Objective:To explore the value of combining gut microbiota and clinical features for preoperative microvascular invasion (MVI) prediction in hepatocellular carcinoma (HCC).Methods:Clinical data and fecal samples were collected from 71 HCC patients who underwent curative resection at Ningbo Second Hospital between Jan 2023 and Aug 2024. Among them, 41 patients were assigned to the training set and 30 to the validation set. Gut microbiota composition was analyzed using 16S rRNA sequencing. Redundancy analysis (RDA) was used to evaluate the influence of clinical features on the microbiota. Differences in alpha and beta diversity between the MVI-negative and MVI-positive groups were assessed. Differential genera were identified using the Wilcoxon test and LEfSe analysis. A random forest model and Logistic regression were employed to screen key differential genera, followed by ROC analysis. Genera with high ROC values were further validated in the validation set.Results:RDA indicated that MVI was a key factor influencing gut microbiota composition. The random forest model (AUC=0.925), combined with Logistic regression analysis, identified four genera: Acidovorax ( OR=0.618), Tissierella ( OR=1.293), Chitinophaga ( OR=4.596), and Virgisporangium ( OR=0.960), as well as two clinical features: tumor diameter ( OR=0.668) and liver cirrhosis ( OR=14.011), as independent risk factors. ROC analysis showed that in the training set, the combination of Chitinophaga (AUC=0.71) and tumor diameter (AUC=0.75) had the best diagnostic performance (AUC=0.87). In the validation set, the combination of Virgisporangium (AUC=0.80) and tumor diameter (AUC=0.79) yielded the highest diagnostic performance (AUC=0.87). Conclusions:A genomics-based model combining gut microbiota and clinical features shows promising predictive value for noninvasive preoperative assessment of MVI status in HCC patients.

The influenza A virus (IAV), renowned for its high contagiousness and potential to catalyze global pandemics, poses significant challenges due to the emergence of drug-resistant strains. Given the critical role of RNA polymerase in IAV replication, it stands out as a promising target for anti-IAV therapies. In this study, we identified a novel C-3-substituted oleanolic acid benzyl amide derivative, A5, as a potent inhibitor of the PA_C-PB1_N polymerase subunit interaction, with an IC₅₀ value of 0.96 ± 0.21 μmol/L. A5 specifically targets the highly conserved PA_C domain and demonstrates remarkable efficacy against both laboratory-adapted and clinically isolated IAV strains, including multidrug-resistant strains, with EC₅₀ values ranging from 0.60 to 1.83 μmol/L. Notably, when combined with oseltamivir, A5 exhibits synergistic effects both in vitro and in vivo. In a murine model, dose-dependent administration of A5 leads to a significant reduction in IAV titers, resulting in a high survival rate among treated mice. Additionally, A5 treatment inhibits virus-induced Toll-like receptor 4 activation, attenuates cytokine responses, and protects against IAV-induced inflammatory responses in macrophages. In summary, A5 emerges as a novel inhibitor with high efficiency and broad-spectrum anti-influenza activity.

Objective:To explore the value of combining gut microbiota and clinical features for preoperative microvascular invasion (MVI) prediction in hepatocellular carcinoma (HCC).Methods:Clinical data and fecal samples were collected from 71 HCC patients who underwent curative resection at Ningbo Second Hospital between Jan 2023 and Aug 2024. Among them, 41 patients were assigned to the training set and 30 to the validation set. Gut microbiota composition was analyzed using 16S rRNA sequencing. Redundancy analysis (RDA) was used to evaluate the influence of clinical features on the microbiota. Differences in alpha and beta diversity between the MVI-negative and MVI-positive groups were assessed. Differential genera were identified using the Wilcoxon test and LEfSe analysis. A random forest model and Logistic regression were employed to screen key differential genera, followed by ROC analysis. Genera with high ROC values were further validated in the validation set.Results:RDA indicated that MVI was a key factor influencing gut microbiota composition. The random forest model (AUC=0.925), combined with Logistic regression analysis, identified four genera: Acidovorax ( OR=0.618), Tissierella ( OR=1.293), Chitinophaga ( OR=4.596), and Virgisporangium ( OR=0.960), as well as two clinical features: tumor diameter ( OR=0.668) and liver cirrhosis ( OR=14.011), as independent risk factors. ROC analysis showed that in the training set, the combination of Chitinophaga (AUC=0.71) and tumor diameter (AUC=0.75) had the best diagnostic performance (AUC=0.87). In the validation set, the combination of Virgisporangium (AUC=0.80) and tumor diameter (AUC=0.79) yielded the highest diagnostic performance (AUC=0.87). Conclusions:A genomics-based model combining gut microbiota and clinical features shows promising predictive value for noninvasive preoperative assessment of MVI status in HCC patients.

Heart failure,as a global public health challenge,is experiencing an increasingly severe disease burden.Given the close relationship be-tween the Nitric Oxide-Soluble Guanylate Cyclase-Cyclic Guanosine Monophosphate(NO-sGC-cGMP)signaling pathway and heart failure,this study,through a comprehensive search and review of re-cent literature on the NO-sGC-cGMP pathway and heart failure,aims to outline the mechanism of ac-tion of this signaling pathway and its connection with heart failure,in order to explore new avenues for the treatment of heart failure.

Heart failure,as a global public health challenge,is experiencing an increasingly severe disease burden.Given the close relationship be-tween the Nitric Oxide-Soluble Guanylate Cyclase-Cyclic Guanosine Monophosphate(NO-sGC-cGMP)signaling pathway and heart failure,this study,through a comprehensive search and review of re-cent literature on the NO-sGC-cGMP pathway and heart failure,aims to outline the mechanism of ac-tion of this signaling pathway and its connection with heart failure,in order to explore new avenues for the treatment of heart failure.

Objective:To understand the results of blind evaluation of dissertation of three-year doctors and eight-year medical doctors, and to explore the improvement measures of eight-year program education.Methods:The data analysis method was manipulated. A total of 47 eight-year doctoral and 88 three-year doctoral dissertations submitted by the first clinical college of Huazhong University of Science and Technology in 2020 were selected as the research material. SPSS 17.0 was used to perform Chi-square test to compare the itemized evaluation opinions of the dissertation, Spearman test was used to analyze the correlation between the defense opinions, itemized evaluation opinions and the overall evaluation.Results:The gap between eight-year and three-year doctoral dissertation is mainly manifested in innovation and research value ( χ2=9.10, P=0.003), topic and review ( χ2=5.70, P=0.017), while there is no significant difference in the overall assessment and oral defense suggestion. The main influencing factor of dissertation defense suggestion for both doctors was the dissertation standardization (eight-year: r s=0.53, P<0.001; three-year: r s=0.45, P<0.001). The evaluation results of eight-year doctor dissertation were closely related to basic knowledge and scientific research ability ( r s=0.74, P<0.001). Conclusion:There is no significant difference between eight-year doctors and full-time doctors in research attitude. But there was a certain gap in scientific research and innovation ability among them. It is suggested to clarify the teaching objectives, formulate and refine the evaluation system of dissertations, and strengthen the cultivation of scientific research interest and academic belief of eight-year study program.

Nasopharyngeal carcinoma (NPC) is a cancer arising from the nasopharynx epithelium, and is one of the most frequent head and neck malignancies in adolescents. Treatment strategies for juvenile NPC follow the guidelines established for adult NPC. However, juvenile NPC has its distinct clinical characteristics. For juvenile patients in the developmental stage, the late toxicity of treatment should not be ignored. Therefore, it is important to seek appropriate treatment strategies for juvenile NPC. This review gives an overview of the epidemiology, clinical characteristics and current treatment of juvenile NPC, along with the promising strategies to reduce the intensity of treatment in adolescents. This review aims to provide new insight for improving the treatment of this disease.

Objective:To investigate the collateral circulation compensation model in patients with favorable prognosis of basilar artery occlusion/severe stenosis treated with drugs or endovascular therapy.Methods:Clinical data of patients with basilar artery occlusion/severe stenosis and good clinical outcome were retrospectively collected in the Department of Neurology, Sixth Medical Center of PLA General Hospital from January 2019 to January 2020. They were divided into intensive drug therapy group and combined endovascular therapy group. The number and ways of collateral compensation pathway described by digital substraction angiography (DSA) were analyzed, and the characteristics of the collateral compensation model were summarized. SPSS22.0 software was used for statistical analysis, and the constituent ratio (%) was used for statistical description of the enumeration data.Results:A total of 32 eligible patients were included, including 27 males and 5 females, with an average age 45-76 (59±10) years. The compensation model included posterior communicating artery-posterior cerebral artery (13 cases, 40.6%), posterior communicating artery-posterior cerebral artery-basilar artery (10 cases, 31.2%), cerebellar artery-anastomotic branches of superior cerebellar artery (8 cases, 25.0%), anterior choroid artery-anastomotic branches of posterior choroid artery (2 cases, 6.2%), collateral circulation not established (11 cases, 34.4%).In drug treatment group, collateral compensation was found in the majority (14/15), with mainly posterior communicating artery (10/14).Most patients in combined treatment group did not develop collateral compensation (10/17), anastomotic branches of PICA-SCA were the main routes (6/7).Conclusion:In patients with basilar artery occlusion/severe stenosis, favorable clinical outcome can be achieved in both groups of patients treated with intensive drug therapy or endovascular therapy.

Mesalamine (5-aminosalicylic acid, 5-ASA) is used for ulcerative colitis, mild Crohn′s disease. The orally taken mesalamine is excreted primarily as N-acetyl-5-aminosalicylic acid (N-acetyl-5-ASA) via urine, renal damage and hematuria are rare. However, red-brown urine discoloration has been noted by some patients, which is associated with the reaction between N-acetyl-5-ASA and remaining hypochlorite in the disinfectant-containing water. This article reports a case of mesalamine-associated red-brown urine discoloration and reviews related literatures.