Lung adenocarcinoma (LUAD) is a global malignancy with significant chemoresistance impacting patient prognosis. The pro-tumorigenic role of hyaluronan-mediated motility receptor (HMMR) in LUAD is recognized. This study was designed to investigate the underlying mechanisms by which HMMR affects chemoresistance in LUAD. Bioinformatics presented the expression patterns of HMMR in LUAD patients and the association between HMMR levels and patient survival, followed by qRT-PCR to verify HMMR expression in LUAD tissues and cells. Further, bioinformatics was leveraged to identify the signaling pathways enriched by HMMR and its relevance to glycolytic genes, we also analyzed changes in the glycolytic activity of LUAD cells by manipulating HMMR expression. Stemness was evaluated through cell aggregation assays and Western blot, and drug responsiveness was gauged using CCK-8 assays, alongside flow cytometry for apoptosis analysis. HMMR was highly expressed in LUAD tissues and cells, and this overexpression correlated with poorer prognoses in patients. GSEA showed that HMMR was notably enriched in the glycolysis and gluconeogenesis pathways, correlating positively with the expression of key glycolytic genes. Cellular experiments confirmed that HMMR knockdown notably suppressed aerobic glycolysis in LUAD cells. Moreover, overexpression of HMMR could further enhance the stemness and cisplatin resistance of LUAD cells by stimulating glycolysis. In brief, this study has validated that high levels of HMMR in LUAD are predictive of poor patient prognosis, and that overexpression of HMMR can catalyze aerobic glycolysis, thus promoting stemness and chemoresistance in LUAD cells. Thus, HMMR could be a target for improving chemosensitivity in LUAD.

Lung adenocarcinoma (LUAD) is a global malignancy with significant chemoresistance impacting patient prognosis. The pro-tumorigenic role of hyaluronan-mediated motility receptor (HMMR) in LUAD is recognized. This study was designed to investigate the underlying mechanisms by which HMMR affects chemoresistance in LUAD. Bioinformatics presented the expression patterns of HMMR in LUAD patients and the association between HMMR levels and patient survival, followed by qRT-PCR to verify HMMR expression in LUAD tissues and cells. Further, bioinformatics was leveraged to identify the signaling pathways enriched by HMMR and its relevance to glycolytic genes, we also analyzed changes in the glycolytic activity of LUAD cells by manipulating HMMR expression. Stemness was evaluated through cell aggregation assays and Western blot, and drug responsiveness was gauged using CCK-8 assays, alongside flow cytometry for apoptosis analysis. HMMR was highly expressed in LUAD tissues and cells, and this overexpression correlated with poorer prognoses in patients. GSEA showed that HMMR was notably enriched in the glycolysis and gluconeogenesis pathways, correlating positively with the expression of key glycolytic genes. Cellular experiments confirmed that HMMR knockdown notably suppressed aerobic glycolysis in LUAD cells. Moreover, overexpression of HMMR could further enhance the stemness and cisplatin resistance of LUAD cells by stimulating glycolysis. In brief, this study has validated that high levels of HMMR in LUAD are predictive of poor patient prognosis, and that overexpression of HMMR can catalyze aerobic glycolysis, thus promoting stemness and chemoresistance in LUAD cells. Thus, HMMR could be a target for improving chemosensitivity in LUAD.

Lung adenocarcinoma (LUAD) is a global malignancy with significant chemoresistance impacting patient prognosis. The pro-tumorigenic role of hyaluronan-mediated motility receptor (HMMR) in LUAD is recognized. This study was designed to investigate the underlying mechanisms by which HMMR affects chemoresistance in LUAD. Bioinformatics presented the expression patterns of HMMR in LUAD patients and the association between HMMR levels and patient survival, followed by qRT-PCR to verify HMMR expression in LUAD tissues and cells. Further, bioinformatics was leveraged to identify the signaling pathways enriched by HMMR and its relevance to glycolytic genes, we also analyzed changes in the glycolytic activity of LUAD cells by manipulating HMMR expression. Stemness was evaluated through cell aggregation assays and Western blot, and drug responsiveness was gauged using CCK-8 assays, alongside flow cytometry for apoptosis analysis. HMMR was highly expressed in LUAD tissues and cells, and this overexpression correlated with poorer prognoses in patients. GSEA showed that HMMR was notably enriched in the glycolysis and gluconeogenesis pathways, correlating positively with the expression of key glycolytic genes. Cellular experiments confirmed that HMMR knockdown notably suppressed aerobic glycolysis in LUAD cells. Moreover, overexpression of HMMR could further enhance the stemness and cisplatin resistance of LUAD cells by stimulating glycolysis. In brief, this study has validated that high levels of HMMR in LUAD are predictive of poor patient prognosis, and that overexpression of HMMR can catalyze aerobic glycolysis, thus promoting stemness and chemoresistance in LUAD cells. Thus, HMMR could be a target for improving chemosensitivity in LUAD.

[Objective] To explore the incidence and risk factors of blood transfusion undergoing total knee revision (TKR) using a nationwide database. [Methods] A retrospective data analysis was conducted based on the Nationwide Inpatient Sample (NIS), enrolling patients who underwent TKR from 2015 to 2019 with complete information. Patients under 18 years old and those using anticoagulants, antiplatelets, antithrombotic and non-steroidal were excluded. The patients were divided into two groups based on whether they received blood transfusion or not. The demographic characteristics, length of stay (LOS), total charge of hospitalization, hospital characteristics, hospital mortality, comorbidities and perioperative complications by Wilcoxon rank test for continuous data and chi-square test for categorical data. Logistic regression was performed to identify risk factors of blood transfusion undergoing TKR. [Results] The NIS database included 63 359 patients who underwent TKR. Among them, 5 271 patients received blood transfusion, with an incidence of blood transfusion of 7.8%. There was a decrease in the incidence over the years from 2015 to 2019, dropping from 10.2% to 6.5%. TKR patients requiring transfusions had experienced longer LOS, incurred higher total medical expenses, utilized Medicare more frequently, and had increased in-hospital mortality rates (all P<0.001). Independent risk factors for blood transfusion included female gender, iron-deficiency anemia, rheumatoid disease, collagen vascular disease, chronic blood loss anemia, congestive heart failure, coagulopathy, diabetes with chronic complications, lymphoma, fluid and electrolyte disorders, peripheral vascular disorders, renal failure, valvular disease and weight loss (malnutrition). In addition, risk factors for transfusion in TKR surgery included sepsis, acute myocardial infarction, deep vein thrombosis, gastrointestinal bleeding, heart failure, pneumonia, urinary tract infection, acute renal failure, postoperative delirium, wound infection, lower limb nerve injury, hemorrhage, seroma, hematoma, wound rupture and non healing. [Conclusion] Our findings highlight the importance of recognizing the risk factors of blood transfusion in TKR and establishing corresponding clinical pathways and intervention measures to reduce the occurrence of adverse events.

Lung adenocarcinoma (LUAD) is a global malignancy with significant chemoresistance impacting patient prognosis. The pro-tumorigenic role of hyaluronan-mediated motility receptor (HMMR) in LUAD is recognized. This study was designed to investigate the underlying mechanisms by which HMMR affects chemoresistance in LUAD. Bioinformatics presented the expression patterns of HMMR in LUAD patients and the association between HMMR levels and patient survival, followed by qRT-PCR to verify HMMR expression in LUAD tissues and cells. Further, bioinformatics was leveraged to identify the signaling pathways enriched by HMMR and its relevance to glycolytic genes, we also analyzed changes in the glycolytic activity of LUAD cells by manipulating HMMR expression. Stemness was evaluated through cell aggregation assays and Western blot, and drug responsiveness was gauged using CCK-8 assays, alongside flow cytometry for apoptosis analysis. HMMR was highly expressed in LUAD tissues and cells, and this overexpression correlated with poorer prognoses in patients. GSEA showed that HMMR was notably enriched in the glycolysis and gluconeogenesis pathways, correlating positively with the expression of key glycolytic genes. Cellular experiments confirmed that HMMR knockdown notably suppressed aerobic glycolysis in LUAD cells. Moreover, overexpression of HMMR could further enhance the stemness and cisplatin resistance of LUAD cells by stimulating glycolysis. In brief, this study has validated that high levels of HMMR in LUAD are predictive of poor patient prognosis, and that overexpression of HMMR can catalyze aerobic glycolysis, thus promoting stemness and chemoresistance in LUAD cells. Thus, HMMR could be a target for improving chemosensitivity in LUAD.

Lung adenocarcinoma (LUAD) is a global malignancy with significant chemoresistance impacting patient prognosis. The pro-tumorigenic role of hyaluronan-mediated motility receptor (HMMR) in LUAD is recognized. This study was designed to investigate the underlying mechanisms by which HMMR affects chemoresistance in LUAD. Bioinformatics presented the expression patterns of HMMR in LUAD patients and the association between HMMR levels and patient survival, followed by qRT-PCR to verify HMMR expression in LUAD tissues and cells. Further, bioinformatics was leveraged to identify the signaling pathways enriched by HMMR and its relevance to glycolytic genes, we also analyzed changes in the glycolytic activity of LUAD cells by manipulating HMMR expression. Stemness was evaluated through cell aggregation assays and Western blot, and drug responsiveness was gauged using CCK-8 assays, alongside flow cytometry for apoptosis analysis. HMMR was highly expressed in LUAD tissues and cells, and this overexpression correlated with poorer prognoses in patients. GSEA showed that HMMR was notably enriched in the glycolysis and gluconeogenesis pathways, correlating positively with the expression of key glycolytic genes. Cellular experiments confirmed that HMMR knockdown notably suppressed aerobic glycolysis in LUAD cells. Moreover, overexpression of HMMR could further enhance the stemness and cisplatin resistance of LUAD cells by stimulating glycolysis. In brief, this study has validated that high levels of HMMR in LUAD are predictive of poor patient prognosis, and that overexpression of HMMR can catalyze aerobic glycolysis, thus promoting stemness and chemoresistance in LUAD cells. Thus, HMMR could be a target for improving chemosensitivity in LUAD.

Gliomas, especially high-grade gliomas such as glioblastoma multiforme (GBM), are primary malignant tumors of the central nervous system, characterized by high proliferative capacity, invasiveness, and therapeutic resistance. The development of GBM relies heavily on continuous metabolic reprogramming to adapt to the unique intracranial microenvironment, with nicotinamide adenine dinucleotide (NAD⁺) metabolic remodeling playing a pivotal role. Dysregulation of NAD⁺ and its associated metabolic pathways sustains increased intracellular NAD⁺ levels, which drive the malignant proliferation and invasive potential of GBM, correlating with worsened patient prognosis. This review systematically summarizes the current research landscape of NAD⁺ metabolic remodeling in GBM, elucidates the mechanisms by which NAD⁺ contributes to GBM pathogenesis and progression, and explores the clinical potential of NAD⁺-targeted diagnostic and therapeutic strategies to provide novel insights and directions for the clinical management of GBM.

Aim To explore whether platelet-derived growth factor C(PDGFC)derived from cancer-associat-ed fibroblasts(CAFs)can promote resistance of breast cancer cells to doxorubicin(DOX)and the underlying mechanisms.Methods CAFs and normal fibroblasts(NFs)were extracted from freshly resected breast cancer tissue and adjacent normal breast tissue respec-tively.Conditioned medium(CM)from CAFs and NFs was collected and co-cultured with breast cancer cells.Cell proliferation and toxicity were assessed using a Cell Counting Kit-8(CCK-8).The expression of PDG-FC in CAFs,NFs and corresponding CM was detected by Western blot and ELISA respectively.The influence of CAFs-CM on intracellular doxorubicin content in breast cancer cells was observed by fluorescence mi-croscopy.The impact of CAFs-CM on apoptosis-related proteins BAX and BCL2 was predicted and valifated u-sing the Starbase database and Western blot.The changes in ROS levels,mitochondrial membrane po-tential,and mitochondrial membrane proteins TOM20 and COX Ⅳ in breast cancer cells were measured using DCFH-DA fluorescence staining,JC-1 assay,and Western blot.Results CAFs-CM decreased the intra-cellular doxorubicin content and inhibited the sensitivi-ty of breast cancer cells to doxorubicin.Additionally,the expression of apoptosis protein BAX decreased while the anti-apoptotic protein BCL2 increased in breast cancer cells cultured with CAFs-CM.Further-more,CAFs-CM led to decreased ROS levels and in-creased mitochondrial membrane potential in breast cancer cells accompanied with elevated expression of mitochondrial membrane proteins TOM20 and COX Ⅳ.Further study found that PDGEF was highly expressed in CAFs and CAFs-CM,recombinant human PDGFC produced resistance of breast cancer cells to DOX simi-lar to CAFs-CM,and the specific inhibitors of PDGFRα significantly inhibited CAFs-CM.Further mechanistic studies revealed that PDGFC in CAFs-CM induced chemoresistance by activating PI3K-mTOR signaling pathway.Conclusion PDGFC secreted by CAFs promotes doxorubicin resistance in breast cancer cells through PI3K-mTOR signaling pathway,which provides a new perspective for the development of anti-cancer drugs targeting CAFs.

Objective:To understand the whole genome and genetic evolution characteristics of the first epidemic influenza A (H3N2) viruses in Wuxi from 2022-2023.Methods:Real time fluorescence quantitative RT-PCR method was used to perform typing on respiratory samples of influenza cases. Virus isolation was performed on samples with positive nucleic acid of subtype A H3N2 influenza virus detected. After cell culture, nucleic acid was extracted from strains with red blood cell agglutination test (HA) ≥ 1∶8, whole genome sequence was amplified, library was constructed, and computer sequencing was performed using MiSeq sequencer. Using NC_007366.1 as reference strain, the data were analyzed using CLC Genomics Workbench (Version 23) software. The phylogenetic tree was constructed using MEGA 7.0 software, and the N-glycosylation sites were predicted by NetNGlyc 1.0 Server software.Results:The nucleotide homology and amino acid homology among 35 strains of influenza A H3N2 virus from 2022 to 2023 were 96.4%-100% and 95.2%-100%, respectively. The 16 epidemic strains in 2022 belong to the 3C.2a1b.2a.1a evolutionary branch, while the 19 epidemic strains in 2023 belong to the 3C.2a1b.2a.2a.3a.1 evolutionary branch. There are 7 differences in the nucleotide sequence of the HA gene between the 2022 epidemic strain and the corresponding vaccine strain, sharing 15 mutation sites; There are 28 differences in the nucleotide sequence of the HA gene between the 2023 epidemic strain and the corresponding vaccine strain, sharing 17 mutation sites. The HA genes of 35 epidemic strains all lack N-glycosylation site 61: NSS, while in 2023, the HA genes of 19 epidemic strains added N-glycosylation site 110: NSS.Conclusions:The HA and NA genes of influenza A H3N2 virus in 2022 and 2023 belong to two evolutionary branches, respectively, and both show specific amino acid site changes compared to the corresponding vaccine strains. The antigen matching between the 2022 epidemic strain and the vaccine strain is relatively good, while there is a risk of low antigen matching between the 2023 epidemic strain and the vaccine strain.

Objective:To evaluate inflammation early in the infarct zone and its dynamic changes after acute myocardial infarction (AMI) using 18F-FDG PET imaging, and analyze its relationship with left ventricular remodeling progression (LVRP). Methods:Sixteen Bama miniature pigs (4-6 months old, 8 females) were selected. AMI models were established by balloon occlusion of the left anterior descending artery. 18F-FDG PET imaging was performed before AMI and at days 1, 5, 8, and 14 post-AMI to evaluate the regional inflammation response. 18F-FDG SUV ratio (SUVR) and the percentage of uptake area of left ventricle (F-extent) in the infarct zone, and the SUVRs of the spleen and bone marrow, were measured. Echocardiography and 99Tc m-methoxyisobutylisonitrile(MIBI) SPECT myocardial perfusion imaging (MPI) were performed at the above time points and on day 28 post-AMI to assess left ventricular end-diastolic volume (LVEDV), left ventricular end-systolic volume (LVESV), left ventricular ejection fraction (LVEF), and myocardial perfusion defect extent. The degree of LVRP at day 28 post-AMI was defined as ΔLVESV(%)=(LVESV AMI 28 d-LVESV AMI 1 d)/LVESV AMI 1 d×100%. Data were analyzed using repeated measures analysis of variance, Kruskal-Wallis rank sum test and Pearson correlation analysis. Results:Twelve pigs were successfully modeled and completed the study. Inflammation in the infarct zone persisted until day 14 post-AMI. The SUVR of the infarct zone pre-AMI and at days 1, 5, 8, and 14 post-AMI were 1.03±0.08, 3.49±1.06, 2.93±0.90, 2.38±0.76, and 1.63±0.62, respectively ( F=49.31, P<0.001). The F-extent values in the infarct zone pre-AMI and at days 1, 5, 8, and 14 post-AMI were 0, (40.08±12.46)%, (40.00±12.76)%, (31.08±12.82)%, and 16.50%(7.25%, 22.00%), respectively ( H=37.61, P=0.001). There were no significant differences in the SUVRs of bone marrow and spleen before and after AMI ( F values: 0.69 and 0.77, both P>0.05). At day 1 post-AMI, both SUVR and F-extent in the infarct zone were significantly correlated with LVRP ( r values: 0.82 and 0.70, P values: 0.001 and 0.035). Conclusions:18F-FDG PET imaging can be used to evaluate inflammation in the infarct area and its dynamic changes after AMI. Inflammation in the infarct area is severe at day 1, and then gradually decreases. The extent and severity of inflammation visible on 18F-FDG PET imaging 1 d after AMI are closely related to LVRP.