As the application of immune checkpoint inhibitors(ICIs)in the perioperative treatment of melanoma is increasingly introduced at earlier stages,it presents a critical opportunity for the development and clinical translation of neoadjuvant therapy.The results of phaseⅠ/Ⅱ clinical trials on neoadjuvant ICI therapy for melanoma demonstrate that neoadjuvant ICIs effectively improve the pathologic re-sponse rate in melanoma patients.Recent studies have shown that combining ICIs with other treatment modalities,including radiotherapy,chemotherapy,and targeted therapies,can enhance antitumor efficacy of neoadjuvant treatment for patients with melanoma.Optimizing treatment regimens,managing adverse events,identifying and addressing pseudoprogression,and handling cases of oligoprogression have become key areas of research in incorporating ICI regimens into neoadjuvant treatment for patients with melanoma.The search for bio-markers to monitor immunotherapy efficacy is expected to become a major focus of future research.This article provides a review of the re-search progress,controversies,and challenges in the application of ICIs in the neoadjuvant treatment of melanoma,and discusses future re-search directions,aiming to offer insights into the clinical application and development of ICIs in melanoma neoadjuvant therapy.

Immunotherapy has recently shown significant potential in treating malignant tumors.However,the immunosuppressive nature of the tumor microenvironment(TME)limits the number of patients who benefit from this approach.Combining ultrasound with drug-loaded microbubble technology can directly induce tumor cell death through cavitation and pore-forming effects;this promotes tumor anti-gen presentation and enhances immune recognition of these antigens.This strategy also modulates the immunosuppressive state of the tu-mor microenvironment,making it more conducive to an effective immune response.It also normalizes blood vessels and reduces interstitial fluid pressure within the tumor,as well as helps therapeutic agents or genes to penetrate tumor tissues,thereby enhancing overall immune efficacy.This review examines the use of low-intensity ultrasound combined with drug-loaded microbubbles to improve the tumor microen-vironment and boost tumor immune responses.

Colorectal cancer(CRC)is one of the most common malignant tumors worldwide,and its incidence and fatality rates rank at the forefront of malignant tumors.In recent years,with the maturity of laparoscopic and robotic technology,and the application of new staplers,the efficacy and safety of surgery for CRC have improved;however,postoperative complications still seriously affect postoperative quality of life and survival time.Identification of nutritional predictors of CRC is conducive to the early identification of high-risk patients,reinforce-ment of individualized care,enhancement of the quality of peri-operative management,reduction in the incidence of postoperative complic-ations,and improvement of the short-and long-term prognosis.In this paper,the literature on nutritional predictors of postoperative com-plications of CRC was reviewed,the evaluation contents and efficacy of nutritional predictors were summarized,and their advantages and disadvantages were analyzed.The aim is to provide a reference for identifying nutritional predictors of postoperative complications of CRC that are readily accessible,low-cost,and adjustable pre-operatively.

This review summarizes recent advances in neoadjuvant immunotherapy for advanced gastric cancer.Through literature search in PubMed,Web of Science,and CNKI databases from 2020 to 2023,we systematically analyzed the mechanisms,clinical applications,and bio-marker research.Programmed death-1(PD-1)inhibitors combined with chemotherapy significantly improve patient outcomes,while mi-crosatellite instability(MSI),programmed death-ligand 1(PD-L1)expression,and tumor mutational burden(TMB)have been identified as important predictive biomarkers.Multi-omics analysis shows great potential in identifying optimal responders,with pyroptosis-related gene scoring system(PRS)positively correlating with anti-tumor immune infiltration.Metabolic reprogramming and epigenetic regulation in the tumor microenvironment play key roles in immune evasion,while emerging targets such as Claudin 18.2 and combination targeting strategies further enhance therapeutic efficacy.Despite significant progress,precise patient selection and overcoming resistance mechan-isms remain major challenges.Future research should focus on biomarker validation,personalized treatment strategy development,tumor microenvironment dynamic analysis,and novel combination therapy exploration to improve clinical outcomes.

Pseudomyxoma peritonei(PMP)is a rare malignant peritoneal syndrome characterized by progressive intra-abdominal accumu-lation and redistribution of gelatinous tumor-derived mucins.This disease primarily originates in the appendix or ovaries and exhibits distinct biological behavior and clinicopathological features.Carbohydrate antigen 19-9(CA19-9),a critical tumor biomarker,is significantly correl-ated with the development and progression of PMP.This association renders CA19-9 increasingly valuable in clinical diagnosis and treat-ment.Furthermore,molecular biological characteristics of CA19-9,including structural properties,biosynthetic pathways,and mechanisms in mediating tumor metastasis,are systematically elaborated.These findings highlight the association between CA19-9 expression and PMP pathological grading,clinical prognosis,and therapeutic response monitoring.Additionally,the study thoroughly analyzed the synergistic role of CA19-9,alongside other tumor biomarkers,in PMP management.Based on current evidence,future research directions are proposed.These include the potential application of CA19-9 in early PMP diagnosis,its therapeutic utility as a molecular target,and the exploration of CA19-9-associated signaling pathways in PMP pathogenesis.The insights provide novel perspectives and a theoretical foundation for PMP-based precision medicine.

Colorectal cancer,one of the most common malignant tumors worldwide,involves various complex pathophysiological processes.With the in-depth study of molecular science,weidentified lactylation,a new post-translational protein modification,as a key regulator in the initiation and progression of colorectal cancer.Lactylation refers to the modification of lysine residues in proteins by the addition of lactyl groups derived from lactic acid.As a glycolytic end product,lactate accumulates in the tumor microenvironment and regulates gene expres-sion and cellular function by inducing lactylation of histone and non-histone proteins.This article describes how lactylation modification drives tumor immune evasion,metabolic reprogramming,and angiogenesis through epigenetic mechanisms,and elaborates on its impact on the occurrence,metastasis,and multidrug resistance in colon cancer.

While tumor immunotherapy has improved the prognosis of many patients,immunotherapy drug resistance develops in most tu-mors.Studies of new targets and therapies are needed to overcome this challenge.Growing evidence indicates that Siglecs function in im-mune checkpoints.Siglecs belong to a family of salivary acid-binding immunoglobulin-like lectins.The majority of Siglecs are immunosup-pressive transmembrane proteins that bind to sialic acid-containing glycans on glycoproteins and glycolipids.Sialoglycan-Siglec interactions contribute to tumor immune escape and are strongly correlated with poor prognosis in tumor patients.This review will discuss Siglec func-tion in immune checkpoints,and how the interaction between sialic acid and Siglecs regulates the tumor microenvironment to exert thera-peutic effects.

Breast cancer is the most common malignant tumor in women worldwide.HER2-positive and HER2-low breast cancers are highly aggressive subtypes with poor prognosis.First-line combination therapies targeting HER2 have significantly improved treatment outcomes for patients with advanced and metastatic breast cancer,but resistance inevitably develops.The emergence of antibody-drug conjugates(ADCs)brings new hope for the treatment of advanced HER2-positive and HER2-low breast cancers.This article analyzes the efficacy and safety of key ADC drugs,including adotrastuzumab emtansine(T-DM1),trastuzumab deruxtecan(DS-8201,T-DXd)and other drugs in the treatment of advanced HER2-positive and HER2-low breast cancers.It also reviews mechanisms of ADC resistance and discusses corres-ponding management strategies,aiming to provide more efficient and personalized treatment options for patients with advanced HER2-pos-itive and HER2-low breast cancers.

Objective:To investigate the role of O-GlcNAcylation in the regulation of the stability of receptor for activated C kinase 1(Rack1)during SHH-type medulloblastoma(SHH-MB)initiation.Methods:SHH-MB tumors and adjacent tissues were selected from the clinical tu-mor specimen library of the Department of Pathology at The General Hospital of Western Theater Command.Rack1 expression and O-GlcNAcylation(O-GlcNAc)levels in these tumor tissues were analyzed.The human medulloblastoma cell line Daoy was treated with a glyc-osyltransferase(OGT)inhibitor(OSMI-1)and adeglycosyltransferase(OGA)inhibitor(TM-G),and their impact on tumor cell proliferation was assessed using a Cell Counting Kit-8(CCK-8)and immunofluorescence staining.The O-GlcNAc enzyme labeling system co-immunoprecipita-tion(Co-IP)and Western blot were used to correlate Rack1 protein levels with O-GlcNAc levels.The impact of O-GlcNAcon Rack1 stability was confirmed using cycloheximide(CHX)and ubiquitination modification experiments.In a medulloblastoma mouse model with Rack1 knockdown,tumor cell proliferation was detected using a Cell Counting Kit-8(CCK-8),immunofluorescence staining,and a scratch assay.Xenograft tumors were transplanted into immunodeficient mice and SHH signaling was detected by Western blot in the obtained tissue samples(sh-NC and sh-Rack1)to verify the role of Rack1 protein in SHH-MB.Results:Rack1 and O-GlcNAcylation levels were significantly in-creased in SHH-MB tumor samples,and a negative correlation was observed between Rack1 levels and patient survival rates.Treatment of Daoy cells with OGT and TM-G revealed that O-GlcNAc significantly promotes Daoy cell proliferation,while inhibiting O-GlcNAc impedes tu-mor cell proliferation.Molecular experiments have confirmed that O-GlcNAc modification of Rack1 protein can regulate tumor cell stability,thereby promoting tumor cell proliferation.When Rack1 expression was knocked down in Daoy cells,cell proliferation was significantly re-duced relative to control cells.Accordingly,proliferation was significantly inhibited in tumor tissues with Rack1 protein knockdown in mouse models,suggesting that Rack1 can participate in the initiation of SHH-MB by regulating SHH signaling.Conclusions:O-GlcNAcylation particip-ates in SHH-MB initiation by regulating Rack1 stability.

Objective:To analyze the mechanism of HOX transcript anti-sense RNA(HOTAIR)promoting invasion and metastasis of gastric cancer from the perspective of its structural domains.Methods:The clinical data of 60 patients with gastric cancer were collected at the Tianjin Medical University Cancer Institute&Hospital from December 2010 to December 2012.Mutants of HOTAIR 3'and 5'domains were constructed as HOT△P and HOT△L,respectively,and the invasion and metastasis of gastric cancer cells were detected using Transwell as-say.Western blot was used to detect epithelial-mesenchymal transition(EMT)-related protein expression;RNAseq was used to analyze the differential genes between the NC and the HOT△L group.RNA was extracted from the clinical tissues for analyzing the correlation between gene expression and clinical information.Results:HOT△L promoted the invasive and metastatic ability of gastric cancer cells more visibly than HOT△P.The mechanistic studies demonstrated that HOT△L more significantly promotes the EMT process in gastric cancer cells com-pared to HOT△P.HOT△L specifically up-regulated the expression of glycine amidinotransferase(GATM).Data analysis and clinical analysis suggested that the high expression of both HOTAIR and GATM group was associated with distal metastasis in gastric cancer patients(P=0.02),which further proved that the high expression of HOTAIR and GATM predicted the poor prognosis of gastric cancer.Molecular in-vestigations suggested that GATM could promote the invasion and metastasis of gastric cancer cells by advancing the progression of EMT.Regulation of EMT by GATM is the key mechanism by which HOT△L promotes the invasive and metastatic ability of gastric cancer,as de-termined by back-complementary experiments.Conclusions:HOTAIR 5'domain regulates the EMT process through specific up-regulation of GATM,thus,promoting the invasion and metastasis of gastric cancer.