Taxifolin (TAX) is a natural compound known for its liver protection effect, but the mechanism remains unknown. Phosphorylated proteomics analyses discovered that the phosphorylation level of NDRG1 at T328 was a key event of TAX-improved liver fibrosis. We established models with NDRG1 knockout (KO) in vivo and in vitro, demonstrating that NDRG1 KO attenuated the development of hepatocyte injury, and combining NDRG1 KO and TAX administration did not result in a reduction in protection against liver injury. Cellular thermal shift assay and surface plasma resonance analysis showed that TAX directly binds to NDRG1 rather than its upstream kinase, subsequently demonstrating that TAX regulated phosphorylation of NDRG1 at T328 through binding to its C289 site. NDRG1 T328A (phosphorylated mutation) and T328E (mimic phosphorylation) in vivo and in vitro confirmed that pNDRG1_T328 exacerbates hepatocyte injury along with DNA damage, inflammatory response, and apoptosis, thereby contributing to hepatic stellate cells (HSCs) activation. In contrast, TAX can inhibit the above pathological abnormalities and block hepatocyte injury-triggered HSCs activation and fibrosis. Overall, TAX is a potent liver protection drug primarily targeting NDRG1 and inhibiting pNDRG1_T328 in hepatocytes.

ObjectiveTo investigate the distribution of traditional Chinese medicine （TCM） syndromes in intrahepatic cholestasis of pregnancy （ICP） and its association with perinatal outcomes， and to provide a basis for precise treatment based on TCM syndrome differentiation. MethodsA cross-sectional study was conducted among 275 patients with ICP who were admitted to The Affiliated Hospital of Chengdu University of Traditional Chinese Medicine from April 2023 to April 2025. A hierarchical cluster analysis was used to summarize TCM syndromes. The Kruskal-Wallis H test was used for comparison of non-normally distributed continuous data between groups， and the chi-square test was used for comparison of categorical data between groups. A multivariate Logistic regression analysis was used to identify the clinical features significantly associated with TCM syndrome. ResultsThe cluster analysis identified three core TCM syndromes among the 275 patients with ICP， i.e.， liver-gallbladder damp-heat syndrome （45.8%）， syndrome of blood deficiency generating wind （30.9%）， and liver depression and spleen deficiency syndrome （23.3%）. There was a significant difference in the distribution of TCM syndromes between different groups stratified by maternal age at delivery， parity， history of ICP recurrence， gestational weeks at disease onset， total bile acid （TBA）， alanine aminotransferase （ALT）， and comorbidity with gestational diabetes mellitus （GDM） （all P<0.05）. The multivariate Logistic regression analysis showed that<34 gestational weeks at disease onset was significantly associated with all three syndromes （damp-heat： odds ratio ［OR］=3.769， P<0.001； blood deficiency： OR=4.031， P<0.001； liver stagnation： OR=3.552， P<0.001）. Liver-gallbladder damp-heat syndrome was associated with maternal age ≥35 years at disease onset （OR=2.048， P=0.014）， parity ≥2 times （OR=1.921， P=0.034）， history of ICP recurrence （OR=2.404， P=0.030）， ALT ≥200 U/L （OR=2.051， P=0.018）， comorbidity with GDM （OR=1.944， P=0.029）， and TBA ≥40 μmol/L （OR=2.542， P=0.024）. The syndrome of blood deficiency generating wind syndrome was associated with maternal age ≥35 years （OR=2.939， P=0.003）， parity ≥2 time （OR=3.222， P=0.003）， history of ICP recurrence （OR=3.809， P=0.010）， ALT ≥200 U/L （OR=2.889， P=0.006）， comorbidity with GDM （OR=3.711， P=0.001）， and comorbidity with hypertensive disorders of pregnancy （OR=4.472， P=0.011）. Liver depression and spleen deficiency syndrome was associated with TBA ≥40 μmol/L （OR=2.995， P=0.044）. The analysis of perinatal outcomes showed that there were significant differences in mode of delivery， gestational weeks at the time of delivery， postpartum blood loss， and neonatal birth weight between the three groups with different TCM syndromes （all P<0.05）. ConclusionLiver-gallbladder damp-heat syndrome， syndrome of blood deficiency generating wind， and liver depression and spleen deficiency syndrome are the main TCM syndrome types in ICP， and the distribution of TCM syndromes is closely associated with clinical factors and perinatal outcomes， which provides a basis for precise TCM syndrome differentiation and individualized treatment.

OBJECTIVES: To investigate the role and mechanism of fibroblast growth factor (FGF) 19 in inflammation-induced injury of vascular endothelial cells caused by high glucose (HG). METHODS: Human umbilical vein endothelial cells (HUVECs) were randomly divided into four groups: control, HG, FGF19, and HG+FGF19 (n=3 each). The effect of different concentrations of glucose and/or FGF19 on HUVEC viability was assessed using the CCK8 assay. Flow cytometry was utilized to examine the impact of FGF19 on HUVEC apoptosis. Levels of interleukin-6 (IL-6), inducible nitric oxide synthase (iNOS), total superoxide dismutase (T-SOD), and malondialdehyde (MDA) were measured by ELISA. Real-time quantitative PCR and Western blotting were used to determine the mRNA and protein expression levels of vascular endothelial growth factor (VEGF), nuclear factor erythroid 2 related factor 2 (Nrf2), and heme oxygenase-1 (HO-1). Cells were further divided into control, siRNA-Nrf2 (siNrf2), HG, HG+FGF19, HG+FGF19+negative control, and HG+FGF19+siNrf2 groups (n=3 each) to observe the effect of FGF19 on oxidative stress injury in HUVECs induced by high glucose after silencing the Nrf2 gene. RESULTS: Compared to the control group, the HG group exhibited increased apoptosis rate, increased IL-6, iNOS and MDA levels, and increased VEGF mRNA and protein expression, along with decreased T-SOD activity and decreased mRNA and protein expression of Nrf2 and HO-1 (P<0.05). Compared to the HG group, the HG+FGF19 group showed reduced apoptosis rate, decreased IL-6, iNOS and MDA levels, and decreased VEGF mRNA and protein expression, with increased T-SOD activity and increased Nrf2 and HO-1 mRNA and protein expression (P<0.05). Compared to the HG+FGF19+negative control group, the HG+FGF19+siNrf2 group had decreased T-SOD activity and increased MDA levels (P<0.05). CONCLUSIONS FGF19 can alleviate inflammation-induced injury in vascular endothelial cells caused by HG, potentially through the Nrf2/HO-1 signaling pathway.
Humans ; NF-E2-Related Factor 2/genetics* ; Signal Transduction ; Human Umbilical Vein Endothelial Cells/drug effects* ; Fibroblast Growth Factors/pharmacology* ; Heme Oxygenase-1/physiology* ; Apoptosis/drug effects* ; Glucose ; Inflammation ; Interleukin-6/analysis* ; Vascular Endothelial Growth Factor A/genetics* ; Nitric Oxide Synthase Type II/analysis* ; Cells, Cultured

As new evidence emerges, treatment strategies toward the functional cure of chronic hepatitis B are evolving. In 2019, a panel of national hepatologists published a Consensus Statement on the functional cure of chronic hepatitis B. Currently, an international group of hepatologists has been assembled to evaluate research since the publication of the original consensus, and to collaboratively develop the updated statements. The 2.0 Consensus was aimed to update the original consensus with the latest available studies, and provide a comprehensive overview of the current relevant scientific literatures regarding functional cure of hepatitis B, with a particular focus on issues that are not yet fully clarified. These cover the definition of functional cure of hepatitis B, its mechanisms and barriers, the effective strategies and treatment roadmap to achieve this endpoint, in particular new surrogate biomarkers used to measure efficacy or to predict response, and the appropriate approach to pursuing a functional cure in special populations, the development of emerging antivirals and immunomodulators with potential for curing hepatitis B. The statements are primarily intended to offer international guidance for clinicians in their practice to enhance the functional cure rate of chronic hepatitis B.

As new evidence emerges, treatment strategies toward the functional cure of chronic hepatitis B are evolving. In 2019, a panel of national hepatologists published a Consensus Statement on the functional cure of chronic hepatitis B. Currently, an international group of hepatologists has been assembled to evaluate research since the publication of the original consensus, and to collaboratively develop the updated statements. The 2.0 Consensus was aimed to update the original consensus with the latest available studies, and provide a comprehensive overview of the current relevant scientific literatures regarding functional cure of hepatitis B, with a particular focus on issues that are not yet fully clarified. These cover the definition of functional cure of hepatitis B, its mechanisms and barriers, the effective strategies and treatment roadmap to achieve this endpoint, in particular new surrogate biomarkers used to measure efficacy or to predict response, and the appropriate approach to pursuing a functional cure in special populations, the development of emerging antivirals and immunomodulators with potential for curing hepatitis B. The statements are primarily intended to offer international guidance for clinicians in their practice to enhance the functional cure rate of chronic hepatitis B.

As new evidence emerges, treatment strategies toward the functional cure of chronic hepatitis B are evolving. In 2019, a panel of national hepatologists published a Consensus Statement on the functional cure of chronic hepatitis B. Currently, an international group of hepatologists has been assembled to evaluate research since the publication of the original consensus, and to collaboratively develop the updated statements. The 2.0 Consensus was aimed to update the original consensus with the latest available studies, and provide a comprehensive overview of the current relevant scientific literatures regarding functional cure of hepatitis B, with a particular focus on issues that are not yet fully clarified. These cover the definition of functional cure of hepatitis B, its mechanisms and barriers, the effective strategies and treatment roadmap to achieve this endpoint, in particular new surrogate biomarkers used to measure efficacy or to predict response, and the appropriate approach to pursuing a functional cure in special populations, the development of emerging antivirals and immunomodulators with potential for curing hepatitis B. The statements are primarily intended to offer international guidance for clinicians in their practice to enhance the functional cure rate of chronic hepatitis B.

Purpose To explore the ultrasound characteristics of female breast cancer patients with different molecular types,and improve the diagnostic value of ultrasound.Materials and Methods The ultrasound diagnostic data of breast cancer patients in Xijing Hospital,the Air Force Medical University from January 2021 to July 2023 were retrospectively analyzed,and the ultrasound diagnosis of breast cancer patients from the aspects of molecular typing and related human epidermal growth factor receptor-2(HER-2)expression and Ki-67 expression were analyzed.Results A total of 1 405 patients were included in this study,including 240 patients with Luminal A type,631 patients with Luminal B type,162 patients with HER-2+hormone receptor(HR)-type,207 patients with HER-2+HR+type and 165 patients with triple-negative breast cancer.Among the ultrasound characteristics of female breast cancer with different molecular classifications,there were statistical differences in breast imaging reporting and data system classification,edge angulation,spiculation,posterior echo and calcification(χ2=13.652-143.178,all P<0.05).According to the analysis of different degrees of invasion,there were statistical differences in breast imaging reporting and data system classification,edge angulation,spiculation,posterior echo and calcification from the Lumina group(Luminal A,Luminal B)and the aggressive group(HER-2+HR-,HER-2+HR+and triple-negative)(χ2=4.702-17.587,all P<0.05).The HER-2-negative and HER-2-positive groups of patients had significant differences in shape,edge angulation,spiculation and calcification,with statistical differences(χ2=3.947-7.944,all P<0.05).According to the Ki-67 level analysis,it was found that edge angulation,spiculation and posterior echo were influencing factors,with statistical differences(χ2=9.309-56.380,all P<0.05).Conclusion Breast cancer with different molecular expression has its own ultrasound characteristics.Preoperative ultrasound can provide a certain reference basis for the diagnosis,treatment and prognosis assessment of breast cancer.

Objective:To investigate feedback on teaching effectiveness and optimization strategies for flipped classrooms in pediatric probation of eight-year clinical medicine programs, and to provide insights for enhancing the educational quality of pediatric probation.Methods:From June to September 2022, eight-year clinical medicine students from the class of 2018 undergoing pediatric probation were included in the study using purposive sampling. The subjects participated in one-on-one, offline, semi-structured, in-depth interviews to provide feedback on traditional lectures and flipped classroom teaching. The sample size was determined based on the principle of data saturation, with nine students participating in-depth interviews. NVivo 12 software was used for coding and classifying the interview data, which were then analyzed using thematic framework analysis to identify key themes.Results:Analysis of the interview data revealed three themes and ten sub-themes. Specifically, theme 1: The flipped classroom enhanced learning effectiveness but increased students' workload; theme 2: The current pediatric probation was scientifically designed but could be improved; theme 3: Several strategies exist for optimizing the flipped classroom teaching in pediatric probation.Conclusions:The flipped classroom in pediatric probation is in its early stages. While offering some benefits, further exploration and optimization are needed in curriculum design, student motivation, and supervision and evaluation methods.

Objective To investigate the clinical efficacy and safety of facilitated percutaneous coronary intervention(PCI)with half-dose recombinant staphylokinase(r-SAK)in patients with ST-segment elevation myocardial infarction(STEMI)who are expected to undergo PCI within 120 minutes.Methods From October 2021 to August 2022,a total of 200 STEMI patients in eight centers were included and randomly assigned in a 1﹕1 ratio to either r-SAK group or control group.Patients received loading doses of aspirin and ticagrelor and intravenous heparin and were randomized to receive an intravenous bolus of either 5 mg r-SAK or normal saline prior to PCI.The outcomes were set as ST-segment resolution(STR)at 60-90 minutes after PCI,the proportion and transition of pathological Q waves on the 5th day after PCI,and the proportion of high-sensitivity cardiac troponin T(hs-cTnT)peaking within 12 hours of onset.The safety outcome was major bleeding events defined as Bleeding Academic Research Consortium(BARC)≥type 3 bleeding during hospitalization.Results Compared with the control group,the r-SAK group had a higher proportion of STR≥70%within 60-90 minutes after PCI(58.3%vs.40.3%,P=0.009);a lower proportion of pathological Q waves(59.1%vs.74.1%,P=0.040);a lower rate of Q wave progression(14.8%vs.43.2%,P＜0.001);a higher rate of Q wave disappearance(12.5%vs.3.7%,P=0.027);and a higher proportion of hs-cTnT peaking within 12 hours of symptom onset[31/40(77.5%)vs.17/33(51.5%),P=0.027].Regarding the safety outcome,no significant difference in BARC≥type 3 bleeding was found between the two groups during hospitalization(P＞0.05).Conclusions For STEMI patients who were expected to undergo primary PCI within 120 minutes of symptom onset,the facilitated PCI with half-dose r-SAK significantly increased the proportion of STR≥70%at 60-90 minutes after PCI,reduced the formation of pathological Q waves,and shortened the time to peak hs-cTnT,without increasing the risk of bleeding,which should be an alternative reperfusion strategy worthy of further study.

Vertebral refracture following percutaneous vertebral augmentation (PVA) is commonly seen in elderly patients with osteoporotic thoracolumbar compression fractures (OTLCF). It can lead to recurrent pain, loss of vertebral height, progression of kyphosis, and even neurological dysfunction, significantly impairing patients′ quality of life. Current diagnosis and treatment face multiple challenges, including high misdiagnosis rate, difficulty in choosing between surgical and non-surgical treatment options, lack of standardized surgical protocols, interference from intralesional bone cement during procedures, inadequate stability of internal fixation in osteoporotic bone, and suboptimal compliance of anti-osteoporotic therapy. Establishing a standardized diagnostic and therapeutic framework is urgently needed. To standardize the management process and improve outcomes for vertebral refractures after PVA in elderly OTLCF patients, Spinal Trauma Group of the Orthopedic Branch of Chinese Medical Doctor Association organized experts in the field to develop Guideline for the diagnosis and treatment of vertebral refracture after percutaneous vertebral augmentation in elderly patients with osteoporotic thoracolumbar compression fractures ( version 2025), based on current literature and clinical experience, and adhering to principles of scientific rigor and clinical applicability. A total of 11 recommendations were proposed, encompassing diagnosis, treatment, and rehabilitation of vertebral refracture after PVA in elderly patients with OTLCF, aiming to provide a foundation for a standardized management.