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BACKGROUND AND AIMS: The duodenal papillae are the primary and essential pathway for ERCP, greatly determining its complexity and outcome. We investigated the association between papilla morphology and post-ERCP pancreatitis (PEP) and constructed a robust model for PEP prediction. METHODS: We retrospectively enrolled patients who underwent ERCP in 2 centers from January 2019 to June 2022. Radiomic features of the papilla were extracted from endoscopic images with deep learning. Potential predictors and their importance were evaluated with 3 machine learning algorithms. A predictive model was developed using best subset selection by logistic regression, and its performance was evaluated in terms of discrimination, calibration, and clinical utility based on the area under curve (AUC) of the receiver-operating characteristic curve, calibration curve, and clinical decision curve, respectively. RESULTS: From 2 centers, 2038 and 334 ERCP patients were enrolled in this study with PEP rates of 7.9% and 9.6%, respectively. The radiomic score was significantly associated with PEP and showed great diagnostic value (AUC, .755-.821). Six hub predictors were selected to conduct a predictive model. The radiomics-based model demonstrated excellent discrimination (AUC, .825-.857) and therapeutic benefits in the training, testing, and validation cohorts. The addition of the radiomic score significantly improved the diagnostic accuracy of the predictive model (net reclassification improvement, .151-.583 [P < .05]; integrated discrimination improvement, .097-.235 [P < .001]). CONCLUSIONS: The radiomic signature of the papilla is a crucial independent predictor of PEP. The papilla radiomics-based model performs well for the clinical prediction of PEP.
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BACKGROUND: Pathological cardiac hypertrophy is associated with cardiac dysfunction and is a key risk factor for heart failure and even sudden death. This study investigates the function of Mycn in cardiac hypertrophy and explores the interacting molecules. METHODS: A mouse model of cardiac hypertrophy was induced by isoproterenol (ISO). The cardiac dysfunction was assessed by the heart weight-to-body weight ratio (HW/BW), echocardiography assessment, pathological staining, biomarker detection, and cell apoptosis. Transcriptome alteration in cardiac hypertrophy was analyzed by bioinformatics analysis. Gain- or loss-of-function studies of MYCN proto-oncogene (Mycn), ubiquitin specific peptidase 2 (USP2), and junction plakoglobin (JUP) were performed. The biological functions of Mycn were further examined in ISO-treated cardiomyocytes. The molecular interactions were verified by luciferase assay or immunoprecipitation assays. RESULTS: Mycn was poorly expressed in ISO-treated mice, and its upregulation reduced HW/BW, cell surface area, oxidative stress, and inflammation while improving cardiac function of mice. It also reduced apoptosis of cardiomyocytes in mice and those in vitro induced by ISO. Mycn bound to the USP2 promoter to activate its transcription. USP2 overexpression exerted similar myocardial protective functions. It stabilized JUP protein by deubiquitination modification, which blocked the Akt/ß-catenin pathway. Knockdown of JUP restored phosphorylation of Akt and ß-catenin protein level, which negated the protective effects of USP2. CONCLUSION: This study demonstrates that Mycn activates USP2 transcription, which mediates ubiquitination and protein stabilization of JUP, thus inactivating the Akt/ß-catenin axis and alleviating cardiac hypertrophy-induced heart failure.
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Insuficiencia Cardíaca , Proteína Proto-Oncogénica N-Myc , Animales , Ratones , beta Catenina/genética , beta Catenina/metabolismo , Cardiomegalia/genética , Cardiomegalia/prevención & control , gamma Catenina/metabolismo , Insuficiencia Cardíaca/genética , Insuficiencia Cardíaca/prevención & control , Isoproterenol , Miocitos Cardíacos/metabolismo , Proteína Proto-Oncogénica N-Myc/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Transducción de SeñalRESUMEN
PURPOSE: This study aims to explore the clinical value of autogenous tibial periosteal bone grafting in the treatment of osteochondral lesions of the talus (OLT) and analyze the three-dimensional factors in the necrotic zone of the talus. METHODS: A retrospective analysis was performed on 36 patients who underwent autogenous tibial periosteal bone grafting in the Foot and Ankle Surgery Department of our hospital between September 2018 and September 2022. The American Orthopaedic Foot and Ankle Society (AOFAS), Visual Analogue Scale (VAS), and Chinese Short-Form 36 Health Survey (SF-36) were used to evaluate treatment efficacy prior to surgery and at the last follow-up. Furthermore, Mimics 21.0 software was employed to measure the three-dimensional data of the necrotic area, including surface area, volume, and depth, in order to investigate their potential impact on patient prognosis. RESULTS: Among the 36 OLT patients who obtained complete follow-up, there were 22 males and 14 females. No complications such as surgical site infection, non-union of cartilage, post-traumatic arthritis, or donor site pain were observed. The AOFAS, VAS, and Chinese SF-36 scores of all patients at the last follow-up showed significant improvement compared to preoperative values. There was no significant correlation between the AOFAS, VAS, and Chinese SF-36 scores at the last follow-up and the depth, surface area, and volume of the necrotic zone. CONCLUSION: The use of autogenous tibial periosteal bone grafting can safely and effectively treat Hepple V OLT. Additionally, there is no significant correlation between the three-dimensional factors of the necrotic area and the prognosis of the patients.
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Trasplante Óseo , Astrágalo , Tibia , Humanos , Masculino , Femenino , Astrágalo/cirugía , Adulto , Estudios Retrospectivos , Trasplante Óseo/métodos , Tibia/cirugía , Persona de Mediana Edad , Adulto Joven , Resultado del Tratamiento , Periostio/trasplante , Adolescente , Trasplante Autólogo/métodos , Necrosis , Imagenología TridimensionalRESUMEN
BACKGROUND: There is lack of research on corticosteroid use for severe and critical COVID-19 patients with Omicron variant infection. METHODS: This multi-center retrospective cohort study involved 1167 patients from 59 ICUs across the mainland of China diagnosed with severe or critical SARS-CoV-2 Omicron variant infection between November 1, 2022, and February 11, 2023. Patients were segregated into two groups based on their corticosteroid treatment-usual dose (equivalent prednisone dose 30-50 mg/day) and higher dose (equivalent prednisone dose > 50 mg/day). The primary outcome was 28-day ICU mortality. Propensity score matching was used to compare outcomes between cohorts. RESULTS: After propensity score matching, 520 patients in the usual dose corticosteroid group and 260 patients in the higher dose corticosteroid group were included in the analysis, respectively. The mortality was significantly higher in the higher dose corticosteroid group (67.3%, 175/260) compared to the usual dose group (56.0%, 291/520). Logistic regression showed that higher doses of corticosteroids were significantly associated with increased mortality at 28-day (OR = 1.62,95% CI 1.19-2.21, p = 0.002) and mortality in ICU stay (OR = 1.66,95% CI 1.21-2.28, p = 0.002). Different types of corticosteroids did not affect the effect. CONCLUSIONS: The study suggests that higher-dose corticosteroids may lead to a poorer prognosis for severe and critical COVID-19 patients with Omicron variant infection in the ICU. Further research is needed to determine the appropriate corticosteroid dosage for these patients.
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Decellularized plant scaffolds have been used to develop edible scaffolds for cell cultured meat because of their natural structures similar to that of mammalian tissues. However, their diverse three-dimensional (3D) porous structures may lead to differences in myogenic differentiation of skeletal muscle cells. In this study, parsley plant tissues were decellularized and modified by type A gelatin and transglutaminase while retaining, respectively, longitudinal fibrous and transverse honeycomb pore structures. The effects of the structure of the decellularized parsley scaffold on the proliferation and myogenic differentiation of C2C12 cells were investigated and the quality of cell cultured meat was evaluated. The results showed that fibrous pore structure guided cells to be arranged in parallel, whereas honeycomb pore structure connected cells in a circular pattern. After induced differentiation, the fibrous scaffolds were more inclined to form multinucleated myotubes with higher expression of myogenic genes and proteins, and the final cell-based meat contained higher total protein content. Decellularized plant scaffolds with fibrous pore structure were more suitable for myogenic differentiation of C2C12 cells, providing support to the development of edible scaffolds for cultured meat. PRACTICAL APPLICATION: This study investigated the different three-dimensional (3D) pore structure of parsley parenchyma to gain insight into how the 3D pore structure of decellularized plant scaffolds regulates myogenic differentiation, which is expected to address the unstable myogenic differentiation of skeletal muscle cells on decellularized plant scaffolds in cell culture meat production.
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Obesity is a risk factor for colorectal cancer (CRC), and the involvement of gut microbiota in the pathogenesis of obesity and CRC is widely recognized. However, the landscape of fecal microbiome and metabolome distinguishing patients with obesity-related CRC from obesity remains unknown. Here, we utilize metagenomic sequencing and metabolomics from 522 patients with CRC and healthy controls to identify the characteristics of obese CRC. Our integrated analysis reveals that obesity-related CRC is characterized by elevated Peptostreptococcus stomatis, dysregulated fatty acids and phospholipids, and altered Kyoto Encyclopedia of Genes and Genomes pathways involving glycerophospholipid metabolism and lipopolysaccharide synthesis. Correlation analysis unveils microbial interactions in obesity, where the probiotic Faecalibacterium prausnitzii and the tumor-promoting species P. stomatis may engage in cross-feeding, thereby promoting tumorigenesis. In vitro experiments affirm enhanced growth under cross-feeding conditions. The mutualistic microbe-microbe interaction may contribute to the association between obesity and elevated CRC risk. Additionally, diagnostic models incorporating BMI-specific microbial biomarkers display promise for precise CRC screening.
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Neoplasias Colorrectales , Microbiota , Humanos , Metaboloma , Obesidad/metabolismo , Neoplasias Colorrectales/microbiología , Interacciones MicrobianasRESUMEN
Brahma-related gene 1 (BRG1) has been implicated in the repair of DNA double-strand breaks (DSBs). Downregulation of BRG1 impairs DSBs repair leading to accumulation of double-stranded DNA (dsDNA). Currently, the role of BRG1 in diabetic cardiomyopathy (DCM) has not been clarified. In this study, we aimed to explore the function and molecular by which BRG1 regulates DCM using mice and cell models. We found that BRG1 was downregulated in the cardiac tissues of DCM mice and in cardiomyocytes cultured with high glucose and palmitic acid (HG/PA), which was accompanied by accumulation of dsDNA and activation of the cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) signaling pathway. shRNA-mediated Brg1 knockdown aggravated DCM mice cardiac functions, enhanced dsDNA accumulation, cGAS-STING signaling activation, which induced inflammation and apoptosis. In addition, the results were further verified in HG/PA-treated primary neonatal rat cardiomyocytes (NRCMs). Overexpression of BRG1 in NRCMs yielded opposite results. Furthermore, a selective cGAS inhibitor RU.521 or STING inhibitor C-176 partially reversed the BRG1 knockdown-induced inflammation and apoptosis in vitro. In conclusion, our results demonstrate that BRG1 is downregulated during DCM in vivo and in vitro, resulting in cardiomyocyte inflammation and apoptosis due to dsDNA accumulation and cGAS-STING signaling activation. Therefore, targeting the BRG1-cGAS-STING pathway may represent a novel therapeutic strategy for improving cardiac function of patients with DCM.
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INTRODUCTION: Knee osteoarthritis (KOA) is one of the most common osteoarthritis, imposing substantial economic and medical burdens on both individuals and society. In China, Tuina has been selected as a complementary and alternative therapy to relieve knee pain and dysfunction symptoms. However, the current evidence is insufficient to support the efficacy of Tuina therapy in addressing knee pain and improving physical function. The trial aims to compare the effectiveness of Tuina with celecoxib, which is considered as the standard treatment, and to assess its potential as an alternative therapy through changes in outcome measures. METHODS AND ANALYSIS: A total of 360 KOA patients aged between 40 and 70 years and classified as Kellgren and Lawrence grades I-II will be recruited from eight subcentral hospitals. The participants will be randomly assigned to either the treatment group (Tuina, Biw) or the control group (celecoxib, Qd), with both groups undergoing a 4-week intervention phase followed by an 8-week follow-up phase. The primary outcome is the change in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain subscale at week 4 compared with baseline. Secondary outcomes including WOMAC stiffness and function subscales, WOMAC total score, 36-item Short-Form Health Survey, Timed Up and Go test, Short Physical Performance Battery, gait analysis parameters and pain medication records will be assessed at weeks 4, 8 and 12. Any adverse events that occur during the trial will be promptly recorded. ETHICS AND DISSEMINATION: This study has been approved by the Ethics Committee of Shanghai Municipal Hospital of Traditional Chinese Medicine (2023SHL-KY-16-01, 2023SHL-KY-16-02). Written informed consent will be obtained from all participants. Study results will be disseminated through peer-reviewed journals and conference presentations. TRIAL REGISTRATION NUMBER: ChiCTR2300069416.
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Osteoartritis de la Rodilla , Humanos , Osteoartritis de la Rodilla/fisiopatología , Osteoartritis de la Rodilla/terapia , China , Persona de Mediana Edad , Anciano , Ensayos Clínicos Controlados Aleatorios como Asunto , Masculino , Dimensión del Dolor , Femenino , Celecoxib/uso terapéutico , Estudios Multicéntricos como Asunto , Adulto , Resultado del Tratamiento , Artralgia/tratamiento farmacológicoRESUMEN
BACKGROUND: Temperature affects influenza transmission; however, currently, limited evidence exists about its effect in China at the national and city levels as well as how temperature can be integrated into influenza interventions. METHODS: Meteorological, pollutant, and influenza data from 201 cities in mainland China between 2013 and 2018 were analyzed at both the city and national levels to investigate the relationship between temperature and influenza prevalence. We examined the impact of temperature on the time-varying reproduction number (Rt) using generalized additive quasi-Poisson regression models combined with the distributed lag nonlinear model. Threshold temperatures were determined for seven regions based on the early warning threshold of serious influenza outbreaks, set at Rt = 1.2. A multivariate random-effects meta-analysis was employed to assess region-specific associations. The excess risk (ER) index was defined to investigate the correlation between Rt and temperature, modified based on seasonal and regional characteristics. RESULTS: At the national level and in the central, northern, northwestern, and southern regions, temperature was found to be negatively correlated with relative risk, whereas the shapes of the data curves for the eastern, southwestern, and northeastern regions were not well defined. Low temperatures had an observable effect on influenza prevalence; however, the effects of high temperatures were not obvious. At an Rt of 1.2, the threshold temperatures for reaching a warning for serious influenza outbreaks were - 24.3 °C in the northeastern region, 16.6 °C in the northwestern region, and between 1â and 10 °C in other regions. CONCLUSION: The study findings revealed that temperature had a varying effect on influenza transmission trends (Rt) across different regions in China. By identifying region-specific temperature thresholds at Rt = 1.2, more effective early warning systems for influenza outbreaks could be tailored. These findings emphasize the significance of the region-specific adaptation of influenza prevention and control measures.
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Ciudades , Gripe Humana , Temperatura , China/epidemiología , Gripe Humana/epidemiología , Humanos , Ciudades/epidemiología , Prevalencia , Estaciones del AñoRESUMEN
As one of the most important food crops in the world, rice yield is directly related to national food security. Lodging is one of the most important factors restricting rice production, and the cultivation of rice varieties with lodging resistance is of great significance in rice breeding. The lodging resistance of rice is directly related to the mechanical strength of the stalks. In this paper, we reviewed the cell wall structure, its components, and its genetic regulatory mechanism, which improved the regulatory network of rice stalk mechanical strength. Meanwhile, we analyzed the new progress in genetic breeding and put forward some scientific problems that need to be solved in this field in order to provide theoretical support for the improvement and application of rice breeding.
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Currently, to overcome the short half-life of the local anesthetic ropivacaine, drug delivery systems such as nanoparticles and liposomes have been used to prolong the analgesic effect, but they are prone to abrupt release from the site of administration or have poor slow-release effects, which increases the risk of cardiotoxicity. In this study, injectable lipid suspensions based on ropivacaine-docusate sodium hydrophobic ion pairing (HIP) were designed to significantly prolong the duration of analgesia. The resulting ion-paired lipid suspension (HIP/LIPO) had a micrometer scale and a high zeta potential, which facilitates stable in situ retention. The strong interaction between docusate sodium and ropivacaine was verified using thermal and spectroscopic analyses, and the formation of micron-sized polymorphic vesicles was attributed to the mutual stabilizing interactions between ropivacaine-docusate sodium HIP, docusate sodium and lecithin. The HIP/LIPO delivery system could maintain drug release for more than 5 days in vitro and achieve high analgesic efficacy for more than 10 days in vivo, reducing the side effects associated with high drug doses. The stable HIP/LIPO delivery system is a promising strategy that offers a clinically beneficial alternative for postoperative pain management and other diseases.
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Anestésicos Locales , Preparaciones de Acción Retardada , Liberación de Fármacos , Ropivacaína , Ropivacaína/administración & dosificación , Ropivacaína/farmacocinética , Ropivacaína/química , Anestésicos Locales/administración & dosificación , Anestésicos Locales/química , Animales , Masculino , Ratas Sprague-Dawley , Anestesia Local/métodos , Ácidos Decanoicos/química , Ácidos Decanoicos/administración & dosificación , Tamaño de la Partícula , Liposomas , Sistemas de Liberación de Medicamentos , Amidas/química , Amidas/administración & dosificación , Ratas , Dolor Postoperatorio/tratamiento farmacológico , Dolor Postoperatorio/prevención & control , Lípidos/química , Interacciones Hidrofóbicas e Hidrofílicas , Lecitinas/química , InyeccionesRESUMEN
Transcription is crucial for the expression of genetic information and its efficient and accurate termination is required for all living organisms. Rho-dependent termination could rapidly terminate unwanted premature RNAs and play important roles in bacterial adaptation to changing environments. Although Rho has been discovered for about five decades, the regulation mechanisms of Rho-dependent termination are still not fully elucidated. Here we report that Rof is a conserved antiterminator and determine the cryogenic electron microscopy structure of Rho-Rof antitermination complex. Rof binds to the open-ring Rho hexamer and inhibits the initiation of Rho-dependent termination. Rof's N-terminal α-helix undergoes conformational changes upon binding with Rho, and is key in facilitating Rof-Rho interactions. Rof binds to Rho's primary binding site (PBS) and excludes Rho from binding with PBS ligand RNA at the initiation step. Further in vivo analyses in Salmonella Typhimurium show that Rof is required for virulence gene expression and host cell invasion, unveiling a physiological function of Rof and transcription termination in bacterial pathogenesis.
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Factor Rho , Factores de Transcripción , Factores de Transcripción/metabolismo , Virulencia/genética , Factor Rho/genética , Factor Rho/metabolismo , Regulación Bacteriana de la Expresión Génica , Transcripción Genética , Bacterias/genética , Salmonella typhimurium/genética , Salmonella typhimurium/metabolismoRESUMEN
Citrus peel is a commonly used food-medicine material in the production of fast-moving consumer goods (FMCGs). For instance, Ganpu tea is manufactured by combining the peel of Citri Reticulatae 'Chachi' (PCRC) with Pu-erh tea. The alleviated irritation of PCRC through years of aging makes Citri reticulatae Pericarpium a traditional Chinese medicine. Herein, we introduced short-term steaming into the processing of PCRC to favor the quick removal of its irritation while retaining its food-medicine properties. Sensory evaluation and volatile component analysis showed that 60-s steaming reduced irritation of freshly prepared PCRC. Biological evaluations indicated no effects of steaming on the neuroprotective activity of PCRC. The process increased the contents of several bioactive ingredients, including hesperidin, nobiletin, tangeretin, and synephrine. In addition, physical indications of accelerating PCRC aging were observed. Taken together, our findings suggest that short-term steaming may offer a promising new possibility for enhancing the quality of citrus peel.
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Citrus , Medicamentos Herbarios Chinos , Medicina Tradicional China , Alimentos , TéRESUMEN
Environmental estrogen exposure has increased dramatically over the past 50 years. In particular, prenatal exposure to estrogen causes many congenital diseases, among which reproductive system development disorders are extremely serious. In this study, the molecular mechanism of hypospadias and the therapeutic effect of genistein (GEN) were investigated through in vivo models prepared by Di-(2-ethylhexyl) phthalate (DEHP) exposure between 12 and 19 days of gestation. With increased DEHP concentrations, the incidence of hypospadias increased gradually. DEHP inhibited the key enzymes involved in steroid synthesis, resulting in decreasing testosterone synthesis. At the same time, DEHP increased reactive oxygen species (ROS) and produced inflammatory factors via NADPH oxidase-1 (NOX1) and NADPH oxidase-4 (NOX4) pathways. It also inhibited Steroid 5 α Reductase 2 (Srd5α2) and decreased dihydrotestosterone (DHT) synthesis. Additionally, DEHP inhibited the androgen receptor (AR), resulting in reduced DHT binding to the AR that ultimately retarded the development of the external reproductive system. GEN, a phytoestrogen, competes with DEHP for binding to estrogen receptor ß (ERß). This competition, along with GEN's antiestrogen and antioxidant properties, could potentially reverse impairments. The findings of this study provide valuable insights into the role of phytoestrogens in alleviating environmental estrogen-induced congenital diseases.