Objective:To explore the application effect of different doses of dexmedetomidine combined with propofol in elderly patients undergoing radical thyroidectomy for thyroid cancer.Methods:This study was a prospective study,102 elderly patients undergoing radical thyroidectomy for thyroid cancer at Shayang County People's Hospital of Jingmen from April 2022 to April 2024 were selected,they were randomly divided into low-dose group and high-dose group used random number table method,with 51 patients in each group.Low-dose group received propofol(2.0 mg/kg)combined with dexmedetomidine(loading dose 0.3 μg/kg)for anesthesia induction,while high-dose group received propofol(1.0 mg/kg)combined with dexmedetomidine(loading dose 0.6 μg/kg)for anesthesia induction.The postoperative recovery indicators,pain level,cognitive function,hemodynamic indicators[mean arterial pressure(MAP)and heart rate(HR)],and adverse reactions between two groups were compared.Results:Compared with high-dose group,low-dose group had shorter awakening time,spontaneous breathing recovery time,tracheal extubation time,and lower incidence of adverse reactions(P＜0.05).Compared with high-dose group at 6 h,12 h,and 24 h after surgery,low-dose group had lower pain visual analog scale(VAS)scores and higher mini-mental state examination(MMSE)scores(P＜0.05).Compared with high-dose group at separation of thyroid gland(T2)to completion of surgery(T3),low-dose group had lower MAP and HR(P＜0.05).Conclusion:Loading dose 0.3 μg/kg dexmedetomidine combined with propofol has a good analgesic effect in elderly patients undergoing radical surgery for thyroid cancer,it can also maintain hemodynamic stability,reduce the impact on cognitive function,and lower the incidence of adverse reactions.

[Purpose]To analyze the survival rate of prostate cancer patients hospitalized in Nan-tong Tumor Hospital from 2007 to 2017.[Methods]A total of 478 prostate cancer patients were admitted in Nantong Tumor Hospital from 2007 to 2017 and 476 cases(99.58％)were followed up till December 31,2020.The survival rate of patients was analyzed with Kaplan-Meier method;Soft-ware SPSS 25.0 and the Log-rank test were employed for statistical analysis.[Results]The aver-age age of prostate cancer patients at admission was(71.74±8.02)years old,and 79.08％were aged 60～79 years.The median survival time was 43 months,and the observed 1-,3-,5-and 10-year survival rates were 77.20％,56.07％,43.01％and 24.53％,respectively.The 5-year survival rates for the age groups of 35～59,60～79 and ≥80 years old were 31.73％,46.64％and 29.65％,respectively(P＜0.05).The 5-year survival rates for patients with stage Ⅰ～Ⅱ,stage Ⅲ,stage IV,and unknown stage were 88.10％,71.66％,33.35％and 37.55％,respectively(P＜0.001).The 5-year survival rates for the periods 2007-2012 and 2013-2017 were 32.85％and 47.79％,re-spectively(P＜0.05).Furthermore survival rates differed significantly across different regions within the jurisdiction(P＜0.05).[Conclusion]Over the past decade,the survival rate of hospital-based prostate cancer patients has significantly improved.Early-stage cases can achieve better survival rates,but the survival rate of elderly patients remains a challenge.Efforts should be made to reduce the proportion of patients with unknown staging Comprehensive measures for prostate cancer prevention and control should be strengthened to reduce incidence,improve prognosis and enhance quality of life of patients.

Objective To investigate the effect of intravenous flurbiprofen axetil on the incidence and severity of catheter-related bladder discomfort(CRBD)after transurethral resection of the prostate(TURP).Methods The elderly patients undergoing TURP under general anesthesia were enrolled,and randomly divided into two groups:flurbiprofen axetil group(group F)and control group(group C).Ten minutes before the end of surgery,group F was given 50 mg of flurbiprofen axetil intravenously,group C was given an equal amount of 0.9％sodium chloride injection.The primary outcome indicator was the incidence of moderate to severe CRBD immediately after entering the resuscitation room(T0).Secondary indicators included the incidence and severity of CRBD at 1 h(T1),2 h(T2),and 6 h(T3)after entering the resuscitation room,the amount of sufentanil used within 24 hours after surgery,postoperative NRS score,flurbiprofen axetil-related and analgesic adverse reactions 24 hours after surgery,and patient satisfaction.Results A total of 90 patients were included and each group was 45 patients.The incidence of moderate to severe CRBD at T0 was significantly lower in group F than that in group C(8.9％vs.33.3％,P=0.004).The incidence of CRBD in T1,T2,and T3 was lower in group F than in group C(P＜0.05).The incidence of mild CRBD at T3 in group F was lower than that in group C(P＜0.05).The incidence of moderate to severe CRBD at T1 and T2 in groups F was lower than that in group C(P＜0.05).The amount of sufentanil used in group F at 24 hours after surgery was significantly lower than that in group C(P=0.001).The pain scores in group F at T0,T1,T2,and T3 were lower than those in group C(P＜0.05);The postoperative patient satisfaction score in group F was higher than that in group C(P=0.001).However,there were no significant differences between the two groups in postoperative anesthesia resuscitation time and 24-hour adverse reactions incidence(P＞0.05).Conclusion Intravenous flurbiprofen axetil can safely and effectively reduce the incidence and severity of CRBD after TURP.It can significantly relieve pain,reduce sufentanil use,and have high clinical application value.

Objective:To explore the application effect of different doses of dexmedetomidine combined with propofol in elderly patients undergoing radical thyroidectomy for thyroid cancer.Methods:This study was a prospective study,102 elderly patients undergoing radical thyroidectomy for thyroid cancer at Shayang County People's Hospital of Jingmen from April 2022 to April 2024 were selected,they were randomly divided into low-dose group and high-dose group used random number table method,with 51 patients in each group.Low-dose group received propofol(2.0 mg/kg)combined with dexmedetomidine(loading dose 0.3 μg/kg)for anesthesia induction,while high-dose group received propofol(1.0 mg/kg)combined with dexmedetomidine(loading dose 0.6 μg/kg)for anesthesia induction.The postoperative recovery indicators,pain level,cognitive function,hemodynamic indicators[mean arterial pressure(MAP)and heart rate(HR)],and adverse reactions between two groups were compared.Results:Compared with high-dose group,low-dose group had shorter awakening time,spontaneous breathing recovery time,tracheal extubation time,and lower incidence of adverse reactions(P＜0.05).Compared with high-dose group at 6 h,12 h,and 24 h after surgery,low-dose group had lower pain visual analog scale(VAS)scores and higher mini-mental state examination(MMSE)scores(P＜0.05).Compared with high-dose group at separation of thyroid gland(T2)to completion of surgery(T3),low-dose group had lower MAP and HR(P＜0.05).Conclusion:Loading dose 0.3 μg/kg dexmedetomidine combined with propofol has a good analgesic effect in elderly patients undergoing radical surgery for thyroid cancer,it can also maintain hemodynamic stability,reduce the impact on cognitive function,and lower the incidence of adverse reactions.

Objective:To investigate the the differential expression of EIF5A2 in intrahepatic cholangiocarcinoma cell lines RBE,HCCC9810,and HUCCT1,and its effects on HCCC9810 cell migration and invasion,epithelial mesenchymal transition,and PI3K/AKT signaling pathway.Methods:The differential expression of EIF5A2 in RBE,HCCC9810,and HUCCT1 cell lines was detected using WB method.The HCCC9810 cell line,with the highest expression of EIF5A2,was selected for this experiment.The expression of EIF5A2 in HCCC9810 cell line was silenced by transient transfection of small interfering RNA.The best silencing effect of small interfering RNA was screened by WB.Scratch assay and Tran-swell migration invasion assay were used to detect the effect of silencing EIF5A2 on the migration and invasion ability of HCCC9810 cells.WB was used to detect the effect of silencing EIF5A2 on PI3K/AKT signaling pathway and epithelial mesenchymal transition in HCCC9810 cells.Results:The WB results showed that EIF5A2 had the highest expression in the HCCC9810 cell line,and siRNA1 had the best silencing effect on EIF5A2 in the HCCC9810 cell line.Scratch assay and Transwell migration invasion assay results showed that silencing EIF5A2 in the HCCC9810 cell line resulted in a decrease in cell invasion and metastasis ability(P＜0.05).At the same time,the expression of p-PI3K and p-AKT in the PI3K/AKT signaling pathway was significantly decreased(P＜0.05),while the epithelial cell marker E-cadherin expression increased(P＜0.05)and the stromal cell marker N-cadherin expression decreased(P＜0.05).Conclusion:EIF5A2 may promote epi-thelial mesenchymal transition and enhance the migration and invasion ability of intrahepatic cholangiocarcinoma cells through the PI3K/AKT signaling pathway.

Objective:To investigate the the differential expression of EIF5A2 in intrahepatic cholangiocarcinoma cell lines RBE,HCCC9810,and HUCCT1,and its effects on HCCC9810 cell migration and invasion,epithelial mesenchymal transition,and PI3K/AKT signaling pathway.Methods:The differential expression of EIF5A2 in RBE,HCCC9810,and HUCCT1 cell lines was detected using WB method.The HCCC9810 cell line,with the highest expression of EIF5A2,was selected for this experiment.The expression of EIF5A2 in HCCC9810 cell line was silenced by transient transfection of small interfering RNA.The best silencing effect of small interfering RNA was screened by WB.Scratch assay and Tran-swell migration invasion assay were used to detect the effect of silencing EIF5A2 on the migration and invasion ability of HCCC9810 cells.WB was used to detect the effect of silencing EIF5A2 on PI3K/AKT signaling pathway and epithelial mesenchymal transition in HCCC9810 cells.Results:The WB results showed that EIF5A2 had the highest expression in the HCCC9810 cell line,and siRNA1 had the best silencing effect on EIF5A2 in the HCCC9810 cell line.Scratch assay and Transwell migration invasion assay results showed that silencing EIF5A2 in the HCCC9810 cell line resulted in a decrease in cell invasion and metastasis ability(P＜0.05).At the same time,the expression of p-PI3K and p-AKT in the PI3K/AKT signaling pathway was significantly decreased(P＜0.05),while the epithelial cell marker E-cadherin expression increased(P＜0.05)and the stromal cell marker N-cadherin expression decreased(P＜0.05).Conclusion:EIF5A2 may promote epi-thelial mesenchymal transition and enhance the migration and invasion ability of intrahepatic cholangiocarcinoma cells through the PI3K/AKT signaling pathway.

To investigate the molecular mechanisms underlying the mechanosensitive ion channel PI-EZO2 in osteoarthritis(OA),we developed a lentiviral vector for endogenous PIEZO2 overexpression and established a stable PIEZO2-high-expressing immortalized human primary chondrocyte line.By map-ping the open reading frame of the PIEZO2 locus and designing sequence-specific sgRNA,we employed the CRISPR/Cas9 synergistic activation mediator(SAM)system to precisely integrate transcriptional ac-tivation elements into the PIEZO2 promoter region.Lentiviral-mediated targeted genomic integration en-sured endogenous PIEZO2 overexpression,confirmed by mCherry fluorescence tracing coupled with flow cytometric sorting,which revealed membrane-specific localization of PIEZO2 protein(localization effi-ciency:78.49％).Quantitative PCR demonstrated a 17-fold upregulation of PIEZO2 mRNA,while Western blotting validated enhanced membrane-localized protein expression.Strikingly,PIEZO2-overex-pressing chondrocytes exhibited hallmark OA metabolic phenotypes compared to wild-type controls:typeⅡ collagen mRNA expression decreased to 50％of baseline levels,whereas matrix metalloproteinase 13(MMP13)mRNA surged by 20-fold.These alterations recapitulated the pathological matrix metabolic phenotype observed in biomechanical OA models induced by cyclic mechanical stress(10％strain,0.5 Hz,8 h/day for 2 consecutive days).Collectively,we successfully generated a human chondrocyte model with stable PIEZO2 overexpression,which faithfully mirrors mechanotransduction-driven OA progression.This engineered cellular system provides a robust platform for dissecting PIEZO2-mediated mechanosig-naling networks and advancing targeted therapeutic discovery.

Background: s/Aims: Sarcomatoid hepatocellular carcinoma (HCC) is a rare histological subtype of HCC characterized by extremely poor prognosis; however, its molecular characterization has not been elucidated. Methods: In this study, we conducted an integrated multiomics study of whole-exome sequencing, RNA-seq, spatial transcriptome, and immunohistochemical analyses of 28 paired sarcomatoid tumor components and conventional HCC components from 10 patients with sarcomatoid HCC, in order to identify frequently altered genes, infer the tumor subclonal architectures, track the genomic evolution, and delineate the transcriptional characteristics of sarcomatoid HCCs. Results: Our results showed that the sarcomatoid HCCs had poor prognosis. The sarcomatoid tumor components and the conventional HCC components were derived from common ancestors, mostly accessing similar mutational processes. Clonal phylogenies demonstrated branched tumor evolution during sarcomatoid HCC development and progression. TP53 mutation commonly occurred at tumor initiation, whereas ARID2 mutation often occurred later. Transcriptome analyses revealed the epithelial–mesenchymal transition (EMT) and hypoxic phenotype in sarcomatoid tumor components, which were confirmed by immunohistochemical staining. Moreover, we identified ARID2 mutations in 70% (7/10) of patients with sarcomatoid HCC but only 1–5% of patients with non-sarcomatoid HCC. Biofunctional investigations revealed that inactivating mutation of ARID2 contributes to HCC growth and metastasis and induces EMT in a hypoxic microenvironment. Conclusions We offer a comprehensive description of the molecular basis for sarcomatoid HCC, and identify genomic alteration (ARID2 mutation) together with the tumor microenvironment (hypoxic microenvironment), that may contribute to the formation of the sarcomatoid tumor component through EMT, leading to sarcomatoid HCC development and progression.

Objective:To explore the effects of anlotinib on the proliferation, apoptosis, and migration of thyroid cancer cells, and investigate its role in inducing redifferentiation and enhancing iodine uptake capacity, providing a preliminary evaluation of its efficacy in tumor treatment.Methods:(1)The cell proliferation was detected by cell counting kit-8 (CCK-8) assay, and different concentrations (0, 1/4 half maximal inhibitory concentration (IC 50), 1/2IC 50, IC 50) of anlotinib were used to treat CAL62 and FTC133 thyroid cancer cells for 24h. The clonogenic formation experiment, cellular activity and drug toxicity staining, scratch healing assay, and apoptosis in situ fluorescence staining were employed to assess cell clonogenicity, apoptosis, and migration abilities. (2) CAL62 and FTC133 cells were treated with various concentrations of anlotinib, and changes in the expression levels of iodine metabolism-related proteins (sodium/iodide symporter (NIS), thyroid peroxidase (TPO), and thyroid-stimulating hormone receptor (TSHR)) were detected using Western blot. (3) Iodine uptake experiments were conducted to observe changes in the iodine uptake functionality of thyroid cancer cells following treatment with different concentrations of anlotinib for 24 h. (4) The thyroid cancer xenograft nude mouse models were established and divided into control group (physiological saline), low-dose group (1mg/kg), medium-dose group (2mg/kg), and high-dose group (4mg/kg). Mice were treated with varying doses of the drug, the therapeutic effects and the changes in iodine harvesting function on tumors were evaluated. One-way analysis of variance was used for comparison among groups. Results:Anlotinib treatment resulted in significantly reduced cell viability, decreased clonogenic formation, increased apoptosis rates, and reduced scratch healing rates in CAL62 and FTC133 cells ( F values: 53.75-211.90, all P<0.001). After anlotinib treatment, the levels of iodine metabolism-related proteins (NIS, TPO and TSHR) significantly increased ( F values: 21.14-710.00, all P<0.001), and iodine uptake rates in thyroid cancer cells also increased significantly ( F values: 36.45, 32.34, both P<0.001). The nude mouse treatment experiment showed tumor growth in the anlotinib treatment group was inhibited, and tumors iodine uptake rates were increased, both were statistically significant ( F values: 74.09, 38.22, both P<0.001). Conclusions:Anlotinib can inhibit thyroid cancer proliferation and growth, promote apoptosis, reduce cell migration capabilities, induce thyroid cancer cells redifferentiation, and enhance iodine uptake capacity. Anlotinib can induce the redifferentiation of thyroid cancer at the animal level and has better efficacy.