Dysregulation of p53 and phosphoinositide (PIPn) signaling are both key drivers of oncogenesis and metastasis. Our recent findings reveal a previously unrecognized interaction between these pathways, converging in the nucleus to form a PIPn-p53 signalosome that modulates nuclear AKT activation and downstream signaling, thereby influencing cancer cell survival and motility. This review examines recent insights into nuclear PIPn signaling in the context of established roles for p53 in cell dynamics and migration while also deliberating current research on how nuclear PIPns interact with p53 to form signalosomes that affect cell motility. We emphasize the critical role of PIPns in stabilizing p53 and activating de novo nuclear AKT signaling, which subsequently modulates key motility-related pathways. Understanding the unique operation and function of the PIPn-p53 signalosome in nuclear phosphatidylinositol 3-kinase (PI3K)-AKT activation offers novel therapeutic strategies for controlling cancer metastasis by targeting pertinent interactions and events.
Humans ; Tumor Suppressor Protein p53/metabolism* ; Signal Transduction ; Cell Movement ; Cell Nucleus/metabolism* ; Phosphatidylinositols/metabolism* ; Proto-Oncogene Proteins c-akt/metabolism* ; Animals ; Neoplasms/pathology* ; Phosphatidylinositol 3-Kinases/metabolism*

Objective To elucidate the role of let-7 in the pathogenesis of oral squamous cell carcinoma(OSCC)and its underlying molecular mechanism.Methods The expression of let-7 in human oral keratinocyte(HOK),OSCC tissues,and OSCC cells(CAL-27,SCC-25,and SCC-9)was detected by quantitative real-time PCR.Colony formation,scratch,Transwell,and flow cytometry assays were used to examine the effects of let-7 on the proliferation,migration,invasion,and apoptosis of SCC-25 cells.Western blotting was used to detect the expression of Wnt and β-catenin proteins.The correlation between let-7 expression and the clinicopathological cha-racteristics and prognosis of OSCC patients was analyzed.Results let-7 was downregulated in OSCC tissues and cells.let-7 over-expression effectively inhibited the proliferation,migration,and invasion of SCC-25 cells while promoting apoptosis by suppressing acti-vation of the Wnt/β-catenin pathway.let-7 expression was closely associated with tumor stage,lymph node metastasis,and patient survival status.Patients with low let-7 expression exhibited lower overall survival rate.Conclusion let-7 targets and regulates the Wnt/β-catenin pathway,thereby inhibiting proliferation,migration,and invasion of OSCC cells while promoting apoptosis.

Objective To elucidate the role of let-7 in the pathogenesis of oral squamous cell carcinoma(OSCC)and its underlying molecular mechanism.Methods The expression of let-7 in human oral keratinocyte(HOK),OSCC tissues,and OSCC cells(CAL-27,SCC-25,and SCC-9)was detected by quantitative real-time PCR.Colony formation,scratch,Transwell,and flow cytometry assays were used to examine the effects of let-7 on the proliferation,migration,invasion,and apoptosis of SCC-25 cells.Western blotting was used to detect the expression of Wnt and β-catenin proteins.The correlation between let-7 expression and the clinicopathological cha-racteristics and prognosis of OSCC patients was analyzed.Results let-7 was downregulated in OSCC tissues and cells.let-7 over-expression effectively inhibited the proliferation,migration,and invasion of SCC-25 cells while promoting apoptosis by suppressing acti-vation of the Wnt/β-catenin pathway.let-7 expression was closely associated with tumor stage,lymph node metastasis,and patient survival status.Patients with low let-7 expression exhibited lower overall survival rate.Conclusion let-7 targets and regulates the Wnt/β-catenin pathway,thereby inhibiting proliferation,migration,and invasion of OSCC cells while promoting apoptosis.

Objective:To explore the feasibility, safety, and effectiveness of a novel suture instrument for closure of full thickness defects of the gastric wall under gastroscopy.Methods:Ten pigs were used as experimental animals. Perforation model (30 mm in long diameter) was created in the stomach of each pig. The perforations were then closed by the novel suture instrument under gastroscopy. The completion time and efficacy of each perforation repair were recorded. The pigs were euthanized 14 days after the procedure. The healing condition was observed under gastroscopy. A postmortem examination was performed to observe the abdominal infection and healing condition of perforation. Ascites sample was taken for bacterial culture.The stomach biopsy were taken for histopathologic examination.Results:All gastric perforation models in the 10 pigs were established successfully. Endoscopic closure for the stomach perforation was technically successful in all 10 pigs. The procedure time was 34.10±10.32 minutes. All animals survived. Gastroscopy and necropsy showed that the perforation healed well with local adhesion. One pig developed abdominal infection. Ascites culture were negative in 9 cases, 1 bacterial infection was caused by Arcanobacterium pyogenes and Escherichiacoli. The pathology results showed that the muscular layer of the gastric wall defect in the entire group was well repaired. Conclusion:The novel suture instrument is safe and effective in repairing full-thickness gastric wall defects under ordinary single clamp gastroscopy, providing an experimental basis for further clinical research.

BACKGROUND:Existing studies have compared patients with degenerative lumbar spondylolisthesis with healthy populations,but comparative studies focusing on differences in this aspect of the parameter between these different lumbar spondylolisthesis are lacking.OBJECTIVE:To explore the differences in paraspinal muscle degeneration between isthmic spondylolisthesis and degenerative lumbar spondylolisthesis,and their correlation with low back pain symptoms.METHODS:A total of 107 patients with lumbar spondylolisthesis treated in Affiliated Hospital of Xuzhou Medical University between February 2019 and August 2023 were analyzed retrospectively.They were divided into the isthmic spondylolisthesis group(39 patients)and the degenerative lumbar spondylolisthesis group(68 patients)according to the type of spondylolisthesis.Paravertebral muscle tissue parameters were compared and analyzed as well as functional scores(visual analog scale for low back pain)in both groups.According to the visual analog scale score,the two groups of patients were divided into two subgroups:those with a visual analog scale score＜45 mm and those with a visual analog scale score＞45 mm,and the relationship between the difference in visual analog scale score and the parameters of paraspinal muscle tissue degeneration was analyzed.RESULTS AND CONCLUSION:(1)The percentage of fat infiltration in the multifidus muscle was higher in the degenerative lumbar spondylolisthesis group than in the isthmic spondylolisthesis group(P=0.003).(2)The percentage of fat infiltration in the multifidus muscle was significantly lower in patients with a visual analog scale score of＜45 mm than in patients with a visual analog scale score of＞45 mm in both groups(P=0.021,P＜0.001).(3)Patients in the isthmic spondylolisthesis group also showed a significantly lower percentage of fat infiltration in patients with visual analog scale score＜45 mm compared with those with visual analog scale score＞45 mm(P=0.002).(4)These results showed that there was a significant difference in paraspinal muscle tissue degeneration between isthmic spondylolisthesis patients and degenerative lumbar spondylolisthesis patients,and that degenerative lumbar spondylolisthesis patients demonstrated more severe paraspinal muscle degeneration compared to isthmic spondylolisthesis patients.In addition,the percentage of fatty infiltration of the multifidus muscle was relatively greater in those with higher pain scores in both groups of lumbar spondylolisthesis patients.

BACKGROUND:Existing studies have compared patients with degenerative lumbar spondylolisthesis with healthy populations,but comparative studies focusing on differences in this aspect of the parameter between these different lumbar spondylolisthesis are lacking.OBJECTIVE:To explore the differences in paraspinal muscle degeneration between isthmic spondylolisthesis and degenerative lumbar spondylolisthesis,and their correlation with low back pain symptoms.METHODS:A total of 107 patients with lumbar spondylolisthesis treated in Affiliated Hospital of Xuzhou Medical University between February 2019 and August 2023 were analyzed retrospectively.They were divided into the isthmic spondylolisthesis group(39 patients)and the degenerative lumbar spondylolisthesis group(68 patients)according to the type of spondylolisthesis.Paravertebral muscle tissue parameters were compared and analyzed as well as functional scores(visual analog scale for low back pain)in both groups.According to the visual analog scale score,the two groups of patients were divided into two subgroups:those with a visual analog scale score＜45 mm and those with a visual analog scale score＞45 mm,and the relationship between the difference in visual analog scale score and the parameters of paraspinal muscle tissue degeneration was analyzed.RESULTS AND CONCLUSION:(1)The percentage of fat infiltration in the multifidus muscle was higher in the degenerative lumbar spondylolisthesis group than in the isthmic spondylolisthesis group(P=0.003).(2)The percentage of fat infiltration in the multifidus muscle was significantly lower in patients with a visual analog scale score of＜45 mm than in patients with a visual analog scale score of＞45 mm in both groups(P=0.021,P＜0.001).(3)Patients in the isthmic spondylolisthesis group also showed a significantly lower percentage of fat infiltration in patients with visual analog scale score＜45 mm compared with those with visual analog scale score＞45 mm(P=0.002).(4)These results showed that there was a significant difference in paraspinal muscle tissue degeneration between isthmic spondylolisthesis patients and degenerative lumbar spondylolisthesis patients,and that degenerative lumbar spondylolisthesis patients demonstrated more severe paraspinal muscle degeneration compared to isthmic spondylolisthesis patients.In addition,the percentage of fatty infiltration of the multifidus muscle was relatively greater in those with higher pain scores in both groups of lumbar spondylolisthesis patients.

Objective:To explore the feasibility, safety, and effectiveness of a novel suture instrument for closure of full thickness defects of the gastric wall under gastroscopy.Methods:Ten pigs were used as experimental animals. Perforation model (30 mm in long diameter) was created in the stomach of each pig. The perforations were then closed by the novel suture instrument under gastroscopy. The completion time and efficacy of each perforation repair were recorded. The pigs were euthanized 14 days after the procedure. The healing condition was observed under gastroscopy. A postmortem examination was performed to observe the abdominal infection and healing condition of perforation. Ascites sample was taken for bacterial culture.The stomach biopsy were taken for histopathologic examination.Results:All gastric perforation models in the 10 pigs were established successfully. Endoscopic closure for the stomach perforation was technically successful in all 10 pigs. The procedure time was 34.10±10.32 minutes. All animals survived. Gastroscopy and necropsy showed that the perforation healed well with local adhesion. One pig developed abdominal infection. Ascites culture were negative in 9 cases, 1 bacterial infection was caused by Arcanobacterium pyogenes and Escherichiacoli. The pathology results showed that the muscular layer of the gastric wall defect in the entire group was well repaired. Conclusion:The novel suture instrument is safe and effective in repairing full-thickness gastric wall defects under ordinary single clamp gastroscopy, providing an experimental basis for further clinical research.

Objective To examine the precise function of influenza A virus target genes(IATGs)in malignancy. Methods Using multi-omics data from the TCGA and TCPA datasets,33 tumor types were evaluated for IATGs.IATG expression in cancer cells was analyzed using transcriptome analysis.Copy number variation(CNV)was assessed using GISTICS 2.0.Spearman's analysis was used to correlate mRNA expression with methylation levels.GSEA was used for the enrichment analysis.Pearson's correlation analysis was used to examine the association between IATG mRNA expression and IC50.The ImmuCellAI algorithm was used to calculate the infiltration scores of 24 immune cell types. Results In 13 solid tumors,IATG mRNA levels were atypically expressed.Except for UCS,UVM,KICH,PCPG,THCA,CHOL,LAMI,and MESO,most cancers contained somatic IATG mutations.The main types of CNVs in IATGs are heterozygous amplifications and deletions.In most tumors,IATG mRNA expression is adversely associated with methylation.RT-PCR demonstrated that EGFR,ANXA5,CACNA1C,CD209,UVRAG were upregulated and CLEC4M was downregulated in KIRC cell lines,consistent with the TCGA and GTEx data. Conclusion Genomic changes and clinical characteristics of IATGs were identified,which may offer fresh perspectives linking the influenza A virus to cancer.

Objective To explore the clinical efficacy of video-assisted thoracoscopic intrathoracic fixation in the treatment of multiple rib fractures.Methods Clinical data of 93 cases of multiple rib fractures in our department from August 2019 to April 2022 were retrospectively compared.They were divided into thoracoscopic group(n=50)and traditional group(n=43)according to surgical methods.In the thoracoscopic group,the memory alloy rib plate was used for thoracoscopic intrathoracic fixation,and in the traditional group,the memory alloy rib plate was used for traditional thoracotomy to treat multiple rib fractures.The operation time,intraoperative blood loss,postoperative hospital stay,postoperative catheter duration,postoperative pain time,postoperative drainage volume,and postoperative complications were compared between the two groups.Results As compared with the traditional group,the thoracoscopic group had significantly shorter operation time[(96.1±24.7)min vs.(110.2±29.1)min,t=-2.526,P=0.013],less intraoperative blood loss[(76.0±38.4)ml vs.(140.2±80.8)ml,t=-4.767,P=0.000],shorter postoperative catheter duration[(3.9±1.6)d vs.(6.2±1.8)d,t=-2.739,P=0.008],less postoperative drainage volume[(132.4±53.9)ml vs.(157.9±50.5)ml,t=-2.345,P=0.021],shorter postoperative hospital stay[(5.8±2.5)d vs.(9.7±2.5)d,t=-4.397,P=0.000],and shorter pain time[(4.9±1.2)d vs.(5.8±1.4)d,t=-2.199,P=0.030].The incidence of postoperative pneumonia,atelectasis,and pleural effusion in the thoracoscopic group was significantly lower than that in the traditional group(P<0.05).Follow-ups at 1,3,and 12 months after surgery showed that the rib plate was firmly fixed without any displacement,deformation,or detachment.Conclusion Video-assisted thoracoscopic intrathoracic fixation in the treatment of multiple rib fractures has advantages of less trauma,less pain,faster recovery,and definite clinical results,which is worthy of clinical application and promotion.

This article aimed to explore the theoretical connotation and mechanism of clearing damp-heat method in the treatment of chronic kidney disease (CKD), provide theoretical support for clearing damp-heat method in the treatment of chronic kidney disease, and further explain the modern scientific connotation of "damp-heat impairing kidney". Modern Traditional Chinese Medicine (TCM) believes that damp-heat is an important pathogenesis of kidney damage. Clearing damp-heat method plays a key role in inhibiting CKD immune inflammatory response, improving oxidative stress and antagonizing renal fibrosis. The mechanism is mainly related to the regulation of TNF-α level, blocking NF-κB signaling pathway, inhibiting inflammatory cytokines, antagonizing TGF-β1 secretion and other pathways.