1.COLEC12high tumor-associated macrophages orchestrate lenvatinib resistance and cancer stemness in hepatocellular carcinoma via paracrine NRG1-HER2/HER3 signaling
Jianxing ZHANG ; Liang QIAO ; Zongfeng WU ; Dinglan ZUO ; Shanshan HUANG ; Shaoru LIU ; Zhenkun HUANG ; Yi ZENG ; Yu LI ; Yichuan YUAN ; Chenwei WANG ; Wei HE ; Jiliang QIU ; Yunfei YUAN ; Yi NIU ; Binkui LI
Clinical and Molecular Hepatology 2026;32(2):772-786
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.
2.Influence of CT examination bony parameters and surgical methods on difficult pelvis and perioperative efficacy of mid-low rectal cancer
Chao LAI ; Ahao WU ; Zongfeng FENG ; Zhengqing CAI ; Yi CAO ; Zhengrong LI
Chinese Journal of Digestive Surgery 2024;23(4):613-621
Objective:To investigate the influence of computer tomography (CT) examination bony parameters and surgical methods on difficult pelvis and perioperative efficacy of mid-low rectal cancer.Methods:The retrospective case-control study was conducted. The clinicopathological data of 191 patients who underwent robotic or laparoscopic total mesorectal excision (TME) for mid-low rectal cancer in the First Affiliated Hospital of Nanchang University from January 2021 to December 2022 were collected. There were 123 males and 68 females, aged (60±11)years. According to the surgical difficulty score, 191 patients were divided into the difficult pelvis group of 41 patients and the non-difficult pelvic group of 150 patients. Thirteen pelvic parameters were obtained on CT images of the 191 patients. Observation indicators: (1) comparison of intraoperative and postoperative conditions of patients in the difficult pelvis group and the non-difficult pelvis group; (2) analysis of factors affecting difficult pelvis in patients with mid-low rectal cancer; (3) stratified analysis of different surgical methods for patients with difficult pelvis. Measurement data with normal distribu-tion were represented as Mean± SD, and comparison between groups was conducted using the t test. Measurement data with skewed distribution were represented as M(range), and comparison between groups was conducted using the Mann-Whitney U test. Count data were expressed as absolute numbers, and comparison between groups was conducted using the chi-square test or Fisher exact probability. Comparison of ordinal data was conducted using the Mann-Whitney U test. Univariate and multivariate analyses were conducted using the Logistic regression model. Results:(1) Com-parison of intraoperative and postoperative conditions of patients in the difficult pelvis group and the non-difficult pelvis group. There were significant differences in operation time, volume of intra-operative blood loss, sum of the product of the longest diameters (SPD) of tumor lesions, postopera-tive complications, duration of postoperative hospital stay, and hospitalization expenses between the two groups ( t=-4.853, -5.816, Z=2.838, χ2=81.498, t=-5.897, -2.770, P<0.05). (2) Analysis of factors affecting difficult pelvis in patients with mid-low rectal cancer. Results of multivariate analysis showed that gender, age, pelvic inlet, distance between the sacral promontory and the coccyx, depth of the pelvis, line AB, angle A, and angle B were independent factors affecting difficult pelvis in patients with mid-low rectal cancer ( odds ratio=0.080, 1.067, 3.065, 0.004, 10 165.062, 0.019, 0.476, 0.662, 95% confidence interval as 0.016-0.409, 1.008-1.130, 1.388-6.767, 0.001-0.024, 477.574-216 361.071, 0.003-0.131, 0.358-0.632, 0.551-0.794, P<0.05). (3) Stratified analysis of different surgical methods for patients with difficult pelvis. ① Comparison of general preoperative data of patients with difficult pelvis receiving different surgical methods. Of the 41 mid-low rectal cancer patients with difficult pelvis, 15 underwent robotic TME, and 26 underwent laparoscopic TME. There was a significant difference in the body mass index between patients receiving the two surgical methods ( t=-2.055, P<0.05). ② Comparison of intraoperative and postoperative conditions of patients with difficult pelvis receiving different surgical methods. There was no significant difference in operation time, volume of intraoperative blood loss, SPD of tumor lesions, number of lymph nodes dissected, number of lymph node metastases, distance between tumor and anal verge, combined organ resection, postoperative complications, duration of postoperative hospital stay, hospitalization costs, T staging, N staging, M staging, vascular tumor thrombus, and nerve invasion ( P>0.05). Conclusions:Gender, age, pelvic inlet, distance between the sacral promontory and the coccyx, pelvic depth, AB line, angle A, and angle B are independent factors affecting difficult pelvis in patients with mid-low rectal cancer. There is no difference in perioperative outcomes between mid-low rectal cancer patients of difficult pelvis who received robotic surgery and laparoscopic surgery.
3.Construction and practice of the golden course "doctor-patient communication skills"
Ying HUANG ; Jing WU ; Wangbin NING ; Meihua XU ; Xinhua LI ; Zehao LIU ; Zongfeng DING ; Weiru ZHANG ; Xiaobin CHEN
Chinese Journal of Medical Education Research 2021;20(4):378-382
Diagnostics is one of the most important bridge courses for medical students from basic to clinical. Doctor-patient communication runs through the whole process of patient diagnosis and treatment. How to improve medical students' ability of doctor-patient communication? Our teaching team has carried out continuous reform and explored the scientific effective teaching mode. Recently, through the construction of "doctor-patient communication skills" quality online course, efforts have made to build an online and offline blended learning mode, which has gradually realize the integration with diagnostics teaching, and has achieved remarkable results. It also provides a scientific practical basis for the integration of doctor-patient communication and other clinical courses, which is worthy of promotion.
4.Epidemiology characteristics of crawfish related rhabdomyolysis in Nanjing, 2016: a multicenter retrospective investigation
Shaolei MA ; Changsheng XU ; Songqiao LIU ; Zongfeng HU ; Wen'ge LIU ; Jinsong ZHANG ; Xufeng CHEN ; Shinan NIE ; Jun ZHANG ; Dujuan SHA ; Jinjin LI ; Haibin NI ; Haidong QIN ; Ying GAO ; Wei WANG ; Chengfang Wu ; Zhan YU ; Congjian ZHU ;
Chinese Critical Care Medicine 2017;29(9):805-809
Objective To investigate the epidemiology characteristics of crawfish related rhabdomyolysis (RM) in Nanjing, 2016.Methods Outpatient and inpatient electronic medical system of 21 hospitals in Nanjing during 2016 were retrospectively searched, and all the patients diagnosed with RM were selected. The patients with none crayfish-related RM was excluded. The epidemiology characteristics were depicted. The geographic information system (GIS) was used to collect, manage and analyze the spatial data, to visualize it, to analyze the spatial distribution features of the disease, and to explore the cause of disease prediction. GeoDa 1.8 software was used to analyze the global and local spatial auto-correlation.Results A total of 1183 patients with crawfish related RM were initially screened, excluding 59 patients with RM caused by trauma, severe exercise, heat stroke, myositis, poisoning, drugs, and genetic diseases, and 1124 patients were enrolled. The proportion of men was 36.48% (410/1124) with an incidence of 12.54/100 thousands; while of women was 63.52% (714/1124) with an incidence of 21.86/100 thousands. The median age at onset was 34 (28, 43) years. From July to August, the incidence of crawfish related RM was the highest, accounting for 96.53% of the total number of cases. The top four incidence areas were Pukou (41.54/100 thousands), Jianye (25.94/100 thousands), Qixia (25.73/100 thousands), Gulou (25.04/100 thousands), all of which were adjacent to the Yangtze River. Global spatial autocorrelation analysis showed: MoranI = 0.427,Z = 2.646,P = 0.003, suggesting that the crawfish related RM had positive spatial autocorrelation. The results showed that the spatial structure of crawfish related RM existed in Nanjing in 2016. Local spatial autocorrelation analysis showed that the high-high concentration areas were Pukou, Jianye and Liuhe. The incidences of above three areas which were the Nanjing section of the lower reaches of the Yangtze River flowed through the region and surrounding areas were higher than the overall incidence of Nanjing.Conclusion The prevalence of crawfish related RM in Nanjing during 2016 had an obvious region-concentrated character and global spatial autocorrelation with the high prevalent regions mainly concentrated in the urban areas adjacent to the Yangtze River.
5.Expressions of Kaposi′ s sarcoma-associated herpesvirus type 8-associated microRNAs k12-1 and k12-12 in Kaposi′s sarcoma and their significance
Xiujuan WU ; Zongfeng ZHAO ; Xiongming PU
Chinese Journal of Dermatology 2015;(12):860-863
Objective To measure the expressions of Kaposi′s sarcoma-associated herpesvirus type 8 associated-microRNAs k12-1 (kshv-miR-k12-1)and k12-12 (kshv-miR-k12-12)in Kaposi′s sarcoma tissue, and to assess their relationship with pathological stage and lesion area of Kaposi′s sarcoma, HIV infection, and human herpesvirus type 8 (HPV-8)infection. Methods Totally, 18 paired tissue specimens stored in liquid nitrogen from Kaposi′ s sarcoma lesions and paralesional skin were collected. Total RNAs were extracted from these specimens by using Trizol reagent, and reversely transcribed into cDNA. SYBR Green real-time fluorescence-based quantitative PCR was performed to measure the expressions of kshv-miR-k12-1 and kshv-miR-k12-12 in these specimens. The relationship of kshv-miR-k12-1 and kshv-miR-k12-12 expressions with the pathological stage and lesion area of Kaposi′s sarcoma, HIV and HPV-8 infections was analyzed. Results Compared with paralesional normal skin, Kaposi′s sarcoma lesions showed significantly increased expressions of kshv-miR-k12-1 (2-ΔΔCt: 1.016 ± 1.645 vs. 0.029 ± 0.019, t = 2.542, P = 0.016)and kshv-miR-k12-12 (2-ΔΔCt: 2.104 ± 1.973 vs. 0.102 ± 0.093, t = 4.301, P = 0.000). There were no significant differences in the expressions of kshv-miR-k12-1 or kshv-miR-k12-12 between patients with HIV or HPV-8 infection and those without, among patients with different pathological stages of Kaposi′s sarcoma, or among patients with different lesion areas (all P > 0.05). Conclusion Both kshv-miR-k12-1 and kshv-miR-k12-12 are highly expressed in Kaposi′s sarcoma, but neither of their expressions is related to HIV or HPV-8 infection, pathological stage or lesion area of Kaposi′s sarcoma.
6.The expression of MiR-34a/c in lesions of psoriasis vulgaris Uyghur and Han patients in XinJiang
Chunli CHEN ; Zongfeng ZHAO ; Huiqin WANG ; Weidong WU
Journal of Chinese Physician 2015;17(11):1658-1661
Objective To investigate the expression differences of MiR-34a/c in lesions of psoriasis vulgaris Uyghur and Han patients and beside-lesional tissue and normal skin tissue in XinJiang.Methods Real-time fluorescent quantitative polymerase chain reaction (PCR) was used to determine the expression levels of MiR-34a/c in the psoriasis vulgaris Uyghur and Han patients with lesion tissues, beside-lesion tissues, and normal skin tissues, respectively.Results The expression level of MiR-34a was higher in lesions of psoriasis vulgaris in XinJiang than in the beside-lesion tissues and normal skin tissues, and differences were statistical significance (P < 0.05).However, the expression level of MiR-34a in beside-lesion tissues and normal skin tissues, and in the Uyghur and Han psoriasis vulgaris werent statistically significant difference (P > 0.05).The expression level of MiR-34c in three types of tissues and in the Uyghur and Han psoriasis vulgaris weren't statistically significant difference (P > 0.05).Conclusions MiR-34a might participate in the pathogenesis of Uyghur and Han psoriasis vulgaris in XinJiang.

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