OBJECTIVE To investigate the apoptosis-inducing effect of esculetin （Esc） on acute myeloid leukemia （AML） HL-60 cells by regulating the protein kinase B （AKT）/S-phase kinase-associated protein 2 （SKP2）/MutT homolog 1 （MTH1） pathway. METHODS AML HL-60 cells were randomly divided into control group （routine culture）， Esc low-concentration group （L-Esc group， 25 μmol/L Esc）， Esc medium-concentration group （M-Esc group， 50 μmol/L Esc）， Esc high-concentration group （H-Esc group， 100 μmol/L Esc）， and high-concentration of Esc+ SC79 （AKT agonist） group （100 μmol/L Esc+5 μmol/L SC79）. Cell proliferation in each group was detected by MTT assay and colony formation assay. The level of reactive oxygen species （ROS） in cells was measured by using the CM-H2DCFDA fluorescent probe. Cell apoptosis was analyzed by flow cytometry. Western blot assay was performed to detect the expression levels of apoptosis-related proteins [B-cell lymphoma 2 （Bcl-2）， Bcl-2-associated X protein （Bax）， cleaved caspase-3]， AKT/SKP2/MTH1 pathway-related proteins （p-AKT， AKT， SKP2， MTH1）， along with the upstream and downstream proteins of AKT phosphatidylinositol 3-kinase （PI3K）， cyclin-dependent kinase inhibitor 1 （P21） and cyclin-dependent kinase inhibitor 1B （P27）. RESULTS Compared with control group， the cell viability， colony number， and the phosphorylation levels of AKT and PI3K proteins as well as protein expressions of SKP2， MTH1 and Bcl-2 were significantly decreased （P＜0.05）， while ROS level， apoptosis rate， and the expression levels of Bax， cleaved caspase-3， P21 and P27 proteins were significantly increased （P＜0.05）. Moreover， the effects of Esc exhibited concentration-dependence （P＜0.05）. Compared with H-Esc group， above indexes of high-concentration of Esc+ SC79 group were reversed significantly （P＜0.05）. CONCLUSIONS Esc may promote massive ROS production and induce activation of apoptosis in HL-60 cells by inhibiting the AKT/SKP2/MTH1 pathway， thus inhibiting the proliferation of HL-60 cells.

Objective: To compare the predictive performance of the seasonal autoregressive integrated moving average (SARIMA) model, the Prophet model, and the Bayesian structural time series (BSTS) model in forecasting the incidence of hand, foot, and mouth disease (HFMD) , so as to provide a basis for optimizing the early warning system of this disease. Methods: Weekly incidence data of HFMD in Longgang District, Shenzhen City from 2014 to 2024 were collected. The HFMD incidence data from 2014-2019 and 2023 were used as the training set to construct SARIMA, Prophet, and BSTS models, while the data from 2024 were used as the test set to compare and evaluate the predictive performance of the three models. The technique for order preference by similarity to ideal solution (TOPSIS) method was employed to calculate the C-value. This approach integrates multiple evaluation metrics, such as the mean absolute error (MAE), mean squared error (MSE), root mean squared error (RMSE), and symmetric mean absolute percentage error (SMAPE), to comprehensively assess model performance. Results: A total of 150 111 cases of HFMD were reported in Longgang District from 2014 to 2024, with an average annual incidence of 400.72/105. The weekly incidence fluctuated between 0 and 63.78/105, exhibiting a bimodal seasonal pattern characterized by a primary peak from May to July and a secondary peak from September to October. In the training set, all three models demonstrated a good fit to the bimodal epidemic trend of HFMD, with the BSTS model achieving the best fit. The BSTS model yielded performance metrics as follows: MAE=0.124, MSE=0.050, RMSE=0.223, SMAPE=0.021, and a C-value of 1.000. In the test set, all three models, including SARIMA, Prophet, and BSTS, performed well for short-term predictions (≤16 weeks), with the Prophet model showing relatively superior predictive performance. However, the prediction accuracy of all models declined as the forecast horizon extended. During the primary peak period (May-July), the Prophet model exhibited better predictive performance, whereas the BSTS model performed relatively better during the secondary peak period (September-October). Conclusions For the short-term forecasting of weekly HFMD incidence, the Prophet model outperformed both the SARIMA and BSTS models. During the primary peak period, the Prophet model demonstrated superior predictive performance, whereas the BSTS model exhibited better accuracy in forecasting the secondary peak period.

The surgical treatment of thoraco-abdominal aortic aneurysm (TAAA) requires a unique multidisciplinary approach. A thorough preoperative examination and evaluation are essential to determine the optimal timing for surgery and to optimize organ function as needed. During the perioperative period, excellent surgical skills and an appropriate strategy for extracorporeal circulation will be employed based on the extent of the aneurysm. Additionally, necessary measures will be taken to monitor and protect the functions of vital organs. Close monitoring and management in the postoperative stage, along with early detection of complications and effective treatment, are crucial for improving the prognosis of TAAA surgery. This article reviews the current research progress in the perioperative management of TAAA surgery.

Objective: To investigate the urban and rural differences in adverse outcomes of pulmonary tuberculosis (PTB) in patients with pulmonary tuberculosis-diabetes mellitus comorbidity (PTB-DM), so as to provide insights into improving the prevention and treatment measures for PTB-DM. Methods: Patients with PTB-DM who were admitted and discharged from 14 designated tuberculosis hospitals in Hangzhou City from 2018 to 2022 were selected. Basic information, and history of diagnosis and treatment were collected through hospital information systems. The adverse outcomes of PTB were defined as endpoints, and the proportions of adverse outcomes of PTB in urban and rural patients with PTB-DM were analyzed. Factors affecting the adverse outcomes of PTB were identified using a multivariable Cox proportional hazards regression model. Results: A total of 823 patients with PTB-DM were enrolled, including 354 (43.01%) urban and 469 (56.99%) rural patients. There were 112 (13.61%) patients with adverse outcomes of PTB. The proportions of adverse outcomes of PTB in urban and rural patients were 14.41% and 13.01%, respectively, with no statistically significant difference (P>0.05). Multivariable Cox proportional hazards regression analysis identified first diagnosed in county-level hospitals or above (HR=2.107, 95%CI: 1.181-3.758) and drug resistance (HR=3.303, 95%CI: 1.653-6.600) as the risk factors for adverse outcomes of PTB in urban patients with PTB-DM, while the treatment/observed management throughout the process (HR=0.470, 95%CI: 0.274-0.803) and fixed-dose combinations throughout the process (HR=0.331, 95%CI: 0.151-0.729) as the protective factors for adverse outcomes in rural patients with PTB-DM. Conclusions There are differences in influencing factors for adverse outcomes of PTB in urban and rural patients with PTB-DM. The adverse outcomes of PTB are associated with first diagnosed hospitals and drug resistance in urban patients, and are associated with the treatment/observed management and fixed-dose combinations throughout the process in rural patients.

BACKGROUND:Flap transplantation technique is a commonly used surgical procedure for the treatment of severe tissue defects,but postoperative flap necrosis is easily triggered by ischemia-reperfusion injury.Therefore,it is still an important research topic to improve the survival rate of transplanted flaps. OBJECTIVE:To review the pathogenesis and latest treatment progress of flap ischemia-reperfusion injury. METHODS:CNKI,WanFang Database and PubMed database were searched for relevant literature published from 2014 to 2024.The search terms used were"flap,ischemia-reperfusion injury,inflammatory response,oxidative stress,Ca2+overload,apoptosis,mesenchymal stem cells,platelet-rich plasma,signaling pathways,shock wave,pretreatment"in Chinese and English.After elimination of irrelevant literature,poor quality and obsolete literature,77 documents were finally included for review. RESULTS AND CONCLUSION:Flap ischemia/reperfusion injury may be related to pathological factors such as inflammatory response,oxidative stress response,Ca2+overload,and apoptosis,which can cause apoptosis of vascular endothelial cells,vascular damage and microcirculation disorders in the flap,and eventually lead to flap necrosis.Studies have found that mesenchymal stem cell transplantation,platelet-rich plasma,signaling pathway modulators,shock waves,and pretreatment can alleviate flap ischemia/reperfusion injuries from different aspects and to varying degrees,and reduce the necrosis rate and necrosis area of the grafted flap.Although there are many therapeutic methods for skin flap ischemia/reperfusion injury,a unified and effective therapeutic method has not yet been developed in the clinic,and the advantages and disadvantages of various therapeutic methods have not yet been compared.Most of the studies remain in the stage of animal experiments,rarely involving clinical observations.Therefore,a lot of research is required in the future to gradually move from animal experiments to the clinic in order to better serve the clinic.

Glioma represents the most prevalent malignant tumor of the central nervous system, with chemotherapy serving as an essential adjunctive treatment. However, most chemotherapeutic agents exhibit limited ability to penetrate the blood-brain barrier (BBB). This study introduced a novel dual-targeting strategy for glioma therapy by modulating the formation of nanobody-driven protein coronas to enhance the brain and tumor-targeting efficiency of hydrophobic cisplatin prodrug-loaded lipid nanoparticles (C8Pt-Ls). Specifically, nanobodies (Nbs) with fibrinogen-binding capabilities were conjugated to the surface of C8Pt-Ls, resulting in the generation of Nb-C8Pt-Ls. Within the bloodstream, Nb-C8Pt-Ls could bound more fibrinogen, forming the protein corona that specifically interacted with LRP-1, a receptor highly expressed on the BBB. This interaction enabled a "Hitchhiking Effect" mechanism, facilitating efficient trans-BBB transport and promoting effective brain targeting. Additionally, the protein corona interacted with LRP-1, which is also overexpressed in glioma cells, achieving precise tumor targeting. Computational simulations and SPR detection clarified the molecular interaction mechanism of the Nb-fibrinogen-(LRP-1) complex, confirming its binding specificity and stability. Our results demonstrated that this strategy significantly enhanced C8Pt accumulation in brain tissues and tumors, induced apoptosis in glioma cells, and improved therapeutic efficacy. This study provides a novel framework for glioma therapy and underscores the potential of protein corona modulation-based dual-targeting strategies in advancing treatments for brain tumors.

Background/Aims: This study assessed the long-term efficacy and safety of tenofovir alafenamide (TAF) in real-world settings. Methods: Patients who were candidates for TAF treatment and were followed up at 12-week intervals over 192 weeks were enrolled in this study. Results: One hundred and forty-four patients (50 treatment-naive and 94 treatment-experienced) were included in this study. The cumulative incidence rates of cirrhosis and hepatocellular carcinoma at 192 weeks were 3.9% and 0.7%, respectively. In treatment-naive patients, the rates of a virological response, HBeAg conversion, and HBsAg loss at 192 weeks were 100%, 33.3%, and 2%, respectively. The treatment-naive patients exhibited higher baseline HBsAg levels than the treatment-experienced patients (4.31 log10IU/mL vs. 3.97 log10IU/mL). A significant decrease in the HBsAg levels from the baseline was observed at 144 and 192 weeks in the treatment-naive patients (p=0.01). The baseline body mass index (BMI) <25 kg/m2 (p=0.02) and HBsAg <3.3 log10IU/mL (p=0.04) were identified as predictive factors for a decrease in HBsAg ≥0.5 log10IU/mL at 48 weeks. The eGFR levels were consistently lower in the treatment-experienced patients throughout the study. Although the treatment-naive patients showed no abnormal increases in urinary URBP, the treatment-experienced patients showed elevated urinary β2MG and NAG levels at the baseline, which decreased over the treatment course. The total cholesterol, triglyceride, and low-density lipoprotein levels were similar in both groups. Conclusions Prolonging the TAF treatment duration enhances the virological response rate. The decline in HBsAg levels was more significant in the treatment-naive patients than in the treatment-experienced patients. The baseline BMI <25 kg/m2 and HBsAg <3.3 log10IU/mL were predictive factors for a significant decline in HBsAg at 48 weeks. TAF has high renal safety and no significant impact on lipid levels.

Background/Aims: This study assessed the long-term efficacy and safety of tenofovir alafenamide (TAF) in real-world settings. Methods: Patients who were candidates for TAF treatment and were followed up at 12-week intervals over 192 weeks were enrolled in this study. Results: One hundred and forty-four patients (50 treatment-naive and 94 treatment-experienced) were included in this study. The cumulative incidence rates of cirrhosis and hepatocellular carcinoma at 192 weeks were 3.9% and 0.7%, respectively. In treatment-naive patients, the rates of a virological response, HBeAg conversion, and HBsAg loss at 192 weeks were 100%, 33.3%, and 2%, respectively. The treatment-naive patients exhibited higher baseline HBsAg levels than the treatment-experienced patients (4.31 log10IU/mL vs. 3.97 log10IU/mL). A significant decrease in the HBsAg levels from the baseline was observed at 144 and 192 weeks in the treatment-naive patients (p=0.01). The baseline body mass index (BMI) <25 kg/m2 (p=0.02) and HBsAg <3.3 log10IU/mL (p=0.04) were identified as predictive factors for a decrease in HBsAg ≥0.5 log10IU/mL at 48 weeks. The eGFR levels were consistently lower in the treatment-experienced patients throughout the study. Although the treatment-naive patients showed no abnormal increases in urinary URBP, the treatment-experienced patients showed elevated urinary β2MG and NAG levels at the baseline, which decreased over the treatment course. The total cholesterol, triglyceride, and low-density lipoprotein levels were similar in both groups. Conclusions Prolonging the TAF treatment duration enhances the virological response rate. The decline in HBsAg levels was more significant in the treatment-naive patients than in the treatment-experienced patients. The baseline BMI <25 kg/m2 and HBsAg <3.3 log10IU/mL were predictive factors for a significant decline in HBsAg at 48 weeks. TAF has high renal safety and no significant impact on lipid levels.

Background/Aims: This study assessed the long-term efficacy and safety of tenofovir alafenamide (TAF) in real-world settings. Methods: Patients who were candidates for TAF treatment and were followed up at 12-week intervals over 192 weeks were enrolled in this study. Results: One hundred and forty-four patients (50 treatment-naive and 94 treatment-experienced) were included in this study. The cumulative incidence rates of cirrhosis and hepatocellular carcinoma at 192 weeks were 3.9% and 0.7%, respectively. In treatment-naive patients, the rates of a virological response, HBeAg conversion, and HBsAg loss at 192 weeks were 100%, 33.3%, and 2%, respectively. The treatment-naive patients exhibited higher baseline HBsAg levels than the treatment-experienced patients (4.31 log10IU/mL vs. 3.97 log10IU/mL). A significant decrease in the HBsAg levels from the baseline was observed at 144 and 192 weeks in the treatment-naive patients (p=0.01). The baseline body mass index (BMI) <25 kg/m2 (p=0.02) and HBsAg <3.3 log10IU/mL (p=0.04) were identified as predictive factors for a decrease in HBsAg ≥0.5 log10IU/mL at 48 weeks. The eGFR levels were consistently lower in the treatment-experienced patients throughout the study. Although the treatment-naive patients showed no abnormal increases in urinary URBP, the treatment-experienced patients showed elevated urinary β2MG and NAG levels at the baseline, which decreased over the treatment course. The total cholesterol, triglyceride, and low-density lipoprotein levels were similar in both groups. Conclusions Prolonging the TAF treatment duration enhances the virological response rate. The decline in HBsAg levels was more significant in the treatment-naive patients than in the treatment-experienced patients. The baseline BMI <25 kg/m2 and HBsAg <3.3 log10IU/mL were predictive factors for a significant decline in HBsAg at 48 weeks. TAF has high renal safety and no significant impact on lipid levels.

Purpose: Leptin interacts not only with leptin receptor (LEPR) but also engages with other receptors. While the pro-oncogenic effects of the adrenergic receptor β2 (ADRB2) are well-established, the role of leptin in activating ADRB2 in triple-negative breast cancer (TNBC) remains unclear. Materials and Methods: The pro-carcinogenic effects of LEPR were investigated using murine TNBC cell lines, 4T1 and EMT6, and a tumor-bearing mouse model. Expression levels of LEPR, NADPH oxidase 4 (NOX4), and ADRB2 in TNBC cells and tumor tissues were analyzed via western blot and quantitative real-time polymerase chain reaction. Changes in reactive oxygen species (ROS) levels were assessed using flow cytometry and MitoSox staining, while immunofluorescence double-staining confirmed the co-localization of LEPR and ADRB2. Results: LEPR activation promoted NOX4-derived ROS and mitochondrial ROS production, facilitating TNBC cell proliferation and migration, effects which were mitigated by the LEPR inhibitor Allo-aca. Co-expression of LEPR and ADRB2 was observed on cell membranes, and bioinformatics data revealed a positive correlation between the two receptors. Leptin activated both LEPR and ADRB2, enhancing intracellular ROS generation and promoting tumor progression, which was effectively countered by a specific ADRB2 inhibitor ICI118551. In vivo, leptin injection accelerated tumor growth and lung metastases without affecting appetite, while treatments with Allo-aca or ICI118551 mitigated these effects. Conclusion This study demonstrates that leptin stimulates the growth and metastasis of TNBC through the activation of both LEPR and ADRB2, resulting in increased ROS production. These findings highlight LEPR and ADRB2 as potential biomarkers and therapeutic targets in TNBC.