Objective To investigate the clinical significance and potential mechanism of NAT10 in hepatocellular carcinoma.Meth-ods A total of 50 normal and 374 tumor samples were obtained based on The Cancer Genome Atlas(TCGA),and the data were pro-cessed by R 4.2.1.Results The expression of NAT10 in tumor samples was significantly higher than that in normal samples(P＜0.001).Compared with patients with low expression of NAT10,patients with high expression of NAT10had worse prognosis(P＜0.001).Logistic regression analysis showed that high NAT10 expression was associated with adverse clinical prognostic factors,and pa-tients with high NAT10 expression were more likely to progress to the advanced stage.Gene set enrichment analysis(GSEA)results showed that the genes related to heterobiotic metabolism,blood coagulation and fatty acid metabolism were differentially enriched in the samples with high expression of NAT10.The protein interaction analysis results showed that NAT10may interact with genes such as IGF2,SST,MUC2,CHGA,AGR2,etc.Conclusion NAT10 is highly expressed in hepatocellular carcinoma,and the expression level is cor-related with the clinical characteristics and survival rate of patients with hepatocellular carcinoma.NAT10may be a potential molecular bio-marker for hepatocellular carcinoma prognosis.

AIM:To investigate the effects of microRNA-200a(miR-200a)on the formation of primary cilia and the apoptosis in X-ray-injured cardiac fibroblasts.METHODS:Hearts were isolated from neonatal Wistar rats and di-gested with trypsin.Cardiac fibroblasts were isolated,irradiated with 1 Gy of X-ray,and subsequently transfected with miR-200a-3p mimic or si-IFT88.Primary cilia were detected by immunofluorescence staining,and tranfoming growth fac-tor-β1(TGF-β1)in the culture medium was detected by ELISA.The viability of cardiac fibroblasts was detected by CCK-8.The mRNA expression of tumor necrosis factor-α(TNF-α)and caspase-3 was detected by RT-qPCR,and the protein expression of TNF-α,caspase-3,collagen type I α1 chain(Col1α1)and TGF-β1 was detected by Western blot.RE-SULTS:Compared with control group,X-ray irradiation significantly decreased the expression of miR-200a-3p and the level of apoptosis,but increased the proportion of cells with primary cilia,the length of primary cilia and the viability of cardiac fibroblasts.Compared with X-ray group,the percentage of apoptotic cardiac fibroblasts in si-IFT88 group was in-creased.Compared with X-ray group,the proportion of cells with primary cilia and the TGF-β1 content in cardiac fibro-blasts were reduced,and the proportion of apoptotic cells increased in miR-200a-3p overexpression group.CONCLU-SION:X-ray-induced down-regulation of miR-200a-3p in neonatal rat cardiac fibroblasts drives the formation of primary cilia and suppresses the apoptosis.

AIM:To investigate the effects of microRNA-200a(miR-200a)on the formation of primary cilia and the apoptosis in X-ray-injured cardiac fibroblasts.METHODS:Hearts were isolated from neonatal Wistar rats and di-gested with trypsin.Cardiac fibroblasts were isolated,irradiated with 1 Gy of X-ray,and subsequently transfected with miR-200a-3p mimic or si-IFT88.Primary cilia were detected by immunofluorescence staining,and tranfoming growth fac-tor-β1(TGF-β1)in the culture medium was detected by ELISA.The viability of cardiac fibroblasts was detected by CCK-8.The mRNA expression of tumor necrosis factor-α(TNF-α)and caspase-3 was detected by RT-qPCR,and the protein expression of TNF-α,caspase-3,collagen type I α1 chain(Col1α1)and TGF-β1 was detected by Western blot.RE-SULTS:Compared with control group,X-ray irradiation significantly decreased the expression of miR-200a-3p and the level of apoptosis,but increased the proportion of cells with primary cilia,the length of primary cilia and the viability of cardiac fibroblasts.Compared with X-ray group,the percentage of apoptotic cardiac fibroblasts in si-IFT88 group was in-creased.Compared with X-ray group,the proportion of cells with primary cilia and the TGF-β1 content in cardiac fibro-blasts were reduced,and the proportion of apoptotic cells increased in miR-200a-3p overexpression group.CONCLU-SION:X-ray-induced down-regulation of miR-200a-3p in neonatal rat cardiac fibroblasts drives the formation of primary cilia and suppresses the apoptosis.

Objective To investigate the effect of hyperglycemia activated CCAAT enhancer binding protein β(C/EBPβ)promoting the expression of thyroid hormone nuclear receptor α1(THα1)on diabetic cardiomyopathy(DCM).Methods Twenty healthy male Wistar rats were randomly divided into diabetes mellitus(DM,n=10)group and DCM(n=10)group.Cardiomyocyte were divided into four groups:DM-cell,glucose intervention(Glu),knockdown C/EBPβ group(cardiomyocyte were transfected with plasmids targeting knockdown C/EBPβ)and si-NC group(cardiomyocyte were transfected with nagetive control sequence of plasmids).HE and Masson staining was performed to detect myocardial injury and collagen deposition.Echocardiography was used to evaluate left ventricular function.The mRNA and protein expression of C/EBP β and THα1 was detected using RT-qPCR,Western blot and immunofluorescence staining in myocardial cells.Apoptosis was analyzed using flow cytometric.Contraction frequency was counted by microscopy.Results Compared to DM group,count of fibroblasts,collagen volume fraction,end-systolic dimension of left ventricular,and the mRNA and protein expression of C/EBPβ and THα1 as well as fluorescence intensity increased(P<0.05);left ventricular ejection fraction and left ventricular fractional shortening(LVFS)decreased in DCM group(P<0.05).The mRNA and protein expression of C/EBPβ and THα1 were higher in the Glu group than in DM-cell group(P<0.05).The percentage of apoptosis,the mRNA and protein expression of THα1 of myocardial cells were lower in the si-C/EBPβ group than in the si-NC group(P<0.05),and LVFS was higher in the si-NC group(P<0.05).Conclusions High glucose regulates C/EBPβ expression,which in turn drives THα1 expression in myocardial tissue,leading to adverse effects on myocardial tissue.Conversely,silencing C/EBPβ downregulates THα1 expression,and exerts a protective effect on cardiomyocytes.

Objective To investigate the effect of hyperglycemia activated CCAAT enhancer binding protein β(C/EBPβ)promoting the expression of thyroid hormone nuclear receptor α1(THα1)on diabetic cardiomyopathy(DCM).Methods Twenty healthy male Wistar rats were randomly divided into diabetes mellitus(DM,n=10)group and DCM(n=10)group.Cardiomyocyte were divided into four groups:DM-cell,glucose intervention(Glu),knockdown C/EBPβ group(cardiomyocyte were transfected with plasmids targeting knockdown C/EBPβ)and si-NC group(cardiomyocyte were transfected with nagetive control sequence of plasmids).HE and Masson staining was performed to detect myocardial injury and collagen deposition.Echocardiography was used to evaluate left ventricular function.The mRNA and protein expression of C/EBP β and THα1 was detected using RT-qPCR,Western blot and immunofluorescence staining in myocardial cells.Apoptosis was analyzed using flow cytometric.Contraction frequency was counted by microscopy.Results Compared to DM group,count of fibroblasts,collagen volume fraction,end-systolic dimension of left ventricular,and the mRNA and protein expression of C/EBPβ and THα1 as well as fluorescence intensity increased(P<0.05);left ventricular ejection fraction and left ventricular fractional shortening(LVFS)decreased in DCM group(P<0.05).The mRNA and protein expression of C/EBPβ and THα1 were higher in the Glu group than in DM-cell group(P<0.05).The percentage of apoptosis,the mRNA and protein expression of THα1 of myocardial cells were lower in the si-C/EBPβ group than in the si-NC group(P<0.05),and LVFS was higher in the si-NC group(P<0.05).Conclusions High glucose regulates C/EBPβ expression,which in turn drives THα1 expression in myocardial tissue,leading to adverse effects on myocardial tissue.Conversely,silencing C/EBPβ downregulates THα1 expression,and exerts a protective effect on cardiomyocytes.

Objective To investigate the clinical significance and potential mechanism of NAT10 in hepatocellular carcinoma.Meth-ods A total of 50 normal and 374 tumor samples were obtained based on The Cancer Genome Atlas(TCGA),and the data were pro-cessed by R 4.2.1.Results The expression of NAT10 in tumor samples was significantly higher than that in normal samples(P＜0.001).Compared with patients with low expression of NAT10,patients with high expression of NAT10had worse prognosis(P＜0.001).Logistic regression analysis showed that high NAT10 expression was associated with adverse clinical prognostic factors,and pa-tients with high NAT10 expression were more likely to progress to the advanced stage.Gene set enrichment analysis(GSEA)results showed that the genes related to heterobiotic metabolism,blood coagulation and fatty acid metabolism were differentially enriched in the samples with high expression of NAT10.The protein interaction analysis results showed that NAT10may interact with genes such as IGF2,SST,MUC2,CHGA,AGR2,etc.Conclusion NAT10 is highly expressed in hepatocellular carcinoma,and the expression level is cor-related with the clinical characteristics and survival rate of patients with hepatocellular carcinoma.NAT10may be a potential molecular bio-marker for hepatocellular carcinoma prognosis.

Objective:To investigate the role of miR-182-5p regulated primary cilia loss on migration of TPC-1 in papillary thyroid cancers(PTC).Methods:Ten cases of PTC and adjacent tissues were collected from the First Hospital of Lanzhou University, The expression of miR-182-5p in PTC tissue and TPC-1 cells was detected by qPCR, and the frequency of primary cilia was detected by immunofluorescence; Overexpressing miR-182-5p, the migrated number of TPC-1 was detected by Transwell assay; Interfering TPC-1 with siRNA-IFT88, the migrated number of TPC-1 and the frequency of primary cilia were detected, respectively.Results:Compared with control, the expression of miR-182-5p was significantly upregulated in PTC and TPC-1, the frequency of primary cilia in PTC and TPC-1 was downregulated. Overexpressing miR-182-5p increased the migrated number of TPC-1 cell and reduced the number of TPC-1 cell migration(27%, P=0.002); After siRNA-IFT88 treatment, primary cilia in TPC-1 became shorter and thinner, with a decrease in frequency( P=0.001), the migrated number of TPC-1 cell increased, and TPC-1 cell showed smaller nuclei and fewer microvilli. Conclusion:The regulation of primary cilia loss by miR-182-5p through the PI3K pathway contributes to the migration of TPC-1 cells. The loss of primary cilia has an adverse impact on the prognosis of PTC.

Diabetes, hypertension, and dyslipidemia, collectively referred to the " Three Highs, " represent increasingly prevalent metabolic risk factors in China. Many individuals experience all three conditions concurrently, significantly heightening the risk of cardiovascular disease and mortality. Although the National Metabolic Management Center(MMC) has been established for over eight years and has its unique features, the awareness, treatment, and control rates of these diseases in China remain low, and the efficiency of community management is insufficient. According to the previous two editions of management guidelines and the most recent domestic and international diagnostic and treatment guidelines, this paper conducts an in-depth analysis of the operational experience and management strategies of the MMC. Its aim is to improve the efficiency of grassroots MMC mode management for " Three Highs" patients and ensure that patients receive more standardized management.

Diabetes, hypertension, and dyslipidemia, collectively referred to the " Three Highs, " represent increasingly prevalent metabolic risk factors in China. Many individuals experience all three conditions concurrently, significantly heightening the risk of cardiovascular disease and mortality. Although the National Metabolic Management Center(MMC) has been established for over eight years and has its unique features, the awareness, treatment, and control rates of these diseases in China remain low, and the efficiency of community management is insufficient. According to the previous two editions of management guidelines and the most recent domestic and international diagnostic and treatment guidelines, this paper conducts an in-depth analysis of the operational experience and management strategies of the MMC. Its aim is to improve the efficiency of grassroots MMC mode management for " Three Highs" patients and ensure that patients receive more standardized management.

Aromatase deficiency (AD) is a rare autosomal recessive genetic disease caused by loss-of-function mutations in aromatase gene (CYP19A1), leading to congenital estrogen deficiency syndrome. Both mothers of AD patients during pregnancy and female AD fetus show virilization, while male patients are usually diagnosed in adulthood due to continued height increase and metabolic abnormalities. In 2019, a patient with AD was admitted in the Second Xiangya Hospital. The patient was a 37-year-old adult male who continued to grow linearly after adulthood. His estradiol was below the measurable line, the follicle-stimulating hormone (FSH) increased, bone age delayed, epiphysis unfused, and the bone mass reduced. CYP19A1 gene detection showed that c.1093C>T, p.R365W was homozygous mutation. This disease is rare in clinic. Clinicians need to raise awareness of the disease for early diagnosis and treatment to improve the long-term prognosis of patients.
46, XX Disorders of Sex Development/genetics* ; Adult ; Aromatase/metabolism* ; Female ; Gynecomastia/genetics* ; Humans ; Infertility, Male ; Male ; Metabolism, Inborn Errors ; Mutation ; Pregnancy