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.

AIM: To assess the gap between the peak of the base curve to the surface of the cornea, as well as examines the correlation between the thickness of the tear film and the fitting of the orthokeratology lens through optical coherence tomography(OCT), providing an intuitive and quantitative clinical evaluation method for the fitting of the orthokeratology lens.METHODS: Myopia patients who fitted orthokeratology at our hospital from January to December 2023 were included. Examinations, including naked vision, slit lamp, non-contact intraocular pressure, ocular fundus, eye position, corneal diameter, corneal topography, tear film rupture time, optometry, etc., were performed on all patients before fitting. The trial lens parameter was selected according to the examination results, and fluorescein staining was performed to evaluate lens fitting state after patients adapted to wearing glasses. According to the performance of fluorescein staining, the inspected eyes are divided into three groups: lens loose group, lens fitting group, and lens tight group. In addition, the tear film thickness of three groups of subjects was measured by OCT, and the differences between the three groups of data were evaluated.RESULTS: A total of 49 myopic patients(77 eyes)were included. The average sphere degree was -3.10±1.25 D, the average cylinder degree was -0.43(-0.75, 0)D, the average horizontal keratometry(HK)was 42.48±0.81 D, and vertical keratometry(VK)was 42.98(42.25, 43.50)D. There were 21 cases(34 eyes)in the lens fitting group, with 13 cases of bilateral eyes, 8 cases of one eye, 14 cases(22 eyes)in the lens loose group, with 8 cases of bilateral eyes, 6 cases of one eye, and 14 cases(21 eyes)in the lens tight group, with 7 cases of bilateral eyes, 7 cases of one eye. There was no statistical difference in the main basic data of the subjects in the three groups(all P>0.05). OCT showed that the tear film thickness of the lens fitting group, the lens loose group, and the lens tight group was 231.18(219.0, 243.0), 220.41(214.0, 224.3), and 249.00(241.5, 258.0)μm, respectively, and there was statistical significance in the thickness among the three groups(P<0.05).CONCLUSION: OCT can serve as a safe and reliable method for measuring the tear film thickness, which can help evaluate the suitability of orthokeratology and provide a non-invasive, more intuitive, and quantitative evaluation method for the fitting and evaluation of orthokeratology.

Objective To evaluate the efficacy of extended-field intensity-modulated radiotherapy (IMRT) in the treatment of patients with early-stage NK/T cell lymphoma (NKTCL),and to examine the clinical characteristics and the effect of treatment factors on the prognosis of these patients.Methods The clinical data of 165 patients with early-stage NKTCL who underwent extended-field IMRT with (n=158,95.8%) or without chemotherapy (n=7,4.2%) were reviewed.Of these 165 patients,140(84.8%) received a radiation dose of ≥50 Gy to the primary lesion,and 25 patients (15.2%) received a radiation dose of<50 Gy.Most patients (n=147,89.1%) were treated with L-asparaginase-based chemotherapy regimens,whereas only 11 patients (6.7%) were treated with doxorubicin-based CHOP/CHOP-like regimens.In addition,109 patients (66.1%) received ≥4 cycles of chemotherapy.Locoregional control (LRC),overall survival (OS),and progression-free survival (PFS) rates were calculated using the Kaplan-Meier method,and the log-rank test was used for survival comparison and univariate prognostic analysis.A multivariate prognostic analysis was performed using the Cox model.Results The 5-year sample size 55.The 5-year OS,PFS,and LRC rates of all patients were 74.2%,72.5%,84.4%,respectively.The patients who received a dose of ≥50 Gy had a significantly higher 5-year LRC rate than those with<50 Gy (91.8% vs.39.7%,P=0.000).The 5-year OS was significantly higher in the low-risk early-stage group than in the high-risk early-stage group (P=0.002).For the high-risk early-stage NKTCL group,patients who received ≥4 cycles of chemotherapy had significantly higher 5-year OS and PFS than those who received<4 cycles of chemotherapy (5-year OS:71.3% vs.59.5%,P=0.032;5-year PFS:70.4% vs.54.4%,P=0.009).In addition,multivariate analysis showed that ECOG≥2,primary tumor invasion (PTI),and Ann Arbor stage Ⅱ were associated with poor OS (P=0.006,0.002,0.014),and ECOG≥2 and PTI were associated with reduced LRC (P=0.004,0.016).Furthermore,ECOG≥2,PTI,Ann Arbor stage Ⅱ,and extranasal primary site were associated with lower PFS (P=0.045,0.003,0.030,0.032).Conclusions Extended-field IMRT at a dose of ≥50 Gy can lead to favorable LRC,OS,and PFS in patients with early-stage NKTCL.However,it is less effective against distant early-stage NKTCL in patients with poor prognosis.Nevertheless,≥4 cycles of chemotherapy can significantly improve the OS and PFS of patients with early-stage NKTCL.

Objective To analyze the apoptosis-related spots like protein (ASC) and caspase -1 in HCC and adjacent noncancerous tissues and its clinical significance. Methods ASC and Caspase 1 were determined with immunohistochemistry LSAB method and the various indexes were analyzed in 30 cases of liver cancer and adjacent tissues which did not receive preoperative radiotherapy and chemotherapy. Results The positive rate of ASC in HCC and adjacent noncancerous tissues was 10.00% (3/30) and 73.33% (22/30). Positive rate between the groups had significant difference (P＜0.01). Caspase-1 positive rate had significantly difference between the groups (23.33% (7/30) vs. 66.67% (20/30), P＜0.01). ASC and the two indicators of Caspase-1 expression in cancer tissues were low, but no significant correlations between the two groups (P＞0.05). ASC and the two indicators of Caspase-1 expression in adjacent tissue were significantly increased, and it showed a very significant correlation (r＝0.722,P＜0.01). Conclusions ASC, Caspase-1 expression in liver cancer were low expressed, and significantly lower than the adjacent tissues, which suggested that ASC and Caspase-1 were closely related to the occurrence and development of the apoptosis of liver cancer, and it might be used as diagnosis and treatment of targets in liver cancer.

Based on some European universities the author wants to analyse their education system and find some enlightenment on our post-graduate education construction of medical laboratory science.