To explore the advantages of traditional Chinese medicine （TCM） and integrative TCM-Western medicine approaches in the treatment of diabetic microvascular complications （DMC）， refine key pathophysiological insights and treatment principles， and promote academic innovation and strategic research planning in the prevention and treatment of DMC. The 38th session of the Expert Salon on Diseases Responding Specifically to Traditional Chinese Medicine， hosted by the China Association of Chinese Medicine， was held in Beijing， 2024. Experts in TCM， Western medicine， and interdisciplinary fields convened to conduct a systematic discussion on the pathogenesis， diagnostic and treatment challenges， and mechanism research related to DMC， ultimately forming a consensus on key directions. Four major research recommendations were proposed. The first is addressing clinical bottlenecks in the prevention and control of DMC by optimizing TCM-based evidence evaluation systems. The second is refining TCM core pathogenesis across DMC stages and establishing corresponding "disease-pattern-time" framework. The third is innovating mechanism research strategies to facilitate a shift from holistic regulation to targeted intervention in TCM. The fourth is advancing interdisciplinary collaboration to enhance the role of TCM in new drug development， research prioritization， and guideline formulation. TCM and integrative approaches offer distinct advantages in managing DMC. With a focus on the diseases responding specifically to TCM， strengthening evidence-based support and mechanism interpretation and promoting the integration of clinical care and research innovation will provide strong momentum for the modernization of TCM and the advancement of national health strategies.

With the rapid development of generative artificial intelligence(GAI)technologies,their widespread application in academic research and writing is continuously expanding the boundaries of sci-entific inquiry.However,this trend has also raised a series of ethical and regulatory challenges,inclu-ding issues related to authorship,content authenticity,citation accuracy,and accountability.In light of the growing involvement of AI in generating academic content,establishing an open,controllable,and trustworthy ethical governance framework has become a key task for safeguarding research integrity and maintaining trust within the academic community.This expert consensus outlines ethical requirements across key stages of AI-assisted academic writing-including topic selection,data management,citation practices,and authorship attribution.It aims to clarify the boundaries and ethical obligations surrounding AI use in academic writing,ensuring that technological tools enhance efficiency without compromising in-tegrity.The goal is to provide guidance and institutional support for building a responsible and sustainable research ecosystem.

Hepatocellular carcinoma(HCC)is difficult to detect in its early stages and current treatment methods are associated with significant side effects and a high risk of developing drug resistance.This study aims to investigate the effect of phycocyanin(PC)on the apoptosis of human HCC HepG2 cells and its potential mechanism.HepG2 cells were treated with PC at concentrations of 0.1,0.25,0.5,1,2.5,5,and 10 μg/mL for 12 h,and with 10 μg/mL PC and 2.5 μmol/L Wip1 inhibitor(Wip1i)alone or in combination for 12 and 24 h,respectively.Cell proliferation levels were assessed using the CCK-8 cell proliferation-toxicity assay kit.Apoptosis levels were measured by Annexin V-FITC/Propidium Iodide double staining combined with flow cytometry.TMT(Tandem Mass Tag)proteomics quantitative technol-ogy was applied to analyze differential protein expression.Western blotting was used to detect the expres-sion levels of Wip1,p53,and phosphorylated-p53(Ser15)proteins.The CCK-8 assay revealed that PC effectively inhibited HepG2 cell proliferation in a concentration-dependent manner,with a half-maximal inhibitory concentration(IC50)of 19.37 μg/mL.Flow cytometry results showed that PC significantly in-duced apoptosis,with an apoptosis rate of 30.40％.Quantitative proteomics analysis indicated that PC induced activation of the p53 pathway.The CCK-8 assay showed that Wip1i enhanced the cytotoxic effect of PC on HepG2 cells.Western blotting confirmed that PC inhibited Wip1 expression,induced p53 pro-tein phosphorylation,and promoted the expression of total p53 protein.Additionally,Wip1i further en-hanced PC-mediated activation of the p53 pathway,increasing the expression of p53 and pP53(S15).In conclusion,PC may induce apoptosis by inhibiting the activity of the p53 negative regulator Wip1,thereby promoting apoptosis through the Wip1/p53 pathway.

This study investigated the potential pathogenicity and genetic characteristics of ST314 Salmonella Kentucky(S.Ken-tucky)isolates from a broiler slaughterhouse.Antimicrobial susceptibility testing and whole-genome sequencing(WGS)were used to determine antimicrobial resistance,virulence factors,and the presence of antimicrobial resistance genes(ARGs)and mobile genetic elements(MGEs)among the isolates.The three multidrug resistant(MDR)isolates exhibited high resistance to multiple antimicrobial agents.The F4-2S strain exhibited resistance to 14 drugs across seven categories,whereas the F4T strain showed resistance to 13 drugs in the same number of categories.In contrast,the Y23 strain was resistant to nine drugs in six categories.Notably,F4-2S dem-onstrated high homology with F4T:both possessed 13 ARGs distributed across nine categories,in addition to a wide range of virulence factors,including secretion systems and effector proteins.The presence of IncR and IncX1 plasmids significantly enhanced both the antimicrobial resistance and pathogenicity of the isolates.The genome map of Y23 revealed a chromosome alongside two plasmids.The chromosome containedonly one resistance gene but several virulence factors,including the type III secretion system(T3SS),which is crucial for bacterial invasion.The plasmid pY23-1 contained eight types of 19 ARGs.Comparative analysis indicated that pY23-1 ex-hibited high homology with pZ1323SSL0055 and pSAL-045,all of which contained multiple ARGs,thus suggesting critical roles of these genes in the evolution of bacterial resistance.In conclusion,ST314 S.Kentucky demonstrated a complex mechanism of resis-tance coupled with significant pathogenic potential.The ARGs and MGEs in the plasmid contributed to the emergence and dissemina-tion of antimicrobial resistance.The multiple virulence factors present in the chromosome may be key factors driving the increasing virulence of ST314 S.Kentucky.

Aim To study the effect of evodiamine(EVO)regulating forkhead box protein Ml(FOXM1)on the proliferation and apoptosis of colorectal cancer-resistant cells HCT8/5-FU.Methods CCK-8 assay and EdU assay were used to detect the effect of EVO on cell proliferation ability.Clone formation assay was employed to detect the effect of EVO on the clone for-mation ability of cells.Flow cytometric counting was applied to detect apoptosis.Western blot was utilized to detect the expression of cellular Bcl-2,Bax,FOXM1,β-catenin,c-MYC,and CyclinD1;Molecular docking was used to explore the EVO-FOXM1 interac-tion.Nude mouse transplant tumor model was estab-lished to validate the effect of EVO on HCT8/5-FU cells in vivo.Results CCK-8 assay showed that EVO inhibited the proliferation of HCT8/5-FU cells in a time-and concentration-dependent manner.EdU assay found that the newly proliferated cells in the EVO-trea-ted group were significantly reduced.The results of the clone formation assay showed that EVO inhibited the clone-forming ability of HCT8/5-FU cells.Flow cyto-metric counting found that apoptosis rate of the cells in the EVO group significantly increased.Western blot showed that FOXM1 and β-catenin were significantly highly expressed in HCT8/5-FU cells,and EVO down-regulated the expression of FOXM1,β-cateniin,c-MYC,CyclinD1,and Bcl-2,and up-regulated the ex-pression of Bax.Molecular docking revealed strong in-teractions between EVO and FOXM1.The in vivo ex-perimental results demonstrated that EVO exerted a substantial inhibitory effect on the growth of subcutane-ously implanted HCT8/5-FU xenograft tumors and regulated the expression of related proteins.HE stai-ning revealed significant nuclear consolidation and fragmentation of tumor cells in the EVO group.Con-clusions The findings suggest that EVO could sup-press the activation of the Wnt signaling pathway through a mechanism involving the downregulation of FOXM1 protein expression,thus inhibiting the prolifer-ation of HCT8/5-FU cells and induce their apoptosis.

Aim To study the therapeutic effect of al-licin on senna-induced diarrhea in mice and to explore the underlying mechanism.Methods Forty-eight C57BL/6J mice were randomly divided into six groups:control,model,loperamide positive control group(2 mg·kg-1),allicin low-dose group(6 mg·kg-1),allicin medium-dose group(12 mg·kg-1)and allicin high-dose group(18 mg·kg-1).Except for the con-trol group,the diarrhea model was induced in the other groups by intragastric administration of senna leaf ex-tract.After drug administration,several diarrhea indi-ces were measured:the rate of loose stools,diarrhea index,accumulated frequency of loose stools at differ-ent time points within 5 hours,and small intestine pro-pelling rate.Serum levels of TNF-α and IL-6 were de-tected by ELISA.Serum NO content was determined u-sing the Griess method.The activities of SOD and CAT,as well as MDA content in the ileum and colon,were measured.The pathological changes and the ex-pression of mRNA related to intestinal barrier proteins in the ileum and colon were evaluated using HE stai-ning and RT-qPCR.Results Allicin improved diar-rhea symptoms in mice induced by senna leaf.It re-duced the rate of loose stools,diarrhea index,cumula-tive number of loose stools in five hours,and the intes-tinal propulsion rate.Allicin also protected the intesti-nal mucosa,decreased serum TNF-α and IL-6 levels,and lowered MDA content in the intestines.It in-creased serum NO levels and enhanced SOD and CAT activities in the intestines.Additionally,allicin upreg-ulated the mRNA expression of AQP1,AQP4,and ZO-1 in intestinal tissues.Conclusions Allicin has a significant therapeutic effect on senna-induced diarrhea in mice.The underlying molecular mechanisms may involve anti-inflammatory and antioxidant effects,in-creased NO content,and upregulation of mRNA ex-pression of aquaporins and tight-junction proteins.

Acute lung injury (ALI) is a severe disease caused by viral infection that triggers an uncontrolled inflammatory response. This study investigated the capacity of jasurolignoside (JO), a natural compound, to bind to Toll-like receptor 4 (TLR4) and treat ALI. The anti-inflammatory properties of JO were evaluated in vitro through Western blotting, enzyme-linked immunosorbent assay (ELISA), immunofluorescence staining, and co-immunoprecipitation. The investigation utilized a lipopolysaccharide (LPS)-induced ALI animal model to examine the therapeutic efficacy and mechanism of JO in vivo. JO attenuated inflammatory symptoms in infected cells and tissues by modulating the NOD-like receptor family pyrin domain containing protein 3 (NLRP3) inflammasome and the nuclear factor κB (NF-κB)/mitogen-activated protein kinase (MAPK) pathway. Molecular docking simulations revealed JO binding to TLR4 active sites, confirmed by cellular thermal shift assay. Surface plasmon resonance (SPR) demonstrated direct interaction between JO and TLR4 with a Kd value of 35.1 μmol·L^-1. Moreover, JO inhibited tumor necrosis factor α (TNF-α), interleukin-1β (IL-1β), and IL-6 secretion and reduced leukocyte, neutrophil, lymphocyte, and macrophage infiltration in ALI-affected mice. JO also enhanced lung function and reduced ALI-related mortality. Immunohistochemical staining demonstrated JO's ability to suppress TLR4 expression in ALI-affected mouse lung tissue. This study establishes that JO can bind to TLR4 and effectively treat ALI, indicating its potential as a therapeutic agent for clinical applications.
Toll-Like Receptor 4/chemistry* ; Animals ; Acute Lung Injury/chemically induced* ; Mice ; Humans ; Ilex/chemistry* ; Molecular Docking Simulation ; Male ; NF-kappa B/immunology* ; Mice, Inbred C57BL ; NLR Family, Pyrin Domain-Containing 3 Protein/immunology* ; Tumor Necrosis Factor-alpha/genetics* ; Interleukin-1beta/genetics* ; RAW 264.7 Cells ; Disease Models, Animal

This study delves into the mechanism of total flavone of Abelmoschus manihot(TFA) in treating ulcerative colitis(UC) and depression via inhibiting M1 polarization of macrophages and reshaping intestinal flora and glycerolphospholipid metabolism. The study established a mouse model of UC and depression induced by chronic restraint stress(CRS) and dextran sulfate sodium(DSS). The fecal microbiota transplantation(FMT) experiment after TFA intervention was conducted. Mice in the FMT donor group were modeled and treated, and fecal samples were taken to prepare the bacterial solution. Mice in the FMT receptor group were treated with antibiotic intervention, and then administered bacterial solution by gavage from mice in the donor group, followed by UC depression modeling. After the experiment, behavioral tests were conducted to evaluate depressive-like behaviors by measuring the levels of 5-hydroxytryptamine(5-HT) and brain-derived neurotrophic factor(BDNF) in the hippocampus of mice. The levels of tumor necrosis factor-α(TNF-α),interleukin-6(IL-6),and interleukin-1β(IL-1β)in the brain and colon tissue of mice were also measured, and the polarization status of macrophages was evaluated by measuring the mRNA levels of CD86 and CD206. 16S ribosomal RNA(16S rRNA) sequencing technology was used to analyze changes in the intestinal flora of mice. Wide target lipidomics was used to detect serum lipid metabolite levels in mice after FMT,and correlation analysis was conducted between lipids and differential intestinal flora significantly regulated by TFA. In vitro experiments, representative glycerophospholipid metabolites and glycerophospholipid inhibitors were used to intervene in Raw264.7 macrophages, and the mRNA levels of TNF-α,IL-6,IL-1β,CD86,and CD206 were detected. The results showed that TFA and FMT after intervention could significantly improve depressive-like behavior and intestinal inflammation in mice with UC and depression, significantly downregulate pro-inflammatory cytokines and CD86 mRNA expression in brain and colon tissue, inhibiting M1 polarization of macrophages, and significantly upregulate CD206 mRNA expression, promoting M2 polarization of macrophages. In addition, the high-dose group had a more significant effect. After TFA intervention, FMT significantly corrected the metabolic disorder of glycerophospholipids in mice with UC and depression, and there was a significant correlation between differential intestinal flora and glycerophospholipids. In vitro experiments showed that glycerophospholipid metabolites, especially lysophosphatidylcholine(LPC),significantly upregulated pro-inflammatory cytokines and CD86 mRNA expression, promote M1 polarization of macrophages, while glycerophospholipid inhibitors had the opposite effect. The results indicate that TFA effectively treats depression and UC by correcting intestinal flora dysbiosis and reshaping glycerophospholipid metabolism, thereby inhibiting M1 polarization of macrophages.
Animals ; Mice ; Gastrointestinal Microbiome/drug effects* ; Abelmoschus/chemistry* ; Macrophages/metabolism* ; Colitis, Ulcerative/immunology* ; Flavones/administration & dosage* ; Male ; Depression/genetics* ; Glycerophospholipids/metabolism* ; Humans ; Drugs, Chinese Herbal/administration & dosage* ; Mice, Inbred C57BL

OBJECTIVES: To assess the preliminary efficacy and safety of a dose-intensified C5VD regimen (cisplatin, 5-fluorouracil, vincristine, and doxorubicin) in children with locally advanced hepatoblastoma. METHODS: This prospective study enrolled 24 children with newly diagnosed, locally advanced hepatoblastoma who received the dose-intensified C5VD regimen at Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine, and Shanghai Children's Hospital between January 2020 and December 2023. Clinical characteristics, treatment outcomes, and chemotherapy-related toxicities were analyzed. RESULTS: Of the 24 patients, 13 were male and 11 were female, with a median age at diagnosis of 18.7 months (range: 3.5-79.4 months). All patients achieved complete macroscopic resection of hepatic lesions without liver transplantation. Serum alpha-fetoprotein levels decreased significantly after two chemotherapy cycles. During a median follow-up of 38.4 months (range: 15.8-50.7 months), all patients maintained continuous complete remission, with 3-year event-free survival and overall survival rates of 100%. Across 144 chemotherapy cycles, the incidence rates of grade 3-4 neutropenia, thrombocytopenia, and infections were 97%, 77%, and 71%, respectively; no treatment-related deaths occurred. Notably, 5 patients (21%) developed Brock grade ≥3 hearing loss, of whom 1 required a hearing aid. CONCLUSIONS The dose-intensified C5VD regimen demonstrates significant efficacy with an overall favorable safety profile in the treatment of newly diagnosed, locally advanced pediatric hepatoblastoma. Grade 3-4 myelosuppression and infection are the predominant toxicities. However, high‑dose cisplatin-induced ototoxicity remains a concern, highlighting the need for improved otoprotective strategies.
Humans ; Hepatoblastoma/pathology* ; Male ; Female ; Infant ; Liver Neoplasms/pathology* ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Child, Preschool ; Prospective Studies ; Doxorubicin/adverse effects* ; Child ; Cisplatin/adverse effects* ; Vincristine/adverse effects* ; Fluorouracil/adverse effects*

OBJECTIVE: To analyze the correlation between baseline ¹⁸F-fluorodeoxyglucose positron emission tomography/computed tomography (¹⁸F-FDG PET/CT) and circulating tumor DNA (ctDNA) parameters in diffuse large B-cell lymphoma (DLBCL) and compare the value of the two methods in the prognosis assessment of DLBCL. METHODS: A total of 50 DLBCL patients confirmed by pathology, including 26 males and 24 females, with a median age of 55.5(43.5, 64.0) years from August 2018 to April 2021 were retrospectively analyzed. PET/CT parameters, including maximum standardized uptake value (SUVmax), metabolic tumor volume (MTV), total lesion glycolysis (TLG), ctDNA parameters, including mutation number, mutation gene number, mean variant allele frequency (meanVAF), and clinical data of patients were collected. The relationship between PET/CT, ctDNA parameters and patient clinical features was analyzed, as well as the correlation between PET/CT and ctDNA parameters. The diagnostic efficacy of PET/CT and ctDNA parameters was compared. Patients were followed up for 36-69 months. Progression-free survival (PFS) was calculated, and survival analysis was performed. RESULTS: PET/CT parameters all had good correlation with ctDNA parameters, among which MTV was moderately correlated with mutation number, mutation gene number, and meanVAF (r_s=0.72, 0.64, 0.71), TLG was strongly correlated with mutation number (r_s=0.83) and moderately correlated with mutation gene number and mean VAF (r_s=0.72, 0.79), while SUVmax was weakly correlated with mutation number, mutation gene number and meanVAF (r_s=0.47, 0.46, 0.47). PET/CT parameters and ctDNA parameters showed no statistically significant differences in predicting the prognosis of DLBCL and area under the curve (AUC) of receiver operating characteristic (ROC) (P >0.05). However, the specificity of MTV and TLG in predicting prognosis of 1-, 2- and 3-year PFS was better than that of meanVAF (all P < 0.05), while the sensitivity of meanVAF in predicting prognosis of 1-, 2- and 3-year PFS was better than that of MTV (all P < 0.05). The optimal cut-off values of SUVmax, MTV, TLG, mutation number, mutation gene number and meanVAF in predicting tumor progression were obtained using ROC curve analysis. Patients were divided into high and low expression groups according to the cut-off values and survival analysis was performed. The results of survival analysis showed that there were statistically significant differences in PFS between the high and low expression groups (all P < 0.05). CONCLUSION Baseline ¹⁸F-FDG PET/CT and ctDNA parameters can both predict the prognosis of DLBCL, and are equally valuable in the evaluation of DLBCL prognosis.
Humans ; Lymphoma, Large B-Cell, Diffuse/diagnosis* ; Positron Emission Tomography Computed Tomography ; Fluorodeoxyglucose F18 ; Middle Aged ; Prognosis ; Female ; Male ; Circulating Tumor DNA ; Retrospective Studies ; Adult ; Mutation