Objective To screen the targets related to the metabolic enzymes involved in the cholesterol synthesis pathway that inhibits the polarization of macrophages towards M1 phenotype,and verify the intervention effects and underlying mechanisms in colorectal cancer cells.Methods Mouse colorectal cancer MC38 cells were divided into control group(si-NC)and experimental groups(the expression of enzymes in cholesterol synthesis pathway was interfered with siRNA for corresponding targets).RT-qPCR was used to detect the mRNA levels of corresponding targets in MC38 cells after transfection.After peritoneal macrophages were extracted from male C57BL/6 mice(6 weeks old,weighing 13～18 g),the macrophages were then treated with the conditioned media of MC38 cells transfected with different siRNAs for 48 h.RT-qPCR was employed to detect the mRNA levels of IL-1β,IL-6 and TNF-α in the macrophages so as to evaluate the effect of the culture media on the M1 polarization.MC38 cells were divided into control groups(OE-NC and sh-NC),farnesyl-diphosphate farnesyltransferase 1(FDFT1)overexpression group(OE-FDFT1)and FDFT1 knockdown group(sh-FDFT1).RT-qPCR was applied to detect the mRNA expression of FDFT1,and Western blotting was conducted to measure the protein level of FDFT1.C57BL/6 mice were subjected randomly to construct a subcutaneous tumor-bearing model and a model of intraperitoneal metastatic tumor(n=5)respectively.The growth of tumor mass was then measured.Flow cytometry was used to observe the proliferation and apoptosis of MC38 cells,and Trans well assay to detect migration ability of MC38 cells.Five C57BL/6 macrophage-depleted mice(established with injection of clodronate liposome suspension through tail vein)received intraperitoneal implantation to construct a metastasis model,and then the obtained tumor masses were then weighted.Results Compared with MC38 cells after si-NC transfection,the mRNA levels of corresponding targets in MC38 cells in the experimental groups were significantly reduced(P＜0.05).Significant increases were found in the mRNA levels of IL-1β,IL-6 and TNF-α of the macrophages with FDFT1 interference than the control cells(P＜0.05).There were no statistical differences in the proliferation,apoptosis and migration of MC38 cells in the control group(OE-NC and sh-NC)and the cells of the FDFT1 overexpression group and FDFT1 knockdown group(P＞0.05).In both the subcutaneous tumor-bearing model and the model of intraperitoneal metastatic tumor,the mass weight was significantly heavier in the OE-FDFT1 group than the OE-NC group(P＜0.01),and was notably smaller in the sh-FDFT1 group than the sh-NC group(P＜0.01).For the macrophage-depleted mouse tumor model,no remarkable change was observed in the tumor weight between the OE-FDFT1 group and the OE-NC group as well as the sh-FDFT1 group and the sh-NC group.Conclusion FDFT1,the metabolic enzyme in the cholesterol synthesis pathway of colorectal cancer tumor cells,is a potential target for tumor immunotherapy targeting macrophages,which promotes tumor progression by regulating macrophages.

Aim To investigate the role and regulatory mechanism of CREB regulated transcription coactivator 2(CRTC2)in cardiomyocyte hypertrophy.Methods A pathological cardiomyocyte hypertrophy model was established in C57BL/6 mice by intraperitoneal injection of isoproterenol(ISO),the expression of CRTC2 in cardiac tissue was detec-ted by Western blot.The CRTC2 knockout mice model was constructed,the cardiac function of mice was detected by small animal echocardiography,the collagen fiber content in mice cardiac tissue was detected by Masson staining,the car-diomyocyte hypertrophy related proteins:skeletal muscle α1-actin(ACTA1)and brain natriuretic peptide(BNP),as well as ferroptosis related proteins:acyl-CoA synthetase long chain family member 4(ACSL4),solute carrier family 7 member 11(SLC7A11)and glutathione peroxidase 4(GPX4)in mice cardiac tissue were detected by Western blot,the iron ion content in mice cardiac tissue was detected by iron ion kit,to evaluate the correlation between CRTC2 and cardiomyocyte hypertrophy and ferroptosis.H9c2 cells were induced by ISO to construct an in vitro model of cardiomyocyte hypertrophy,the protein expressions of CRTC2,ACTA1,BNP,ACSL4,SLC7A11 and GPX4 were detected after intervention with fer-roptosis inhibitor ferrostatin-1(Fer-1).H9c2 cells with CRTC2 overexpression induced by ISO were used to construct an in vitro model of cardiomyocyte hypertrophy,the related indicators of cardiomyocyte hypertrophy and ferroptosis were detec-ted to explore the mechanism of CRTC2 in cardiomyocyte hypertrophy.Results Compared with the control group,the expression of CRTC2 protein in the cardiac tissue of ISO induced cardiomyocyte hypertrophy mice was increased(P＜0.05).Compared with wild-type mice,CRTC2-/-mice showed worsened cardiac function,manifested as increased left ventricular end-diastolic diameter(LVEDD),left ventricular end-systolic diameter(LVESD),left ventricular posterior wall thickness(LVPWT),heart weight/tibia length(HW/TL)and heart weight/body weight(HW/BW),decreased short axis shortening(FS)and ejection fraction(EF),increased collagen fiber content in cardiac tissue,upregulated ex-pression of cardiomyocyte hypertrophy-related proteins ACTA1 and BNP,increased mRNA and protein expression of ferrop-tosis-related protein ACSL4,decreased mRNA and protein expression of SLC7A11 and GPX4,and elevated iron ion content in cardiac tissue(P＜0.05 or P＜0.01).In vitro experiments showed that compared with ISO group,the ISO+Fer-1 group had no significant change in CRTC2 protein expression(P＞0.05),the expression of ACTA1 and BNP protein decreased,the surface area of cardiomyocyte reduced,the expression of ACSL4 protein decreased,and the expression of SLC7A11 and GPX4 proteins increased(P＜0.05 or P＜0.01).Compared with the ISO group,the LV-CRTC2+ISO group showed a decrease in surface area of cardiomyocytes(P＜0.01),a decrease in ACTA1,BNP and ACSL4 protein ex-pression,an increase in SLC7A11 and GPX4 protein expression,and a decrease in ROS and iron ion content(P＜0.05 or P＜0.01).Conclusion CRTC2 alleviates cardiomyocyte hypertrophy and protect cardiac function by suppressing fer-roptosis in cardiomyocytes.

Objective To analyze the feasibility and advantage of indocyanine green(ICG)fluorescence imaging technique in the thoracoscopic anatomical segmentectomy.Methods Patients with small pulmonary nodules who underwent thoracoscopic anatomical segmentectomy in our department from January 2023 to June 2024 were selected and divided into the ICG fluorescence group(35 cases determining intersegmental plane through ICG fluorescence imaging method)and the modified inflation-deflation group(42 cases determining intersegmental plane through modified inflation-deflation method)according to different methods of determining intersegmental plane.The surgery-related indicators including time of intersegmental plane occurrence,operation time,number of lymph node dissection,postoperative duration of chest tube and postoperative hospital stay as well as the occurrence of complications in the two groups were counted.Patients over 60 years old in two groups were selected and the differences in surgery-related indicators were analyzed.Results The time of intersegmental plane occurrence and operation time in the ICG fluorescence group were shorter than those in the modified inflation-deflation group,with statistically significant differences(P<0.05).There was no significant difference in the number of lymph node dissection,postoperative duration of chest tube or postoperative hospital stay between the two groups(P>0.05).There was no significant difference in the incidence of postoperative complications between the two groups(P>0.05).The time of intersegmental plane occurrence,operation time and postoperative hospital stay of patients over 60 years old in the ICG fluorescence group were shorter than those in the modified inflation-deflation group,with statistically significant differences(P<0.05).Conclusion ICG fluorescence imaging method can display the intersegmental plane clearly and quickly,which can shorten the time of intersegmental plane occurrence and hospital stay in elderly patients with pulmonary nodules.

Objective To analyze the feasibility and advantage of indocyanine green(ICG)fluorescence imaging technique in the thoracoscopic anatomical segmentectomy.Methods Patients with small pulmonary nodules who underwent thoracoscopic anatomical segmentectomy in our department from January 2023 to June 2024 were selected and divided into the ICG fluorescence group(35 cases determining intersegmental plane through ICG fluorescence imaging method)and the modified inflation-deflation group(42 cases determining intersegmental plane through modified inflation-deflation method)according to different methods of determining intersegmental plane.The surgery-related indicators including time of intersegmental plane occurrence,operation time,number of lymph node dissection,postoperative duration of chest tube and postoperative hospital stay as well as the occurrence of complications in the two groups were counted.Patients over 60 years old in two groups were selected and the differences in surgery-related indicators were analyzed.Results The time of intersegmental plane occurrence and operation time in the ICG fluorescence group were shorter than those in the modified inflation-deflation group,with statistically significant differences(P<0.05).There was no significant difference in the number of lymph node dissection,postoperative duration of chest tube or postoperative hospital stay between the two groups(P>0.05).There was no significant difference in the incidence of postoperative complications between the two groups(P>0.05).The time of intersegmental plane occurrence,operation time and postoperative hospital stay of patients over 60 years old in the ICG fluorescence group were shorter than those in the modified inflation-deflation group,with statistically significant differences(P<0.05).Conclusion ICG fluorescence imaging method can display the intersegmental plane clearly and quickly,which can shorten the time of intersegmental plane occurrence and hospital stay in elderly patients with pulmonary nodules.

Objective To observe the clinical effect of abdominal full-thickness skin graft combined with adipose stem cells in repairing soft tissue defects after resection of facial benign tumors.Methods A total of 180 patients with soft tissue defects after resection of facial benign tumor in our hospital from January 2019 to June 2022 were selected,the study was designed by a double-blind method,and patients were divided into the observation group and the control group by a random number table method,with 90 cases in each group.Patients in the control group were repaired by abdominal full-thickness skin graft treatment,while these in the observation group were repaired by a combination of abdominal full-thickness skin graft and adipose stem cells.The scar status scores in the surgical area,clinical efficacy,incidence of complications and satisfaction of patients in the two groups were compared.Results Compared with preoperative results,the scores of color and thickness of scars,vascular distribution,and softness in face 6 months after surgery in both groups decreased,with statistically significant differences(P<0.05).Six months after surgery,the observation group had significantly lower scores on scar color and thickness,vascular distribution,and softness compared to the control group(P<0.05);there was no difference in the effective rate of the forehead,nose,eyelids,lips,or cheeks between the observation group and the control group(P>0.05);while the observation group had higher overall effective rate than the control group(P<0.05).There was no statistically significant difference in the incidence of complica-tions between the two groups(P>0.05).There was statistically significant difference in the distribution of the satisfaction of patients between the two groups(P<0.05),and the observation group showed significantly higher satisfaction of patients than the control group(P<0.05).Conclusion Abdominal full-thickness skin graft combined with adipose stem cells can improve facial scars in repairing soft tissue defects after resection of facial benign tumors,and enhance the repair effects and satisfaction of patients,with high safety.

Acute ischemic stroke is the most common type of stroke, characterized by high mortality, disability, and recurrence rates. Intravenous thrombolysis is the core treatment method. Among them, alteplase is effective as the standard drug, but it has limitations such as narrow time window, high risk of bleeding, and the need for continuous infusion. The new generation of improved drug tenecteplase has the advantages of single intravenous injection and higher fibrin specificity, making it a potential alternative drug to alteplase. In addition, endovascular therapy compensates for the low recanalization rate of large vessel occlusion on the basis of intravenous thrombolysis. This article reviews the clinical progress of teneplase in the treatment of acute ischemic stroke, aiming to provide reference for optimizing the treatment plan of acute ischemic stroke.

Aim To investigate the role and regulatory mechanism of CREB regulated transcription coactivator 2(CRTC2)in cardiomyocyte hypertrophy.Methods A pathological cardiomyocyte hypertrophy model was established in C57BL/6 mice by intraperitoneal injection of isoproterenol(ISO),the expression of CRTC2 in cardiac tissue was detec-ted by Western blot.The CRTC2 knockout mice model was constructed,the cardiac function of mice was detected by small animal echocardiography,the collagen fiber content in mice cardiac tissue was detected by Masson staining,the car-diomyocyte hypertrophy related proteins:skeletal muscle α1-actin(ACTA1)and brain natriuretic peptide(BNP),as well as ferroptosis related proteins:acyl-CoA synthetase long chain family member 4(ACSL4),solute carrier family 7 member 11(SLC7A11)and glutathione peroxidase 4(GPX4)in mice cardiac tissue were detected by Western blot,the iron ion content in mice cardiac tissue was detected by iron ion kit,to evaluate the correlation between CRTC2 and cardiomyocyte hypertrophy and ferroptosis.H9c2 cells were induced by ISO to construct an in vitro model of cardiomyocyte hypertrophy,the protein expressions of CRTC2,ACTA1,BNP,ACSL4,SLC7A11 and GPX4 were detected after intervention with fer-roptosis inhibitor ferrostatin-1(Fer-1).H9c2 cells with CRTC2 overexpression induced by ISO were used to construct an in vitro model of cardiomyocyte hypertrophy,the related indicators of cardiomyocyte hypertrophy and ferroptosis were detec-ted to explore the mechanism of CRTC2 in cardiomyocyte hypertrophy.Results Compared with the control group,the expression of CRTC2 protein in the cardiac tissue of ISO induced cardiomyocyte hypertrophy mice was increased(P＜0.05).Compared with wild-type mice,CRTC2-/-mice showed worsened cardiac function,manifested as increased left ventricular end-diastolic diameter(LVEDD),left ventricular end-systolic diameter(LVESD),left ventricular posterior wall thickness(LVPWT),heart weight/tibia length(HW/TL)and heart weight/body weight(HW/BW),decreased short axis shortening(FS)and ejection fraction(EF),increased collagen fiber content in cardiac tissue,upregulated ex-pression of cardiomyocyte hypertrophy-related proteins ACTA1 and BNP,increased mRNA and protein expression of ferrop-tosis-related protein ACSL4,decreased mRNA and protein expression of SLC7A11 and GPX4,and elevated iron ion content in cardiac tissue(P＜0.05 or P＜0.01).In vitro experiments showed that compared with ISO group,the ISO+Fer-1 group had no significant change in CRTC2 protein expression(P＞0.05),the expression of ACTA1 and BNP protein decreased,the surface area of cardiomyocyte reduced,the expression of ACSL4 protein decreased,and the expression of SLC7A11 and GPX4 proteins increased(P＜0.05 or P＜0.01).Compared with the ISO group,the LV-CRTC2+ISO group showed a decrease in surface area of cardiomyocytes(P＜0.01),a decrease in ACTA1,BNP and ACSL4 protein ex-pression,an increase in SLC7A11 and GPX4 protein expression,and a decrease in ROS and iron ion content(P＜0.05 or P＜0.01).Conclusion CRTC2 alleviates cardiomyocyte hypertrophy and protect cardiac function by suppressing fer-roptosis in cardiomyocytes.

Objective To observe the clinical effect of abdominal full-thickness skin graft combined with adipose stem cells in repairing soft tissue defects after resection of facial benign tumors.Methods A total of 180 patients with soft tissue defects after resection of facial benign tumor in our hospital from January 2019 to June 2022 were selected,the study was designed by a double-blind method,and patients were divided into the observation group and the control group by a random number table method,with 90 cases in each group.Patients in the control group were repaired by abdominal full-thickness skin graft treatment,while these in the observation group were repaired by a combination of abdominal full-thickness skin graft and adipose stem cells.The scar status scores in the surgical area,clinical efficacy,incidence of complications and satisfaction of patients in the two groups were compared.Results Compared with preoperative results,the scores of color and thickness of scars,vascular distribution,and softness in face 6 months after surgery in both groups decreased,with statistically significant differences(P<0.05).Six months after surgery,the observation group had significantly lower scores on scar color and thickness,vascular distribution,and softness compared to the control group(P<0.05);there was no difference in the effective rate of the forehead,nose,eyelids,lips,or cheeks between the observation group and the control group(P>0.05);while the observation group had higher overall effective rate than the control group(P<0.05).There was no statistically significant difference in the incidence of complica-tions between the two groups(P>0.05).There was statistically significant difference in the distribution of the satisfaction of patients between the two groups(P<0.05),and the observation group showed significantly higher satisfaction of patients than the control group(P<0.05).Conclusion Abdominal full-thickness skin graft combined with adipose stem cells can improve facial scars in repairing soft tissue defects after resection of facial benign tumors,and enhance the repair effects and satisfaction of patients,with high safety.

A serum metabolomics analysis method based on gas chromatography-mass spectrometry(GC-MS) was used to investigate the metabolic regulation mechanism of Hericium erinaceus(H. erinaceus) polysaccharides on radiation injury. A mouse model of radiation injury was established by ~(60)Co-γ irradiation. High and low dose groups of H. erinaceus polysaccharide injection were designed, and Rubiae Radix et Rhizoma extract was set as the positive control group to investigate the therapeutic effects and metabolic reaction pathways of H. erinaceus polysaccharides on radiation injury. The metabolites of serum samples were collected by GC-MS, and principal component analysis(PCA) was conducted to establish the metabolic profiles of each group of mice. Partial least squares discriminant analysis(PLS-DA), t-test(P<0.05), and variable importance in the projection(VIP>1) were used to screen out the differential metabolite. Metabolite identification and construction of related metabolic pathways and metabolic networks were achieved by using online databases such as HMDB and METLIN. The results showed that 12 differential metabolites in the serum of mice irradiated at 6.5 Gy that were associated with the radiation injury model, including lactic acid, alanine, urea, serine, threonine, glycerol, L-5-oxoproline, L-lysine, stearic acid, stearic acid, oleic acid, and 1-monopalmitoylglucoside. Two metabolic pathways were enriched: glycerolipid metabolism and metabolism of glycine, serine, and threonine. 18 differential metabolites in the serum of mice irradiated at 8.5 Gy were associated with the radiation injury model, including lactic acid, alanine, urea, L-leucine, glycerol, nonanoic acid, serine, threonine, L-5-oxoproline, phenylalanine, L-ornithine, 1,5-dehydroorbital, L-lysine, L-tyrosine, pectic, oleic, stearic, and cholesterol. Four metabolic pathways were enriched: phenylalanine, tyrosine, and tryptophan synthesis, phenylalanine metabolism, glyceride metabolism, and glycine, serine, and threonine metabolism. It was suggested that H. erinaceus polysaccharides could intervene in radiation injury by altering amino acid and fatty acid synthesis in mice. It was assumed that H. erinaceus polysaccharides regulated the level of metabolic pathways through lipid metabolism and amino acid metabolism, thus affecting energy metabolism and amino acid metabolism and exerting its therapeutic effect on radiation damage.
Animals ; Mice ; Metabolomics/methods* ; Gas Chromatography-Mass Spectrometry/methods* ; Polysaccharides/pharmacology* ; Male ; Hericium/chemistry* ; Drugs, Chinese Herbal/administration & dosage* ; Metabolome/drug effects* ; Gamma Rays/adverse effects*