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.

OBJECTIVE To explore the protective effect and mechanism of Longshengzhi capsules on cerebral ischemia- reperfusion injury in rats. METHODS The model of middle cerebral artery occlusion （MCAO） was established by using the improved thread occlusion method. The experiment was divided into six groups： sham surgery group （only separating blood vessels without inserting thread plugs， given the same volume of normal saline）， model group （modeling， given the same volume of normal saline）， nimodipine group （positive control， modeling， dose of 20 mg/kg）， and low-dose， medium-dose， and high-dose groups of Longshengzhi capsules （modeling， doses of 0.72， 1.44 and 2.88 g/kg， respectively）， with 10 mice in each group. Each group was given corresponding medication solution/normal saline by gavage， once a day， for 7 consecutive days. One hour after the last administration， the Zea Longa scoring method was used to score the neurological deficits in each group of rats， and the ABC enzyme-linked immunosorbent assay was used to detect the serum levels of tumor necrosis factor-α （TNF-α） and interleukin-6 （IL-6） in rats； TTC staining was used to observe the volume of cerebral infarction in rats and calculate the cerebral infarction volume ratio. Hematoxylin eosin staining was used to observe the pathological changes in the brain tissue of rats. Immunohistochemical staining was used to detect the positive expression of NLRP3 protein in the brain tissue of rats. Real-time fluorescence quantitative PCR was used to detect mRNA relative expressions of Toll-like receptor 4 （TLR4） and nuclear factor-κB （NF-κB） in the brain tissue of rats. Western blot assay was adopted to detect the relative expressions of TLR4， NLRP3 and phosphorylated NF-κB （p-NF-κB） protein in the brain tissue of rats and its intracellular NF-κB protein. RESULTS Compared with the sham surgery group， the neural dysfunction score， serum levels of TNF-α and IL-6， cerebral infarction volume ratio， relative expression levels of NF-κB and TLR4 mRNA， as well as protein relative expressions of TLR4， NLRP3 and p-NF-κB in the brain tissue， and relative protein expression of intracellular NF-κB were increased significantly in the model group （P＜0.01）； the enlarged gap and significant edema were observed in cortical nerve cells of brain tissue in rats， with a large amount of inflammatory cell infiltration； the positive expression of NLRP3 protein in brain tissue of rats obviously increased. Compared with the model group， the levels of the above indicators in the medium-dose and high-dose groups of Longshengzhi capsules， as well as the Nimodipine group， were reversed to varying degrees， and most differences were statistically significant （P＜0.05 or P＜0.01）； the pathological morphology observation showed a significant improvement， and the positive expression of NLRP3 protein in the brain tissue of rats was obviously reduced. CONCLUSIONS Longshengzhi capsules may inhibit TLR4/NF-κB/NLRP3 signaling pathway and neuroinflammatory response， thereby achieving a protective effect against cerebral ischemia-reperfusion injury in rats.

Objective: To understand current situation epidemiology and associated factors of suicidal ideation among high school students in Yixing, so as to provide basis for targeted intervention. Methods: From March to May 2019, a questionnaire survey was conducted on 12 799 students from 3 junior high schools and 4 senior high schools in Yixing City, Jiangsu Province, using a stratified cluster random sampling method. Latent profile analysis was used to classify suicidal ideation among high school students, the chi square test was used to compare the differences in suicidal ideation among different characteristics of students, multiple Logistic regression was used to analyze influencing factors, a risk predictive nomogram model was constructed and then verified. Results: Three latent classes of suicidal ideation among high school students was divided into three categories were observed: none or mild, moderate, and severe. Among them, 3 034 (23.7%) had moderate suicidal ideation and 753 (5.9%) had severe suicidal ideation. The Logistic regression results showed that gender was female, academic performance was lower midrange, smoking, drinking, popularity with classmates(less popular and unpopularity), family member relationships(general/occasional contradictions/contradictions), trust in others(more trusted/less trusted/less trusted at all), past or current relationships, physical bullying, relationship bullying, verbal bullying, and sexual bullying were the influencing factors for severe suicidal ideation among students ( OR =3.27； 2.18 ；1.63；1.72；2.66, 6.05；3.00,3.29, 6.38；1.71, 6.04, 12.48； 2.50； 1.59； 2.16； 1.45； 1.63, P <0.05). The nomogram prediction model had good discrimination. Conclusions Suicide ideation is influenced by multiple factors. Family and peer situations, as well as being bullied, are all related to the degree the severity of suicidal ideation. Efforts can be made to improve students family and interpersonal relationships, control bullying, then reduce their suicidal ideation which might help prevent suicide ideation among students.

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.

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.

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.

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.

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.

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.

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.