Abstract:Objective：To investigate the functional impact of lactate on triple - negative breast cancer（TNBC）malignancy and elucidate an m6A-dependent epigenetic mechanism through which insulin-like growth factor 2 mRNA-binding protein 3（IGF2BP3） orchestrates metabolic reprogramming via regulation of EP300. Methods：TNBC cells were treated with exogenous sodium lactate supplementation to investigate their oncogenic effects. Cell proliferation and migration were assessed via CCK -8，colony formation， wound healing，and Transwell assays. Stable IGF2BP3-knockdown cell models were established using shRNA lentiviral vectors，with histone lactylation modification levels analyzed by Western blot. RNA immunoprecipitation sequencing（RIP - seq）and m6A - specific methylated RNA immunoprecipitation sequencing（MeRIP-seq）were used to identify IGF2BP3’s m6A target genes，validated by qRT- PCR and Western blot for key molecule expression. Results：Sodium lactate treatment significantly enhanced TNBC cell proliferation and migration，with pan -lactylation levels increasing dose -dependently. IGF2BP3 knockdown reduced histone lactylation. Integrated RIP - seq/MeRIP - seq analysis identified 699 candidate genes whose transcripts bore both IGF2BP3 - specific binding and m6A modifications，significantly enriched in epigenetic regulation and metabolic pathways. IGF2BP3-binding regions on EP300 transcripts overlapped extensively with m6A sites，and EP300 expression was markedly downregulated post - IGF2BP3 knockdown. Conclusion：Exogenous lactate drives TNBC malignant progression by orchestrating pan - lactylation modifications. IGF2BP3 regulates EP300 expression through m6A - dependent mechanisms，mediating the synergistic interplay between histone lactylation and metabolic reprogramming to drive TNBC progression. These findings provide a theoretical basis for novel therapeutic strategies targeting metabolism-epigenetics crosstalk.

Abstract:Breast cancer（BC），as the most common malignant tumor among women globally，has become a significant public health issue worldwide. Although improvements in early diagnosis and treatment technologies，the therapeutic outcomes remain less than satisfactory. BC，characterized by its high heterogeneity and multiple molecular subtypes，poses a considerable challenge to treatment due to its complex biological properties. Traditional chemotherapy and immunotherapy suffer from issues such as insufficient precision， severe side effects，and the tendency to develop drug resistance，thus highlighting the urgent need to develop new therapeutic strategies. Oncolytic viruses（OV）have emerged as an innovative cancer treatment method. Their uniqueness lies in the ability to precisely identify and attack cancer cells while simultaneously activating the body’s immune system to combat cancer. Currently， various OVs have been applied in cancer therapy，including herpes simplex virus（HSV），newcastle disease virus（NDV），vesicular stomatitis virus（VSV），measles virus（MV），adenovirus（AdV），and vaccinia virus（VV）. Moreover，significant progress has been made in the construction of novel OV and the combination with traditional therapies. This article reviews the research progress of common OV in the field of BC treatment over the past five years，thus affirming the great potential of OV.

Abstract:Objective：To explore the expression of β-galactoside-α-2，3-sialyltransferase-3（ST3GAL3）in esophageal squamous cell carcinoma（ESCC）and its relationship with patient prognosis and correlation with clinicopathologic characteristics，as well as to investigate the function and molecular mechanism of ST3GAL3 in cell proliferation and migration. Methods：Bioinformatic analysis， qRT-PCR，and immunohistochemistry（IHC）were employed to measure ST3GAL3 mRNA and protein expression levels in ESCC and adjacent normal tissues，followed by correlation analysis with patient prognosis and clinicopathological data. The expression of ST3GAL3 gene in different ESCC cell lines was analyzed through the CCLE database. We established ST3GAL3-WT and its catalytic site mutant overexpression，as well as ST3GAL3 knockdown and its rescue cells. We assessed cell proliferation，migration，and spreading abilities on ECM using cell proliferation assay and Transwell assay，respectively. The effect of ST3GAL3 on the expression of proteins related to adhesion signaling and the α-2，3-sialylation of Integrin α5 and β1catalyzed by ST3GAL3 was detected by Western blot and lectin-immunoprecipitation（Lectin-IP），respectively. Results：The mRNA expression levels of ST3GAL3 were significantly higher in the ESCC tissues than in the ajacent normal tissues（P ＜ 0.01），with concurrent elevated protein levels in tumor samples. High expression of ST3GAL3 in ESCC was positively correlated with patient poor prognosis and was associated with TNM staging （P=0.004），T classification（P ＜ 0.001），and lymph node metastasis（P=0.017）. ST3GAL3 promoted ESCC cell migration on ECM in a catalytic function - dependent manner. Furthermore，ST3GAL3 mediated cell spreading and adhesion signaling under ECM - coating conditions. Moreover，ST3GAL3 catalyzed the α - 2，3 - sialylation of Integrin α5 and β1. Conclusion：The expression of ST3GAL3 was increased in ESCC tissues，and its high expression was positively correlated with patients’poor prognosis，TNM stage，T classification，and lymph node metastasis. ST3GAL3 enhanced ESCC cell spreading and adhesion signaling on ECM，therefore promoting ECM-mediated cell migration，possibly through the α-2，3 sialylation of adhesion receptors such as Integrin α5 and β1.

Abstract:Objective：To investigate the effects and molecular mechanisms in Wnt/PCP signaling pathway and extracellular matrix （ECM）collaboratively regulating calponin-2（CNN2）to drive collective migration in hepatocellular carcinoma（HCC）cells. Methods： The expression characteristics of CNN2 across various tissues were analyzed by integrating data from The Cancer Genome Atlas （TCGA）and the Human Protein Atlas（HPA）. Its expression level and prognostic relevance in HCC were further evaluated using tissue microarrays. To investigate the functional role of CNN2 in cell migration，transwell and wound healing assays were performed. Furthermore，shRNA - lentivirus mediated knockdown of Wnt11 and CNN2 was employed to elucidate the regulatory relationship between the Wnt/PCP signaling pathway and CNN2，as well as the underlying molecular mechanisms. Finally，rigid substrates was used to mimic the ECM environment，aiming to explore its association with CNN2 expression and the migratory capacity of HCC cells. Results：CNN2 was highly expressed in HCC tissues and was predominantly enriched at the invasive tumor front，suggesting a potential role in the early stages of tumor cell migration. Functional assays further demonstrated that CNN2 significantly promoted collective migration of HCC cells，and its high expression was markedly associated with poor patient prognosis. Mechanistically，CNN2 was regulated by the Wnt/PCP signaling pathway，and its expression was notably upregulated under conditions simulating the mechanical properties of the ECM，indicating a critical role in the cellular perception and response to biomechanical signal. Conclusion：The Wnt/PCP signaling pathway regulates the expression and function of CNN2，while CNN2，as a mediator of mechanical signals，is regulated by ECM mechanical signals. Together，they synergistically drive the collective migration of HCC cells.

Abstract:Objective：To isolate and purify novel Pseudomonas aeruginosa（P. aeruginosa）bacteriophages. Methods： Bacteriophages were isolated from Nanjing Medical University campus Tianyuan lake，followed by genome sequencing and biological characterization of purified phages. In vitro antibacterial assays，including growth inhibition curves and biofilm eradication experiments，were conducted. Results：A novel P. aeruginosa phage named PAPX was successfully isolated. Genomic analysis revealed 98% identity with Pseudomonas phage Epa12，classifying it within the Pbunavirus genus. Transmission electron microscopy demonstrated its myoviral morphology featuring an icosahedral head（∼90 nm diameter）and a contractile tail（∼50 nm length，26 nm diameter）. Biological characterization showed a strong lytic activity against 17 of 24 clinical strains. In vitro experiments confirmed its ability to suppress bacterial growth during early proliferation phase and effectively eradicate P. aeruginosa biofilms. Conclusion：The successful isolation and characterization of phage PAPX，validated through biological profiling and in vitro assays，demonstrates its promising clinical potential for treating P. aeruginosa infections，particularly in combating antibiotic - resistant strains and biofilm -associated infections.

Abstract:Objective：This study aims to explore the relationship between the oxidative stress-lipid metabolism composite biomarker Hpx·apoB[the product of hemopexin（Hpx）and apolipoprotein B（apoB）]and coronary artery disease（CAD），and evaluate its value in clinical risk stratification. Methods：The study utilized liquid chromatography-tandem mass spectrometry to quantify plasma Hpx levels in 107 CAD patients and 33 controls without CAD，collected the clinical data，and constructed a multivariate logistic regression model to analyze the association strength between Hpx ·apoB and CAD. The predictive efficacy of the model was evaluated by area under the receiver operating characteristic（ROC）curve（AUC）and net reclassification index（NRI）. Results：The Hpx·apoB value in the CAD group was significantly higher than that in the control group（P ＜ 0.01）. The Hpx·apoB value was significantly increased in patients with acute myocardial infarction，acute coronary syndrome，and multi - vessel coronary artery disease（all P ＜ 0.01）. Multivariate logistic regression analysis showed that Hpx·apoB was an independent risk factor for CAD（OR=2.554，95%CI：1.336-4.881，P ＜ 0.01）. The ROC curve showed that its AUC for predicting CAD was 0.667，and the predictive efficacy was significantly improved when combined with C-reactive protein（CRP）+low-density lipoprotein cholesterol（LDL-C）：ΔAUC=0.106（P ＜ 0.05），NRI=15.6%（P ＜ 0.05）. After integration with the clinical risk model，it showed a higher predictive value，when integrated with Framingham score：ΔAUC=0.076（P= 0.139），NRI=27.0%（P ＜ 0.01）；when integrated with SCORE model：ΔAUC=0.142（P=0.093），NRI=37.55%（P ＜ 0.001）. Further subgroup analysis revealed that Hpx·apoB has a stronger predictive ability for CAD in men, smokers，and patients with impaired renal function（P ＜ 0.05）. Conclusion：Hpx · apoB，as a composite indicator of oxidative stress and lipid metabolism，can independently predict the risk of CAD. When combined with the clinical risk score，it significantly improves the risk prediction efficacy.

Abstract:Objective：To evaluate the short-and long-term efficacy and safety of adding anti-angiogenic agents to programmed cell death protein 1（PD-1）inhibitors combined with chemotherapy in patients with recurrent or metastatic nasopharyngeal carcinoma（R/M NPC）from non-endemic regions，with the aim of exploring novel combination treatment strategies. Methods：A retrospective analysis was conducted on 171 patients with R/M NPC confirmed by pathology or imaging at Jiangsu Cancer Hospital between January 2019 and December 2024. Patients were divided into two groups：the combination group received anti-angiogenic agents plus PD-1 inhibitors and chemotherapy，while the non - combination group received PD - 1 inhibitors and chemotherapy alone. Clinical data including objective response rate（ORR），disease control rate（DCR），overall survival（OS），progression -free survival（PFS），and treatment - related adverse events were collected. The chi - square test was used to compare baseline characteristics，short - term efficacy，and adverse events between groups. Survival outcomes were analyzed using the Kaplan-Meier method and compared with the log-rank test. Prognostic factors for PFS were evaluated via multivariate Cox regression，and a forest plot was generated. Results：The median follow-up duration was 31.7（2.8-61.8）months. The ORR in the combination group was significantly higher than that in the non-combination group（69.1% vs. 49.5%，P = 0.011）. The median PFS was 28.9 months in the combination group versus 14.2 months in the non - combination group（P=0.025）. No statistically significant difference in OS was observed between the two groups（P=0.203）. Subgroup analysis revealed that the survival benefit of combination therapy was more pronounced in patients aged ≤50 years，without pre - treatment anemia or liver metastasis，with positive EBV - DNA，and those who had not previously received immunotherapy or received ≥2 lines of therapy（P ＜ 0.05）. Apart from rash and anemia，the incidence of other adverse events did not differ significantly between the groups. Conclusion：Combination therapy exhibits favorable antitumor activity and an acceptable safety profile in nonendemic R/M NPC patients who are younger，have no pre-treatment anemia，are EBV-DNA positive，and failed first-line chemotherapy.

Abstract:Objective：To compare the long-term prognosis of endoscopic submucosal dissection（ESD）versus surgical treatment in patients with early Siewert type Ⅱ adenocarcinoma of the esophagogastric junction（AEGJ）. Methods：A retrospective analysis was conducted on 562 patients with early Siewert type Ⅱ AEGJ who underwent ESD or radical surgery at a single tertiary medical center between January 2010 and February 2021，including 393 cases treated with ESD and 169 cases treated with radical surgery. After balancing baseline characteristics using propensity score matching（PSM），the Kaplan-Meier analysis was used to compare long-term survival outcomes between ESD and surgical treatment. Results：The median follow-up time for all 562 patients was 57.7 months （range 6.2-147.0 months）. After PSM，two balanced cohorts of 163 patients each were generated. The 5-year overall survival（OS） rates showed no significant difference between the ESD and surgery groups（92.5% vs. 90.7%，P=0.734）. Similarly，no significant differences were observed in OS（P=0.95）or disease-specific survival（P=0.18）between the two groups. The analysis of adverse events showed no significant differences between the two groups in lymph node metastasis（6.7% vs. 7.4%，P=0.829），local recurrence（4.9% vs. 9.2%，P=0.130），postoperative stenosis（3.7% vs. 1.2%，P=0.152），or bleeding（1.2% vs. 0.6%，P=0.562）. However，the incidence of acid reflux symptoms was significantly higher in the surgery group（11.0% vs. 3.1%，P=0.005）. Conclusion：ESD and surgical treatment for early-stage Siewert type Ⅱ AEGJ demonstrate similar long-term survival outcomes，suggesting that ESD can be an effective alternative treatment for this patient population.

Abstract:Objective：To investigate the abnormalities in routine blood parameters among gastric cancer patients and analyze their trends over the course of the disease. Methods：This study included the population who participated in the Taihu Tumour Biomarkers Biobank（TBTB）in Wuxi from August 2020 to December 2021，with 1 920 cases who already had gastric cancer at baseline as the gastric cancer group and 7 680 cancer-free cases matched 1∶4 for age and sex as the healthy control group. A study design was adopted to explore the association between routine blood tests and the prevalence of gastric cancer using multiple linear regression model，and the Kruskal -Wallis H test was further used to compare the differences in routine blood tests across different stages of the disease between groups. Results：Multiple linear regression model showed that levels of hemoglobin（HGB），platelet count（PLT），red blood cell count（RBC），white blood cell count（WBC），mean hemoglobin content（MCH）and mean corpuscular hemoglobin concentration （MCHC）were lower in gastric cancer patients than in controls，with HGB levels decreasing the most（β=-0.78，95% CI：-0.83--0.73， P ＜ 0.001），and red blood cell volume distribution width（RDW）（β=0.13，95% CI：0.08-0.17，P ＜ 0.001）and hematocrit（HCT）（β= 0.16，95% CI：0.10-0.22，P ＜ 0.001）levels were higher than those of the control group，suggesting that anemia-related signs were more common in gastric cancer patients. We found that WBC level showed a gradual decreasing trend during the disease progression in gastric cancer patients（P ＜ 0.001），and HGB，RBC and hematocrit（HCT）levels tended to increase with the duration of gastric cancer （all P ＜ 0.001），but they were still lower than those of the control group. Conclusion：This study indicates that gastric cancer patients are more likely to exhibit anemia - related abnormalities compared with healthy individuals. Additionally，certain blood routine parameters show significant changing trends with disease progression，providing valuable insights for clinical monitoring and management of gastric cancer.

Abstract:Objective：To clarify the association between cheese intake and healthspan，and further explore the underlying metabolic mechanisms. Methods：This study employed a nested case - control design and defined healthspan terminated（HST）based on eight reported sub-events of HST in UK Biobank（UKB）. 93 214 HST participants and 279 642 controls were included. Conditional logistic regression was used to evaluate the association between cheese intake and HST，and Mendelian randomization（MR）was used to assess the causal effect. Furthermore，we explored the mediating role of metabolites in this relationship by Two - step MR and observational analysis. Results：Cheese intake is a protective factor for healthspan（P_trend ＜ 0.05）. Specifically，participants with high cheese intake （≥5 times/week）had a lower risk of HST（OR=0.93，95% CI：0.89-0.98）compared to those who never intake cheese. MR analysis confirmed this protective effect. Mediation analysis suggested that plasma high density lipoprotein cholesterol（HDL -C）and glucose mediated 6.33% and 14.82% of this effect，respectively. Conclusion：These findings suggested that cheese intake might improve the healthspan by decreasing plasma glucose and increasing plasma HDL -C. As an important component of healthy diet，cheese intake might be recommended in our daily diet structure.

Abstract:Objective：This study retrospectively analyzed data from patients with Gram-negative（G- ）bacilli bloodstream infections to summarize the incidence and clinical outcomes of sepsis-associated encephalopathy（SAE）in these patients. Methods：The data of febrile patients treated in the Emergency Medicine Center of the First Affiliated Hospital of Nanjing Medical University from January 2021 to June 2024 were reviewed. Patients with G-bacilli - positive blood cultures at initial emergency presentation meeting sepsis diagnostic criteria were enrolled. Based on SAE development during the disease course，patients were categorized into SAE and non -SAE groups. Propensity score matching（PSM）was used to adjust for confounding factors between groups，followed by 30- day Kaplan-Meier（K-M）survival curves analysis. Results：A total of 207 patients were included in the study，with 92（44.4%）developing SAE. The 30- day survival rate was lower in the SAE group than in the non - SAE group（69.6% vs. 97.4%，P ＜ 0.001）. After PSM adjustment for baseline characteristics，the SAE group exhibited worse outcomes：lower the 30-day survival（72.3% vs. 100.0%，P ＜ 0.001）， longer ICU stays[5（0，11）d vs. 0（0，5）d，P ＜ 0.001]，higher rates of invasive mechanical ventilation（MV）（40.0% vs. 1.5%，P ＜ 0.001）， continuous renal replacement therapy（CRRT）（32.3% vs. 4.6%，P ＜ 0.001），and use of vasoactive drugs（50.8% vs. 15.4%，P ＜ 0.001）. The K-M curve demonstrated significantly poorer 30-day survival in the SAE group（HR=8.730，95% CI：3.443-22.140，P ＜ 0.001）. Conclusion：SAE is a common complication in septic patients with G-bacilli bloodstream infections and leads to poor prognosis.

Abstract:The classification of central nervous system diseases is complicated and the harm is serious. Because of the existence of blood -brain barrier（BBB），the treatment of central nervous system diseases has great difficulties in drug delivery. Transdermal drug delivery system（TDDS），as a novel drug delivery system that delivers drugs into the blood circulation through the skin，has played a significant role in the treatment of central nervous system diseases in recent years. Due to its unique advantages of painless and convenient administration，transdermal patch has good patient compliance and therapeutic effect，and significantly reduces the first pass effect and adverse reactions. This paper reviews the application of transdermal patches in the treatment of central nervous system diseases such as neurodegenerative diseases and mental diseases，and focuses on the research progress of new technologies such as nanocarriers and microneedle technology in improving the efficiency of drug delivery. However，individual differences and long -term drug safety are still urgent problems to be solved. Future research should focus on the development of novel drug delivery technology and clinical translational application，so as to promote the further development of TDDS in the treatment of central nervous system diseases.

Abstract:Frailty is a common multi-dimensional clinical syndrome in the elderly，with diverse definitions. Most literature considers frailty as a non-specific state characterized by a decline in physiological reserves and increased vulnerability. As the number of elderly patients undergoing cardiac surgery increases，the impact of frailty on these patients has gained increasing attention from clinicians. This article briefly describes the assessment methods of preoperative frailty，and reviews the impact of frailty on the clinical outcomes after cardiac surgery，such as increased risks of adverse prognosis and postoperative complications，reduced the postoperative quality of life of patients，and higher medical costs. Additionally，it summarizes the intervention and management strategies for frail elderly patients with heart disease，aiming to clarify the goals of intervention and treatment，and enhance the survival outcomes and quality of life of patients.

Abstract:Multiple myeloma（MM）is an acquired hematologic malignancy with an unclear etiology. Imaging examinations are essential for MM detection. PET/CT，which combines metabolic and anatomical information，plays a crucial role in the diagnosis， treatment response evaluation，and prognosis prediction of MM. Currently，18F - FDG is the most widely used radiotracer for PET imaging. However，as a glucose analog，18F-FDG uptake lacks specificity，and its imaging can be easily affected by various factors. In recent years，research teams worldwide have been investigating novel PET tracers for MM to develop more specific imaging agents. This review article provides a comprehensive analysis of both conventional and emerging PET tracers in MM，aiming to help healthcare professionals understand the value and advances of PET imaging in this disease.

Abstract:Prostate cancer is one of the most common malignant tumors in men. Prostate biopsy can directly obtain prostate tissue samples for pathological analysis to preoperatively diagnose or exclude prostate cancer. However，as an invasive examination method， it inevitably causes complications such as bleeding，infection，vagal reflex，and acute urinary retention. Therefore，reducing unnecessary biopsies and improving biopsy techniques are crucial. Currently，with the development of various imaging technologies and artificial intelligence，the techniques for guiding prostate biopsies are gradually improving. This article aims to elucidate the advantages and disadvantages of prostate biopsy techniques under different guidance methods and the research progress of new technologies.

Abstract:Perivascular adipose tissue（PVAT）of the carotid artery is a specialized type of adipose tissue closely adjacent to the arterial adventitia，possessing unique anatomical and functional characteristics. Unlike ordinary adipose tissue，PVAT releases a variety of bioactive molecules through endocrine and paracrine mechanisms，interacting with adjacent vascular wall cells and participating in the regulation of local inflammatory responses and vascular homeostasis. The inflammatory status of PVAT is closely associated with the formation，progression，and vulnerability of carotid atherosclerotic plaques，while also playing a critical role in the development and progression of cerebrovascular diseases. In recent years，with the rapid advancement of imaging technologies，non - invasive assessment of PVAT inflammation has become feasible. These techniques provide new tools for early identification of high-risk patients with cerebrovascular diseases and hold promise for optimizing preventive strategies and personalized treatment. This article systematically reviews the pathophysiological mechanisms of carotid PVAT，the latest advances in imaging assessment techniques，and their clinical application value.

Abstract:Early childhood is a critical stage of growth and development，and the nutritional status of this period not only affects physical growth and development，but also lays a solid foundation for lifelong health. However，due to the rapid growth and metabolic characteristics of infants and young children，coupled with the immaturity of multiple physiological systems and the high incidence of infectious diseases，they face nutritional risks. This review synthesizes relevant domestic and international studies to elucidate the current landscape of infant nutrition risk，as well as the associated influencing factors such as environment，age，disease，and high-risk conditions. The paper also shows the design，application，scope，and limitations of existing infant nutrition risk screening tools，along with the clinical significance of nutritional risk screening for infants and young children in inpatient，outpatient clinics，and specialized settings. The primary objective of this paper is to raise awareness among pediatric clinicians regarding infant nutrition issues and to promote proactive nutritional risk screening，thereby facilitating early identification of nutritional risks and ultimately achieving standardized and scientific nutrition management.

Abstract: