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We present a novel approach for measuring the differential static scalar polarizability of a target ion utilizing a "polarizability scale" scheme with a reference ion co-trapped in a linear Paul trap. The differential static scalar polarizability of the target ion can be precisely extracted by measuring the ratio of the ac Stark shifts induced by an add-on infrared laser shed on both ions. This method circumvents the need for the calibration of the intensity of the add-on laser, which is usually the bottleneck for measurements of the polarizability of trapped ions. As a demonstration, ^{27}Al^{+} (the target ion) and ^{40}Ca^{+} (the reference ion) are used in this work, with an add-on laser at 1068 nm injected into the ion trap along the trap axis. The differential static scalar polarizability of ^{27}Al^{+} is extracted to be 0.416(14) a.u. by measuring the ratio of the ac Stark shifts of both ions. Compared to the most recent result [Phys. Rev. Lett. 123, 033201 (2019)PRLTAO0031-900710.1103/PhysRevLett.123.033201], the relative uncertainty of the differential static scalar polarizability of ^{27}Al^{+} is reduced by approximately a factor of 4, to 3.4%. This improvement is expected to be further enhanced by using an add-on laser with a longer wavelength.
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BACKGROUND: Sirolimus is increasingly utilized in treating diseases associated with mTOR pathway overactivation. Despite its potential, the lack of evidence regarding its long-term safety across all age groups, particularly in pediatric patients, has limited its further application. This study aims to assess the long-term safety of sirolimus, with a specific focus on its impact on growth patterns in pediatric patients. METHODS: This pooled analysis inlcudes two prospective cohort studies spanning 10 years, including 1,738 participants (aged 5 days to 69 years) diagnosed with tuberous sclerosis and/or lymphangioleiomyomatosis. All participants were mTOR inhibitor-naive and received 1 mg/m²/day of sirolimus, with dose adjustments during a two-week titration period to maintain trough blood concentrations between 5 and 10 ng/ml (maximum dose 2 mg). Indicators of physical growth, hematopoietic, liver, renal function, and blood lipid levels were all primary outcomes and were analyzed. The adverse events and related management were also recorded. RESULTS: Sirolimus administration did not lead to deviations from normal growth ranges, but higher doses exhibited a positive association with Z-scores exceeding 2 SD in height, weight, and BMI. Transient elevations in red blood cell and white blood cell counts, along with hyperlipidemia, were primarily observed within the first year of treatment. Other measured parameters remained largely unchanged, displaying only weak correlations with drug use. Stomatitis is the most common adverse event (920/1738, 52.9%). In adult females, menstrual disorders were observed in 48.5% (112/217). CONCLUSIONS: Sirolimus's long-term administration is not associated with adverse effects on children's physical growth pattern, nor significant alterations in hematopoietic, liver, renal function, or lipid levels. A potential dose-dependent influence on growth merits further exploration. TRIAL REGISTRATION: Pediatric patients: Chinese clinical trial registry, No. ChiCTR-OOB-15,006,535. Adult patients: ClinicalTrials, No. NCT03193892.
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Sirolimus , Humanos , Sirolimus/efectos adversos , Sirolimus/uso terapéutico , Niño , Femenino , Adolescente , Preescolar , Adulto , Masculino , Lactante , Adulto Joven , Persona de Mediana Edad , Recién Nacido , Anciano , Esclerosis Tuberosa/tratamiento farmacológico , Linfangioleiomiomatosis/tratamiento farmacológico , Estudios ProspectivosRESUMEN
Acute lung injury (ALI) including acute respiratory distress syndrome (ARDS) is a major complication and increase the mortality of patients with cardiac surgery. We previously found that the protein cargoes enriched in circulating extracellular vesicles (EVs) are closely associated with cardiopulmonary disease. We aimed to evaluate the implication of EVs on cardiac surgery-associated ALI/ARDS. The correlations between "oncoprotein-induced transcript 3 protein (OIT3) positive" circulating EVs and postoperative ARDS were assessed. The effects of OIT3-overexpressed EVs on the cardiopulmonary bypass (CPB) -induced ALI in vivo and inflammation of human bronchial epithelial cells (BEAS-2B) were detected. OIT3 enriched in circulating EVs is reduced after cardiac surgery with CPB, especially with postoperative ARDS. The "OIT3 positive" EVs negatively correlate with lung edema, hypoxemia and CPB time. The OIT3-overexpressed EVs can be absorbed by pulmonary epithelial cells and OIT3 transferred by EVs triggered K48- and K63-linked polyubiquitination to inactivate NOD-like receptor protein 3 (NLRP3) inflammasome, and restrains pro-inflammatory cytokines releasing and immune cells infiltration in lung tissues, contributing to the alleviation of CPB-induced ALI. Overexpression of OIT3 in human bronchial epithelial cells have similar results. OIT3 promotes the E3 ligase Cbl proto-oncogene B associated with NLRP3 to induce the ubiquitination of NLRP3. Immunofluorescence tests reveal that OIT3 is reduced in the generation from the liver sinusoids endothelial cells (LSECs) and secretion in liver-derived EVs after CPB. In conclusion, OIT3 enriched in EVs is a promising biomarker of postoperative ARDS and a therapeutic target for ALI after cardiac surgery.
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BACKGROUND: Synchronous liver metastasis (SLM) is a significant contributor to morbidity in colorectal cancer (CRC). There are no effective predictive device integration algorithms to predict adverse SLM events during the diagnosis of CRC. AIM: To explore the risk factors for SLM in CRC and construct a visual prediction model based on gray-level co-occurrence matrix (GLCM) features collected from magnetic resonance imaging (MRI). METHODS: Our study retrospectively enrolled 392 patients with CRC from Yichang Central People's Hospital from January 2015 to May 2023. Patients were randomly divided into a training and validation group (3:7). The clinical parameters and GLCM features extracted from MRI were included as candidate variables. The prediction model was constructed using a generalized linear regression model, random forest model (RFM), and artificial neural network model. Receiver operating characteristic curves and decision curves were used to evaluate the prediction model. RESULTS: Among the 392 patients, 48 had SLM (12.24%). We obtained fourteen GLCM imaging data for variable screening of SLM prediction models. Inverse difference, mean sum, sum entropy, sum variance, sum of squares, energy, and difference variance were listed as candidate variables, and the prediction efficiency (area under the curve) of the subsequent RFM in the training set and internal validation set was 0.917 [95% confidence interval (95%CI): 0.866-0.968] and 0.09 (95%CI: 0.858-0.960), respectively. CONCLUSION: A predictive model combining GLCM image features with machine learning can predict SLM in CRC. This model can assist clinicians in making timely and personalized clinical decisions.
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BACKGROUND: Preoperative anxiety is a common emotional problem during the perioperative period and may adversely affect postoperative recovery. Emergence agitation (EA) is a common complication of general anesthesia that may increase patient discomfort and hospital stay and may be associated with the development of postoperative complications. Pre-anesthetic anxiety may be associated with the development of EA, but studies in this area are lacking. AIM: To determine the relationship between pre-anesthetic anxiety and EA after radical surgery in patients with non-small cell lung cancer (NSCLC). METHODS: Eighty patients with NSCLC undergoing surgical treatment between June 2020 and June 2023 were conveniently sampled. We used the Hospital Anxiety and Depression Scale's (HADS) anxiety subscale (HADS-A) to determine patients' anxiety at four time points (T1-T4): Patients' preoperative visit, waiting period in the surgical waiting room, after entering the operating room, and before anesthesia induction, respectively. The Riker Sedation-Agitation Scale (RSAS) examined EA after surgery. Scatter plots of HADS-A and RSAS scores assessed the correlation between patients' pre-anesthesia anxiety status and EA. We performed a partial correlation analysis of HADS-A scores with RSAS scores. RESULTS: NSCLC patients' HADS-A scores gradually increased at the four time points: 7.33 ± 2.03 at T1, 7.99 ± 2.22 at T2, 8.05 ± 2.81 at T3, and 8.36 ± 4.17 at T4. The patients' postoperative RSAS score was 4.49 ± 1.18, and 27 patients scored ≥ 5, indicating that 33.75% patients had EA. HADS-A scores at T3 and T4 were significantly higher in patients with EA (9.67 ± 3.02 vs 7.23 ± 2.31, 12.56 ± 4.10 vs 6.23 ± 2.05, P < 0.001). Scatter plots showed the highest correlation between HADS-A and RSAS scores at T3 and T4. Partial correlation analysis showed a strong positive correlation between HADS-A and RSAS scores at T3 and T4 (r = 0.296, 0.314, P < 0.01). CONCLUSION: Agitation during anesthesia recovery in patients undergoing radical resection for NSCLC correlated with anxiety at the time of entering the operating room and before anesthesia induction.
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Microplastics ï¼MPsï¼ are ubiquitous in the marine environment and have become an emerging pollutant that is attracting great attention. To reveal the pollution characteristics of MPs in surface seawater of coastal waters in Guangdong Province, nine bays ï¼estuariesï¼ were selected from Jiangmen to Shantou. The distribution and compositional characteristics of MPs were investigated through field sampling, oxidation digestion, and visual and compositional identification, and their potential sources were analyzed. The ecological risks were assessed by combining the pollution load index and the polymer risk index. The results showed that MPs were detected in all 30 surface seawater samples from the coastal waters of Guangdong Province, with an abundance range of 70-920 n·m-3 and an average abundance of ï¼295.3 ±175.3ï¼ n·m-3. The highest MPs abundance was found in the Pearl River estuary, and the lowest abundance was found in Shenquan bay. The distribution patterns were mainly influenced by human activities and ocean currents. The dominant polymer types included polypropylene ï¼31.2%ï¼, phenol resin ï¼16.0%ï¼, polyethylene terephthalate ï¼15.3%ï¼, and polyethylene ï¼10.9%ï¼. The main shape, color, and size categories of MPs were fiber ï¼57.5%ï¼, transparent ï¼72.0%ï¼, and 0.5-1 mm ï¼32.8%ï¼, respectively. The possible sources of MPs mainly included aquaculture, fishing, navigation, tourism, municipal sewage discharge, and ocean current transportation. The model assessment results showed that the pollution load risk of MPs was relatively low, but the polymer risk was at a medium-high level. This study provides a data basis for the action plan of plastic pollution control in Guangdong Province and supports the prevention and control of marine MPs pollution.
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Gastric cancer is a leading cause of cancer-related deaths in China. Affecting more than 40% of the world's population, Helicobacter pylori is a major risk factor for gastric cancer. While previous clinical trials indicated that eradication of H. pylori could reduce gastric cancer risk, this remains to be shown using a population-based approach. We conducted a community-based, cluster-randomized, controlled, superiority intervention trial in Linqu County, China, with individuals who tested positive for H. pylori using a 13C-urea breath test randomly assigned to receiving either (1) a 10-day, quadruple anti-H. pylori treatment (comprising 20 mg of omeprazole, 750 mg of tetracycline, 400 mg of metronidazole and 300 mg of bismuth citrate) or (2) symptom alleviation treatment with a single daily dosage of omeprazole and bismuth citrate. H. pylori-negative individuals did not receive any treatment. We examined the incidence of gastric cancer as the primary outcome. A total of 180,284 eligible participants from 980 villages were enrolled over 11.8 years of follow-up, and a total of 1,035 cases of incident gastric cancer were documented. Individuals receiving anti-H. pylori therapy showed a modest reduction in gastric cancer incidence in intention-to-treat analyses (hazard ratio 0.86, 95% confidence interval 0.74-0.99), with a stronger effect observed for those having successful H. pylori eradication (hazard ratio 0.81, 95% confidence interval 0.69-0.96) than for those who failed treatment. Moderate adverse effects were reported in 1,345 participants during the 10-day treatment. We observed no severe intolerable adverse events during either treatment or follow-up. The findings suggest the potential for H. pylori mass screening and eradication as a public health policy for gastric cancer prevention. Chinese Clinical Trial Registry identifier: ChiCTR-TRC-10000979 .
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Importance: Helicobacter pylori treatment and nutrition supplementation may protect against gastric cancer (GC), but whether the beneficial effects only apply to potential genetic subgroups and whether high genetic risk may be counteracted by these chemoprevention strategies remains unknown. Objective: To examine genetic variants associated with the progression of gastric lesions and GC risk and to assess the benefits of H pylori treatment and nutrition supplementation by levels of genetic risk. Design, Setting, and Participants: This cohort study used follow-up data of the Shandong Intervention Trial (SIT, 1989-2022) and China Kadoorie Biobank (CKB, 2004-2018) in China. Based on the SIT, a longitudinal genome-wide association study was conducted to identify genetic variants for gastric lesion progression. Significant variants were examined for incident GC in a randomly sampled set of CKB participants (set 1). Polygenic risk scores (PRSs) combining independent variants were assessed for GC risk in the remaining CKB participants (set 2) and in an independent case-control study in Linqu. Exposures: H pylori treatment and nutrition supplementation. Main Outcomes and Measures: Primary outcomes were the progression of gastric lesions (in SIT only) and the risk of GC. The associations of H pylori treatment and nutrition supplementation with GC were evaluated among SIT participants with different levels of genetic risk. Results: Our analyses included 2816 participants (mean [SD] age, 46.95 [9.12] years; 1429 [50.75%] women) in SIT and 100â¯228 participants (mean [SD] age, 53.69 [11.00] years; 57â¯357 [57.23%] women) in CKB, with 147 GC cases in SIT and 825 GC cases in CKB identified during follow-up. A PRS integrating 12 genomic loci associated with gastric lesion progression and incident GC risk was derived, which was associated with GC risk in CKB (highest vs lowest decile of PRS: hazard ratio [HR], 2.54; 95% CI, 1.80-3.57) and further validated in the analysis of 702 case participants and 692 control participants (mean [SD] age, 54.54 [7.66] years; 527 [37.80%] women; odds ratio, 1.83; 95% CI, 1.11-3.05). H pylori treatment was associated with reduced GC risk only for individuals with high genetic risk (top 25% of PRS: HR, 0.45; 95% CI, 0.25-0.82) but not for those with low genetic risk (HR, 0.81; 95% CI, 0.50-1.34; P for interaction = .03). Such effect modification was not found for vitamin (P for interaction = .93) or garlic (P for interaction = .41) supplementation. Conclusions and Relevance: The findings of this cohort study indicate that a high genetic risk of GC may be counteracted by H pylori treatment, suggesting primary prevention could be tailored to genetic risk for more effective prevention.
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Predisposición Genética a la Enfermedad , Infecciones por Helicobacter , Helicobacter pylori , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/genética , Neoplasias Gástricas/epidemiología , Femenino , Masculino , Persona de Mediana Edad , Infecciones por Helicobacter/tratamiento farmacológico , Infecciones por Helicobacter/complicaciones , China/epidemiología , Estudio de Asociación del Genoma Completo , Estudios de Casos y Controles , Adulto , Factores de Riesgo , Suplementos Dietéticos , Estudios de Cohortes , Anciano , Antibacterianos/uso terapéuticoRESUMEN
White matter injury (WMI) causes oligodendrocyte precursor cell (OPC) differentiation arrest and functional deficits, with no effective therapies to date. Here, we report increased expression of growth hormone (GH) in the hypoxic neonatal mouse brain, a model of WMI. GH treatment during or post hypoxic exposure rescues hypoxia-induced hypomyelination and promotes functional recovery in adolescent mice. Single-cell sequencing reveals that Ghr mRNA expression is highly enriched in vascular cells. Cell-lineage labeling and tracing identify the GHR-expressing vascular cells as a subpopulation of pericytes. These cells display tip-cell-like morphology with kinetic polarized filopodia revealed by two-photon live imaging and seemingly direct blood vessel branching and bridging. Gain-of-function and loss-of-function experiments indicate that GHR signaling in pericytes is sufficient to modulate angiogenesis in neonatal brains, which enhances OPC differentiation and myelination indirectly. These findings demonstrate that targeting GHR and/or downstream effectors may represent a promising therapeutic strategy for WMI.
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Vaina de Mielina , Neovascularización Fisiológica , Pericitos , Animales , Pericitos/metabolismo , Pericitos/efectos de los fármacos , Ratones , Vaina de Mielina/metabolismo , Neovascularización Fisiológica/efectos de los fármacos , Neovascularización Fisiológica/fisiología , Hormona del Crecimiento/metabolismo , Hormona del Crecimiento/farmacología , Animales Recién Nacidos , Hipoxia/metabolismo , Diferenciación Celular/efectos de los fármacos , Ratones Endogámicos C57BL , Células Precursoras de Oligodendrocitos/metabolismo , Células Precursoras de Oligodendrocitos/efectos de los fármacos , Receptores de Somatotropina/metabolismo , Receptores de Somatotropina/genética , AngiogénesisRESUMEN
Fuchs endothelial corneal dystrophy (FECD) is one of the most common corneal diseases that causes loss of visual acuity in the world. FECD is a genetically and pathogenetically heterogeneous disease that results in the failure of corneal endothelial cells to maintain fluid balance and functional homeostasis of the cornea. Corneal edema, central guttae formation, and bullae development are common corneal pathologies. Currently, the mainstay of FECD treatment is surgery. However, limited sources of corneal graft and postsurgical complications remain problematic. In recent years, with advances in medical science and technology, there have been a few promising trials of new treatment modalities for FECD. In addition to new surgical methods, novel modalities can be classified into pharmacological-associated treatment, cell therapy-associated treatment, and gene therapy-associated treatment. In this article, our primary focus is on the most recent clinical trials related to FECD, and we present a stepwise approach to enhance FECD management and ultimately improve patient outcomes. We thoroughly searched for FECD clinical trials and reviewed the study designs, methodologies, and outcomes of each trial conducted within the past decade. It is imperative for physicians to stay up-to-date with these cutting-edge treatment approaches.
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BACKGROUND: Type 2 diabetes mellitus (T2DM), a fast-growing issue in public health, is one of the most common chronic metabolic disorders in older individuals. Osteoporosis and sarcopenia are highly prevalent in T2DM patients and may result in fractures and disabilities. In people with T2DM, the association between nutrition, sarcopenia, and osteoporosis has rarely been explored. AIM: To evaluate the connections among nutrition, bone mineral density (BMD) and body composition in patients with T2DM. METHODS: We enrolled 689 patients with T2DM for this cross-sectional study. All patients underwent dual energy X-ray absorptiometry (DXA) examination and were categorized according to baseline Geriatric Nutritional Risk Index (GNRI) values calculated from serum albumin levels and body weight. The GNRI was used to evaluate nutritional status, and DXA was used to investigate BMD and body composition. Multivariate forward linear regression analysis was used to identify the factors associated with BMD and skeletal muscle mass index. RESULTS: Of the total patients, 394 were men and 295 were women. Compared with patients in tertile 1, those in tertile 3 who had a high GNRI tended to be younger and had lower HbA1c, higher BMD at all bone sites, and higher appendicular skeletal muscle index (ASMI). These important trends persisted even when the patients were divided into younger and older subgroups. The GNRI was positively related to ASMI (men: r = 0.644, P < 0.001; women: r = 0.649, P < 0.001), total body fat (men: r = 0.453, P < 0.001; women: r = 0.557, P < 0.001), BMD at all bone sites, lumbar spine (L1-L4) BMD (men: r = 0.110, P = 0.029; women: r = 0.256, P < 0.001), FN-BMD (men: r = 0.293, P < 0.001; women: r = 0.273, P < 0.001), and hip BMD (men: r = 0.358, P < 0.001; women: r = 0.377, P < 0.001). After adjustment for other clinical parameters, the GNRI was still significantly associated with BMD at the lumbar spine and femoral neck. Additionally, a low lean mass index and higher ß-collagen special sequence were associated with low BMD at all bone sites. Age was negatively correlated with ASMI, whereas weight was positively correlated with ASMI. CONCLUSION: Poor nutrition, as indicated by a low GNRI, was associated with low levels of ASMI and BMD at all bone sites in T2DM patients. Using the GNRI to evaluate nutritional status and using DXA to investigate body composition in patients with T2DM is of value in assessing bone health and physical performance.
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Non-small cell lung cancer (NSCLC), characterized by low survival rates and a high recurrence rate, is a major cause of cancer-related mortality. Aberrant activation of the PI3K/AKT/mTOR signaling pathway is a common driver of NSCLC. Within this study, the inhibitory activity of (+)-anthrabenzoxocinone ((+)-ABX), an oxygenated anthrabenzoxocinone compound derived from Streptomyces, against NSCLC is demonstrated for the first time both in vitro and in vivo. Mechanistically, it is confirmed that the PI3K/AKT/mTOR signaling pathway is targeted and suppressed by (+)-ABX, resulting in the induction of S and G2/M phase arrest, apoptosis, and autophagy in NSCLC cells. Additionally, the augmentation of intracellular ROS levels by (+)-ABX is revealed, further contributing to the inhibition of the signaling pathway and exerting inhibitory effects on tumor growth. The findings presented in this study suggest that (+)-ABX possesses the potential to serve as a lead compound for the treatment of NSCLC.
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Apoptosis , Autofagia , Carcinoma de Pulmón de Células no Pequeñas , Puntos de Control del Ciclo Celular , Neoplasias Pulmonares , Fosfatidilinositol 3-Quinasas , Proteínas Proto-Oncogénicas c-akt , Transducción de Señal , Serina-Treonina Quinasas TOR , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/metabolismo , Carcinoma de Pulmón de Células no Pequeñas/patología , Serina-Treonina Quinasas TOR/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Humanos , Apoptosis/efectos de los fármacos , Autofagia/efectos de los fármacos , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patología , Transducción de Señal/efectos de los fármacos , Fosfatidilinositol 3-Quinasas/metabolismo , Animales , Línea Celular Tumoral , Puntos de Control del Ciclo Celular/efectos de los fármacos , Ratones Desnudos , Ratones , Proliferación Celular/efectos de los fármacos , Ratones Endogámicos BALB C , Ensayos Antitumor por Modelo de Xenoinjerto , Especies Reactivas de Oxígeno/metabolismo , Antineoplásicos/farmacologíaRESUMEN
BACKGROUND: The development and progression of hepatocellular carcinoma (HCC) have been reported to be associated with immune-related genes and the tumor microenvironment. Nevertheless, there are not enough prognostic biomarkers and models available for clinical use. Based on seven prognostic genes, this study calculated overall survival in patients with HCC using a prognostic survival model and revealed the immune status of the tumor microenvironment (TME). AIM: To develop a novel immune cell-related prognostic model of HCC and depict the basic profile of the immune response in HCC. METHODS: We obtained clinical information and gene expression data of HCC from The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) datasets. TCGA and ICGC datasets were used for screening prognostic genes along with developing and validating a seven-gene prognostic survival model by weighted gene coexpression network analysis and least absolute shrinkage and selection operator regression with Cox regression. The relative analysis of tumor mutation burden (TMB), TME cell infiltration, immune checkpoints, immune therapy, and functional pathways was also performed based on prognostic genes. RESULTS: Seven prognostic genes were identified for signature construction. Survival receiver operating characteristic curve analysis showed the good performance of survival prediction. TMB could be regarded as an independent factor in HCC survival prediction. There was a significant difference in stromal score, immune score, and estimate score between the high-risk and low-risk groups stratified based on the risk score derived from the seven-gene prognostic model. Several immune checkpoints, including VTCN1 and TNFSF9, were found to be associated with the seven prognostic genes and risk score. Different combinations of checkpoint blockade targeting inhibitory CTLA4 and PD1 receptors and potential chemotherapy drugs hold great promise for specific HCC therapies. Potential pathways, such as cell cycle regulation and metabolism of some amino acids, were also identified and analyzed. CONCLUSION: The novel seven-gene (CYTH3, ENG, HTRA3, PDZD4, SAMD14, PGF, and PLN) prognostic model showed high predictive efficiency. The TMB analysis based on the seven genes could depict the basic profile of the immune response in HCC, which might be worthy of clinical application.
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Background: The traditional audiovisual sexual stimulation (AVSS) test may experience limitations including low erectile response rate and lack of unified diagnostic criteria. Aim: We aimed to explore the clinical value of AVSS with virtual reality (VR-AVSS) test in assessing erectile function and diagnosing erectile dysfunction (ED). Methods: Participants 18 to 60 years of age were screened for analysis in 3 clinical centers from June 2020 to March 2022. Demographic data, 5-item International Index of Erectile Function (IIEF-5), erectile hardness score (EHS), and self-reported symptom questions were collected. The ED patients and control patients were confirmed according to the IIEF-5 and EHS. All subjects watched a 60-minute erotic video by VR device during RigiScan recording. The parameters including tip average rigidity, tip effective erectile duration (duration of rigidity ≥60%, tip effective erectile duration), base average rigidity, and base effective erectile duration were evaluated. Outcomes: The main outcome of interest was the application of VR immersion technology to improve the traditional AVSS test. Results: A total of 301 ED cases and 100 eligible control patients were included for final analysis. Compared with control patients, ED cases had significantly lower IIEF-5 scores, EHS, positive response rate, and erectile rigidity and duration. The positive response rate of ED and control patients were 75.5% and 90.9%, respectively. The cutoff points of tip average rigidity, tip effective erectile duration, base average rigidity, and base effective erectile duration were 40.5% (sensitivity: 77.6%, specificity: 70.2%; P < .001), 4.75 minutes (sensitivity: 75.9%, specificity: 75.4%; P < .001), 48.5% (sensitivity: 77.6%, specificity: 75.1%; P < .001), and 7.75 minutes (sensitivity: 79.3%, specificity: 75.7%; P < .001). Clinical Implications: The technological superiority of VR will enable the VR-AVSS immersion test to be a more accurate detection than traditional AVSS modes. Strengths and Limitations: Our study applied VR immersion technology to establish the standard operation procedure for the AVSS test, which could effectively reduce the interference of adverse factors and minimize the detecting errors. However, the test data only included positive response subjects, so the true erectile status of men with a negative response to the AVSS test cannot be obtained. Conclusions: The VR-AVSS test can effectively improve the diagnostic accuracy of ED. The average rigidity and effective erectile duration were the optimal diagnostic parameters for excluding ED.
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Patients with lymphangioleiomyomatosis (LAM) are considered high risk for most surgeries and require specific anesthetic considerations mainly because of the common spontaneous pneumothorax (PTX). To explore whether intraoperative mechanical ventilation could increase the risk of PTX in those patients, we included 12 surgical patients with LAM in this study, of whom four (33.3%) experienced postoperative PTX. According to our results, patients with higher CT grade, poorer pulmonary function, and a history of preoperative PTX might be more likely to develop postoperative PTX. However, intraoperative mechanical ventilation did not show obvious influence, which might help clinicians reconsider the perioperative management of LAM patients.
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Neoplasias Pulmonares , Linfangioleiomiomatosis , Neumotórax , Humanos , Neumotórax/epidemiología , Neumotórax/etiología , Linfangioleiomiomatosis/epidemiología , Incidencia , Respiración Artificial/efectos adversos , Neoplasias Pulmonares/cirugíaRESUMEN
BACKGROUND: Emerging evidence suggests a common pathophysiological basis for metabolic disorders and mental diseases. Despite the existence of reports suggesting a strong connection between dyslipidemia and depression, a comprehensive and reliable indicator to identify depression is still lacking. Cardiometabolic index (CMI) is an integrated index calculated from three vital metabolic indicators, including triglyceride (TG), high-density lipoprotein cholesterol (HDLC) and waist height ratio (WHtR). OBJECTIVE: This study aims to explore the association between CMI and depression. METHODS: Cross-sectional data of participants with complete information of CMI, depression, and other covariates were obtained from the National Health and Nutrition Examination Survey (NHANES). Weighted student's t-test and Chi-square test were used to identify the differences between two groups. Weighted multivariate logistic regression model, restricted cubic spline (RCS) regression analysis, subgroup analysis and interaction tests were conducted to explore the association between CMI and depression. Receiver operating curve (ROC) analysis and area under the curve (AUC) were also utilized to evaluate the performance of CMI in identifying depression. RESULTS: A positive correlation between CMI and depression was observed in 3794 participants included in the study, which was further confirmed to be non-linear via RCS regression analysis, with two significant inflection points being identified, including 0.9522 and 1.58. In the crude or adjusted models, individuals with a CMI level ≥ 0.9522 exhibited remarkably increased risk for developing depression. CMI got an AUC of 0.748 in identifying depression. Subgroup analyses and interaction tests indicate that the association between CMI and depression remained consistent across different subgroups and was not modified by other covariates except drinking. Those who are current drinkers and with a high CMI are more susceptible to suffer depression. CONCLUSIONS: An elevated CMI is linked to increased risk for depression. Addressing dyslipidemia and improving lipid levels may potentially lower the risk for depression.
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Enfermedades Cardiovasculares , Dislipidemias , Humanos , Encuestas Nutricionales , Estudios Transversales , Depresión/epidemiología , Enfermedades Cardiovasculares/epidemiología , Dislipidemias/epidemiologíaRESUMEN
The coronavirus disease 2019 (COVID-19) pandemic has had a major impact on human life. This review highlights the versatile roles of both classical and modern structure-based approaches for COVID-19. X-ray crystallography, nuclear magnetic resonance spectroscopy, and cryogenic electron microscopy are the three cornerstones of classical structural biology. These technologies have helped provide fundamental and detailed knowledge regarding severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the related human host proteins as well as enabled the identification of its target sites, facilitating the cessation of its transmission. Further progress into protein structure modeling was made using modern structure-based approaches derived from homology modeling and integrated with artificial intelligence (AI), facilitating advanced computational simulation tools to actively guide the design of new vaccines and the development of anti-SARS-CoV-2 drugs. This review presents the practical contributions and future directions of structure-based approaches for COVID-19.
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COVID-19 , Humanos , SARS-CoV-2 , Inteligencia Artificial , Vacunas contra la COVID-19 , Simulación por ComputadorRESUMEN
BACKGROUND: Patients with relapsing polychondritis (RP) sometimes experience upper airway collapse or lower airway stenosis, and bronchoscopy may provide a valuable typical image to confirm the diagnosis. This study aimed to identify potential risk factors associated with severe adverse effects during bronchoscopy. METHODS: We performed a retrospective cohort study of 82 consecutive patients with RP hospitalized at Peking Union Medical College Hospital between January 1, 2012 and December 31, 2022. Clinical features and disease patterns were compared among patients with RP undergoing bronchoscopy with or without severe adverse effects. Binary logistic regression analysis was performed to identify the associated risk factors. RESULTS: For patients with RP undergoing bronchoscopy with severe adverse effects, the forced vital capacity (FVC), forced vital capacity percent predicted values (FVC%), and peak expiratory flow were significantly lower (P = 0.001, P = 0.001, and P = 0.021, respectively) than those in the non-severe adverse effect subgroup. Binary logistic regression analysis revealed that low FVC% (odds ratio, 0.930; 95% confidence interval, 0.880-0.982; P = 0.009) was an independent risk factor for severe adverse events in patients undergoing bronchoscopy. CONCLUSIONS: Low FVC or FVC% suggests a high risk of severe adverse effects in patients with RP undergoing bronchoscopy. Patients with such risk factors should be carefully evaluated before bronchoscopy and adequately prepared for emergency tracheal intubation or tracheostomy.
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Broncoscopía , Policondritis Recurrente , Humanos , Broncoscopía/efectos adversos , Broncoscopía/métodos , Estudios Retrospectivos , Policondritis Recurrente/complicaciones , Policondritis Recurrente/diagnóstico , Pruebas de Función Respiratoria , Factores de RiesgoRESUMEN
PURPOSE: The study aims to characterize the robustness of distinct clinical assessments in identifying the underlying conditions of dry eye disease (DED), with a specific emphasis on the involvement of conjunctival goblet cells. METHODS: Seven rabbits receiving surgical removal of the lacrimal and Harderian glands were divided into two groups, one with ablation of conjunctival goblet cells by topical soaking of trichloroacetic acid (TCA) to the bulbar conjunctiva (n = 3) and one without (n = 4), and the conditions of DED were assessed weekly using Schirmer test, tear breakup time (TBUT), tear osmolarity, and National Eye Institute (NEI) fluorescein staining grading. After 8 weeks, the rabbits were sacrificed, and the eyes were enucleated for histopathological examination. RESULTS: Histopathological analysis revealed corneal epithelial thinning in both groups. While TCA soaking significantly decreased the density of conjunctival goblet cells, DED rabbits without TCA also showed a partial reduction in goblet cell density, potentially attributable to dacryoadenectomy. Both groups showed significant decreases in Schirmer test and TBUT, as well as an increase in tear osmolarity. In DED rabbits with TCA soaking, tear osmolarity increased markedly, suggesting that tear osmolarity is highly sensitive to loss and/or dysfunction of conjunctival goblet cells. Fluorescein staining was gradually and similarly increased in both groups, suggesting that fluorescein staining may not reveal an early disruption of the tear film until the prolonged progression of DED. CONCLUSION: The Schirmer test, TBUT, tear osmolarity, and NEI fluorescein grading are distinct, yet complementary, clinical assessments for the evaluation of DED. By performing these assessments in definitive DED rabbit models, both with and without ablation of conjunctival goblet cells, the role of these cells in the homeostasis of tear osmolarity is highlighted. Characterizing the robustness of these assessments in identifying the underlying conditions of DED will guide a more appropriate management for patients with DED.
Asunto(s)
Conjuntiva , Modelos Animales de Enfermedad , Síndromes de Ojo Seco , Células Caliciformes , Aparato Lagrimal , Lágrimas , Animales , Conejos , Síndromes de Ojo Seco/diagnóstico , Síndromes de Ojo Seco/metabolismo , Lágrimas/metabolismo , Lágrimas/química , Células Caliciformes/patología , Conjuntiva/patología , Conjuntiva/metabolismo , Concentración Osmolar , Aparato Lagrimal/metabolismo , Aparato Lagrimal/patología , Glándula de Harder , Recuento de Células , FluoresceínaRESUMEN
Tuberous sclerosis complex (TSC) and focal cortical dysplasia (FCD) type IIb are the predominant causes of drug-refractory epilepsy in children. Dysmorphic neurons (DNs), giant cells (GCs), and balloon cells (BCs) are the most typical pathogenic profiles in cortical lesions of TSC and FCD IIb patients. However, mechanisms underlying the pathological processes of TSC and FCD IIb remain obscure. The Plexin-B2-Sema4C signalling pathway plays critical roles in neuronal morphogenesis and corticogenesis during the development of the central nervous system. However, the role of the Plexin-B2 system in the pathogenic process of TSC and FCD IIb has not been identified. In the present study, we investigated the expression and cell distribution characteristics of Plexin-B2 and Sema4C in TSC and FCD IIb lesions with molecular technologies. Our results showed that the mRNA and protein levels of Plexin-B2 expression were significantly increased both in TSC and FCD IIb lesions versus that in the control cortex. Notably, Plexin-B2 was also predominantly observed in GCs in TSC epileptic lesions and BCs in FCD IIb lesions. In contrast, the expression of Sema4C, the ligand of Plexin-B2, was significantly decreased in DNs, GCs, and BCs in TSC and FCD IIb epileptic lesions. Additionally, Plexin-B2 and Sema4C were expressed in astrocytes and microglia cells in TSC and FCD IIb lesions. Furthermore, the expression of Plexin-B2 was positively correlated with seizure frequency in TSC and FCD IIb patients. In conclusion, our results showed the Plexin-B2-Sema4C system was abnormally expressed in cortical lesions of TSC and FCD IIb patients, signifying that the Plexin-B2-Sema4C system may play a role in the pathogenic development of TSC and FCD IIb.