1.Effect and mechanism of Erastin on ferroptosis of acute myeloid leukemia cells
Xiandong Jiang ; Yingying Huang ; Xiaoying Hong ; Xindi Lin ; Donghong Lin ; Liping Lin
Acta Universitatis Medicinalis Anhui 2025;60(1):15-21
Objective :
To explore the role of lysophosphatidylcholine acyltransferase 3(LPCAT3) in Erastin-induced ferroptosis of acute myeloid leukemia(AML) cells and its related molecular regulatory mechanisms.
Methods :
Tetrazolium salt(MTS) method was used to detect the sensitivity of different AML cells to the classic ferroptosis inducer Erastin, real time quantitative polymerase chain reaction(qPCR) was used to detect the basal expression level ofLPCAT3mRNA, and the correlation between them was analyzed. Lentivirus-mediatedLPCAT3overexpression AML cell lines(OE group) and negative control lines(NC group) were constructed. After Erastin intervention, MTS, flow cytometry, and micromethods were used to detect cell viability, lipid reactive oxygen species(ROS), and Malondialdehyde(MDA), respectively. qPCR and Western blot were used to detect unfolded protein response(UPR) classic pathway signaling molecules(PERK, ATF4, GRP78, etc.) expression levels. The above ferroptosis-related indicators were detected after combined intervention with the UPR inhibitor 4-phenylbutyric acid(4-PBA), and the regulatory relationship was analyzed.
Results :
Four different types of AML cells had different sensitivities to ferroptosis, among which K562 cells were relatively insensitive. The IC50of the four types of AML cells to Erastin was negatively correlated with the expression level ofLPCAT3(r=-0.919,P<0.001). After Erastin intervention, the cell viability of K562 cells in the OE group was significantly inhibited by Erastin compared with the NC group(P<0.001), and the levels of lipid ROS and MDA increased(P<0.001). The results of qPCR and Western blot showed that, compared with the NC group, the mRNA and protein expression of UPR classic pathway moleculesPERK,ATF4, andGRP78mRNA and protein increased in the OE group(P<0.01). After inhibiting the UPR pathway by 4-PBA, the viability of K562 cells decreased(P<0.01), and lipid ROS and MDA levels increased(P<0.01) compared with the uninhibited state.
Conclusion
Overexpression ofLPCAT3can promote ferroptosis in K562 cells, and this process is negatively regulated by the classical UPR pathway PERK/ATF.
2.The Effects of Tai Chi Training on Bone Density,Bone Turnover Markers,and Heart Rate Variability in High-Risk Osteoporosis Population
Jiaming LIN ; Chao LI ; Wei ZHAO ; Jun ZHOU ; Xiaoying CHEN ; Xiangyu XI ; Haijun HE ; Baohong MI ; Yuefeng CHEN ; Weiheng CHEN
Journal of Traditional Chinese Medicine 2025;66(15):1566-1571
ObjectiveTo explore the effects of the Tai Chi training on bone density, bone turnover markers, and heart rate variability for people with high-risk osteoporosis, and to provide evidence for the prevention of osteoporosis at early stage. MethodsSixty-six cases of people with high risk of osteoporosis were included, and they were divided into 33 cases each in the intervention group and the control group using the random number table method. The control group received osteoporosis health education three times a week, and the intervention group received Tai Chi training under the guidance of a trainer three times a week for 40 mins each time on the basis of the control group, and both groups were intervened for 12 weeks. Dual-energy X-ray absorptiometry was used to measure the bone density of L1~L4 vertebrae, bilateral femoral necks and bilateral total hips in the two groups before and after the intervention; enzyme-linked immunosorbent assay was used to determine bone turnover markers before and after the intervention, including pro-collagen type Ⅰ pro-amino-terminal prepropyl peptide (P1NP) and β-collagen type Ⅰ cross-linking carboxy-terminal peptide (β-CTX). Seven cases with good compliance in the intervention group were selected. After wearing the heart rate sensor, they successively performed Tai Chi training and walking activities recommended by the guideline for 20 mins each, and the heart rate variability (HRV) during exercise was collected, including time-domain indexes such as standard deviation of normal sinus intervals (SDNN), root-mean-square of the difference between adjacent RR intervals (RMSSD), frequency-domain metrics such as low-frequency power (LF), high-frequency power (HF), and low-frequency/high-frequency power ratio (LF/HF), as well as nonlinear metrics such as approximate entropy (ApEn), sample entropy (SampEn). ResultsFinally, 63 cases were included in the outcome analysis, including 30 cases in the intervention group and 33 cases in the control group. After the intervention, the differences of L1~L4 vertebrae, bone density of bilateral femoral neck and bilateral total hip in the intervention group were not statistically significant when compared with those before intervention (P>0.05), while the bone density of all parts of the control group decreased significantly compared with that before intervention (P<0.05), and the difference in the bone density of the L1~L4 vertebrae, bilateral femoral neck, and the right total hip before and after the intervention of the intervention group was smaller than that of the control group (P<0.05). The differences in P1NP and β-CTX between groups before and after intervention was not statistically significant (P>0.05). Compared with walking exercise, LF decreased, HF increased and LF/HF decreased during Tai Chi exercise (P<0.05); the time domain indexes and non-linear indexes between groups had no statistically significant difference (P>0.05). ConclusionTai Chi exercise can maintain lumbar, hip, and femoral bone density and improve sympathetic/parasympathetic balance in people at high risk for osteoporosis, but cannot significantly improve bone turnover markers.
3.Comparing the effects of dual-task training and single-task training on walking, balance and cognitive functions in individuals with Parkinson’s disease: A systematic review
Xiaoying LIN ; Yanming ZHANG ; Xiaowei ZHANG ; Xi CHEN ; Jianhua LIU ; Lei YANG ; Pang Marco Yiu Chung
Chinese Medical Journal 2024;137(13):1535-1543
Background::This systematic review aimed to examine whether dual-task (DT) training was superior to single-task (ST) training in improving DT walking, balance and cognitive functions for individuals with Parkinson’s disease (PD).Methods::Literature search was performed in the following electronic databases: PubMed, the Cochrane Library, Web of Science, and Metstr covering inception to May 10, 2023. And in order to facilitate comparison across trials, we calculated the effect size (Hedges’ g) of gait, balance, cognitive, and other parameters under both ST and DT conditions, using the mean change score and standard deviation (SD) of change score of the experimental and control groups. Randomized controlled trials that examined the effects of DT motor and cognitive training in individuals with Parkinson’s disease were included for this systematic review.Results::A total of 214 participants recruited from six articles (actually five trials) were involved in this review. In terms of walking ability, only double support time and stride time variability showed significant between-group difference (Hedges’ g = 0.34, 0.18, respectively). Compared to ST training group, DT training group had a more improvement effect in laboratory balance measurement (Hedges’ g = 0.18, 1.25), but no significant improvement in clinical balance measurement. No significant between-group differences were observed, thus its training effect on cognitive function was inconclusive.Conclusions::The DT training failed to achieve promising results better than ST training in improving DT walking and balance functions for individuals with PD. Any firm conclusion cannot be drawn at present, due to the limited number of eligible publications. Larger sample size and high-quality studies are needed to investigate the effectiveness of DT training in individuals with PD.
4.IFN-β inhibits proliferation and promotes apoptosis of AML cells by STAT1-induced SARI
Yanfeng LIN ; Xiaoying HONG ; Yingying HUANG ; Xiaohua WANG ; Wei WU ; Donghong LIN ; Yan XUE
Chinese Journal of Immunology 2024;40(6):1137-1141
Objective:To investigate effect of SARI expression induced by IFN-β on proliferation and apoptosis of acute myelo-blastic leukemia(AML)cells,and to explore its potential regulatory molecules.Methods:qPCR and Western blot were used to screen AML cells with low SARI expression as experimental cell lines.AML cells were treated with different concentrations of IFN-β,and expression of SARI was detected by qPCR and Western blot at different time to select appropriate concentration and time of IFN-β.RNA-Seq transcriptome sequencing and KEGG enrichment analysis were used to preliminarily screen potential regulatory molecules of IFN-β-induced SARI expression in AML cells.AML cells were treated with corresponding molecular inhibitors combined with IFN-β,cell proliferation was detected by MTS assay,and apoptosis was detected by flow cytometry.To clear this molecule was involved in IFN-β-induced SARI expression on AML cell proliferation and apoptosis.Results:SARI expression in HL60 and NB4 cells were rela-tively decreased,so they were selected as experimental cell lines.After treatment with 1 ng/ml IFN-β for 12 h,SARI expression in AML cells was increased,cell proliferation was inhibited and apoptosis were increased.STAT1 was screened as a potential regulatory mole-cule for IFN-β-induced SARI expression.After inhibiting STAT1,effects of IFN-β on SARI expression,proliferation inhibition and apop-tosis promotion of AML cells were reversed significantly.Conclusion:IFN-β can promote SARI expression in AML cells by STAT1,in-hibit cell proliferation and promote apoptosis.
5.Correlation of fibroblast growth factor 23 with insulin resistance and sex hormone levels in patients with polycystic ovary syndrome
Yu LI ; Zixuan TANG ; Qi HUANG ; Xiaoying YUAN ; Qian WANG ; Lin ZHANG ; Han ZHANG ; Ying ZHANG ; Yachao BA ; Dingyan LUO ; Jiaoyang FENG ; Xin LIAO
Chinese Journal of Endocrinology and Metabolism 2024;40(6):475-480
Objective:To investigate the association of serum fibroblast growth factor 23(FGF23) level with insulin resistance(IR) and sex hormone levels in patients with polycystic ovary syndrome(PCOS).Methods:A retrospective study was performed in eighty-seven patients with PCOS, fifty-seven patients with simple IR, and sixty-one healthy women who were admitted to Affiliated Hospital of Zunyi Medical University during October 2021 and November 2022. According to the homeostasis model assessment-IR index, all subjects were divided into normal control group( n=61), IR group( n=57), PCOS without IR group(PCOS group, n=15), and PCOS+ IR group( n=72). The levels of serum FGF23, adiponectin, and sex hormones in all groups were compared, and their correlations with glucose and lipid metabolism indicators were analyzed. Results:The FGF23 level was significantly elevated in the IR group, while markedly reduced in the PCOS group and PCOS+ IR group, with the PCOS group showing a significantly lower concentration. The adiponectin levels were significantly decreased in the IR group, PCOS group, and PCOS+ IR group(all P<0.05). The correlation analysis showed that FGF23 level was positively correlated with adiponectin and sex hormone binding globulin, and negatively correlated with luteinizing hormone, luteinizing hormone/follicle stimulating hormone, and free testosterone index(all P<0.05). Logistic regression results indicated that both FGF23 and adiponectin could be used as good indicators for the diagnosis of PCOS and PCOS with IR(all P<0.05). Conclusion:FGF23 is closely related to IR and androgen as well, and under certain conditions, it can reflect the severity of IR and hyperandrogenemia in PCOS patients. The cutoff value of FGF23 obtained in this study can provide a good reference for the diagnosis of PCOS diseases.
6.Efficacy and safety of tirzepatide for weight reduction in Chinese adults with overweight/obesity: A randomized clinical trial
Lin ZHAO ; Zhifeng CHENG ; Yibing LU ; Ming LIU ; Hong CHEN ; Min ZHANG ; Rui WANG ; Yuan YUAN ; Xiaoying LI
Chinese Journal of Endocrinology and Metabolism 2024;40(8):637-640
This article introduces a recent paper published in JAMA titled " Tirzepatide for weight reduction in Chinese adults with obesity: The SURMOUNT-CN randomised clinical trial". The paper details the design, results, and implications of a randomized controlled clinical study of the efficacy and safety of tirzepatide in overweight/obese adults in China(SURMOUNT-CN). This study represents the first Chinese evidence supporting tirzepatide for the treatment of obesity, offering a potent therapeutic option for the prevention and treatment of obesity and weight-related comorbidity.
7.Metabolomic characteristics of amniotic fluid in fetal growth restriction
Cheng HUANG ; Xiaoying LIN ; Xiaojuan FU ; Jiaxue WEI
Chinese Journal of Perinatal Medicine 2024;27(11):923-931
Objective:To investigate the metabolomic characteristics of amniotic fluid in pregnant women with fetal growth restriction (FGR) by targeted metabolomics, identify differential metabolites with biomarker potential, analyze metabolic pathways, and provide metabolic clues for the study of FGR pathogenesis.Methods:From June 2020 to November 2023, amniotic fluid samples were prospectively collected from 19 FGR fetuses (FGR group) and 30 normal-weight fetuses (control group) at the Affiliated Guangdong Second Provincial General Hospital of Jinan University. Targeted metabolomic analysis of amniotic fluid samples (taken at 16-32 gestational weeks) was performed using liquid chromatography- tandem mass spectrometry. Cluster analysis and multivariate statistical analysis were used to analyze the differences in metabolic profiles between the FGR and control groups. Metabolic pathway enrichment analysis was conducted using metabolomics databases, and potential biomarkers were identified using receiver operating characteristic (ROC) curve analysis.Results:A total of 16 differential metabolites were identified between the FGR and control groups, including gallic acid, 6-hydroxy-nicotinic-acid, 2-methyl-valeric-acid, undecanoic acid, trimethylamine, γ-linolenic acid, decanoylcarnitine, α-linolenic acid, 4-ethyl-caprylic-acid, oleic acid, O-hexyl carnitine, L-theanine,turanose, 4-hydrocinnamic acid, L-aspartic acid, and 3-methyl-valeric-acid. These metabolites were involved in metabolic pathways such as unsaturated fatty acid biosynthesis, niacin and nicotinamide metabolism, carbon metabolism, and fatty acid biosynthesis. ROC curve analysis of the 16 differential metabolites revealed that nine had an area under the ROC curve (AUC)>0.7, including oleic acid (AUC= 0.851, 95% CI: 0.737-0.965), α-linolenic acid (AUC=0.798, 95% CI: 0.664-0.933), 4-hydrocinnamic acid (AUC=0.756, 95% CI: 0.619-0.895), L-aspartic acid (AUC=0.747, 95% CI: 0.595-0.900), 4-ethyl-caprylic- acid (AUC=0.746, 95% CI: 0.610-0.881), O-hexyl carnitine (AUC=0.746, 95% CI: 0.610-0.881), decanoylcarnitine (AUC=0.735, 95% CI: 0.589-0.881), turanose (AUC=0.735, 95% CI: 0.589-0.882), and 2-methyl-valeric-acid (AUC=0.725, 95% CI: 0.577-0.872), indicating their potential as biomarkers. Conclusions:FGR fetuses exhibit significant differences in metabolites, involving fatty acids and amino acids related to hypoxic stress and inflammatory responses. Oleic acid and other metabolites can serve as potential biomarkers related to the growth and development of FGR fetuses.
8.Investigation and Analysis of the Establishment of Pharmaceutical Service Fees in Hospitals of Shaanxi Province
Qian LIU ; Biqi REN ; Jiang NIU ; Shuzhi LIN ; Shuang LEI ; Wei LIU ; Xiaoying ZHU ; Lin YIN ; Bianling FENG
Herald of Medicine 2024;43(9):1416-1422
Objective To investigate the current awareness of pharmaceutical service fees among pharmacists in hospitals of Shaanxi province to provide a theoretical basis and decision-making framework for establishing such fees in hospitals of various provinces and cities in the future.Methods A questionnaire survey was conducted among 47 representative hospitals and 53 pharmacists within these hospitals in Shaanxi province.The results were analyzed using differential analysis.Results In most hospitals of Shaanxi province,pharmaceutical services are not provided or not charged for,indicating a lack of practical experience in the establishment of pharmaceutical service fees.Among hospitals that provide and charge for pharmaceutical services,there remains a need for uniformity in specific service content and fee standards,clear regulatory policy support,and a unified evaluation system.Significant differences exist among hospitals of different levels and types in terms of their capacity to provide pharmaceutical services and the forms in which they are offered.There is inconsistency among pharmacists within hospitals regarding crucial aspects of establishing pharmaceutical service fees,and further enhancement is needed in their awareness of relevant policies and the latest guidelines.Conclusions There is considerable room for improvement in establishing pharmaceutical service fees in hospitals of Shaanxi province.Stakeholders should promptly establish and standardize the fee establishment model,differentiate the fee standards for various services,enhance the publicity and dissemination of relevant document requirements to support the smooth implementation of pharmaceutical service fee policies.
9.Contrast-Enhanced Ultrasound Evaluation of Muscle Microcirculation Around Zusanli Point in Acupuncture
Zhenhong XU ; Piaopiao LIU ; Xiaoying WANG ; Zecheng WANG ; Guorong LV ; Yufen LIN ; Jiaxiang WU
Chinese Journal of Medical Imaging 2024;32(7):726-730
Purpose To explore the application of contrast-enhanced ultrasound in evaluating the local muscle microcirculation before and after acupuncture at Zusanli point in normal people.Materials and Methods A total of 72 healthy volunteers who visited the Department of Ultrasound,the Second Affiliated Hospital of Fujian Medical University from September 2018 to May 2020 were prospectively collected,all subjects performed ultrasound contrast before acupuncture,acupuncture with strongest deqi,and two hours after acupuncture to observe the blood flow perfusion of the microvessels in the tibialis anterior muscle.The pre-selected areas of interest the small arteries,muscle tissues and venules in the middle were analyzed to obtain the time-intensity curve and contrast transit time(CTTs)perfusion parameters.Needle sensation was evaluated using objective scoring criteria for acupuncture combined with moxibustion recipients.Gastrin,plasma gastrin,cholecystokinin,and secretin were measured in all subjects before acupuncture,when acupuncture had the strongest deqi,and two hours after acupuncture.Results ①CTTs of arterial-muscle,muscle-venous and arterial-venous of the tibialis anterior muscle at acupuncture with strongest deqi were significantly shorter than those at before acupuncture and two hours after acupuncture(all P<0.001),and there was no significant difference in CTTs before and after acupuncture and moxibustion(P>0.05);②when acupuncture deqi was strongest,serum gastrin,plasma prokinetics,cholecystokinin,and secretin were significantly increased compared with those before acupuncture and two hours after acupuncture,with statistically significant difference(all P<0.001),while there was no significant difference in these parameters between before acupuncture and two hours after acupuncture(P>0.05);③when acupuncture had the strongest deqi,there were positive correlations between gastrin,plasma prokinetic hormone,cholecystokinin,and secretin values and CTTs of arterial-muscle,muscle-venous,and arterial-venous(r=0.360-0.702,P<0.001).Conclusion Acupuncture of the Zusanli,when it gains the strongest deqi,can cause changes in the microcirculation around the skeletal muscle,leading to a significant shortening of CTTs,and also promotes the secretory function of the gastrointestinal tract.
10.Effects of different polymers on biomimetic mineralization of small intestine submu-cosal scaffolds
Xiaoying CHEN ; Yi ZHANG ; Yuke LI ; Lin TANG ; Yuhua LIU
Journal of Peking University(Health Sciences) 2024;56(1):17-24
Objective:To explore the effects of different polymers on in vitro biomimetic mineralization of small intestinal submucosa(SIS)scaffolds,and to evaluate the physicochemical properties and bio-compatibility of the SIS scaffolds.Methods:The SIS scaffolds prepared by freeze-drying method were im-mersed in simulated body fluid(SBF),mineralized liquid containing polyacrylic acid(PAA)and mine-ralized liquid containing PAA and polyaspartic acid(PASP).After two weeks in the mineralized solu-tion,the liquid was changed every other day.SBF@SIS,PAA@SIS,PAA/PASP@SIS scaffolds were ob-tained.The SIS scaffolds were used as control group to evaluate their physicochemical properties and bio-compatibility.We observed the bulk morphology of the scaffolds in each group,analyzed the microscopic morphology by environment scanning electron microscopy and determined the porosity and pore size.We also analyzed the surface elements by energy dispersive X-ray spectroscopy(EDX),analyzed the struc-ture of functional groups by Flourier transformed infrared spectroscopy(FTIR),detected the water ab-sorption rate by using specific gravity method,and evaluated the compression strength by universal me-chanical testing machine.The pro-cell proliferation effect of each group of scaffolds were evaluated by CCK-8 cell proliferation method.Results:Under scanning electron microscopy,the scaffolds of each group showed a three-dimensional porous structure with suitable pore size and porosity,and crystal was observed in all the mineralized scaffolds of each group,in which the crystal deposition of PAA/PASP@SIS scaffolds was more regular.At the same time,the collagen fibers could be seen to thicken.EDX analysis showed that the characteristic peaks of Ca and P were found in the three groups of mineralized scaffolds,and the highest peaks were found in the PAA/PASP@SIS scaffolds.FTIR analysis proved that all the three groups of mineralized scaffolds were able to combine hydroxyapatite with SIS.All the scaf-folds had good hydrophilicity.The compressive strength of the mineralized scaffold in the three groups was higher than that in the control group,and the best compressive strength was found in PAA/PASP@SIS scaffold.The scaffolds of all the groups could effectively adsorb proteins,and PAA/PASP@SIS group had the best adsorption capacity.In the CCK-8 cell proliferation experiment,the PAA/PASP@SIS scaffold showed the best ability to promote cell proliferation with the largest number of living cells observed.Con-clusion:Compared with other mineralized scaffolds,PAA/PASP@SIS scaffolds prepared by mineralized solution containing both PAA and PASP have better physicochemical properties and biocompatibility and have potential applications in bone tissue engineering.


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