Liposomes as versatile agents for the management of traumatic and nontraumatic central nervous system disorders: drug stability, targeting efficiency, and safety.

Various nanoparticle-based drug delivery systems for the treatment of neurological disorders have been widely studied. However, their inability to cross the blood-brain barrier hampers the clinical translation of these therapeutic strategies. Liposomes are nanoparticles composed of lipid bilayers, which can effectively encapsulate drugs and improve drug delivery across the blood-brain barrier and into brain tissue through their targeting and permeability. Therefore, they can potentially treat traumatic and nontraumatic central nervous system diseases. In this review, we outlined the common properties and preparation methods of liposomes, including thin-film hydration, reverse-phase evaporation, solvent injection techniques, detergent removal methods, and microfluidics techniques. Afterwards, we comprehensively discussed the current applications of liposomes in central nervous system diseases, such as Alzheimer's disease, Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis, traumatic brain injury, spinal cord injury, and brain tumors. Most studies related to liposomes are still in the laboratory stage and have not yet entered clinical trials. Additionally, their application as drug delivery systems in clinical practice faces challenges such as drug stability, targeting efficiency, and safety. Therefore, we proposed development strategies related to liposomes to further promote their development in neurological disease research.

Sclerosing epithelioid fibrosarcoma of the pancreas: A case report.

BACKGROUND: A sclerosing epithelioid fibrosarcoma (SEF) is a rare malignant fibroblastic soft tissue tumor that rarely occurs in intra-abdominal organs. A case of a SEF in the pancreatic head is reported herein, including its clinical manifestations, preoperative imaging features, gross specimen and pathological findings. CASE SUMMARY: A 33-year-old male patient was admitted to Peking Union Medical College Hospital in December 2023 due to a one-year history of intermittent upper abdominal pain and the discovery of a pancreatic mass. The patient underwent an enhanced computed tomography scan of the abdomen, which revealed a well-defined, round mass with clear borders and calcifications in the pancreatic head. The mass exhibited progressive, uneven mild enhancement, measuring approximately 6.6 cm × 6.3 cm. The patient underwent laparoscopic pylorus-preserving pancreaticoduodenectomy. Postoperative pathological examination revealed that the lesion was consistent with a SEF. At the 3-month postoperative follow-up, the patient did not report any short-term complications, and there were no signs of tumor recurrence. CONCLUSION: SEFs are rare malignant fibrous soft tissue tumors. SEFs rarely develop in the pancreas, and its preoperative diagnosis depends on imaging findings, with confirmation depending on pathological examination and immunohistochemistry. Currently, only four cases of pancreatic SEF have been reported in studies written in English. This case is the first reported case of a pancreatic SEF by a clinical physician.

Lymph node involvement is associated with overall survival for elderly patients with non-metastatic gallbladder adenocarcinoma.

Background: Lymph node involvement is recognized as a prognostic factor for patients with gallbladder cancer. However, the N stage varied from different editions of the American Joint Committee on Cancer (AJCC) TNM Classification. Our objective was to investigate the impact of lymph node involvement on overall survival in elderly patients with non-metastatic gallbladder adenocarcinoma. Methods: Patients older than 65 years with non-metastatic gallbladder adenocarcinoma were identified from the SEER data. We used Cox proportional hazard regression analysis to select the independent risk factor. A nomogram was built to identify the 1-, 3-, and 5-years' prognostic impact. Univariate and multivariate models were used to examine the correlation of overall survival (OS) with the number of metastatic nodes. Results: A total of 1,654 patients (706 with and 948 without nodal involvement) were included. Cox proportional hazard regression analyses found that age, gender, tumor size, lymph node involvement, and surgical options were risk factors for the prognosis and were integrated into the nomogram. After adjustment, OS was compromised for patients who receive surgery with nodal involvement [hazard ratio (HR), 2.238; P < 0.01]. Furthermore, after adjustment the presence of more than two metastatic lymph nodes was associated with decreased OS (HR, 3.305; P < 0.01). Conclusions: Our results suggest that lymph node involvement is associated with compromised survival in elderly patients. A nomogram was developed to predict the prognosis of gallbladder cancer. A change point of more than two metastatic lymph nodes seems to carry prognostic significance, calling for closer monitoring of elderly patients with gallbladder cancer with involvement of increased number of lymph nodes.

Laparoscopic spleen-preserving total pancreatectomy for the treatment of low-grade malignant pancreatic tumors: Two case reports and review of literature.

BACKGROUND: Function-preserving pancreatectomy can improve the long-term quality of life of patients with benign or low-grade malignant tumors, such as intraductal papillary mucinous neoplasms (IPMNs) and mucinous cystic neoplasms. However, there is limited literature on laparoscopic spleen-preserving total pancreatectomy (L-SpTP) due to technical difficulties. CASE SUMMARY: Patient 1 was a 51-year-old male diagnosed with IPMN based on preoperative imaging, showing solid nodules in the pancreatic head and diffuse dilation of the main pancreatic duct with atrophy of the distal pancreas. We performed L-SpTP with preservation of the splenic vessels, and the postoperative pathology report revealed IPMN with invasive carcinoma. Patient 2 was a 60-year-old male with multiple cystic lesions in the pancreatic head and body. L-SpTP was performed, and intraoperatively, the splenic vein was injured and required ligation. Postoperative pathology revealed a mucinous cystic tumor of the pancreas with low-grade dysplasia. Both patients were discharged on postoperative day 7, and there were no major complications during the perioperative period. CONCLUSION: We believe that L-SpTP is a safe and feasible treatment for low-grade malignant pancreatic tumors, but more case studies are needed to evaluate its safety, efficacy, and long-term outcomes.

Locally advanced breast cancer patients should be cautious about the immediate breast reconstruction after mastectomy: a pooling analysis of safety and efficacy.

BACKGROUND: The purpose of this study was to compare safety and efficacy outcomes between immediate breast reconstruction (IBR) and mastectomy alone in locally advanced breast cancer patients. METHODS: We conducted a comprehensive literature search of PUBMED, EMBASE, and Cochrane databases. The primary outcomes evaluated were overall survival, disease-free survival, and local recurrence. The secondary outcome was the incidence of surgical complications. All data were analyzed using Review Manager 5.3. RESULTS: Sixteen studies, involving 15,364 participants were included in this meta-analysis. Pooled data demonstrated that patients underwent IBR were more likely to experience surgical complications than those underwent mastectomy alone (HR: 3.96, 95%CI [1.07,14.67], p = 0.04). No significant difference was found in overall survival (HR: 0.94, 95%CI [0.73,1.20], p = 0.62), disease-free survival (HR: 1.03, 95%CI [0.83,1.27], p = 0.81), or breast cancer specific survival (HR: 0.93, 95%CI [0.71,1.21], p = 0.57) between IBR group and Non-IBR group. CONCLUSIONS: Our study demonstrates that IBR after mastectomy does not affect the overall survival and disease-free survival of locally advanced breast cancer patients. However, IBR brings with it a nonnegligible higher risk of complications and needs to be fully evaluated and carefully decided.

The potential contribution of aberrant cathepsin K expression to gastric cancer pathogenesis.

The role of cathepsin K (CTSK) expression in the pathogenesis and progression of gastric cancer (GC) remains unclear. Hence, the primary objective of this study is to elucidate the precise expression and biological role of CTSK in GC by employing a combination of bioinformatics analysis and in vitro experiments. Our findings indicated a significant upregulation of CTSK in GC. The bioinformatics analysis revealed that GC patients with a high level of CTSK expression exhibited enrichment of hallmark gene sets associated with angiogenesis, epithelial-mesenchymal transition (EMT), inflammatory response, KRAS signaling up, TNFα signaling via KFκB, IL2-STAT5 signaling, and IL6-JAK-STAT3 signaling. Additionally, these patients demonstrated elevated levels of M2-macrophage infiltration, which was also correlated with a poorer prognosis. The results of in vitro experiments provided confirmation that the over-expression of CTSK leads to an increase in the proliferative and invasive abilities of GC cells. However, further evaluation was necessary to determine the impact of CTSK on the migration capability of these cells. Our findings suggested that CTSK has the potential to facilitate the initiation and progression of GC by augmenting the invasive capacity of GC cells, engaging in tumor-associated EMT, and fostering the establishment of an immunosuppressive tumor microenvironment (TME).

Ileum excision partially reverses improvement of glucose metabolism in diabetic rats after biliopancreatic diversion with duodenal switch.

BACKGROUND: Bile acids can stimulate the secretion of glucagon-like peptide-1 (GLP-1) and be mostly reabsorbed in the ileum. OBJECTIVES: We aimed to investigate whether ileum excision could reverse the glucose improvement after biliopancreatic diversion with duodenal switch (BPD/DS). SETTING: Peking Union Medical College Hospital. METHODS: Thirty diabetic rats were randomly divided into the BPD/DS group, BPD/DS plus ileectomy (BDI) group, and control group. The fasting blood glucose, bile acids, and glucagon-like peptide-1(GLP-1) levels in plasma samples were analyzed. RESULTS: In postoperative week 20, the fasting blood glucose level in the BDI group was significantly higher than that in the BPD/DS group (11.5 ± 1.4 mmol/L versus 7.6 ± 1.0 mmol/L, P < .001), and the AUCOGTT value was also significantly higher than that in the BPD/DS group (2186.1 ± 237.2 mmol/L·min versus 1551.2 ± 136.9 mmol/L·min, P < .001). The plasma level of bile acids in the BDI group was lower than that in the BPD/DS group (P = .012) and was not significantly different from that in the control group (P = .629). The plasma level of GLP-1 in the BDI group was lower than that in the BPD/DS group (P = .009) and was not significantly different from that in the control group (P = .530). Moreover, the intestinal TGR5 expression in the BDI group was significantly lower than that in the BPD/DS group (P < .001). CONCLUSIONS: The results show that excision of the ileum can partially reverse the improvement in glucose metabolism after BPD/DS.

Phytic Acid-Promoted Deposition of Gold Nanoparticles with Grafted Cationic Polymer Brushes for the Construction of Synergistic Contact-Killing and Photothermal Bactericidal Coatings.

Medical implants are constantly facing the risk of bacterial infections, especially infections caused by multidrug resistant bacteria. To mitigate this problem, gold nanoparticles with alkyl bromide moieties (Au NPs-Br) on the surfaces were prepared. Xenon light irradiation triggered the plasmon effect of Au NPs-Br to induce free radical graft polymerization of 2-(dimethylamino)ethyl methacrylate (DMAEMA), leading to the formation of poly(DMAEMA) brush-grafted Au NPs (Au NPs-g-PDM). The Au NPs-g-PDM nanocomposites were conjugated with phytic acid (PA) via electrostatic interaction and van der Waals interaction. The as-formed aggregates were deposited on the titanium (Ti) substrates to form the PA/Au NPs-g-PDM (PAP) hybrid coatings through surface adherence of PA and the gravitational effect. Synergistic bactericidal effects of contact-killing caused by the cationic PDM brushes, and local heating generated by the Au NPs under near-infrared irradiation, conferred strong antibacterial effects on the PAP-deposited Ti (Ti-PAP) substrates. The synergistic bactericidal effects reduced the threshold temperature required for the photothermal sterilization, which in turn minimized the secondary damage to the implant site. The Ti-PAP substrates exhibited 97.34% and 99.97% antibacterial and antiadhesive efficacy, respectively, against Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli), compared to the control under in vitro antimicrobial assays. Furthermore, the as-constructed Ti-PAP surface exhibited a 99.42% reduction in the inoculated S. aureus under in vivo assays. In addition, the PAP coatings exhibited good biocompatibility in the hemolysis and cytotoxicity assays as well as in the subcutaneous implantation of rats.

YTHDF1 promotes gallbladder cancer progression via post-transcriptional regulation of the m6A/UHRF1 axis.

Gallbladder cancer is a rare but fatal malignancy. However, the mechanisms underlying gallbladder carcinogenesis and its progression are poorly understood. The function of m6A modification and its regulators was still unclear for gallbladder cancer. The current study seeks to investigate the function of YTH m6A RNA-binding protein 1 (YTHDF1) in gallbladder cancer. Transcriptomic analysis and immunochemical staining of YTHDF1 in gallbladder cancer tissues revealed its upregulation compared to paracancerous tissues. Moreover, YTHDF1 promotes the proliferation assays, Transwell migration assays, and Transwell invasion assays of gallbladder cancer cells in vitro. And it also increased tumour growth in xenograft mouse model and metastases in tail vein injection model in vivo. In vitro, UHRF1 knockdown partly reversed the effects of YTHDF1 overexpression. Mechanistically, dual-luciferase assays proved that YTHDF1 promotes UHRF1 expression via direct binding to the mRNA 3'-UTR in a m6A-dependent manner. Overexpression of YTHDF1 enhanced UHRF1 mRNA stability, as demonstrated by mRNA stability assays, and Co-IP studies confirmed a direct interaction between YTHDF1 and PABPC1. Collectively, these findings provide new insights into the progression of gallbladder cancer as well as a novel post-transcriptional mechanism of YTHDF1 via stabilizing target mRNA.

Predicting pathological complete response to neoadjuvant chemotherapy in breast cancer patients: use of MRI radiomics data from three regions with multiple machine learning algorithms.

OBJECTIVE: To construct a multi-region MRI radiomics model for predicting pathological complete response (pCR) in breast cancer (BCa) patients who received neoadjuvant chemotherapy (NACT) and provide a theoretical basis for the peritumoral microenvironment affecting the efficacy of NACT. METHODS: A total of 133 BCa patients who received NACT, including 49 with confirmed pCR, were retrospectively analyzed. The radiomics features of the intratumoral region, peritumoral region, and background parenchymal enhancement (BPE) were extracted, and the most relevant features were obtained after dimensional reduction. Then, combining different areas, multivariate logistic regression analysis was used to select the optimal feature set, and six different machine learning models were used to predict pCR. The optimal model was selected, and its performance was evaluated using receiver operating characteristic (ROC) analysis. SHAP analysis was used to examine the relationship between the features of the model and pCR. RESULTS: For signatures constructed using three individual regions, BPE provided the best predictions of pCR, and the diagnostic performance of the intratumoral and peritumoral regions improved after adding the BPE signature. The radiomics signature from the combination of all the three regions with the XGBoost machine learning algorithm provided the best predictions of pCR based on AUC (training set: 0.891, validation set: 0.861), sensitivity (training set: 0.882, validation set: 0.800), and specificity (training set: 0.847, validation set: 0.84). SHAP analysis demonstrated that LZ_log.sigma.2.0.mm.3D_glcm_ClusterShade_T12 made the greatest contribution to the predictions of this model. CONCLUSION: The addition of the BPE MRI signature improved the prediction of pCR in BCa patients who received NACT. These results suggest that the features of the peritumoral microenvironment are related to the efficacy of NACT.

Application of AI on cholangiocarcinoma.

Cholangiocarcinoma, classified as intrahepatic, perihilar, and extrahepatic, is considered a deadly malignancy of the hepatobiliary system. Most cases of cholangiocarcinoma are asymptomatic. Therefore, early detection of cholangiocarcinoma is significant but still challenging. The routine screening of a tumor lacks specificity and accuracy. With the application of AI, high-risk patients can be easily found by analyzing their clinical characteristics, serum biomarkers, and medical images. Moreover, AI can be used to predict the prognosis including recurrence risk and metastasis. Although they have some limitations, AI algorithms will still significantly improve many aspects of cholangiocarcinoma in the medical field with the development of computing power and technology.

M6A RNA methylation in biliary tract cancer: the function roles and potential therapeutic implications.

Biliary tract cancers (BTCs) are relatively rare malignancies with a poor prognosis. For advanced BTCs, the efficacy of current chemotherapeutic approaches is limited. Consequently, there is an urgent need to deepen our understanding of the molecular mechanisms underlying BTC tumorigenesis and development for the exploration of effective targeted therapies. N6-methyladenosine (m6A), the most abundant RNA modifications in eukaryotes, is found usually dysregulated and involved in tumorigenesis, progression, and drug resistance in tumors. Numerous studies have confirmed that aberrant m6A regulators function as either oncogenes or tumor suppressors in BTCs by the reversible regulation of RNA metabolism, including splicing, export, degradation and translation. In this review, we summarized the current roles of the m6A regulators and their functional impacts on RNA fate in BTCs. The improved understanding of m6A modification in BTCs also provides a reasonable outlook for the exploration of new diagnostic strategies and efficient therapeutic targets.

Prediction of neoadjuvant chemotherapy pathological complete response for breast cancer based on radiomics nomogram of intratumoral and derived tissue.

BACKGROUND: Non-invasive identification of breast cancer (BCa) patients with pathological complete response (pCR) after neoadjuvant chemotherapy (NACT) is critical to determine appropriate surgical strategies and guide the resection range of tumor. This study aimed to examine the effectiveness of a nomogram created by combining radiomics signatures from both intratumoral and derived tissues with clinical characteristics for predicting pCR after NACT. METHODS: The clinical data of 133 BCa patients were analyzed retrospectively and divided into training and validation sets. The radiomics features for Intratumoral, peritumoral, and background parenchymal enhancement (BPE) in the training set were dimensionalized. Logistic regression analysis was used to select the optimal feature set, and a radiomics signature was constructed using a decision tree. The signature was combined with clinical features to build joint models and generate nomograms. The area under curve (AUC) value of receiver operating characteristic (ROC) curve was then used to assess the performance of the nomogram and independent predictors. RESULTS: Among single region, intratumoral had the best predictive value. The diagnostic performance of the intratumoral improved after adding the BPE features. The AUC values of the radiomics signature were 0.822 and 0.82 in the training and validation sets. Multivariate logistic regression analysis revealed that age, ER, PR, Ki-67, and radiomics signature were independent predictors of pCR in constructing a nomogram. The AUC of the nomogram in the training and validation sets were 0.947 and 0.933. The DeLong test showed that the nomogram had statistically significant differences compared to other independent predictors in both the training and validation sets (P < 0.05). CONCLUSION: BPE has value in predicting the efficacy of neoadjuvant chemotherapy, thereby revealing the potential impact of tumor growth environment on the efficacy of neoadjuvant chemotherapy.

Tumor immune microenvironment-based clusters in predicting prognosis and guiding immunotherapy in breast cancer.

The development and progression of breast cancer (BC) depend heavily on the tumor microenvironment (TME), especially tumor infiltration leukocytes (TILs). TME-based classifications in BC remain largely unknown and need to be clarified. Using the bioinformatic analysis, we attempted to construct a prognostic nomogram based on clinical features and TME-related differentially expressed genes (DEGs). We also tried to investigate the association between the prognostic nomogram and clinical characteristics, TILs, possible signaling pathways, and response to immunotherapy in BC patients. DEGs for BC patients were identified from The Cancer Genome Atlas Breast Invasive Carcinoma database. TME-related genes were downloaded from the Immunology Database and Analysis Portal. After intersecting DEGs and TME-related genes, 3985 overlapping TME-related DEGs were selected for non-negative matrix factorization clustering, microenvironment cell populations-counter (MCP-counter), LASSO Cox regression, tumor immune dysfunction, and exclusion (TIDE) algorithm analyses. BC patients were divided into three clusters based on the TME-related DEGs and survival data, in which cluster 3 had the best overall survival (OS). Of note, cluster 3 exhibited the highest infiltration or lowest infiltration of CD3+ T-cells, CD8+ T-cells, cytotoxic lymphocytes, B-lymphocytes, monocytic lineage, and myeloid dendritic cells (MDCs). A total of 33 TME-related DEGs were identified as a prognostic gene signature by the LASSO regression analysis. The prognostic gene signature separated BC patients into low- and high-risk groups with significant differences in OS (p<0.01) and demonstrated powerful effectiveness (TCGA all group: 1-year area under the curve [AUC] = 0.773, 3-year AUC = 0.770, 5-year AUC = 0.792). By integrating demographic features, tumor-node metastasis (TNM) stages, and prognostic gene signature, we constructed a nomogram with better predictive value than other clinical features alone. TMErelated DEGs in the low-risk BC patients (with better OS) were enriched in chemokine, cytokine-cytokine receptor interaction, and JAK-STAT and Toll-like receptor signaling pathways. BC patients in the low-risk group exhibited higher TIDE scores associated with worse immune checkpoint blockade response. A prognostic nomogram based on TME-related DEGs and clinical characteristics could predict prognosis and guide immunotherapy in BC patients.

Radiomics-based machine learning and deep learning to predict serosal involvement in gallbladder cancer.

OBJECTIVE: Our study aimed to determine whether radiomics models based on contrast-enhanced computed tomography (CECT) have considerable ability to predict serosal involvement in gallbladder cancer (GBC) patients. MATERIALS AND METHODS: A total of 152 patients diagnosed with GBC were retrospectively enrolled and divided into the serosal involvement group and no serosal involvement group according to paraffin pathology results. The regions of interest (ROIs) in the lesion on all CT images were drawn by two radiologists using ITK-SNAP software (version 3.8.0). A total of 412 features were extracted from the CT images of each patient. The Mann‒Whitney U test was applied to identify features with significant differences between groups. Seven machine learning algorithms and a deep learning model based on fully connected neural networks (f-CNNs) were used for radiomics model construction. The prediction efficacy of the models was evaluated using receiver operating characteristic (ROC) curve analysis. RESULTS: Through the Mann‒Whitney U test, 75 of the 412 features extracted from the CT images of patients were significantly different between groups (P < 0.05). Among all the algorithms, logistic regression achieved the highest performance with an area under the curve (AUC) of 0.944 (sensitivity 0.889, specificity 0.8); the f-CNN deep learning model had an AUC of 0.916, and the model showed high predictive power for serosal involvement, with a sensitivity of 0.733 and a specificity of 0.801. CONCLUSION: Radiomics models based on features derived from CECT showed convincing performances in predicting serosal involvement in GBC.

Safety and Survival Outcomes of Liver Resection following Triple Combination Conversion Therapy for Initially Unresectable Hepatocellular Carcinoma.

Triple combination conversion therapy, involving transcatheter arterial chemoembolization (TACE) or hepatic arterial infusion chemotherapy (HAIC) combined with tyrosine kinase inhibitors (TKIs) and immune checkpoint inhibitors (ICIs), has shown an encouraging objective response rate (ORR) and successful conversion surgery rate in initially unresectable hepatocellular carcinoma (HCC). However, the safety and long-term survival outcomes of subsequent liver resection after successful conversion still remain to be validated. From February 2019 to February 2023, 726 patients were enrolled in this retrospective study (75 patients received hepatectomy after conversion therapy [CLR group], and 651 patients underwent pure hepatectomy [LR group]). Propensity score matching (PSM) was used to balance the preoperative baseline characteristics. After PSM, 68 patients in the CLR group and 124 patients in the LR group were analyzed, and all the matching variables were well-balanced. Compared with the LR group, the CLR group experienced longer Pringle maneuver time, longer operation time, and longer hospital stays. In addition, the CLR group had significantly higher incidence rates of intra-abdominal bleeding, biliary leakage, post-hepatectomy liver failure (PHLF), and Clavien-Dindo grade IIIa complications than the LR group. There were no significant statistical differences in overall survival (OS) (hazard ratio [HR] 0.724; 95% confidence interval [CI] 0.356-1.474; p = 0.374) and recurrence-free survival (RFS) (HR 1.249; 95% CI 0.807-1.934; p = 0.374) between the two groups. Liver resection following triple combination conversion therapy in initially unresectable HCC may achieve favorable survival outcomes with manageable safety profiles; presenting as a promising treatment option for initially unresectable HCC.

Effect of Nb Content and Second Heat Cycle Peak Temperatures on Toughness of X80 Pipeline Steel.

The microstructure evolution and variation of impact toughness in the heat-affected zone (HAZ) of X80 pipeline steel with different Nb content under different peak temperatures in the secondary thermal cycle were studied through welding thermal simulation, the Charpy impact test, EBSD analysis, SEM observation, and TEM observation in this study. The results indicate that when the peak temperatures of the second pass were lower than Ac1, both X80 pipeline steels had high impact toughness. For secondary peak temperatures in the range of Ac1 to Ac3, both X80 pipeline steels had the worst impact toughness, mainly due to the formation of massive blocky M-A constituents in chain form on grain boundaries. When the secondary peak temperatures were higher than Ac3, both X80 pipeline steels had excellent impact toughness. Smaller grain size and higher proportions of HAGBs can effectively improve the impact toughness. Meanwhile, high Nb X80 pipeline steel had higher impact absorption energy and smaller dispersion. Adding an appropriate amount of Nb to X80 pipeline steel can ensure the impact toughness of SCCGHAZ and SCGHAZ in welded joints.

YTHDF2 promotes gallbladder cancer progression and gemcitabine resistance via m6A-dependent DAPK3 degradation.

N6-methyladenosine (m6A) is the most abundant internal modification in eukaryotic RNA and involved in the carcinogenesis of various malignancies. However, the functions and mechanisms of m6A in gallbladder cancer (GBC) remain unclear. In this study, we investigated the role and underlying mechanism of the RNA-binding protein YT521-B homology domain-containing family protein 2 (YTHDF2), an m6A reader, in GBC. Herein, we detected that YTHDF2 was remarkably upregulated in GBC tissues compared to normal gallbladder tissues. Functionally, YTHDF2 overexpression promoted the proliferation, tumor growth, migration, and invasion of GBC cells while inhibiting the apoptosis in vitro and in vivo. Conversely, YTHDF2 knockdown induced opposite results. Mechanistically, we further investigated the underlying mechanism by integrating RNA immunoprecipitation sequencing (RIP-seq), m6A-modified RIP-seq, and RNA sequencing, which revealed that death-associated protein kinase 3 (DAPK3) is a direct target of YTHDF2. YTHDF2 binds to the 3'-UTR of DAPK3 mRNA and facilitates its degradation in an m6A-dependent manner. DAPK3 inhibition restores the tumor-suppressive phenotype induced by YTHDF2 deficiency. Moreover, the YTHDF2/DAPK3 axis induces the resistance of GBC cells to gemcitabine. In conclusion, we reveal the oncogenic role of YTHDF2 in GBC, demonstrating that YTHDF2 increases the mRNA degradation of the tumor suppressor DAPK3 in an m6A-dependent way, which promotes GBC progression and desensitizes GBC cells to gemcitabine. Our findings provide novel insights into potential therapeutic strategies for GBC.