therapy proved effective in promoting DU healing and preventing new DUs in SSc patients.
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Escleroderma Sistêmico , Úlcera Cutânea , Masculino , Feminino , Humanos , Dedos , Úlcera Cutânea/tratamento farmacológico , Úlcera Cutânea/etiologia , Escleroderma Sistêmico/complicaçõesRESUMO
Background: Metabolic reprogramming is involved in different stages of tumorigenesis. There are six widely recognized tumor-associated metabolic pathways, including cholesterol catabolism process, fatty acid metabolism, glutamine metabolic process, glycolysis, one carbon metabolic process, and pentose phosphate process. This study aimed to classify gastric cancer patients into different metabolic bio-similar clusters. Method: We analyzed six tumor-associated metabolic pathways and calculated the metabolic pathway score through RNA-seq data using single sample gene set enrichment analysis. The consensus clustering analysis was performed to classify patients into different bio-similar clusters by multi-dimensional scaling. Kaplan-Meier curves were presented between different metabolic bio-similar groups for OS analysis. Results: A training set of 370 patients from the Cancer Genome Atlas database with primary gastric cancer was chosen. Patients were classified into four metabolic bio-similar clusters, which were identified as metabolic non-specificity, metabolic-active, cholesterol-silence, and metabolic-silence clusters. Survival analysis showed that patients in metabolic-active cluster and metabolic-silence cluster have significantly poor prognosis than other patients (p=0.031). Patients in metabolic-active cluster and metabolic-silence cluster had significantly higher intra-tumor heterogeneity than other patients (p=0.032). Further analysis was performed in metabolic-active cluster and cholesterol-silence cluster. Three cell-cycle-related pathways, including G2M checkpoints, E2F targets, and MYC targets, were significantly upregulated in metabolic-active cluster than in cholesterol-silence cluster. A validation set of 192 gastric cancer patients from the Gene Expression Omnibus data portal verified that metabolic bio-similar cluster can predict prognosis in gastric cancer. Conclusion: Our study established a multi-dimension metabolic prognostic model in gastric cancer, which may be feasible for predicting clinical outcome.
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Neoplasias Gástricas , Humanos , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/genética , Prognóstico , Metabolismo dos Lipídeos , Carcinogênese , ColesterolRESUMO
STUDY QUESTION: How do the types and frequency of chromosome aberrations in couples in central China affect fertility and ART treatment? SUMMARY ANSWER: Men with chromosome aberrations or polymorphisms have an increased risk of semen quality impairment and infertility, and couples affected by reciprocal translocations had a lower pregnancy rate compared with other chromosome aberrations. WHAT IS KNOWN ALREADY: Karyotyping is crucial for patients affected by infertility as chromosome aberrations play an important role in the etiology of male infertility. However, the influence of chromosome aberrations and polymorphisms on sperm motility and morphology remains controversial. Data on ART treatment outcomes in infertile couples affected by chromosome aberrations are insufficient. STUDY DESIGN, SIZE, DURATION: We conducted a retrospective study involving 17â054 patients affected by infertility who underwent karyotyping in our center between January 2020 and May 2022. PARTICIPANTS/MATERIALS, SETTING, METHODS: Karyotyping was performed on 17â054 patients with reproductive failure. All patients were from the central regions of China. The following data were collected from a medical records system using patient identification numbers: couples' ages, history of pregnancy and childbirth, type of infertility, years of infertility, cause of infertility, chromosome karyotypes, semen analysis results, assisted reproductive techniques performed, and treatment outcomes of ART. MAIN RESULTS AND THE ROLE OF CHANCE: The incidence of chromosome aberrations was 2.04%; 2.49% in men and 1.57% in women. By analyzing the relationships between chromosome aberrations/polymorphisms and abnormal semen parameters, we found that there were significantly higher rates of asthenozoospermia, oligospermia, and teratozoospermia among men with Robertsonian translocations and sex chromosomal structural aberrations compared with those with normal karyotypes. Higher rates of asthenozoospermia and teratozoospermia were also observed among men with autosomal reciprocal translocations. The incidence of chromosome aberrations in azoospermic men (13.75%), and in men with cryptozoospermia or severe oligospermia (6.97%) was significantly higher than that in men with mild oligospermia or normospermia (0.88-2.12%). In addition, we found that the progressive movement of sperm is impaired in men with Chromosome 21 polymorphisms compared with men with normal karyotypes (39.46% ± 20.51% vs 48.61% ± 18.76%, P = 0.026). The percentage of morphologically normal forms was lower in the chromosomal polymorphism group than in the normal karyotype group (5.01% ± 2.41% vs 5.59% ± 2.14%, P = 0.001), especially in men with polymorphisms on Chromosome 9 (enlarged Chromosome 9 heterochromatin [9qh+]: 4.48% ± 2.22% vs 5.59% ± 2.14%, P = 0.006; pericentric inversion of Chromosome 9 [inv(9)]: 5.09% ± 3.11% vs 5.59% ± 2.14%, P = 0.008). ART treatment was successful in 36.00% of couples affected by chromosome aberrations. However, couples affected by reciprocal translocations achieved a lower pregnancy rate (24.07%), which may be due to the lower euploidy rates (27.31%) when compared with that in other chromosome aberrations. LIMITATIONS, REASONS FOR CAUTION: First, although the initial cohort was large, chromosome aberrations were identified in a small number of patients. Second, the observational nature of the study design is limiting. Third, the couples affected by infertility in this study were all outpatients that did not undergo identical comprehensive examinations except for karyotyping, leading to the incomplete collection of medical records. Also, the population included in this study mainly focused on couples affected by infertility, which may not be included in the European Association of Urology (EAU) recommendation on male infertility. WIDER IMPLICATIONS OF THE FINDINGS: Men with chromosome aberrations or polymorphisms have an increased risk of semen quality impairment and infertility. Constitutional chromosome analysis is recommended for men affected by infertility and severe oligospermia or azoospermia to facilitate early and appropriate guidance for the most suitable treatment. Carriers of chromosome aberrations can achieve acceptable pregnancy outcomes through IVF. However, couples affected by reciprocal translocations have lower pregnancy rates, and more treatment cycles are needed before a successful pregnancy. A possible explanation may be the fewer euploid embryos obtained. STUDY FUNDING/COMPETING INTEREST(S): This work was supported by Grant 2021YFC2700603 from the National Key Research & Development Program of China. The authors declare no conflicts of interest. TRIAL REGISTRATION NUMBER: N/A.
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Astenozoospermia , Infertilidade Masculina , Oligospermia , Teratozoospermia , Gravidez , Masculino , Humanos , Feminino , Estudos Retrospectivos , Análise do Sêmen , Sêmen , Motilidade dos Espermatozoides , Aberrações Cromossômicas , Translocação Genética , Infertilidade Masculina/genética , Infertilidade Masculina/terapia , FertilidadeRESUMO
Background: Acute kidney injury (AKI) is one of the most common clinical emergencies characterized by rapid progression, difficulty in early diagnosis, and high mortality. Currently, there are no effective AKI early diagnostic methods and treatments. Therefore, identifying new mechanisms of AKI have become urgent for development new targets for early diagnosis and treatment of AKI in the current clinical setting. Methods: In this study, systematic analysis and comparison of serum metabolic profiles of clinical AKI patients, chronic kidney disease (CKD) patients, and healthy subjects were performed using untargeted metabolomics. Moreover, the first spatial metabolomic analysis of kidney tissues in an AKI mouse model using MALDI-TOF MS technology was conducted. Differentially expressed metabolites were identified using a comprehensive, publicly available database. The metabolic data obtained were evaluated using principal component analysis, (orthogonal) partial least squares discriminant analysis, and metabolic pathway analysis to explore the unique serum metabolic profile of the patients, as well as to characterize the spatial distribution of differential metabolites in the kidneys of AKI mice. Results: Significant changes in the metabolite levels of amino acids, carnitine, and lipids were observed in the AKI and CKD groups versus the healthy population, suggesting that kidney injury may lead to abnormalities in various metabolic pathways, such as amino acids, fatty acids, and lipids. The significant difference between the AKI and CKD groups were found for the first time in these indexes including amino acid, carnitine, fatty acid, and lipid levels. Additionally, spatial metabolomics results revealed that amino acid, carnitine, organic acid, and fatty acid metabolites were more likely significantly altered in the renal cortex, while lipid metabolites were both differentially distributed in the cortex and medulla of the AKI group. Conclusion: Abnormalities in the serum metabolism of amino acids, carnitine, and lipids in patients with kidney diseases, such as AKI and CKD, are closely associated with the physiological dysfunction of kidney injury. Metabolic differences between patients with AKI and CKD were compared for the first time, showing that fatty acid oxidative inhibition was more severe in patients with AKI. Furthermore, spatial metabolomics has revealed metabolic reprogramming with tissue heterogeneity in AKI mice model. Our study provides valuable information in the molecular pathological features of AKI in the kidney tissues.
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Objective To investigate the fluorescence resonance energy transfer (FRET) effect between dylight (DL) and AuNP (AuNP), and to construct a new fluorescence immunoassay for insulin in combination with the immunocompetition method. Methods Insulin antigen (Ag) and insulin antibody (Ab) were conjugated with DL and AuNP respectively to form DL-Ag conjugate and AUNp-AB conjugate. A novel fluorescence immunoassay for insulin was developed on the basis of FRET effect and the immune competition response between them. Then the performance of the method was evaluated and its application in actual samples was explored. Results The fluorescence immunoassay showed high sensitivity (0.015 ng/mL), short measurement time (4 min) and good specificity. It was successfully used in the measurement of serum insulin, and the recovery was between 96.9% and 121.1%. Conclusion FRET effect between AuNP and DL can be applied to develop a fluorescence immunoassay for the measurement of serum insulin.