Chronic, unresolved inflammation correlates with persistent hepatic injury and fibrosis, ultimately progressing to hepatocellular carcinoma (HCC). Bisdemethoxycurcumin (BDMC) demonstrates therapeutic potential against HCC, yet its mechanism in preventing hepatic "inflammation-carcinoma transformation" remains incompletely understood. In the current research, clinical HCC specimens underwent analysis using hematoxylin-eosin (H&E) staining and immunohistochemistry (IHC) to evaluate the expression of fibrosis markers, M2 macrophage markers, and CXCL12. In vitro, transforming growth factor-β1 (TGF-β1)-induced LX-2 cells and a co-culture system of LX-2, THP-1, and HCC cells were established. Cell functions underwent assessment through 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), flow cytometry, and Transwell assays. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR), Western blotting and immunofluorescence evaluated the differential expression of molecules. The interaction between β-catenin/TCF4 and CXCL12 was examined using co-immunoprecipitation (Co-IP), dual luciferase, and chromatin immunoprecipitation (ChIP) assays. A DEN-induced rat model was developed to investigate BDMC's role in liver fibrosis-associated HCC (LFAHCC) development in vivo. Our results showed that clinical HCC tissues exhibited elevated fibrosis and enriched M2 macrophages. BDMC delayed liver fibrosis progression to HCC in vivo. BDMC inhibited the inflammatory microenvironment induced by activated hepatic stellate cells (HSCs). Furthermore, BDMC suppressed M2 macrophage-induced fibrosis and HCC cell proliferation and metastasis. Mechanistically, BDMC repressed TCF4/β-catenin complex formation, thereby reducing CXCL12 transcription in LX-2 cells. Moreover, CXCL12 overexpression reversed BDMC's inhibitory effect on macrophage M2 polarization and its mediation of fibrosis, as well as HCC proliferation and metastasis. BDMC significantly suppressed LFAHCC development through CXCL12 in rats. In conclusion, BDMC inhibited LFAHCC progression by reducing M2 macrophage polarization through suppressing β-catenin/TCF4-mediated CXCL12 transcription.
Animals ; Liver Neoplasms/etiology* ; Humans ; Carcinoma, Hepatocellular/immunology* ; Liver Cirrhosis/complications* ; Macrophages/drug effects* ; Male ; Rats ; Chemokine CXCL12/genetics* ; Diarylheptanoids/pharmacology* ; Rats, Sprague-Dawley ; beta Catenin/genetics*

Extensive epigenetic reprogramming involves in memory CD8+ T-cell differentiation. The elaborate epigenetic rewiring underlying the heterogeneous functional states of CD8+ T cells remains hidden. Here, we profile single-cell chromatin accessibility and map enhancer-promoter interactomes to characterize the differentiation trajectory of memory CD8+ T cells. We reveal that under distinct epigenetic regulations, the early activated CD8+ T cells divergently originated for short-lived effector and memory precursor effector cells. We also uncover a defined epigenetic rewiring leading to the conversion from effector memory to central memory cells during memory formation. Additionally, we illustrate chromatin regulatory mechanisms underlying long-lasting versus transient transcription regulation during memory differentiation. Finally, we confirm the essential roles of Sox4 and Nrf2 in developing memory precursor effector and effector memory cells, respectively, and validate cell state-specific enhancers in regulating Il7r using CRISPR-Cas9. Our data pave the way for understanding the mechanism underlying epigenetic memory formation in CD8+ T-cell differentiation.
CD8-Positive T-Lymphocytes/metabolism* ; Cell Differentiation ; Chromatin/immunology* ; Animals ; Mice ; Immunologic Memory ; Epigenesis, Genetic ; SOXC Transcription Factors/immunology* ; NF-E2-Related Factor 2/immunology* ; Mice, Inbred C57BL ; Gene Regulatory Networks ; Enhancer Elements, Genetic

Ivonescimab is a humanized bispecific antibody targeting human vascular endothelial growth factor-A(VEGF-A)and programmed death protein-1(PD-1).It was approved by National Medi-cal Products Administration on May 24th,2024,and can be used in combination with pemetrexed and carboplatin for locally advanced or positive EG-FR gene mutation after treatment with epidermal growth factor receptor(EGFR)tyrosine kinase inhib-itor.This paper mainly introduces the research progress of the world's first PD-1/VEGF bispecific antibody ivonescimab,and summarizes the mecha-nism of action,pharmacokinetics,phase Ⅰ-Ⅲ clinical trials and drug safety.

Objective:To explore the application effects of traditional Chinese medicine five-tone therapy combined with personalized emotional counseling in patients with post-stroke insomnia, aiming to provide a reference for improving patients′ sleep quality in clinical practice.Methods:A quasi-experimental study was conducted. A total of 70 inpatients with post-stroke insomnia from the Department of Neurology and the Department of Rehabilitation at Lianyungang Hospital of Traditional Chinese Medicine between January 2023 and February 2024 were selected using convenience sampling method. Of these, 35 patients admitted between January and July 2023 were assigned to the control group, while 35 patients admitted between August 2023 and February 2024 were assigned to the experimental group. The control group received routine treatment and care, while the experimental group was additionally provided with traditional Chinese medicine five-tone therapy combined with personalized emotional counseling. The intervention period was four weeks for both groups. Evaluations were conducted using polysomnography, the Pittsburgh Sleep Quality Index, the Insomnia Severity Index (ISI), and the patients′ use of hypnotic medications.Results:The control group consisted of 18 males and 17 females, with an average age of (58.02 ± 5.22) years; the experimental group consisted of 22 males and 13 females, with an average age of (56.41 ± 5.49) years. After the intervention, the total sleep time, the Pittsburgh Sleep Quality Index score, and the Insomnia Severity Index score in experimental group were (376.22 ± 52.39) min, (9.36 ± 3.22) points, and (13.89 ± 2.16) points, respectively, compared to (343.78 ± 74.51) min, (12.02 ± 3.76) points, and (16.66 ± 3.04) points in the control group, with statistically significant ( t=2.11, 3.18, 4.39, all P<0.05). The experimental group′s hypnotic medication usage rate and nursing satisfaction score were 11.43% (4/35) and (81.05 ± 3.68) points, respectively, compared to 34.29% (12/35) and (76.21 ± 5.22) points in the control group, with statistically significant differences ( χ2=5.51, t=4.48; both P<0.05). Conclusions:Traditional Chinese medicine five-tone therapy combined with personalized emotional counseling can effectively improve sleep quality in post-stroke insomnia patients, reduce the use of hypnotic medications, and enhance patient satisfaction.

Objective:To develop a Knowledge-Attitude-Practice (KAP) Scale for Dietary Management During Hemodialysis and to test its reliability and validity.Methods:Based on the KAP theoretical framework, an initial version of the scale was developed through a literature review and expert consultations. A convenience sampling method was used to recruit hemodialysis patients from four hospitals in Suzhou in March 2024. Questionnaire item analysis and reliability and validity tests were conducted.Results:A total of 460 questionnaires were distributed and 438 valid responses were collected, with an effective response rate of 95.22%. The final scale included three dimensions (knowledge, attitude, and practice) with 34 items. Content validity at the scale level was 0.910, and the item level ranged from 0.800 to 1.000. Exploratory factor analysis extracted three common factors, with a cumulative variance contribution rate of 74.520%. Confirmatory factor analysis showed a good model fit. The total Cronbach's α coefficient of the scale was 0.971, and the Cronbach's αcoefficients for the three dimensions were 0.963, 0.933, and 0.934, respectively. The test-retest reliability coefficient was 0.839.Conclusions:The Knowledge-Attitude-Practice Scale for Dietary Management During Hemodialysis demonstrates good reliability and validity, making it a valuable tool for assessing the KAP level of dietary management in hemodialysis patients.

OBJECTIVE To investigate and analyze the current situation and problems of the advanced personnel en-gaging in the hospital-acquired infection control during their training period and explore the existing countermeas-ures and future development.METHODS The literatures regarding to the advanced study in China were retrieved from databases,the subjects of the literatures covered infection control-related advanced study practice,discipline construction,position competence,talent cultivation,scientific research innovation,professional title evaluation,laws,regulations and development plans.From Aug.2024 to Nov.2024,a questionnaire survey and face-to-face interviews were conducted among 36 advanced study personnel from 9 provinces of China who engaged in hos-pital-acquired infection control in the First Medical Center of Chinese PLA General Hospital.Eventually,36 ques-tionnaires were retrieved,all of which were valid with a questionnaire recovery rate of 100.00％.RESULTS Among the 36 advanced study personnel of hospital-acquired infection control,58.33％were medium-grade professional ti-tle;preventive medicine(41.67％),clinical medicine(25.00％)and nursing(16.67％)ranked the top 3 majors.The personnel engaged in the infection control for more than 6 years,and the duration of the advanced study was generally 3 or 6 months.In reality,the personnel faced the choices in terms of the purposes of further education,learning approaches and learning contents.The advanced study personnel also encountered the problems of challenges from promotion,improvement of position competency,integration with clinical training,supervision and practice,as well as physiological,psychological and family pressure.CONCLUSION Aiming at the problems that the advanced study personnel are generally concerned about,such as how to scientifically and effectively carry out hospital-acquired infection control advanced study and preset and solve the problems that may encounter,it is necessary to formulate targeted training programmes so as to provide bases and enlightenment for establishment of a long-term mechanism for advanced study of infection control in China.

Ivonescimab is a humanized bispecific antibody targeting human vascular endothelial growth factor-A(VEGF-A)and programmed death protein-1(PD-1).It was approved by National Medi-cal Products Administration on May 24th,2024,and can be used in combination with pemetrexed and carboplatin for locally advanced or positive EG-FR gene mutation after treatment with epidermal growth factor receptor(EGFR)tyrosine kinase inhib-itor.This paper mainly introduces the research progress of the world's first PD-1/VEGF bispecific antibody ivonescimab,and summarizes the mecha-nism of action,pharmacokinetics,phase Ⅰ-Ⅲ clinical trials and drug safety.

Objective:To explore the application effects of traditional Chinese medicine five-tone therapy combined with personalized emotional counseling in patients with post-stroke insomnia, aiming to provide a reference for improving patients′ sleep quality in clinical practice.Methods:A quasi-experimental study was conducted. A total of 70 inpatients with post-stroke insomnia from the Department of Neurology and the Department of Rehabilitation at Lianyungang Hospital of Traditional Chinese Medicine between January 2023 and February 2024 were selected using convenience sampling method. Of these, 35 patients admitted between January and July 2023 were assigned to the control group, while 35 patients admitted between August 2023 and February 2024 were assigned to the experimental group. The control group received routine treatment and care, while the experimental group was additionally provided with traditional Chinese medicine five-tone therapy combined with personalized emotional counseling. The intervention period was four weeks for both groups. Evaluations were conducted using polysomnography, the Pittsburgh Sleep Quality Index, the Insomnia Severity Index (ISI), and the patients′ use of hypnotic medications.Results:The control group consisted of 18 males and 17 females, with an average age of (58.02 ± 5.22) years; the experimental group consisted of 22 males and 13 females, with an average age of (56.41 ± 5.49) years. After the intervention, the total sleep time, the Pittsburgh Sleep Quality Index score, and the Insomnia Severity Index score in experimental group were (376.22 ± 52.39) min, (9.36 ± 3.22) points, and (13.89 ± 2.16) points, respectively, compared to (343.78 ± 74.51) min, (12.02 ± 3.76) points, and (16.66 ± 3.04) points in the control group, with statistically significant ( t=2.11, 3.18, 4.39, all P<0.05). The experimental group′s hypnotic medication usage rate and nursing satisfaction score were 11.43% (4/35) and (81.05 ± 3.68) points, respectively, compared to 34.29% (12/35) and (76.21 ± 5.22) points in the control group, with statistically significant differences ( χ2=5.51, t=4.48; both P<0.05). Conclusions:Traditional Chinese medicine five-tone therapy combined with personalized emotional counseling can effectively improve sleep quality in post-stroke insomnia patients, reduce the use of hypnotic medications, and enhance patient satisfaction.

Objective:To develop a Knowledge-Attitude-Practice (KAP) Scale for Dietary Management During Hemodialysis and to test its reliability and validity.Methods:Based on the KAP theoretical framework, an initial version of the scale was developed through a literature review and expert consultations. A convenience sampling method was used to recruit hemodialysis patients from four hospitals in Suzhou in March 2024. Questionnaire item analysis and reliability and validity tests were conducted.Results:A total of 460 questionnaires were distributed and 438 valid responses were collected, with an effective response rate of 95.22%. The final scale included three dimensions (knowledge, attitude, and practice) with 34 items. Content validity at the scale level was 0.910, and the item level ranged from 0.800 to 1.000. Exploratory factor analysis extracted three common factors, with a cumulative variance contribution rate of 74.520%. Confirmatory factor analysis showed a good model fit. The total Cronbach's α coefficient of the scale was 0.971, and the Cronbach's αcoefficients for the three dimensions were 0.963, 0.933, and 0.934, respectively. The test-retest reliability coefficient was 0.839.Conclusions:The Knowledge-Attitude-Practice Scale for Dietary Management During Hemodialysis demonstrates good reliability and validity, making it a valuable tool for assessing the KAP level of dietary management in hemodialysis patients.

Objective To evaluate clinical effect of remote ischemic conditioning(RIC)in patients with spontaneous intracerebral hemorrhage(sICH).Methods Sixty-four patients with sICH who were diagnosed and admitted to the Department of Neurosurgery,the Sixth Medical Center of PLA General Hospital from January 2023 to May 2024 were selected as research subjects.Following the principle of matching baseline characteristics between groups,a computerized random grouping program was used to divide them into an observation group of 32 cases and a control group of 32 cases.Patients in the control group received standard basic medication according to the'Chinese Clinical Management Guidelines for Cerebrovascular Diseases',while the observation group received RIC treatment in addition to the control group's treatment,with a course of 14 d.The changes in National Institutes of Health Stroke Scale(NIHSS)scores and Barthel index(BI,daily living ability score table)on the day of admission and after 14 d of treatment,the changes in hematoma volume on computed tomography(CT)imaging,and the incidence of adverse events were compared between the two groups.Results At admission,the difference is not statistically significant in NIHSS scores,BI,and CT imaging hematoma volume between the two groups(P>0.05).After 14 d of treatment,the NIHSS scores of both groups were reduced compared to before treatment,and the scores of the observation group were lower than those of the control group(P<0.05);the BI of both groups was increased compared to before,and the scores of the observation group were higher than those of the control group(P<0.05);there were no significant differences in CT imaging hematoma volume and the incidence of adverse events between the two groups(P>0.05).Conclusion Continuous RIC treatment for 14 d is safe and well-tolerated in patients with spontaneous intracerebral hemorrhage and can effectively improve the neurological function of patients.