Non-alcoholic fatty liver disease （NAFLD） is one of the most prevalent forms of liver diseases globally. Its progression can lead to cirrhosis and end-stage liver disease， and there is currently a lack of effective pharmacological treatments. Adenosine monophosphate-activated protein kinase （AMPK）， as a regulatory hub for maintaining cellular energy homeostasis， can coordinate key cellular processes such as adipogenesis， glucose metabolism， and mitochondrial functions. Its activation exerts metabolic regulatory effects through pathways including inhibiting lipogenesis， enhancing mitochondrial β-oxidation， regulating inflammation and oxidative stress， and promoting autophagy. Accordingly， AMPK emerges as a potential target for the prevention and treatment of NAFLD. Traditional Chinese Medicine （TCM）， with low toxicity， high accessibility， and multi-component， multi-target synergistic effects， has demonstrated unique value in NAFLD treatment， particularly showing notable advantages in regulating the AMPK signaling pathway. Sichuan is known as the treasure house of TCM， and the active components of its authentic medicinal materials such as Coptidis Rhizoma not only reflect regional characteristics in AMPK signaling regulation but also form a multi-level metabolic regulatory network through crosstalk with pathways such as sirtuin 1 （SIRT1） and peroxisome proliferator-activated receptor α （PPARα）. They can achieve specific regulation by directly activating AMPK and modulating upstream and downstream targets， exerting prominent effects in ameliorating hepatic steatosis and inflammation. This study systematically reviews the research findings on TCM for the prevention and treatment of NAFLD over the past five years， elaborating the mechanisms by which TCM treats NAFLD through regulating the AMPK signaling pathway. It aims to provide new perspectives and references for clinical diagnosis and treatment， basic research， and drug development.

In recent years， the number of special clinical cases related to assisted reproductive technology （ART） for pregnancy has been on the rise annually. For example， gamete donation， assisted reproduction for couples of advanced maternal ages， and the ownership and disposition of embryos when one or both partners pass away， all involve the health of offspring and conflicts of interest in the implementation of ART. Although China’s ethical principles for ART include the protection of the offspring， the detailed rules are vague and urgently need to be supplemented and improved. In addition， the clinical application of ART lacks legislative collaborative governance. The corresponding administrative departments， practitioners， and infertile couples should work together. Starting from the perspective of focusing on the well-being of offspring born from the clinical application of ART， while conducting clinical research to address technical challenges， efforts should be made to overcome ethical dilemmas in the application of technology， comprehensively consider the well-being of offspring born from assisted reproductive treatments and help them seek the best care to promote their healthy growth.

Trophoblast cells serve as the foundation for placental development. We analyzed published multiomics sequencing data and found that trophoblast cells highly expressed RRS1 compared to primitive endoderm and epiblast. We used HTR-8/SVneo cells for further investigation, and Western blot and immunofluorescence staining confirmed that HTR-8/SVneo cells highly expressed RRS1. RRS1 was successfully knocked down in HTR-8/SVneo cells using siRNA. Using IncuCyte S3 live-cell analysis system based on continuous live-cell imaging and real-time data, we observed that proliferation, migration, and invasion abilities were all significantly decreased in RRS1-knockdown cells. RNA-seq revealed that knockdown of RRS1 affected the gene transcription, and upregulated pathways in extracellular matrix organization, DNA damage response, and intrinsic apoptotic signaling, downregulated pathways in embryo implantation, trophoblast cell migration, and wound healing. Differentially expressed genes were enriched in diseases related to placental development. Consistent with these findings, human chorionic villus samples collected from spontaneous abortion cases exhibited significantly reduced RRS1 expression compared to normal controls. Our results highlight the functional importance of RRS1 in human trophoblasts and suggest that its deficiency contributes to early pregnancy loss.
Humans ; Trophoblasts/physiology* ; Cell Movement/genetics* ; Cell Proliferation/genetics* ; Female ; Pregnancy ; Abortion, Spontaneous/metabolism* ; Cell Line ; Placentation/genetics*

The production of healthy agricultural products has increased the demand for innovative and sustainable plant protection technologies, and the rapid advancement of nanotechnology has brought revolutionary breakthroughs to traditional agriculture. Nanocarrier-based drug delivery systems can not only significantly improve the utilization efficiency of pesticides, achieving enhanced efficacy and reduced application, but also decrease the pesticide residues and environmental pollution. Additionally, they have made breakthrough progress in the stability and persistence of RNA pesticides. This review summarized the research progress on nanopesticides and RNA pesticides, focusing on the mechanisms of nanocarriers in improving pesticide bioactivity and RNA interference (RNAi) efficiency. It also systematically summarized the types of nanomaterials and their applications in pest and disease management and provided an in-depth outlook for the future development of nanopesticides and RNA pesticides, which provided technical support for the high-quality development of agriculture in the future.
Pesticides/chemistry* ; Nanotechnology ; Nanostructures ; RNA ; Agriculture/methods* ; RNA Interference ; Drug Delivery Systems

Objective: To investigate the effects of different storage temperatures and durations on the activities of coagulation factor Ⅷ (Factor Ⅷ, FⅧ) and coagulation factor Ⅸ (Factor Ⅸ, FⅨ) after whole blood collection, so as to provide data support for the optimal storage conditions. Methods: A total of 16 mL of whole blood was collected from each of the 20 healthy volunteers at our blood center and aliquoted into 8 sodium citrate anticoagulant tubes. Two tubes were immediately centrifuged for the measurement of FⅧ and FⅨ activity levels. The remaining 6 tubes of whole blood were respectively stored under room temperature and low-temperature conditions. At 2, 4, and 6 h, the whole blood samples were centrifuged and analyzed for FⅧ and FⅨ activity levels. The mean values of the two immediately tested tubes were used as the control group, while other tubes were designated as the experimental groups for comparison. Statistical analysis was performed using SPSS 26.0. Results: The activity of FⅧ in whole blood remained stable after 4 hours of storage at both room temperature and low temperature (116.53±25.95 vs 125.22±27.33, 109.77±23.23 vs 125.22±27.33) (P>0.05 for both). However, by 6 hours, FⅧ activity showed a statistically significant decline compared to the control group (108.65±22.92 vs 125.22±27.33, 100.46±20.19 vs 125.22±27.33) (P<0.05 for both), though the room temperature group results were closer to the control values. The activity of FⅨ in whole blood remained stable after 6 hours of storage under both conditions (97.14±19.48 vs 96.76±19.67, 97.10±17.45 vs 96.76±19.6) (P>0.05 for all comparisons). Conclusion: For whole blood samples after collection, storage at either room temperature or low temperature for up to 4 hours does not compromise the accuracy of test results. When stored for 6 hours, FⅨ activity remains stable, whereas FⅧ activity decreases significantly. Notably, FⅧ activity demonstrates better stability at room temperature than under low-temperature conditions within the 6-hour storage.

ObjectiveTo investigate the potential machanism of Xiaozhong Zhitong Mixture （消肿止痛合剂， XZM） in the treatment of diabetes foot ulcer （DFU）. MethodsFifty SD rats were randomly divided into blank group， model group， XZM group， inhibitor group， XZM plus inhibitor group （combination group）， with 10 rats in each group. Except for the blank group， rats were fed with high-sugar， high-fat， high-cholesterol diet， intraperitoneally injected with streptozotocin， and subjected to skin defect to establish DFU model. After successful modeling， the XZM group and the combination group were given 1 ml/（100 g·d）of XZM by gavage， while the blank group， model group， and inhibitor group were all given an equal volume of 0.9% sodium chloride injection by gavage. Thirty minutes later， the inhibitor group and the combination group were intraperitoneally injected with 5 mg/（kg·d） of Notch1 inhibitor DAPT. All groups were treated once a day. After 14 days of administration， the skin tissue from the dorsal foot of the blank group rats and wound tissue from the other groups were collected. The pathological changes of granulation tissue in the wound were detected using hematoxylin eosin （HE） staining. The microvascular density （MVD） in wounds was detected through immunohistochemical staining. Real time fluorescence quantitative polymerase chain reaction （RT-PCR） and western blotting were used to detect the mRNA and protein levels of Notch1 homolog （Notch1）， Delta-like ligand 4 （Dll4）， Delta-like ligand 4 （VEGF）， and angiopoietin 2 （Ang-2）， respectively. ResultsHistological results showed that the epidermal structure in the dorsal foot skin tissue of the rats in the blank group was intact. In the wound tissue of the model group， the epidermis exhibited excessive keratinization， vacuolar cytoplasm， and a large number of inflammatory cells infiltrating the tissue， while in the XZM group， a large amount of scab formation was observed in the epidermis， with no significant inflammatory cell infiltration and a noticeable increase in fibroblasts. In the combination group and the inhibitor group， partial epidermal scab formation was observed in the wound tissue with a small amount of inflammatory cell infiltration. Compared to those in the blank group， the MVD in the wound tissue increased in the model group， as well as the mRNA expression and protein levels of Notch1 and Dll4， while VEGFA and Ang-2 mRNA expression and protein levels significantly decreased （P＜0.05 or P＜0.01）. Compared to those in the model group， the MVD in the wound tissue of all medication groups significantly increased， and the mRNA and protein levels of Notch1 and Dll4 decreased， while VEGFA and Ang-2 mRNA expression and protein levels increased （P＜0.05 or P＜0.01）. Compared to the XZM group， the inhibitor group and the combination group showed decreased MVD in wound tissue， increased Notch1 and Dll4 mRNA and protein levels， and decreased expression of VEGFA and Ang-2 mRNA and proteins （P＜0.05 or P＜0.01）. ConclusionXZM can effectively promote wound healing in DFU rats， and its mechanism of action may be related to the inhibition of Dll4/Notch1 signaling pathway in the wound tissue， therey promoting angiogenesis.

Aging is a natural process in which tissue and organ function declines as organisms age. Aging is the inevitable outcome of the organism and is irreversible. The aging process is accompanied by degenerative changes in the morphological structure of multiple organs of the body, leading to an increase in the incidence of chronic diseases such as hypertension, cardiovascular and cerebrovascular diseases, hyperlipidemia, and diabetes year by year. In recent years, natural phytochemicals have attracted widespread attention from the public due to their advantages such as non-toxicity or low toxicity, low cost, and various biological activities. Epigallocatechin gallate (EGCG) is a dietary polyphenol extracted from green tea, which has a variety of biological functions including anti-oxidation, anti-inflammation, hypoglycemic, hypolipidemic and anti-aging activities. The EGCG-mediated anti-aging mechanism has been investigated in many studies with different aging models. This article reviews the research progress on rodents, nematodes, fruit flies, and cell aging models, focusing on summarizing the lifespan extension and physiological changes of rodents, nematodes and fruit flies after EGCG intervention from multiple angles, and exploring potential mechanism by which EGCG delays aging and extends lifespan. This review provides a theoretical reference for the study of the anti-aging mechanism of phytochemicals.

Objective: To study the correlation between activated partial thromboplastin time (APTT) mixing test results and the inhibitor titers in hemophilia A inhibitor-positive patients. Methods: In this cross-sectional study, 41 patients with severe hemophilia A and inhibitors (and negative for lupus anticoagulant) were included from the hemophilia clinic of Shandong Blood Center from February 2022 to February 2024. All patients underwent APTT mixing test. The Rosner's index (RI, including the immediate RI and the RI after 2-hour water bath incubation [water bath 2h RI]), the time-dependent difference (Δ value), and the corrected percentage were calculated based on results of APTT mixing test. The median (interquartile range) of the corresponding indexes were calculated, and the ROC curves for identification of high inhibitor titers using the four indexes (the immediate RI, the water bath 2h RI, the Δ value, and the corrected percentage) were plotted, The correlations between APTT mixing test and inhibitor titers for coagulation factor Ⅷ (Factor Ⅷ, FⅧ) were investigated. Results: The median (lower quartile, upper quartile) of immediate RI, water bath 2h RI, Δ-value and corrected percentage for FⅧ inhibitor positive patients were 11.0 (5.4, 29.3)%, 45.0 (25.7, 75.0)%, 26.2 (7.6, 41.8) s, and 82.2 (58.5, 91.6)%, respectively. The median (lower quartile, upper quartile) of the immediate RI, water bath 2h RI, Δ-value and corrected percentage were 25.2 (13.0, 37.5)%, 64.1 (44.6, 72.6)%, 38.0 (14.3, 38.3) s, and 66.5 (50.1, 82.1)% for the high-titer inhibitor group, and 5.2 (4.2, 9.4)%, 17.9 (8.8, 28.0)%, 13.0 (7.6, 25.4) s, and 92.3 (88.0, 94.3)% for the low-titer inhibitor group. The AUCs of the ROC curves for discrimination between high and low titer inhibitor were: 0.9105 for immediate RI, 0.9118 for water bath 2h RI, 0.8873 for correcter percentage, and 0.6532 for Δ-value. Conclusion: High-titer inhibitors can be highly suspected in hemophiliac patients with an immediate RI >10% and a water bath 2h RI >45%, and the presence of low-titer inhibitors is suspected in patients with a 4-second < immediate RI <10% and a 13% < water bath 2h RI <45%.

BACKGROUND: Metabolic-associated fatty liver disease (MAFLD) is the predominant form of chronic liver disease worldwide. This study was designed to investigate the proportion and characteristics of MAFLD within the general Chinese population and to identify the contributory risk factors for liver fibrosis among MAFLD individuals. METHODS: The participants were recruited from a cohort undergoing routine health evaluations at the Third Hospital of Hebei Medical University between May 2019 and March 2023. The diagnosis of MAFLD was based on the established clinical practice guidelines. The fibrosis-4 index score (FIB-4) was employed to evaluate hepatic fibrosis, with a FIB-4 score of ≥1.3 indicating significant fibrosis. Binary logistic regression analyses were used to determine risk factors associated with significant hepatic fibrosis in MAFLD. RESULTS: A total of 22,970 participants who underwent comprehensive medical examinations were included in the analysis. The overall proportion of MAFLD was 28.77% (6608/22,970), with 16.87% (1115/6608) of these patients showing significant fibrosis as assessed using FIB-4. Independent risk factors for significant liver fibrosis in MAFLD patients were male (odds ratio [OR] = 0.676, 95% confidence interval [CI]: 0.558-0.821), hepatitis B surface antigen (HBsAg) positivity (OR = 2.611, 95% CI: 1.557-4.379), body mass index ≥23.00 kg/m 2 (OR = 0.632, 95% CI: 0.470-0.851), blood pressure ≥130/85 mmHg (OR = 1.885, 95% CI: 1.564-2.272), and plasma glucose ≥5.6 mmol/L (OR = 1.815, 95% CI: 1.507-2.186) (all P <0.001). CONCLUSIONS The proportion of MAFLD in an urban Chinese population is 28.77%. About 16.87% of MAFLD patients presented with significant liver fibrosis. Independent risk factors for significant liver fibrosis in MAFLD patients should be noticed.
Humans ; Male ; Female ; Liver Cirrhosis/pathology* ; Middle Aged ; Risk Factors ; Adult ; Fatty Liver/pathology* ; Aged ; China/epidemiology* ; Logistic Models ; Urban Population ; East Asian People