Background::Homoharringtonine (HHT) is an effective anti-inflammatory, anti-viral, and anti-tumor protein synthesis inhibitor that has been applied clinically. Here, we explored the therapeutic effects of HHT in a mouse heart transplant model.Methods::Healthy C57BL/6 mice were used to observe the toxicity of HHT in the liver, kidney, and hematology. A mouse heart transplantation model was constructed, and the potential mechanism of HHT prolonging allograft survival was evaluated using Kaplan–Meier analysis, immunostaining, and bulk RNA sequencing analysis. The HHT-T cell crosstalk was modeled ex vivo to further verify the molecular mechanism of HHT-induced regulatory T cells (Tregs) differentiation. Results::HHT inhibited the activation and proliferation of T cells and promoted their apoptosis ex vivo. Treatment of 0.5 mg/kg HHT for 10 days significantly prolonged the mean graft survival time of the allografts from 7 days to 48 days ( P <0.001) without non-immune toxicity. The allografts had long-term survival after continuous HHT treatment for 28 days. HHT significantly reduced lymphocyte infiltration in the graft, and interferon-γ-secreting CD4 + and CD8 + T cells in the spleen ( P <0.01). HHT significantly increased the number of peripheral Tregs (about 20%, P <0.001) and serum interleukin (IL)-10 levels. HHT downregulated the expression of T cell receptor (TCR) signaling pathway-related genes ( CD4, H2-Eb1, TRAT1, and CD74) and upregulated the expression of IL-10 and transforming growth factor (TGF) -β pathway-related genes and Treg signature genes ( CTLA4, Foxp3, CD74, and ICOS). HHT increased CD4 + Foxp3 + cells and Foxp3 expression ex vivo, and it enhanced the inhibitory function of inducible Tregs. Conclusions::HHT promotes Treg cell differentiation and enhances Treg suppressive function by attenuating the TCR signaling pathway and upregulating the expression of Treg signature genes and IL-10 levels, thereby promoting mouse heart allograft acceptance. These findings may have therapeutic implications for organ transplant recipients, particularly those with viral infections and malignancies, which require a more suitable anti-rejection medication.

Based on the views of FAN's Eight Dynamic-Static Sequential Methods,Professor FAN Guan-Jie believes that the obesity has the pathological factor of blood stasis in addition to qi deficiency and phlegm-damp.The compatibility of blood-activating and stasis-removing drugs for the treatment of obesity is accorded to the progression of the disease.In the clinic,Crataegi Fructus associated medicinal cluster of activating blood and removing stasis is usually recommended.The medicinal cluster is with Crataegi Fructus as the chief medicinal,and is compatible with drug pairs of Salviae Miltiorrhizae Radix et Rhizoma-Carthami Flos and Moutan Cortex-Paeoniae Radix Rubra.Crataegi Fructus associated medicinal cluster is able to treat qi and blood simultaneously,mainly aimed at removing blood stasis,supplemented by nourishing blood,promoting qi and blood movement,and invigorating spleen and stomach,which has the features of simultaneous dispersing and astringency,and proper combination of static therapy and dynamic therapy,and is suitable for obese patients with blood stasis obstruction in the vessels.

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.

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.

Objective To investigate the characteristics of clopidogrel-associated thrombocytopenia to provide references for clinically safe drug use.Methods The case reports of thrombocytopenia induced by clopidogrel published in PubMed,Embase,CNKI,Wanfang and VIP were searched from the establishment of each database to November 2022,and their occurrence was collated and analysed.Results A total of 44 cases from 43 articles were identified and included in the analysis.There were 30 males(68.2％)and 14 females(31.8％).Ages ranged from 37 to 88(65.0±11.4)years,of which 30(68.2％)were ≥60 years old.Thrombocytopenia was found from 8 h to 9 months after medication,of which 29 cases(65.9％)appeared within two weeks.There were 31 cases(70.5％)with severe thrombocytopenia and 38 cases(86.4％)with complications,of which 24 cases(63.2％)with bleeding and 19 cases(50.0％)with thrombotic thrombocytopenic purpura(TTP).The platelet countof41 cases(93.2％)returned to normal after drug withdrawal and symptomatic treatment,and 3 cases(6.8％)died finally.Conclusion Clopidogrel related thrombocytopenia is mainly severe thrombocytopenia,and often accompanied by bleeding or thrombotic thrombocytopenic purpura(TTP),but the overall outcome is good.Platelet count should be regularly monitored within the first two weeks after medication.Clopidogrel should be stopped and symptomatic treatment should be given in case of any abnormality.

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.

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.

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.

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.

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.