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Background: Understanding the dynamic relationship between depressive symptoms and quality of life (QOL) is essential in improving long-term outcomes for patients with Major Depressive Disorder (MDD). While previous studies often relied on cross-sectional data, there is a pressing need for stronger evidence based on longitudinal data to better inform the development of effective clinical interventions. By focusing on key depressive symptoms, such interventions have the potential to ultimately enhance QOL in individuals with MDD. Methods: This multi-center prospective study, conducted between 2016 and 2020, enrolled outpatients and inpatients diagnosed with MDD across twelve psychiatric hospitals in China. Longitudinal data on Patient Health Questionnaire - 9 (PHQ-9) and Quality of Life Enjoyment and Satisfaction Questionnaire-Short Form (Q-LES-Q-SF) was analyzed using an Extended Bayesian Information Criterion (EBIC) graphical least absolute shrinkage and selection operator (gLASSO) network model to explore the connections between depressive symptom changes and QOL changes. Flow network was applied to investigate relationships between individual symptom changes and overall QOL score change, as well as daily functional independence. Results: This study included 818 participants with complete data after 8-week antidepressant treatment. Apart from the overlapping items from PHQ-9 and Q-LES-Q-SF, the three edges between "mood" (delta-QLES2) and "anhedonia" (delta-DEP1), between "physical health" (delta-QLES1) and "sleep problems" (delta-DEP3), and between "physical health" (delta-QLES1) and "sad mood" (delta-DEP2) were the most strong bridges between the cluster of depressive symptoms alleviation and the cluster of QOL change. "Anhedonia" (delta-DEP1), "sad mood" (delta-DEP2) and "loss of energy" (delta-DEP4) had the highest bridge strength between the alleviations of depressive symptoms and the total score change of Q-LES-Q-SF. Anhedonia had the greatest connection with participants' satisfaction with function in daily life. Conclusion: This study highlighted the potential for developing highly effective interventions by targeting on central symptoms, thereby to ultimately improve QOL for patients with MDD.
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Hepatocellular carcinoma (HCC) is a prevalent and aggressive malignancy associated with high risks of recurrence and metastasis. Liver cancer stem cells (CSCs) are increasingly recognized as pivotal drivers of these processes. In our previous research, we demonstrated the involvement of TFCP2L1 in maintaining the pluripotency of embryonic stem cells. However, its relevance to liver CSCs remains unexplored. In this study, we report an inverse correlation between TFCP2L1 protein levels in HCC tissue and patient outcomes. The knockdown of TFCP2L1 significantly reduced HCC cell proliferation, invasion, metastasis, clonal formation, and sphere-forming capacity, while its overexpression enhanced these functions. In addition, experiments using a nude mouse model confirmed TFCP2L1's essential role in liver CSCs' function and tumorigenic potential. Mechanistically, we showed that TFCP2L1 promotes the stemness of CSCs by upregulating NANOG, which subsequently activates the JAK/STAT3 pathway, thereby contributing to HCC pathogenesis. Importantly, we identified a specific small molecule targeting TFCP2L1's active domain, which, in combination with Sorafenib, sensitizes hepatoma cells to treatment. Together, these findings underscore TFCP2L1's pathological significance in HCC progression, supporting its potential as a prognostic biomarker and therapeutic target in this disease.
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Background: Multiple sclerosis (MS), a chronic autoimmune disorder marked by demyelination in the central nervous system, is exceptionally uncommon in China, and remains poorly understood in terms of its peripheral blood manifestations. Methods: We conducted a cohort study comprising 39 MS patients and 40 normal controls (NC). High-dimensional mass cytometry, protein arrays, and targeted metabolomics were utilized to profile immune subsets, proteins, and metabolites in blood. Differences in multi-omics signatures were scrutinized across varying MS subtypes. Results: Immune profiling demonstrated an elevation in various B cell subsets and monocytes, alongside a reduction in dendritic cells among MS patients. Proteomic data revealed a downregulation in neurotrophic and tissue repair proteins. Metabolomic assessment showed a noted decrease in anti-inflammatory molecules and sphingolipids. Integrated analysis identified distinct molecular patterns distinguishing MS from controls. Additionally, multi-omics differences among different MS subtypes were uncovered. Notably, hippuric acid levels was consistently lower in MS subgroups with greater disease severity. Conclusion: This study represents the pioneering exploration of multi-omics in Chinese MS patients, presenting a comprehensive view of the peripheral blood changes in MS. Our study underscores the robust capability of multi-omics assessments in identifying peripheral blood biomarkers that delineate the varied clinical presentation, and facilitates future development of biomarkers and targeted therapeutic interventions in MS.
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BACKGROUND: Older adults with heart disease often experience higher rates of comorbid anxiety and depression. This study examined depression and anxiety network structures among older adults with heart disease and their heart disease free peers. METHODS: Network analyses of secondary cross-sectional data from the 2017 to 2018 wave of CLHLS were used to construct groups of older adults with and without heart disease using propensity score matching. Depression and anxiety symptoms were assessed using Center for Epidemiological Studies Depression Scale and Generalized Anxiety Disorder Scale, respectively. Central symptoms and bridge symptoms were identified using expected influence. RESULTS: 1689 older adults with heart disease and matched control sample of 1689 older adults without heart disease were included. The prevalence and severity of depression and anxiety were significantly higher in older adults with heart disease compared to the control group. There was no significant difference in overall structures of depression and anxiety network models between two the groups. Key central symptoms and bridge symptoms within these groups were highly similar; GAD 2 "Uncontrollable worrying" and GAD 4 "Trouble relaxing" were identified as the most central symptoms, while GAD 1 "Nervousness" and CESD 1 "Feeling bothered" were identified as key bridge symptoms across both network models. CONCLUSION: Depression and anxiety are more prevalent in older adults with heart disease than demographically-matched heart disease free controls. However, network structures of these symptoms do not differ between two groups. Accordingly, depression and anxiety psychosocial interventions developed for older adults without heart disease may also benefit older adults with heart disease.
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To develop a clean-up material suitable for high-fat food matrices for detecting mycotoxins in yak ghee, an octadecyl-bonded hectorite (Hectorite@NHCO(CH2)17CH3) was synthesized through multi-step chemical reactions. A modified QuEChERS-HPLC-MS/MS method for detecting ten mycotoxins in sesame oil in yak ghee was established using Hectorite@NHCO(CH2)17CH3 as clean-up agent. It involved extracting mycotoxin contaminants using acidified acetonitrile and employing the Hectorite@NHCO(CH2)17CH3 to remove interfering substances from the extract. The purified samples were then analyzed using HPLC-MS/MS. Within a linear range of 1.0-500 µg/kg, there was a good linear relationship between the quantification ion peak area of the target analytes and the corresponding concentrations (R2 ≥ 0.9991). The limit of detection (LOD) ranged from 0.10 µg/kg to 18.62 µg/kg and the limit of quantitation (LOQ) ranged 0.32-62.07 µg/kg. The recoveries at low, medium and high concentrations (25, 100 and 500 µg/kg) ranged from 72.2% to 113.9%, with relative standard deviations (RSD) between 3.2% and 17.5%. The intra-day and inter-day precision met experimental requirements. The proposed method was characterized by a high accuracy and precision, and it could cater to the current demand for detecting ten mycotoxins in yak ghee.
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Coronary artery segmentation is crucial for physicians to identify and locate plaques and stenosis using coronary computed tomography angiography (CCTA). However, the low contrast of CCTA images and the intricate structures of coronary arteries make this task challenging. To address these difficulties, we propose a novel model, the DFS-PDS network. This network comprises two subnetworks: a discriminative frequency segment subnetwork (DFS) and a position domain scales subnetwork (PDS). DFS introduced a gated mechanism within the feed-forward network, leveraging the Joint Photographic Experts Group (JPEG) compression algorithm, to discriminatively determine which low- and high-frequency information of the features should be preserved for latent image segmentation. The PDS aims to learn the shape prototype by predicting the radius. Additionally, our model has the consistent ability to guarantee region and boundary features through boundary consistency loss. During training, both subnetworks are optimized jointly, and in the testing stage, the coarse segmentation and radius prediction are produced. A coronary-geometric refinement method refines the segmentation masks by leveraging the shape prior to being reconstructed from the radius map, reducing the difficulty of segmenting coronary artery structures from complex surrounding structures. The DFS-PDS network is compared with state-of-the-art (SOTA) methods on two coronary artery datasets to evaluate its performance. The experimental results demonstrate that the DFS-PDS network performs better than the SOTA models, including Vnet, nnUnet, DDT, CS2-Net, Unetr, and CAS-Net, in terms of Dice or connectivity evaluation metrics.
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Vasos Coronarios , Humanos , Vasos Coronarios/diagnóstico por imagen , Algoritmos , Angiografía por Tomografía Computarizada/métodos , Angiografía Coronaria/métodos , Procesamiento de Imagen Asistido por Computador/métodosRESUMEN
BACKGROUND: Cervical cancer has the second-highest mortality rate among malignant tumors of the female reproductive system. Immune checkpoint inhibitors such as programmed cell death protein 1 (PD-1) blockade are promising therapeutic agents, but their efficacy when combined with neoadjuvant chemotherapy (NACT) has not been fully tested, and how they alter the tumor microenvironment has not been comprehensively elucidated. METHODS: In this study, we conducted single-cell RNA sequencing using 46,950 cells from nine human cervical cancer tissues representing sequential different stages of NACT and PD-1 blockade combination therapy. We delineated the trajectory of cervical epithelial cells and identified the crucial factors involved in combination therapy. Cell-cell communication analysis was performed between tumor and immune cells. In addition, THP-1-derived and primary monocyte-derived macrophages were cocultured with cervical cancer cells and phagocytosis was detected by flow cytometry. The antitumor activity of blocking CD74 was validated in vivo using a CD74 humanized subcutaneous tumor model. RESULTS: Pathway enrichment analysis indicated that NACT activated cytokine and complement-related immune responses. Cell-cell communication analysis revealed that after NACT therapy, interaction strength between T cells and cancer cells decreased, but intensified between macrophages and cancer cells. We verified that macrophages were necessary for the PD-1 blockade to exert antitumor effects in vitro. Additionally, CD74-positive macrophages frequently interacted with the most immunoreactive epithelial subgroup 3 (Epi3) cancer subgroup during combination NACT. We found that CD74 upregulation limited phagocytosis and stimulated M2 polarization, whereas CD74 blockade enhanced macrophage phagocytosis, decreasing cervical cancer cell viability in vitro and in vivo. CONCLUSIONS: Our study reveals the dynamic cell-cell interaction network in the cervical cancer microenvironment influenced by combining NACT and PD-1 blockade. Furthermore, blocking tumor-associated macrophage-derived CD74 could augment neoadjuvant therapeutic efficacy.
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Inhibidores de Puntos de Control Inmunológico , Terapia Neoadyuvante , Macrófagos Asociados a Tumores , Neoplasias del Cuello Uterino , Neoplasias del Cuello Uterino/tratamiento farmacológico , Neoplasias del Cuello Uterino/inmunología , Neoplasias del Cuello Uterino/patología , Humanos , Femenino , Terapia Neoadyuvante/métodos , Macrófagos Asociados a Tumores/metabolismo , Macrófagos Asociados a Tumores/inmunología , Macrófagos Asociados a Tumores/efectos de los fármacos , Ratones , Animales , Inhibidores de Puntos de Control Inmunológico/farmacología , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Receptor de Muerte Celular Programada 1/antagonistas & inhibidores , Receptor de Muerte Celular Programada 1/metabolismo , Microambiente Tumoral , Antígenos de Diferenciación de Linfocitos B/metabolismo , Protocolos de Quimioterapia Combinada Antineoplásica/farmacología , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Antígenos de Histocompatibilidad Clase IIRESUMEN
ConspectusElectrides make up a fascinating group of materials with unique physical and chemical properties. In these materials, excess electrons do not behave like normal electrons in metals or form any chemical bonds with atoms. Instead, they "float" freely in the gaps within the material's structure, acting like negatively charged particles called anions (see the graph). Recently, there has been a surge of interest in van der Waals (vdW) electrides or electrenes in two dimensions. A typical example is layered lanthanum bromide (LaBr2), which can be taken as [La3+(Br1-)2]+â¢(e-). Each excess free electron is trapped within a hexagonal pore, forming dense dots of electron density. These anionic electrons are loosely bound, giving vdW electrides some unique properties such as ferromagnetism, superconductivity, topological features, and Dirac plasmons. The high density of the free electron makes electrides very promising for applications in thermionic emission, organic light-emitting diodes, and high-performance catalysts.In this Account, we first discuss the discovery of numerous vdW electrides through high-throughput computational screening of over 67,000 known inorganic crystals in Materials Project. A dozen of them have been newly discovered and have not been reported before. Importantly, they possess completely different structural prototypes and properties of anionic electrons compared to widely studied electrides such as Ca2N. Finding these new vdW electrides expands the variety of electrides that can be made in the experiment and opens up new possibilities for studying their unique properties and applications.Then, based on the screened vdW electrides, we delve into their various emerging properties. For example, we developed a new magnetic mechanism specific to atomic-orbital-free ferromagnetism in electrides. We uncover the dual localized and extended nature of the anionic electrons in such electrides and demonstrate the formation of the local moment by the localized feature and the ferromagnetic interaction by the direct overlapping of their extended states. We further show the effective tuning of the magnetic properties of vdW electrides by engineering their structural, electronic, and compositional properties. Besides, we show that the complex interaction between the multiple quantum orderings in vdW electrides leads to many interesting properties including valley polarization, charge density waves, a topological property, a superconducting property, and a thermoelectrical property.Moreover, we discuss strategies to leverage the unique intrinsic properties of vdW electrides for practical applications. We show that these properties make vdW electrides potential candidates for advanced applications such as spin-orbit torque memory devices, valleytronic devices, K-ion batteries, and thermoelectricity. Finally, we discuss the current challenges and future perspectives for research using these emerging materials.
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Air pollutants have been investigated to be associated with many health issues. Recently, increasing epidemiological studies have suggested the association between air pollution exposure and risk of frailty with inconsistent findings. This systematic review and meta-analysis was to summarize and evaluate effects of exposure to various air pollutants on risk of frailty. PubMed, Embase, Scopus and Web of Science were systematically searched for relevant studies published before May 11, 2024. Studies that explored the potential relationship between exposure to air pollutants (PM2.5, PM10, O3, NOx, solid fuel, secondhand tobacco, and air quality) and risk of frailty were included. The quality of cross-sectional and cohort studies was evaluated using an eight-item assessment instrument for epidemiological studies and Newcastle-Ottawa Scale, respectively. A total of 9,929 papers were retrieved, of which 20 met the inclusion criteria. Meta-analysis indicated that PM2.5 exposure was significantly associated with frailty assessed by the frailty index [OR (95% CI): 1.24 (1,11-1.38) per 10 µg/m3 increment]. Moreover, solid fuel exposures were significantly associated with an increased risk of frailty assessed by the frailty phenotype [OR (95% CI): 1.91 (1.09-3.34)] or the frailty index [OR (95% CI): 1.25 (1.11-1.41)]. Exposure to PM2.5 and solid fuel increases the risk of frailty. Environmental protection policies and public health measures should be developed to reduce PM2.5 concentrations. Effective measures, such as improving stoves and using clean fuels, should be taken to reduce indoor air pollution levels.
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BACKGROUND: The triglyceride glucose (TyG) index, as a reliable marker of insulin resistance, is associated with the incidence and poor prognosis of various cardiovascular diseases. However, the relationship between the TyG index and clinical outcomes in patients with severe aortic stenosis (AS) who underwent transcatheter aortic valve replacement (TAVR) remains unclear. METHODS: This study consecutively enrolled 1569 patients with AS underwent TAVR at West China Hospital of Sichuan University between April 2014 and August 2023. The outcomes of interest included all-cause mortality, cardiovascular mortality, and major adverse cardiovascular events (MACE). Multivariate adjusted Cox regression and restricted cubic splines (RCS) regression analyses were used to assess the associations between the TyG index and the clinical outcomes. The incremental prognostic value of the TyG index was further assessed by the time-dependent Harrell's C-index, integrated discrimination improvement (IDI) and the net reclassification improvement (NRI). RESULTS: During a median follow-up of 1.09 years, there were 146, 70, and 196 patients experienced all-cause death, cardiovascular death, and MACE, respectively. After fully adjusting for confounders, a per-unit increase of TyG index was associated with a 441% (adjusted HR: 5.41, 95% CI: 4.01-7.32), 385% (adjusted HR: 4.85, 95% CI: 3.16-7.43), and 347% (adjusted HR: 4.47, 95% CI: 3.42-5.85) higher risk of all-cause mortality, cardiovascular mortality and MACE, respectively. The RCS regression analyses revealed a linear association between TyG index and endpoints (all P for non-linearity > 0.05) with 8.40 as the optimal binary cutoff point. Furthermore, adding TyG index to the basic risk model provided a significant incremental value in predicting poor prognosis (Time-dependent Harrell's C-index increased for all the endpoints; All-cause mortality, IDI: 0.11, P < 0.001; NRI: 0.32, P < 0.001; Cardiovascular mortality, IDI: 0.043, P < 0.001; NRI: 0.37, P < 0.001; MACE, IDI: 0.092, P < 0.001; NRI: 0.32, P < 0.001). CONCLUSIONS: In patients with severe AS receiving TAVR, there was a positive linear relationship between TyG index and poor prognosis, with 8.4 as the optimal bivariate cutoff value. Our findings suggest TyG index holds potential value for risk stratification and guiding therapeutic decisions in patients after TAVR.
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Estenosis de la Válvula Aórtica , Biomarcadores , Glucemia , Valor Predictivo de las Pruebas , Índice de Severidad de la Enfermedad , Reemplazo de la Válvula Aórtica Transcatéter , Triglicéridos , Humanos , Estenosis de la Válvula Aórtica/cirugía , Estenosis de la Válvula Aórtica/sangre , Estenosis de la Válvula Aórtica/mortalidad , Estenosis de la Válvula Aórtica/diagnóstico , Reemplazo de la Válvula Aórtica Transcatéter/efectos adversos , Reemplazo de la Válvula Aórtica Transcatéter/mortalidad , Masculino , Femenino , Estudios Retrospectivos , Anciano , Medición de Riesgo , Factores de Riesgo , Anciano de 80 o más Años , Factores de Tiempo , Resultado del Tratamiento , China/epidemiología , Biomarcadores/sangre , Glucemia/metabolismo , Triglicéridos/sangre , Causas de Muerte , Resistencia a la InsulinaRESUMEN
Schizophrenia is recognized as one of the most severe psychiatric disorders, with its pathogenesis likely involving genetic, epigenetic, developmental, and environmental factors. Members of the Methyl-CpG Binding Domain (MBD) Family play a crucial role in the regulation of genomic DNA methylation, and studies have implicated the association between MBD family and neurodevelopmental disorders. Copy number variations (CNVs) are a significant genetic basis for human genomic variation, also playing a critical role in the genetic processes of schizophrenia. Therefore, we aimed to evaluate the susceptibility of MBD family CNVs to schizophrenia by exploring and validating them in two separate populations using CNVplex™ and qPCR methods, and to explore the relationship between MBD family CNVs and clinical phenotypes in the overall population using chi-square tests and Fisher's exact tests. Results suggest that an increase in MBD1 gene copy number and a deficiency in MBD2 gene copy number may be associated with the risk of schizophrenia. The deficiency in MBD2 gene copy number may increase the risk of delusion of reference and delusion of persecutory in the overall sample, as well as in males. This research provides preliminary evidence supporting the association between MBD family CNVs and schizophrenia, highlighting the potential role of the MBD family in the pathogenesis of schizophrenia.
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Variaciones en el Número de Copia de ADN , Proteínas de Unión al ADN , Predisposición Genética a la Enfermedad , Esquizofrenia , Humanos , Esquizofrenia/genética , Masculino , Femenino , Proteínas de Unión al ADN/genética , Adulto , Metilación de ADN , Persona de Mediana Edad , Estudios de Casos y Controles , Factores de TranscripciónRESUMEN
BACKGROUND: Persistent infection with high-risk human papillomavirus (HR-HPV) plays a key role in the onset of cervical cancer. This study was designed to examine the epidemiological trends and genotype distribution of HPV from 2014 to 2023 in the plateau region of Southwest China. METHODS: The findings could offer valuable insights for clinical screening of cervical cancer and the formulation of HPV vaccination policies. This retrospective study analyzed 66,000 women who received HPV-DNA testing at the First People's Hospital of Qujing, Yunnan, China, between 2014 and 2023. The cohort consisted of 33,512 outpatients, 3,816 inpatients, and 28,672 individuals undergoing health examinations. Cervical cells were collected for DNA extraction, and PCR amplification along with Luminex xMAP technology were used to detect 27 HPV genotypes. The data analysis was conducted using GraphPad Prism and IBM SPSS Statistics 27 software. RESULTS: The overall HPV infection rate at the First People's Hospital of Qujing declined from 24.92% in 2014 to 16.29% in 2023, averaging 16.02%. Specific infection rates were 18.50% among outpatients, 12.97% among inpatients, and 13.53% for health examination attendees. The predominant high-risk HPV genotypes identified were HPV52 (2.61%), HPV16 (2.06%), HPV58 (1.81%), HPV53 (1.55%), and HPV39 (1.09%). Meanwhile, the most frequent low-risk HPV genotypes were HPV6 (1.30%), HPV61 (1.21%), and HPV11 (0.85%). In HPV-positive cases, the distribution of single, double, triple, and quadruple or more infections were 79.90%, 15.17%, 3.59%, and 1.33%, respectively. The proportions of pure LR-HPV, pure HR-HPV, and mixed infections were 22.16%, 67.82%, and 10.02%, respectively. Age-specific analysis revealed a bimodal distribution of HPV infection, with the infection rate rapidly decreasing from 44.02% in the ≤ 19 age group to 19.55% in the 20-29 age group and 13.84% in the 30-39 age group, followed by a gradual increase to 14.64% in the 40-49 age group, 16.65% in the 50-59 age group, and 22.98% in the ≥ 60 age group. The coverage rates of the three available vaccines are all below 50%. The results of this study indicated a declining trend in HPV prevalence in the plateau region of Southwest China over the period from 2014 to 2023, especially in the reduction of genotypes targeted by vaccines. CONCLUSION: There were significant variations in the genotypes prevalent among different age groups, years, and patient sources within the same region. The underwhelming vaccination rates emphasize the critical need for developing either a multivalent vaccine or a personalized vaccine that targets the HPV genotypes common in the Chinese population. Furthermore, vaccinating adolescents to curb HPV infection and ensuring regular cervical cancer screenings for postmenopausal women are crucial steps.
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Genotipo , Papillomaviridae , Infecciones por Papillomavirus , Humanos , Femenino , Infecciones por Papillomavirus/epidemiología , Infecciones por Papillomavirus/virología , China/epidemiología , Adulto , Prevalencia , Persona de Mediana Edad , Estudios Retrospectivos , Adulto Joven , Papillomaviridae/genética , Papillomaviridae/clasificación , Papillomaviridae/aislamiento & purificación , Adolescente , Anciano , Neoplasias del Cuello Uterino/virología , Neoplasias del Cuello Uterino/epidemiología , ADN Viral/genética , Cuello del Útero/virologíaRESUMEN
BACKGROUND: Hydroxychloroquine (HCQ) effectively improves lipid levels in patients with autoimmune diseases. This study aimed to examine the effect of HCQ on lipid profiles in patients with immunoglobulin A (IgA) nephropathy (IgAN) and determine whether alterations in lipid profiles can predict the efficacy of HCQ. METHODS: This study retrospectively analyzed 77 patients, and the total cholesterol to high-density lipoprotein cholesterol (TC/HDL-C) decline rate after 3 months of HCQ treatment was selected as a predictor based on receiver operating curve analysis. Patients were then divided into low and high TC/HDL-C decline rate groups based on the optimal cutoff value. The Cox proportional hazard model and Kaplan-Meier curve were used to evaluate the value of the TC/HDL-C decline rate in predicting the efficacy of HCQ in patients with IgAN. RESULTS: Patients in the high TC/HDL-C decline rate group with ≥50% decrease in proteinuria from baseline experienced a significant improvement during the follow-up. Kaplan-Meier analysis revealed that a high TC/HDL-C decline rate was strongly associated with a higher proteinuria reduction rate in patients with IgAN. Furthermore, multivariate Cox analysis indicated that a higher reduction in the TC/HDL-C ratio (hazard ratio: 2.314; 95% confidence interval: 1.234-4.340; p = 0.009) was an independent predictive indicator for achieving ≥50% reduction in proteinuria with HCQ therapy in IgAN. CONCLUSION: HCQ effectively improves lipid profiles in patients with IgAN, and an early decrease in the TC/HDL-C ratio serves as a predictor of better outcomes in patients treated with HCQ.
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HDL-Colesterol , Glomerulonefritis por IGA , Hidroxicloroquina , Humanos , Hidroxicloroquina/uso terapéutico , Masculino , Femenino , Estudios Retrospectivos , Adulto , HDL-Colesterol/sangre , Glomerulonefritis por IGA/tratamiento farmacológico , Glomerulonefritis por IGA/sangre , Persona de Mediana Edad , Colesterol/sangre , Modelos de Riesgos Proporcionales , Estimación de Kaplan-Meier , Proteinuria/tratamiento farmacológico , Proteinuria/etiología , Resultado del Tratamiento , Curva ROCRESUMEN
Background: This research aimed to create a predictive model and an innovative risk classification system for patients with gallbladder cancer who undergo radical surgery. Methods: A cohort of 1387 patients diagnosed with gallbladder cancer was selected from the SEER database. The researchers devised a prognostic tool known as a nomogram, which was subjected to assessment and fine-tuning using various statistical measures such as the concordance index (C-index), receiver operating characteristic (ROC) curve, and calibration curve, decision curve analysis (DCA), and risk stratification were included in the catalog of comparisons. An external validation set comprising 93 patients from Nanchong Central Hospital was gathered for evaluation purposes. Results: The nomogram effectively incorporated seven variables and demonstrated satisfactory discriminatory ability, as evidenced by the C-index (training cohort: 0.737, validation cohort: 0.730) and time-dependent AUC (>0.7). Additionally, calibration plots confirmed the excellent alignment between the nomogram and actual observations. Our investigation unveiled NRI scores of 0.79, 0.81, and 0.81 in the training group, while the validation group exhibited NRI values of 0.82, 0.77, and 0.78. Additionally, when evaluating CSS at three-, six-, and nine-year intervals using DCA curves, our established nomograms demonstrated significantly improved performance compared to the old model (P < 0.05), showcasing enhanced discriminatory ability. The results of the external validation set proved the above results. Conclusions: The current investigation has devised a practical prognostic nomogram and risk stratification framework to aid healthcare practitioners in evaluating the postoperative outlook of individuals who have received extensive surgical treatment for gallbladder carcinoma.
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The study investigated the effect of Compound Shougong Powder(CSGP) on the biological functions of triple-negative breast cancer(TNBC) cells and whether its mechanism of action was related to the epithelial-mesenchymal transition(EMT) signaling pathway. TNBC cells(MDA-MB-231 and BT-549) were treated with different concentrations of CSGP-containing serum. MTS assay was used to detect the effect of CSGP on the proliferation of TNBC cells. The EdU staining was used to detect the effect of CSGP on the proliferation of TNBC cells. Flow cytometry was used to examine the impact of CSGP on apoptosis of TNBC cells. Wound-healing and Transwell assays were used to evaluate the effects of different concentrations of CSGP on the migration and invasion capabilities of TNBC cells. RNA sequencing technology was utilized to elucidate its mechanism. Subsequently, qRT-PCR was performed to measure the mRNA expression levels of E-cadherin, N-cadherin, Slug, Snail, Vimentin, Twist, Zinc finger E-box-Binding homeobox 1(Zeb1), and Zinc finger E-box-Binding homeobox 2(Zeb2). Western blot was used to assess the protein expression levels of Slug, Vimentin, and E-cadherin. After intervention with CSGP, the proliferation of MDA-MB-231 and BT-549 cells significantly decreased, while the apoptosis rate markedly increased. The expression levels of the epithelial marker protein E-cadherin significantly increased, while the expression levels of the EMT-related transcription factors Slug and Vimentin showed a decrease. In conclusion, CSGP inhibits the EMT, thereby suppressing the malignant progression of TNBC.
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Apoptosis , Proliferación Celular , Medicamentos Herbarios Chinos , Transición Epitelial-Mesenquimal , Neoplasias de la Mama Triple Negativas , Transición Epitelial-Mesenquimal/efectos de los fármacos , Humanos , Neoplasias de la Mama Triple Negativas/tratamiento farmacológico , Neoplasias de la Mama Triple Negativas/genética , Neoplasias de la Mama Triple Negativas/metabolismo , Neoplasias de la Mama Triple Negativas/patología , Medicamentos Herbarios Chinos/farmacología , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Femenino , Apoptosis/efectos de los fármacos , Movimiento Celular/efectos de los fármacos , Polvos/química , Cadherinas/genética , Cadherinas/metabolismoRESUMEN
Deuteration of amine compounds has been widely of concern because of its practical role in organic reaction mechanisms and drug research; however, only limited deuteration label methods are accessible with D2O as a deuterium source. Herein, we propose a convenient deuteration protocol, including preparing D2 by the AlGa activation method, using PtRu nanowires as catalysts, and utilizing the elementary step in the couple reaction involving an imine unit, to realize the rapid preparation of a secondary amine with a diversified deuteration label. The self-coupling between nitriles not only provides a symmetric secondary amine with four α-D atoms but also produces high-valued ND3 in an atomic-economic way.
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BACKGROUND: The bidirectional relationships between metabolic syndrome (MetS) and major depressive disorder (MDD) were discovered, but the influencing factors of the comorbidity were barely investigated. We aimed to fully explore the factors and their associations with MetS in MDD patients. METHODS: The data were retrieved from the electronic medical records of a tertiary psychiatric hospital in Beijing from 2016 to 2021. The influencing factors were firstly explored by univariate analysis and multivariate logistic regressions. The propensity score matching was used to reduce the selection bias of participants. Then, the Bayesian networks (BNs) with hill-climbing algorithm and maximum likelihood estimation were preformed to explore the relationships between influencing factors with MetS in MDD patients. RESULTS: Totally, 4126 eligible subjects were included in the data analysis. The proportion rate of MetS was 32.6 % (95 % CI: 31.2 %-34.1 %). The multivariate logistic regression suggested that recurrent depression, uric acid, duration of depression, marriage, education, number of hospitalizations were significantly associated with MetS. In the BNs, number of hospitalizations and uric acid were directly connected with MetS. Recurrent depression and family history psychiatric diseases were indirectly connected with MetS. The conditional probability of MetS in MDD patients with family history of psychiatric diseases, recurrent depression and two or more times of hospitalizations was 37.6 %. CONCLUSION: Using the BNs, we found that number of hospitalizations, recurrent depression and family history of psychiatric diseases contributed to the probability of MetS, which could help to make health strategies for specific MDD patients.
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Teorema de Bayes , Comorbilidad , Trastorno Depresivo Mayor , Síndrome Metabólico , Humanos , Trastorno Depresivo Mayor/epidemiología , Síndrome Metabólico/epidemiología , Femenino , Masculino , Persona de Mediana Edad , Adulto , Factores de Riesgo , China/epidemiología , Modelos Logísticos , Hospitalización/estadística & datos numéricos , Ácido Úrico/sangre , Puntaje de PropensiónRESUMEN
BACKGROUND: Semaglutide, a glucagon-like peptide-1 receptor agonist, is reported to have cardiac benefits, but its effects on preventing atrial fibrillation (AF) remain inconclusive. This study aimed to investigate whether semaglutide can prevent AF occurrence in patients with type 2 diabetes mellitus (T2DM), obesity, or overweight. METHODS: We searched MEDLINE, EMBASE, the Cochrane CENTRAL database, and clinicaltrials.gov from inception to December 29, 2023. Randomized controlled trials of semaglutide in patients with T2DM, obesity, or overweight were included. The primary outcome was AF occurrence. Relative risks (RRs) with 95 % confidence intervals (CIs) were calculated for the overall population and subgroups. RESULTS: Twenty-one trials comprising 25957 patients were included. In the overall pooled analysis, semaglutide decreased AF occurrence compared to control drugs (RR 0.70, 95 % CI 0.52-0.95). This result was consistent in trials using other antihyperglycemic medications as controls (RR 0.43, 95 % CI 0.21-0.89), but not in placebo-controlled trials (RR 0.77, 95 % CI 0.56-1.07). The outcome was favorable for patients with T2DM (RR 0.71, 95 % CI 0.52-0.97), but not for patients with overweight or obesity (RR 0.56, 95 % CI 0.18-1.73). Results varied by type of semaglutide, with oral semaglutide showing an RR of 0.49 (95 % CI 0.25-0.97) and subcutaneous semaglutide showing an RR of 0.77 (95 % CI 0.55-1.07). CONCLUSION: Semaglutide was associated with a reduced risk of AF occurrence in the overall analysis. Favorable outcomes were observed in subsets using other antihyperglycemic medications as controls, in patients with T2DM, and with oral semaglutide.
Asunto(s)
Fibrilación Atrial , Diabetes Mellitus Tipo 2 , Péptidos Similares al Glucagón , Humanos , Péptidos Similares al Glucagón/uso terapéutico , Fibrilación Atrial/tratamiento farmacológico , Fibrilación Atrial/prevención & control , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Hipoglucemiantes/uso terapéutico , Obesidad/complicaciones , Obesidad/tratamiento farmacológico , Pronóstico , Ensayos Clínicos Controlados Aleatorios como Asunto , Sobrepeso/complicacionesRESUMEN
Background Preoperative local-regional tumor staging of gastric cancer (GC) is critical for appropriate treatment planning. The comparative accuracy of multiparametric MRI (mpMRI) versus dual-energy CT (DECT) for staging of GC is not known. Purpose To compare the diagnostic accuracy of personalized mpMRI with that of DECT for local-regional T and N staging in patients with GC receiving curative surgical intervention. Materials and Methods Patients with GC who underwent gastric mpMRI and DECT before gastrectomy with lymphadenectomy were eligible for this single-center prospective noninferiority study between November 2021 and September 2022. mpMRI comprised T2-weighted imaging, multiorientational zoomed diffusion-weighted imaging, and extradimensional volumetric interpolated breath-hold examination dynamic contrast-enhanced imaging. Dual-phase DECT images were reconstructed at 40 keV and standard 120 kVp-like images. Using gastrectomy specimens as the reference standard, the diagnostic accuracy of mpMRI and DECT for T and N staging was compared by six radiologists in a pairwise blinded manner. Interreader agreement was assessed using the weighted κ and Kendall W statistics. The McNemar test was used for head-to-head accuracy comparisons between DECT and mpMRI. Results This study included 202 participants (mean age, 62 years ± 11 [SD]; 145 male). The interreader agreement of the six readers for T and N staging of GC was excellent for both mpMRI (κ = 0.89 and 0.85, respectively) and DECT (κ = 0.86 and 0.84, respectively). Regardless of reader experience, higher accuracy was achieved with mpMRI than with DECT for both T (61%-77% vs 50%-64%; all P < .05) and N (54%-68% vs 51%-58%; P = .497-.005) staging, specifically T1 (83% vs 65%) and T4a (78% vs 68%) tumors and N1 (41% vs 24%) and N3 (64% vs 45%) nodules (all P < .05). Conclusion Personalized mpMRI was superior in T staging and noninferior or superior in N staging compared with DECT for patients with GC. Clinical trial registration no. NCT05508126 © RSNA, 2024 Supplemental material is available for this article. See also the editorial by Méndez and Martín-Garre in this issue.