1.Rehmanniae Radix Praeparata Improves Neurological Function of Ischemic Stroke Rats by Inhibiting Autophagy and Ferroptosis
Saifei LI ; Peipei YUAN ; Yaxin WEI ; Liyuan GAO ; Panying LI ; Yuan RUAN ; Yi CHEN ; Yang FU ; Xiaoke ZHENG ; Weisheng FENG
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(8):26-33
ObjectiveTo investigate the effect of Rehmanniae Radix Praeparata on neurological function injury in ischemic stroke rats and explore its mechanism. MethodMale SD rats were randomized into sham operation, model, low- and high -dose (3.5 g·kg-1 and 7 g·kg-1) Rehmannia Radix Praeparata, and nimodipine (0.01 g·kg-1) groups. The rat model of middle cerebral artery occlusion (MCAO) was established with the modified suture occlusion method. Zea-Longa 5-point scoring was employed to evaluate the neurological function of rats. The cerebral infarction volume was detected by 2,3,5-triphenyltetrazolium chloride (TTC) staining. Hematoxylin-eosin staining and Nissl staining were employed to observe the morphology and damage of the brain tissue. Meanwhile, the serum levels of lactate dehydrogenase (LDH), oxidative stress-related indicators superoxide dismutase (SOD), glutathione peroxidase 4 (GPX4), and malondialdehyde (MDA), and the iron (Fe) content in the brain tissue were determined. To explore the mechanism of Rehmanniae Radix Preparata in mitigating the neurological damage in ischemic stroke rats, Western blotting was employed to determine the expression levels of proteins in the ischemic brain tissue. The autophagy-associated proteins included autophagy effector (beclin-1), microtubule-associated protein light chain 3 (LC3B), and ubiquitin-binding protein p62 (p62). The ferroptosis-associated proteins included transferrin (TF), transferrin receptor 1 (TFR1), ferritin heavy chain 1 (FTH1), and ferropotin (FPN1). The neurological function injury-associated proteins included brain-derived neurotrophic factor (BDNF) and tyrosine kinase receptor B (TrkB). ResultCompared with the sham operation group, the model group showed increased neurological function score, cerebral infarction volume, and appearance of nuclear pyknosis and vacuole of cells in the cerebral cortex. In addition, the model group presented elevated levels of LDH, MDA, and Fe (P<0.01) and lowered levels of SOD and GPX4 (P<0.01). Compared with the model group, Rehmanniae Radix Praeparata decreased the content of LDH, MDA, and Fe (P<0.05, P<0.01) and elevated the levels of SOD and GPX4 (P<0.05, P<0.01). Compared with the sham operation group, the modeling promoted the expression of beclin-1,LC3B Ⅱ/Ⅰ, TF, and TFR1 and inhibited the expression of p62, FTH1, FPN1, BDNF, and TrkB (P<0.01). The expression levels of these proteins were recovered after the treatment with Rehmanniae Radix Praeparata. ConclusionRehmanniae Radix Praeparata may inhibit ferroptosis and improve the neurological function in ischemic stroke rats by down-regulating the autophagy level in the brain tissue.
2.Effect of Different Endometrial Implantation Window Detection Methods on Pregnancy Outcome in Patients with Repeated Implantation Failure
Yanfei WANG ; Guangmei XIE ; Yuankun SANG ; Li WANG ; Ruoxin ZHU ; Jialing WANG ; Liyuan ZHANG ; Fan FENG
Journal of Practical Obstetrics and Gynecology 2024;40(5):381-385
Objective:To evaluate the endometrial implantation window in patients with recurrent implantation failure using endometrial receptive array(ERA)sequencing or endometrial histological detection methods,and to explore the effectiveness and cost-effectiveness analysis of two technologies for improving clinical outcomes in such patients.Methods:A retrospective cohort study was conducted on clinical data of 125 patients diagnosed with repeated implantation failure in Gansu Maternal and Child Health Hospital from January 2018 to December 2022.According to whether endometrial receptivity testing was accepted and different detection techniques were used,they were divided into a control group(n=36),a genomic group(n=35),and a histological group(n=54).The clinical data and pregnancy outcomes of the three groups were compared.Results:①The results of one-way ANOVA showed that the embryo implantation rate in the genomic group and histological group was significantly higher than that in the control group,and the difference was statistically significant(P<0.05).There was no sta-tistically significant difference in embryo implantation rate between genomic and histological groups(P=0.48).②There was no statistically significant difference in clinical pregnancy rate and live birth rate among the three groups(P>0.05).③Log rank test showed:The time for 50%of patients to reach live labor was significantly shorter than that of the control group,and the difference was statistically significant(P<0.05);There was no sta-tistically significant difference in the time to live birth in 50%of patients between the genomic and histological groups of 50%of patients(P>0.05).④The average number of embryos transferred in the control group was significantly higher than that in the genomic and histological groups,with statistical significance(P<0.05).The cost of genomic patients was significantly higher than that of histology group,and the difference was statistically significant(P<0.05).Conclusions:①Endometrial implantation window detection is feasible for patients with re-peated implantation failure,which can effectively shorten the time to live birth and reduce the number of transplan-ted embryos;②Both ERA sequencing and endometrial histology detection have limitations as methods to evaluate endometrial implantation window,and it is not clear which detection method has more advantages in accuracy and practicability.
3.Effect of Different Endometrial Implantation Window Detection Methods on Pregnancy Outcome in Patients with Repeated Implantation Failure
Yanfei WANG ; Guangmei XIE ; Yuankun SANG ; Li WANG ; Ruoxin ZHU ; Jialing WANG ; Liyuan ZHANG ; Fan FENG
Journal of Practical Obstetrics and Gynecology 2024;40(5):381-385
Objective:To evaluate the endometrial implantation window in patients with recurrent implantation failure using endometrial receptive array(ERA)sequencing or endometrial histological detection methods,and to explore the effectiveness and cost-effectiveness analysis of two technologies for improving clinical outcomes in such patients.Methods:A retrospective cohort study was conducted on clinical data of 125 patients diagnosed with repeated implantation failure in Gansu Maternal and Child Health Hospital from January 2018 to December 2022.According to whether endometrial receptivity testing was accepted and different detection techniques were used,they were divided into a control group(n=36),a genomic group(n=35),and a histological group(n=54).The clinical data and pregnancy outcomes of the three groups were compared.Results:①The results of one-way ANOVA showed that the embryo implantation rate in the genomic group and histological group was significantly higher than that in the control group,and the difference was statistically significant(P<0.05).There was no sta-tistically significant difference in embryo implantation rate between genomic and histological groups(P=0.48).②There was no statistically significant difference in clinical pregnancy rate and live birth rate among the three groups(P>0.05).③Log rank test showed:The time for 50%of patients to reach live labor was significantly shorter than that of the control group,and the difference was statistically significant(P<0.05);There was no sta-tistically significant difference in the time to live birth in 50%of patients between the genomic and histological groups of 50%of patients(P>0.05).④The average number of embryos transferred in the control group was significantly higher than that in the genomic and histological groups,with statistical significance(P<0.05).The cost of genomic patients was significantly higher than that of histology group,and the difference was statistically significant(P<0.05).Conclusions:①Endometrial implantation window detection is feasible for patients with re-peated implantation failure,which can effectively shorten the time to live birth and reduce the number of transplan-ted embryos;②Both ERA sequencing and endometrial histology detection have limitations as methods to evaluate endometrial implantation window,and it is not clear which detection method has more advantages in accuracy and practicability.
4.Effect of Different Endometrial Implantation Window Detection Methods on Pregnancy Outcome in Patients with Repeated Implantation Failure
Yanfei WANG ; Guangmei XIE ; Yuankun SANG ; Li WANG ; Ruoxin ZHU ; Jialing WANG ; Liyuan ZHANG ; Fan FENG
Journal of Practical Obstetrics and Gynecology 2024;40(5):381-385
Objective:To evaluate the endometrial implantation window in patients with recurrent implantation failure using endometrial receptive array(ERA)sequencing or endometrial histological detection methods,and to explore the effectiveness and cost-effectiveness analysis of two technologies for improving clinical outcomes in such patients.Methods:A retrospective cohort study was conducted on clinical data of 125 patients diagnosed with repeated implantation failure in Gansu Maternal and Child Health Hospital from January 2018 to December 2022.According to whether endometrial receptivity testing was accepted and different detection techniques were used,they were divided into a control group(n=36),a genomic group(n=35),and a histological group(n=54).The clinical data and pregnancy outcomes of the three groups were compared.Results:①The results of one-way ANOVA showed that the embryo implantation rate in the genomic group and histological group was significantly higher than that in the control group,and the difference was statistically significant(P<0.05).There was no sta-tistically significant difference in embryo implantation rate between genomic and histological groups(P=0.48).②There was no statistically significant difference in clinical pregnancy rate and live birth rate among the three groups(P>0.05).③Log rank test showed:The time for 50%of patients to reach live labor was significantly shorter than that of the control group,and the difference was statistically significant(P<0.05);There was no sta-tistically significant difference in the time to live birth in 50%of patients between the genomic and histological groups of 50%of patients(P>0.05).④The average number of embryos transferred in the control group was significantly higher than that in the genomic and histological groups,with statistical significance(P<0.05).The cost of genomic patients was significantly higher than that of histology group,and the difference was statistically significant(P<0.05).Conclusions:①Endometrial implantation window detection is feasible for patients with re-peated implantation failure,which can effectively shorten the time to live birth and reduce the number of transplan-ted embryos;②Both ERA sequencing and endometrial histology detection have limitations as methods to evaluate endometrial implantation window,and it is not clear which detection method has more advantages in accuracy and practicability.
5.Effect of Different Endometrial Implantation Window Detection Methods on Pregnancy Outcome in Patients with Repeated Implantation Failure
Yanfei WANG ; Guangmei XIE ; Yuankun SANG ; Li WANG ; Ruoxin ZHU ; Jialing WANG ; Liyuan ZHANG ; Fan FENG
Journal of Practical Obstetrics and Gynecology 2024;40(5):381-385
Objective:To evaluate the endometrial implantation window in patients with recurrent implantation failure using endometrial receptive array(ERA)sequencing or endometrial histological detection methods,and to explore the effectiveness and cost-effectiveness analysis of two technologies for improving clinical outcomes in such patients.Methods:A retrospective cohort study was conducted on clinical data of 125 patients diagnosed with repeated implantation failure in Gansu Maternal and Child Health Hospital from January 2018 to December 2022.According to whether endometrial receptivity testing was accepted and different detection techniques were used,they were divided into a control group(n=36),a genomic group(n=35),and a histological group(n=54).The clinical data and pregnancy outcomes of the three groups were compared.Results:①The results of one-way ANOVA showed that the embryo implantation rate in the genomic group and histological group was significantly higher than that in the control group,and the difference was statistically significant(P<0.05).There was no sta-tistically significant difference in embryo implantation rate between genomic and histological groups(P=0.48).②There was no statistically significant difference in clinical pregnancy rate and live birth rate among the three groups(P>0.05).③Log rank test showed:The time for 50%of patients to reach live labor was significantly shorter than that of the control group,and the difference was statistically significant(P<0.05);There was no sta-tistically significant difference in the time to live birth in 50%of patients between the genomic and histological groups of 50%of patients(P>0.05).④The average number of embryos transferred in the control group was significantly higher than that in the genomic and histological groups,with statistical significance(P<0.05).The cost of genomic patients was significantly higher than that of histology group,and the difference was statistically significant(P<0.05).Conclusions:①Endometrial implantation window detection is feasible for patients with re-peated implantation failure,which can effectively shorten the time to live birth and reduce the number of transplan-ted embryos;②Both ERA sequencing and endometrial histology detection have limitations as methods to evaluate endometrial implantation window,and it is not clear which detection method has more advantages in accuracy and practicability.
6.Effect of Different Endometrial Implantation Window Detection Methods on Pregnancy Outcome in Patients with Repeated Implantation Failure
Yanfei WANG ; Guangmei XIE ; Yuankun SANG ; Li WANG ; Ruoxin ZHU ; Jialing WANG ; Liyuan ZHANG ; Fan FENG
Journal of Practical Obstetrics and Gynecology 2024;40(5):381-385
Objective:To evaluate the endometrial implantation window in patients with recurrent implantation failure using endometrial receptive array(ERA)sequencing or endometrial histological detection methods,and to explore the effectiveness and cost-effectiveness analysis of two technologies for improving clinical outcomes in such patients.Methods:A retrospective cohort study was conducted on clinical data of 125 patients diagnosed with repeated implantation failure in Gansu Maternal and Child Health Hospital from January 2018 to December 2022.According to whether endometrial receptivity testing was accepted and different detection techniques were used,they were divided into a control group(n=36),a genomic group(n=35),and a histological group(n=54).The clinical data and pregnancy outcomes of the three groups were compared.Results:①The results of one-way ANOVA showed that the embryo implantation rate in the genomic group and histological group was significantly higher than that in the control group,and the difference was statistically significant(P<0.05).There was no sta-tistically significant difference in embryo implantation rate between genomic and histological groups(P=0.48).②There was no statistically significant difference in clinical pregnancy rate and live birth rate among the three groups(P>0.05).③Log rank test showed:The time for 50%of patients to reach live labor was significantly shorter than that of the control group,and the difference was statistically significant(P<0.05);There was no sta-tistically significant difference in the time to live birth in 50%of patients between the genomic and histological groups of 50%of patients(P>0.05).④The average number of embryos transferred in the control group was significantly higher than that in the genomic and histological groups,with statistical significance(P<0.05).The cost of genomic patients was significantly higher than that of histology group,and the difference was statistically significant(P<0.05).Conclusions:①Endometrial implantation window detection is feasible for patients with re-peated implantation failure,which can effectively shorten the time to live birth and reduce the number of transplan-ted embryos;②Both ERA sequencing and endometrial histology detection have limitations as methods to evaluate endometrial implantation window,and it is not clear which detection method has more advantages in accuracy and practicability.
7.Effect of Different Endometrial Implantation Window Detection Methods on Pregnancy Outcome in Patients with Repeated Implantation Failure
Yanfei WANG ; Guangmei XIE ; Yuankun SANG ; Li WANG ; Ruoxin ZHU ; Jialing WANG ; Liyuan ZHANG ; Fan FENG
Journal of Practical Obstetrics and Gynecology 2024;40(5):381-385
Objective:To evaluate the endometrial implantation window in patients with recurrent implantation failure using endometrial receptive array(ERA)sequencing or endometrial histological detection methods,and to explore the effectiveness and cost-effectiveness analysis of two technologies for improving clinical outcomes in such patients.Methods:A retrospective cohort study was conducted on clinical data of 125 patients diagnosed with repeated implantation failure in Gansu Maternal and Child Health Hospital from January 2018 to December 2022.According to whether endometrial receptivity testing was accepted and different detection techniques were used,they were divided into a control group(n=36),a genomic group(n=35),and a histological group(n=54).The clinical data and pregnancy outcomes of the three groups were compared.Results:①The results of one-way ANOVA showed that the embryo implantation rate in the genomic group and histological group was significantly higher than that in the control group,and the difference was statistically significant(P<0.05).There was no sta-tistically significant difference in embryo implantation rate between genomic and histological groups(P=0.48).②There was no statistically significant difference in clinical pregnancy rate and live birth rate among the three groups(P>0.05).③Log rank test showed:The time for 50%of patients to reach live labor was significantly shorter than that of the control group,and the difference was statistically significant(P<0.05);There was no sta-tistically significant difference in the time to live birth in 50%of patients between the genomic and histological groups of 50%of patients(P>0.05).④The average number of embryos transferred in the control group was significantly higher than that in the genomic and histological groups,with statistical significance(P<0.05).The cost of genomic patients was significantly higher than that of histology group,and the difference was statistically significant(P<0.05).Conclusions:①Endometrial implantation window detection is feasible for patients with re-peated implantation failure,which can effectively shorten the time to live birth and reduce the number of transplan-ted embryos;②Both ERA sequencing and endometrial histology detection have limitations as methods to evaluate endometrial implantation window,and it is not clear which detection method has more advantages in accuracy and practicability.
8.Effect of Different Endometrial Implantation Window Detection Methods on Pregnancy Outcome in Patients with Repeated Implantation Failure
Yanfei WANG ; Guangmei XIE ; Yuankun SANG ; Li WANG ; Ruoxin ZHU ; Jialing WANG ; Liyuan ZHANG ; Fan FENG
Journal of Practical Obstetrics and Gynecology 2024;40(5):381-385
Objective:To evaluate the endometrial implantation window in patients with recurrent implantation failure using endometrial receptive array(ERA)sequencing or endometrial histological detection methods,and to explore the effectiveness and cost-effectiveness analysis of two technologies for improving clinical outcomes in such patients.Methods:A retrospective cohort study was conducted on clinical data of 125 patients diagnosed with repeated implantation failure in Gansu Maternal and Child Health Hospital from January 2018 to December 2022.According to whether endometrial receptivity testing was accepted and different detection techniques were used,they were divided into a control group(n=36),a genomic group(n=35),and a histological group(n=54).The clinical data and pregnancy outcomes of the three groups were compared.Results:①The results of one-way ANOVA showed that the embryo implantation rate in the genomic group and histological group was significantly higher than that in the control group,and the difference was statistically significant(P<0.05).There was no sta-tistically significant difference in embryo implantation rate between genomic and histological groups(P=0.48).②There was no statistically significant difference in clinical pregnancy rate and live birth rate among the three groups(P>0.05).③Log rank test showed:The time for 50%of patients to reach live labor was significantly shorter than that of the control group,and the difference was statistically significant(P<0.05);There was no sta-tistically significant difference in the time to live birth in 50%of patients between the genomic and histological groups of 50%of patients(P>0.05).④The average number of embryos transferred in the control group was significantly higher than that in the genomic and histological groups,with statistical significance(P<0.05).The cost of genomic patients was significantly higher than that of histology group,and the difference was statistically significant(P<0.05).Conclusions:①Endometrial implantation window detection is feasible for patients with re-peated implantation failure,which can effectively shorten the time to live birth and reduce the number of transplan-ted embryos;②Both ERA sequencing and endometrial histology detection have limitations as methods to evaluate endometrial implantation window,and it is not clear which detection method has more advantages in accuracy and practicability.
9.Effect of Different Endometrial Implantation Window Detection Methods on Pregnancy Outcome in Patients with Repeated Implantation Failure
Yanfei WANG ; Guangmei XIE ; Yuankun SANG ; Li WANG ; Ruoxin ZHU ; Jialing WANG ; Liyuan ZHANG ; Fan FENG
Journal of Practical Obstetrics and Gynecology 2024;40(5):381-385
Objective:To evaluate the endometrial implantation window in patients with recurrent implantation failure using endometrial receptive array(ERA)sequencing or endometrial histological detection methods,and to explore the effectiveness and cost-effectiveness analysis of two technologies for improving clinical outcomes in such patients.Methods:A retrospective cohort study was conducted on clinical data of 125 patients diagnosed with repeated implantation failure in Gansu Maternal and Child Health Hospital from January 2018 to December 2022.According to whether endometrial receptivity testing was accepted and different detection techniques were used,they were divided into a control group(n=36),a genomic group(n=35),and a histological group(n=54).The clinical data and pregnancy outcomes of the three groups were compared.Results:①The results of one-way ANOVA showed that the embryo implantation rate in the genomic group and histological group was significantly higher than that in the control group,and the difference was statistically significant(P<0.05).There was no sta-tistically significant difference in embryo implantation rate between genomic and histological groups(P=0.48).②There was no statistically significant difference in clinical pregnancy rate and live birth rate among the three groups(P>0.05).③Log rank test showed:The time for 50%of patients to reach live labor was significantly shorter than that of the control group,and the difference was statistically significant(P<0.05);There was no sta-tistically significant difference in the time to live birth in 50%of patients between the genomic and histological groups of 50%of patients(P>0.05).④The average number of embryos transferred in the control group was significantly higher than that in the genomic and histological groups,with statistical significance(P<0.05).The cost of genomic patients was significantly higher than that of histology group,and the difference was statistically significant(P<0.05).Conclusions:①Endometrial implantation window detection is feasible for patients with re-peated implantation failure,which can effectively shorten the time to live birth and reduce the number of transplan-ted embryos;②Both ERA sequencing and endometrial histology detection have limitations as methods to evaluate endometrial implantation window,and it is not clear which detection method has more advantages in accuracy and practicability.
10.Effects of Siglec-E on parthenolide inhibiting microglia M1 polarization and targeting MAPK/NF-κB pathway
Wenying FU ; Pengbo WANG ; Xiangyu TANG ; Liyuan FENG ; Yuting HUANG ; Peng LI
Journal of Army Medical University 2024;46(7):651-660
Objective To explore the impact of the sialic acid binding lectin-E(Siglec-E)on the inhibitory properties of parthenolide(PTL)against lipopolysaccharide(LPS)-induced M1 polarization of microglia(BV2).Methods ①Single cell sequencing data of Siglece related mouse brain tissue was obtained from Gene Expression Omnibus(GEO)database and divided into the WT group(n=3)and the Siglece-/-group(n=4).The microglia cells were screened,and the enrichment analysis was performed to analyze related differential genes and pathways.BV2 cells were constructed by the shRNA interference technique and were divided into NC-shRNA and Siglece-shRNA to detect the expression level of Siglec-E(Siglece).② NC-shRNA and Siglece-shRNA cells were respectively divided into the Control group,LPS group,PTL group and PTL+LPS group(n=3).The mRNA levels of markers of M1 polarization in microglia,iNOS,IL-1 β and IL-6,were detected by RT-qPCR.Siglecefl/fl and Cx3cr1cre mice were mated to obtain microglia-specific Siglece deletion(Siglecefl/fl×Cx3cr1cre)mice,and LPS-induced neuroinflammation model was established.③ Nine WT and Siglecefl/fl×Cx3cr1cre male mice were assigned to the Control group,LPS group and PTL+LPS group(n=3).RT-qPCR,immunofluorescence assay and Western blotting were used to verify the knock-out effect and polarization-related pathways,and to investigate the mechanism of Siglec-E affecting PTL inhibition of M1 polarization of microglia.Results Compared with the NC-shRNA group,the expression of Siglec-E in the Siglece-shRNA group was significantly decreased(P<0.01),indicating that the Siglec-E knock-down cell model was successfully established.With the stimulation of LPS,mRNA levels ofiNOS,IL-1 β and IL-6 were significantly up-regulated compared with the Control group both in shRNA cells and Siglece-shRNA cells(P<0.01).With the influence of PTL and LPS,the markers of M1 polarization in NC-shRNA cells mentioned before were significantly decreased(P<0.05),while for Siglice-shRNA cells,there were no significant changes in the markers of M1 polarization.PTL inhibited the phosphorylation of JNK and IκB protein(P<0.01)and the nuclear translocation of NF-κB in BV2 cells,down-regulated Siglec-E,and weakened the inhibitory effect.Compared with mice in the WT group,the expression of Siglec-E in microglia of Siglecefl/fl×Cx3cr1cre mice was decreased significantly(P<0.01),and the inhibitory effect of PTL on the phosphorylation of NF-κB in microglia of Siglecefl/fl×Cx3cr1cre mice was also decreased.Conclusion The absence of Siglec-E in microglia attenuates the inhibition of M1 polarization by the MAPK/NF-κB pathway targeted by PTL.

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