Emodin is a hydroxyanthraquinone compound that is widely distributed and has multiple pharmacological activities, including anti-diarrheal, anti-inflammatory, and liver-protective effects. Research indicates that emodin may be one of the main components responsible for inducing hepatotoxicity. However, studies on the mechanisms of liver injury are relatively limited, particularly those related to bile acids(BAs) metabolism. This study aims to systematically investigate the effects of different dosages of emodin on BAs metabolism, providing a basis for the safe clinical use of traditional Chinese medicine(TCM)containing emodin. First, this study evaluated the safety of repeated administration of different dosages of emodin over a 5-week period, with a particular focus on its impact on the liver. Next, the composition and content of BAs in serum and liver were analyzed. Subsequently, qRT-PCR was used to detect the mRNA expression of nuclear receptors and transporters related to BAs metabolism. The results showed that 1 g·kg~(-1) emodin induced hepatic damage, with bile duct hyperplasia as the primary pathological manifestation. It significantly increased the levels of various BAs in the serum and primary BAs(including taurine-conjugated and free BAs) in the liver. Additionally, it downregulated the mRNA expression of farnesoid X receptor(FXR), retinoid X receptor(RXR), and sodium taurocholate cotransporting polypeptide(NTCP), and upregulated the mRNA expression of cholesterol 7α-hydroxylase(CYP7A1) in the liver. Although 0.01 g·kg~(-1) and 0.03 g·kg~(-1) emodin did not induce obvious liver injury, they significantly increased the level of taurine-conjugated BAs in the liver, suggesting a potential interference with BAs homeostasis. In conclusion, 1 g·kg~(-1) emodin may promote the production of primary BAs in the liver by affecting the FXR-RXR-CYP7A1 pathway, inhibit NTCP expression, and reduce BA reabsorption in the liver, resulting in BA accumulation in the peripheral blood. This disruption of BA homeostasis leads to liver injury. Even doses of emodin close to the clinical dose can also have a certain effect on the homeostasis of BAs. Therefore, when using traditional Chinese medicine or formulas containing emodin in clinical practice, it is necessary to regularly monitor liver function indicators and closely monitor the risk of drug-induced liver injury.
Emodin/administration & dosage* ; Bile Acids and Salts/metabolism* ; Animals ; Male ; Liver/injuries* ; Chemical and Drug Induced Liver Injury/genetics* ; Drugs, Chinese Herbal/adverse effects* ; Humans ; Rats, Sprague-Dawley ; Mice ; Rats

In this study, lipopolysaccharide(LPS), ovalbumin(OVA), and compound 48/80(C48/80) were administered to establish non-infectious pneumonia models under simulated clinical conditions, and the correlation between their pathological characteristics and traditional Chinese medicine(TCM) syndromes was compared, providing the basis for the selection of appropriate animal models for TCM efficacy evaluation. An acute pneumonia model was established by nasal instillation of LPS combined with intraperitoneal injection for intensive stimulation. Three doses of OVA mixed with aluminum hydroxide adjuvant were injected intraperitoneally on days one, three, and five and OVA was administered via endotracheal drip for excitation on days 14-18 to establish an OVA-induced allergic pneumonia model. A single intravenous injection of three doses of C48/80 was adopted to establish a C48/80-induced pneumonia model. By detecting the changes in peripheral blood leukocyte classification, lung tissue and plasma cytokines, immunoglobulins(Ig), histamine levels, and arachidonic acid metabolites, the multi-dimensional analysis was carried out based on pathological evaluation. The results showed that the three models could cause pulmonary edema, increased wet weight in the lung, and obvious exudative inflammation in lung tissue pathology, especially for LPS. A number of pyrogenic cytokines, inclading interleukin(IL)-6, interferon(IFN)-γ, IL-1β, and IL-4 were significantly elevated in the LPS pneumonia model. Significantly increased levels of prostacyclin analogs such as prostaglandin E2(PGE2) and PGD2, which cause increased vascular permeability, and neutrophils in peripheral blood were significantly elevated. The model could partly reflect the clinical characteristics of phlegm heat accumulating in the lung or dampness toxin obstructing the lung. The OVA model showed that the sensitization mediators IgE and leukotriene E4(LTE4) were increased, and the anti-inflammatory prostacyclin 6-keto-PGF2α was decreased. Immune cells(lymphocytes and monocytes) were decreased, and inflammatory cells(neutrophils and basophils) were increased, reflecting the characteristics of "deficiency", "phlegm", or "dampness". Lymphocytes, monocytes, and basophils were significantly increased in the C48/80 model. The phenotype of the model was that the content of histamine, a large number of prostacyclins(6-keto-PGE1, PGF2α, 15-keto-PGF2α, 6-keto-PGF1α, 13,14-D-15-keto-PGE2, PGD2, PGE2, and PGH2), LTE4, and 5-hydroxyeicosatetraenoic acid(5S-HETE) was significantly increased, and these indicators were associated with vascular expansion and increased vascular permeability. The pyrogenic inflammatory cytokines were not increased. The C48/80 model reflected the characteristics of cold and damp accumulation. In the study, three non-infectious pneumonia models were constructed. The LPS model exhibited neutrophil infiltration and elevated inflammatory factors, which was suitable for the efficacy study of TCM for clearing heat, detoxifying, removing dampness, and eliminating phlegm. The OVA model, which took allergic inflammation as an index, was suitable for the efficacy study of Yiqi Gubiao formulas. The C48/80 model exhibited increased vasoactive substances(histamine, PGs, and LTE4), which was suitable for the efficacy study and evaluation of TCM for warming the lung, dispersing cold, drying dampness, and resolving phlegm. The study provides a theoretical basis for model selection for the efficacy evaluation of TCM in the treatment of pneumonia.
Animals ; Disease Models, Animal ; Mice ; Pneumonia/genetics* ; Medicine, Chinese Traditional ; Male ; Humans ; Cytokines/immunology* ; Female ; Lipopolysaccharides/adverse effects* ; Lung/drug effects* ; Drugs, Chinese Herbal ; Ovalbumin ; Mice, Inbred BALB C

Apical microsurgery is accurate and minimally invasive, produces few complications, and has a success rate of more than 90%. However, due to the lack of awareness and understanding of apical microsurgery by dental general practitioners and even endodontists, many clinical problems remain to be overcome. The consensus has gathered well-known domestic experts to hold a series of special discussions and reached the consensus. This document specifies the indications, contraindications, preoperative preparations, operational procedures, complication prevention measures, and efficacy evaluation of apical microsurgery and is applicable to dentists who perform apical microsurgery after systematic training.
Microsurgery/standards* ; Humans ; Apicoectomy ; Contraindications, Procedure ; Tooth Apex/diagnostic imaging* ; Postoperative Complications/prevention & control* ; Consensus ; Treatment Outcome

Gene regulation relies on the precise binding of transcription factors (TFs) at regulatory elements, but simultaneously detecting hundreds of TFs on chromatin is challenging. We developed cFOOT-seq, a cytosine deaminase-based TF footprinting assay, for high-resolution, quantitative genome-wide assessment of TF binding in both open and closed chromatin regions, even with small cell numbers. By utilizing the dsDNA deaminase SsdAtox, cFOOT-seq converts accessible cytosines to uracil while preserving genomic integrity, making it compatible with techniques like ATAC-seq for sensitive and cost-effective detection of TF occupancy at the single-molecule and single-cell level. Our approach enables the delineation of TF footprints, quantification of occupancy, and examination of chromatin influences on TF binding. Notably, cFOOT-seq, combined with FootTrack analysis, enables de novo prediction of TF binding sites and tracking of TF occupancy dynamics. We demonstrate its application in capturing cell type-specific TFs, analyzing TF dynamics during reprogramming, and revealing TF dependencies on chromatin remodelers. Overall, cFOOT-seq represents a robust approach for investigating the genome-wide dynamics of TF occupancy and elucidating the cis-regulatory architecture underlying gene regulation.
Transcription Factors/genetics* ; Humans ; Chromatin/genetics* ; Animals ; Binding Sites ; Mice ; DNA Footprinting/methods*

Objective:To explore the occurrence and clinical characteristics of nephrogenic systemic fibrosis (NSF) induced by gadolinium-based contrast agents (GBCA).Methods:CNKI, Wanfang, VIP and PubMed databases were searched (as of October 28, 2024) and case reports on GBCA-related NSF were collected; the following information was extracted, including the publication year of the literature, country, patient gender, age, basic kidney diseases and renal replacement therapy, variety of GBCA used, exposure frequency, time of occurrence or diagnosis of NSF, clinical manifestations, pathological examination, main intervention measures and outcomes. The data were analyzed by descriptive statistics.Results:A total of 45 case reports were collected, involving 97 patients. The literature were reported mainly from the United States and published mainly in 2006 and 2007. Number of the relevant literature decreased significantly after 2008, but there were still new cases reports in China in the following years (for example, in 2023). Among the 97 patients, 53 (54.6%) were male and 44 (45.4%) were female; the age ranged from 9 to 83 years with a median age of 53 years. One patient was with severe malnutrition, while the other 96 had severe basic kidney diseases, including chronic kidney disease in 85 (88.5%) patients and acute kidney injury in 11 (11.5%) patients. Variety of GBCA exposed was described in 76 patients, including gadodiamide in 67 (88.2%) patients. Exposure frequency of GBCA before NSF occurrence was described in 88 patients, 48 (54.5%) of which were exposed only once and 23 (26.1%) were exposed twice. Time from the first GBCA exposure to the occurrence of NSF was described in 92 patients, with the shortest time of 2 days and the longest time of more than 10 years; 70.7% (65/92) occurred within 3 months after GBCA exposure. All patients had typical skin symptoms of NSF, which were confirmed by pathological examination. Among them, 43 (44.3%) had joint disorders, 9 patients had eye involvement, a few patients had cardiac fibrosis, respiratory failure, metabolic acidosis, rhabdomyolysis, muscle necrosis, etc. Follow-up information was described in 82 patients with a range of 4 months to 11 years. Among them, 21 patients (25.6%) died, mainly due to the basic kidney diseases and complications; 11 (13.4%) were severely disabled; 7 (8.5%) were mildly disabled or slowly deteriorated; 43 (52.4%) had stable disease or slightly improved condition.Conclusion:NSF caused by GBCA mainly occurs in patients with severe basic renal diseases, mostly caused by gadodiamide. Severe skin damage is often accompanied by joint involvement or even disability, and the overall prognosis is poor.

Objective:To explore the occurrence and clinical characteristics of nephrogenic systemic fibrosis (NSF) induced by gadolinium-based contrast agents (GBCA).Methods:CNKI, Wanfang, VIP and PubMed databases were searched (as of October 28, 2024) and case reports on GBCA-related NSF were collected; the following information was extracted, including the publication year of the literature, country, patient gender, age, basic kidney diseases and renal replacement therapy, variety of GBCA used, exposure frequency, time of occurrence or diagnosis of NSF, clinical manifestations, pathological examination, main intervention measures and outcomes. The data were analyzed by descriptive statistics.Results:A total of 45 case reports were collected, involving 97 patients. The literature were reported mainly from the United States and published mainly in 2006 and 2007. Number of the relevant literature decreased significantly after 2008, but there were still new cases reports in China in the following years (for example, in 2023). Among the 97 patients, 53 (54.6%) were male and 44 (45.4%) were female; the age ranged from 9 to 83 years with a median age of 53 years. One patient was with severe malnutrition, while the other 96 had severe basic kidney diseases, including chronic kidney disease in 85 (88.5%) patients and acute kidney injury in 11 (11.5%) patients. Variety of GBCA exposed was described in 76 patients, including gadodiamide in 67 (88.2%) patients. Exposure frequency of GBCA before NSF occurrence was described in 88 patients, 48 (54.5%) of which were exposed only once and 23 (26.1%) were exposed twice. Time from the first GBCA exposure to the occurrence of NSF was described in 92 patients, with the shortest time of 2 days and the longest time of more than 10 years; 70.7% (65/92) occurred within 3 months after GBCA exposure. All patients had typical skin symptoms of NSF, which were confirmed by pathological examination. Among them, 43 (44.3%) had joint disorders, 9 patients had eye involvement, a few patients had cardiac fibrosis, respiratory failure, metabolic acidosis, rhabdomyolysis, muscle necrosis, etc. Follow-up information was described in 82 patients with a range of 4 months to 11 years. Among them, 21 patients (25.6%) died, mainly due to the basic kidney diseases and complications; 11 (13.4%) were severely disabled; 7 (8.5%) were mildly disabled or slowly deteriorated; 43 (52.4%) had stable disease or slightly improved condition.Conclusion:NSF caused by GBCA mainly occurs in patients with severe basic renal diseases, mostly caused by gadodiamide. Severe skin damage is often accompanied by joint involvement or even disability, and the overall prognosis is poor.

Objective:To analyze the MYH9 gene sequence of a patient with hereditary thrombocytopenia and diffuse large B-cell lymphoma and his family members,and to explore the relationship between MYH9 gene and tumors.Methods:Peripheral blood samples were collected from the patients and their family members for complete blood count analysis.The platelet morphology was observed under microscope.The MYH9 gene sequence was analyzed by Whole Exon Sequencing and Sanger Sequencing.Results:The mutation site c.279C＞A:p.(Asn93Lys)in exon 2 of the MYH9 gene were found in patient and his family members,both presenting as thrombocytopenia.The platelet count was significantly increased after the administration of Avatrombopag.Conclusion:A novel mutation of MYH9 was found in this study,and the case was sensitive to Avatrombopag,by exploring the relationship between the MYH9 gene and tumors,suggesting that the MYH9 gene may be associated with the development of diffuse large B-cell lymphoma.

Objective This study aimed to comprehensively analyze and compare the clinicopathological features and prognosis of Chinese patients with human epidermal growth factor receptor 2(HER2)-low early breast cancer(BC)and HER2-IHC0 BC. Methods Patients diagnosed with HER2-negative BC(N=999)at our institution between January 2011 and December 2015 formed our study population.Clinicopathological characteristics,association between estrogen receptor(ER)expression and HER2-low,and evolution of HER2 immunohistochemical(IHC)score were assessed.Kaplan-Meier method and log-rank test were used to compare the long-term survival outcomes(5-year follow-up)between the HER2-IHC0 and HER2-low groups. Results HER2-low BC group tended to demonstrate high expression of ER and more progesterone receptor(PgR)positivity than HER2-IHC0 BC group(P<0.001).The rate of HER2-low status increased with increasing ER expression levels(Mantel-Haenszel χ2 test,P<0.001,Pearson's R=0.159,P<0.001).Survival analysis revealed a significantly longer overall survival(OS)in HER2-low BC group than in HER2-IHC0 group(P=0.007)in the whole cohort and the hormone receptor(HR)-negative group.There were no significant differences between the two groups in terms of disease-free survival(DFS).The discordance rate of HER2 IHC scores between primary and metastatic sites was 36.84%. Conclusion HER2-low BC may not be regarded as a unique BC group in this population-based study due to similar clinicopathological features and prognostic roles.

Objective To investigate the application value of combining the Demirjian's method with ma-chine learning algorithms for dental age estimation in northern Chinese Han children and adolescents.Methods Oral panoramic images of 10 256 Han individuals aged 5 to 24 years in northern China were collected.The development of eight permanent teeth in the left mandibular was classified into different stages using the Demirjian's method.Various machine learning algorithms,including support vector re-gression(SVR),gradient boosting regression(GBR),linear regression(LR),random forest regression(RFR),and decision tree regression(DTR)were employed.Age estimation models were constructed based on total,female,and male samples respectively using these algorithms.The fitting performance of different machine learning algorithms in these three groups was evaluated.Results SVR demonstrated superior estimation efficiency among all machine learning models in both total and female samples,while GBR showed the best performance in male samples.The mean absolute error(MAE)of the op-timal age estimation model was 1.246 3,1.281 8 and 1.153 8 years in the total,female and male samples,respectively.The optimal age estimation model exhibited varying levels of accuracy across dif-ferent age ranges,which provided relatively accurate age estimations in individuals under 18 years old.Conclusion The machine learning model developed in this study exhibits good age estimation effi-ciency in northern Chinese Han children and adolescents.However,its performance is not ideal when applied to adult population.To improve the accuracy in age estimation,the other variables can be con-sidered.