1.ALKBH3-regulated m1A of ALDOA potentiates glycolysis and doxorubicin resistance of triple negative breast cancer cells.
Yuhua DENG ; Zhiyan CHEN ; Peixian CHEN ; Yaming XIONG ; Chuling ZHANG ; Qiuyuan WU ; Huiqi HUANG ; Shuqing YANG ; Kun ZHANG ; Tiancheng HE ; Wei LI ; Guolin YE ; Wei LUO ; Hongsheng WANG ; Dan ZHOU
Acta Pharmaceutica Sinica B 2025;15(6):3092-3106
Chemotherapy is currently the mainstay of systemic management for triple-negative breast cancer (TNBC), but chemoresistance significantly impacts patient outcomes. Our research indicates that Doxorubicin (Dox)-resistant TNBC cells exhibit increased glycolysis and ATP generation compared to their parental cells, with this metabolic shift contributing to chemoresistance. We discovered that ALKBH3, an m1A demethylase enzyme, is crucial in regulating the enhanced glycolysis in Dox-resistant TNBC cells. Knocking down ALKBH3 reduced ATP generation, glucose consumption, and lactate production, implicating its involvement in mediating glycolysis. Further investigation revealed that aldolase A (ALDOA), a key enzyme in glycolysis, is a downstream target of ALKBH3. ALKBH3 regulates ALDOA mRNA stability through m1A demethylation at the 3'-untranslated region (3'UTR). This methylation negatively affects ALDOA mRNA stability by recruiting the YTHDF2/PAN2-PAN3 complex, leading to mRNA degradation. The ALKBH3/ALDOA axis promotes Dox resistance both in vitro and in vivo. Clinical analysis demonstrated that ALKBH3 and ALDOA are upregulated in breast cancer tissues, and higher expression of these proteins is associated with reduced overall survival in TNBC patients. Our study highlights the role of the ALKBH3/ALDOA axis in contributing to Dox resistance in TNBC cells through regulation of ALDOA mRNA stability and glycolysis.
2.Tetrandrine enhances the host antiviral response through cGAMP-mediated cGAS-STING signaling pathway
Zhiwen WANG ; Yaming ZHANG ; Zhihui XIE
Chinese Journal of Microbiology and Immunology 2024;44(1):17-26
Objective:To investigate whether tetrandrine could be used as an agonist of cGAMP to enhance the activation of cGAS-STING signaling pathway and analyze the antiviral function of tetrandrine.Methods:THP1-Lucia-ISRE and RAW-Lucia-ISRE cells were incubated with different doses of tetrandrine in combination with cGAMP, respectively. IRF3 reporter activity was analyzed by luciferase reporter assay. Western blot was used to detect the activation of cGAS-STING signaling pathway. The expression of IFN-β, CXCL10 and CCL5 at mRNA level was quantified by real-time quantitative PCR. The expression of IFN-β at protein level was assessed by ELISA. HeLa cells stably expressing STING-GFP gene (HeLa-STNG-GFP cells) were constructed and stimulated with tetrandrine and cGAMP, then puncta-like structures were imaged by ZEISS LSM780. THP1-Lucia-ISRE cells were infected with herpes simplex virus type 1 (HSV-1) in the presence or absence of tetrandrine or cGAMP. The antiviral function of tetrandrine was analyzed by Western blot and fluorescence intensity assay.Results:Tetrandrine enhanced cGAMP-mediated IRF3 responses and activated cGAS-STING signaling pathway in combination with cGAMP. Tetrandrine combined with cGAMP triggered STING translocation and the formation of puncta-like structures in HeLa-STNG-GFP cells. The titer of HSV-1, the expression of HSV-glycoprotein D/UL30 and the fluorescence intensity of HSV-GFP were all decline after treating HSV-1-infected THP1-Lucia-ISRE cells with tetrandrine and cGAMP.Conclusions:Tetrandrine combined with cGAMP activates cGAS-STING signaling pathway, thus enhancing the host antiviral response.
3.Safety and efficacy of domestic Kangduo endoscopic robotic surgical system in lapa-roscopic partial nephrectomy
Mingxin DIAO ; Bing WANG ; Yaming GU ; Yingzhi DIAO ; Zhongyuan ZHANG ; Cheng SHEN ; Xuesong LI ; Zheng ZHANG
Journal of Modern Urology 2024;29(7):622-626
Objective To investigate the safety and efficacy of domestic Kangduo endoscopic robotic surgical system(SR1500)in laparoscopic partial nephrectomy via abdominal approach.Methods Perioperative data of 5 patients with renal tumors undergoing transabdominal partial nephrectomy with SR1500 at Miyun Hospital during Jul.and Aug.2023 were prospectively collected.The surgical procedure,operation time,pathological margins,intraoperative bleeding,hospital stay,and catheter removal time were recorded.Results The average tumor diameter was 1.92 cm,staged as T1a in TNM classification,with an average R.E.N.A.L score of 5.80.The mean docking time of equipment was 3.00 min,robotic arm operating time 97.20 min,and renal warm ischemia time 19.80 min.Postoperative pathology revealed negative surgical margins in all patients.No high-grade perioperative complications or device-related adverse events occurred.Conclusion Laparoscopic partial nephrectomy using the Kangduo endoscopic robotic surgical system(SR1500)via abdominal approach is safe and effective in the treatment of T1a renal tumors.
4.The Relationship between the Duration of Folic Acid Supplementation,Gesta-tional Diabetes Mellitus and Adverse Perinatal Outcomes
Jinyi WANG ; Chunxing MA ; Yueyue GAO ; Yaming ZHANG ; Fengying WANG ; Xuntao LIU ; Yunchun LIU
Journal of Practical Obstetrics and Gynecology 2024;40(8):664-669
Objective:To investigate the relationship between the duration of folic acid supplementation,gesta-tional diabetes mellitus(GDM)and adverse perinatal outcomes based on generalized linear mixed model.Meth-ods:Clinical data was collected of 759 pairs of mothers and children who delivered at the First Affiliated Hospital of Hebei North University from January 2021 to December 2022.The adverse perinatal outcomes of this study in-cluded cesarean section,premature birth,macrosomia,low birth weight(LBW),large for gestational age(LGA),and small for gestational age infant(SGA).Generalized linear mixed model was used to analyze the impact of GDM and supplementation with folic acid for a duration of ≥3 months on the risk of adverse perinatal outcomes.A stratified analysis of the duration of folic acid supplementation was conducted to determine whether it was a con-founding factor or influencing factor of GDM and adverse birth outcomes.Results:A total of 748 patients(98.55%)received folic acid supplementation before and during pregnancy,with a total of 743 patients(97.89%)receiving folic acid supplementation during pregnancy and 496 patients(65.35%)receiving folic acid supplementation before pregnancy.77 mothers were diagnosed with GDM,with an incidence rate of 10.14%.Compared with those who received folic acid supplementation before pregnancy for<3 months,those who re-ceived folic acid supplementation before pregnancy for ≥ 3 months were associated with an increased risk of GDM.The adjusted RR(aRR)was 1.72(95%CI 1.17-2.53).The GDM patients who received folic acid sup-plementation for≥3 months before pregnancy was associated with a reduced risk of SGA,with an aRR of 0.40(95%CI 0.18-0.89).In the subgroup of pregnant women who received folic acid supplementation for≥3 months,GDM was associated with an increased risk of cesarean section(aRR 1.36,95%CI 1.06-1.75))and macrosomia(aRR2.11,95%CI 1.06-4.20),but both aRR were lower than fixed effect RR of 1.53(95%CI 1.01-2.34)and 2.43(95%CI 12.7-4.66),respectively.and the above differences were statistically signifi-cant(P<0.01).Conclusions:Supplementing folic acid for≥3 months before pregnancy increases the risk of GDM,but reduces the risk of SGA birth in patients with GDM.Supplementing folic acid during pregnancy for≥3 months has a reducing effect on the risk of adverse perinataloutcomes of cesarean section and macrosomia in women with GDM.
5.The Relationship between the Duration of Folic Acid Supplementation,Gesta-tional Diabetes Mellitus and Adverse Perinatal Outcomes
Jinyi WANG ; Chunxing MA ; Yueyue GAO ; Yaming ZHANG ; Fengying WANG ; Xuntao LIU ; Yunchun LIU
Journal of Practical Obstetrics and Gynecology 2024;40(8):664-669
Objective:To investigate the relationship between the duration of folic acid supplementation,gesta-tional diabetes mellitus(GDM)and adverse perinatal outcomes based on generalized linear mixed model.Meth-ods:Clinical data was collected of 759 pairs of mothers and children who delivered at the First Affiliated Hospital of Hebei North University from January 2021 to December 2022.The adverse perinatal outcomes of this study in-cluded cesarean section,premature birth,macrosomia,low birth weight(LBW),large for gestational age(LGA),and small for gestational age infant(SGA).Generalized linear mixed model was used to analyze the impact of GDM and supplementation with folic acid for a duration of ≥3 months on the risk of adverse perinatal outcomes.A stratified analysis of the duration of folic acid supplementation was conducted to determine whether it was a con-founding factor or influencing factor of GDM and adverse birth outcomes.Results:A total of 748 patients(98.55%)received folic acid supplementation before and during pregnancy,with a total of 743 patients(97.89%)receiving folic acid supplementation during pregnancy and 496 patients(65.35%)receiving folic acid supplementation before pregnancy.77 mothers were diagnosed with GDM,with an incidence rate of 10.14%.Compared with those who received folic acid supplementation before pregnancy for<3 months,those who re-ceived folic acid supplementation before pregnancy for ≥ 3 months were associated with an increased risk of GDM.The adjusted RR(aRR)was 1.72(95%CI 1.17-2.53).The GDM patients who received folic acid sup-plementation for≥3 months before pregnancy was associated with a reduced risk of SGA,with an aRR of 0.40(95%CI 0.18-0.89).In the subgroup of pregnant women who received folic acid supplementation for≥3 months,GDM was associated with an increased risk of cesarean section(aRR 1.36,95%CI 1.06-1.75))and macrosomia(aRR2.11,95%CI 1.06-4.20),but both aRR were lower than fixed effect RR of 1.53(95%CI 1.01-2.34)and 2.43(95%CI 12.7-4.66),respectively.and the above differences were statistically signifi-cant(P<0.01).Conclusions:Supplementing folic acid for≥3 months before pregnancy increases the risk of GDM,but reduces the risk of SGA birth in patients with GDM.Supplementing folic acid during pregnancy for≥3 months has a reducing effect on the risk of adverse perinataloutcomes of cesarean section and macrosomia in women with GDM.
6.The Relationship between the Duration of Folic Acid Supplementation,Gesta-tional Diabetes Mellitus and Adverse Perinatal Outcomes
Jinyi WANG ; Chunxing MA ; Yueyue GAO ; Yaming ZHANG ; Fengying WANG ; Xuntao LIU ; Yunchun LIU
Journal of Practical Obstetrics and Gynecology 2024;40(8):664-669
Objective:To investigate the relationship between the duration of folic acid supplementation,gesta-tional diabetes mellitus(GDM)and adverse perinatal outcomes based on generalized linear mixed model.Meth-ods:Clinical data was collected of 759 pairs of mothers and children who delivered at the First Affiliated Hospital of Hebei North University from January 2021 to December 2022.The adverse perinatal outcomes of this study in-cluded cesarean section,premature birth,macrosomia,low birth weight(LBW),large for gestational age(LGA),and small for gestational age infant(SGA).Generalized linear mixed model was used to analyze the impact of GDM and supplementation with folic acid for a duration of ≥3 months on the risk of adverse perinatal outcomes.A stratified analysis of the duration of folic acid supplementation was conducted to determine whether it was a con-founding factor or influencing factor of GDM and adverse birth outcomes.Results:A total of 748 patients(98.55%)received folic acid supplementation before and during pregnancy,with a total of 743 patients(97.89%)receiving folic acid supplementation during pregnancy and 496 patients(65.35%)receiving folic acid supplementation before pregnancy.77 mothers were diagnosed with GDM,with an incidence rate of 10.14%.Compared with those who received folic acid supplementation before pregnancy for<3 months,those who re-ceived folic acid supplementation before pregnancy for ≥ 3 months were associated with an increased risk of GDM.The adjusted RR(aRR)was 1.72(95%CI 1.17-2.53).The GDM patients who received folic acid sup-plementation for≥3 months before pregnancy was associated with a reduced risk of SGA,with an aRR of 0.40(95%CI 0.18-0.89).In the subgroup of pregnant women who received folic acid supplementation for≥3 months,GDM was associated with an increased risk of cesarean section(aRR 1.36,95%CI 1.06-1.75))and macrosomia(aRR2.11,95%CI 1.06-4.20),but both aRR were lower than fixed effect RR of 1.53(95%CI 1.01-2.34)and 2.43(95%CI 12.7-4.66),respectively.and the above differences were statistically signifi-cant(P<0.01).Conclusions:Supplementing folic acid for≥3 months before pregnancy increases the risk of GDM,but reduces the risk of SGA birth in patients with GDM.Supplementing folic acid during pregnancy for≥3 months has a reducing effect on the risk of adverse perinataloutcomes of cesarean section and macrosomia in women with GDM.
7.The Relationship between the Duration of Folic Acid Supplementation,Gesta-tional Diabetes Mellitus and Adverse Perinatal Outcomes
Jinyi WANG ; Chunxing MA ; Yueyue GAO ; Yaming ZHANG ; Fengying WANG ; Xuntao LIU ; Yunchun LIU
Journal of Practical Obstetrics and Gynecology 2024;40(8):664-669
Objective:To investigate the relationship between the duration of folic acid supplementation,gesta-tional diabetes mellitus(GDM)and adverse perinatal outcomes based on generalized linear mixed model.Meth-ods:Clinical data was collected of 759 pairs of mothers and children who delivered at the First Affiliated Hospital of Hebei North University from January 2021 to December 2022.The adverse perinatal outcomes of this study in-cluded cesarean section,premature birth,macrosomia,low birth weight(LBW),large for gestational age(LGA),and small for gestational age infant(SGA).Generalized linear mixed model was used to analyze the impact of GDM and supplementation with folic acid for a duration of ≥3 months on the risk of adverse perinatal outcomes.A stratified analysis of the duration of folic acid supplementation was conducted to determine whether it was a con-founding factor or influencing factor of GDM and adverse birth outcomes.Results:A total of 748 patients(98.55%)received folic acid supplementation before and during pregnancy,with a total of 743 patients(97.89%)receiving folic acid supplementation during pregnancy and 496 patients(65.35%)receiving folic acid supplementation before pregnancy.77 mothers were diagnosed with GDM,with an incidence rate of 10.14%.Compared with those who received folic acid supplementation before pregnancy for<3 months,those who re-ceived folic acid supplementation before pregnancy for ≥ 3 months were associated with an increased risk of GDM.The adjusted RR(aRR)was 1.72(95%CI 1.17-2.53).The GDM patients who received folic acid sup-plementation for≥3 months before pregnancy was associated with a reduced risk of SGA,with an aRR of 0.40(95%CI 0.18-0.89).In the subgroup of pregnant women who received folic acid supplementation for≥3 months,GDM was associated with an increased risk of cesarean section(aRR 1.36,95%CI 1.06-1.75))and macrosomia(aRR2.11,95%CI 1.06-4.20),but both aRR were lower than fixed effect RR of 1.53(95%CI 1.01-2.34)and 2.43(95%CI 12.7-4.66),respectively.and the above differences were statistically signifi-cant(P<0.01).Conclusions:Supplementing folic acid for≥3 months before pregnancy increases the risk of GDM,but reduces the risk of SGA birth in patients with GDM.Supplementing folic acid during pregnancy for≥3 months has a reducing effect on the risk of adverse perinataloutcomes of cesarean section and macrosomia in women with GDM.
8.The Relationship between the Duration of Folic Acid Supplementation,Gesta-tional Diabetes Mellitus and Adverse Perinatal Outcomes
Jinyi WANG ; Chunxing MA ; Yueyue GAO ; Yaming ZHANG ; Fengying WANG ; Xuntao LIU ; Yunchun LIU
Journal of Practical Obstetrics and Gynecology 2024;40(8):664-669
Objective:To investigate the relationship between the duration of folic acid supplementation,gesta-tional diabetes mellitus(GDM)and adverse perinatal outcomes based on generalized linear mixed model.Meth-ods:Clinical data was collected of 759 pairs of mothers and children who delivered at the First Affiliated Hospital of Hebei North University from January 2021 to December 2022.The adverse perinatal outcomes of this study in-cluded cesarean section,premature birth,macrosomia,low birth weight(LBW),large for gestational age(LGA),and small for gestational age infant(SGA).Generalized linear mixed model was used to analyze the impact of GDM and supplementation with folic acid for a duration of ≥3 months on the risk of adverse perinatal outcomes.A stratified analysis of the duration of folic acid supplementation was conducted to determine whether it was a con-founding factor or influencing factor of GDM and adverse birth outcomes.Results:A total of 748 patients(98.55%)received folic acid supplementation before and during pregnancy,with a total of 743 patients(97.89%)receiving folic acid supplementation during pregnancy and 496 patients(65.35%)receiving folic acid supplementation before pregnancy.77 mothers were diagnosed with GDM,with an incidence rate of 10.14%.Compared with those who received folic acid supplementation before pregnancy for<3 months,those who re-ceived folic acid supplementation before pregnancy for ≥ 3 months were associated with an increased risk of GDM.The adjusted RR(aRR)was 1.72(95%CI 1.17-2.53).The GDM patients who received folic acid sup-plementation for≥3 months before pregnancy was associated with a reduced risk of SGA,with an aRR of 0.40(95%CI 0.18-0.89).In the subgroup of pregnant women who received folic acid supplementation for≥3 months,GDM was associated with an increased risk of cesarean section(aRR 1.36,95%CI 1.06-1.75))and macrosomia(aRR2.11,95%CI 1.06-4.20),but both aRR were lower than fixed effect RR of 1.53(95%CI 1.01-2.34)and 2.43(95%CI 12.7-4.66),respectively.and the above differences were statistically signifi-cant(P<0.01).Conclusions:Supplementing folic acid for≥3 months before pregnancy increases the risk of GDM,but reduces the risk of SGA birth in patients with GDM.Supplementing folic acid during pregnancy for≥3 months has a reducing effect on the risk of adverse perinataloutcomes of cesarean section and macrosomia in women with GDM.
9.The Relationship between the Duration of Folic Acid Supplementation,Gesta-tional Diabetes Mellitus and Adverse Perinatal Outcomes
Jinyi WANG ; Chunxing MA ; Yueyue GAO ; Yaming ZHANG ; Fengying WANG ; Xuntao LIU ; Yunchun LIU
Journal of Practical Obstetrics and Gynecology 2024;40(8):664-669
Objective:To investigate the relationship between the duration of folic acid supplementation,gesta-tional diabetes mellitus(GDM)and adverse perinatal outcomes based on generalized linear mixed model.Meth-ods:Clinical data was collected of 759 pairs of mothers and children who delivered at the First Affiliated Hospital of Hebei North University from January 2021 to December 2022.The adverse perinatal outcomes of this study in-cluded cesarean section,premature birth,macrosomia,low birth weight(LBW),large for gestational age(LGA),and small for gestational age infant(SGA).Generalized linear mixed model was used to analyze the impact of GDM and supplementation with folic acid for a duration of ≥3 months on the risk of adverse perinatal outcomes.A stratified analysis of the duration of folic acid supplementation was conducted to determine whether it was a con-founding factor or influencing factor of GDM and adverse birth outcomes.Results:A total of 748 patients(98.55%)received folic acid supplementation before and during pregnancy,with a total of 743 patients(97.89%)receiving folic acid supplementation during pregnancy and 496 patients(65.35%)receiving folic acid supplementation before pregnancy.77 mothers were diagnosed with GDM,with an incidence rate of 10.14%.Compared with those who received folic acid supplementation before pregnancy for<3 months,those who re-ceived folic acid supplementation before pregnancy for ≥ 3 months were associated with an increased risk of GDM.The adjusted RR(aRR)was 1.72(95%CI 1.17-2.53).The GDM patients who received folic acid sup-plementation for≥3 months before pregnancy was associated with a reduced risk of SGA,with an aRR of 0.40(95%CI 0.18-0.89).In the subgroup of pregnant women who received folic acid supplementation for≥3 months,GDM was associated with an increased risk of cesarean section(aRR 1.36,95%CI 1.06-1.75))and macrosomia(aRR2.11,95%CI 1.06-4.20),but both aRR were lower than fixed effect RR of 1.53(95%CI 1.01-2.34)and 2.43(95%CI 12.7-4.66),respectively.and the above differences were statistically signifi-cant(P<0.01).Conclusions:Supplementing folic acid for≥3 months before pregnancy increases the risk of GDM,but reduces the risk of SGA birth in patients with GDM.Supplementing folic acid during pregnancy for≥3 months has a reducing effect on the risk of adverse perinataloutcomes of cesarean section and macrosomia in women with GDM.
10.The Relationship between the Duration of Folic Acid Supplementation,Gesta-tional Diabetes Mellitus and Adverse Perinatal Outcomes
Jinyi WANG ; Chunxing MA ; Yueyue GAO ; Yaming ZHANG ; Fengying WANG ; Xuntao LIU ; Yunchun LIU
Journal of Practical Obstetrics and Gynecology 2024;40(8):664-669
Objective:To investigate the relationship between the duration of folic acid supplementation,gesta-tional diabetes mellitus(GDM)and adverse perinatal outcomes based on generalized linear mixed model.Meth-ods:Clinical data was collected of 759 pairs of mothers and children who delivered at the First Affiliated Hospital of Hebei North University from January 2021 to December 2022.The adverse perinatal outcomes of this study in-cluded cesarean section,premature birth,macrosomia,low birth weight(LBW),large for gestational age(LGA),and small for gestational age infant(SGA).Generalized linear mixed model was used to analyze the impact of GDM and supplementation with folic acid for a duration of ≥3 months on the risk of adverse perinatal outcomes.A stratified analysis of the duration of folic acid supplementation was conducted to determine whether it was a con-founding factor or influencing factor of GDM and adverse birth outcomes.Results:A total of 748 patients(98.55%)received folic acid supplementation before and during pregnancy,with a total of 743 patients(97.89%)receiving folic acid supplementation during pregnancy and 496 patients(65.35%)receiving folic acid supplementation before pregnancy.77 mothers were diagnosed with GDM,with an incidence rate of 10.14%.Compared with those who received folic acid supplementation before pregnancy for<3 months,those who re-ceived folic acid supplementation before pregnancy for ≥ 3 months were associated with an increased risk of GDM.The adjusted RR(aRR)was 1.72(95%CI 1.17-2.53).The GDM patients who received folic acid sup-plementation for≥3 months before pregnancy was associated with a reduced risk of SGA,with an aRR of 0.40(95%CI 0.18-0.89).In the subgroup of pregnant women who received folic acid supplementation for≥3 months,GDM was associated with an increased risk of cesarean section(aRR 1.36,95%CI 1.06-1.75))and macrosomia(aRR2.11,95%CI 1.06-4.20),but both aRR were lower than fixed effect RR of 1.53(95%CI 1.01-2.34)and 2.43(95%CI 12.7-4.66),respectively.and the above differences were statistically signifi-cant(P<0.01).Conclusions:Supplementing folic acid for≥3 months before pregnancy increases the risk of GDM,but reduces the risk of SGA birth in patients with GDM.Supplementing folic acid during pregnancy for≥3 months has a reducing effect on the risk of adverse perinataloutcomes of cesarean section and macrosomia in women with GDM.

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