Objective To prepare Zanthoxylum alkaloid thermosensitive hydrogel, optimize the preparation process and conduct related performance studies. Methods Zanthoxylum alkaloids were obtained by reflux extraction, followed by enrichment and purification using macroporous adsorption resin. Poloxamer 407 and Poloxamer 188 were used as substrates to prepare the thermosensitive hydrogel of Zanthoxylum alkaloids, and the preparation process was optimized by orthogonal design. The quality of the hydrogel was systematically evaluated based on its gelation temperature, gelation time, Fourier transform infrared （FTIR） spectroscopy, scanning electron microscopy （SEM） images, mechanical properties, and in vitro release profile. Results The optimal preparation conditions for the Zanthoxylum alkaloid thermosensitive hydrogel were: 20% （g/ml） poloxamer 407, 2% （g/ml） poloxamer 188 and 100 μg/ml Zanthoxylum alkaloid. The gelation temperature was 32.6℃, and the average gelling time was 143.3 s. The hydrogel appeared as a transparent liquid at room temperature and was transformed into a semi-solid gel state when the temperature exceeded 33℃. Experimental results confirmed the successful preparation of poloxamer 407 and poloxamer 188 thermosensitive hydrogel loaded with Zanthoxylum alkaloids, which exhibited good bio adhesion, self-healing properties, and tensile strength. Conclusion The Zanthoxylum alkaloid thermosensitive hydrogel demonstrated favorable mechanical properties and a sustained-release effect, showing promising potential for further development and application.

ObjectiveTo explore the effects and mechanism of the modified Danggui Yinzi on "itch-anxiety" model rats of chronic urticaria （CU）. MethodsThe 36 SPF-grade 6-8-week-old female SD rats were randomly divided into a blank control group，a model group，a positive control group，a low-dose modified Danggui Yinzi group，a medium-dose modified Danggui Yinzi group，and a high-dose modified Danggui Yinzi group. A "itch-anxiety" model was established by intraperitoneal injection of a suspension of sodium chloride and aluminum hydroxide and ovalbumin，combined with chronic unpredictable emotional stress stimulation. After successful modeling，rats in each group were administered drugs by gavage. The positive control group was given intragastric administration of the drug solutions of cetirizine and fluoxetine （2.08 mg·kg^-1·d^-1 fluoxetine， 2 mg·kg^-1·d^-1 cetirizine）， the low-，medium-，and high-dose modified Danggui Yinzi groups were administered traditional Chinese medicine at 1.44，2.88， 5.76 g·kg^-1， respectively，while the blank control group and model group were given an equal volume of normal saline. All interventions lasted for 15 days. Behavioral changes were evaluated by the elevated plus-maze test （detecting the percentage of entries into the open arms （OE%），the percentage of time spent in the open arms （OT%），and the total number of entries into the open and closed arms （TNE）），the open-field test （detecting total activity，average movement speed，and latency to enter the central area），and scratching behavior observation. Pathological changes of skin tissues were observed by hematoxylin-eosin （HE） staining and toluidine blue staining，while those of amygdala tissues were observed by HE staining，Nissl staining，and immunofluorescence detection of ionized calcium-binding adapter molecule-1 （Iba-1）. The content of immunoglobulin E （IgE），interleukin-33 （IL-33），histamine in serum and glutamate in the amygdala was detected by enzyme-linked immunosorbent assay （ELISA）. Western blot was used to detect the protein expression of striatal-enriched protein tyrosine phosphatase （STEP），N-methyl-D-aspartate receptor subunit 2B （NR2B）， calmodulin-dependent protein kinase Ⅱ （CaMKⅡ），phosphorylated CaMKⅡ （p-CaMKⅡ），mitogen-activated protein kinase （MAPK），phosphorylated MAPK （p-MAPK），nuclear factor kappa-light-chain-enhancer of activated B cells （NF-κB），phosphorylated NF-κB （p-NF-κB），and postsynaptic density protein-95 （PSD-95） in the amygdala. ResultsCompared with the blank control group，the model group rats showed obvious anxiety-like behaviors （decreased OE%，OT%，and TNE，reduced total activity，slower average movement speed，and prolonged latency to enter the central area），increased scratching times，obvious skin inflammation and mast cell degranulation，severe amygdala tissue damage，increased glutamate content in the amygdala，and elevated levels of IgE and IL-33 in serum. The expression of STEP，NF-κB，p-NF-κB，NR2B，MAPK，p-MAPK，CaMKⅡ，and p-CaMKⅡ proteins in the amygdala increased，while the expression of PSD-95 protein decreased （P<0.05）. Compared with the model group，the modified Danggui Yinzi group of each dose had increased OE%，OT%，TNE，total activity，and average movement speed，shortened latency to enter the central area， reduced scratching times，alleviated skin inflammation and mast cell degranulation，relieved amygdala tissue damage，decreased glutamate content in the amygdala，and reduced levels of IgE and IL-33 in serum. Moreover，compared with the model group，the low -，medium-，and high-dose modified Danggui Yinzi groups showed decreased expression levels of STEP，NF-κB，p-NF-κB，NR2B，MAPK，p-MAPK，CaMKⅡ，and p-CaMKⅡ proteins in the amygdala，and increased expression of PSD-95 protein. There was a significant dose-effect relationship，with the high-dose group showing the most significant regulatory effect （P<0.05）. ConclusionThe modified Danggui Yinzi has a therapeutic effect on "itch-anxiety" model rats of CU. Its mechanism may be related to regulating glutamate metabolism in the amygdala，modulating the STEP/NR2B/CaMKⅡ/MAPK/NF-κB pathway，and regulating the expression of PSD-95.

Yttrium-90 microsphere selective internal radiation therapy (SIRT), also known as transarterial radioembolization, has become one of the pivotal treatments for liver cancer, particularly for selected advantageous patient groups. This review summarizes the characteristics of different patients with liver cancer that could obtain maximum benefit from SIRT and discusses key factors affecting efficacy and safety, including tumor characteristics, liver function, patient performance status, and treatment intent. In evaluating appropriate candidates, mapping serves as a crucial simulation procedure to assess tumor vascular anatomy, predict lung shunting, and guide catheter positioning and dose planning. This procedure substantially enhances therapeutic precision while minimizing the risk of nontarget radiation-related adverse events, such as radiation-induced pneumonitis and gastrointestinal toxicity. Several studies have suggested that SIRT is not only suitable for patients with early or limited hepatocellular carcinoma but can also be used as a bridging therapy for liver transplantation and conversion therapy for unresectable liver cancers. In combination with systemic treatments, SIRT has demonstrated survival benefits in patients with unresectable liver cancer. This review also highlights the importance of further optimizing patient screening through personalized dosimetry and mapping to ensure the precision and safety of treatment. A thorough review of relevant literature and clinical practice offers clinicians comprehensive suggestions on patient screening and clarifies the promise of SIRT in the liver cancer population.

Objective: To identify the latent profile characteristics and associated factors of family intergenerational transmission of proactive health behaviors in overweight and obesity junior high school students, so as to provide a reference for promoting active health in adolescents. Methods: From October to December 2024, a stratified cluster random sampling method was employed to select 4 932 junior high school students with overweight and obesity from 18 junior high schools of three cities representing the eastern (Yantai), central (Zibo), and western (Zaozhuang) regions of Shandong Province. Latent profile analysis was used to explore the heterogeneity of family intergenerational transmission among those students. Univariate analysis and multiple Logistic regression analysis were conducted to identify factors associated with different profiles and to examine the influence of profile membership on junior high school students proactive health levels. Results: The intergenerational transmission of health behaviors in junior high school students could be classified into 3 latent profiles:the moderate modeling dysfunctional group (5.88%, n =290), the low modeling advantage deficient group (41.79%, n =2 061), and the high modeling functional harmonious group ( 52.33 % n =2 581). Univariate analysis showed that gender, urban/rural area, region location, paternal/maternal education level, family economic status, and only child status were significantly associated with the classification of latent profiles of intergenerational transmission in families of overweight and obesity junior high school students ( χ 2=7.63-165.22, all P <0.05). Multiple Logistic regression analysis revealed that, using the moderate modeling dysfunctional group as the reference, male students ( OR =0.71) and those residing in coastal cities ( OR =0.74) were less likely to belong to the low modeling advantage deficient group (both P <0.05); students with moderate family economic status were more likely to belong to the low modeling advantage deficient group ( OR =1.72， P <0.05). Conversely, students living in urban areas ( OR =1.43), those with fathers ( OR =2.53) or mothers ( OR =2.48) having a college degree or above, and those with moderate ( OR =3.89) or good ( OR =2.42) family economic status were more likely to be classified into the high modeling functional harmonious group (all P < 0.05 ). Using the low modeling advantage deficient group as the reference, residing in coastal cities ( OR =1.26), living in urban residence ( OR =1.14), having parents (father or mother) with a college education or above ( OR =1.91, 2.33), moderate or good family economic status ( OR = 2.27 , 3.17), and being an only child ( OR =1.19) were associated with a higher probability of belonging to the high modeling functional harmonious group (all P < 0.05 ). There was a statistically significant difference in active health behaviors among students across different latent profiles of family intergenerational transmission ( F =494.79, P <0.01). Conclusions The heterogeneity of family intergenerational transmission is associated the level of proactive health behaviors among junior high school students. Therefore, precision interventions should be implemented based on different categories of family intergenerational transmission, so as to strengthen the efficacy of intergenerational transmission of health behaviors and promote proactive health among junior high school students.

Objective: To explore the relationship of family function with sleep and externalizing problem behaviors of preschool children, so as to provide a guidance for externalizing problem prevention and intervention among preschool children. Methods: From October 2023 to January 2024, a convenience sampling method was used to select 5 138 preschool children from kindergartens in 8 districts of Wuhan City, Hubei Province. Parents completed the survey for Family Adaptability and Cohesion Scale, children s sleep habits and Child Behavior Checklist (CBCL). Spearman correlation analysis was used to examine the correlation of family function with scores of sleep quality and externalizing problem behaviors among preschool children. A mediation model analysis and bootstrap test were conducted to further investigate the mediating role of sleep quality between family function and externalizing problem behaviors. Mplus 8.7 software was used for latent profile analysis of family function. Results: The reported rates of poor sleep quality and externalizing problem behaviors among preschool children were 11.8% ( n =607), 20.0% ( n =1 026). The relevant analysis results showed that family function was negatively correlated with sleep quality and externalizing problem behaviors ( r = -0.20, -0.23), and sleep quality was positively correlated with externalizing problem behaviors ( r =0.27) ( P <0.01). The mediation effect test showed that family function negatively predicted externalizing problem behaviors ( β =-0.079) and sleep quality ( β = -0.075), while sleep quality positively predicted externalizing problem behaviors ( β =0.215) ( P <0.01). The latent profile analysis results showed that family function could be classified into 4 categories: high family function group (23.01%), upper middle family function group (44.65%), moderate family function group (26.24%) and low family function group (6.11%). Compared to high family function, the other three categories significantly positively predicted externalizing problem behaviors, and the mediating effects of sleep quality on different categories of family function were statistically significant [upper middle family function: mediation effect value was 0.022 (95% CI =0.004-0.041) and direct effect value was 0.329 (95% CI =0.263-0.396); middle family function: mediation effect value was 0.087 (95% CI =0.063-0.115) and direct effect value was 0.491 (95% CI =0.416-0.565); low family function: mediation effect value was 0.144 (95% CI =0.107-0.185) and direct effect 0.621 (95% CI =0.503-0.740)] ( P < 0.05 ). Conclusion Family function negatively predicts the externalizing problem behaviors of preschool children, and sleep quality plays a partial mediating role.

Animal experiments are essential tools in biomedical research, serving as a bridge between basic research and clinical trials. Systematic reviews and meta-analyses (SRs/MAs) of animal experiments are crucial methods for integrating evidence from animal experiment, which can facilitate the translation of findings into clinical research, reduce translational risks, and promote resource integration in basic research. With the continuous development of the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) methodology, its application in SRs/MAs of animal experiments has gained increasing attention. This article first outlines the principles and specific applications of the GRADE methodology in SRs/MAs of animal experiments, including qualitative descriptive systematic reviews, meta-analyses, and network meta-analyses. It then deeply analyzes the misuse of the GRADE methodology in practice, including incorrect evidence grading, improper classification of evidence, misapplication in qualitative systematic reviews, inconsistencies between the documentation of the upgrading and downgrading process and results, and inappropriate use for making recommendations. Furthermore, this article comprehensively discusses the factors influencing the grading of evidence certainty in SRs/MAs of animal experiments, including the impact of bias risk, indirectness, inconsistency, imprecision, and publication bias on evidence downgrading, as well as the role of large effect sizes and cross-species consistency in evidence upgrading. Finally, in response to the issues discussed, improvement strategies are proposed, including further research and optimization of the GRADE methodology for SRs/MAs of animal experiments, the development of reporting guidelines tailored to the characteristics of SRs/MAs in animal experiment research, and enhanced professional training for researchers in the GRADE methodology. This article aims to improve the quality of evidence in SRs/MAs of animal experiments, strengthen their reliability in clinical decision-making, and promote the more efficient translation of findings from animal experiment research into clinical practice.

OBJECTIVE To explore the effect of superoxide dismutase （SOD） administration on the malignant behavior of PLC/PRF/5 liver cancer cells， and analyze the correlation between SOD and alpha-fetoprotein （AFP） expression， to provide new ideas for targeting AFP with SOD as a drug for hepatocellular carcinoma. METHODS Normal human liver cells L-02， AFP- negative human liver cancer cells HLE， and AFP-positive human liver cancer cells PLC/PRF/5 were used as experimental cells. Western blot assay and SOD activity detection kit were used to detect the expression of AFP， SOD and activity of SOD in cells before and after changing AFP expression； the effects of different concentrations of SOD [0 （control）， 0.188， 0.375， 0.75， 1.5， 3 U/mL] administration on the migration and proliferation of PLC/PRF/5 cells were detected using cell scratch assay and CCK-8 assay. The effects of SOD overexpression on the expression of malignant biological behavior-related proteins AFP and sarcoma virus protein （Src） in PLC/PRF/5 cells were detected using Western blot. RESULTS Compared with L-02 group and HLE group， the expression levels of SOD1 and SOD2， and SOD activity in PLC/PRF/5 cells were significantly reduced （P＜0.05）. After down-regulating AFP expression in PLC/PRF/ 5 cells， compared with PLC/PRF/5 group， the expression levels of SOD1 and SOD2， as well as SOD activity， were significantly increased in the PLC/PRF/5-shAFP group （low-expression） （P＜0.05）. After 48 hours of SOD treatment， compared with control group， the scratch healing rates of PLC/PRF/5 cells in the 0.375， 0.75， 1.5 and 3 U/mL SOD groups were significantly reduced （P＜0.05）； after 72 hours of SOD treatment， compared with control group， the scratch healing rates of PLC/PRF/5 cells in the 0.375， 0.75， and 1.5 U/mL SOD groups were significantly reduced （P＜0.05 or P＜0.01）. Compared with control group， proliferation rates of PLC/PRF/5 cells were significantly reduced in the 0.375， 0.75， 1.5 and 3 U/mL SOD groups （P＜0.05 or P＜0.01）. Compared with the PLC/PRF/5 group before up-regulating SOD1 and SOD2 expression， the expression levels of AFP and Src in the PLC/PRF/5-oeSOD1 and PLC/PRF/5-oeSOD2 groups （over-expression） after up-regulating SOD1 and SOD2 expression were significantly reduced （P＜0.05）. CONCLUSIONS A certain concentration of SOD can inhibit malignant behavior such as migration and proliferation of PLC/PRF/5 cells， and the expression level and activity of SOD are negatively correlated with AFP.

ObjectiveTo improve the efficacy of Astragalus membranaceus (Fisch.) Bunge (A. membranaceus, Huang Qi), and to further develop and utilize it, fermentation technology was applied to the stem and leaf of A. membranaceus to enhance its immune function.MethodsIn this study, we fermented A. membranaceus stem and leaf (ASL) with probiotics and investigated its immune function. Firstly, we screened suitable strains for ASL fermentation and optimized the fermentation process. Secondly, we determined the antioxidant capacity of fermented ASL and its effect on inflammation in mouse monocyte-macrophage cell. Finally, the immunocompromised mice were treated with fermented ASL to investigate the changes in their immune ability.ResultsAmong the 10 selected probiotics, Lactobacillus plantarum was the most suitable strain for ASL fermentation. After optimization of the fermentation process, the content of saponins in fermented ASL was significantly increased. The fermented ASL exhibited strong anti-inflammatory and antioxidant activities in vitro. The in vivo immune efficacy improved by promoting the development of the spleen and thymus, as well as raising the immunoglobulin M, tumor necrosis factor-α, and interleukin-1β levels of in the serum.ConclusionThis study contributes to developing the non-medicinal parts of A. membranaceus, expands its medicinal resources, highlights the potential of fermentation technology to enhance these parts, and provides a reference for further development. Based on this approach, we can promote using non-medicinal parts of herbal medicines, minimize drug waste, and offer a reference for developing non-medicinal components in Chinese herbal medicines.

Objective:To explore the efficacy and safety of orelabrutinib combined with R-CHOP in patients with high-risk nongerminal center B-cell (non-GCB) diffuse large B-cell lymphoma (DLBCL) with extranodal involvement.Methods:This retrospective study was conducted on 35 patients who were seen at Guangxi Medical University Cancer Hospital and were immunohistochemically confirmed to have non-GCB DLBCL, had an International Prognostic Index score of 3 - 5, and confirmed to have ≥2 extranodal involvement on PET/CT. The treatment comprised the standard R-CHOP regimen combined with oral orelabrutinib (150 mg/day) for six cycles. In patients who developed neutropenia or grade 3 neutropenia with fever during treatment, administration of prophylactic pegylated granulocyte colony-stimulating factor 48 h after the end of chemotherapy was started on the next cycle. The endpoints included overall response rate (ORR), complete response (CR) rate, progression-free survival (PFS) time, overall survival (OS) time, and safety assessment.Results:The 35 eligible patients enrolled had a median age of 53 years (21 - 72 years) and a median follow-up time of 28 months (12 - 36 months) ; 19 patients had double-expressor (DE) status. The ORR was 88.6%, and the CR rate was 68.6%. The 2-year PFS and OS rates were 68.6% (95% CI 54.0% - 7.2%) and 87.5% (95% CI 76.7% - 100%), respectively. The 2-year PFS rate was significantly lower in patients with DE status than in those without DE status [54.4% (95% CI 35.4% - 84.2%) vs. 85.2% (95% CI 68.3% - 100%), P=0.048]. Serious adverse events included febrile neutropenia, pneumonia, and atrial flutter, but no treatment-related deaths. Conclusion:In patients with high-risk non-GCB DLBCL and extranodal involvement, the combination of orelabrutinib with R-CHOP regimen had good efficacy and manageable toxicity.

Extramedullary plasmacytoma(EMP)is a malignant neoplasm characterized by monoclonal plasma cell proliferation originating outside the bone marrow and hematopoietic tissues.The co-occurrence of multiple myeloma(MM)with mammary EMP is clinically rare.This case report describes the diagnostic and therapeutic management of a middle-aged female patient with MM and mammary EMP,accompanied by a litera-ture review.The patient presented with persistent fever and was found to have a right breast mass via PET/CT during routine follow-up for MM.The lesion was biopsy-confirmed as mammary EMP,and the patient subse-quently underwent chemotherapy.This case highlights the critical importance of differential diagnosis between breast cancer and rare hematologic metastatic tumors in early prevention of disease progression.