Background/Aims: Lenvatinib resistance remains a critical barrier in advanced hepatocellular carcinoma (HCC) therapy. However, the underlying mechanisms and strategies for reversing resistance remain incompletely understood. Methods: Integrated transcriptomics of lenvatinib-resistant patient tumors and an acquired-resistance murine model identified a novel macrophage subpopulation. Functional validation employed CRISPR-SAM screening, conditioned medium (CM) assays, subcutaneous/orthotopic xenografts, patient-derived organoids (PDOs), and patient-derived xenografts (PDXs). Mechanistic studies included ChIP-qPCR, co-immunoprecipitation, and pharmacologic targeting. Clinical relevance was assessed in a retrospective cohort. Results: Resistant HCC exhibited significant enrichment of a COLEC12high TAM subset , which correlated with poor survival and treatment response. These TAMs secreted neuregulin-1 (NRG1) , activating HER2/HER3-AKT signaling in tumor cells to drive cancer stemness and lenvatinib resistance. Mechanistically, in TAMs COLEC12 sequestered STAT1 in the cytoplasm, preventing its phosphorylation, and thereby derepressing STAT3-mediated NRG1 transcription. Depletion of NRG1 reversed the stemness phenotypes and resensitized tumors to lenvatinib both in vitro and in vivo. Clinically, high NRG1 expression predicted an inferior lenvatinib response and shorter survival. Crucially, the bispecific anti-HER2/HER3 antibody zenocutuzumab restored lenvatinib efficacy in PDOs, PDXs, and murine models. Conclusions Our work establishes the COLEC12high TAM/NRG1 axis as a master regulator of therapeutic resistance and identifies NRG1 as a predictive biomarker, providing a clinically actionable strategy to overcome lenvatinib resistance in HCC.

Tumors exhibit abnormal glucose metabolism, consuming excessive glucose and excreting lactate, which constructs a tumor microenvironment that facilitates cancer progression and disrupts immunotherapeutic efficacy. Currently, tumor glucose metabolic dysregulation to reshape the immunosuppressive microenvironment and enhance immunotherapy efficacy is emerging as an innovative therapeutic strategy. However, glucose metabolism modulators lack specificity and still face significant challenges in overcoming tumor delivery barriers, microenvironmental complexity, and metabolic heterogeneity, resulting in poor clinical benefit. Nanomedicines, with their ability to selectively target tumors or immune cells, respond to the tumor microenvironment, co-deliver multiple drugs, and facilitate combinatorial therapies, hold significant promise for enhancing immunotherapy through tumor glucose metabolic reprogramming. This review explores the complex interactions between tumor glucose metabolism-specifically metabolite transport, glycolysis processes, and lactate-and the immune microenvironment. We summarize how nanomedicine-mediated reprogramming of tumor glucose metabolism can enhance immunotherapy efficacy and outline the prospects and challenges in this field.

Epidural labor analgesia aims to provide effective medical services to alleviate labor pain in parturients, while adhering to the principles of voluntary participation and clinical safety. In 2018, Peking Union Medical College Hospital(PUMCH)became one of the first pilot units for labor analgesia in China, and has achieved satisfactory results in high-quality development of labor analgesia. This article mainly introduces the achievements and experience of labor analgesia at PUMCH, including: (1) prioritizing maternal and infant safety, arranging personnel rationally, and developing standardized treatment processes through multidisciplinary collaboration to ensure safe and comfortable childbirth; (2) leveraging the hospital's comprehensive capabilities in emergency treatment, and improving collaborative rescue plans for critically ill parturients and newborns; (3) implementing advanced teaching methods to effectively train and conduct simulated drills for labor analgesia and rescue of critically ill parturients; (4) conducting patient education and informative lectures to help parturients acquire a scientific understanding of labor analgesia. We hope that this experience can provide reference and inspiration for other hospitals.

Objective:To investigate the relationship between resilience, perceived social support, and adaptability in military freshmen.Methods:A total of 195 freshmen were randomly selected from a military medical university. The Chinese version of Connor-Davidson Resilience Scale (CD-RISC), the Perceived Social Support Scale (PSSS), and a self-test questionnaire of college students' psychological adaptability were used to investigate their resilience, perceived social support, and adaptability. SPSS 26.0 was used to perform an independent samples t-test and a Pearson correlation analysis to analyze the differences in these scores between freshmen with different demographic characteristics and the correlation between these scores. By using the PROCESS plug-in, a structural equation model was used to analyze the mediating effect of resilience on the relationship between social support and psychological adaptation, which was further tested using the Bootstrap method. Results:The independent samples t-test showed that females had a significantly higher score of other support than males ( t = -2.05, P = 0.041), and student leaders had significantly higher scores of family support and other support, total score of social support, and score in psychological adaptability than other students (all P<0.05). The correlation analysis showed that there were significant positive correlations between the scores of PSSS and its each item, CD-RISC, and self-test of college students' psychological adaptability (all P<0.05). The structural equation model showed that resilience partially mediated the relationship between social support and psychological adaptation, and the Bootstrap method revealed a significant indirect effect (95%CI: 0.102-0.253). Conclusion:Resilience plays a partial mediating role between perceived social support and adaptability in military freshmen. They should be guided to correctly perceive external support and develop strong resilience.

Objective: Based on observational, longitudinal and intervention study of common diseases among students in Jiangsu Province, this paper presents the current progress of two year follow up of myopia cohort regarding the association between growth parameters with progression of myopia among children and adolescents in areas with rapid economic growth. Methods: This survey adopted the stratified cluster sampling method for school selection. The full automatic computer optometry (TOPCON RM800) was used to track myopia related parameters for all participants from 2019 to 2020 under the condition of mydriasis (compound topicamide eye drops). Relationship between growth parameters of children and adolescents and the incidence and progression of myopia was analyzed by using Cox regression multiple statistical model. Results: The myopia rates of students from grade 1 to grade 3 in 2019 were 5.4%, 21.5% and 37.3% respectively. After one year, the myopia rates of all school stages increased to 25.3%, 43.3% and 58.1% respectively( χ 2=53.59, 49.63, 32.52, P <0.01). The mean diopter of right eye and left eye after mydriasis were ( 0.30± 1.24/0.39±1.26)D in 2019 and (-0.33±1.54/-0.19±1.55)D in 2020, respectively based on Cox multiple regression results, age ( HR =1.21, 95% CI =1.09-1.34), naked eye vision ( HR =0.08, 95% CI =0.07-0.11), height ( HR =0.98, 95% CI =0.97-0.99) showed a strong correlation with the incidence and progression of myopia( P <0.05). Conclusion Myopia is growing rapidly in the central region of Jiangsu Province. It is suggested that diopter, axial length, naked eye vision, age, height and other indicators should be included in the refractive archives of children and adolescents in the region.

Objective:To explore the relationship between proactive personality, resilience and achievement motivation of military cadets, and to explore the mediating role of resilience between proactive personality and achievement motivation, as well as the moderating effect of cadets’leading ability on this mediating role.Methods:In this study, 109 military cadets were measured with proactive personality scale, Connor-Davidson resilience scale (CD-RISC) and achievement motivation scale. SPSS 26.0 was used for descriptive statistical analysis and correlation analysis.Results:①There was a significant correlation among the total scores of proactive personality, resilience and achievement motivation ( Ps<0.01). ②Proactive personality could significantly predict the level of achievement motivation ( a=0.454, P<0.001), and resilience could significantly predict the level of achievement motivation ( b=0.231, P=0.019). ③Resilience significantly mediated the relationship between proactive personality and achievement motivation ( c′=0.3, P=0.003). ④Cadets' leading ability moderated the effect of resilience on achievement motivation (index=0.338, 95% CI: 0.057 to 0.881). The mediating effect of resilience between proactive personality and achievement motivation was significant for cadets' leaders (Effect=0.381, 95% CI: 0.085 to 1.005), but not significant for other students (Effect=0.043, 95% CI: -0.069 to 0.252). Conclusion:The proactive personality of military cadets can affect the level of achievement motivation through psychological resilience, which is also moderated by cadre identity, suggesting that military education should improve the level of achievement motivation in many ways.

Objective:To investigate the level of psychological stress, anxiety and posttraumatic stress disorder (PTSD) of military medical students under the condition of normalized prevention and control of the epidemic.Methods:A total of 225 students from a military university were selected by random sampling method. Chinese perceived stress scale (CPSS), Perceived social support scale (PSSS), Self-rating anxiety scale (SAS) and PTSD Checklist-5 (PCL-5) were used to measure the mental health of the subjects and influencing factors. SPSS 26.0 was used to conduct independent sample t test and ANOVA analysis. Pearson correlation analysis was conducted, and multiple regression equation was used to further analyze the relationship between psychometric factors. Results:The SAS scores of 22.2% (50/225) of the subjects and PCL-5 scores of 30.7% (69/225) of the subjects reached the positive standard. The results of correlation analysis showed that the total score of PSSS was negatively correlated with CPSS ( r=-0.315, P<0.01), SAS ( r=-0.336, P<0.01) and PCL-5 ( r=-0.137, P<0.05) scores. The score of family support negatively predicted the level of psychological stress ( B=-0.595, P<0.001), anxiety ( B=-0.635, P<0.001) and PTSD level ( B=-0.769, P=0.006) of the students. Conclusion:Social support, especially family support, has a significant protective effect on psychological stress, anxiety and PTSD during the period of normalized prevention and control of the epidemic.

The complement system is a complex protein network.Complement is important in disease severity and response to therapy.This review summarizes recent advances on the role of complement analysis in complement function or activity,complement factors concentrations,complement activation products,complement autoantibody and genetic analysis.And it also focuses on pre-analytical and post-analytical quality control for complement analysis.

Diabetic kidney disease is one of the main causes of end-stage renal disease .During the past decades , proteomic analysis based on mass spectrometry has been playing a momentous role in revealing potential biomarkers of diabetic kidney disease .Assays using New combination of multiple biomarkers can help identify high risk patients and give positive guidance of therapies .

Diarrhea is a common intestinal symptom in macaque.The corresponding intestinal lesions of macaque are mainly described at autopsy but less observed by colonoscopy.The aim of this study was to develop a colonoscopic technique and to obtain endoscopic images of the entire colon in macaques.Eight healthy adult macaques ( 5 males and 3 females) without diarrhea for 2 months, were fed Glauber’ s salt through nasogastric tubes.The colon cleanliness was well matched to the endoscopic observation of macaque colon.The procedure took 10-20 min for each animal.There was no obvious abnormality in the colon of four animals except some slight differences of mucosal structure from that of human beings.Small pieces of erosion and ulcer in the colons were observed in four macaques which presented mild diarrhea for less than 1 day, while a severe stenosis was observed in one of those four macaques.No animal died during and one week after the endoscopic procedure.Colonoscopy may safely performed in macaques.The images taken by colonoscopy may be important to establish diagnosis and treatment of colitis in macaques in time and to evaluate the efficacy of drug intervention as well.This technique is also helpful to provide qualified macaques for scientific researches.