Clinical value of a machine learning model integrating ultrasound radiomics and clinical features for predicting pathological complete response to neoadjuvant therapy in HER2-positive breast cancer
Development of a prediction model for high Ki-67 expression in invasive breast cancer based on dual-energy CT quantitative parameters
Clinical value of ultrasound-guided guidewire localization in reoperation for recurrent metastatic lymph nodes after thyroid cancer surgery
Anti-tumor effects and potential mechanisms of oyster glycogen in papillary thyroid carcinoma: a network pharmacology and in vitro experimental study
Comparison and interpretation of Chinese and international expert consensuses on intersphincteric resection from an anatomical perspective
Complications and surgical optimization of terminal ileostomy: focus on the one-stitch technique
Short-term outcomes of circular-stapled esophagojejunostomy after totally laparoscopic versus laparoscopy-assisted total gastrectomy: a propensity score-matched study (with video)
Efficacy and safety of endoluminal vacuum-assisted closure for esophagojejunal anastomotic leakage: a retrospective analysis of 21 cases (with video)
Guidelines for the diagnosis and treatment of primary liver cancer (2026 edition)
Injury severity-dependent differences in pancreatic regeneration and repair in cerulein-induced acute pancreatitis
Laparoscopic spleen-preserving distal pancreatectomy combined with autologous islet transplantation for intraductal papillary mucinous neoplasms: a case report and literature review
Pancreaticojejunostomy guided by the theory of mucosal priority healing
Global and Chinese disease burden of alcoholic pancreatitis and its causal association with alcohol consumption
Application of Y-shaped reconstruction using allogeneic common iliac vein and its branches in pancreatic cancer with long-segment portal vein-superior mesenteric vein involvement
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Obesity Metabolic Surgery Comprehensive Management, Nursing Support Group, Chinese College of Surgeons
2026,35(5):855-872, DOI: 10.7659/j.issn.1005-6947.260051
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Metabolic and bariatric surgery (MBS) is a key treatment for moderate-to-severe obesity and its related metabolic diseases. However, patients may still experience weight loss plateaus, recurrent weight gain, nutritional deficiencies, and psychological-behavioral issues after surgery, compromising long-term outcomes and quality of life. Although domestic expert consensuses on weight loss plateau management and postoperative follow-up exist, there remains a lack of a comprehensive clinical pathway covering the entire process from preoperative assessment and perioperative management to long-term follow-up. This consensus was developed by the Expert Working Group on Obesity Metabolic Surgery Comprehensive Management and Nursing Support Group, Chinese College of Surgeons. Based on a systematic review of domestic and international guidelines, consensuses, and evidence-based literature, recommendations were formulated through two rounds of expert consultation and discussion. The consensus addresses six aspects: definition and goals of weight management, preoperative evaluation and intensive management, staged postoperative weight management, identification and management of recurrent weight gain, multidisciplinary collaboration and long-term follow-up system, and patient education and self-management. It establishes a full-cycle clinical pathway covering "assessment-intervention-follow-up-support", aiming to provide a standardized reference for weight management in MBS patients, enhance long-term weight maintenance and metabolic benefits, and promote the standardization of weight management in metabolic and bariatric surgery in China.
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Youth Committee of the Expert Working Group on Surgical Diagnosis, Treatment of Gastroesophageal Reflux Disease, Surgeons Branch of the Chinese Medical Doctor Association, Hernia, Abdominal Wall Surgery Branch of the Guangdong Medical Association, Gastrointestinal Hernia, Abdominal Wall Branch jointly established by the Guangdong Science, Technology Achievement Transformation Promotion Association, the Guangdong Institute for the Development of All-People's Health, Working Group on Hiatal Hernia, Gastroesophageal Reflux Disease, Hernia, Abdominal Wall Surgery Branch of the Guangdong Medical Doctor Association
2026,35(5):873-882, DOI: 10.7659/j.issn.1005-6947.260115
Abstract:
Hiatal hernia (HH) is an important etiological factor of gastroesophageal reflux disease (GERD). However, the preoperative evaluation strategies for HH-related antireflux surgery remain insufficiently standardized, and controversies still exist regarding the indications, combinations, and interpretation of different diagnostic modalities, which may affect surgical decision-making and postoperative outcomes. To standardize the preoperative assessment of HH-related antireflux surgery in China, the Expert Working Group on Gastroesophageal Reflux Disease of the Chinese Medical Doctor Association, together with multiple academic societies, convened 104 experts nationwide to develop consensus recommendations through face-to-face discussions and Delphi voting. Based on the latest international and domestic guidelines, consensus statements, and current evidence, recommendations were established for seven core aspects of preoperative evaluation, including 24-hour esophageal pH monitoring, high-resolution esophageal manometry, endoscopy, upper gastrointestinal contrast studies, chest and abdominal computed tomography, gastroesophageal contrast-enhanced ultrasonography, and other adjunctive examinations. This consensus emphasizes a multidimensional preoperative assessment system centered on symptoms, function, and anatomy, advocates individualized and stratified diagnostic strategies, and highlights the importance of multidisciplinary collaboration in the management of complex cases. The aim of this consensus is to provide practical guidance for the standardized preoperative evaluation of HH-related antireflux surgery. Given the overall limited quality of current evidence, more high-quality research is still needed in the future to further optimize the preoperative assessment system.
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TANG Shuijuan, WANG Zhiyuan, WU Fang, LI Wenbin, CHEN Wenjuan, SONG Zhixuan, YU Xiaoping, ZHENG Hong
2026,35(5):883-896, DOI: 10.7659/j.issn.1005-6947.260016
Abstract:
Background and Aims HER2-positive breast cancer is characterized by strong invasiveness and marked heterogeneity. Although neoadjuvant chemotherapy (NAC) combined with anti-HER2 targeted therapy significantly improves the pathological complete response (pCR) rate, therapeutic responses vary substantially among patients. Therefore, developing a noninvasive pretreatment predictive model is of great importance for individualized treatment optimization. This study aimed to evaluate the clinical value of machine learning models based on ultrasound radiomics and clinicopathological features in predicting pCR in HER2-positive breast cancer after NAC combined with anti-HER2 targeted therapy.Methods A total of 353 patients with pathologically confirmed HER2-positive breast cancer who received NAC combined with anti-HER2 targeted therapy between October 2019 and October 2024 were retrospectively enrolled from Hunan Cancer Hospital and the Third Xiangya Hospital of Central South University. Among them, 275 patients from Hunan Cancer Hospital were assigned to the internal dataset, while 78 patients from the Third Xiangya Hospital were used as the external validation dataset. Ultrasound radiomics features were extracted from pretreatment ultrasound images and combined with clinicopathological features. After correlation analysis and least absolute shrinkage and selection operator (LASSO) regression for feature selection, Extreme Gradient Boosting (XGBoost), Random Forest, and Na?ve Bayes algorithms were applied to construct clinical models, radiomics models, and combined models. Receiver operating characteristic curves were used to evaluate predictive performance, decision curve analysis (DCA) was performed to assess clinical utility, and Shapley Additive Explanation (SHAP) analysis was used to interpret feature importance in the optimal model.Results Twelve clinicopathologic features and seven ultrasound radiomics features were finally selected for model construction. Among the three algorithms, the XGBoost model demonstrated the best predictive performance. Compared with the clinical model or radiomics model alone, the combined model achieved superior predictive efficacy. The AUCs of the XGBoost combined model for predicting pCR were 0.964 (95% CI=0.893-0.965), 0.857 (95% CI=0.822-0.960), and 0.771 (95% CI=0.765-0.946) in the training, internal validation, and external validation cohorts, respectively. DCA demonstrated favorable net clinical benefits across a wide range of threshold probabilities. SHAP analysis revealed that HER2 expression status, targeted therapy strategy, estrogen receptor status, and several texture features contributed substantially to model prediction.Conclusion The XGBoost machine learning model integrating ultrasound radiomics and clinicopathological features can effectively predict pCR after NAC combined with anti-HER2 targeted therapy in HER2-positive breast cancer, showing promising clinical utility for individualized therapeutic decision-making.
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HUA Bangjiang, YANG Hao, ZHAO Chenjin, SHEN Xiaocheng, LI Fangfang, YANG Hongwei, MOU Dewu, DU Songli, YANG Lei, CHEN Maoshan
2026,35(5):897-906, DOI: 10.7659/j.issn.1005-6947.250445
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Background and Aims Ki-67 is an important biomarker reflecting proliferative activity in breast cancer and plays a critical role in prognosis evaluation and treatment decision-making. Currently, Ki-67 assessment mainly relies on invasive immunohistochemical examination, and effective non-invasive evaluation methods remain limited. This study aimed to develop a nomogram based on dual-energy computed tomography (DECT) quantitative parameters for predicting Ki-67 expression in invasive breast cancer.Methods A total of 128 patients with pathologically confirmed invasive breast cancer who underwent DECT examination at Suining Central Hospital between October 2023 and June 2024 were prospectively enrolled. According to a Ki-67 cutoff value of 20%, patients were classified into a high-expression group (n=85) and a low-expression group (n=43). Quantitative DECT parameters from the non-contrast, arterial, and venous phases were collected, including spectral curve slope (λ), iodine concentration (IC), normalized iodine concentration (NIC), effective atomic number (Zeff), normalized effective atomic number (NZeff), and tumor-arterial iodine fraction (TAIF). Receiver operating characteristic (ROC) analysis was used to evaluate the predictive performance of each parameter. Subsequently, the Boruta algorithm was employed to select feature variables, and a logistic regression model was constructed to develop a nomogram. Internal validation was performed using Bootstrap resampling, and model performance was evaluated by ROC analysis, calibration curves, and decision curve analysis (DCA).Results Compared with the low-expression group, the high Ki-67 expression group showed significantly higher values in non-contrast λ, arterial-phase λ, arterial-phase IC, arterial-phase NIC, arterial-phase Zeff, arterial-phase NZeff, venous-phase NIC, venous-phase Zeff, and TAIF (all P<0.05). ROC analysis demonstrated that all DECT quantitative parameters had predictive value for Ki-67 expression, among which arterial-phase IC showed the best performance (AUC=0.721). Five variables, including TAIF, arterial-phase Zeff, arterial-phase IC, arterial-phase λ, and venous-phase λ, were selected to establish the prediction model. Internal validation showed that the model achieved an AUC of 0.818 (95% CI=0.728-0.900). The calibration curve demonstrated good agreement between predicted and observed probabilities (Hosmer-Lemeshow test, P=0.312), and DCA indicated favorable clinical utility across a wide range of threshold probabilities.Conclusion The nomogram based on DECT quantitative parameters can effectively predict high Ki-67 expression in invasive breast cancer and may provide a useful non-invasive tool for molecular characterization and clinical decision-making.
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XIA Weizhi, ZENG Wenjing, LUO Shayang, HUANG Juan, RONG Zhuoxian, WANG Shouman
2026,35(5):907-918, DOI: 10.7659/j.issn.1005-6947.260035
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Background and Aims Triple-negative breast cancer (TNBC) is characterized by strong invasiveness and poor prognosis. Metabolic reprogramming, particularly oxidative phosphorylation (OXPHOS) dysregulation, plays a critical role in TNBC progression. This study aimed to identify OXPHOS-related prognostic genes and construct a prognostic prediction model for TNBC based on multi-omics data.Methods Genes associated with poor prognosis in breast cancer were screened from the Human Protein Atlas database. Combined with GSE176078 single-cell RNA sequencing data and COSMIC cell line data, TNBC-related metabolic genes were identified. A prognostic model was established using the TCGA-BRCA Basal-like cohort through univariate Cox, LASSO, and multivariate Cox regression analyses. A nomogram integrating clinicopathological variables was subsequently constructed. External validation was performed using the ICGC-BRCA-US cohort. In addition, the ESTIMATE and CIBERSORT algorithms were applied to investigate the relationship between the risk score and the tumor immune microenvironment.Results A total of 63 metabolism-related genes associated with poor prognosis in breast cancer were identified, mainly enriched in oxidative phosphorylation and ATP metabolic pathways. Among them, 16 genes were significantly overexpressed in TNBC tumor cells and were primarily involved in the electron transport chain process. The dCTP pyrophosphatase 1 (DCTPP1) and cytochrome C1 (CYC1) were ultimately identified as independent prognostic risk genes and used to construct the risk model. Patients in the high-risk group exhibited significantly worse overall survival than those in the low-risk group (P=0.006). The AUC values for predicting 1-, 3-, 5-, and 10-year overall survival were 0.664, 0.655, 0.662, and 0.775, respectively, with a C-index of 0.634. The nomogram incorporating age and M stage achieved a C-index of 0.726. External validation using the ICGC cohort confirmed the robustness of the model. Immune infiltration analysis demonstrated that the risk score was negatively correlated with Immune score, Stromal score, and ESTIMATE score, but positively correlated with tumor purity. Moreover, CD8+ T-cell infiltration was significantly reduced in the high-risk group.Conclusion This study successfully developed and validated an OXPHOS-related prognostic model for TNBC using multi-omics data. DCTPP1 and CYC1 may serve as key metabolic drivers of poor prognosis and therapeutic targets in TNBC. This model may provide a useful tool for prognostic stratification and individualized treatment of TNBC patients.
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LIANG Sibo, DING Zhaoming, BI Wen, NIE Chunlei
2026,35(5):919-926, DOI: 10.7659/j.issn.1005-6947.250691
Abstract:
Background and Aims Reoperation for recurrent cervical lymph node metastasis after thyroid cancer surgery is technically challenging because of postoperative scar adhesion, distorted anatomy, and an increased risk of complications. Conventional ultrasound-guided surface marking has limited accuracy in intraoperative localization. This study aimed to compare the efficacy and safety of ultrasound-guided guidewire localization and ultrasound-guided surface marking in the surgical management of recurrent lymph nodes after thyroid cancer surgery.Methods Clinical data of 27 patients with recurrent cervical lymph node metastasis after thyroid cancer surgery who underwent reoperation at Harbin Medical University Cancer Hospital between May 2023 and May 2025 were retrospectively analyzed. Twelve patients underwent ultrasound-guided guidewire localization (guidewire group), and 15 patients underwent ultrasound-guided surface marking (surface-marking group). Perioperative outcomes, metastatic lymph node detection, and postoperative complications were compared between the two groups.Results In both the lateral neck and central compartment subgroups, operative time and intraoperative blood loss were significantly lower in the guidewire group than in the surface-marking group (all P<0.05). In patients undergoing lateral neck dissection, postoperative drainage volume was significantly lower in the guidewire group (P<0.05), whereas no significant difference was observed in the central compartment subgroup (P>0.05). A total of 20 metastatic lymph nodes were identified among 35 dissected lymph nodes in the guidewire group, with a positive lymph node rate of 57.14%, compared with 22 positive lymph nodes among 52 dissected lymph nodes in the surface-marking group, yielding a positive lymph node rate of 42.31% (P=0.019). The postoperative complication rates were 16.67% and 20.00% in the guidewire and surface-marking groups, respectively, without significant difference (P>0.05). During the 3-month follow-up, suspicious residual lymph nodes were detected in one patient in the surface-marking group.Conclusion Ultrasound-guided guidewire localization improves the accuracy of intraoperative localization for recurrent metastatic lymph nodes after thyroid cancer surgery, shortens operative time, reduces intraoperative blood loss and tissue dissection, and may improve metastatic lymph node detection rates. This technique is safe and shows promising clinical application value.
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LIU Shiguang, YAO Yi, LI Jiahao, HU Yaojie
2026,35(5):927-935, DOI: 10.7659/j.issn.1005-6947.250648
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Background and Aims Patients with high-risk papillary thyroid carcinoma (PTC) remain at substantial risk of postoperative recurrence. Identification of simple and reliable prognostic biomarkers is therefore of clinical importance. This study aimed to evaluate the predictive value of preoperative neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and systemic immune-inflammation index (SII) for postoperative recurrence in patients with high-risk PTC.Methods Clinical data of 337 patients with high-risk PTC who underwent radical surgery at Tangshan Workers' Hospital between January 2018 and December 2024 were retrospectively analyzed. According to follow-up outcomes, patients were divided into recurrence (n=41) and non-recurrence (n=296) groups. Clinicopathological characteristics and preoperative inflammatory indices were compared between groups. Receiver operating characteristic (ROC) curve analysis was performed to evaluate predictive performance. Logistic regression analysis was used to identify independent predictors of recurrence, and recurrence-free survival (RFS) was analyzed using the Kaplan-Meier method.Results During follow-up, 41 patients (12.2%) developed recurrence. Compared with the non-recurrence group, the recurrence group exhibited significantly lower NLR, PLR, and SII levels (all P<0.05). ROC analysis showed that the AUC values of NLR, PLR, and SII for predicting recurrence were 0.728, 0.780, and 0.823, respectively, with SII demonstrating the best predictive performance. Multivariate Logistic regression analysis identified PLR≤118.26 (OR=5.894, 95% CI=1.615-21.508, P=0.007) and SII≤397.56 (OR=5.715, 95% CI=1.721-18.983, P=0.004) as independent risk factors for postoperative recurrence. Kaplan-Meier analysis showed significantly lower RFS rates in patients with low PLR and low SII levels than in those with higher values (both P<0.05).Conclusion Preoperative PLR and SII are independently associated with postoperative recurrence in patients with high-risk PTC. SII exhibits favorable predictive performance and may serve as a useful biomarker for risk stratification and prognostic evaluation in this population.
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LUO Chang, XUE Mengyao, LI Dan, DU Yi, SUN Haidong
2026,35(5):936-944, DOI: 10.7659/j.issn.1005-6947.260149
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Background and Aims Papillary thyroid carcinoma (PTC) is the most common type of thyroid malignancy. Despite favorable outcomes in most patients, recurrence, metastasis, and radioiodine-refractory disease remain important clinical challenges. Glycogen, a major bioactive component derived from oyster, has demonstrated antitumor activity; however, its effects and underlying mechanisms in PTC remain unclear. This study aimed to investigate the potential anti-PTC mechanisms of oyster glycogen through network pharmacology, molecular docking, and in vitro experiments.Methods Potential targets of oyster glycogen were predicted using the ChEMBL, ETCM, and SwissTargetPrediction databases, while PTC-related targets were collected from the GeneCards, OMIM, and PharmGKB databases. Common targets were identified and subjected to protein-protein interaction (PPI) network construction, Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. Core targets were screened and further validated by molecular docking using AutoDock Vina. TPC-1 cells were treated with different concentrations of oyster glycogen. Cell viability was evaluated using the CCK-8 assay, and apoptosis was assessed by Annexin V-FITC/PI staining followed by flow cytometry.Results A total of 48 common targets were identified between oyster glycogen and PTC. PPI analysis revealed PTGS2, GSK3β, AR, and PGR as key targets. GO and KEGG analyses suggested that these targets were mainly involved in epithelial cell proliferation, transcription factor binding, and the PI3K-Akt signaling pathway. Molecular docking demonstrated favorable binding affinities between oyster glycogen and the core targets, with the strongest interaction observed for PTGS2 (-9.1 kcal/mol). CCK-8 assays showed that oyster glycogen inhibited TPC-1 cell viability in a dose- and time-dependent manner, with IC20 and IC50 values of 37.7 μmol/L and 233.6 μmol/L, respectively, at 48 h. Flow cytometric analysis demonstrated that treatment with 37.7 μmol/L oyster glycogen for 48 h increased the total apoptosis rate from 0.20% to 18.61% (P<0.01).Conclusion Oyster glycogen inhibits the proliferation of PTC cells and promotes apoptosis. These effects may be associated with PTGS2, GSK3β, and the PI3K-Akt signaling pathway. Further molecular studies are required to validate the underlying mechanisms.
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HUANG Chengcheng, LIU Weiwei, LI Jing, ZHENG Lu, WANG Chaoqun
2026,35(5):945-959, DOI: 10.7659/j.issn.1005-6947.260218
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Background and Aims Gamma-aminobutyric acid type A receptor delta subunit (GABRD) has been implicated in the progression of several malignancies, whereas its biological role and therapeutic relevance in hepatocellular carcinoma (HCC) remain largely unknown. This study aimed to investigate the expression pattern, oncogenic function, and potential molecular mechanisms of GABRD in HCC and to identify candidate small-molecule inhibitors targeting GABRD.Methods Public datasets from HCCDB and TCGA, together with clinical specimens, were used to evaluate GABRD expression and prognostic significance. Gain- and loss-of-function models were established using lentiviral overexpression and CRISPR/Cas9-mediated knockout approaches. Cell proliferation, migration, and invasion were assessed by CCK-8, EdU incorporation, colony formation, wound-healing, and Transwell assays. The in vivo effects were evaluated using subcutaneous xenograft, spontaneous HCC, and pulmonary metastasis models. RNA sequencing combined with GO, KEGG, and GSEA analyses was performed to explore downstream mechanisms. Structure-based virtual screening, molecular docking, and molecular dynamics simulations were applied to identify potential GABRD-targeting compounds, followed by in vitro and in vivo validation.Results GABRD was significantly upregulated in HCC tissues and cell lines, and its elevated expression was associated with unfavorable overall survival, disease-specific survival, and progression-free survival. GABRD knockout markedly inhibited HCC cell proliferation, migration, and invasion, whereas GABRD overexpression exerted opposite effects. In vivo studies further demonstrated that GABRD deficiency suppressed tumor growth and pulmonary metastasis. Transcriptomic analyses suggested that GABRD might promote HCC progression through cytokine-cytokine receptor interaction, JAK-STAT signaling, and epithelial-mesenchymal transition-related pathways. Structure-based virtual screening identified memantine as a potential GABRD-binding compound with high binding affinity. Memantine reduced GABRD expression and significantly reversed the pro-tumorigenic effects mediated by GABRD both in vitro and in vivo.Conclusion GABRD acts as an oncogenic regulator in HCC and may serve as a prognostic biomarker and therapeutic target. Memantine suppresses HCC growth and metastasis by targeting GABRD, providing experimental evidence for drug repurposing and novel targeted therapeutic strategies in HCC.
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WANG Jiamin, ZENG Huilan, CHENG Jie, CUI Fangfang, YANG Taoyu, HUANG Anqi, MO Jiaqiang, YE Qing, XIONG Zihui, WANG Qiuting, HE Jia'nan
2026,35(5):960-977, DOI: 10.7659/j.issn.1005-6947.260026
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Background and Aims Invasion and metastasis are major causes of poor prognosis in hepatocellular carcinoma (HCC). Although homeobox A11 (HOXA11) has been implicated in various malignancies, its biological role and underlying mechanisms in HCC remain unclear. This study investigated the epigenetic regulation of HOXA11 and its effects on HCC progression and metastasis.Methods Eleven paired HCC and adjacent non-tumor tissues were collected. HOXA11 expression and promoter methylation were examined using Western blotting, immunohistochemistry, and bisulfite sequencing PCR (BSP). Decitabine (DAC) was used for demethylation treatment. Stable HOXA11 knockdown and overexpression cell lines were established. Cell proliferation, migration, and invasion were assessed by CCK-8 and Transwell assays. Expression of the TGF-β/Smad pathway- and epithelial-mesenchymal transition (EMT)-related proteins was analyzed by Western blotting. TGF-β1 rescue experiments were performed to verify the underlying mechanism. A nude mouse lung metastasis model was established to evaluate the effect of HOXA11 on metastatic potential in vivo.Results HOXA11 expression was significantly decreased in HCC tissues, whereas promoter methylation was significantly increased compared with adjacent tissues (both P<0.05). DAC treatment reduced promoter methylation and restored HOXA11 expression. HOXA11 knockdown significantly enhanced HCC cell proliferation, migration, and invasion, whereas HOXA11 overexpression exerted the opposite effects (all P<0.05). Mechanistically, HOXA11 negatively regulated the TGF-β/Smad signaling pathway and suppressed EMT, as evidenced by increased E-cadherin expression and decreased expression of Snail, N-cadherin, vimentin, and fibronectin. TGF-β1 rescue experiments further demonstrated that HOXA11 overexpression partially antagonized TGF-β1-induced Smad phosphorylation and EMT progression. Clinical analyses confirmed significant associations between low HOXA11 expression, activation of the TGF-β/Smad pathway, and EMT-related alterations. In vivo, HOXA11 overexpression significantly reduced pulmonary metastatic burden (P<0.05).Conclusion HOXA11 is epigenetically silenced through promoter hypermethylation in HCC. By negatively regulating the TGF-β/Smad signaling pathway and suppressing EMT, HOXA11 inhibits HCC invasion and metastasis. These findings suggest that HOXA11 may serve as a potential therapeutic target for epigenetic and anti-metastatic intervention in HCC.
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MA Min, WU Runliu, ZHOU Qiang, GUO Yihang, CHEN Miao
2026,35(5):978-989, DOI: 10.7659/j.issn.1005-6947.260112
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Background and Aims Krüppel-like factor 5 (KLF5) and endothelial cell-specific molecule 1 (ESM1) are closely associated with tumor progression. However, whether KLF5 promotes gastric cancer progression through transcriptional regulation of ESM1 remains unclear. This study investigated the regulatory relationship between KLF5 and ESM1 and their roles in GC progression.Methods Thirty paired gastric cancer and adjacent normal tissues were collected. The expression of KLF5 and ESM1 was determined by qRT-PCR, Western blot and immunohistochemistry. The UALCAN and JASPAR databases were used to analyze gene expression and predict potential binding sites. Dual-luciferase reporter assays and chromatin immunoprecipitation-qPCR (ChIP-qPCR) were performed to verify the transcriptional regulation of ESM1 by KLF5. Functional assays including colony formation, wound-healing and Transwell assays were conducted to evaluate cell proliferation, migration and invasion. A nude mouse xenograft model was established to assess the in vivo effects.Results ESM1 expression was significantly elevated in gastric cancer tissues and cell lines compared with corresponding controls (all P<0.05). KLF5 was also highly expressed in GC tissues. Bioinformatics analysis predicted a KLF5-binding site within the ESM1 promoter region. Dual-luciferase reporter and ChIP-qPCR assays confirmed that KLF5 directly bound to the ESM1 promoter and transcriptionally activated ESM1 expression. Knockdown of either KLF5 or ESM1 significantly inhibited the proliferation, migration and invasion of AGS and HGC-27 cells (all P<0.05). ESM1 overexpression markedly reversed the suppressive effects induced by KLF5 silencing (all P<0.05). In vivo experiments further demonstrated that KLF5 knockdown inhibited xenograft tumor growth, whereas ESM1 overexpression partially rescued tumor growth.Conclusion KLF5 promotes gastric cancer cell proliferation, migration, invasion, and tumorigenesis by directly transcriptionally activating ESM1. The KLF5-ESM1 regulatory axis may serve as a promising molecular target for the diagnosis and treatment of gastric cancer.
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YE Ke, ZHU Zhongcheng, LU Zichuan, TANG Tiantian, LIANG Shuai
2026,35(5):990-1002, DOI: 10.7659/j.issn.1005-6947.260125
Abstract:
Background and Aims Pancreatic cancer is characterized by high aggressiveness and a profoundly immunosuppressive microenvironment, while the mechanisms underlying its immune evasion remain incompletely understood. Enhanced glycolysis in tumor cells leads to excessive lactate accumulation, which can regulate gene transcription through histone lactylation. However, the role of histone lactylation in remodeling the immune microenvironment of pancreatic cancer and its underlying molecular mechanisms remains unclear. This study aimed to investigate the role and molecular mechanism of histone H3 lysine 18 lactylation (H3K18la) in regulating nuclear pore membrane protein 121 (POM121)-mediated immune escape in pancreatic cancer.Methods The expression patterns and prognostic significance of lactate dehydrogenase A (LDHA) and POM121 in pancreatic cancer were analyzed using The Cancer Genome Atlas (TCGA) database. Western blotting was performed to determine the levels of pan-lysine lactylation (Pan-Kla), H3K18la, and POM121 in pancreatic cancer cells. Lactate production was inhibited by treatment with the LDH inhibitor oxamate or by siRNA-mediated LDHA silencing, followed by assessment of intracellular lactate levels, cell proliferation, and colony-forming ability using lactate assays, CCK-8 assays, and colony formation assays. A co-culture system of pancreatic cancer cells and CD8+ T cells was established, and the expression of GZMB, TNF-α, and IFN-γ was analyzed by flow cytometry. ChIP-qPCR and dual-luciferase reporter assays were used to verify the transcriptional regulation of POM121 by H3K18la. Gain- and loss-of-function experiments of POM121 were performed to determine its role in lactylation-mediated immune regulation. A PANC02 tumor-bearing mouse model was established to validate the in vivo effects.Results LDHA and POM121 were significantly upregulated in pancreatic cancer tissues and were associated with poor patient prognosis. Levels of Pan-Kla and H3K18la were markedly increased in pancreatic cancer cells. Oxamate treatment or LDHA silencing reduced intracellular lactate production and H3K18la levels, suppressed pancreatic cancer cell proliferation, and enhanced CD8+ T-cell effector functions, as evidenced by increased expression of GZMB, TNF-α, and IFN-γ. POM121 was highly expressed in pancreatic cancer cells and positively regulated by H3K18la. ChIP-qPCR and dual-luciferase assays demonstrated that H3K18la was enriched at the POM121 promoter region and enhanced its transcriptional activity. Knockdown of POM121 inhibited tumor cell proliferation and enhanced CD8+ T-cell function, whereas POM121 overexpression partially reversed the antitumor immune effects induced by oxamate. In vivo experiments further confirmed that inhibition of lactate production reduced POM121 expression and promoted CD8+ T-cell infiltration, while POM121 overexpression attenuated these effects.Conclusion Lactate generated by glycolytic reprogramming promotes H3K18 lactylation, which transcriptionally activates POM121, thereby suppressing CD8+ T-cell-mediated antitumor immunity and facilitating immune escape in pancreatic cancer. The lactate-H3K18la-POM121 signaling axis may represent a promising therapeutic target for pancreatic cancer immunotherapy.
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TIAN Zhongming, ZANG Longjun, ZHU Hongwei, TIAN Xiaodong, ZHANG Fusheng, ZHANG Baoming, MIAO Qingwang
2026,35(5):1003-1011, DOI: 10.7659/j.issn.1005-6947.250707
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Background and Aims Acute pancreatitis (AP) is an acute gastrointestinal emergency characterized by damage to pancreatic acinar cells and an inflammatory response. Circular RNAs (circRNAs) have been implicated in the regulation of various inflammatory disorders; however, the role of circSMARCA5 in AP remains unclear. This study aimed to investigate the function of circSMARCA5 and its underlying mechanism involving the miR-181-5p/LAMP-2 axis in AP.Methods An in vitro AP model was established by treating AR42J cells with cerulein. The expression levels of circSMARCA5, miR-181-5p, and LAMP-2 were determined by qRT-PCR. Cell viability was assessed using the MTT assay, and the levels of TNF-α, IL-1β, and IL-6 were measured by ELISA. Dual-luciferase reporter assays were performed to verify the interactions between circSMARCA5 and miR-181-5p as well as between miR-181-5p and LAMP-2. Gain-of-function and rescue experiments were conducted to evaluate their biological effects.Results CircSMARCA5 expression was significantly decreased, whereas miR-181-5p expression was markedly increased in cerulein-treated AR42J cells (all P<0.05). Overexpression of circSMARCA5 significantly enhanced cell viability and reduced the secretion of TNF-α, IL-1β, and IL-6 (all P<0.05). Dual-luciferase reporter assays confirmed that circSMARCA5 directly bound to miR-181-5p, while LAMP-2 was identified as a downstream target of miR-181-5p. Overexpression of miR-181-5p suppressed LAMP-2 expression, decreased cell viability, and aggravated inflammatory responses. These effects were partially reversed by circSMARCA5 or LAMP-2 overexpression.Conclusion CircSMARCA5 alleviates inflammatory injury in AP by acting as a competing endogenous RNA for miR-181-5p and thereby upregulating LAMP-2 expression. The circSMARCA5/miR-181-5p/LAMP-2 regulatory axis may represent a potential therapeutic target for AP.
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GU Tianqi, WANG Xuelian, LI Liya, ZENG Wenjing, WANG Lei, JI Lu, HUANG Juan, LUO Shayang, CAO Ayong
2026,35(5):1012-1023, DOI: 10.7659/j.issn.1005-6947.250705
Abstract:
Malignant phyllodes tumor (MPT) is a rare fibroepithelial neoplasm of the breast characterized by a relatively high risk of local recurrence and distant metastasis. However, controversies remain regarding its diagnosis and optimal management. This review summarizes recent advances in the clinical diagnosis, pathological and molecular characteristics, treatment strategies, and future perspectives of MPT. Imaging modalities provide valuable preoperative information, whereas histopathological examination remains the gold standard for diagnosis. Core needle biopsy is associated with a certain false-negative rate and may underestimate tumor grade. Recent genomic studies have identified recurrent alterations involving the TERT promoter, CDKN2A, TP53, NF1, PIK3CA, and RB1, providing potential targets for precision therapy. Surgical excision with negative margins remains the cornerstone of treatment, and routine axillary surgery is generally unnecessary. Adjuvant radiotherapy may improve local control, although evidence supporting a survival benefit remains limited. The efficacy of adjuvant chemotherapy and systemic therapy is still uncertain, and current treatment strategies are largely extrapolated from soft-tissue sarcoma management. Advances in multi-omics technologies are expected to facilitate molecular classification and promote the development of targeted and immune-based therapies. Future multicenter prospective studies are warranted to establish risk-stratification systems and individualized treatment strategies for improving patient outcomes.
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YANG Chunyan, NIU Song, LIU Yingming, WU Gang, DING Chao, SHI Chenlei, HAN Yi, SHI Tiefeng
2026,35(5):1024-1032, DOI: 10.7659/j.issn.1005-6947.250394
Abstract:
Papillary thyroid carcinoma (PTC) is the most common type of thyroid malignancy. Although most patients have a favorable prognosis, a proportion still develop locoregional recurrence or distant metastasis after initial treatment, which adversely affects long-term outcomes and quality of life. Conventional risk stratification systems based on clinicopathological features have limited ability in individualized recurrence prediction, prompting increasing interest in biomarker-based precision assessment. In recent years, substantial advances have been achieved in serological biomarkers, genetic alterations, tumor microenvironment-related immune markers, and liquid biopsy technologies. Among them, BRAFV600E mutation, TERT promoter mutation, inflammation-related indicators, and circulating tumor-derived components have demonstrated promising value in recurrence risk evaluation. Meanwhile, the integration of multi-omics approaches and artificial intelligence has further promoted the transition from single-parameter prediction to multidimensional dynamic risk models. This review summarizes the current progress in biomarkers associated with PTC recurrence risk, discusses their underlying mechanisms, clinical applications, and existing limitations, and further explores emerging strategies, including liquid biopsy, multi-omics integration, and artificial intelligence. These advances may facilitate precise risk stratification and individualized management of patients with PTC.
