Objective:To identify HLA-G-binding proteins(HGBPs)by screening targeting ankyrin sequences from a phage display-based ankyrin protein library using human leukocyte antigen G(HLA-G)as the target,and to evaluate their functions.Methods:The expression of HLA-G in tumor tissues and its correlation with clinical prognosis and immune infiltration were analyzed using bioinformatics tools such as TCGA and GTEx databses.The extracellular domain of HLA-G was subjected to biopanning with a phage-displayed ankyrin protein library,followed by random selection and sequencing of monoclonal phage clones.The functional properties of dominant phage clones were validated using ELISA and immunofluorescence staining.HGBPs were produced and purified using a prokaryotic expression system,and their affinity and tumor-specific binding ability were evaluated using ELISA,surface plasmon resonance(SPR),and immunofluorescence staining.Results:Bioinformatics analysis revealed that HLA-G is widely overexpressed in tumor tissues and is correlated with overall survival(OS)and immune cell infiltration(P<0.05).After five rounds of biopanning,dominant clones were obtained.Both ELISA and immunofluorescence staining results showed that these dominant phages had a significantly higher affinity to HLA-G positive cells compared to HLA-G negative cells(P<0.05,P<0.001).The purified HGBPs exhibited an affinity of up to 17 nmol/L for HLA-G.ELISA results showed significant binding of HGBP to HLA-G(P<0.05),and immunofluorescence staining confirmed that HGBP could specifically bind to HLA-G-positive cells(P<0.01).Conclusion:The HGBPs identified via phage display exhibit high affinity and specificity to HLA-G on tumor cells.

Advanced atherosclerosis is the major global cause of death, as featured by the aggregation of apoptotic cells (ACs) in necrotic cores. The defective efferocytosis and dysfunctional cholesterol efflux of macrophages are the main reasons for forming necrotic cores in advanced atherosclerosis. In this study, we constructed self-assembled procyanidins (PC) NPs for loading pitavastatin (Pita). The designed HA@PC@Pita NPs with hyaluronic acid (HA) modification combined the advantages of efferocytosis restoration of Pita and cholesterol efflux enhancement of PC. In vitro assay indicated that HA@PC@Pita NPs could induce M1/M2 repolarization and upregulate ERK5/Mertk expression to restore efferocytosis of macrophages. Simultaneously, HA@PC@Pita NPs notably promoted cholesterol efflux by promoting macrophage lipophagy, a selective autophagy of lipid droplets. In vivo study showed that HA@PC@Pita NPs cleared necrotic core and enhanced plaque stability in the ApoE ^-/- mice model with advanced atherosclerosis. Taken together, this study demonstrated the potential of HA@PC@Pita NPs for the treatment of advanced atherosclerosis.

Objectives:To investigate the predictive value of the hemoglobin to serum creatinine ratio(Hb/SCr)for all-cause mortality within 3 years after percutaneous coronary intervention(PCI)in patients with ST-segment elevation myocardial infarction(STEMI).Methods:A total of 687 STEMI patients who successfully underwent the first PCI at the Department of Cardiology,Gansu Provincial People's Hospital,from June 2016 to June 2020 were retrospectively enrolled.Patients were divided into survival and non-survival groups according to their vital status at 3 years post-PCI.Cox regression analysis was performed to identify predictive factors of all-cause mortality.Receiver operating characteristic(ROC)curves were constructed to evaluate the predictive value of Hb/SCr for all-cause mortality,and Kaplan-Meier survival curves were used to compare cumulative survival rates between subgroups stratified by Hb/SCr levels.Results:The median follow-up duration was 37(25,50)months.Among the 663 patients(96.51%)with complete follow-up data,41 cases(6.18%)experiencing all-cause death.Multivariable Cox regression analysis revealed that age(HR=1.086,95%CI:1.037-1.137,P=0.000),body mass index(HR=1.195,95%CI:1.128-1.266,P=0.000),fasting blood glucose(HR=1.069,95%CI:1.007-1.135,P=0.030),fibrinogen(HR=1.418,95%CI:1.120-1.795,P=0.004),TIMI flow grade 1(HR=4.968,95%CI:1.194-20.667,P=0.028),TIMI flow grade 2(HR=3.861,95%CI:1.336-11.156,P=0.013),and Hb/SCr(HR=0.858,95%CI:0.766-0.961,P=0.008)were the independent predictors of all-cause mortality.ROC curve analysis demonstrated that the area under the curve(AUC)of Hb/SCr was 0.721(95%CI:0.645-0.798)for predicting all-cause mortality,with a sensitivity of 65.9%and specificity of 71.2%,at the optimal cut-offvalue of 16.627.Kaplan-Meier analysis showed that patients with Hb/SCr<16.627 had significantly lower survival rates than those with Hb/SCr≥16.627(log-rank P=0.000).Conclusions:Hb/SCr is an independent predictor of 3-year all-cause mortality in STEMI patients after PCI and this indicator could be used as risk stratification parameter and patients with lower Hb/SCr might benefit comprehensive post-PCI management to improve their outcome.

Objectives:To investigate the predictive value of the hemoglobin to serum creatinine ratio(Hb/SCr)for all-cause mortality within 3 years after percutaneous coronary intervention(PCI)in patients with ST-segment elevation myocardial infarction(STEMI).Methods:A total of 687 STEMI patients who successfully underwent the first PCI at the Department of Cardiology,Gansu Provincial People's Hospital,from June 2016 to June 2020 were retrospectively enrolled.Patients were divided into survival and non-survival groups according to their vital status at 3 years post-PCI.Cox regression analysis was performed to identify predictive factors of all-cause mortality.Receiver operating characteristic(ROC)curves were constructed to evaluate the predictive value of Hb/SCr for all-cause mortality,and Kaplan-Meier survival curves were used to compare cumulative survival rates between subgroups stratified by Hb/SCr levels.Results:The median follow-up duration was 37(25,50)months.Among the 663 patients(96.51%)with complete follow-up data,41 cases(6.18%)experiencing all-cause death.Multivariable Cox regression analysis revealed that age(HR=1.086,95%CI:1.037-1.137,P=0.000),body mass index(HR=1.195,95%CI:1.128-1.266,P=0.000),fasting blood glucose(HR=1.069,95%CI:1.007-1.135,P=0.030),fibrinogen(HR=1.418,95%CI:1.120-1.795,P=0.004),TIMI flow grade 1(HR=4.968,95%CI:1.194-20.667,P=0.028),TIMI flow grade 2(HR=3.861,95%CI:1.336-11.156,P=0.013),and Hb/SCr(HR=0.858,95%CI:0.766-0.961,P=0.008)were the independent predictors of all-cause mortality.ROC curve analysis demonstrated that the area under the curve(AUC)of Hb/SCr was 0.721(95%CI:0.645-0.798)for predicting all-cause mortality,with a sensitivity of 65.9%and specificity of 71.2%,at the optimal cut-offvalue of 16.627.Kaplan-Meier analysis showed that patients with Hb/SCr<16.627 had significantly lower survival rates than those with Hb/SCr≥16.627(log-rank P=0.000).Conclusions:Hb/SCr is an independent predictor of 3-year all-cause mortality in STEMI patients after PCI and this indicator could be used as risk stratification parameter and patients with lower Hb/SCr might benefit comprehensive post-PCI management to improve their outcome.

Objective:To explore the expression levels of adrenomedullin (ADM) in follicular fluid of patients with polycystic ovary syndrome (PCOS) and its correlation with ovarian function and inflammation.Methods:To conduct a cohort study, the data on infertile couples who received an antagonistic regimen of in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) to promote ovulation from March to December 2023 at the Reproductive Medicine Center of Shanxi Children's Hospital (Shanxi Maternal and Child Health Hospital) were collected. PCOS patients were selected as the PCOS group, and patients who underwent IVF/ICSI assisted pregnancy solely due to tubal and/or male factors during the same period were selected as control group. The general clinical data of two groups of patients were analyzed, and the expression of ADM, interleukin 1β (IL-1β), IL-18, transforming growth factor β (TGF-β) in the follicular fluid were compared between the two groups of patients. And taking the concentration of ADM in follicular fluid as the main research indicator, correlation and multiple linear regression analysis were conducted with other indicators. Simultaneously the ADM mRNA expression, cell cycle and cell apoptosis of granulosa cells were compared between the two groups. Results:This study included 20 cases in the PCOS group and 20 cases in control group. Compared with control group, the expression of ADM in follicular fluid and granulosa cells of patients with PCOS were significantly lower (both P<0.001), while its testosterone, the ratio of luteinizing hormone and follicle-stimulating hormone, antral follicle count (AFC), number of retrieved eggs, ovarian sensitivity index, as well as IL-1β, IL-18 and TGF-β in follicular fluid were higher and negatively correlated with ADM ( r=-0.37, P=0.019; r=-0.32, P=0.047; r=-0.50, P<0.001; r=-0.38, P=0.017; r=-0.38, P=0.016; r=-0.44, P=0.005; r=-0.37, P=0.018; r=-0.54, P<0.001). Multiple linear regression showed that AFC, gonadotropin initiation dose, IL-1β and TGF-β were the independent related factors that affect local ADM levels ( r=-0.37, P=0.008; r=-0.27, P=0.035; r=-0.28, P=0.028; r=-0.45, P<0.001). There was no statistically significant difference in the cell cycle of granulocytes between the two groups ( P>0.05), but the apoptosis rate (AR) of granulocytes was higher in the PCOS group than in control group (median AR in the PCOS group was 46.07%, median AR in control group was 28.57%, n=10, P=0.036). Conclusion:The decreased expression of ADM in follicles of PCOS patients is related to ovarian endocrine disorders, multiple vesicles, high ovarian responsiveness and local inflammatory status.

Objective:To explore the expression levels of adrenomedullin (ADM) in follicular fluid of patients with polycystic ovary syndrome (PCOS) and its correlation with ovarian function and inflammation.Methods:To conduct a cohort study, the data on infertile couples who received an antagonistic regimen of in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) to promote ovulation from March to December 2023 at the Reproductive Medicine Center of Shanxi Children's Hospital (Shanxi Maternal and Child Health Hospital) were collected. PCOS patients were selected as the PCOS group, and patients who underwent IVF/ICSI assisted pregnancy solely due to tubal and/or male factors during the same period were selected as control group. The general clinical data of two groups of patients were analyzed, and the expression of ADM, interleukin 1β (IL-1β), IL-18, transforming growth factor β (TGF-β) in the follicular fluid were compared between the two groups of patients. And taking the concentration of ADM in follicular fluid as the main research indicator, correlation and multiple linear regression analysis were conducted with other indicators. Simultaneously the ADM mRNA expression, cell cycle and cell apoptosis of granulosa cells were compared between the two groups. Results:This study included 20 cases in the PCOS group and 20 cases in control group. Compared with control group, the expression of ADM in follicular fluid and granulosa cells of patients with PCOS were significantly lower (both P<0.001), while its testosterone, the ratio of luteinizing hormone and follicle-stimulating hormone, antral follicle count (AFC), number of retrieved eggs, ovarian sensitivity index, as well as IL-1β, IL-18 and TGF-β in follicular fluid were higher and negatively correlated with ADM ( r=-0.37, P=0.019; r=-0.32, P=0.047; r=-0.50, P<0.001; r=-0.38, P=0.017; r=-0.38, P=0.016; r=-0.44, P=0.005; r=-0.37, P=0.018; r=-0.54, P<0.001). Multiple linear regression showed that AFC, gonadotropin initiation dose, IL-1β and TGF-β were the independent related factors that affect local ADM levels ( r=-0.37, P=0.008; r=-0.27, P=0.035; r=-0.28, P=0.028; r=-0.45, P<0.001). There was no statistically significant difference in the cell cycle of granulocytes between the two groups ( P>0.05), but the apoptosis rate (AR) of granulocytes was higher in the PCOS group than in control group (median AR in the PCOS group was 46.07%, median AR in control group was 28.57%, n=10, P=0.036). Conclusion:The decreased expression of ADM in follicles of PCOS patients is related to ovarian endocrine disorders, multiple vesicles, high ovarian responsiveness and local inflammatory status.

Cognitive dysfunction refers to dysfunction of individual perception,memory,understanding,learning,creation and other dysfunctions caused by abnormal brain function and structure.Based on the fact that the spleen can't regulate transportation and transformation,govern blood and send up essential substance,combined with the microbiota-gut-brain axis,this article discussed the etiology and pathogenesis of intestinal flora imbalance affecting cognitive dysfunction in TCM.It was proposed that the spleen in TCM and intestinal flora are connected in physiology and pathology:the spleen regulates spirit and governs cognition,when the spleen fails to function normally that it can't dominate transportation and transformation,govern blood and send up essential substance will cause that the brain spirit can not be nourished;intestinal flora is closely related to the spleen in TCM,and affects brain function through the nervous system,endocrine,immune and metabolic mechanisms.This article can provide explore new ideas for the clinical research and treatment of cognitive dysfunction of traditional Chinese and Western medicine.

Objective:To analyse the influence of endometrial polyps (EPs) treatment on the frozen-thawed embryo transfer (FET) pregnancy outcome.Methods:Using a retrospective case-control study, the data of patients were collected who received in vitro fertilization (IVF) and hysteroscopy in the Reproductive Medicine Center of Children's Hospital of Shanxi and Women Health Center of Shanxi from June 2021 to December 2022. Patients undergoing hysteroscopy were studied. According to the diagnosis results of hysteroscopy and pathology, they were selected as the EPs group or the non-endometrial polyps (NEPs) group. Then analysis of EPs risk factors was made, and the pregnancy outcome of FET after the EPs treatment was compared. Results:A total of 3 413 patients underwent hysteroscopy in this study. The EPs group included 444 patients and the NEPs group included 1 501 patients respectively. The prevalence of EPs was 13.01% (444/3 413). There were significant differences between EPs group and NEPs group in gravidity, parity, spontaneous abortion times, induced abortions times, basal follicle-stimulating hormone (bFSH), basal luteinizing hormone (bLH), infertility duration, infertility types, the prevalence of chronic endometritis, the history of polyps removal and endometriosis (all P<0.05). Multivariate logistic regression analysis of risk factors associated with EPs showed that infertility duration ( OR=1.068, 95% CI: 1.029-1.109, P<0.001), chronic endometritis ( OR=1.925, 95% CI: 1.481-2.502, P<0.001), primary infertility ( OR=1.803, 95% CI: 1.408-2.308, P<0.001), history of polyps removal ( OR=9.424, 95% CI: 5.586-15.897, P<0.001), endometriosis ( OR=2.432, 95% CI: 1.344-4.401, P=0.003) were independent risk factors for EPs, and bLH ( OR=0.954, 95% CI: 0.916-0.993, P=0.022) was an independent protective factor for EPs. Compared with NEPs transplantation group, there were no significant differences in clinical pregnancy rate, on-going pregnancy rate and none implantation rate in the EPs treatment transplantation group (all P>0.05). Conclusion:Infertility duration, chronic endometritis, primary infertility, history of polyps removal, endometriosis were independent risk factors, and bLH was an independent protective factor. Patients in EPs treatment transplantation group could achieve the similar pregnancy outcome as NEPs transplantation group.

Objective:To analyse the influence of endometrial polyps (EPs) treatment on the frozen-thawed embryo transfer (FET) pregnancy outcome.Methods:Using a retrospective case-control study, the data of patients were collected who received in vitro fertilization (IVF) and hysteroscopy in the Reproductive Medicine Center of Children's Hospital of Shanxi and Women Health Center of Shanxi from June 2021 to December 2022. Patients undergoing hysteroscopy were studied. According to the diagnosis results of hysteroscopy and pathology, they were selected as the EPs group or the non-endometrial polyps (NEPs) group. Then analysis of EPs risk factors was made, and the pregnancy outcome of FET after the EPs treatment was compared. Results:A total of 3 413 patients underwent hysteroscopy in this study. The EPs group included 444 patients and the NEPs group included 1 501 patients respectively. The prevalence of EPs was 13.01% (444/3 413). There were significant differences between EPs group and NEPs group in gravidity, parity, spontaneous abortion times, induced abortions times, basal follicle-stimulating hormone (bFSH), basal luteinizing hormone (bLH), infertility duration, infertility types, the prevalence of chronic endometritis, the history of polyps removal and endometriosis (all P<0.05). Multivariate logistic regression analysis of risk factors associated with EPs showed that infertility duration ( OR=1.068, 95% CI: 1.029-1.109, P<0.001), chronic endometritis ( OR=1.925, 95% CI: 1.481-2.502, P<0.001), primary infertility ( OR=1.803, 95% CI: 1.408-2.308, P<0.001), history of polyps removal ( OR=9.424, 95% CI: 5.586-15.897, P<0.001), endometriosis ( OR=2.432, 95% CI: 1.344-4.401, P=0.003) were independent risk factors for EPs, and bLH ( OR=0.954, 95% CI: 0.916-0.993, P=0.022) was an independent protective factor for EPs. Compared with NEPs transplantation group, there were no significant differences in clinical pregnancy rate, on-going pregnancy rate and none implantation rate in the EPs treatment transplantation group (all P>0.05). Conclusion:Infertility duration, chronic endometritis, primary infertility, history of polyps removal, endometriosis were independent risk factors, and bLH was an independent protective factor. Patients in EPs treatment transplantation group could achieve the similar pregnancy outcome as NEPs transplantation group.

Objective: To explore the acute effect of fine particulate matters (PM_2.5), O₃, NO₂ on daily non-accidental mortality, cardiovascular disease mortality and respiratory mortality data in thirteen cities of Jiangsu province. Methods: Daily average concentrations of non-accidental mortality, cardiovascular disease mortality, respiratory mortality data and environmental data were collected from January 1, 2015 to December 31, 2017 in thirteen cities of Jiangsu Province. Daily air quality, mortality and meteorology data were collected from the Information System of Air Pollution and Health Impact Monitoring of Chinese Center for Disease Control and Prevention. We used generalized additive model to evaluate the association between daily concentrations of air pollutants and mortality at single-city level and multi-city level, after adjusting the long-term and seasonal trend, as well as meteorological factors and the effect of "days and weeks" . A multivariate Meta-analysis with random effects was applied to estimate dose-response relationship between air pollutants and mortality. Results: At multi-city level, per interquartile range increase of PM_2.5, O₃, NO₂ was associated with an increase of 1.10% (95%CI: 0.66%, 1.54%), 0.59% (95%CI: 0.18%, 1.00%), 2.00% (95%CI: 1.29%, 2.72%) of daily non-accidental mortality respectively; 1.01% (95%CI: 0.63%, 1.38%), 0.66% (95%CI: 0.02%, 1.30%), 1.62% (95%CI: 1.00%, 2.23%) of daily cardiovascular mortality respectively; 1.09% (95%CI: 0.35%, 1.82%), 0.44% (95%CI: -0.29%, 1.16%), 2.75% (95%CI: 1.42%, 4.08%) of daily respiratory mortality respectively. The air pollutants effect varied across different cities. The strongest effect of PM_2.5 was current day (excess risk (ER)=1.10%, 95%CI: 0.66%, 1.54%)), the strongest effect of O₃ was 2-day lag (ER=1.82%, 95%CI: 0.69%, 2.97%) and the strongest effect of NO₂ was 1-day lag (ER=2.09%, 95%CI: 1.34%, 2.83%) of daily non-accidental mortality respectively. Conclusion The increases of PM_2.5 and NO₂ concentration could result in the increases of daily non-accidental mortality, cardiovascular disease mortality and respiratory mortality. O₃ could result in the increases of daily non-accidental mortality and cardiovascular disease mortality. The acute effects for non-accidental mortality from high to low were NO₂, PM_2.5 and O_3, and the strongest effect of PM_2.5 was current day. O₃ and NO₂ had lagged effects.