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Liver cancer is the sixth most common type of cancer worldwide and the third leading cause of cancer-related deaths. Approximately 30% of patients are diagnosed at an early stage of liver cancer, at which point curative treatments such as partial liver resection and liver transplantation can be performed, leading to a median overall survival exceeding 60 months. However, most patients are diagnosed at an advanced stage of liver cancer, where treatment options often include targeted therapies and immune checkpoint inhibitors. Systemic treatments including immune checkpoint inhibitors play a crucial role in significantly improving the prognosis of patients with advanced liver cancer. Therefore, in-depth exploration of the immune microenvironment characteristics of liver cancer and active identification of biomarkers for immunotherapy are crucial to advancing and improving immunotherapy for liver cancer.

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Objective To investigate the role of squalene epoxidase(SQLE) knockout in anti-tumor effect vial improving CD8+T cell infiltration in melanoma tumor microenvironment. Methods Both immunodeficient and immunocompetent mice were inoculated withSQLEknockout B16F10 cells to determine the cell-autonomous and non-autonomous regulation of malignancy. Antibody blockade, Luminex multiplex assays, and flow cytometry were employed to explore the impact ofSQLEgene knockout on the secretion of cytokines/chemokines and immune cell infiltration. Bioinformatics analysis was conducted to validate the correlation betweenSQLEexpression and immune infiltration as well as clinical prognosis in melanoma patients. Results Compared with immunodeficient mice,SQLEknockout significantly inhibited melanoma proliferation in immunocompetent mice and prolonged their survival.SQLEknockout induced the secretion of cytokines and chemokines from tumor cells, improved CD8+T cell infiltration in the tumor microenvironment, thereby potentiating anti-tumor immunity. Bioinformatics analysis suggested a significant correlation betweenSQLEand its corresponding immune infiltration markers with the prognosis of melanoma patients. Conclusion SQLEregulates anti-tumor immunity by controlling cytokines and chemokines releasing in tumor microenvironment, thus holding promise as a novel tumor immunotherapy target and efficacy prediction molecular indicator.

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Objective To investigate the characteristic genes of Programmed cell death protein 1(PD-1) immunotherapy sensitivity in Hepatocellular carcinoma(HCC). Methods The common differential genes in GSE202069 and ERP117672 data sets were investigated by Weighted Gene Co-expression Network Analysis(WGCNA) and Difference analysis, and the characteristic genes of PD-1 immunotherapy sensitivity were screened through Lassoregression. The expression levels of characteristic genes in HCC were predicted by GEPIA and Ualcan databases, and their expression was verified by real-time quantitative reverse transcription polymerase chain reaction(RT-qPCR), Western blot(WB) and Immunohistochemistry(IHC). 3-hydroxybutyrate dehydrogenase 1(BDH1) overexpressed cell line was constructed, followed by cell counting kit-8(CCK-8), EdU, cell scratches and Transwell experiment to investigate the effects ofBDH1on the proliferation, migration and invasion of HCC cells. Results Total of 118 common differentially expressed genes were identified in two datasets by WGCNA and differential analysis. The characteristic genes associated with PD-1 immunotherapy sensitivity screened through Lasso regression including Flavin containing dimethylaniline monoxygenase 3(FMO3), Peroxisomal trans-2-enoyl-CoA reductase(PECR),BDH1, Solute carrier family 7 member 1(SLC7A1), Cytochrome b5 type A(CYB5A) and Phosphoenolpyruvate carboxykinase 1(PCK1). Survival analysis showed thatBDH1was most associated with HCC(Overall survival:P<0.001, Recurrence:P=0.007). GEPIA and Ualcan databases showed low expression ofBDH1in HCC tissues, while RT-qPCR, WB, and IHC further confirmed this. CCK-8, plate cloning assay, EdU staining, cell scratch, and Transwell experiments showed that compared with the Hep3B pCDH group, overexpression ofBDH1resulted in a decrease in the absorbance of HCC cells(t=4.766,P<0.01), a decrease in the number of clone formation(t=16.02,P<0.000 1), a decrease in the proportion of proliferating cells(t=23.13,P<0.000 1), a decrease in cell migration rate(t=25.28,P<0.000 1), and a decrease in the number of small compartments(t=10.78,P=0.004). Conclusion BDH1is a characteristic gene for observing the sensitivity of PD-1 immunotherapy in HCC patients.BDH1could inhibit the proliferation, migration, and invasion ability of HCC cellsin vitro.

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Objective To investigate the role of Glutathione peroxidase 2(GPX2) in the occurrence and progression of intrahepatic cholangiocarcinoma(ICC). Methods The Omicshare website was used to analyzeGPX2expression levels in ICC. The expression levels in ICC were validated using quantitative real-time reverse transcription PCR(RT-qPCR), Western blot, and immunohistochemistry. Stable GPX2 knockdown and overexpression HuCCT1 cell lines were constructed. The effects of GPX2 on ICC cell proliferation, migration, apoptosis, and epithelial-mesenchymal transition(EMT) were investigated using colony formation assays, cell counting kit-8(CCK-8) assays, wound healing assays, Transwell assays, and flow cytometry. A mouse model of cholangiocarcinoma was constructed to assess GPX2 expression in mouse cholangiocarcinoma tissues. Results Based on the analysis results from the Omicshare website,GPX2was generally upregulated in intrahepatic cholangiocarcinoma(ICC)(P<0.001). Western blot(P<0.000 1), RT-qPCR(P<0.001), and immunohistochemistry experiments showed that, compared to adjacent non-cancerous tissues, the expression of GPX2 was significantly elevated in ICC. When GPX2 was knocked down, the colony formation rate of cells decreased significantly(P<0.01), and the proliferation capacity was reduced(P<0.001). Conversely, overexpression of GPX2 led to a significant increase in colony formation rate(P<0.01) and enhanced proliferation capacity(P<0.01). Results from wound healing and Transwell assays demonstrated that GPX2 knockdown slowed down cell wound healing(P<0.01) and reduced migration ability(P<0.01). Additionally, GPX2 knockdown resulted in an increase in E-cadherin(P<0.01) and a decrease in N-cadherin(P<0.01) and Vimentin(P<0.05). On the other hand, overexpression of GPX2 accelerated wound healing(P<0.05) and enhanced migration ability(P<0.05), while E-cadherin expression decreased(P<0.05) and N-cadherin(P<0.01) and Vimentin(P<0.001) expression increased. Flow cytometry for apoptosis and Western blot experiments indicated that GPX2 knockdown increased the apoptosis rate(P<0.001), decreased the expression of Bcl-2(P<0.001), and increased the expression of BAX(P<0.01). But overexpression of GPX2 reduced the apoptosis rate(P<0.01), increased Bcl-2 expression(P<0.000 1), and decreased BAX expression(P<0.001). Finally, elevated levels of GPX2 were observed in a mouse model of cholangiocarcinoma. Conclusion GPX2 is highly expressed in human and mouse cholangiocarcinoma tissues, and it may enhance cholangiocarcinoma cell proliferation and migration, promote tumor cell EMT, and inhibit tumor cell apoptosis.

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Objective To investigate the expression of urocanase domain containing 1(UROC1) in Hepatocellular carcinoma(HCC) and its effect on the development of HCC. Methods UROC1 expression and prognostic data in tumor and para-tumor tissues from protein mass spectrometry and TCGA database were analyzed. Immunohistochemical staining, real time quantitative polymerase chain reaction(qPCR) and Western blot experiments were utilized to verify the expression of UROC1 in HCC. The effect of UROC1 expression level on tumor differentiation was analyzed by HE staining to determine the tumor differentiation level. Hep3B and LM3 cell lines stably overexpressing UROC1 and its mutants were constructed for in vitro phenotyping experiments. Effects of UROC1 on HCC cell proliferation and migration were explored by cell counting kit-8(CCK-8) assay, colony formation, EdU assay, scratch assay and Transwell assay. Results The results of database analysis showed that UROC1 was generally downregulated in HCC tissues,and patients in the UROC1 low-expression group had a worse prognosis. Immunohistochemical staining and scoring,qPCR and Western blot experiments verified the low expression of UROC1 in HCC. Immunohistochemical staining of tumor tissues with different differentiation levels demonstrated that the poorer the differentiation of HCC tissues,the lower the expression level of UROC1. CCK-8,colony formation and EdU assays suggested that overexpression of UROC1 inhibited the proliferation of HCC cells. The results of scratch and Transwell assays showed that overexpression of UROC1 inhibited the migration of HCC cells. However,the results of the above experimental phenotypes after active site mutation converged with those of the control group. Conclusion UROC1 is lowly expressed in HCC tissues,and overexpression of UROC1 in HCC cells may inhibit the ability of cell proliferation and migration.

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Objective To investigate the effect of N-myc downstream regulatory gene 1(NDRG1) on Hepatocellular carcinoma(HCC) and whether NDRG1 affects the sensitivity of HCC to Sorafenib. Methods The expression level of NDRG1 in HCC was predicted by TCGA database, and verified by Western blot(WB) and Immunohistochemistry(IHC). NDRG1 knockout cell lines were constructed, followed by cell counting kit-8(CCK-8), EdU, cell scratches and Transwell experiment to investigate the effects of NDRG1 and its combination with Sorafenib on the proliferation, migration and invasion of HCC cells. In addition, flow cytometry was used to detect the apoptosis of HCC cells. The effect of NDRG1 and Sorafenib on HCC tumor formation was studiedin vivoby subcutaneous tumor bearing in nude mice. WB and IHC were used to determine the pathway regulating the sensitivity of HCC to Sorafenib. Results WB and IHC confirmed that NDRG1 is highly expressed in HCC, consistent with the results of TCGA data. Tumor functional experiments showed that NDRG1 knockout or Sorafenib stimulation weakened the proliferation, migration, and invasion ability of HCC cells, and increased tumor cell apoptosis. However, NDRG1 knockout combined with Sorafenib further weakened the proliferation, migration and invasion ability of HCC cells, and further increased tumor cell apoptosis(P<0.000 1). Mouse subcutaneous tumor model showed that NDRG1 knockout or Sorafenib stimulation reduced the tumor volume and quality, while NDRG1 knockout combined with Sorafenib further reduced the tumor volume and quality(P<0.000 1). The WB and IHC results indicated that NDRG1 knockout combined with Sorafenib could reduce the phosphorylation level of Erk1/2. Conclusion NDRG1 is highly expressed in HCC, which promotes the proliferation, migration and invasion of HCC cells, and restricts apoptosis. NDRG1 knockout enhances HCC sensitivity to Sorafenib by reducing ERK signaling pathway phosphorylation.

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Objective To investigate the mechanism by which human hypoxia up-regulation 1(HYOU1) regulates pancreatic cancer development. Methods Bioinformatic and immunohistochemical staining analyses of HYOU1 expression level in pancreatic tumor tissues, normal and paracancerous tissues and its correlation with patients′ survival. Quantitative real-time PCR(qPCR) and Western blot were used to clarify the expression level of HYOU1 in a number of human pancreatic ductal adenocarcinoma cell lines and a normal human pancreatic ductal cell line. Two cell lines with the highest expression levels of HYOU1, BXPC-3 and Panc-1, were selected to knock out HYOU1 by CRISPR-Cas9,and then cell survival, proliferation and migration of these cells were examined by cell counting kit-8(CCK-8),colony formation assay and wound healing experiment separately,as well as apoptosis was detected by flow cytometry. Subsequently,the protein levels of the PI3K/Akt signaling including PI3K,p-PI3K,Akt,and pAkt were detected by Western blot in parental and HYOU1-ablated BXPC-3 and Panc-1 cells. Cell proliferation was also examined in HYOU1-ablated cells after treatment of recilisib,an activator of the PI3K/Akt pathway. Results The expression of HYOU1 in pancreatic tumor tissues was significantly higher than that in normal tissues,and the patients with high expression of HYOU1 had a much shorter survival compared to the patients with low HYOU1(P<0.01). Immunohistochemical staining of pancreatic cancer specimens showed that the expression of HYOU1 was higher in tumor tissues than in paracancerous tissues(P<0.01). The mRNA and protein levels of HYOU1 were higher in all pancreatic cancer cell lines compared to the human normal pancreatic ductal cell(P<0.001,P<0.01). HYOU1 ablation inhibited BXPC-3 and Panc-1 cells survival,proliferation and migration,and promoted early cell apoptosis. In addition,loss of HYOU1 decreased PI3K/Akt signaling activity,whereas the PI3K/Akt activator Recilisib reversed the effects of HYOU1 ablation on cell survival and proliferation. Conclusion HYOU1promotes pancreatic cancer progression by activating the PI3K/Akt signaling pathway.

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Objective To investigate the role of Tre2-Bub2-Cdc16 1 domain family member5(TBC1D5) in the development of hepatocellular carcinoma(HCC). Methods Western blot(WB), Immunohistochemistry(IHC) and quantitative real-time PCR(qPCR) were used to verify the difference inTBC1D5expression in clinical samples. The HCC cell lines MHCC97H and Hep3B were chosen to construct the knockdown model. The effects on cell proliferation were detected by cell proliferation assay, colony formation assay and EdU assay. Wound assay and Transwell assay were used to detect cell migration and invasion. Flow cytometry was used to detect the changes of cell cycle and H2O2-induced apoptosis of HCC cells. Finally, the effects of knockdown and overexpression ofTBC1D5on JAK/STAT pathway were detected by WB. Results The results of WB, IHC and qPCR showed that the expression ofTBC1D5in HCC tissues was higher at the protein level(P<0.000 1) and mRNA level(P<0.01) than that in corresponding adjacent tissues. Compared with the control group, the proliferation level of HCC cells withTBC1D5knockdown was decreased(P<0.05), the formation of plate colony number decreased(P<0.001), and the proportion of EdU-positive cells decreased(P<0.001). The results of scratch assay and Transwell assay showed that the migration(P<0.01) and invasion ability(P<0.01) of HCC cells afterTBC1D5knockdown were significantly lower than those in the control group. AfterTBC1D5knockdown, the cell cycle of HCC cells was slowed down(P<0.05) and the ability to resist apoptosis was reduced(P<0.01)than those in the control group. Compare with the control group, knockdown ofTBC1D5decreased the phosphorylation level of JAK and STAT proteins and inhibit the JAK/STAT pathway. Conclusion TBC1D5is highly expressed in HCC. After knocking downTBC1D5, the proliferation, migration and invasion ability, cell cycle rate and anti-apoptosis ability of HCC cells decreased and may affect HCC progression through the JAK/STAT pathway.

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Objective To preliminarily explore the phenomenon and mechanism of apoptosis induced by microsecond pulsed electric field in hepatocellular carcinoma cells HepG2. Methods CCK-8 was used to test the effects of microsecond pulsed electric fields with different parameters on the proliferation of human hepatocellular carcinoma cells HepG2 and human normal hepatocytes L-O2. The effects of microsecond pulsed electric field ablation on HepG2 cell apoptosis under different electric field intensities were observed by flow cytometry; morphological changes of ablated HepG2 cells were observed by transmission electron microscopy; differentially expressed genes between ablated and control cells were screened by transcriptome sequencing and bioinformatics analysis, and the RNA and protein expression of differentially expressed genes in HepG2 cells after pulse ablation was verified by quantitative real-time PCR(qPCR) and Western blot. Results CCK-8 experiments showed the proliferative and inhibitory abilities of microsecond pulsed electric field ablation on hepatocellular carcinoma cells HepG2 and human hepatocytes L-O2 increased gradually with the increase of electric field intensity. However, there was no significant difference in the ablation ability of microsecond pulsed electric field between HepG2 cell and L-O2 cell. When the voltage was increased to 1 600 V/cm, the microsecond pulsed electric field significantly induced apoptosis in HepG2 cells compared to control group, with an apoptosis cells ratio of nearly 80%(P<0.000 1). Using transmission electron microscopy, it was found that the HepG2 cell membrane was fragmented, the mitochondria were irregular in morphology and typical apoptotic vesicles appeared after microsecond pulsed electric field ablation. Transcriptomics analysis showed the major genes revealed to be involved in microsecond pulse ablation were thousand and one amino acid protein kinase 1(TAOK1), frizzled protein family receptor 3(FZD3), calpain 10(CAPN10), matrix metalloproteinase 9(MMP-9), and transforming growth factor β-1-induced transcript(TGFB1) and qPCR analysis showed that the differentially expressed genes were mainly involved in the regulation of RNA polymerase II, signaling, and apoptosis after ablation of HepG2 cells by microsecond pulses at 1 600 V/cm, the RNA expression levels ofTAOK1(P<0.05),FZD3(P<0.01) were significantly up-regulated, and the RNA expression levels ofCAPN10(P<0.001),MMP-9(P<0.01), andTGFB1(P<0.05) were significantly reduced in HepG2 cells. Western blot experiments further confirmed that TAOK1 and FZD3 showed an increase in expression levels after microsecond pulse treatment, while CAPN10, MMP-9 and TGFB1 showed a down-regulation of expression levels. Conclusion Microsecond pulsed electric field ablation can effectively promote apoptosis of hepatocellular carcinoma HepG2 cells, and genes such asCAPN10,FZD3may be involved in the regulation of apoptosis of hepatocellular carcinoma HepG2 cells promoted by microsecond pulsed ablation.

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Objective To explore the influence of IL-6 secreted by cancer-associated fibroblasts(CAFs) on promoting the proliferation and invasion of ovarian cancer cells and the possible mechanisms. Methods CAFs and normal ovarian fibroblasts(NFs) were isolated and cultured respectively from epithelial ovarian cancer and normal ovarian epithelial tissues. Cell markers alpha-smooth muscle actin(α-SMA), E-cadherin were detected by Western blot and immunofluorescence. CAFs and normal ovarian fibroblasts(NFs) were collected and cultured, and their supernatants were used to establish an indirect co-culture system with ovarian cancer SKOV3 cells, including SKOV3 cells alone(SKOV3) group, SKOV3 combined with the supernatants of NFs(NFs) group and SKOV3 combined with the supernatants of CAFs(CAFs) group. Cell immunochemistry was used to detect the expression of alcohol dehydrogenase 1B(ADH1B) in SKOV3 cells co-cultured with the supernatant of CAFs or NFs. Before and after treatment with the methylation inhibitor 5-aza-2′-deoxycytidine(5-Aza-dC), methylation-specific PCR(MSP), Reverse transcription quantitative real-time PCR(RT-qPCR), enzyme-linked immunosorbent assay(ELISA), and Western blot were used to detect the mRNA level and methylation status of ADH1B, and the phosphorylation level of signal transducers and activators of transcription 3(p-STAT3).The cell counting kit-8(CCK-8) method and Transwell assay were used to investigate the effects of the IL-6 inhibitor LMT-286 and recombinant human interleukin-6(rhIL-6) on cell proliferation and invasion. Results The protein levels of α-SMA was highly expressed, however, CAFs and NFs cells almost lacked the E-cadherin protein. Compared with the SKOV3 and NFs groups, CAFs group exhibited significantly downregulated mRNA and protein expression of ADH1B. After treatment with 5-Aza-dC,ADH1Bmethylation was partially reversed, and the mRNA and protein expression of ADH1B increased in all groups. The phosphorylation level of STAT3 proteins was significantly reduced in CAFs group, while there were no significant changes in SKOV3 and NFs groups. Intervention with LMT-286 and rhIL-6 only inhibited or promoted the proliferation and invasion of cells in CAFs group, while there were no significant changes in SKOV3 and NFs groups. Conclusion CAFs can enhance the methylation ofADH1Bin ovarian cancer cellsviaIL-6/STAT3 pathway, and may promote the proliferation and invasion.

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Objective To monitor and evaluate the synergistic antitumor effects of programmed death-1(PD-1) checkpoint inhibitor combined with radiation therapy through whole-body dynamic18F-Fluorodeoxy glucose positron emission computed tomography(18F-FDG PET/CT) and Patlak multi-parametric analysis. Methods B16F10 melanoma dual-tumor mouse model was established and randomly divided into control, PD-1 monoclonal antibody, radiation-only, and combination groups(n=6). Whole-body18F-FDG PET/CT imaging was performed before and 24 hours post-treatment. The changes of maximum standardized uptake value(SUVmax) and metabolic rate of FDG(MRFDG) changes were analyzed and compared. Mice were then euthanized, tumors excised and underwent histopathology with HE, CD8, Ki-67 staining to assess immune infiltration and proliferation. Distal tumor volumes were monitored during treatment. Results At 24 hours post-treatment, in the primary tumors, SUVmaxand MRFDGvalues increased compared to pre-treatment in the control group(P<0.000 1), while they decreased in the combination treatment group(P<0.000 1), with statistically significant differences. In the distal tumors, SUVmaxand MRFDGvalues increased compared to pre-treatment in the control group, PD-1 monoclonal antibody group, and radiotherapy-alone group. The SUVmaxdifferences were statistically significant in the control group before and after treatment(P<0.000 1). MRFDGvalues in the distal tumors showed statistically significant differences in all three groups(P<0.01 orP<0.000 1). In the combination treatment group, SUVmaxand MRFDGvalues in the distal tumors decreased significantly compared to pre-treatment(P<0.000 1). Post-treatment comparison of SUVmaxand MRFDGvalues in the distal tumors showed that statistically significant differences in SUVmaxand MRFDGvalues were observed among all groups except between the radiotherapy-alone and PD-1 monoclonal antibody groups(allP<0.05). Immunohistochemistry results showed that the mean absorbance value of CD8 T lymphocytes in the distal tumor was significantly higher than that in the other three groups(P<0.001); the mean absorbance value of Ki-67 immunohistochemistry in the distal tumor proliferation index was significantly lower than that in the other three groups(P<0.001). Conclusion The synergistic effects of combined treatment reduced distal tumor growth. Whole-body18F-FDG PET/CT Patlak multi-parametric imaging can monitor the synergistic effects of PD-1 antibody and radiotherapy in B16F10 melanoma, providing reliable imaging parameters for optimizing combinatorial therapies.

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Objective To explore the effects of different phenotypes macrophages(Mφs) on the proliferation, migration and osteogenic differentiation of periodontal ligament stem cells(PDLSCs). Methods PDLSCs were isolated and cultured by tissue block method. Tohoku Hospital Pediatrics-1(THP-1) cell line was stimulated to activate into unpolarized Mφs(M0), then induced to polarize into type I Mφs(M1) and type II Mφs(M2). Quantitative real-time PCR(qPCR) detected the inflammatory factors tumor necrosis factor α(TNF-α), interleukin(IL)-1β, IL-6, IL-10 and transforming growth factor-β(TGF-β) mRNA expression level. After collecting culture supernatants with different phenotypes, PDLSCs were stimulated, native control(NC) group did not receive the culture supernatant of Mφs. The effects of PDLSCs proliferation were assessed via Methylthiazolyldiphenyl-tetrazolium bromide(MTT) assay, while scratch assays were employed to evaluate their migration. Western blot was utilized to analyze the protein expression of Runt-related transcription factor 2(RUNX2) and alkaline phosphatase(ALP). Additionally, Alizarin Red staining was performed to investigate the deposition of calcified nodules in PDLSCs. Results qPCR showed the relative expression of TNF-α, IL-1β and IL-6 in M1 Mφs were higher than those in M0 and M2 Mφs(P<0.05),and the relative expression of IL-10 and TGF-β in M2 Mφs were higher than those in M0and M1 Mφs(P<0.05); Western blot showed the expression of RUNX2 and ALP proteins in PDLSCs in M0 and M2 groups was higher than those in the NC group(P<0.05),Alizarin Red staining showed increased calcified nodule deposition in PDLSCs in M0,M1 and M2 groups compared to the NC group; MTT assay showed the proliferation of PDLSCs in the M0 and M1 groups was suppressed compared to the NC group(P<0.05); and scratch experiment showed the migratory capacity of PDLSCs in the M1 and M2 groups was stronger than that in the NC group. Conclusion M0 and M1 Mφs inhibit PDLSCs proliferation,M1 and M2 Mφs promote PDLSCs migration,and all types of Mφs promote osteogenic differentiation of PDLSCs.

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Objective To explore the effect of ephedrine on airway remodeling and its regulation effect on transforming growth factor-β1(TGF-β1)/Smads pathway in asthmatic mice. Methods All mice were randomly separated into control group, model group, dexamethasone group, ephedrine low-dose group, ephedrine high-dose group, and ephedrine high-dose+TGF-β1 activator group, with 12 mice in each group. Except for the control group, mice in other groups were intraperitoneally injected with 40 μg ovalbumin(OVA) and 2 mg 10% aluminium hydroxide sensitizer to induce asthma models. After 8 weeks, the airway hyperresponsiveness of mice in each group was detected; eosinophils in bronchoalveolar lavage fluid(BALF) were counted; ELISA was applied to detect the levels of interleukin(IL)-4, IL-5, and IL-13 in BALF; hematoxylin-eosin(HE) staining and Masson staining were applied to observe the pathological changes and collagen fiber area of mouse lung tissue; immunohistochemistry was applied to detect the expression of α-smooth muscle actin(α-SMA) protein in mouse lung tissue; Western blot was applied to detect the expression of TGF-β1/Smads pathway related proteins in mouse lung tissue. Results Compared with the control group, the airway hyperreactivity at different doses of methacholine, total area of airway wall(Wat)/perimeter of the basement membrane(Pbm) ratio, collagen fiber area, eosinophil, the contents of IL-4, IL-5, IL-13, the expression of α-SMA, TGF-β1, the ratios of p-Smad2/Smad2 and p-Smad3/Smad3 in the model group increased(P<0.05), the expression of Smad7 decreased(P<0.05); compared with the model group, the airway hyperreactivity at different doses of methacholine, Wat/Pbm ratio, collagen fiber area, eosinophil, the contents of IL-4, IL-5, IL-13, the expression of α-SMA, TGF-β1, the ratios of p-Smad2/Smad2 and p-Smad3/Smad3 in the dexamethasone group, the ephedrine low-dose and high-dose groups decreased(P<0.05), the expression of Smad7 increased(P<0.05); compared with the ephedrine high-dose group, the airway hyperreactivity at different doses of methacholine, Wat/Pbm ratio, collagen fiber area, eosinophil, the contents of IL-4, IL-5, IL-13, the expression of α-SMA, TGF-β1, the ratios of p-Smad2/Smad2 and p-Smad3/Smad3 in the ephedrine high-dose+TGF-β1 activator group increased(P<0.05), the expression of Smad7 decreased(P<0.05). Conclusion Ephedrine can improve airway remodeling in asthmatic mice, and its mechanism is related to the regulation of TGF-β1/Smads signaling pathway.

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Objective To investigate the protective effect of mitochondria-derived peptide MOTS-c on myocardial ischemia reperfusion injury(MIRI) in rats and elucidate its mechanism. Methods The SD rats were randomly divided into sham group, MIRI group, MOTS-c group and MOTS-c+PGC-1α inhibitor SR-18292 group(MOTS-c+SR-18292), with 10 rats in each group. The MIRI model was established by ligating the anterior descending branch of the coronary artery MOTS-c peptide(1 mg/kg), SR-18292(20 mg/kg) and equal volume concentration of 1% dimethyl sulfoxide were administeredviatail vein at 1 h before operation and immediately after operation. At 24 h after surgery, TTC staining was used to observe myocardial infarction size. HE staining was used to observe the pathological changes of myocardial tissue. TUNEL staining was used to detect myocardial apoptosis. ELISA and biochemical kits were used to measure the levels of myocardial injury markers and oxidation indicators in serum of each group. The relative copy number of mtDNA in myocardial tissues was detected by qRT-PCR. The mitochondrial biosynthesis-related protein expression levels in myocardial tissues were detected by Western blot. Results Compared with sham group, MIRI group had serious myocardial injury, myocardial infarction size and increased apoptosis level(P<0.05). The mtDNA relative copy number in myocardial tissue decreased(P<0.05). The contents of CK-MB, LDH, cTnI in serum and MDA in myocardial tissue increased(P<0.05). SOD content and PGC-1α, NRF-1 and TFAM protein expression levels in myocardial tissue decreased(P<0.05). Compared with MIRI group, myocardial injury in MOTS-c group was significantly improved, myocardial infarction size and apoptosis level decreased(P<0.05). The mtDNA relative copy number in myocardial tissue increased(P<0.05). The contents of CK-MB, LDH, cTnI in serum and MDA in myocardial tissue decreased(P<0.05). The SOD content and the expression levels of PGC-1α, NRF-1 and TFAM in myocardial tissue increased(P<0.05). Compared with MOTS-c group, the myocardial infarction size and apoptosis level of rats in MOTS-c+SR-18292 group increased(P<0.05). The mtDNA relative copy number in myocardial tissue decreased(P<0.05). The contents of CK-MB, LDH, cTnI in serum and MDA in myocardial tissue increased(P<0.05). SOD content and PGC-1α, NRF-1 and TFAM protein expression levels in myocardial tissue decreased(P<0.05). Conclusion MOTS-c peptide can improve myocardial injury in MIRI rats by promoting mitochondrial biosynthesis and inhibiting cardiomyocyte apoptosis, and its mechanism may be related to up-regulation of PGC-1α expression.

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Objective To investigate the protective effect of wogonin on acute kidney injury(AKI) induced by lipopolysaccharide(LPS). Methods The model of septic-induced AKI was established on male C57BL/6J mice by a single intraperitoneal injection of LPS and normal C57BL/6J mice were used as normal control group. Twenty-four male C57BL/6 mice were randomly divided into 4 groups(6 mice in each group): normal control group(NC), normal control+wogonin(NC+WOG 12.5 mg/kg), LPS model group(LPS 10 mg/kg), LPS model+wogonin(LPS 10 mg/kg+WOG 12.5 mg/kg). After LPS intervention for 24 h, serum samples were collected to detect blood creatinine(CRE) and urea nitrogen(BUN) levels. HE staining and PAS staining were performed to observe the degree of renal pathological injury. Immunohistochemistry was performed to detect the degree of expression of inflammatory markers interleukin(IL)-1β, IL-6 and tumor necrosis factor(TNF)-α in renal tissues. PCR was performed to detect the expression of KIM-1 and NGAL in renal tissues. Western blot was performed to detect the changes in protein expression of NF-κB signaling pathway subunits P65 and PP65 in renal tissues. Results Compared with NC group, CRE and BUN levels in LPS group increased(FCRE=60.90,P<0.001,FBUN=82.13,P<0.001); compared with LPS group, these indexes decreased in LPS+WOG group(P<0.001). PCR test results showed that compared with the NC group, the expression ofKIM-1andNGALmRNA was significantly increased in LPS group(FKIM-1=146.3,P<0.001,FNGAL=161.2,P<0.001). In contrast,KIM-1andNGALmRNA expression was decreased in the LPS+WOG group(P<0.01). Renal histopathological examination showed that compared with the NC group, renal tissues of mice had renal tubular dilatation and inflammatory cell infiltration in LPS group; compared with LPS group, the number of tubular dilatation reduced and inflammatory cell infiltration was reduced in LPS+WOG group(FHE=721.4,P<0.001;FPAS=518.9,P<0.001). Immunohistochemical staining showed that the expression of IL-1β, IL-6 and TNF-α was significantly increased in the LPS group; compared with the LPS groups(FIL-1β=114.6,FIL-6=108.9,FTNF-α=251.6, allP<0.001), these indexes decreased in LPS+WOG group(allP<0.01). Further studies using Western blot showed that the NF-κB signaling pathway of LPS-treated mice had been activated and produced a hyperphosphorylated state in comparison to the NC group(FPP65=13.02,P<0.01), yet this pathway in the LPS+WOG group showed the opposite effect, namely attenuated activity and reduced phosphorylation when the control was LPS(P<0.01). Conclusion WOG effectively blocked the NF-κB signaling pathway in the LPS-induced acute kidney injury model mice, thereby attenuating the inflammatory response and tissue damage in the kidneys of LPS-induced acute kidney injury mice.

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Objective To explore the effects of isogenous micro-grafting(MG) technology and the combined use of botulinum toxin type A(BTX-A) on hair regeneration in mice. Methods Forty-five C57BL/6 mice were randomly divided into five groups: normal saline group(NS group), MG group(MB-0 group), MG+low-dose BTX-A group(MB-2 group), MG+medium dose BTX-A group(MB-10 group), MG+high-dose BTX-A group(MB-50 group). The growth of hair on the backs of the mice was observed after the administration of the drugs, and the hair follicles were evaluated by hematoxylin-eosin(HE) staining on the 7th, 14th, and 21st days of the experiment, and the expression of vascular endothelial growth factor(VEGF) and β-catenin was evaluated by immunohistochemical staining on day 21. Results After treatment with micrograft and botulinum toxin type A, the skin darkening time was shortened(P<0.05), and the coverage rate of new hair increased on the 14 th day(P<0.05). Compared with the NS group, the number of hair follicles increased(P<0.05) and the expression of VEGF and β-catenin increased in each other group. Conclusion Isogenous micro-grafting technology combined with botulinum toxin type A has a promotional effect on hair regeneration in mice, and the mechanism may be related to the promotion of vascular growth and activation of β-catenin signaling.

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Objective To investigate the impact of naringenin(Nar) on insulin resistance(IR) in HepG2 cells and evaluate the role ofmircoRNA-29b(miR-29b) expression in mediating this effect, thereby providing a foundation for further exploration into the mechanisms underlying naringenin's potential as a preventative and therapeutic agent for diabetes. Methods Insulin resistant HepG2(IR-HepG2) was established by stimulating HepG2 cells with 100 nmol/L insulin. Nar was treated with different concentrations(0, 25, 50, 100 μg/ml) in IR-HepG2 cells. The effect of Nar on glucose consumption in IR-HepG2 cells was determined with glucose kit.miR-29b mimicand inhibitor were transfected into IR-HepG2 cells of the 50 μg/ml Nar intervention group, and the expressions of insulin receptor substrate-1(IRS-1), protein kinase B(Akt)/phosphorylated Akt(p-Akt), glucose transporter-4(GLUT4) genes and proteins in the insulin signaling pathway were detected by Real-time fluorescence quantitative reverse transcription polymerase chain reaction(RT-qPCR) and Western blot, respectively. Results Compared with IR-HepG2 model group, glucose consumption was increased in Nar intervention group with different concentrations(P<0.01), among which 50 μg/ml Nar intervention group was the most significant(P<0.001), and mRNA expressions ofIRS-1andAktwere increased in Nar intervention group with different concentrations(P<0.05), the mRNA expression ofIRS-1andAktin 50 μg/ml Nar intervention group was the most significantly increased(P<0.001), andGLUT4mRNA expression in 50 μg/ml Nar intervention group was increased(P<0.05). The protein expressions ofIRS-1andp-Aktwere increased in different Nar concentration groups(P<0.001). Compared with IR-HepG2 model group, mRNA expression ofIRS-1,AktandGLUT4and protein expression of IRS-1 and p-Akt were decreased inmiR-29b mimictransfected cells(P<0.001), mRNA expression ofIRS-1,AktandGLUT4and protein expression of IRS-1 and p-Akt were not different inmiR-29b inhibitortransfection group, Nar intervention model group and Nar intervention transfectedmiR-29b mimicgroup increased the mRNA expression ofIRS-1,AktandGLUT4(P<0.001), and the protein expression of IRS-1 and p-Akt increased(P<0.05). Compared with Nar intervention model group, Nar transfectedmiR-29b mimicwith Nar intervention did not change the mRNA expressions ofIRS-1,Akt and GLUT4, while the protein expressions of IRS-1 and p-Akt were increased(P<0.05), Nar interfered with mRNA expression of IRS-1, Akt and GLUT4 and protein expression of IRS-1 and p-Akt inmiR-29b inhibitorgroup(P<0.001). Conclusion Nar can increase glucose consumption in IR-HepG2 cells, increase the expression ofIRS-1,AktandGLUT4genes, and increase the expression of IRS-1 and p-Akt proteins in IR-HepG2 cells. Nar increases the expression of IRS-1 and p-Akt in IR-HepG2 cells by inhibiting the overexpression ofmiR-29b, and improves insulin resistance in HepG2 cells. Nar, as a plant compound, is expected to be a potential drug for the prevention and treatment of diabetes.

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Objective Based on a novel type of cell death induced by disulfide stress, known as disulfidptosis, this study explores the role of long non-coding RNA( LncRNA) in gastric cancer and establishes a prognosis model related to disulfidptosis,providing a new method for assessing the prognosis of gastric cancer treatment. Methods Transcriptomic data from gastric cancer and normal tissue samples were obtained from the public database TCGA,and disulfidptosis-related LncRNAs were selected through Pearson analysis and LASSO-Cox regression analysis. A relevant prognostic model for gastric cancer was constructed based on the above LncRNAs and validated by functional enrichment analysis,tumour microenvironment and immune cell infiltration analysis,drug sensitivity analysis and quantitative reverse transcription PCR(RT-qPCR). Results In this study,400 disulfide death-associated LncRNAs were identified and five of them were screened to construct a prognostic model for assessing the prognosis of gastric cancer patients. The models showed in validation that the survival of the high-risk score group was shorter than that of the low-risk score group(P<0.05). In addition,the predictive ability of the prognostic model(AUC=0.725) was better than that based only on basic characteristics such as age and gender. The expression levels of disulfide death-associated LncRNAs differed between normal and gastric cancer tissues(P<0.001). Conclusion The disulfidptosis-related LncRNA prognosis model developed in this study can effectively assess the prognosis of gastric cancer patients and the tumor microenvironment,providing potential targets and a theoretical basis for new immunotherapeutic strategies for gastric cancer.

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Objective To explore whether 5/6 nephrectomy can establish a rat model of chronic renal failure-induced sarcopenia. Methods The rats were randomly divided into control group, sham operation group and 5/6 nephrectomy model group. Chronic renal failure and sarcopenia were further verified. Results Compared with the sham group:(1) In the model group, the qualitative analysis of urinary protein, serum creatinine, blood urea nitrogen and serum uric acid levels were increased(P<0.05);(2) In the model group, the degree of renal fibrosis and the rate of apoptosis were high(P<0.05);(3) In the model group, the muscle strength and function declined(P<0.05);(4) In the model group, the degree of muscle fibrosis was obvious(P<0.05). Conclusion Through the 5/6 nephrectomy method, an animal model of chronic renal failure-induced sarcopenia can be established, which provides an experimental basis for further prevention and treatment of this disease.

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Objective To investigate the effect of miR-495-3p targeting budding uninhibited by benzimidazoles(BUB1) on signal transducer and activator of transcription 3(STAT3) signaling pathway on biological behavior of esophageal cancer(EC) cells. Methods The differentially expressed genes in EC tissues and normal tissues were screened by the cDNA microarray technique. The differentially expressed genes were analyzed by bioinformatics methods. The target genes of miRNAs were predicted by the TargetScan database and verified by a dual luciferase gene reporter assay. KYSE150 cells were divided into blank control group, NC mimics group and miR-495-3p mimics group. The activity of KYSE150 cells were detected by the CCK-8 method. Cell cycle and apoptosis were measured by flow cytometry. The expression ofBUB1mRNA was measured by real-time fluorescence quantitative reverse transcription polymerase chain reaction(RT-qPCR). The levels of BUB1, STAT3, phosphor(p)-STAT3, cyclin dependent kinase 1(CCNB1), cyclin dependent kinase 1(CDK1), B-cell lymphoma-2(Bcl-2), cysteinyl aspartate-specific proteinase-3(Caspase-3) and cysteinyl aspartate-specific proteinase-3(Caspase-9) were measured by Western blot. The migration and invasion abilities of the cells were measured by wound-healing and Transwell invasion assays. Results Differentially expressed genes were involved in biological processes, signaling pathways and network construction, which were mainly related to cell cycle.BUB1is the key(Hub) gene, andBUB1is the target gene of miR-495-3p.In vitroexperiments showed that overexpression of miR-495-3p could significantly inhibit the migration and invasion of EC cells and induce apoptosis and G2/M phase arrest. After treatment with overexpression of miR-495-3p, the expression of Caspase-3 and Caspase-9 in EC cells increased significantly(P<0.01), while the expression of Bcl-2,BUB1, CCNB1, CDK1 and p-STAT3 decreased significantly(P<0.01). Moreover, the STAT3 signaling pathway might play an important role in this process. Conclusion miR-495-3p may influence the biological behavior of esophageal cancer cells by down-regulating BUB1-mediated STAT3 signaling pathway.

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Objective To understand current epidemic trend of coronavirus disease-2019(COVID-19) in Anhui province in the optimization policy stage, and to analyze the pathogenic characteristics of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2) in different population. Methods Using a cross-sectional survey design, from December 19 to 20, 2022, an online questionnaire survey was conducted among residents of Anhui province through the official Wechat public accounts of provincial and municipal institutions with high traffic, to collect information on the incidence and clinic situation of COVID-19.The chi-square test was used to compare the proportion of COVID-19 suspected symptoms in different regions, ages and occupations. Results A total of 69 014 questionnaires were distributed and 68 232 valid questionnaires were recovered with an effective rate of 98.97%. The proportion of the participants with COVID-19 suspected symptoms in the past 2 weeks was 51.37%, of which 77.88% self-medicated at home. The top three cities were Bozhou, Fuyang and Bengbu. The age group of 15-59 had the highest proportion of COVID-19 suspected symptoms(51.96%). Among various occupations, service providers had the highest proportion of COVID-19 suspected symptoms(61.07%). 70.20% of the respondents felt anxious about the infection of SARS-CoV-2 and thought it was more serious than the flu. Conclusion The relatively high number of the infected cases and the anxiety of the people are all challenges faced by Anhui province in the stage of optimizing policies. Under the new situation of the epidemic, it is necessary to continuously monitor the local prevalent strains and strengthen the monitoring of clinical symptoms of the infected cases, and effectively control the speed of the virus spread through public health policies and various economic and publicity measures, so as not to cause a run on medical resources and excessive excess deaths.

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Objective To compare pregnancy outcomes among pregnant women undergoing cervical polypectomy during different gestational periods. Methods A total of 125 pregnant women were diagnosed with cervical polyps and underwent surgical removal. These participants were divided into the natural pregnancy group(n=71) and thein vitrofertilization and embryo transfer group(IVF-ET group,n=54). Retrospective analysis was conducted on various clinical parameters including age, gestational times, delivery times, abortion times, history of adverse pregnancy outcomes, history of endometrial polyps, pre-polyp removal vaginal bleeding episodes, gestational age at the time of polyp removal procedure, number of polyps detected during surgery, postoperative pathology results as well as pregnancy outcomes. Results Vaginal bleeding was the most common symptom of pregnancy combined with cervical polyps, accounting for 111 cases(88.8%)(62 cases in the natural pregnancy group(87.32%) and 49 cases in the IVF-ET group(90.74%)). Some patients had increased vaginal discharge or were found during a gynecological exam, accounting for 11.2% of the patients. All patients underwent cervical polypectomy during pregnancy, except for 9 cases of continued pregnancy(4 cases in the natural pregnancy group and 5 cases in the IVF-ET group), of which 13 had miscarriage, 10 had preterm birth(6 in the natural pregnancy group and 4 in the IVF group)and 93(54 cases in natural pregnancy group, 39 cases in IVF group)(74.4%) delivered at full term. Postoperative pathology was mostly inflammatory polyps(105 cases, 84%), deciduous polyps(20 cases, 8%)(10 cases in the natural pregnancy group and 10 cases in the IVF-ET group, 14.09% and 18.52%, respectively). The incidence of preoperative vaginal bleeding, decidual polyp, postoperative abortion, and postoperative preterm birth in the IVF-ET group exhibited higher rates compared to those observed in the natural pregnancy group; however, these differences did not reach statistical significance. Conclusion The cervical polypectomy procedure was performed during pregnancy for both the natural conception group and the IVF-ET group, with no significant disparity observed in pregnancy outcomes between these two cohorts.

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Objective To investigate the effect of standardized lymph node sorting on postoperative results of gastroesophageal junction malignant tumors. Methods The data of all patients with malignant gastroesophageal junction in gastric cancer database were analyzed retrospectively. Lymph nodes were sorted according to whether surgeons were present immediately after surgery. Patients were divided into lymph node sorting group(sorting group) and lymph node unsorting group(unsorting group). General data included gender, age, body mass index(BMI), carcinogenic antigen(CEA), postoperative albumin level, preoperative hemoglobin, etc. Perioperative and pathological data included operation time, intraoperative blood loss, postoperative hospital stay, tumor differentiation, distance from superior incisal margin, total number of lymph nodes, number of positive lymph nodes, etc. Kaplan-Meier curve and Log-rank test were used for survival analysis, and propensity score matching analysis adjusted for confounding factors between groups. Results A total of 386 patients were included, including 133 in lymph node sorting group and 253 in non-sorting group. The median follow-up time was 40.18 months. The total number of lymph nodes and the number of positive lymph nodes in the sorting group were(26.38±12.18) and(6.63±10.14), respectively, while the total number and the number of positive lymph nodes in the non-sorting group were(12.25±7.06) and(3.07±3.77), respectively. There were statistically significant differences in the total number of lymph nodes and the number of positive lymph nodes between the sorting group and the non-sorting group(P<0.05). There was no statistically significant difference in survival between the sorting group and the non-sorting group before matching. There were 112 and 203 patients with advanced gastric cancer in the two groups, respectively. The overall survival curve of patients in the sorting group was better than that in the non-sorting group, and the difference in median survival time was statistically significant(P<0.05). The caliper value was set to 0.02, and 94 pairs of patients were preferentially matched. After matching, the total number of lymph nodes and the number of positive lymph nodes in the sorting group were(24.71±12.03) and(5.70±9.95), respectively, while the total number and the number of positive lymph nodes in the non-sorting group were(13.05±7.63) and(3.37±4.32), respectively. The difference between the two groups was statistically significant(P<0.05). The overall survival curve of patients in the sorting group was better than that in the non-sorting group, and the median survival time was statistically significant(P<0.05). Conclusion Postoperative lymph node sorting for gastric cancer can significantly increase the number of total lymph nodes and positive lymph nodes, reduce lymph node migration, and improve postoperative survival time.

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Objective To analyze and verify the factors influencing the prediction model of suicidal ideation of burn patients in hospital based on international scale. Methods The clinical data of 194 burn patients treated in hospital were retrospectively analyzed. General data questionnaire, ISI, HAMD, HAMA, ASDS and BSHS-B were used to evaluate the influencing factors of suicidal ideation. According to the presence or absence of suicidal ideation, the patients were divided into the suicidal ideation group and the non-suicidal ideation group. The baseline data between the groups were compared, univariate screening of meaningful variables was conducted, and multivariate Logistic regression modeling was further conducted. ROC analysis evaluated model differentiation, and internal verification was conducted. Results According to the baseline data analysis results, there were no statistically significant differences in age, BMI, years of education, smoking history, estimated percentage of burned area, head and neck burns, hip and perineal burns, and pain scores in the suicidal ideation group(21/194) compared with the non-suicidal ideation group(173/194). Gender(P=0.047), presence or absence of trunk burn(P=0.022), severity of burn(moderate burn: P=0.002; severe burn: P=0.458; extremely severe burn: P=0.169), ISI score(P=0.001), HAMD score(P=0.001), HAMA score(P<0.001), ASDS score(P=0.003), BSHS-B score(P=0.011) had statistical significance. Multivariate Logistic regression analysis showed that the severity of burn( moderate burn: OR=0.103,P=0.009; severe burn: OR=0.351,P=0.223; extremely severe burn: OR=0.103,P=0.095) and HAMA score(OR=1.136,P=0.007) were independent influencing factors for burn patients with suicidal ideation.The Logistic regression prediction model was established by two independent influencing factors. ROC analysis results showed that the model had good differentiation(AUC=0.880,95% CI:0.808-0.952,P<0.001) and the internal verification accuracy was 79.38%. Conclusion The prediction model built on the basis of two independent influencing factors,burn severity and HAMA score,has a good prediction accuracy,which is helpful for clinicians to intervene as soon as possible for burn patients with suicidal ideation in hospital,in order to reduce the incidence and enrich clinical psychological research.

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Objective To investigate the function and clinical significance of nuclear matrix binding region binding protein 1(SATB1) and epidermal growth factor receptor(EGFR) in gastric cancer. Methods The expression of SATB1 and EGFR was detected by immunohistochemistry in 60 cases of paraffin-embedded gastric cancer and 39 cases of gastric mucosal inflammation. Small interfering RNA(siRNA) was transfected into gastric cancer cells. The expression of SATB1 and EGFR after transfection was detected by real-time fluorescence quantitative reverse transcription polymerase chain reaction(RT-qPCR) and Western blot. The cell migration and invasion changes of MGC803 after transfection were detected by cell scratch test and Transwell test. The prognosis of gastric cancer patients with different SATB1 and EGFR expression was analyzed by KM survival analysis. Results The expression of SATB1 and EGFR in gastric cancer tissues was higher than that in gastric mucosa inflammation tissues, and the difference was statistically significant(P<0.05). The expression of SATB1 was correlated with lymph node metastasis and distant metastasis of gastric cancer, and the difference was statistically significant(P<0.05). EGFR expression was also associated with distant metastasis, and the difference was statistically significant(P<0.05). There was a positive correlation between the expression of SATB1 and EGFR in gastric cancer tissues(r=0.49,P<0.05). RT-qPCR and Western blot showed that siRNA could effectively knock down the expression of SATB1 and EGFR in gastric cancer cells. The results of cell scratch and Transwell experiments showed that the migration and invasion of gastric cancer cells were inhibited by knocking down SATB1 and EGFR. The results of KM survival curve showed that gastric cancer patients with low expression of SATB1 had a better prognosis, while those with low expression of EGFR had a better prognosis. Conclusion The expression levels of SATB1 and EGFR are closely related to lymph node metastasis and distant metastasis of gastric cancer, and decreasing the expression levels of SATB1 and EGFR can inhibit the migration and invasion of gastric cancer.

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Objective To investigate the clinical characteristics and prognosis of acute myeloid leukemia(AML) patients withPTPN11gene mutation. Methods Total 115 adult AML patients who underwent initial diagnosis, treatment, and second-generation sequencing(NGS) detecting at hospital were recruited in this study. Clinical data included disease characteristics, treatment efficacy, long-term prognosis, immune cell subpopulations, and leukemia stem cells were collected to analyze the clinical characteristics and prognosis of AML patients withPTPN11gene mutation. Results PTPN11gene mutation rate in newly diagnosed adult AML was 9.57%, and the mutation site mainly occurred in exon 3 region with all mutation type being point mutation. Compared withPTPN11wild-type group,PTPN11gene mutation group had a higher early mortality rate(18.18%vs4.00%,P=0.048), a lower complete response rate(33.33%vs67.71%,P=0.039), a higher recurrence rate(83.33%vs42.31%,P=0.043), a shorter median overall survival time(9 monthsvs20 months,P=0.026), a lower proportion of effector T cells[(1.39±0.12)%vs(3.56±0.46)%,P=0.038], and a higher proportion of leukemia stem cells[(13.82±3.66)%vs(3.87±1.40)%,P=0.021]. Conclusion PTPN11gene mutation is a poor prognostic marker for AML. Those patients have a high early mortality rate, low complete remission rate, high recurrence rate, short median overall survival time, a low proportion of effector T cells, and a high proportion of leukemia stem cells.