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.
2.80 kVp combined with artificial intelligence iterative reconstruction in lower extremity CT angiography of diabetic foot
Yichuan LIANG ; Huiying WANG ; Mingrui SONG ; Haonan ZHAO ; Quanliang MAO ; Yuning PAN
Chinese Journal of Medical Imaging Technology 2025;41(4):548-552
Objective To observe the value of 80 kVp combined with artificial intelligence iterative reconstruction(AIIR)in lower extremity CT angiography(CTA)of diabetic foot.Methods Sixty patients with diabetic foot were prospectively enrolled and divided into experimental group and control group(each n=30).Lower extremity CTA was performed using 80 kVp combined with AIIR in experimental group,while using 120 kVp combined with hybrid iterative reconstruction(HIR)in control group.The subjective and objective evaluation results of imaging quality,as well as the radiation dose of scanning were compared between groups.Results Compared with control group,images in experimental group showed higher subjective scores(5[5,5]vs.4[4,4]),displayed more branches of lower limb arteries(both P<0.05),while the radiation dose decreased by 59.76% ([8.29±0.53]mSv vs.[20.60±2.42]mSv).CT values,signal-to-noise ratio(SNR)and contrast-to-noise ratio(CNR)of each lower extremity artery segments were higher,while the noise of each lower extremity artery segments in experimental group were lower than those in control group(all P<0.05).Conclusion 80 kVp combined with AIIR could reduce radiation dose and improve imaging quality of lower extremity CTA of diabetic foot,hence being helpful to displaying small arteries of lower extremity,such as dorsalis pedis arteries and common plantar metatarsal arteries.
3.Reforming general practitioner training in China: system construction and practical exploration for a new era
Zequan JI ; Bingjie HU ; Yuyin LIAN ; Fangjian LI ; Xiang LIANG ; Yichuan LUO
Chinese Journal of General Practitioners 2025;24(9):1163-1167
This paper analyzes current issues in general practitioners (GP) education (e.g., inadequate systems, faculty shortages, misaligned training with community needs, low workforce attractiveness) and proposes strategies for reform in the new development era. Key recommendations include: strengthening academic discipline building in general practice within medical universities; innovating curricula to integrate prevention with treatment and emphasize practical skills; leveraging institutional resources to foster clinician-educator-researcher roles; tailoring training pathways to regional contexts; deepening collaboration between medical education and healthcare delivery systems; and building a robust lifelong learning framework for GPs. Furthermore, the paper details the comprehensive reform initiatives undertaken by Guangzhou Medical University (GMU). These include establishing integrated education platforms spanning university, hospital, and community settings. GMU′s experience offers valuable insights for enhancing GP training quality and scalability in China.
4.Safety and feasibility of Da Vinci robotic-assisted proximal gastrectomy for proximal gastric cancer and esophagogastric junction adenocarcinoma
Yichuan FAN ; Chi ZHANG ; Pin LIANG ; Xiang HU
Chinese Journal of General Surgery 2025;40(8):613-618
Objective:To evaluate the safety and feasibility of Da Vinci robot-assisted proximal gastrectomy (PG) for proximal gastric cancer (PGC) and adenocarcinoma of the esophagogastric junction (AEG).Method:Twenty-five patients (PGC: n=7; AEG: n=18) undergoing Da Vinci-assisted PG at the First Affiliated Hospital of Dalian Medical University from Jan 2021 to Mar 2025 were divided into (indocyanine green ,ICG) ( n=9) and non-ICG ( n=16) groups based on whether intraoperative ICG navigation was used. Perioperative outcomes and pathological data were compared. Results:All operations were successfully completed without conversion to open surgery. The median proximal resection margin was 3.0 cm (2.5-3.0) cm, and the median distal resection margin was 4.0 cm (3.0-5.0) cm. Operative time in the ICG and non-ICG groups was (294.4±41.3) min and (354.4±67.4) min, respectively, with a statistically significant difference ( t=2.760, P< 0.05). The total number of lymph nodes harvested, as well as D 1 and D 2 LN stations, was (29.3±14.8) vs. (21.8±6.3), 17.0 (10.0-24.8) vs. 14.0 (11.0-22.5), and 10.0 (2.0-17.0) vs. 7.2 (2.0-7.5) in the ICG and non-ICG groups, respectively. Although the ICG group showed a trend toward higher LN yield, the difference was not statistically significant ( P>0.05). Conclusions:Da Vinci robotic assisted proximal gastrectomy is safe and feasible for treating PGC and AEG. ICG fluorescence imaging demonstrates promising clinical value.
5.80 kVp combined with artificial intelligence iterative reconstruction in lower extremity CT angiography of diabetic foot
Yichuan LIANG ; Huiying WANG ; Mingrui SONG ; Haonan ZHAO ; Quanliang MAO ; Yuning PAN
Chinese Journal of Medical Imaging Technology 2025;41(4):548-552
Objective To observe the value of 80 kVp combined with artificial intelligence iterative reconstruction(AIIR)in lower extremity CT angiography(CTA)of diabetic foot.Methods Sixty patients with diabetic foot were prospectively enrolled and divided into experimental group and control group(each n=30).Lower extremity CTA was performed using 80 kVp combined with AIIR in experimental group,while using 120 kVp combined with hybrid iterative reconstruction(HIR)in control group.The subjective and objective evaluation results of imaging quality,as well as the radiation dose of scanning were compared between groups.Results Compared with control group,images in experimental group showed higher subjective scores(5[5,5]vs.4[4,4]),displayed more branches of lower limb arteries(both P<0.05),while the radiation dose decreased by 59.76% ([8.29±0.53]mSv vs.[20.60±2.42]mSv).CT values,signal-to-noise ratio(SNR)and contrast-to-noise ratio(CNR)of each lower extremity artery segments were higher,while the noise of each lower extremity artery segments in experimental group were lower than those in control group(all P<0.05).Conclusion 80 kVp combined with AIIR could reduce radiation dose and improve imaging quality of lower extremity CTA of diabetic foot,hence being helpful to displaying small arteries of lower extremity,such as dorsalis pedis arteries and common plantar metatarsal arteries.
6.Reforming general practitioner training in China: system construction and practical exploration for a new era
Zequan JI ; Bingjie HU ; Yuyin LIAN ; Fangjian LI ; Xiang LIANG ; Yichuan LUO
Chinese Journal of General Practitioners 2025;24(9):1163-1167
This paper analyzes current issues in general practitioners (GP) education (e.g., inadequate systems, faculty shortages, misaligned training with community needs, low workforce attractiveness) and proposes strategies for reform in the new development era. Key recommendations include: strengthening academic discipline building in general practice within medical universities; innovating curricula to integrate prevention with treatment and emphasize practical skills; leveraging institutional resources to foster clinician-educator-researcher roles; tailoring training pathways to regional contexts; deepening collaboration between medical education and healthcare delivery systems; and building a robust lifelong learning framework for GPs. Furthermore, the paper details the comprehensive reform initiatives undertaken by Guangzhou Medical University (GMU). These include establishing integrated education platforms spanning university, hospital, and community settings. GMU′s experience offers valuable insights for enhancing GP training quality and scalability in China.
7.Safety and feasibility of Da Vinci robotic-assisted proximal gastrectomy for proximal gastric cancer and esophagogastric junction adenocarcinoma
Yichuan FAN ; Chi ZHANG ; Pin LIANG ; Xiang HU
Chinese Journal of General Surgery 2025;40(8):613-618
Objective:To evaluate the safety and feasibility of Da Vinci robot-assisted proximal gastrectomy (PG) for proximal gastric cancer (PGC) and adenocarcinoma of the esophagogastric junction (AEG).Method:Twenty-five patients (PGC: n=7; AEG: n=18) undergoing Da Vinci-assisted PG at the First Affiliated Hospital of Dalian Medical University from Jan 2021 to Mar 2025 were divided into (indocyanine green ,ICG) ( n=9) and non-ICG ( n=16) groups based on whether intraoperative ICG navigation was used. Perioperative outcomes and pathological data were compared. Results:All operations were successfully completed without conversion to open surgery. The median proximal resection margin was 3.0 cm (2.5-3.0) cm, and the median distal resection margin was 4.0 cm (3.0-5.0) cm. Operative time in the ICG and non-ICG groups was (294.4±41.3) min and (354.4±67.4) min, respectively, with a statistically significant difference ( t=2.760, P< 0.05). The total number of lymph nodes harvested, as well as D 1 and D 2 LN stations, was (29.3±14.8) vs. (21.8±6.3), 17.0 (10.0-24.8) vs. 14.0 (11.0-22.5), and 10.0 (2.0-17.0) vs. 7.2 (2.0-7.5) in the ICG and non-ICG groups, respectively. Although the ICG group showed a trend toward higher LN yield, the difference was not statistically significant ( P>0.05). Conclusions:Da Vinci robotic assisted proximal gastrectomy is safe and feasible for treating PGC and AEG. ICG fluorescence imaging demonstrates promising clinical value.
8.Short-term outcomes of the Da Vinci Xi (fourth generation) robotic surgical system and laparoscopic-assisted gastrectomy for gastric cancer: a retrospective cohort study
Yichuan FAN ; Chi ZHANG ; Pin LIANG ; Xiang HU
Chinese Journal of Gastrointestinal Surgery 2024;27(8):808-815
Objective:To compare and analyze the short-term efficacy of the Da Vinci Xi (fourth generation) robotic surgical system and laparoscopic-assisted radical gastrectomy for gastric cancer.Method:In this retrospective cohort study, clinical pathological data of 190 patients with gastric cancer were collected from the clinical database of the First Affiliated Hospital of Dalian Medical University from 2020 Dec to 2023 May. The cohort comprised 136 men and 54 women aged 65 (30–85) years. Ninety of these patients had undergone robot assisted radical resection of gastric cancer and reconstruction of the digestive tract and were assigned to the robot-assisted group. The remaining 100 patients had undergone laparoscopic- assisted radical resection of gastric cancer and reconstruction of the digestive tract and were assigned to the laparoscopic control group. Variables investigated included surgical and postoperative factors and postoperative complications.Result:The procedure was successfully completed without the need to transition to open surgery in every patient in both groups. The median duration of surgery was 315 (270, 360) minutes and 240 (202, 280) minutes, median intraoperative blood loss 20 (10, 30) mL and 30 (10, 50) mL, median incision length 12.0 (10.8,13.0) cm and 10.0 (8.0, 10.8) cm, median time to first postoperative passage of flatus 4 (3, 5) days and 4 (4, 5) days, median time to first postoperative fluid intake 6 (4, 7) days and 8 (6, 9) days, time to gastric tube removal 4 (3, 7) days and 6 (5, 8) days, median time to drainage tube removal 8 (7, 10) days and 10 (9, 12) days, median duration of postoperative hospitalization 8 (7, 11) days and 12 (10, 14) days, and cost of surgery (7.6±1.2)×10 4 yuan and (4.0±0.6)×10 4 yuan in the robot-assisted and laparoscopic control groups, respectively. All the differences in the above indicators between the two groups of patients were statistically significant (all P<0.05). There were also significantly fewer complications in the robot-assisted than the laparoscopic control group (28.9% [26/90] vs. 44.0% [44/100], χ 2=0.31, P=0.031). Further subgroup analysis showed that the following factors were associated with greater improvement in the robot-assisted than laparoscopic control group: male sex (OR=0.41, 95%CI: 0.20–0.83, P=0.015), body mass index Conclusion:The Da Vinci robotic surgical system is safe and feasible for gastrectomy achieving a shorter recover period and fewer preoperative comorbidities.
9.Short-term outcomes of the Da Vinci Xi (fourth generation) robotic surgical system and laparoscopic-assisted gastrectomy for gastric cancer: a retrospective cohort study
Yichuan FAN ; Chi ZHANG ; Pin LIANG ; Xiang HU
Chinese Journal of Gastrointestinal Surgery 2024;27(8):808-815
Objective:To compare and analyze the short-term efficacy of the Da Vinci Xi (fourth generation) robotic surgical system and laparoscopic-assisted radical gastrectomy for gastric cancer.Method:In this retrospective cohort study, clinical pathological data of 190 patients with gastric cancer were collected from the clinical database of the First Affiliated Hospital of Dalian Medical University from 2020 Dec to 2023 May. The cohort comprised 136 men and 54 women aged 65 (30–85) years. Ninety of these patients had undergone robot assisted radical resection of gastric cancer and reconstruction of the digestive tract and were assigned to the robot-assisted group. The remaining 100 patients had undergone laparoscopic- assisted radical resection of gastric cancer and reconstruction of the digestive tract and were assigned to the laparoscopic control group. Variables investigated included surgical and postoperative factors and postoperative complications.Result:The procedure was successfully completed without the need to transition to open surgery in every patient in both groups. The median duration of surgery was 315 (270, 360) minutes and 240 (202, 280) minutes, median intraoperative blood loss 20 (10, 30) mL and 30 (10, 50) mL, median incision length 12.0 (10.8,13.0) cm and 10.0 (8.0, 10.8) cm, median time to first postoperative passage of flatus 4 (3, 5) days and 4 (4, 5) days, median time to first postoperative fluid intake 6 (4, 7) days and 8 (6, 9) days, time to gastric tube removal 4 (3, 7) days and 6 (5, 8) days, median time to drainage tube removal 8 (7, 10) days and 10 (9, 12) days, median duration of postoperative hospitalization 8 (7, 11) days and 12 (10, 14) days, and cost of surgery (7.6±1.2)×10 4 yuan and (4.0±0.6)×10 4 yuan in the robot-assisted and laparoscopic control groups, respectively. All the differences in the above indicators between the two groups of patients were statistically significant (all P<0.05). There were also significantly fewer complications in the robot-assisted than the laparoscopic control group (28.9% [26/90] vs. 44.0% [44/100], χ 2=0.31, P=0.031). Further subgroup analysis showed that the following factors were associated with greater improvement in the robot-assisted than laparoscopic control group: male sex (OR=0.41, 95%CI: 0.20–0.83, P=0.015), body mass index Conclusion:The Da Vinci robotic surgical system is safe and feasible for gastrectomy achieving a shorter recover period and fewer preoperative comorbidities.
10.Clinical efficacy of da Vinci Xi robotic surgical system assisted pylorus and vagus preser-ving partial gastrectomy for early gastric cancer
Yichuan FAN ; Chi ZHANG ; Maohua WEI ; Hua ZHONG ; Haitao DUAN ; Weifeng SUN ; Liang CAO ; Jian ZHANG ; Pin LIANG ; Xiang HU
Chinese Journal of Digestive Surgery 2023;22(8):1014-1020
Objective:To investigate the clinical efficacy of da Vinci Xi robotic surgical system assisted pylorus and vagus preserving partial gastrectomy (RaPPG) for early gastric cancer.Methods:The retrospective cohort study was conducted. The clinicopathological data of 40 patients with early gastric cancer who were admitted to the First Affiliated Hospital of Dalian Medical University from December 2020 to November 2022 were collected. There were 26 males and 14 females, aged (64±8)years. Of the 40 patients, 19 patients undergoing da Vinci Xi RaPPG were divided into the robotic assisted group, and 21 patients undergoing laparoscopic assisted pylorus and vagus preserving partial gastrectomy (PPG) were divided into the laparoscopic control group. Observation indicators: (1) surgical situations; (2) postoperative complications; (3) follow-up. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was conducted using the independent t test. Measurement data with skewed distribution were represented as M( Q1, Q3) or M(range), and comparison between groups was conducted using the Mann-Whitney U test. Count data were described 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 rank sum test. Results:(1) Surgical situations. All patients in the two groups underwent surgery successfully, without conversion to laparotomy. The operation time, volume of intraoperative blood loss, time to postoperative first flatus, time to postoperative first liquid food intake, time to post-operative drainage tube removal, duration of postoperative hospital stay, tumor diameter, distance from distal resection margin to tumor were (298±52)minutes, 10(10, 10)mL, 3.0(3.0, 3.0)days, 3.0(3.0,4.0)days, 6.0(6.0,8.0)days, 7.0(6.0,8.0)days, (2.3±0.7)cm, 3.0(2.0,3.0)cm in patients of the robotic assisted group, versus (236±37)minutes, 25(15,50)mL, 5.0(4.0,5.0)days, 6.0(5.5,7.0)days, 8.0(8.0,9.5)days, 8.0(7.5,9.5)days, (2.9±1.1)cm ,2.0(1.5,2.0)cm in patients of the laparoscopic control group, showing significant differences in the above indicators between the two groups ( t=4.41, Z=-3.38, -4.75, -4.38, -2.98, -2.58, t=-2.10, Z=-3.03, P<0.05). (2) Postoperative complications. Cases with postoperative complications, cases with delayed gastric emptying, cases with acid regurgita-tion, cases with atelectasis, cases with infection of incision, cases with hyperamylasemia, cases with uroschesis were 6, 1, 1, 0, 1, 3, 0 in patients of the robotic assisted group. The above indicators were 20, 4, 3, 2, 1, 9, 1 in patients of the laparoscopic control group. There was a significant difference in the postoperative complications between the two groups ( χ2=17.77, P<0.05). (3) Follow-up. Of the 40 patients, 34 patients were followed up. There were 16 patients in the robotic assisted group who were followed up for 9(range, 6-18)months, and there were 18 patients in the laparoscopic control group who were followed up for 16(range, 9-23)months. During the follow-up period, all patients had good anastomosis healing, pyloric contraction function, and gastric emptying function. Conclusions:da Vinci Xi RaPPG is safe and feasible for the treatment of early gastric cancer. Compared with laparoscopic assisted PPG, treatment of gastric cancer with da Vinci Xi RaPPG can significantly reduce the volume of intraoperative blood loss, shorten the time to postoperative first flatus, time to postoperative first liquid food intake, time to postoperative drainage tube removal, duration of postoperative hospital stay, benefit the distance from distal resection margin to tumor, and reduce the incidence of postoperative complications.

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