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.Efficacy of intelligent wireless endoscopy in transurethral resection of the prostate
Chao FANG ; Zeping ZUO ; Chaozhao LIANG ; Zongyao HAO ; Hongtao YU ; Jinhai ZHU ; Yuesheng WANG
Journal of Modern Urology 2026;31(2):135-139
Objective To analyze the clinical efficacy of intelligent wireless endoscopy in transurethral resection of the prostate, so as to provide evidence for clinical application. Methods A retrospective analysis was conducted on the clinical data of 70 patients with benign prostatic hyperplasia (BPH) who underwent transurethral resection of the prostate at Tongling People's Hospital during Jan. 2023 and Dec. 2024. Based on the type of endoscopes used, patients were divided into a wireless endoscopy group and a traditional endoscopy group, with 35 patients in either group. Differences between the two groups were compared in terms of surgical preparation time, operation time, postoperative hospital stay, catheter indwelling time, intraoperative blood loss, surgical complications, and operating comfort during the procedure. Results All 70 operations were successfully completed without severe urinary incontinence. The wireless laparoscopy group demonstrated significantly shorter surgical preparation time compared to the traditional laparoscopy group [(12.14±2.39)min vs. (14.89±0.80)min, P<0.001].There was no statistically significant difference in the operation time between the two groups [(93.51±34.49)min vs. (101.71±34.87)min, P=0.326]. There were no statistically significant differences between the two groups in postoperative hospital stay, catheter indwelling time, intraoperative blood loss, and surgical complications (P>0.05). The wireless endoscopy group demonstrated significantly higher operating comfort compared to the traditional endoscopy group [(3.94±0.77) vs. (2.57±0.61), P<0.001]. Conclusion The use of intelligent wireless endoscopy for transurethral resection of the prostate is comparable to traditional endoscopy in surgical efficacy and patient safety, but it can shorten preoperative preparation time and improve operator comfort.
3.Development of an organoid-based pan-TKI precision screening platform to enhance therapeutic efficacy of ET+CDK4/6 inhibitors in HR+/HER2-low breast cancer
Yingchao WU ; Liushan CHEN ; Yuqi LIANG ; Jieting CHEN ; Junfeng HUANG ; Qian ZUO ; Qianjun CHEN
The Journal of Practical Medicine 2025;41(18):2786-2795
Objective To investigate the underlying mechanisms contributing to the limited therapeutic efficacy of endocrine therapy combined with CDK4/6 inhibitors in HR+/HER2-low breast cancer,and to develop a breast cancer organoid model as a tool for the precise identification of HR+/HER2-low patients who are responsive to pan-TKI treatment.Methods Transcriptomics was employed to identify differentially expressed genes in HR+/HER2-0 and HR+/HER2-low breast cancer samples and to perform functional enrichment analysis.Tumor organoid models were established using breast cancer tissues obtained from clinical sources,and the differential sensitivity of these samples to therapeutic agents was assessed using Calcein-AM/PI cell viability staining and EdU-based cell proliferation assays.Results The results of transcriptomic enrichment analysis indicated that EGFR was signifi-cantly activated in HR+/HER2-low breast cancer and exhibited characteristics of resistance to TKIs.Breast cancer organoids were successfully established.Drug sensitivity testing revealed that the therapeutic efficacy of ET combined with CDK4/6 inhibitors was suboptimal in certain cases of HR+/HER2-low breast cancer,while the addition of TKIs effectively restored sensitivity to the ET+CDK4/6 inhibitor regimen(P<0.05).Conclusions TKI can restore the reduced sensitivity of HR+/HER2-low breast cancer to endocrine therapy combined with CDK4/6 inhibitors.Breast cancer organoids hold promise as screening tools for assessing drug sensitivity in clinical settings for patients with HR+/HER2-low breast cancer.
4.Key Quality Attributes and Technical Control Points of Aluminum Foil for Pharmaceutical Packaging in the 2025 Edition of the Pharmacopoeia of the People's Republic of China
Yanchun RAO ; Wei XIONG ; Junfeng ZUO ; Lei CHEN ; Huizheng FU ; Majian XIONG ; Fangfang ZHANG ; Liang CHANG
Herald of Medicine 2025;44(11):1763-1767
Aluminum foil for pharmaceutical packaging is a material used for solid dosage forms.Guideline 9625 of the Pharmacopoeia of the People's Republic of China(2025 edition),built on the concepts of whole-process quality control and risk management,specifies the quality requirements for aluminum foil.This article analyzed and discussed the critical quality attributes and technical control points of aluminum foil by examining its fundamental characteristics,production processes,and relevant domestic and international standards.This article aimed to provide guidance for stakeholders in understanding and applying the guidelines,thereby enhancing pharmaceutical packaging quality and fostering standardization across the industry.
5.Interpretation of"Standard for infection prevention and control in hemodialysis department(center)"WS/T854-2025
Yanyan WU ; Min DENG ; Huixue JIA ; Anhua WU ; Li ZUO ; Yunxi LIU ; Jiancheng ZHAO ; Jiansheng LIANG ; Yun YANG ; Ling LIN
Chinese Journal of Nosocomiology 2025;35(20):3045-3048
Hemodialysis patients exhibit compromised immune function and require long-term repeated vascular punctures as therapeutic approach,the risk of infection increases.Hospital-associated infection in hemodialysis de-partment(center)happens from time to time,which has already become a concern for the medical community,patients and social media.This paper outlines the task origin of China's"Standard for infection prevention and control in hemodialysis department(center)"(WS/T854-2025),the compilation basis and explanations for its key content,feasibility and implementation recommendations,as well as the clarifications on common issues encoun-tered during its promotion and enforcement.
6.Evaluation of clinical effectiveness of retrograde recanalization of occluded radial artery via distal transradial approach
Xiao-fei XIE ; Sheng-xin ZUO ; Jin-peng XU ; Xiao-liang HAN ; Gang-cheng SUN ; Liang LI
Chinese Journal of Interventional Cardiology 2025;33(3):135-140
Objective Radial artery occlusion(RAO)is one of the common complications following coronary intervention via the traditional radial artery approach.This study aims to evaluate the clinical effectiveness of retrograde recanalization of occluded radial arteries through the distal transradial approach(dTRA)approach.Methods A total of 35 patients with RAO admitted to the cardiovascular department of the Anhui Chest hospital between December 2022 and April 2024,who were scheduled to undergo coronary intervention and had attempted recanalization of RAO via dTRA approach were selected.The primary result was the success rate of recanalizing RAO via dTRA.The secondary results included factors influencing the failure of recanalization via dTRA,postoperative puncture complications,and the patency rate at the 3-month follow-up.Results This study divided the patients into a successful group(29 cases,82.9%)and a failed group(6 cases,17.1%)based on whether the distal radial artery was successfully opened and occluded.The proportion of smoking(100.00%vs.17.24%,P=0.040),history of diabetes(100.00%vs.10.34%,P=0.025),and chronic total occlusion of coronary artery(83.33%vs.17.24%,P=0.030)in the failure group were higher than those in the success group,and the difference was statistically significant.The application rate of balloon tracking assisted technology in the failed group(16.67%vs.58.62%,P=0.045),and the diameter of the radial artery at 3 days after surgery[(1.63±0.13)mm vs.(2.13±0.32)mm,P=0.021]and the peak radial artery blood flow velocity at 3 days postoperatively[(0.10±0.78)m/s vs.(0.50±0.13)m/s,P<0.001]were all lower in the successful group,and the differences were statistically significant.Logistic regression analysis 3 days after surgery showed that chronic complete occlusion of the coronary artery was an independent risk factor for surgical opening failure(OR 0.042,95%CI 0.004-0.438,P=0.008).After 3 months of follow-up,the patency rate of the successful group was 55.2%.Conclusions Retrograde recanalization of RAO via dTRA is safe and feasible,but its long-term patency rate is not high.
7.Expression and clinical significance of microtubule-associated protein 4 in pancreatic adenocarcinoma tissues
Longyan ZUO ; Yingfei LIANG ; Xinmiao XIAN ; Tonggang QI
Chinese Journal of Clinical Laboratory Science 2025;43(3):185-192
Objective To investigate the expression pattern and clinical significance of microtubule-associated protein 4(MAP4)in pancreatic adenocarcinoma(PAAD).Methods The immunofluorescence technique was used to detect the expression level of MAP4 in the tissues from 60 PAAD patients visited Liaocheng People's Hospital.The expression levels of MAP4 mRNA and their correlations with patients'prognosis were analyzed using the transcriptome data from 179 PAAD and 332 normal pancreatic tissues in the TCGA and GTEx databases.The correlations of the expression levels of MAP4 with tumor stemness indices,tumor-infiltrating immune cells,and immune checkpoints were analyzed by the bioinformatics method.The small interfering RNA technology was used to silence the expres-sion of MAP4 in PAAD cell lines such as MiaPaCa-2 and PANC-1,and its effects on cell proliferation,migration,and invasion abili-ties were evaluated by the CCK-8 and Transwell assays.Results The results of immunofluorescence showed that the expression levels of MAP4 in PAAD tissues were significantly higher than that in normal pancreatic tissues(P<0.05).The bioinformatics analysis indi-cated that the expression levels of MAP4 mRNA in PAAD tissues were significantly up-regulated(P<0.05),and that their high expres-sion was significantly correlated with shorter disease-free and progression-free intervals in patients(P<0.05).The expression levels of MAP4 were significantly negatively correlated with RNA-related tumor stemness indices(r=-0.55,P<0.05),but significantly posi-tively correlated with macrophage and dendritic cell infiltration(r>0.5,P<0.05).In vitro experimental results confirmed that silencing MAP4 could significantly inhibit the proliferation,migration,and invasion abilities of PAAD cells(P<0.05).Conclusion MAP4 is highly expressed in PAAD tissues,and its expression levels are closely related to patients'prognosis,tumor stemness,and immune cell infiltration.MAP4 may participate in the progression of PAAD by regulating the biological behavior and immune microenvironment of tumor cells,which provides a new potential target for the diagnosis and treatment of PAAD.
8.Key Quality Attributes and Technical Control Points of Aluminum Foil for Pharmaceutical Packaging in the 2025 Edition of the Pharmacopoeia of the People's Republic of China
Yanchun RAO ; Wei XIONG ; Junfeng ZUO ; Lei CHEN ; Huizheng FU ; Majian XIONG ; Fangfang ZHANG ; Liang CHANG
Herald of Medicine 2025;44(11):1763-1767
Aluminum foil for pharmaceutical packaging is a material used for solid dosage forms.Guideline 9625 of the Pharmacopoeia of the People's Republic of China(2025 edition),built on the concepts of whole-process quality control and risk management,specifies the quality requirements for aluminum foil.This article analyzed and discussed the critical quality attributes and technical control points of aluminum foil by examining its fundamental characteristics,production processes,and relevant domestic and international standards.This article aimed to provide guidance for stakeholders in understanding and applying the guidelines,thereby enhancing pharmaceutical packaging quality and fostering standardization across the industry.
9.Progress in research on the prevention and treatment of diabetic retinopathy by the intervention of the nuclear red blood cell related factor 2 signaling pathway with effective components of traditional Chinese medicine
Yixin CHEN ; Chen LI ; Bin SONG ; Liping ZUO ; Jianjun LIU ; Lumin LIANG ; Ruixiong NAN ; Jiahao WANG ; Libin PAN ; Jingrong WANG
Recent Advances in Ophthalmology 2025;45(8):667-672
Diabetic retinopathy(DR)is a kind of microvascular disease caused by the long-term influence of diabetes mellitus(DM),and it is one of the main cause of global visual impairment and blindness.Its typical characteristics include microaneurysms,hard exudates,macular edema(DME)and neovascularization.Its pathogenesis is diverse,and the root cause is oxidative stress and advanced glycosylation end products.The nuclear red blood cell related factor 2(Nrf2)signa-ling pathway plays an important role in preventing various diseases.As one of the characteristics of DM,hyperglycemia will activate the generation of reactive oxygen species(ROS)in mitochondria.These oxidative stress factors activate the nucle-ar transcription factor κB pathway,becoming the main inducement of various complications of DM.This pathway will in-duce increased transcription of proinflammatory cytokines,including tumor necrosis factor-alpha,transforming growth fac-tor-beta and interleukin-1.The active ingredients of traditional Chinese medicine have significant antioxidant,anti-inflam-matory,anti-apoptotic and angiogenesis-promoting effects,and can block the progression of DR through various mecha-nisms.In this article,the research status of traditional Chinese medicine targeting the Nrf2 signaling pathway in the preven-tion and treatment of DR is reviewed to guide clinical and scientific research.
10.Exercise-based pre-rehabilitation before surgery for patients with lung cancer:a scoping review
Xinyi ZHENG ; Xianwu LUO ; Lanfang ZUO ; Yuwei LI ; Ying LIANG
Modern Clinical Nursing 2025;24(3):69-75
Objective To review literature on exercise-based pre-rehabilitation before surgery in patients with lung cancer,hence to provide a guidance for development of standardised programs for pre-rehabilitative exercise.Methods Following the Australian JBI Evidence-based Health Care Centre Scope Review guidelines,a comprehensive search was conducted across the databases of PubMed,Embase,Web of Science,CINAHL,CNKI,WanFang Data and SinoMed.The search covered the inception of databases to 29th February,2024.The retrieved literature was then screened and relevant information was extracted.Results A total of 20 articles were included in this review.Exercise-based pre-rehabilitation for lung cancer patients was mainly divided into single-modality pre-rehabilitation and multimodal pre-rehabilitation(exercise combined with interventions in nutrition,psychology and health behaviour).The period of intervention for exercise-based pre-rehabilitation was typically 2-3 weeks before surgery,with 3-5 sessions per week.The outcome indicators mainly included respiratory function,capacity of physical activity,quality of life,psychological status and postoperative complications.Conclusion The preoperative exercise-based pre-rehabilitation before surgery for the patients with lung cancer is feasible and effective in enhancing physical function of the patients.Further studies can focus on the development of patient-centred standardised exercise pre-rehabilitation programs.

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