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.Lone-Star perineal exposure technique in abdominoperineal resection for rectal cancer
Jun MA ; Daibin TANG ; Chunxia ZHAO ; Yaming ZHANG ; Bin GAO
International Journal of Surgery 2024;51(9):627-631
Objective:To analyse the clinical application value of Lone-Star perineal exposure technique in performing abdominal perineal resection (APR).Methods:Conducted a retrospective review of 17 rectal cancer patients, including 13 males, 4 females, aged from 44 to 82 years old, with the average age of (67.6±9.7) years who underwent APR at Anqing Municipal Hospital from January 2020 to July 2024. The Lone-Star retractor-assisted (LSR) exposure method was employed for the perineal operation. After incising the skin and subcutaneous tissue, a Lone-Star retractor was utilized, with eight small hooks used to extend the incision in multiple directions, facilitating the release of deep tissues. The hooks were dynamically adjusted to optimize surgical field exposure.Results:All 17 patients were successfully underwent laparoscopic-assisted APR. Fifteen operations were independently performed by a single surgeon, while 2 required assistance for intraoperative arterial hemostasis. No perforations occurred, and all specimens had a negative circumferential resection margin (CRM). Postoperative complications were observed in 4 patients, including urinary retention in one, pulmonary infection in one, wound seroma in one, and stoma mucosal detachment in one, all of which were classified as Clavien-Dindo grade 3 or lower and cured.Conclusions:The LSR exposure technique may significantly improve perineal exposure during APR for rectal cancer. It could potentially enhance intraoperative safety and efficiency, and facilitate single-operator surgery.
3.Latent classes and associated factors of suicidal ideation among high school students
Chinese Journal of School Health 2024;45(1):66-71
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 midrange, 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.
4.Protective effect and mechanism of Longshengzhi capsules on cerebral ischemia-reperfusion injury in rats
Huanle FANG ; Xiaoming LI ; Yaming ZHOU ; Xin ZHANG ; Xiaoxi LIU ; Yanbin CHEN
China Pharmacy 2024;35(7):813-818
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.
5.Distribution of potential suitable habitats for Ixodes persulcatus in Heilongjiang Province based on the maximum entropy model
Yue WANG ; Yaming ZHANG ; Shuang YUAN ; Yang DING ; Xin GUAN ; Shengnan GAO ; Guangping SONG ; Lei TANG
Chinese Journal of Endemiology 2024;43(11):885-890
Objective:To investigate the distribution of potential suitable habitats for Ixodes persulcatus in Heilongjiang Province during different climatic periods. Methods:The geographical location data of Ixodes persulcatus in Heilongjiang Province from 1980 to 2023 were collected through literature search and field ecological investigation. The environmental factor variables were downloaded from the WorldClim website and the Resource and Environmental Science and Data Platform. A combination of SDMtune, ENMTools packages, and the maximum entropy (MaxEnt) model were used to predict the potential habitats of Ixodes persulcatus in Heilongjiang Province during different climatic periods and determine its dominant environmental factors. Among them, the time range of historical climatic period data was 1970 - 2000. The future climatic period data (2021 - 2040, 2041 - 2060) were selected as the low forcing scenario (SSP126 scenario) of the shared socioeconomic pathways (SSP) in the Beijing Climate Center - Climate System Model version 2-Medium Resolution, to simulate the impact of global warming on the distribution of potential habitats for Ixodes persulcatus in Heilongjiang Province. Results:A total of 83 geographical distribution sites of Ixodes persulcatus in Heilongjiang Province were obtained. After screening, 10 environmental factors were included in the MaxEnt model. Among them, the cumulative contribution percentage of annual precipitation, average annual temperature, and vegetation type was 67.3%. Compared with historical climatic period, the total potential habitats of Ixodes persulcatus in Heilongjiang Province increased from 29.81 × 10 4 km 2 to 32.24 × 10 4 km 2 in 2041 - 2060. The center of potential habitats moved to 47.75° N, and 128.66° E, with a northwest offset of 126.07° and a migration distance of 45.83 km. Conclusion:With global climate warming, the total potential habitats of Ixodes persulcatus in Heilongjiang Province has increased, showing an overall trend of migration to the northwest.
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.Effect of Naples prognostic score on prognosis of hepatocellular carcinoma patients undergoing hepatectomy
Yaming XIE ; Lei LIANG ; Zunqiang XIAO ; Junwei LIU ; Chengwu ZHANG ; Dongsheng HUANG
Chinese Journal of Hepatobiliary Surgery 2024;30(5):341-346
Objective:To assess the impact of preoperative Naples prognostic score on the prognosis of patients with hepatocellular carcinoma (HCC) after hepatic resection.Methods:Retrospective analysis was conducted on the data of 323 patients with HCC who underwent radical hepatectomy in Zhejiang Provincial People's Hospital from January 2012 to December 2017, including 281 males and 42 females, aged (56.6±11.3) years. All patients were divided into three groups according to their preoperative Naples prognostic scores: group A (0) ( n=37), group B (1-2) ( n=193), group C (3-4) ( n=93). Survival was analysed by the Kaplan-Meier method, and differences in survival were compared by the log-rank test. Univariate and multivariate Cox regression were used to analyse the effect of Naples prognostic score on prognosis. Results:The 1-, 3- and 5-year cumulative survival rates of HCC patients after hepatectomy were 91.9%, 78.4% and 68.3% in the A group, 89.1%, 76.1% and 64.4% in the B group, and 84.9%, 63.3% and 43.5% in the C group, respectively, and the cumulative survival rates showed a decreasing trend among the three groups, and the differences were statistically significant (all P<0.05). The recurrence-free survival rates at 1, 3 and 5 years after hepatectomy were 93.4%, 63.3% and 44.3% in the A group, 77.7%, 46.5% and 35.6% in the B group, and 64.1%, 41.1% and 28.2% in the C group, respectively, and the recurrence-free survival rates showed a decreasing trend among the three groups, and the differences were statistically significant (all P<0.05). On Cox multivariate analysis, patients with HCC of 3-4 had a higher risk of death after hepatic resection than those patients of 0 ( HR=2.011, 95% CI: 1.048-3.859, P=0.036), and the risk of postoperative recurrence was also higher than those patients of 0 ( HR=1.820, 95% CI: 1.081-3.066, P=0.024). Conclusion:Preoperative Naples prognostic score performs as a prognostic influence factor on survival and recurrence-free survival after hepatectomy in patients with HCC.
8.Metformin ameliorates PM2.5-induced functional impairment of placental trophoblasts by inhibiting ferroptosis
Shuxian LI ; Shuping YU ; Yaming MU ; Kai WANG ; Yu LIU ; Meihua ZHANG
Journal of Southern Medical University 2024;44(3):437-446
Objective To investigate the protective effect of metformin against PM2.5-induced functional impairment of placental trophoblasts and explore the underlying mechanism.Methods Sixteen pregnant Kunming mice were randomly assigned into two groups(n=8)for intratracheal instillation of PBS or PM2.5 suspension at 1.5,7.5,and 12.5 days of gestation.The pregnancy outcome of the mice was observed,and placental zonal structure and vascular density of the labyrinth area were examined with HE staining,followed by detection of ferroptosis-related indexes in the placenta.In cultured human trophoblasts(HTR8/SVneo cells),the effects of PM2.5 exposure and treatment with metformin on cell viability,proliferation,migration,invasion,and tube formation ability were evaluated using CCK8 assay,EDU staining,wound healing assay,Transwell experiment,and tube formation experiment;the cellular expressions of ferroptosis-related proteins were analyzed using ELISA and Western blotting.Results M2.5 exposure of the mice during pregnancy resulted in significantly decreased weight and number of the fetuses and increased fetal mortality with a reduced placental weight(all P<0.001).PM2.5 exposure also caused obvious impairment of the placental structure and trophoblast ferroptosis.In cultured HTR8/SVneo cells,PM2.5 significantly inhibited proliferation,migration,invasion,and angiogenesis of the cells by causing ferroptosis.Metformin treatment obviously attenuated PM2.5-induced inhibition of proliferation,migration,invasion,and angiogenesis of the cells,and effectively reversed PM2.5-induced ferroptosis in the trophoblasts as shown by significantly increased intracellular GSH level and SOD activity,reduced MDA and Fe2+ levels,and upregulated GPX4 and SLC7A11 protein expression(P<0.05 or 0.01).Conclusion PM2.5 exposure during pregnancy causes adverse pregnancy outcomes and ferroptosis and functional impairment of placental trophoblasts in mice,and metformin can effectively alleviate PM2.5-induced trophoblast impairment.
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.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.


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