Objective: To summarize the circumstances of rescue events in hospitalized patients after radiotherapy for head and neck cancer in order to provide a reference for clinical decision-making. Methods: This study was approved by the hospital's medical ethics committee. A retrospective analysis was conducted on the clinical data of 86 hospitalized patients admitted between 2015 and 2023 for oral and maxillofacial diseases following radiotherapy for head and neck cancer. Based on the occurrence of rescue events, patients were divided into a rescue group (n=20) and a non-rescue group (n=66). In addition, 20 healthy subjects matched for age and gender with the rescue group were included as a control group. First, baseline characteristics were compared between the rescue and non-rescue groups. Second, a descriptive analysis of the clinical characteristics and rescue events of the rescue group patients was performed. Third, differences in laboratory inflammatory and nutritional indicators, as well as tracheostomy status, were compared between the rescue and non-rescue groups. Fourth, Dolphin Imaging software was used to measure cone beam computed tomography images of the rescue group, non-rescue group, and control group. Upper airway parameters were measured, including the sagittal and coronal diameters of the nasopharyngeal, palatopharyngeal, glossopharyngeal, and laryngopharyngeal segments Results: ① A comparison of baseline characteristics between the rescue and non-rescue groups showed no statistically significant differences in age, gender, or body mass index, but the proportion of patients with comorbid pulmonary diseases was higher in the rescue group (P<0.05). ② In the rescue group, the primary reasons for radiotherapy were nasopharyngeal carcinoma (65%) and tongue cancer (25%). The mean age was (54.75 ± 11.59) years, with a male-to-female ratio of 3:1. The main reasons for this admission included radio-osteomyelitis in the mandible (55%) and recurrence of oral and maxillofacial tumors or new primary tumors in the oral and maxillofacial region (40%). The primary reason for rescue during hospitalization was dyspnea (55%), followed by acute massive hemorrhage (15%) and cardiac arrest (15%). Rescue events occurred mostly postoperatively (65%), with a median time of occurrence at 5 days post-operatively; 30% occurred preoperatively, and 5% occurred intraoperatively. ③ Laboratory indicators and tracheostomy status: preoperative and postoperative neutrophil counts, as well as the proportion of patients undergoing tracheostomy, were higher in the rescue group compared to the non-rescue group, while postoperative albumin levels were lower (P<0.05). ④ Upper airway measurements: the coronal and sagittal diameters of the nasopharyngeal segment and the coronal diameter of the glossopharyngeal segment were smaller in both the rescue and non-rescue groups compared to the control group (P<0.001). Conclusion The data from this study indicate that hospitalized patients experiencing rescue events after radiotherapy for head and neck cancer often have comorbid pulmonary diseases or tumor recurrence/new primary tumors, and frequently present with dyspnea. They exhibit a higher inflammatory state, poorer nutritional status, a greater need for emergency airway intervention, and share a common anatomical basis for dyspnea--upper airway narrowing. Clinical attention should be fully given to high-risk patients with these characteristics.

OBJECTIVE To investigate the mechanism of Xihuang pill （XHP） against diffuse large B-cell lymphoma （DLBCL）. METHODS The active ingredients of XHP and potential therapeutic targets for DLBCL were identified using TCMSP， GeneCards and DisGeNET databases. Protein-protein interaction networks were constructed using the String database and Cytoscape software to screen core components and core targets. Gene ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses were then performed. The clinical relevance of core targets was analyzed using the GEPIA and PanCanSurvPlot databases. Molecular docking and molecular dynamics （MD） simulation were conducted to verify the interactions between core components and core targets， and the binding free energy was calculated using the molecular mechanics Poisson-Boltzmann surface area （MM-PBSA） method. The effects of XHP on DLBCL and the related molecular mechanisms were validated using CCK-8 assay， flow cytometry and Western blot. RESULTS Network pharmacology analysis identified 108 active ingredients of XHP and 410 potential therapeutic targets for DLBCL. Six core components （e.g.， 17 beta-estradiol， quercetin） and ten core targets [e.g.， tumor protein 53 （TP53）， proto-oncogene tyrosine-protein kinase Src （SRC）] were obtained. Enrichment analysis indicated that the anti-DLBCL effects of XHP were primarily associated with the apoptotic signaling pathway， the phosphoinositide 3-kinase （PI3K）/protein kinase B （Akt） signaling pathway and so on. Clinical correlation analysis revealed that TP53 and SRC expression were significantly up-regulated in DLBCL tissues and associated with poor patient prognosis （P＜0.05）. Molecular docking， MD simulations and MM-PBSA calculations confirmed that the SRC-quercetin complex had a mail：stronger and more stable binding affinity. In vitro experiments demonstrated that XHP concentration-dependently inhibited the proliferation of DLBCL cells； compared with control group， XHP medium- and high-dose groups could significantly induce the apoptosis of SU-DHL2 and SU-DHL4 cells， and significantly down- regulated the expressions of SRC protein， phosphorylated （p）-PI3K/PI3K and p-Akt/Akt in SU-DHL4 cells （P＜0.05）. CONCLUSIONS XHP may inhibit the proliferation and induce the apoptosis of DLBCL cells by regulating the SRC/PI3K/Akt signaling pathway.

Objective To quantitatively assess the exposure-response association between exposure to heatwave and sudden death, estimate the attributable excess deaths, and identify potential vulnerable subgroups. Methods A time-stratified case-crossover study was conducted among residents who died from sudden death in Jiangsu Province, China between 2015 and 2021. Heatwave events in Jiangsu Province, defined using varying relative temperature thresholds and durations, were identified using temperature data from the China Meteorological Administration Land Data Assimilation System (CLDAS V2.0). Individual heatwave exposure was assessed based on each subject's residential address. The exposure-response association between heatwave and sudden death was evaluated using conditional logistic regression model combined with a Distributed Lag Nonlinear Model(DLNM). Heatwave-attributable excess deaths were estimated. Stratified analyses by sex and age were performed to assess potential effect modifications. Results Under all definitions, exposure to heatwave was significantly associated with an increased risk of sudden death, and the risk increased with the intensity of heatwave. Using the P95_3d definition (temperature exceeding the 95th percentile for ≥3 consecutive days), heatwave was significantlyassociated with a 56% increased risk of sudden death (95% CI: 31%, 86%). The population-attributable fraction of sudden death due to heatwave exposure was 1.45% (95% CI: 0.97%, 1.90%). Stratified analyses indicated no statistically significant differences in the association between heatwave exposure and sudden death across age or sex subgroups. Conclusion Heatwave exposure was associated with an increased risk of sudden death. Reducing heatwave exposure during summer may help lower the occurrence of sudden death.

ObjectiveTo investigate the effects of jatrorrhizine on endogenous metabolites and metabolic pathways in the mouse model of ulcerative colitis. MethodsThirty male C57BL/6J mice were randomly divided into the normal group， the model group， the low-dose and high-dose jatrorrhizine groups （0.04， 0.16 g·kg^-1）， and the mesalazine group （0.52 g·kg^-1）The mouse model of ulcerative colitis was established with 3% dextran sulfate sodium （DSS） and treated with different doses of jatrorrhizine by gavage. The changes in body weight， colon length， disease activity index （DAI）， and colonic histopathology were analyzed to evaluate the therapeutic effects of jatrorrhizine. UPLC-Q-TOF/MS was employed to determine the serum and fecal levels of metabolites in mice. Metabolomics methods were used to screen the differential metabolites， on the basis of which the potential therapeutic mechanism of jatrorrhizine on DSS-induced ulcerative colitis in mice was investigated. ResultsAfter intervention with jatrorrhizine， the model mice showed significantly decreased DAI（P<0.05，P<0.01）， recovered colon length，（P<0.05，P<0.01） and alleviated histopathology of the colon. The metabolomics study screened out 13 differential metabolites in the serum and 8 differential metabolites in the feces. The pathway enrichment analysis predicted three potential metabolic pathways： Biosynthesis of unsaturated fatty acids， phenylalanine， tyrosine and tryptophan biosynthesis， and phenylalanine metabolism. ConclusionJatrorrhizine may treat ulcerative colitis by regulating the biosynthesis and metabolism of amino acids and the synthesis of unsaturated fatty acids.

AIM: To investigate the changes in serum levels of platelet-derived growth factor A(PDGFA), heme oxygenase 1(HMOX1)and suppressor of cytokine signaling 6(SOCS6)in patients with diabetic retinopathy(DR)at different stages, and their predictive value for prognosis. METHODS: Patients diagnosed with DR in Zibo No.148 Hospital from April 2023 to April 2024 were included as the study group, and patients with simple type 2 diabetes mellitus(T2DM)during the same period were included as the control group. DR patients were separated into non proliferative DR group(NPDR group)and proliferative DR group(PDR group)based on DR staging, and into good prognosis group and poor prognosis group based on prognosis. Enzyme-linked immunosorbent assay(ELISA)method was used to detect serum levels of PDGFA, HMOX1, and SOCS6, and Pearson method was performed to analyze their correlation with laboratory indicators. Multivariate logistic regression was used to explore the risk factors affecting poor prognosis in DR patients. Receiver operating characteristic(ROC)curves were plotted to explore the prognostic value of serum PDGFA, HMOX1, and SOCS6 levels for DR patients. RESULTS: Totally 128 DR patients(67 males and 61 females)with the mean age 50.65±8.57 y were included. The control group consisted of 120 T2DM patients(63 males, 57 females)with the mean age of 50.32±8.65 y. The NPDR group comprised 74 patients(39 males, 35 females)with mean age of 50.42±8.71 y; the PDR group included 54 patients(28 males, 26 females)with the mean age of 50.96±8.40 y; The good prognosis group comprised 81 patients(43 males, 38 females)with the mean age of 50.51±8.62 y; the poor prognosis group included 47 patients(24 males, 23 females)with the mean age of 50.89±8.48 y. Compared with the control group, the study group had significantly higher serum levels of PDGFA, HMOX1, and SOCS6(all P<0.05). The PDR group had significantly higher serum levels of PDGFA, HMOX1, and SOCS6 than the NPDR group(all P<0.05). The poor prognosis group had significantly higher serum levels of FBG, HbA1c, SOD, MDA, IL-6, TNF-α, PDGFA, HMOX1, and SOCS6 than the good prognosis group(all P<0.05). The serum PDGFA of DR patients was positively related to FBG, HbA1c, IL-6, and TNF-α levels(all P<0.05), HMOX1 was positively related to FBG, HbA1c, SOD, MDA, IL-6, and TNF-α levels(all P<0.05), and SOCS6 was positively related to FBG, IL-6, and TNF-α levels(all P<0.05). Elevated levels of serum PDGFA, HMOX1, SOCS6, and HbA1c were risk factors for the prognosis of DR patients(all P<0.05). The AUC values of serum PDGFA, HMOX1, and SOCS6 alone in predicting the prognosis of DR patients were 0.806, 0.822, and 0.826, respectively. The AUC of their joint prediction was 0.912, and the joint prediction was superior to individual prediction(Z joint-PDGFA=2.183, P=0.029; Z joint-HMOX1=2.308, P=0.021; Z joint-SOCS6=2.620, P=0.009). CONCLUSION: Serum PDGFA, HMOX1, SOCS6 are significantly correlated with DR staging and prognosis, all showing high predictive efficiency for the prognosis of DR patients, with certain clinical value.

Objective: The CT/MRI Liver Imaging Reporting and Data System (LI-RADS) demonstrates high specificity with relatively limited sensitivity for diagnosing hepatocellular carcinoma (HCC) in high-risk patients. This study aimed to explore the possibility of improving sensitivity by combining CT/MRI LI-RADS v2018 with second-line contrast-enhanced ultrasound (CEUS) LI-RADS v2017 using sulfur hexafluoride (SHF) or perfluorobutane (PFB). Materials and Methods: This retrospective analysis of prospectively collected multicenter data included high-risk patients with treatment-naive hepatic observations. The reference standard was pathological confirmation or a composite reference standard (only for benign lesions). Each participant underwent concurrent CT/MRI, SHF-enhanced US, and PFB-enhanced US examinations. The diagnostic performances for HCC of CT/MRI LI-RADS alone and three combination strategies (combining CT/ MRI LI-RADS with either LI-RADS SHF, LI-RADS PFB, or a modified algorithm incorporating the Kupffer-phase findings for PFB [modified PFB]) were evaluated. For the three combination strategies, apart from the CT/MRI LR-5 criteria, HCC was diagnosed if CT/MRI LR-3 or LR-4 observations met the LR-5 criteria using LI-RADS SHF, LI-RADS PFB, or modified PFB. Results: In total, 281 participants (237 males; mean age, 55 ± 11 years) with 306 observations (227 HCCs, 40 non-HCC malignancies, and 39 benign lesions) were included. Using LI-RADS SHF, LI-RADS PFB, and modified PFB, 20, 23, and 31 CT/MRI LR-3/4 observations, respectively, were reclassified as LR-5, and all were pathologically confirmed as HCCs. Compared to CT/MRI LI-RADS alone (74%, 95% confidence interval [CI]: 68%–79%), the three combination strategies combining CT/MRI LI-RADS with either LI-RADS SHF, LI-RADS PFB, or modified PFB increased sensitivity (83% [95% CI: 77%–87%], 84% [95% CI: 79%–89%], 88% [95% CI: 83%–92%], respectively; all P < 0.001), while maintaining the specificity at 92% (95% CI: 84%–97%). Conclusion The combination of CT/MRI LI-RADS with second-line CEUS using SHF or PFB improved the sensitivity of HCC diagnosis without compromising specificity.

Objective: The CT/MRI Liver Imaging Reporting and Data System (LI-RADS) demonstrates high specificity with relatively limited sensitivity for diagnosing hepatocellular carcinoma (HCC) in high-risk patients. This study aimed to explore the possibility of improving sensitivity by combining CT/MRI LI-RADS v2018 with second-line contrast-enhanced ultrasound (CEUS) LI-RADS v2017 using sulfur hexafluoride (SHF) or perfluorobutane (PFB). Materials and Methods: This retrospective analysis of prospectively collected multicenter data included high-risk patients with treatment-naive hepatic observations. The reference standard was pathological confirmation or a composite reference standard (only for benign lesions). Each participant underwent concurrent CT/MRI, SHF-enhanced US, and PFB-enhanced US examinations. The diagnostic performances for HCC of CT/MRI LI-RADS alone and three combination strategies (combining CT/ MRI LI-RADS with either LI-RADS SHF, LI-RADS PFB, or a modified algorithm incorporating the Kupffer-phase findings for PFB [modified PFB]) were evaluated. For the three combination strategies, apart from the CT/MRI LR-5 criteria, HCC was diagnosed if CT/MRI LR-3 or LR-4 observations met the LR-5 criteria using LI-RADS SHF, LI-RADS PFB, or modified PFB. Results: In total, 281 participants (237 males; mean age, 55 ± 11 years) with 306 observations (227 HCCs, 40 non-HCC malignancies, and 39 benign lesions) were included. Using LI-RADS SHF, LI-RADS PFB, and modified PFB, 20, 23, and 31 CT/MRI LR-3/4 observations, respectively, were reclassified as LR-5, and all were pathologically confirmed as HCCs. Compared to CT/MRI LI-RADS alone (74%, 95% confidence interval [CI]: 68%–79%), the three combination strategies combining CT/MRI LI-RADS with either LI-RADS SHF, LI-RADS PFB, or modified PFB increased sensitivity (83% [95% CI: 77%–87%], 84% [95% CI: 79%–89%], 88% [95% CI: 83%–92%], respectively; all P < 0.001), while maintaining the specificity at 92% (95% CI: 84%–97%). Conclusion The combination of CT/MRI LI-RADS with second-line CEUS using SHF or PFB improved the sensitivity of HCC diagnosis without compromising specificity.

Endosomes are characterized by the presence of various phosphoinositides that are essential for defining the membrane properties. However, the interplay between endosomal phosphoinositides metabolism and innate immunity is yet to be fully understood. Here, our findings highlight the evolutionary continuity of RAB-10/Rab10's involvement in regulating innate immunity. Upon infection of Caenorhabditis elegans with Pseudomonas aeruginosa, an increase in RAB-10 activity was observed in the intestine. Conversely, when RAB-10 was absent, the intestinal diacylglycerols (DAGs) decreased, and the animal's response to the pathogen was impaired. Further research revealed that UNC-16/JIP3 acts as an RAB-10 effector, facilitating the recruitment of phospholipase EGL-8 to endosomes. This leads to a decrease in endosomal phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2) and an elevation of DAGs, as well as the activation of the PMK-1/p38 MAPK innate immune pathway. It is noteworthy that the dimerization of UNC-16 is a prerequisite for its interaction with RAB-10(GTP) and the recruitment of EGL-8. Moreover, we ascertained that the rise in RAB-10 activity, due to infection, was attributed to the augmented expression of LET-413/Erbin, and the nuclear receptor NHR-25/NR5A1/2 was determined to be indispensable for this increase. Hence, this study illuminates the significance of endosomal PI(4,5)P2 catabolism in boosting innate immunity and outlines an NHR-25-mediated mechanism for pathogen detection in intestinal epithelia.
Animals ; Caenorhabditis elegans/genetics* ; Endosomes/immunology* ; Caenorhabditis elegans Proteins/immunology* ; Phosphatidylinositol 4,5-Diphosphate/immunology* ; Immunity, Innate ; Pseudomonas aeruginosa/immunology* ; rab GTP-Binding Proteins/genetics* ; Diglycerides/metabolism*

Computational analysis can accurately detect drug-gene interactions (DGIs) cost-effectively. However, transductive learning models are the hotspot to reveal the promising performance for unknown DGIs (both drugs and genes are present in the training model), without special attention to the unseen DGIs (both drugs and genes are absent in the training model). In view of this, this study, for the first time, proposed an inductive learning-based model for the precise identification of unseen DGIs. In our study, by integrating disease nodes to avoid data sparsity, a multi-relational drug-disease-gene (DDG) graph was constructed to achieve effective fusion of data on DDG intro-relationships and inter-actions. Following the extraction of graph features by utilizing graph embedding algorithms, our next step was the retrieval of the attributes of individual gene and drug nodes. In this way, a hybrid feature characterization was represented by integrating graph features and node attributes. Machine learning (ML) models were built, enabling the fulfillment of transductive predictions of unknown DGIs. To realize inductive learning, this study generated an innovative idea of transforming known node vectors derived from the DDG graph into representations of unseen nodes using node similarities as weights, enabling inductive predictions for the unseen DGIs. Consequently, the final model was superior to existing models, with significant improvement in predicting both external unknown and unseen DGIs. The practical feasibility of our model was further confirmed through case study and molecular docking. In summary, this study establishes an efficient data-driven approach through the proposed modeling, suggesting its value as a promising tool for accelerating drug discovery and repurposing.

Iron is an essential trace element in the human body, crucial in maintaining normal physiological functions. Recent studies have identified iron ions as a significant factor in initiating the ferroptosis process, a novel mode of programmed cell death characterized by iron overload and lipid peroxide accumulation. The iron metabolism pathway is one of the primary mechanisms regulating ferroptosis, as it maintains iron homeostasis within the cell. Numerous studies have demonstrated that abnormalities in iron metabolism can trigger the Fenton reaction, exacerbating oxidative stress, and leading to cell membrane rupture, cellular dysfunction, and damage to tissue structures. Therefore, regulation of iron metabolism represents a key strategy for ameliorating ferroptosis and offers new insights for treating diseases associated with iron metabolism imbalances. This review first summarizes the mechanisms that regulate iron metabolic pathways in ferroptosis and discusses the connections between the pathogenesis of various diseases and iron metabolism. Next, we introduce natural and synthetic small molecule compounds, hormones, proteins, and new nanomaterials that can affect iron metabolism. Finally, we provide an overview of the challenges faced by iron regulators in clinical translation and a summary and outlook on iron metabolism in ferroptosis, aiming to pave the way for future exploration and optimization of iron metabolism regulation strategies.