BACKGROUND:Osteosarcoma has a complex pathogenesis and a poor prognosis.While advancements in medical technology have led to some improvements in the 5-year survival rate,substantial progress in its treatment has not yet been achieved. OBJECTIVE:To screen key molecular markers in osteosarcoma,analyze their relationship with osteosarcoma treatment drugs,and explore the potential disease mechanisms of osteosarcoma at the molecular level. METHODS:GSE99671 and GSE284259(miRNA)datasets were obtained from the Gene Expression Omnibus database.Differential gene expression analysis and Weighted Gene Co-expression Network Analysis(WGCNA)on GSE99671 were performed.Functional enrichment analysis was conducted using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes separately for the differentially expressed genes and the module genes with the highest positive correlation to the disease.The intersection of these module genes and differentially expressed genes was taken as key genes.A Protein-Protein Interaction network was constructed,and correlation analysis on the key genes was performed using CytoScape software,and hub genes were identified.Hub genes were externally validated using the GSE28425 dataset and text validation was conducted.The drug sensitivity of hub genes was analyzed using the CellMiner database,with a threshold of absolute value of correlation coefficient|R|>0.3 and P<0.05. RESULTS AND CONCLUSION:(1)Differential gene expression analysis identified 529 differentially expressed genes,comprising 177 upregulated and 352 downregulated genes.WGCNA analysis yielded a total of 592 genes with the highest correlation to osteosarcoma.(2)Gene Ontology enrichment results indicated that the development of osteosarcoma may be associated with extracellular matrix,bone cell differentiation and development,human immune regulation,and collagen synthesis and degradation.Kyoto Encyclopedia of Genes and Genomes enrichment results showed the involvement of pathways such as PI3K-Akt signaling pathway,focal adhesion signaling pathway,and immune response in the onset of osteosarcoma.(3)The intersection analysis revealed a total of 59 key genes.Through Protein-Protein Interaction network analysis,8 hub genes were selected,which were LUM,PLOD1,PLOD2,MMP14,COL11A1,THBS2,LEPRE1,and TGFB1,all of which were upregulated.(4)External validation revealed significantly downregulated miRNAs that regulate the hub genes,with hsa-miR-144-3p and hsa-miR-150-5p showing the most significant downregulation.Text validation results demonstrated that the expression of hub genes was consistent with previous research.(5)Drug sensitivity analysis indicated a negative correlation between the activity of methotrexate,6-mercaptopurine,and pazopanib with the mRNA expression of PLOD1,PLOD2,and MMP14.Moreover,zoledronic acid and lapatinib showed a positive correlation with the mRNA expression of PLOD1,LUM,MMP14,PLOD2,and TGFB1.This suggests that zoledronic acid and lapatinib may be potential therapeutic drugs for osteosarcoma,but further validation is required through additional basic experiments and clinical studies.

OBJECTIVE: To investigate the common mechanisms among collagen-induced arthritis (CIA), bleomycin (BLM)-induced pulmonary fibrosis, and CIA+BLM to evaluate the therapeutic effect of triptolide (TP) on CIA+BLM. METHODS: Thirty-six male Sprague-Dawley rats were randomly assigned to 6 groups according to a random number table (n=6 per group): normal control (NC), CIA, BLM, combined CIA+BLM model, TP low-dose (TP-L, 0.0931 mg/kg), and TP high-dose (TP-H, 0.1862 mg/kg) groups. The CIA model was induced by intradermal injection at the base of the tail with emulsion of bovine type II collagen and incomplete Freund's adjuvant (1:1), with 200 µL administered on day 0 and a booster of 100 µL on day 7. Pulmonary fibrosis was induced via a single intratracheal injection of BLM (5 mg/kg). The CIA+BLM model combined both protocols, and TP was administered orally from day 14 to 35. After successful modeling, arthritis scores were recorded every 3 days, and pulmonary function was assessed once at the end of the treatment period. Lung tissues were collected for histological analysis (hematoxylin eosin and Masson staining), immunohistochemistry, measurement of hydroxyproline (HYP) content, and calculation of lung coefficient. In addition, HE staining was performed on the ankle joint. Total RNA was extracted from lung tissues for transcriptomic analysis. Differentially expressed genes (DEGs) were compared with those from the RA-associated interstitial lung diseases patient dataset GSE199152 to identify overlapping genes, which were then used to construct a protein-protein interaction network. Hub genes were identified using multiple topological algorithms. RESULTS: The successfully established CIA+BLM rat model exhibited significantly increased arthritis scores and severe pulmonary fibrosis (P<0.01). By intersecting the DEGs obtained from transcriptomic analysis of lung tissues in CIA, BLM, and CIA+BLM rats with DEGs from rheumatoid arthritis-interstitial lung disease patients (GSE199152 dataset), 50 upregulated and 44 downregulated genes were identified. Through integrated PPI network analysis using multiple topological algorithms, IGF1 was identified as a central hub gene. TP intervention significantly improved pulmonary function by increasing peak inspiratory flow (P<0.01), and reduced lung index and HYP content (P<0.01). Histopathological analysis showed that TP alleviated alveolar collapse, interstitial thickening, and collagen deposition in the lung tissues (P<0.01). Moreover, TP treatment reduced the expression of collagen type I and α-SMA and increased E-cadherin levels (P<0.01). TP also significantly reduced arthritis scores and ameliorated synovial inflammation (P<0.05). Both transcriptomic and immunohistochemical analyses confirmed that IGF1 expression was elevated in the CIA+BLM group and downregulated following TP treatment (P<0.05). CONCLUSION TP exerts protective effects in the CIA+BLM model by alleviating arthritis and pulmonary fibrosis through the inhibition of IGF1-mediated EMT.
Animals ; Pulmonary Fibrosis/complications* ; Bleomycin/adverse effects* ; Phenanthrenes/pharmacology* ; Male ; Rats, Sprague-Dawley ; Diterpenes/pharmacology* ; Epoxy Compounds/therapeutic use* ; Arthritis, Experimental/complications* ; Insulin-Like Growth Factor I/metabolism* ; Rats ; Lung/physiopathology*

HDAC7, a member of class IIa HDACs, plays a pivotal regulatory role in tumor, immune, fibrosis, and angiogenesis, rendering it a potential therapeutic target. Nevertheless, due to the high similarity in the enzyme active sites of class IIa HDACs, inhibitors encounter challenges in discerning differences among them. Furthermore, the substitution of key residue in the active pocket of class IIa HDACs renders them pseudo-enzymes, leading to a limited impact of enzymatic inhibitors on their function. In this study, proteolysis targeting chimera (PROTAC) technology was employed to develop HDAC7 drugs. We developed an exceedingly selective HDAC7 PROTAC degrader B14 which showcased superior inhibitory effects on cell proliferation compared to TMP269 in various diffuse large B cell lymphoma (DLBCL) and acute myeloid leukemia (AML) cells. Subsequent investigations unveiled that B14 disrupts BCL6 forming a transcriptional inhibition complex by degrading HDAC7, thereby exerting proliferative inhibition in DLBCL. Our study broadened the understanding of the non-enzymatic functions of HDAC7 and underscored the importance of HDAC7 in the treatment of hematologic malignancies, particularly in DLBCL and AML.

OBJECTIVES: To explore the efficacy of DSA-guided intrathecal drug delivery system combined with Zi Wu Liu Zhu Acupoint Therapy for management of cancer pain and provide reference for its standardized clinical application. Methods and. RESULTS: Recommendations were formulated based on literature review and expert group discussion, and consensus was reached following expert consultation. The consensus recommendations are comprehensive, covering the entire treatment procedures from preoperative assessment and preparation, surgical operation process, postoperative management and traditional Chinese medicine treatment to individualized treatment planning. The study results showed that the treatment plans combining traditional Chinese with Western medicine effectively alleviated cancer pain, reduced the use of opioid drugs, and significantly improved the quality of life and enhanced immune function of the patients. Postoperative follow-up suggested good treatment tolerance among the patients without serious complications. CONCLUSIONS The formulated consensus is comprehensive and can provide reference for clinicians to use DSA-guided intrathecal drug delivery system combined with Zi Wu Liu Zhu Acupoint Therapy. The combined treatment has a high clinical value with a good safety profile for management of cancer pain.
Humans ; Medicine, Chinese Traditional ; Cancer Pain/therapy* ; Drugs, Chinese Herbal/therapeutic use* ; Drug Delivery Systems ; Pain Management/methods* ; China

Cancer stem cells (CSCs) are widely acknowledged as primary mediators to the initiation and progression of tumors. The association between microbial infection and cancer stemness has garnered considerable scholarly interest in recent years. Porphyromonas gingivalis (P. gingivalis) is increasingly considered to be closely related to the development of oral squamous cell carcinoma (OSCC). Nevertheless, the role of P. gingivalis in the stemness of OSCC cells remains uncertain. Herein, we showed that P. gingivalis was positively correlated with CSC markers expression in human OSCC specimens, promoted the stemness and tumorigenicity of OSCC cells, and enhanced tumor formation in nude mice. Mechanistically, P. gingivalis increased lipid synthesis in OSCC cells by upregulating the expression of stearoyl-CoA desaturase 1 (SCD1) expression, a key enzyme involved in lipid metabolism, which ultimately resulted in enhanced acquisition of stemness. Moreover, SCD1 suppression attenuated P. gingivalis-induced stemness of OSCC cells, including CSCs markers expression, sphere formation ability, chemoresistance, and tumor growth, in OSCC cells both in vitro and in vivo. Additionally, upregulation of SCD1 in P. gingivalis-infected OSCC cells was associated with the expression of KLF5, and that was modulated by P. gingivalis-activated NOD1 signaling. Taken together, these findings highlight the importance of SCD1-dependent lipid synthesis in P. gingivalis-induced stemness acquisition in OSCC cells, suggest that the NOD1/KLF5 axis may play a key role in regulating SCD1 expression and provide a molecular basis for targeting SCD1 as a new option for attenuating OSCC cells stemness.
Porphyromonas gingivalis/pathogenicity* ; Stearoyl-CoA Desaturase/metabolism* ; Humans ; Carcinoma, Squamous Cell/pathology* ; Mouth Neoplasms/metabolism* ; Animals ; Neoplastic Stem Cells/microbiology* ; Mice, Nude ; Mice ; Nod1 Signaling Adaptor Protein/metabolism* ; Kruppel-Like Transcription Factors/metabolism* ; Cell Line, Tumor

OBJECTIVE: To investigate the efficacy and safety of autologous blood transfusion during weaning from venous-arterial extracorporeal membrane oxygenation (VA-ECMO) under controlled rotational speed. METHODS: A retrospective study was conducted, selecting patients who underwent extracorporeal membrane oxygenation (ECMO) and successfully weaned at the emergency and critical care medicine center of Henan Provincial Third People's Hospital from January 2023 to May 2024. General data including gender, age, body mass index (BMI), European system for cardiac operative risk evaluation (EuroScore), and disease types were collected. Vital signs at weaning [heart rate, systolic blood pressure (SBP), diastolic blood pressure (DBP), and peripheral oxygen saturation], parameters before and after weaning [B-type natriuretic peptide (BNP), hemoglobin (Hb), partial pressure of arterial oxygen (PaO₂), partial pressure of arterial carbon dioxide (PaCO₂), arterial lactate, central venous pressure (CVP), inferior vena cava collapsibility index, left ventricular ejection fraction (LVEF), and right heart load], post-weaning inflammatory markers at 1-day and 3-day [body temperature, white blood cell count (WBC), neutrophil percentage (NEU%), C-reactive protein (CRP), procalcitonin (PCT), interleukin-10 (IL-10)], as well as complications (infection, thrombosis, renal failure, gastrointestinal bleeding) and post-weaning blood return status were recorded. Patients were divided into an observation group (with post-weaning blood return) and a control group (without post-weaning blood return) based on the presence of blood return after weaning. The changes in the aforementioned parameters were compared between the two groups. RESULTS: A total of 62 patients were included, with 31 cases in each group. No statistically significant differences were observed between the two groups in baseline characteristics including gender, age, BMI, and EuroScore. At weaning, the observation group exhibited relatively stable vital signs, with no significant differences in heart rate, SBP, DBP, or peripheral oxygen saturation compared to the control group. After weaning, the observation group showed significantly lower levels of BNP, PaCO₂, arterial lactate, CVP, and right heart load compared to pre-weaning values [BNP (ng/L): 2 325.96±78.51 vs. 4 878.48±185.47, PaCO₂ (mmHg, 1 mmHg≈0.133 kPa): 35.23±3.25 vs. 40.75±4.41, arterial lactate (mmol/L): 2.43±0.61 vs. 6.19±1.31, CVP (cmH₂O, 1 cmH₂O≈0.098 kPa): 8.32±0.97 vs. 15.34±1.74, right heart load: 13.24±0.97 vs. 15.69±1.31, all P < 0.05], while Hb, PaO₂, inferior vena cava collapsibility index, and LVEF were significantly higher than pre-weaning values [Hb (g/L): 104.42±9.78 vs. 96.74±6.39, PaO₂ (mmHg): 94.12±7.78 vs. 75.51±4.39, inferior vena cava collapsibility (%): 28±7 vs. 17±3, LVEF (%): 62.41±6.49 vs. 45.30±4.51, all P < 0.05]. No statistically significant differences were found between the observation group and control group in these parameters. At 3 days post-weaning, the observation group demonstrated significantly lower levels of body temperature, WBC, NEU%, CRP, PCT, and IL-10 compared to 1 day post-weaning [body temperature (centigrade): 36.83±1.15 vs. 37.94±1.41, WBC (×10⁹/L): 7.82±0.96 vs. 14.34±2.15, NEU%: 0.71±0.05 vs. 0.80±0.07; CRP (mg/L): 4.34±0.78 vs. 8.94±1.21, PCT (μg/L): 0.11±0.02 vs. 0.26±0.05, IL-10 (ng/L): 8.93±1.52 vs. 13.51±2.17, all P < 0.05], with no significant differences compared to the control group. No statistically significant differences were observed between the two groups in the incidence of complications including infection, thrombosis, renal failure, and gastrointestinal bleeding. CONCLUSION Autologous blood reinfusion during VA-ECMO weaning under controlled rotational speed is safe and effective, without increasing risks of infection or thrombosis.
Humans ; Retrospective Studies ; Extracorporeal Membrane Oxygenation/methods* ; Blood Transfusion, Autologous ; Male ; Female ; Adult ; Middle Aged ; Natriuretic Peptide, Brain/blood*

Objective:To explore the diagnostic value of preoperative diffusion weighted imaging (DWI) histogram parameters in the depth of invasion of early rectal cancer.Methods:A total of 180 patients with early rectal cancer admitted to 904th Hospital of Joint Logistics Support Force of Chinese People's Liberation Army from August 2020 to August 2024 were selected as the study objects. Patients were divided into intramucosal cancer group ( n=102) and submucosal cancer group ( n=78) according to the depth of tumor invasion. The general data of the two groups were compared. The intraclass correlation coefficient (ICC) was used to analyze the consistency of DWI histogram parameters extracted by the two radiologists, and the differences between the two groups were compared. Receiver operator characteristic (ROC) curve was used to analyze the predictive value of each parameter to the depth of tumor invasion. Multivariate logistic regression was used to analyze the independent influencing factors of invasion depth, and a predictive model was constructed. The ROC curve was drawn to analyze the predictive value of the model for tumor invasion depth, and the Hosmer-Lemeshow test was used to analyze the goodness of fit of the model. Results:There were statistically significant differences in age ( t=8.15, P<0.001), maximum tumor diameter ( χ2=29.29, P<0.001), endoscopic type ( χ2=20.96, P<0.001), histological type ( χ2=24.93, P<0.001) and differentiation degree ( χ2=73.35, P<0.001) between intramucosal cancer group and submucosal cancer group. The mean, variance, skewness, kurtosis, the 1 st, 10 th, 50 th, 90 th, and 99 th percentiles of the histogram parameters of DWI had good consistency (all ICC>0.75). There were statistically significant differences in the mean ( t=5.69, P<0.001), variance ( t=9.75, P<0.001), skewness ( t=10.88, P<0.001), kurtosis ( t=10.06, P<0.001), the 1 st percentile ( t=3.43, P<0.001), 10 th percentile ( t=3.59, P<0.001), 50 th percentile ( t=9.97, P<0.001), 90 th percentile ( t=4.63, P<0.001), and 99 th percentile ( t=2.44, P=0.016) of the DWI histogram parameters between the intramucosal cancer group and the submucosal cancer group. ROC curve analysis results showed that mean [area under the curve (AUC) =0.77], variance (AUC=0.88), skewness (AUC=0.88), kurtosis (AUC=0.78), 50 th percentile (AUC=0.86) and 90 th percentile (AUC=0.82) had certain diagnostic value for submucous cancer. Multivariate analysis showed that age ( OR=9.98, 95% CI: 1.10-90.70, P=0.041), maximum tumor diameter ( OR=7.36, 95% CI: 1.08-50.23, P=0.042), and differentiation degree ( OR=19.88, 95% CI: 1.21-327.92, P=0.037), variance ( OR=16.24, 95% CI: 2.26-116.68, P=0.006), skewness ( OR=21.13, 95% CI: 2.80-59.61, P=0.003), 1 st percentile ( OR=9.78, 95% CI: 1.17-81.76, P=0.035) were independent factors in predicting tumor invasion depth in patients with early rectal cancer. The predictive model based on the above indicators was logit ( P) =1.51+2.30×age+2.00×maximum tumor diameter+2.99×differentiation degree+2.79×variance+3.05×skewness+ 2.28×the 1 st percentile. ROC curve analysis showed that the predictive model had an AUC of 0.97 (95% CI: 0.95-0.99) for judging the occurrence of submucosal cancer in patients with early rectal cancer, the sensitivity was 0.95, and the specificity was 0.88. The Hosmer-Lemeshow test results showed that the goodness of fit of the model was ideal ( P=0.823) . Conclusions:Age, maximum tumor diameter, differentiation degree, variance, skewness, and the 1 st percentile are independent factors in predicting tumor invasion depth in patients with early rectal cancer. The predictive model constructed based on these factors can effectively predict the risk of submucosal cancer in patients with early rectal cancer.

Objective To explore the feasibility,effectiveness,and safety of balloon catheter-assisted total hepatic vascular exclusion.Methods We designed and manufactured an endovascular catheter with three lumens and double balloons,which can be inserted into the retrahepatic inferior vena cava through the femoral vein.The superior and inferior vena cava of the liver can be blocked by filling balloon,and the total hepatic vascular exclusion was achieved by combining with pringle method.In animal experiments,total hepatic vascular exclusion was performed by balloon catheter-assist method(experimental group)or traditional methods(control group),and the complete time was compared between the two groups.Blood flow blocking effect was observed by angiography and incision of retrahepatic inferior vena cava under direct vision.The complications were recorded.Results Total hepatic vascular exclusion was successfully completed in both groups.The completion time in the experimental group was significantly shorter than that in the control group([12.5±1.2]min vs.[35.8±4.9]min,P<0.05).CT angiography,DSA,and direct vision of blood vessels all confirmed the effectiveness of balloon catheter-assisted hepatic blood flow exclusion.No catheter displacement,balloon rupture,or air embolism occurred.Conclusion The balloon catheter-assisted hepatic total vascular exclusion is simpler and more feasible than traditional method.

Methicillin-sensitive Staphylococcus aureus(MSSA)bloodstream infections are associ-ated with high mortality rates.This study reviewed the current epidemiological status,pathogenic mechanisms,risk factors for infection,and novel treatment strategies for MSSA,providing a reference for early treatment of bloodstream infections.