BACKGROUND:In previous studies,glass materials were infiltrated into 5Y-PSZ ultra-translucent zirconia by a double sintering method to prepare 5Y-PSZ-YGI graded glass infiltrated ultra-translucent zirconia materials that can maintain high transparency and high flexural strength.OBJECTIVE:To evaluate the in vitro biocompatibility of 5Y-PSZ-YGI graded glass infiltrated ultra-translucent zirconia materials.METHODS:(1)Glass materials were infiltrated into 5Y-PSZ ultra-translucent zirconia by double sintering to prepare 5Y-PSZ-YGI graded glass infiltrated ultra-translucent zirconia.5Y-PSZ-YGI graded glass infiltrated ultra-translucent zirconia(or 5Y-PSZ ultra-translucent zirconia,3Y-TZP transparent zirconia)was placed in DMEM culture medium containing 10％fetal bovine serum for 12,24 and 72 hours,and the surface area ratio of culture medium to sample was 3 mL/cm2,and the 12-,24-and 72-hour material extracts were obtained.(2)After culturing mouse fibroblast L929 for 24 hours,the original culture medium was discarded and divided into 7 groups for culture:the control group was replaced with DMEM culture medium containing 10％fetal bovine serum by volume,and the other 6 groups were replaced with 24-hour extract of 3Y-TZP transparent zirconia,24-hour extract of 5Y-PSZ ultra-translucent zirconia,24-hour extract of 5Y-PSZ-YGI graded glass infiltrated ultra-translucent zirconia,72-hour extract of 3Y-TZP transparent zirconia,72-hour extract of 5Y-PSZ ultra-translucent zirconia,and 72-hour extract of 5Y-PSZ-YGI graded glass infiltrated ultra-translucent zirconia.After 1,3,and 5 days of culture,cell growth was observed under a microscope,and the cell proliferation rate was obtained by CCK-8 assay to determine cytotoxicity.(3)Human anticoagulated blood was mixed with 5Y-PSZ-YGI graded glass infiltrated ultra-translucent zirconia,5Y-PSZ ultra-translucent zirconia,and 3Y-TZP transparent zirconia,and the hemolysis rate was detected after 0.5 hours.Human anticoagulated blood was mixed with 12-hour extract of 3Y-TZP transparent zirconia,12-hour extract of 5Y-PSZ ultra-translucent zirconia,and 12-hour extract of 5Y-PSZ-YGI graded glass infiltrated ultra-translucent zirconia,and the hemolysis rate was detected after 0.5 hours.RESULTS AND CONCLUSION:(1)Under the microscope,it could be seen that the number of cells in each group increased with the extension of culture time,and the cell morphology of each experimental group was basically the same as that of the control group.The cytotoxicity grade of the 24-hour extract of 3Y-TZP transparent zirconia group on the first day of culture was grade 0,and the cytotoxicity grade of the other experimental groups at each time period was grade 1.(2)Neither the material nor the material extract caused obvious hemolytic reaction,and the hemolytic rate was less than 5％.(3)The results showed that 5Y-PSZ-YGI graded glass infiltrated ultra-translucent zirconia had no significant effect on the growth and proliferation of mouse fibroblasts L929,and did not cause hemolytic reaction with human blood,and had good in vitro biocompatibility.

BACKGROUND:Autophagy,as a key regulatory mechanism of cell development,plays an important role in different stages of embryonic development.The mechanism of how autophagy regulates embryonic development through histone modifications is currently unclear.OBJECTIVE:To investigate the effect of autophagy on trimethylation of lysine 4 on histone H3(H3K4me3)modification in embryos and its effect on embryonic development.METHODS:Mouse fertilized eggs were divided into control and autophagy inhibitor-treated groups(chloroquine phosphate-treated group and 3-methyladenine-treated group),and cultured in vitro to different periods of time,and were then classified as early 2-cell embryos,middle 2-cell embryos,late 2-cell embryos,4-cell embryos,8-cell embryos,morula stage,and blastocyst stage.Levels of reactive oxygen species,autophagy marker proteins LC3B and P62,DNA loss marker γH2AX,and H3K4me3 were analyzed by immunofluorescence assay in late 2-cell embryos of each group.Changes in H3K4me3 modification in late 2-cell embryos of each group were detected by CUT&Tag.RESULTS AND CONCLUSION:(1)Autophagy inhibition caused embryo development arrest.(2)There was no significant difference in reactive oxygen species and γH2AX between the autophagy inhibitor-treated groups and control group.(3)H3K4me3 levels were significantly elevated in the autophagy inhibitor-treated group compared with the control group.(4)CUT&Tag results showed a significantly increased H3K4me3 peaks on the proximal promoter region of the genes after autophagy inhibition and an increase of H3K4me3-specific modification genes.These findings suggest that autophagy may affect embryonic development by regulating the level of H3K4me3 modification.

The prescription of Qidong Yixin oral liquid is derived from the experience of national medical master Ren Jixue in treating viral myocarditis （VMC）. It has the functions of tonifying Qi， nourishing the heart，calming the mind， and relieving palpitations. It is used to treat VMC and angina pectoris of coronary heart disease caused by deficiency of both Qi and Yin. However，the understanding of its efficacy evidence， advantageous aspects， dosage and administration， and medication safety remains insufficient in clinical practice. Therefore，the development of the Expert Consensus on the Clinical Application of Qidong Yixin Oral Liquid （hereinafter referred to as consensus） was initiated. Consensus strictly followed the process and methods of the expert consensus on the clinical application of Chinese patent medicines of the China Association of Chinese Medicine，successively completing multiple tasks such as the consensus project initiation，determination of clinical problems，evidence search and evaluation，formation of recommendation opinions and consensus suggestions，solicitation of opinions，peer review， submission for review and release， and so on. Consensus formed a total of 10 recommendation opinions and 12 consensus suggestions，clarifying the clinical positioning，efficacy advantages，syndrome differentiation，dosage and administration，combination therapy，timing of medication，adverse reactions，contraindications， and precautions of Qidong Yixin oral liquid，indicating that it has good clinical advantages and safety in the treatment of VMC and angina pectoris of coronary heart disease，providing norms and references for physicians to safely and rationally apply Qidong Yixin oral liquid. Consensus was reviewed and approved for release by the Standardization Office of the China Association of Chinese Medicine on December 23， 2024. Standard number：GSCACM-376-2024.

Objective To summarize and analyze the efficacy and influencing factors of second allogeneic hematopoietic stem cell transplantation (allo-HSCT) for acute leukemia relapsing after the first allo-HSCT. Methods Clinical data of 17 patients with acute leukemia who underwent second allo-HSCT at Peking University First Hospital from January 2005 to December 2024 were retrospectively analyzed. Results Among the 17 patients, 7 achieved long-term disease-free survival after second transplantation. The median progression-free survival after successful second transplantation was 7 months (range 8 days to 69 months). The relapse fatality was 24%, and the transplant-related fatality was 35%. Conclusions Second transplantation is an effective treatment for relapsed and refractory acute leukemia, but the relapse fatality and transplant-related fatality remain high. Patient age, time of relapse after the first transplantation and disease status before second transplantation are all factors that affect the efficacy of second transplantation. Younger age, late relapse and complete remission of disease before second transplantation are all beneficial for long-term disease-free survival after second transplantation.

BACKGROUND:In previous studies,glass materials were infiltrated into 5Y-PSZ ultra-translucent zirconia by a double sintering method to prepare 5Y-PSZ-YGI graded glass infiltrated ultra-translucent zirconia materials that can maintain high transparency and high flexural strength.OBJECTIVE:To evaluate the in vitro biocompatibility of 5Y-PSZ-YGI graded glass infiltrated ultra-translucent zirconia materials.METHODS:(1)Glass materials were infiltrated into 5Y-PSZ ultra-translucent zirconia by double sintering to prepare 5Y-PSZ-YGI graded glass infiltrated ultra-translucent zirconia.5Y-PSZ-YGI graded glass infiltrated ultra-translucent zirconia(or 5Y-PSZ ultra-translucent zirconia,3Y-TZP transparent zirconia)was placed in DMEM culture medium containing 10％fetal bovine serum for 12,24 and 72 hours,and the surface area ratio of culture medium to sample was 3 mL/cm2,and the 12-,24-and 72-hour material extracts were obtained.(2)After culturing mouse fibroblast L929 for 24 hours,the original culture medium was discarded and divided into 7 groups for culture:the control group was replaced with DMEM culture medium containing 10％fetal bovine serum by volume,and the other 6 groups were replaced with 24-hour extract of 3Y-TZP transparent zirconia,24-hour extract of 5Y-PSZ ultra-translucent zirconia,24-hour extract of 5Y-PSZ-YGI graded glass infiltrated ultra-translucent zirconia,72-hour extract of 3Y-TZP transparent zirconia,72-hour extract of 5Y-PSZ ultra-translucent zirconia,and 72-hour extract of 5Y-PSZ-YGI graded glass infiltrated ultra-translucent zirconia.After 1,3,and 5 days of culture,cell growth was observed under a microscope,and the cell proliferation rate was obtained by CCK-8 assay to determine cytotoxicity.(3)Human anticoagulated blood was mixed with 5Y-PSZ-YGI graded glass infiltrated ultra-translucent zirconia,5Y-PSZ ultra-translucent zirconia,and 3Y-TZP transparent zirconia,and the hemolysis rate was detected after 0.5 hours.Human anticoagulated blood was mixed with 12-hour extract of 3Y-TZP transparent zirconia,12-hour extract of 5Y-PSZ ultra-translucent zirconia,and 12-hour extract of 5Y-PSZ-YGI graded glass infiltrated ultra-translucent zirconia,and the hemolysis rate was detected after 0.5 hours.RESULTS AND CONCLUSION:(1)Under the microscope,it could be seen that the number of cells in each group increased with the extension of culture time,and the cell morphology of each experimental group was basically the same as that of the control group.The cytotoxicity grade of the 24-hour extract of 3Y-TZP transparent zirconia group on the first day of culture was grade 0,and the cytotoxicity grade of the other experimental groups at each time period was grade 1.(2)Neither the material nor the material extract caused obvious hemolytic reaction,and the hemolytic rate was less than 5％.(3)The results showed that 5Y-PSZ-YGI graded glass infiltrated ultra-translucent zirconia had no significant effect on the growth and proliferation of mouse fibroblasts L929,and did not cause hemolytic reaction with human blood,and had good in vitro biocompatibility.

BACKGROUND:Autophagy,as a key regulatory mechanism of cell development,plays an important role in different stages of embryonic development.The mechanism of how autophagy regulates embryonic development through histone modifications is currently unclear.OBJECTIVE:To investigate the effect of autophagy on trimethylation of lysine 4 on histone H3(H3K4me3)modification in embryos and its effect on embryonic development.METHODS:Mouse fertilized eggs were divided into control and autophagy inhibitor-treated groups(chloroquine phosphate-treated group and 3-methyladenine-treated group),and cultured in vitro to different periods of time,and were then classified as early 2-cell embryos,middle 2-cell embryos,late 2-cell embryos,4-cell embryos,8-cell embryos,morula stage,and blastocyst stage.Levels of reactive oxygen species,autophagy marker proteins LC3B and P62,DNA loss marker γH2AX,and H3K4me3 were analyzed by immunofluorescence assay in late 2-cell embryos of each group.Changes in H3K4me3 modification in late 2-cell embryos of each group were detected by CUT&Tag.RESULTS AND CONCLUSION:(1)Autophagy inhibition caused embryo development arrest.(2)There was no significant difference in reactive oxygen species and γH2AX between the autophagy inhibitor-treated groups and control group.(3)H3K4me3 levels were significantly elevated in the autophagy inhibitor-treated group compared with the control group.(4)CUT&Tag results showed a significantly increased H3K4me3 peaks on the proximal promoter region of the genes after autophagy inhibition and an increase of H3K4me3-specific modification genes.These findings suggest that autophagy may affect embryonic development by regulating the level of H3K4me3 modification.

Background/Aims: Liver transplantation (LT) following total hepatectomy is a life-saving treatment for hepatocellular carcinoma (HCC). The HCC recurrence after LT hinders the effectiveness of the procedure. The objective of this study is to develop a pre-operative risk stratification model based on a liquid biopsy. Methods: We conducted a comprehensive multi-omics study of 260 HCC patients from three centers, including clinical data, low-coverage whole-genome sequencing of cell-free DNA (cfDNA) from plasma, as well as whole-exome, single-nucleus RNA, and spatial transcriptomics from matched tumor and non-tumor tissues. Results: We identified cfDNA-derived copy number alteration (CNA) signatures associated with post-transplant recurrence. By integrating cfDNA-derived CNA profiles with single-cell transcriptomic data, we traced recurrence-associated cfDNA to a distinct subpopulation of malignant cells within the primary tumor. These cells were embedded in a pro-metastatic microenvironment of specialized endothelial subtypes and cancer-associated fibroblasts. Notably, most recurrence-associated lesions were detectable in cfDNA prior to liver transplantation (LT). Building on these insights, we developed the ZJU Criteria based on CNA fragments and tumor markers, a pre-LT risk prediction tool that integrates conventional clinical factors with cfDNA-derived CNA signatures, and validated it using internal and independent external cohorts. Conclusion Our findings suggest that post-transplant recurrence commonly originates from advanced subclones that emerge late during tumor evolution. The ZJU Criteria provides an accurate, non-invasive strategy that significantly improves pre-LT risk stratification and clinical decision-making for patients with HCC.

This study investigated the influence of Leptospira interrogans infection on the expression of the autophagy-related proteinsmyosin-like BCL2 interacting protein(Beclin-1),microtubule-associated proteinlight chain 3B(LC3B),and sequestosome 1(P62).C3H/HeJ mice were infected with L.interrogansserovar stain Lai for construction of an animal model of leptospirosis.Silver strain-ing was used to detect leptospires in lung,liver,and kidney tissues of L.interrogans-infected mice.Histological changes in these tis-sues were detected with hematoxylin and eosin(HE)staining.The morphology of autophagosomes and leptospires in the lung,liver,and kidney tissues of L.interrogans-infected micewere determined through transmission electron microscopy.Expression of the autophagy-related proteins Beclin-1,LC3B,and P62 in the lung,liver,and kidney tissues of L.interrogans-infected C3H/HeJ mice was measured with immunohistochemistry.In these tissues,silver straining examination revealed leptospires.These tissues also showed histopathological changes typical of leptospirosis,such as pulmonary hemorrhage,extensive hepatocyte necrosis,both glomerular and tubular necrosis,and inflammatory cell infiltration;moreover,the leptospires were surrounded by autophagosomes.Immunohistochemi-cal examination indicated elevated expression of both Beclin-1 and LC3B in the lung,liver and kidney tissues of L.interrogans-infected mice(P<0.05),whereas the P62 level was significantly diminished in every tissue sample during L.interrogans infection(P<0.05).These results indicated that autophagy is activated during L.interrogans infection in the lung,liver,and kidney tissues of C3H/HeJ mice.

Aim To explore the compatibility and po-tential mechanism of effective components of Biejia-Ezhu against triple negative breast cancer(TNBC)and verify it by experiments.Methods Effective compo-nents and targets of Biejia-Ezhu were obtained by TC-MSP and Swiss Target Prediction.Disease targets of TNBC were obtained from OMMI and GeneCards data-bases.The PPI network was constructed using STRING database.GO and KEGG path enrichment analysis was performed using DAVID database.Cytoscape3.9.1 software was used to construct the"drug-component-target-disease"network,screen key targets and compo-nents for molecular docking,and further verify the com-patibility of key components and targets in vitro.Re-sults ① A total of 71 effective components were iden-tified in the Biejia-Ezhu drug pair.There were 146 drug targets associated with the disease.A total of 113 signaling pathways were identified by KEGG analysis.The 71 potential active components of Biejia-Ezhu mainly acted on key targets such as mTORC1,ULK1,TNF,EGFR,ESR1,STAT3,HIF1A,and PTGS2.Mo-lecular docking results showed that glycine and curcu-min were the key active components of Biejia-Ezhu,and both had strong docking activity against key target proteins mTORC1 and ULK1.②The results of in vitro experiment showed that glycine combined with curcu-min significantly inhibited the proliferation and clonal formation ability of TNBC cells(P＜0.05),up-regula-ted the expression of autophagy marker LC3 Ⅱ/Ⅰ,down-regulated the expression of EGFR,down-regula-ted the expression of pathway protein mTORC1,p-mTOR,p-ULK1,and promoted the expression of path-way protein ULK1(P＜0.05).Conclusion The key component of Biejia-Ezhu against triple-negative breast cancer is glycine-curcumin,the mechanism of which may be related to the regulation of the mTORC1/ULK1 signaling pathway to promote autophagy.

Objective:To explore the potential categories and influencing factors of medication compliance in patients with cardiometabolic multimorbidity, and provide a reference for formulating targeted intervention measures.Methods:A cross-sectional study design was adopted. From March to October 2024, the patients with cardiometabolic multimorbidity in the First Hospital Affiliated with Hunan Normal University (Hunan Provincial People′s Hospital) were selected by convenience sampling method as research objects. Data were collected using a general information questionnaire, Medication Adherence Rating Scale (MARS), Perceived Social Support Scale (PSSS), and Medication Literacy Questionnaire. The latent class analysis was used to explore the characteristics and classifications of medication compliance in cardiometabolic multimorbidity, and unordered multivariate Logistic regression was used to analyze the influencing factors of different latent classes.Results:A total of 421 subjects were included, consisting of 291 males and 130 females, aged (64.28±9.74) years old. The overall medication adherence score was 6.00 (5.00, 8.00) points, which could be divided into four categories: overall good adherence group (24.47%, 103/421), subjective perception-poor adherence group (15.91%, 67/421), forgetfulness-poor adherence group (37.53%, 158/421), and overall poor adherence group (22.09%, 93/421). The results showed that when taking the overall good adherence group as a reference, the inability to obtain pharmaceutical information from social media, medication literacy scores, social support scores were the influencing factors for the subjective perception-poor adherence group ( OR=4.210, 0.516, 0.733, all P<0.05). Occupational characteristics (employees in public institutions or government-affiliated institutions), age, social support scores were the influencing factors for the forgetfulness-poor adherence group( OR=0.173, 1.155, 0.781, all P<0.05). Occupational characteristics (employees in public institutions or government-affiliated institutions), failure to receive medication guidance from medical staff, medication literacy scores and social support scores were the influencing factors for the overall poor adherence group( OR values were 0.136-5.275, all P<0.05). When taking the overall poor adherence group as a reference, failure to receive medication guidance from medical staff and medication literacy scores were the influencing factors for the subjective perception-poor adherence group ( OR=0.310, 1.752, both P<0.05). Failure to receive medication guidance from medical staff, age, medication literacy scores and social support scores were the influencing factors for the forgetfulness-poor adherence group ( OR values were 0.315-2.554, all P<0.05). Conclusions:There is significant heterogeneity in medication adherence among patients with cardiometabolic multimorbidity. Healthcare professionals should consider individual characteristics in clinical practice and provide targeted, precise interventions to improve adherence in different patient categories.