Hepatocellular carcinoma （HCC） is a common malignant tumor with a high mortality rate， an insidious onset， and complex pathological mechanisms. In the tumor microenvironment， tumor-promoting immune cells protect tumor cells from immune attacks， while dysfunction of anti-tumor immune cells causes the inhibition of immune response， thereby leading to the continuous deterioration of cancer. In recent years， traditional Chinese medicine has shown good efficacy in the treatment of HCC， and it can inhibit the proliferation and metastasis of cancer cells by regulating immune cells. By analyzing related articles in China and globally， this article summarizes how immune cells affect the progression of HCC through the immunosuppressive pathway and how traditional Chinese medicine exerts an anti-HCC effect by regulating immune cells， in order to provide theoretical basis and reference for optimizing the treatment of HCC.

Abstract To analyzes the characteristics, problems and enlightenment of physical activity observation tools, so as to provide reference for researchers to quickly and accurately choose appropriate observation tools to evaluate children s and adolescents physical activity. Literature search is conducted in eight databases of Chinese and English, including CNKI, Wanfang, VIP, Web of Science, PubMed, Medline, ERIC, and SPORTDiscus. Ultimately, eight observation tools for assessing physical activity in children and adolescents are included. Through summarization and comparison, it is found that the applications of those tools cover multiple age groups, the observation indicators cover multiple dimensions for each with varying emphases, and the applicable contexts vary in their specific background information, and recording methods tend to be quantitative. However, several issues remain to be addressed in practical applications. First, the observation indicators need to be supplemented and improved; second, physical activity in community environments and academic classrooms requires further attention; third, physical activity intensity needs to be scientifically evaluated; fourth, observation and recording methods need to be integrated and innovated; fifth, the number of observation subjects needs to be expanded. Future research could focus on developing observation tools tailored to the characteristics of Chinese children and adolescents, while drawing on foreign observation tools to comprehensively assess physical activity among children and adolescents.

Objective: To evaluate the platelet transfusion requirements in children with high-risk stage Ⅳ neuroblastoma undergoing autologous hematopoietic stem cell transplantation (ASCT), and to identify risk factors for increased transfusion needs and prolonged time to platelet transfusion independence. Methods: This single-center retrospective clinical study included 96 children with high-risk stage Ⅳ neuroblastoma who underwent ASCT from January 2019 to May 2024 in our hospital. Relevant clinical data were collected and analyzed, including age, gender, body surface area, platelet count (PLT) on stem cell infusion day (day 0), conditioning regimen, CD34 stem cell dose, platelet transfusion requirements during transplantation, and time to platelet transfusion independence post-transplant. Results: All 96 (100%) children received transfusion after ASCT. From day 0 to transfusion independence, the median number of platelet transfusion was 3 (2, 4.50), and the median volume of platelet transfused was 3 (2, 4.25) units. Platelet transfusion was required in almost all children in pseudo-healing stage (day 4 to day 6) and polar stage (day 7 to day 14), with transfusion rates as high as 83.33%(n=80) and 100%(n=96), respectively. The median time to platelet transfusion independence post-transplant was 13(11,17) days. Multivariate analysis showed that PLT<100×10 /L on day 0, platelet transfusion within one week before ASCT, the use of “busulfan+ melphalan” conditioning regimen, and CD34 stem cell dose<4.0×10 /kg were associated with significantly increased platelet requirements and numbers of transfusion (P<0.05). PLT<100×10 /L on day 0, platelet transfusion within one week before ASCT, and CD34 stem cell dose<4.0×10 /kg were associated with significantly delayed platelet transfusion independence (P<0.05). Age, sex, and blood type showed no statistically significant association (P>0.05) with post-transplant platelet transfusion requirements or time to transfusion independence in neuroblastoma patients. Conclusion: This study provided quantitative data for platelet transfusion after ASCT in children with high-risk stage Ⅳ neuroblastoma, and identified PLT<100×10 /L on day 0, platelet transfusion within one week before ASCT, CD34 stem cell dose<4.0×10 /kg were risk factors for increased platelet transfusions and delayed transfusion independence. Furthermore, the use of the BuMel (busulfan-melphalan) conditioning regimen was also found to contribute to increased transfusion requirements.

Objective: To evaluate the platelet transfusion requirements in children with high-risk stage Ⅳ neuroblastoma undergoing autologous hematopoietic stem cell transplantation (ASCT), and to identify risk factors for increased transfusion needs and prolonged time to platelet transfusion independence. Methods: This single-center retrospective clinical study included 96 children with high-risk stage Ⅳ neuroblastoma who underwent ASCT from January 2019 to May 2024 in our hospital. Relevant clinical data were collected and analyzed, including age, gender, body surface area, platelet count (PLT) on stem cell infusion day (day 0), conditioning regimen, CD34 stem cell dose, platelet transfusion requirements during transplantation, and time to platelet transfusion independence post-transplant. Results: All 96 (100%) children received transfusion after ASCT. From day 0 to transfusion independence, the median number of platelet transfusion was 3 (2, 4.50), and the median volume of platelet transfused was 3 (2, 4.25) units. Platelet transfusion was required in almost all children in pseudo-healing stage (day 4 to day 6) and polar stage (day 7 to day 14), with transfusion rates as high as 83.33%(n=80) and 100%(n=96), respectively. The median time to platelet transfusion independence post-transplant was 13(11,17) days. Multivariate analysis showed that PLT<100×10 /L on day 0, platelet transfusion within one week before ASCT, the use of “busulfan+ melphalan” conditioning regimen, and CD34 stem cell dose<4.0×10 /kg were associated with significantly increased platelet requirements and numbers of transfusion (P<0.05). PLT<100×10 /L on day 0, platelet transfusion within one week before ASCT, and CD34 stem cell dose<4.0×10 /kg were associated with significantly delayed platelet transfusion independence (P<0.05). Age, sex, and blood type showed no statistically significant association (P>0.05) with post-transplant platelet transfusion requirements or time to transfusion independence in neuroblastoma patients. Conclusion: This study provided quantitative data for platelet transfusion after ASCT in children with high-risk stage Ⅳ neuroblastoma, and identified PLT<100×10 /L on day 0, platelet transfusion within one week before ASCT, CD34 stem cell dose<4.0×10 /kg were risk factors for increased platelet transfusions and delayed transfusion independence. Furthermore, the use of the BuMel (busulfan-melphalan) conditioning regimen was also found to contribute to increased transfusion requirements.

Lymphatic metastasis is the main metastatic route for colorectal cancer, which increases the risk of cancer recurrence and distant metastasis. The properties of the lymph node metastatic colorectal cancer (LNM-CRC) cells are poorly understood, and effective therapies are still lacking. Here, we found that hypoxia-induced fibroblast activation protein alpha (FAPα) expression in LNM-CRC cells. Gain- or loss-function experiments demonstrated that FAPα enhanced tumor cell migration, invasion, epithelial-mesenchymal transition, stemness, and lymphangiogenesis via activation of the STAT3 pathway. In addition, FAPα in tumor cells induced extracellular matrix remodeling and established an immunosuppressive environment via recruiting regulatory T cells, to promote colorectal cancer lymph node metastasis (CRCLNM). Z-GP-DAVLBH, a FAPα-activated prodrug, inhibited CRCLNM by targeting FAPα-positive LNM-CRC cells. Our study highlights the role of FAPα in tumor cells in CRCLNM and provides a potential therapeutic target and promising strategy for CRCLNM.

This study aims to observe the effect of Panax notoginseng extracts on inflammatory re-sponse in immunosuppressed broilers and to investigate the mechanism through network pharma-cology and molecular docking combined with in vivo animal tests.Based on the TCMSP database and GeneCard and other disease databases,we searched for targets related to Panax notoginseng and broiler inflammation,screened key compounds and targets by applying Cytoscape 3.7.1 and String databases,respectively,and constructed a network relationship diagram of traditional Chi-nese medicine(TCM)-key components-targets,and carried out GO functional enrichment and KEGG pathway enrichment analyses by using the DAVID platform.The GO functional enrichment analysis and KEGG pathway enrichment analysis were carried out by the DAVID platform,visual-ized by the Chiplot online website,and finally,the core clustered proteins were analyzed by Pymol software to obtain the core targets,and molecular docking technology was used to predict the de-gree of matching between the active ingredients and the core targets as well as the animal experi-ments to further explore the pharmacological mechanism of Panax notoginseng extracts.Sixty 1-day-old red-feathered broilers were randomly divided into three groups(LPS group,CON group,and PN group),and the test period was 35 days.The LPS and PN groups were injected intraperito-neally with 250 μg/kg body weight of LPS,and the CON group was injected with an equal amount of sterile physiological saline on the 12,14,33,and 35 d.The LPS and PN groups were injected with 250 μg/kg body weight of LPS,and the CON group was injected with an equal amount of sterile physiological saline.The effect of Panax notoginseng extract on inflammatory cytokines in serum was detected by ELISA,and the hormone content in serum was also detected in each group,and fluorescence quantitative PCR was used to detect the effect of each group on the mRNA ex-pression levels of STAT3,IL-6,and CASP3.The results showed that the serum levels of IFN-γ,IL-6,iNOS,TNF-α,and TNF-β were significantly increased(P＜0.05),while the level of IL-10 was significantly decreased(P＜0.05)after LPS tapping at weeks 2 and 5.The serum levels of IFN-y,IL-6,iNOS,TNF-α,and TNF-β were significantly decreased(P＜0.05)and IL-10 was sig-nificantly increased(P＜0.05)by the addition of Panax ginseng extracts to the basal diet com-pared with the LPS group.Panax notoginseng extracts significantly decreased the serum levels of adrenocorticotropic hormone(ACTH)and corticosterone(CORT)(P＜0.05)and increased the levels of growth hormone(GH)(P＜0.05).A total of 8 active ingredients and 123 potential tar-gets for broiler inflammation were predicted by network pharmacology.The protective mechanism of Panax notoginseng against broiler inflammation may be related to the C-type lectin receptor(CLR)signaling pathway,Toll-like receptor(TLR)signaling pathway,MAPK signaling pathway,NOD-like receptor(NLR)signaling pathway,and FoxO signaling pathway.According to the pre-diction,the alleviation of inflammatory response in broiler chickens by Panax notoginseng may be related to the action on 12 key targets.Fluorescence quantitative PCR showed that Panax notogin-seng extract down-regulated the mRNA expression of IL-6 and CASP3(P＜0.05)and up-regula-ted that of STAT3(P＜0.05),and molecular docking results also showed that the active ingredi-ents in Panax notoginseng extracts could exert anti-inflammatory effects through IL-6 and CASP3.The results suggested that Panax quinquefolium extracts might alleviate the inflammatory response of immune-stressed broilers through multi-components,multi-targets,and multi-path-ways,and this study helps propose new therapeutic strategies and provides a theoretical basis for the development of feed additives based on Penthorum chinense Pursh extract.

ObjectiveTo investigate whether cytotoxic T lymphocyte （CTL）－derived exosomes can downregulate HBx expression and inhibit hepatic stellate cell （HSC） activation. MethodsThe supernatants of HepG2， HepGA14， and CTL cells were collected to extract exosomes， which were referred to as NC－exo， HBV－exo， and CTL－exo， respectively）. Transmission electron microscopy was used to observe their morphology， and Western Blot was used to measure the expression of the markers of exosomes CD63 and TSG101. NC－exo， HBV－exo， and CTL－exo labeled by BODIPY dye were mixed with HBV－exo at different ratios and were then co－cultured with HSC LX－2 （HSC－LX2）. A fluorescence microscope was used to observe whether exosomes could enter LX－2 cells， and an fluorescence microscope was used to observe cell morphological changes； quantitative real－time PCR （qPCR） was used to measure the expression of the activated biomarkers such as transforming growth factor－β1 （TGF－β1）， ɑ－smooth muscle actin （ɑ－SMA）， and collagen type I （Collagen I） in LX－2 cells. CTL－exo was added to the HepGA14 culture system； then qPCR was used to measure the mRNA expression level of HBV DNA， cccDNA， and HBx in exosomes in HepGA14 cells， and Western Blot was used to measure the protein expression level of HBx in exosomes. The t-test was used for comparison of normally distributed continuous data between two groups； a one-way analysis of variance was used for comparison between multiple groups， and the least significant difference t-test was used for further comparison between two groups. ResultsThe exosomes were all microcysts with a double－layer membrane structure and were circular or elliptical in shape， with the expression of the signature proteins CD63 and TSG101， and the vesicles had a diameter of 50－100 nm. The fluorescence microscope showed that exosomes could enter LX－2 cells， and HSC were enlarged with extended cell processes. The results of qPCR showed that there were significant differences in the expression levels of TGF－β1， ɑ－SMA， and Collagen I genes between the NC－exo， HBV－exo， NC－exo+HBV－exo， and Con groups （F=444.678， 417.144， and 571.508， all P<0.05）. After the intervention of HepGA14 cells with CTL－exo， qPCR results showed that compared with the control group， there were significant reductions in the expression levels of HBV DNA and cccDNA in HepGA14 cells （all P<0.05）， the relative mRNA expression level of HBx in exosomes （P<0.05）， and the protein expression level of HBx （P<0.05）. CTL－exo and HBV－exo were mixed at different ratios （2∶1， 5∶1， 10∶1） and were then used for the intervention of LX－2 cells， and qPCR results showed that the expression levels of TGF－β1， ɑ－SMA， and Collagen I genes in LX－2 cells gradually decreased with the increase in the ratio of CTL－exo between groups （P<0.05）. ConclusionCTL－exo can downregulate the protein expression of HBx in HBV－exo to inhibit HSC activation， suggesting that CTL－exo has an anti－hepatitis B liver fibrosis effect.

Candida albicans is one of the most common species of Candida, which is an important cause of invasive candidiasis in clinic. Due to the frequently use of classical antifungal agents, there are amounts of drug resistant C. albicans being isolated, causing the significantly decreasing of the efficacy of some antifungal agents in clinical treatment. Besides, the use of some compounds in clinic has been limited because of their toxicities. In such a context, drug combination therapy shows great potential on antifungal because of the synergy of different drugs or therapeutic methods that could bring, which could improve the weaknesses of single drug.

Objective:To explore the clinical short-term efficacy of venetoclax (Ven) combined with azacitidine (AZA) in treatment of newly treated and relapsed/refractory patients with acute myeloid leukemia (AML).Methods:The data of 18 newly treated and relapsed/refractory patients with AML who received Ven+AZA treatment in Suzhou Traditional Chinese Medicine Hospital Affiliated to Nanjing University of Chinese Medicine from April 2020 to June 2022 were retrospectively analyzed. The complete remission or complete remission with incomplete recovery of blood cell count (CR/CRi) and objective remission rate (ORR) [calculated as CR/CRi+partial remission (PR)] were analyzed in newly treated and relapsed/refractory patients or patients with different gene mutations. The patients were followed up until June 30, 2022, and the overall survival (OS) of relapsed/refractory patients was analyzed. The occurrence of adverse reactions was summarized.Results:The median age of the 18 patients was 58 years old (23-81 years old), 8 were males and 10 were females; 6 were newly treated and 12 were relapsed/refractory; the median follow-up time was 3 months (1-15 months). In 6 newly treated patients, after the first cycle of Ven+AZA, 5 cases achieved CR/CRi, and the ORR was 83.3% (5/6). In 12 relapsed/refractory patients, after the first cycle of Ven+AZA, 5 cases achieved CR/CRi, 3 achieved PR, and the ORR was 66.7% (8/12). Among the 18 patients, 7 cases had FLT3-ITD/TKD mutation, after the first cycle of Ven+AZA, 1 case achieved CR/CRi, 1 case achieved PR, and the ORR was 28.6% (2/7); 3 cases had NPM1 mutation combined with FLT3-ITD/TKD mutation, 1 case achieved CR/CRi, and the ORR was 33.3% (1/3); 4 cases had IDH1/2 mutation, and 3 cases of them combined with FLT3-ITD/TKD mutation, all of which were non-remission, and the other 1 relapsed/refractory patient combined with K/NRAS mutation achieved CR/CRi; among the 4 cases with K/NRAS mutation, 2 cases combined with FLT3-ITD/TKD mutation, including 1 case of NR and 1 case of PR, and the other 2 cases achieved CR/CRi, the ORR was 75.0% (3/4). Of the 12 relapsed/refractory patients, 6 died by the end of follow-up, with a median OS time of 2.6 months (1- 8 months), including 4 cases of disease progression and 2 cases of disease relapse; the 6 surviving patients had stable disease. All the 18 patients had ≥grade 3 hematologic adverse reactions, and non-hematologic adverse reactions included lung infection, nausea, vomiting and diarrhea.Conclusions:Ven+AZA treatment for newly treated and relapsed/refractory AML patients results in a high response rate with tolerable adverse reactions, but it is not effective in AML patients with FLT3-ITD/TKD mutation.

Objective To study the antifungal activity of N2 derivatives. Methods The anti-fungal activity of N2 compounds was investigated by micro-liquid dilution. Then the activity of N2 compounds on hyphal and biofilm formation was investigated. Results N2 compounds had significant antifungal activity against Candida albicans. It also expressed actively inhibitory effect on hyphal and biofilm formation. The mechanism of its fungicidal function was to damage the structure of candida albicans’ cell membrane and cell wall. Conclusion The results showed that N2 had obvious antifungal activity against Candida albicans., which provided a new idea for the development of antifungal drugs and the solution of antifungal drugs resistance.