Objective To establish a prediction model for the occurrence of non-occupational carbon monoxide poisoning events in Beijing, and to provide scientific basis and theoretical support for the prevention and warning of poisoning events. Methods Based on the monitoring data of non-occupational carbon monoxide poisoning events in Beijing from 2016 to 2024, the seasonal ARIMA model and seasonal index model were established to analyze the data and predict the occurrence of events. Results Between 2016 and 2024, a total of 436 cases of non-occupational carbon monoxide poisoning were reported in Beijing, showing a downward trend. The established SARIMA model and seasonal index model were SARIMA (1,0,0) (1,1,0) 12, Yt = (-0.0339t+5.8863) × St, and the average relative errors were 65.42% and 29.19%, respectively. In terms of months, the SARIMA model had better predictive performance during April and summer (June to August), while the seasonal index model was superior in other months. By combining the two models, the predicted number of events in 2025 was as follows: 3, 2, 2, 3, 1, 5, 2, 7, 1, 1, 1, and 2. Conclusion The seasonal index model has the best prediction effect on the non-occupational carbon monoxide poisoning events in Beijing throughout the year, and the number of summer events predicted by SARIMA model is closer to the actual values. The two models can be combined to predict the trend of non-occupational carbon monoxide poisoning, which provides a scientific basis for the prevention and control of carbon monoxide poisoning in the future.

This study aims to explore the effects and mechanisms of the traditional Chinese medicine Cordyceps sinensis(CS) in ameliorating heart aging and injury in mice based on animal experiments and network pharmacology. A mouse model of heart aging was established by continuously subcutaneous injection of D-galactose(D-gal). Thirty mice were randomly assigned into a normal group, a model group, a low-dose CS(CS-L) group, a high-dose CS(CS-H) group, and a vitamin E(VE) group. Mice in these groups were administrated with normal saline, different doses of CS suspension, or VE suspension via gavage daily. After 60 days of treatment with D-gal and various drugs, all mice were euthanized, and blood and heart tissue samples were collected for determination of the indicators related to heart aging and injury in mice. Experimental results showed that both high and low doses of CS and VE ameliorated the aging phenotype, improved the heart index and myocardial enzyme spectrum, restored the expression levels of proteins associated with cell cycle arrest and senescence-associated secretory phenotypes(SASP), and alleviated the fibrosis and histopathological changes of the heart tissue in model mice. From the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP),259 active ingredients of CS were retrieved. From Gene Cards and OMIM, 2 568 targets related to heart aging were identified, and 133common targets shared by CS and heart aging were obtained. The Gene Ontology(GO) functional annotation and Kyoto Encyclopedia of Genes and Genomes( KEGG) pathway enrichment revealed that the pathways related to heart aging involved oxidative stress,apoptosis, inflammation-related signaling pathways, etc. The animal experiment results showed that both high and low doses of CS and VE ameliorated oxidative stress and apoptosis in the heart tissue to varying degrees in model mice. Additionally, CS-H and VE activated the nuclear factor E2-related factor 2(Nrf2)/heme oxygenase-1(HO-1) pathway and inhibited the expression of key proteins in the nuclear factor-κB(NF-κB) pathway in the heart tissue of model mice. In conclusion, this study demonstrated based on network pharmacology and animal experiments that CS may alleviate heart aging and injury in aging mice by reducing oxidative stress,apoptosis, and inflammation in the heart via the Nrf2/HO-1/NF-κB pathway.
Animals ; Cordyceps/chemistry* ; Mice ; NF-E2-Related Factor 2/genetics* ; NF-kappa B/genetics* ; Aging/genetics* ; Male ; Signal Transduction/drug effects* ; Network Pharmacology ; Drugs, Chinese Herbal/pharmacology* ; Heme Oxygenase-1/genetics* ; Heart/drug effects* ; Humans ; Myocardium/metabolism* ; Membrane Proteins/genetics*

This study aimed to investigate the effect of Dahuang Zhechong Pills(DHZCP) in delaying heart aging(HA) and explore the potential mechanism. Network pharmacology and molecular docking were employed to explore the targets and potential mechanisms of DHZCP in delaying HA. Furthermore, in vitro experiments were conducted with the DHZCP-containing serum to verify key targets and pathways in D-galactose(D-gal)-induced aging of cardiomyocytes. Active components of DHZCP were searched against the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCSMP), and relevant targets were predicted. HA-related targets were screened from the GeneCards, Online Mendelian Inheritance in Man(OMIM), and DisGeNET. The common targets shared by the active components of DHZCP and HA were used to construct a protein-protein interaction network in STRING 12.0, and core targets were screened based on degree in Cytoscape 3.9.1. Metaspace was used for Gene Ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) enrichment analyses of the core targets to predict the mechanisms. Molecular docking was performed in AutoDock Vina. The results indicated that a total of 774 targets of the active components of DHZCP and 4 520 targets related to HA were screened out, including 510 common targets. Core targets included B-cell lymphoma 2(BCL-2), serine/threonine kinase 1(AKT1), and hypoxia-inducible factor 1 subunit A(HIF1A). The GO and KEGG enrichment analyses suggested that DHZCP mainly exerted its effects via the phosphatidylinositol 3-kinase(PI3K)/AKT signaling pathway, HIF-1α signaling pathway, longevity signaling pathway, and apoptosis signaling pathway. Among the pathways predicted by GO and KEGG enrichment analyses, the PI3K/AKT/HIF-1α signaling pathway was selected for verification. The cell-counting kit 8(CCK-8) assay showed that D-gal significantly inhibited the proliferation of H9c2 cells, while DHZCP-containing serum increased the viability of H9c2 cells. SA-β-gal staining revealed a significant increase in the number of blue-green positive cells in the D-gal group, which was reduced by DHZCP-containing serum. TUNEL staining showed that DHZCP-containing serum decreased the number of apoptotic cells. After treatment with DHZCP-containing serum, the protein levels of Klotho, BCL-2, p-PI3K/PI3K, p-AKT1/AKT1, and HIF-1α were up-regulated, while those of P21, P16, BCL-2 associated X protein(Bax), and cleaved caspase-3 were down-regulated. The results indicated that DHZCP delayed HA via multiple components, targets, and pathways. Specifically, DHZCP may delay HA by reducing apoptosis via activating the PI3K/AKT/HIF-1α signaling pathway.
Proto-Oncogene Proteins c-akt/genetics* ; Drugs, Chinese Herbal/pharmacology* ; Signal Transduction/drug effects* ; Apoptosis/drug effects* ; Myocytes, Cardiac/cytology* ; Hypoxia-Inducible Factor 1, alpha Subunit/genetics* ; Phosphatidylinositol 3-Kinases/genetics* ; Animals ; Rats ; Humans ; Molecular Docking Simulation ; Aging/metabolism* ; Protein Interaction Maps/drug effects* ; Heart/drug effects* ; Network Pharmacology

In recent years, there have been frequent adverse reactions/events associated with traditional Chinese medicine(TCM), especially liver injury related to traditional non-toxic TCM, which requires adequate attention. Liver injury related to traditional non-toxic TCM is characterized by its sporadic and insidious nature and is influenced by various factors, making its detection and identification challenging. There is an urgent need to develop a strategy and method for early detection and recognition of traditional non-toxic TCM-related liver injury. This study was based on national adverse drug reaction monitoring center big data, integrating methodologies such as reporting odds ratio(ROR), network toxicology, and computational chemistry, so as to systematically research the risk signal identification and evaluation methods for TCM-related liver injury. The optimized ROR method was used to discover potential TCM with a risk of liver injury, and network toxicology and computational chemistry were used to identify potentially high-risk TCM. Additionally, typical clinical cases were analyzed for confirmation. An integrated strategy of "discovery via big data, identification via dry/wet method, confirmation via typical cases, and precise risk prevention and control" was developed to identify the risk of TCM-related liver injury. Corydalis Rhizoma was identified as a TCM with high risk, and its toxicity-related substances and potential toxicity mechanisms were analyzed. The results revealed that liver injury is associated with components such as tetrahydropalmatine and tetrahydroberberine, with potential mechanisms related to immune-inflammatory pathways such as the tumor necrosis factor signaling pathway, interleukin-17 signaling pathway, and Th17 cell differentiation. This paper innovatively integrated real-world evidence and computational toxicology methods, offering insights and technical support for establishing a risk discovery and identification strategy for TCM-related liver injury based on real-world big data, providing innovative ideas and strategies for guiding the safe and rational use of medication in clinical practices.
Corydalis/adverse effects* ; Drugs, Chinese Herbal/adverse effects* ; Humans ; Chemical and Drug Induced Liver Injury/etiology* ; Medicine, Chinese Traditional/adverse effects* ; Rhizome/adverse effects* ; Male ; Female

Cholangiocarcinoma (CCA) is a malignant tumor originating from cholangiocytes. However, it remains unclear about the pathogenesis of this carcinoma, which may be related to multiple factors. Currently, CCA is mainly treated by surgery, chemotherapy, and radiotherapy. Among them, surgery is the only potentially curative option for CCA. Nevertheless, the high malignancy and asymptomatic nature of CCA may lead to poor treatment outcomes. It has been demonstrated that Chinese medicine (CM) plays a significant role in various antitumor applications. Meanwhile, CM exhibits fewer side effects and high availability. Moreover, the in vitro application of CM monomers has been explored in many domestic and foreign studies. This article mainly reviews the signaling pathways and molecular mechanisms of CM monomers in the treatment of CCA in recent years. These findings are expected to provide new insights into the treatment of CCA.
Cholangiocarcinoma/drug therapy* ; Humans ; Drugs, Chinese Herbal/pharmacology* ; Bile Duct Neoplasms/drug therapy* ; Medicine, Chinese Traditional ; Animals ; Signal Transduction/drug effects*

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*

Aim To investigate the protective effects of curcumin(CUR)on crystal-induced renal injury and its underlying mechanism in the mouse model of neph-rolithiasis.Methods The mouse model of stone for-mation was established via successive intraperitoneal injection of glyoxylate.Proximal tubular epithelial cell line HK-2 treated with calcium oxalate monohydrate(COM)was used as an in vitro model.The protective role of CUR on nephrolithiasis was tested by determina-tion of tubular injury,crystal deposition and adhesion,levels of inflammatory cytokines.In vitro,the effects of CUR on the cell viability and inflammatory factors of HK-2 cells were measured.The proteins in the Toll-like receptor 4(TLR4)/nuclear factor κB(NF-κB)and nuclear factor erythroid 2-related factor 2(NRF2)/hemeoxygenase-1(HO-1)signaling path-ways were measured by Western blot for confirming the relationship between CUR and these pathways.Final-ly,NRF2 inhibitor ML385 and TLR4 activator CCL-34 were respectively used on COM-induced HK-2 cells ex-posed to CUR for the conduction of gain-of-function and loss-of-function assays.Results CUR improves the damage in the mouse model of kidney stone forma-tion,inhibits inflammation and antioxidative effects;promotes the viability of HK-2 cells induced by COM,and inhibits the expression of inflammatory factors.CUR suppresses the expression of proteins in the TLR4/NF-κB pathway,promotes the transfer of NRF2 from the cytoplasm to the nucleus,and enhances the ex-pression of HO-1.ML385 and CCL-34 respectively counteract the anti-inflammatory effects of CUR on COM-induced HK-2 cells.Conclusions Taken togeth-er,our study demonstrates the protective effect of CUR on the deposition of kidney stone and consequent tubu-lar injury.CUR through regulation of the TLR4/NF-κB and NRF2/HO-1 pathways improves renal injury.

Patients with severe trauma require an extremely timely treatment and transfusion plays an irreplaceable role in the emergency treatment of such patients. An increasing number of evidence-based medicinal evidences and clinical practices suggest that patients with severe traumatic bleeding benefit from early transfusion of low-titer group O whole blood or hemostatic resuscitation with red blood cells, plasma and platelet of a balanced ratio. However, the current domestic mode of blood supply cannot fully meet the requirements of timely and effective blood transfusion for emergency treatment of patients with severe trauma in clinical practice. In order to solve the key problems in blood supply and blood transfusion strategies for emergency treatment of severe trauma, Branch of Clinical Transfusion Medicine of Chinese Medical Association, Group for Trauma Emergency Care and Multiple Injuries of Trauma Branch of Chinese Medical Association, Young Scholar Group of Disaster Medicine Branch of Chinese Medical Association organized domestic experts of blood transfusion medicine and trauma treatment to jointly formulate Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients ( version 2024). Based on the evidence-based medical evidence and Delphi method of expert consultation and voting, 10 recommendations were put forward from two aspects of blood support mode and transfusion strategies, aiming to provide a reference for transfusion resuscitation in the emergency treatment of severe trauma and further improve the success rate of treatment of patients with severe trauma.

Objective:To investigate the correlation between nutritional status and quality of life in inpatients with nasopharyngeal carcinoma and to analyze the factors affecting nutritional status,so as to provide evidence for clinical nutritional support treatment.Methods:In this study,we retrospectively collected data from patients with nasopharyngeal carcinoma who met the inclusion and exclusion criteria in the Head and Neck Oncology Department of Zunyi Medical University Affiliated Hospital from 2014 to 2019.The NRS 2002 scale was used for nutritional risk screening,the PG-SGA scale for nutritional status assessment and the EORTCQLQ-C30 V3.0 scale for quality of life assessment.To further explore the correlation between nutritional status and quality of life,as well as the factors affecting nutritional status.Results:A total of 216 patients were collected,including 168 male(77.78%);average age(50.5±10.58)years;26.85%were at nutritional risk(NRS 2002 score≥3);28.70%were moderate malnutrition(PG-SGA score 4-8),and 23.15%were severe malnutrition(PG-SGA score≥9).There were significant differences in several physical examinations(such as body weight,body mass index,muscle circumference at the midpoint of the upper arm,etc.)and blood biochemical indexes(such as prealbumin,neutrophils,urea nitrogen,etc.)of patients with different nutritional status were differed between groups(P<0.05).Univariate analysis showed that age≥65 years was a risk factor for the development of severe malnutrition(OR:3.429,95%CI:1.467 to 8.014,P=0.004),whereas a high level of education(senior high school and above)was a protective factor(OR:0.027,95%CI:0.011 to 0.064,P=0.000).The poorer the nutritional status of nasopharyngeal carcinoma patients,the lower the quality of life.Conclusion:Nasopharyngeal carcinoma patients have a high incidence of malnutrition;the poorer the nutritional status of the patient,the lower the quality of life;routine nutritional diagnosis and treatment of nasopharyngeal carcinoma patients after admission to the hospital is recommended to improve clinical outcomes.

Objective:To analyze the relationship between CT attenuation value of pulmonary artery thrombi and the efficacy of interventional thrombolysis in patients with acute pulmonary embolism (APE).Methods:This was a single center cross-sectional study. The clinical and imaging data of 89 APE patients who underwent interventional thrombolysis in Affiliated Hospital of Xuzhou Medical University from January 2018 to December 2022, were retrospectively analyzed. All patients underwent CT pulmonary angiography (CTPA) before and after thrombolysis, the CT attenuation value of pulmonary artery thrombi and ratio of CT attenuation value of thrombi to left subscapularis muscle CT value were obtained; and the difference of Qanadli embolism index (ΔQ) before and after thrombolysis was calculated. According to the median ΔQ, patients were classified as good efficacy group (ΔQ>50%) and poor efficacy group (ΔQ≤50%). The clinical characteristics and quantitative parameters of CT were compared between the two groups, and the factors associated with efficacy of thrombolysis were analyzed with univariate and multivariate logistic regression. The correlation between CT attenuation value of pulmonary artery thrombi and ΔQ was analyzed by Spearman correlation analysis.Results:The CT attenuation value of thrombi and ratio of attenuation value of thrombi to left subscapularis muscle CT value showed significant difference between the two groups ( P<0.05). Multivariate analysis showed that compared with CT attenuation value of emboli≤53.47 HU, the value>53.47 HU might be associated with the good efficacy of thrombosysis ( OR=9.175, 95% CI: 0.937-89.846, P=0.057). There was a positive correlation between CT value of pulmonary artery thrombi and ΔQ ( r=0.365, P<0.001). Conclusion:The CT attenuation value of thrombi can predict the efficacy of interventional thrombolysis in APE patients, and patients with higher CT attenuation value would have a better treatment response.