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The Consortium of Eosinophilic Gastrointestinal disease Researchers (CEGIR) and The International Gastrointestinal Eosinophil Researchers (TIGERS) organized a day-long symposium at the 2024 Annual Meeting of the American Academy of Allergy, Asthma & Immunology. The symposium featured new discoveries in basic and translational research and debates on the mechanisms and management of eosinophilic gastrointestinal diseases (EGIDs). Updates on recent clinical trials and consensus guidelines were also presented. Herein, we summarize the updates on EGIDs presented at the symposium.
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This real-world retrospective cohort study using Australian Pharmaceutical Benefits Scheme (PBS) 10% investigated changes in chronic lymphocytic leukemia (CLL) treatment by line of therapy, time-to-next-treatment, treatment duration, and overall survival (OS). Overall, 803 patients received their first PBS-reimbursed CLL medication between 1 January 2011 to 31 July 2021 (median age: 70 years; 64.6% male), 289 post-1 August 2020. In 2011, most first-line (1 L) prescribing was fludarabine, cyclophosphamide, and rituximab (FCR). By 2021, common 1L were chlorambucil ± CD20 (26.1%), Bruton Tyrosine Kinase inhibitor (BTKi) (26.1%), and CD20 monotherapy (23.9%). In 2011, relapsed/refractory (R/R) CLL treatment was CD20 monotherapy or FCR. By 2021, BTKi (57.7%) and venetoclax ± CD20 (26.1%) were most common. Compared to FCR, 1 L treatment duration (Hazard Ratio) was shorter for CD20 monotherapy (1.7) or chlorambucil ± CD20 (2.5). In R/R CLL, median duration was 24 (ibrutinib) and 19 months (venetoclax). Median OS was 127 months. CLLtreatment pattern shave greatly changed in Australia since the introduction of novel therapies.
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Despite extensive research on the impact of warming and nitrogen deposition on soil organic carbon components, the response mechanisms of microbial community composition and enzyme activity to soil organic carbon remain poorly understood. This study investigated the effects of warming and nitrogen deposition on soil organic carbon components in the Tibetan Plateau alpine meadow and elucidated the regulatory mechanisms of microbial characteristics, including soil microbial community, enzyme activity, and stoichiometry, on organic carbon components. Results indicated that both warming and nitrogen deposition significantly increased soil organic carbon, readily oxidizable carbon, dissolved organic carbon, and microbial biomass carbon. The interaction between warming and nitrogen deposition influenced soil carbon components, with soil organic carbon, readily oxidizable carbon, and dissolved organic carbon reaching maximum values in the W0N32 treatment, while microbial biomass carbon peaked in the W3N32 treatment. Warming and nitrogen deposition also significantly increased soil Cellobiohydrolase, ß-1,4-N-acetylglucosaminidase, leucine aminopeptidase, and alkaline phosphatase. Warming decreased the soil enzyme C: N ratio and C:P ratio but increased the soil enzyme N:P ratio, while nitrogen deposition had the opposite effect. The bacterial Chao1 index and Shannon index increased significantly under warming conditions, particularly in the N32 treatment, whereas there were no significant changes in the fungal Chao1 index and Shannon index with warming and nitrogen addition. Structural equation modeling revealed that soil organic carbon components were directly influenced by the negative impact of warming and the positive impact of nitrogen deposition. Furthermore, warming and nitrogen deposition altered soil bacterial community composition, specifically Gemmatimonadota and Nitrospirota, resulting in a positive impact on soil enzyme activity, particularly soil alkaline phosphatase and ß-xylosidase, and enzyme stoichiometry, including N:P and C:P ratios. In summary, changes in soil organic carbon components under warming and nitrogen deposition in the alpine meadows of the Tibetan Plateau primarily depend on the composition of soil bacterial communities, soil enzyme activity, and stoichiometric characteristics.
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BACKGROUND: Droplet digital PCR (ddPCR) is increasingly used in diagnosing clinical pathogens, but its effectiveness in cirrhosis patients with suspected ascites infection remains uncertain. METHODS: The diagnostic performance of ddPCR was assessed in 305 ascites samples, utilizing culture and clinical composite standards. The quantitative value and potential clinical impact of ddPCR were further analyzed in patients with spontaneous bacterial peritonitis. RESULTS: With culture standards, ddPCR demonstrated a sensitivity of 86.5% and specificity of 83.2% for bacterial or fungal detection. After adjustment of clinical composite criteria, specificity increased to 96.4%. Better diagnostic performance for all types of targeted pathogens, particularly fungi, was observed with ddPCR compared to culture, and more polymicrobial infections were detected (30.4% versus 5.7%, p < 0.001). Pathogen loads detected by ddPCR correlated with white blood cell count in ascites and blood, as well as polymorphonuclear cell (PMN) count in ascites, reflecting infection status rapidly. A positive clinical impact of 55.8% (43/77) was observed for ddPCR, which was more significant among patients with PMN count ≤ 250/mm3 in terms of medication adjustment and new diagnosis. ddPCR results for fungal detection were confirmed by clinical symptoms and other microbiological tests, which could guide antifungal therapy and reduce the risk of short-term mortality. CONCLUSIONS: ddPCR, with appropriate panel design, has advantages in pathogen detection and clinical management of ascites infection, especially for patients with fungal and polymicrobial infections. Patients with atypical spontaneous bacterial peritonitis benefited more from ddPCR.
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Ascitis , Infecciones Bacterianas , Cirrosis Hepática , Peritonitis , Reacción en Cadena de la Polimerasa , Humanos , Cirrosis Hepática/complicaciones , Cirrosis Hepática/microbiología , Cirrosis Hepática/diagnóstico , Femenino , Masculino , Reacción en Cadena de la Polimerasa/métodos , Persona de Mediana Edad , Peritonitis/diagnóstico , Peritonitis/microbiología , Ascitis/microbiología , Infecciones Bacterianas/diagnóstico , Infecciones Bacterianas/microbiología , Sensibilidad y Especificidad , Anciano , Micosis/diagnóstico , Micosis/microbiologíaRESUMEN
Culter alburnus (topmouth culter)is an economically valuable freshwater fish. However, its insufficient tolerance to dissolved oxygen (DO) and ammonia nitrogen (AN) hinders its industrialisation. 360 experimental fish (4.87 ± 1.10 g) were placed in breathing chambers (oxygen level was 0.70-6.50 mg/L) or water tanks (control AN, 0 mg/L; low AN, 8 mg/L; high AN, 16 mg/L). This study analysed the effects of DO and AN on C. alburnus at physiological, biochemical, and molecular levels. (1) Physiology level: the floating point, coma critical point, and coma point at 20 °C group were significantly higher than those at 30 °C. The oxygen consumption rate of C. alburnus at 20 °C, 25 °C, and 30 °C was (256.65 ± 25.87), (470.47 ± 83.84), and (520.87 ± 55.40) mg/kg.h. The LC50 of AN after 96 h was 24.13 mg/L, and the safe concentration was 2.41 mg/L. The survival rate in the high AN group was significantly lower than that in the other two groups. (2) Biochemistry level: The change curves of antioxidant enzyme activity in the liver tissue under hypoxic stress reached a maximum at 12 h and then decreased. In addition, the increase and decrease in enzyme activity (except malondialdehyde) in the high AN group was lower than that in the low AN group. (3) Molecular level: the angiotensin-converting enzyme and carboxypeptidase genes were the major differentially expressed genes (DEGs) in hypoxic stress, and the DEGs were mainly enriched in the ABC transporter signal transduction pathway. In addition, the serum/glucocorticoid-regulated kinase, stearoyl-CoA desaturase, and 3-hydroxy-3-methylglutaryl-coenzyme A reductase genes were among the major DEGs under high AN stress. The DEGs were mainly enriched in steroid biosynthesis or glycine, serine, and threonine metabolism transporter signal transduction pathways. In summary, it is necessary to focus on the DO and AN during C. alburnus breeding.
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ABSTRACT: Introduction: Previous studies have manifested that those sedatives acting on γ-aminobutyric acid A (GABAa) receptor could produce effective brain protection against regional and global ischemic stimulation. The present study was designed to investigate the effect of a novel GABAa receptor agonist, remimazolam postconditioning (RP) on cerebral outcome after global ischemic stimulation induced by cardiac arrest and resuscitation in swine. Methods: A total of 24 swine were used in this study, in which the animals were randomly divided into the following three groups: sham group (n = 6), cardiopulmonary resuscitation (CPR) group (n = 9), and CPR + RP group (n = 9). The experimental model was established by the procedure of 10 min of cardiac arrest and 5 min of CPR. Those resuscitated swine in the CPR + RP group received an intravenous infusion of 2.5 mg/kg of remimazolam within 60 min. Postresuscitation cerebral injury biomarkers and neurological function were evaluated for a total of 24 h. At 24 h after resuscitation, brain cortex was harvested to evaluate the severity of pathologic damage, including tissue inflammation, oxidative stress, apoptosis, and necroptosis. Results: Baseline characteristics and CPR outcomes were not significantly different between the CPR and CPR + RP groups. After resuscitation, significantly greater cerebral injury and neurological dysfunction were observed in the CPR and CPR + RP groups than in the sham group. However, remimazolam postconditioning significantly alleviated cerebral injury and improved neurological dysfunction after resuscitation when compared with the CPR group. At 24 h after resuscitation, tissue inflammation, oxidative stress, and cell apoptosis and necroptosis were significantly increased in the CPR and CPR + RP groups when compared with the sham group. Nevertheless, the severity of pathologic damage mentioned previously were significantly milder in those swine treated with the remimazolam when compared with the CPR group. Conclusions: In a swine model of cardiac arrest and resuscitation, the remimazolam administered after resuscitation significantly improved the markers of postresuscitation cerebral injury and therefore protected the brain against global ischemic stimulation.
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Benzodiazepinas , Reanimación Cardiopulmonar , Modelos Animales de Enfermedad , Paro Cardíaco , Animales , Porcinos , Paro Cardíaco/terapia , Benzodiazepinas/uso terapéutico , Benzodiazepinas/farmacología , Biomarcadores/metabolismo , Lesiones Encefálicas , Masculino , Femenino , Apoptosis/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacosRESUMEN
Rare eosinophil-associated disorders (EADs), including hypereosinophilic syndrome, eosinophilic granulomatosis with polyangiitis, and eosinophilic gastrointestinal disorders, are a heterogeneous group of conditions characterized by blood and/or tissue hypereosinophilia and eosinophil-related clinical manifestations. Although the recent availability of biologic therapies that directly and indirectly target eosinophils has the potential to dramatically improve treatment options for all EADs, clinical trials addressing their safety and efficacy in rare EADs have been relatively few. Consequently, patient access to therapy is limited for many biologics, and the establishment of evidence-based treatment guidelines has been extremely difficult. In this regard, multicenter retrospective collaborative studies focusing on disease manifestations and treatment responses in rare EADs have provided invaluable data for physicians managing patients with these conditions and helped identify important questions for future translational research. During the Clinical Pre-Meeting Workshop held in association with the July 2023 biennial meeting of the International Eosinophil Society in Hamilton, Ontario, Canada, the successes and limitations of pivotal multicenter retrospective studies in EADs were summarized and unmet needs regarding the establishment of guidelines for use of biologics in rare EADs were discussed. Key topics of interest included (1) clinical outcome measures, (2) minimally invasive biomarkers of disease activity, (3) predictors of response to biologic agents, and (4) long-term safety of eosinophil depletion. Herein, we report a summary of these discussions, presenting a state-of-the-art overview of data currently available for each of these topics, the limitations of the data, and avenues for future data generation through implementation of multidisciplinary and multicenter studies.
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Eosinófilos , Investigación Biomédica Traslacional , Humanos , Eosinófilos/inmunología , Terapia Biológica/métodos , Enfermedades Raras/tratamiento farmacológico , Enfermedades Raras/terapia , Eosinofilia/tratamiento farmacológico , Síndrome Hipereosinofílico/tratamiento farmacológico , Síndrome Hipereosinofílico/terapiaAsunto(s)
Eosinófilos , Inmunoglobulina E , Humanos , ARN Mensajero/genética , Receptores de IgE/genéticaRESUMEN
OBJECTIVE@#To assess the outcomes after acupoint application in patients with pharyngeal pain in a real-world settings, and analyze the characteristics of effective population and prescription characteristics of acupoint application.@*METHODS@#Based on CHUNBO platform, patients with pharyngeal pain who were candidates for acupoint application on the basis of physician-evaluation, were enrolled in a nationwide, prospective, 69-week multicenter observational study from August 2020 to February 2022. Propensity score matching (PSM) was used to match the confounding factors and the association rules were used to analyze the characteristics of effective population and prescription characteristics of acupoint application. Outcome assessments included the disappearance rate of pharyngeal pain (within 3, 7, and 14 days), disappearance time of pharyngeal pain, as well as adverse events.@*RESULTS@#Of 7,699 enrolled participants, 6,693 (86.9%) received acupoint application and 1,450 (21.7%) with non-acupoint application. After PSM, there were 1,004 patients each in the application group (AG) and non-application group (NAG). The disappearance rate of pharyngeal pain in the AG at 3, 7, and 14 days were all higher than those in the NAG (P<0.05). The disappearance time of pharyngeal pain in the AG were shorter than that in the NAG (logrank P<0.001, hazard ratio=1.51, 95% confidence interval: 1.41-1.63). The median age of effective cases was 4 years, mainly 3-6 years old (40.21%). The disappearance rate of pharyngeal pain in the application group with tonsil diseases was 2.19 times higher than that in the NAG (P<0.05). The commonly used acupoints for the effective cases were Tiantu (RN 22), Shenque (RN 8) and Dazhui (DU 14). The commonly used herbs for the effective cases were Natrii sulfas, Radix et Rhizoma Rhei, and Herba Ephedrae. Among them, Natrii sulfas was applied to RN 8 most frequently (support 84.39%). A total of 1,324 (17.2%) patients experienced AEs, and mainly occurred in the AG, with significant difference in the incidence of AEs between goups (P<0.05). All AEs reported were the first grade, and the average regression days of AEs was 2.8 days.@*CONCLUSIONS@#Acupoint application in patients with pharyngeal pain resulted in improved effective rate and shortened duration, especially children aged 3-6 years old, and those with tonsil diseases. Acupoint of RN 22, RN 8 and DU 14, Natrii sulfas, Radix et Rhizoma Rhei, and Herba Ephedrae were the most commonly used herbs in the treatment of pharyngeal pain.
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Niño , Humanos , Preescolar , Puntos de Acupuntura , Medicina Tradicional China/métodos , Estudios Prospectivos , DolorRESUMEN
Objective:To analyze the characteristics and electrogastrogram features of patients with functional dyspepsia (FD) overlapping lower gastrointestinal symptoms (LGS).Methods:The clinical data of 61 patients with FD from January 2018 to December 2020 in the First Affiliated Hospital of Nanjing Medical University were retrospectively analyzed. Among them, FD overlapping LGS was in 33 cases (FD overlapping LGS group), and simple FD in 28 cases (simple FD group). The manifestations of patients with FD overlapping LGS were recorded. The dyspeptic symptom score was assessed using the Rome Ⅳ criteria. Anxiety and depression status were evaluated using the hospital anxiety and depression scale (HADS), and sleep disorder was assessed using the Pittsburgh sleep quality index (PSQI). The electrogastrogram was performed, and the normal slow wave percentage (N%), bradygastria percentage (B%), tachygastria percentage (T%), arrhythmia percentage (A%), dominant frequency, dominant power and postprandial-to-fasting power ratio (PR) were recorded.Results:The most common symptom in FD patients overlapping LGS was lower abdomen distention, the incidence was 84.85% (28/33). The upper abdominal bloating score in FD overlapping LGS group was significantly higher than that in simple FD group: 7.00 (6.50, 7.00) scores vs. 5.00 (0.50, 7.00) scores, and there was statistical difference ( P<0.01); there were no statistical differences in other dyspeptic symptoms scores and total score between the two groups ( P>0.05). The incidences of depression and sleep disorder in FD overlapping LGS group were significantly higher than those in simple FD group: 42.42% (14/33) vs. 14.29% (4/28) and 69.70% (23/33) vs. 39.29% (11/28), and there were statistical differences ( χ2 = 5.77 and 5.68, P<0.05); there was no statistical difference in the incidence of anxiety between the two groups ( P>0.05). In FD overlapping LGS group, the postprandial T% in the gastric fundus and postprandial A% in the gastric body were significantly lower than those before meal: 13.79% (6.79%, 21.46%) vs. 20.69% (12.45%, 27.59%) and 3.45% (0, 6.90%) vs. 6.90% (3.45%, 13.79%), and there were statistical differences ( P<0.01). In simple FD group, the postprandial N% in the gastric fundus was significantly lower than that before meal: 55.92% (43.71%, 70.02%) vs. 69.27% (48.07%, 78.45%), and there was statistical difference ( P<0.05). In the gastric fundus, the preprandial N% in FD overlapping LGS group was significantly lower than that in simple FD group, preprandial B% and T% were significantly higher than those in simple FD group, and there were statistical differences ( P<0.01 or <0.05). In the gastric body, the preprandial N% in FD overlapping LGS group was significantly lower than that in simple FD group, and there was statistical difference ( P<0.05). In the pyloric region, the PR in FD overlapping LGS group was significantly lower than that in simple FD group, and there was statistical difference ( P<0.05). In the overall stomach, the preprandial N% in FD overlapping LGS group was significantly lower than that in simple FD group, the preprandial B% and T% were significantly higher than those in simple FD group, and there were statistical differences ( P<0.01 or <0.05). Spearman correlation analysis result showed that the disease course was not correlated with electrogastrogram parameters in patients with FD overlapping LGS ( P>0.05); the total score of dyspeptic symptoms was positively correlated with postprandial A% in the overall stomach ( r = 0.345, P<0.05), and negatively correlated with postprandial dominant frequency in the overall stomach and pyloric region ( r = -0.357 and -0.473, P<0.05 or <0.01). Conclusions:FD patients can overlap with various LGS. The patients with FD overlapping LGS have more severe dyspepsia symptoms, higher proportions of comorbid depression and sleep disorders, and more severe abnormalities in fasting proximal gastric electrical rhythm and emptying function. The severity of dyspeptic symptoms in patients with FD overlapping LGS is correlated with postprandial gastric electrical rhythm abnormalities.
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Stroke is one of the most serious complications of transcatheter aortic valve replacement(TAVR),tremendously increasing mortality and the loss of neurocognitive function.Since TAVR is expected to further spread into lower-risk patient groups,there will be greater emphasis to obviate such serious complications.One possible technique for preventing stroke is using cerebral embolic protection devices(CEPDs).CEPDs are designed for capturing or deflecting emboli that are enter route to the brain and hence to protect the brain from embolism.Since this is a rapidly growing field with recent advances,and the impact of CEPD on preventing neurological events is still limited,there is an urgent need for understanding the role of CEPD in preventing clinically significant strokes.Although their clinical utilization is increasing,the risk factors for stroke related to TAVR and evidence for using CEPDs are not yet clear.In this review,we present an overview of the available literature on TAVR related stroke and CEPD,and outline recent advances within this field.
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Objective:To explore the optimal index of rotational displacement of femoral neck fractures by modeling the axial rotational displacement of femoral neck fractures after reduction and based on X-ray projections.Methods:Six dry human femur specimens, comprising 2 males and 4 females, were utilized in the study. Design and manufacture a proximal femur ortholateral and oblique X-ray casting jigs and mounts. The femoral neck fracture was modeled on the femoral specimen, with Pauwells 30°, 50°, and 70° models (2 each) made according to Pauwells typing. The fractures were manually repositioned with residual anterior 20°, 40° and 60° axial rotational displacements. Each fracture model was projected at different angles (pedicled 40°, pedicled 20°, vertical 0°, cephalad 20°, and cephalad 40°), and the trabecular angle and Garden's alignment index of the model were measured to observe the imaging characteristics of the fracture line on the medial oblique and lateral oblique radiographs.Results:In the presence of a 20° and 40° anterior rotational displacement following reduction of a femoral neck fracture, the trabecular angle in the rotationally displaced group was not significantly different from that of the anatomically repositioned group in various projection positions. However, when a residual rotational displacement of 60° was present, the trabeculae appeared blurred at most projection angles in the Pauwells 30° and 50° models, failing to measure trabecular angles. In the Pauwells 70° fracture model, the trabecular angle in the rotational displacement group was significantly different from that in the anatomical reduction group. In anteroposterior radiographs, when the anterior rotation displacement was 60° in the Pauwells 70° group, Garden's contralateral index showed an unsatisfactory restoration (150°, 142°), whereas all rotationally displaced models in the Pauwells 30° and Pauwells 50° groups had a Garden's contralateral index of >155°, which achieved an acceptable restoration. In lateral radiographs, all rotational displacement models with Garden's alignment index>180° failed to achieve acceptable repositioning, and the larger the Pauwells angle the greater the Garden's alignment index at the same rotational displacement. In the internal oblique position with a bias towards the foot side, the image showed partial overlap between the femoral head and the shaft, making it difficult to assess the quality of the reduction. Conversely, when projected cephalad, the femoral neck appeared longer, particularly at a projection angle of 40° cephalad, allowing for clear observation of the fracture line and the anatomy of the proximal femur. The trabeculae were not well visualized in the external oblique position.Conclusion:There are limitations in applying the trabecular angle to assess the axial rotational displacement of the femoral head after reduction of femoral neck fractures. The Pauwells 70° with residual rotational anterior displacement of 60° was the only way to detect axial rotational displacement of the femoral head on anteroposterior radiographs Garden's alignment index. For the determination of axial rotational displacement of the femoral head, the Garden's alignment index on lateral radiographs provides higher reliability.
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@#Transcatheter aortic valve replacement (TAVR) has seen a surge in clinical research, basic research, and innovative device development both domestically and internationally in the previous 2023. This article aims to review the progress of TAVR in the past year from the perspectives of international, and domestic research development of application. It highlights new clinical and basic research findings both domestically and internationally, the emergence of new devices and technologies, and the development and use of TAVR in China. Finally, it provides an outlook on the trajectory of TAVR development in 2024.
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【Objective】 To analyze the clinical features of patients with infected pancreatic necrosis (IPN) complicated with fungal infection so as to identify possible risk factors for death. 【Methods】 We analyzed the clinical data of patients with IPN admitted to Xuanwu Hospital Capital Medical University from January 1, 2017 to December 31, 2021. According to the results of pancreatic necrotic tissue and drainage fluid culture, the patients were divided into the group with fungal infection and the group without fungal infection. The baseline data, clinical features and outcomes of the two groups were compared, and the risk factors for death in patients with fungal infection were analyzed. 【Results】 We included a total of 214 patients in the study, of whom 49 patients in the fungal infection group had wider necrotic involvement, lower hematopoietic volume, and higher blood glucose at admission. Patients with fungal infection had a higher proportion of multidrug-resistant bacteria (MDRB), and hospital and ICU stay as well as parenteral nutrition duration were also longer. In the group of patients with fungal infection, the proportion of patients undergoing surgery did not increase (P>0.05), but the proportion of patients with perioperative organ failure and death was higher (P<0.05). Candida albicans (44.8%) was the most common fungus detected, followed by Candida parapsilosis (28.6%) and Candida tropicalis (8.2%). Logistic regression analysis showed that MDRB infection (OR=1.37, 95% CI:1.02-1.83), fungemia (OR=1.53, 95% CI:1.06-2.23), hyperglycemia (OR=1.65, 95% CI:1.28-2.10), new organ failure (OR=1.65, 95% CI:1.19-2.29) and bleeding complications (OR=1.64, 95% CI:1.28-2.10) after surgery were risk factors for death in patients with fungal infection. 【Conclusion】 Fungal infection increases mortality in patients with IPN and the incidence of new organ failure after surgery. Attention to fungemia, MDRB infection, hyperglycemia, organ failure and postoperative bleeding can help reduce the risk of death.
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【Objective】 To construct a nomogram survival prediction model for patients with locally advanced renal cell carcinoma based on SEER database (n=7893), so as to provide reference for future prognosis study. 【Methods】 Case data were downloaded from the SEER database, and divided into the experimental group and validation group with a ratio of 7∶3 by simple randomization.The clinical information was analyzed, independent risk factors influencing prognosis were screened, and the overall survival (OS) and tumor-specific survival (CSS) were mapped.Model performance was evaluated using consistency index, area under the receiver operating characteristic curve (AUC), internal and external validation, and calibration curves. 【Results】 Patients’ age, tumor size, disease progression tpye, TNM stage, number of positive lymph nodes, marital status and pathological type were significantly correlated with OS and CSS (P<0.01).Based on the above predictors, the internal verification AUC of the 1-, 3- and 5- year OS nomogram model was 0.809, 0.721 and 0.715, respectively.The internal validation AUC of the nomogram model for 1-, 3- and 5- year CSS was 0.802, 0.745 and 0.735, respectively.The external validation AUC of the OS nomogram model was 0.792, 0.628 and 0.620 at 1, 3 and 5 years, respectively, and the external validation AUC of CSS was 0.943, 0.803 and 0.737 at 1.3 and 5 years, respectively, showing good model differentiation and accuracy. 【Conclusion】 The prediction performance of the nomogram model is good, and it can provide reference for individualized treatment.
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Objective:To investigate the efficacy of Balanophora involucrata Hook.f.in treatment of hyperuricemia(HUA)based on network pharmacology,molecular docking,and hyperuricemia models in vivo and in vitro,and to clarify the main targets of its active components and related signaling pathway mechanism.Methods:The potential targets of Balanophora involucrata Hook.f.in treatment of HUA were identified by Databases such as the Traditional Chinese Medicine Database in Taiwan,the Chinese Herbal Medicine Identification Database,Professional Chemical Database,TargetNet Database,SwissTargetPrediction Database,GeneCards,Therapeutic Target Database(TTD),DrugBank Database,DisGeNET Database,Online Mendelian Inheritance in Man(OMIM)Database,and Venny Database.STRING Database and Cytoscape software were used to construct the active component-predictive target network and protein-protein interaction(PPI)network for Balanophora involucrata Hook.f.;topological analysis was used to select the main active components and core targets;Gene Ontology(GO)functional and Kyoto Encyclopedia of Genes and Genomes(KEGG)signaling pathway enrichment analysis were performed by R software;AutoDock Vina software was used for molecular docking validation.The NRK-52E cells were divided into blank control group,blank administration group,model group,and different concentrations(2.0,10.0,and 50.0 μmol·L-1)of erythrodiol(EDT)groups.High-performance liquid chromatography culture(HPLC)was used to detect the uric acid(UA)levels in the cell culture supernatants in various groups.The male ICR mice were divided into blank control group,blank administration group,model group,and EDT group;the mice in the last two groups were used to prepare the HUA models;kits were used to detect the levels of UA,creatinine(Cr),and blood urea nitrogen(BUN)in serum of the mice in various groups;the bilateral kidney tissue of the mice was harvested and weighed;the kidney indexes of the mice in various groups were calculated;TUNEL staining was used to observe the apoptosis in kidney tissue of the mice in various groups;Western blotting method was used to detect the expression levels of protein kinase B(AKT),phosphorylated AKT(p-AKT),phosphoinositide 3-kinase(PI3K),phosphorylated PI3K(p-PI3K),B-cell lymphoma-2(Bcl-2),Bcl-2-associated X protein(Bax),and matrix metalloproteinase-9(MMP-9)proteins in kidney tissue of the mice in various groups.Results:Six active components of Balanophora involucrata Hook.f.were identified,involving 116 intersecting targets and 14 core targets.The enrichment analysis yielded 1 828 GO terms and 145 signaling pathways.The molecular docking results showed that EDT had good binding activity with MMP-9.The high uric acid cell experiment results showed that compared with blank control group,the UA level in the cells in model group was significantly increased(P<0.01);compared with model group,the UA levels in the cells in 2.0,10.0,and 50.0 μmol·L-1 EDT groups were significantly decreased(P<0.01).Compared with blank control group,the levels of UA,Cr,and BUN in serum of the mice in model group were increased(P<0.01),and the kidney indexes were significantly increased(P<0.01);compared with model group,the levels of UA,Cr,and BUN in serum of the mice in EDT group were decreased(P<0.05 or P<0.01),and the kidney index was significantly decreased(P<0.05 or P<0.01).Compared with blank control group,the number of apoptotic cells in kidney tissue of the mice in model group was increased;compared with model group,the number of the apoptotic cells in kidney tissue of the mice in EDT group was significantly decreased.Compared with blank control group,the ratios of p-AKT/AKT and p-PI3K/PI3K and expression level of Bcl-2 protein in kidney tissue of the mice in model group were significantly decreased(P<0.05 or P<0.01),while the expression levels of Bax and MMP-9 proteins were significantly increased(P<0.01);compared with model group,the ratios of p-AKT/AKT and p-PI3K/PI3K and expression level of Bcl-2 protein in kidney tissue of the mice in EDT group were significantly increased(P<0.05 or P<0.01),and the expression levels of Bax and MMP-9 proteins were significantly decreased(P<0.01).Conclusion:The active component of Balanophora involucrata Hook.f.,EDT,has a UA-decreasing effect and may inhibit the apoptosis and alleviate the kidney injury by activating the PI3K/AKT signaling pathway.
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With reference to Xin Diao Sun Zhen Ren Qian Jin Fang,the Xindiao's edition of Bei Ji Qian Jin Yao Fang(Invaluable Prescriptions for Emergencies)which was the popular edition before official block printing of the Northern Song Dynasty),we analyzed the collation for proof-reading method in Song's edition of Bei Ji Qian Jin Yao Fang(Invaluable Prescriptions for Emergencies)printed by Bureau of Correcting Medical Books in Northern Song Dynasty.The results showed that there are many omissions and erroneous annotations in the collation records of the Song's edition,indicating that the judgment of the scholarly value of textual difference and the criteria of selecting and omitting the annotations of textual difference in the Song's edition require further studies.Some of the collation records in the Song's edition were consistent with those of the Xindiao's edition,suggesting that the Xindiao's edition was referenced during the collation by the officials of the Song Dynasty.In compiling Bei Ji Qian Jin Yao Fang,the original edition and the collated edition were not defined by the officials of the Song Dynasty,multiple hand copies in Tang Dynasty were collected for reference,and multiple medical records in Tang Dynasty and before Tang Dynasty were referenced.For the proofreading work of the Bureau for Revising Medical Books was in charge by scholars and Confucian ministers,we proposed that the complexity during compiling the book and the uncertainty of the text should be paid more attention.It is necessary to further clarify the basic issues such as the origin,basic structure,references and citation methods of the Song's edition,so as to provide reference for understanding the characteristics of the edition correctly and making effective use of the literature.
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This article aims to analyze LI Fei's academic thinking and experience in treating facial paralysis.LI Fei proposes that the diagnosis and treatment of facial paralysis should follow the principle of"identify the cause of the disease when it is occured at first time,followed by exploring the pathogenesis of the disease,then differentiating the syndrome and treating the disease,and recognizing the syndrome and treating the disease",and that the basic treatment principle should be"dispelling wind and unblocking the collaterals,regulating the tendons and meridians".In clinical treatment,"put emphasis on anatomy,treat the disease according to symptoms"is the basic policy;meanwhile,integrating Chinese and western theories,combining the anatomical structure of the expression muscle,dynamically judging the recovery of nerves and muscles,and selecting the corresponding empirical acupoints according to the symptoms.LI Fei emphasizes the integration of theories and summarizes the"triple"methods of differentiation by reasoning,staging and symptoms,and the"triple"theory of treatment by regulating menstruation,tendon and spirit,which is worthy of reference in the clinic.
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Objective To explore the correlation of glucose and lipid metabolism indicators combined with antiphospholipid antibodies with the prognosis of patients with atherosclerosis.Methods A total of 128 patients with atherosclerosis treated in our hospital from April 2021 to March 2023 were selected as study group,and 48 healthy individuals as control group.Glycolipid metabolism indexes and antiphospholipid antibody level of the two groups were compared,and the predictive value of glycolipid metabolism indexes,antiphospholipid antibodies and combined detection for the prognosis of patients with atherosclerosis were analyzed by ROC.Results TC,TG,ACL,and anti-β2-GP1 in the study group was higher than that in the control group(P<0.05).The study group was divided into two sub-groups according to the prognosis.The expression level of TC,TG,ACL,and anti-β 2-GP1 in poor prognosis group was higher than that in good prognosis group(P<0.05).TC,TG,ACL,and anti-β 2-GP1 was positively correlated with the poor prognosis of patients with atherosclerosis(P<0.05).ROC curve showed that the predictive value of six combined tests for the prognosis of patients with atherosclerosis was higher than that of single test of TC,TG,ACL,and anti-β2-GP1(P<0.05).Conclusion The combined detection of TC,TG,ACL,and anti-β2-GP1 has high predictive value for the prognosis of patients with atherosclerosis.
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Objective To investigate the effect of berberine hydrochloride tablets combined with compound glutamine in treating ulcerative colitis(UC).Methods One hundred and two patients with UC admitted to our hospital were collected and grouped into two groups according to the random number table.Fifty-one patients in the control group were given conventional treatment+compound glutamine,and 51 patients in the experimental group were given berberine hydrochloride tablets based on the control group.Both groups were treated for 8 weeks.The efficacy,modified Mayo score,intestinal mucosal barrier function,soluble late glycation end product receptor(sRAGE),interleukin-17(IL-17),IL-6 and incidence of untoward reactions were compared between the two groups.Results The total effective rate of the experimental group was higher than that of the control group(92.2%vs.76.5%,P<0.05).After treatment,scores of defecation frequency,blood in stool,endoscopic findings,physician's overall evaluation,diamine oxidase(DAO),D-lactic acid,endotoxin,sRAGE,IL-17 and IL-6 were lower in both groups than those before treatment(P<0.05),and the research group was lower than the control group(P<0.05).There was no significant difference in the total incidence of untoward reactions between the experimental group and the control group(P>0.05).Conclusion Berberine hydrochloride tablets combined with compound glutamine are effective in treating UC,which can reduce the activity of UC,improve the intestinal mucosal barrier function,regulate serum sRAGE,IL-17 and IL-6 levels,without increasing adverse reactions.