OBJECTIVE: To evaluate the dynamic changes of glucocorticoid (GC) dose and the feasibility of GC discontinuation in rheumatoid arthritis (RA) patients under the background of Chinese medicine (CM). METHODS: This multicenter retrospective cohort study included 1,196 RA patients enrolled in the China Rheumatoid Arthritis Registry of Patients with Chinese Medicine (CERTAIN) from September 1, 2019 to December 4, 2023, who initiated GC therapy. Participants were divided into the Western medicine (WM) and integrative medicine (IM, combination of CM and WM) groups based on medication regimen. Follow-up was performed at least every 3 months to assess dynamic changes in GC dose. Changes in GC dose were analyzed by generalized estimator equation, the probability of GC discontinuation was assessed using Kaplan-Meier curve, and predictors of GC discontinuation were analyzed by Cox regression. Patients with <12 months of follow-up were excluded for the sensitivity analysis. RESULTS: Among 1,196 patients (85.4% female; median age 56.4 years), 880 (73.6%) received IM. Over a median 12-month follow-up, 34.3% (410 cases) discontinued GC, with significantly higher rates in the IM group (40.8% vs. 16.1% in WM; P<0.05). GC dose declined progressively, with IM patients demonstrating faster reductions (median 3.75 mg vs. 5.00 mg in WM at 12 months; P<0.05). Multivariate Cox analysis identified age <60 years [P<0.001, hazard ratios (HR)=2.142, 95% confidence interval (CI): 1.523-3.012], IM therapy (P=0.001, HR=2.175, 95% CI: 1.369-3.456), baseline GC dose ⩽7.5 mg (P=0.003, HR=1.637, 95% CI: 1.177-2.275), and absence of non-steroidal anti-inflammatory drugs use (P=0.001, HR=2.546, 95% CI: 1.432-4.527) as significant predictors of GC discontinuation. Sensitivity analysis (545 cases) confirmed these findings. CONCLUSIONS RA patients receiving CM face difficulties in following guideline-recommended GC discontinuation protocols. IM can promote GC discontinuation and is a promising strategy to reduce GC dependency in RA management. (Trial registration: ClinicalTrials.gov, No. NCT05219214).
Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; Arthritis, Rheumatoid/drug therapy* ; Glucocorticoids/therapeutic use* ; Medicine, Chinese Traditional ; Retrospective Studies

Compounds isolated from Epimedium include the total flavonoids of Epimedium , icariin, and its metabolites (icaritin, icariside I, and icariside II), which have similar molecular structures. Modern pharmacological research and clinical practice have proved that Epimedium and its active components have a wide range of pharmacological effects, especially in improving sexual function, hormone regulation, anti-osteoporosis, immune function regulation, anti-oxidation, and anti-tumor activity. To date, we still need a comprehensive source of knowledge about the pharmacological effects of Epimedium and its bioactive compounds on the male reproductive system. However, their actions in other tissues have been reviewed in recent years. This review critically focuses on the Epimedium , its bioactive compounds, and the biochemical and molecular mechanisms that modulate vital pathways associated with the male reproductive system. Such intrinsic knowledge will significantly further studies on the Epimedium and its bioactive compounds that protect the male reproductive system and provide some guidances for clinical treatment of related male reproductive disorders.
Male ; Epimedium/chemistry* ; Humans ; Genitalia, Male/drug effects* ; Flavonoids/therapeutic use* ; Animals

Objective:To investigate the predictive value of pre-infarction angina(PIA)combined with serum lipo-protein-associated phospholipase A2(Lp-PLA2)for no-reflow during primary percutaneous coronary interven-tion(PCI)in elderly patients with new-onset acute ST-segment elevation myocardial infarction(STEMI).Meth-ods:A total of 189 patients who hospitalized because of acute STEMI and underwent primary PCI within 12h in De-partment of Cardiology,Cangzhou People's Hospital between January 2018 and December 2022 were enrolled.Ac-cording to their TIMI blood flow during PCI,the patients were divided into no reflow group(n=42)and normal re-flow group(n=147).The baseline data were compared between two groups.Multivariate Logistic regression analy-sis was used to analyze the risk factors of no-reflow during PCI.The receiver operating characteristic(ROC)curve was plotted to evaluate the predictive value of PIA and Lp-PLA2 for no-reflow.Results:PI A occurred in 73 cases(38.6％),and no reflow occurred in 42 cases(22.2％)during primary PCI.Compared with patients in normal re-flow group,those in no reflow group had significant higher Lp-PLA2[(341.33±98.32)ng/ml vs.(261.95±75.21)ng/ml]and onset to reperfusion time[(7.02±1.28)h vs.(5.14±1.48)h],and significant lower incidence of PIA(23.8％ vs.42.9％)(P＜0.05 or＜0.01).Multivariate Logistic regression analysis showed that Lp-PLA2(OR=1.528,95％CI 1.028～2.030,P＜0.001),onset to reperfusion time(OR=2.602,95％CI 1.848～3.665,P＜0.001)were independent risk factors for no reflow during PCI in elderly STEMI patients,while PIA was an inde-pendent protective factor(OR=0.261,95％CI 0.101～0.671,P=0.005).The area under ROC curve of Lp-PLA2 combined PIA was 0.863(95％CI 0.806～0.909),which was significantly higher than those of Lp-PLA2[0.733(95％CI 0.664～0.794),Z=2.690,P=0.007]and PIA alone[0.609(95％CI 0.535～0.679),Z=5.657,P＜0.001].Conclusion:Pre-infarction angina has an important protective effect on no-reflow in STEMI patients.High Lp-PLA2 and absence of pre-infarction angina at admission may be good predictors of no-reflow during primary PCI in elderly patients with newly-onset acute STEMI,and it contributes to risk stratification of high risk patients.

Objective:To investigate the association of systemic immune-inflammation index(SII)and serum cysta-tin C(CysC)with the severity of acute pulmonary embolism(APE),and their predictive value for prognosis.Meth-ods:A total of 181 patients who were first diagnosed with APE in Cangzhou People's Hospital between January 2018 and January 2023 were retrospectively selected.The severity of APE was determined according to risk stratification criteria for pulmonary embolism,and the patients were divided into low-risk group(n=67),middle-risk group(n=81)and high-risk group(n=33).General clinical data and venous blood neutrophils,platelet and lymphocyte counts,CysC and other indicators were collected,and SII was calculated according to the formula.The relevant in-dicators were compared among three groups,and their correlation with the severity of APE was analyzed by Spearman correlation analysis.According to the prognosis,all APE patients were divided into favorable outcome group(n=129)and unfavorable outcome group(n=52).The general clinical data were compared and multivariate Cox regression analysis was used to study the influencing factors of unfavorable outcome in APE patients.The re-ceiver operating characteristic curve(ROC)was drawn to evaluate the predictive value of SII,CysC and their com-bination for the prognosis of APE patients.Nomogram model for prognosis was constructed.Results:Compared with patients in low-risk group,those in the middle-risk group and the high-risk group had significantly higher levels of serum creatinine,CysC and uric acid(P＜0.05 or＜0.01).The SII in the high-risk group was significant-ly higher than those of middle-risk group and low-risk group(P＜0.001 all).Spearman correlation analysis showed that serum creatinine,CysC,uric acid and SII were significant positively correlated with the severity of APE(r=0.356,0.358,0.233,0.353,P＜0.01 all).Compared with patients in the favorable outcome group,those in the unfavorable outcome group had significantly higher levels of D-dimer,serum creatinine,CysC,uric acid and SII(P＜0.01 all).There was a statistically significant difference in the severity of APE between the two groups(P=0.001).Multivariate Cox regression analysis showed that CysC,SII,and middle or high risk of disease severity were independent risk factors for unfavorable outcome in APE patients(HR=1.001～14.453,P＜0.05 or＜0.01).ROC curve indicated that the AUC of SII,CysC and their combination in predicting unfavorable outcome of APE patients were 0.815(95％CI 0.749～0.881),0.747(95％CI 0.661～0.832)and 0.878(95％CI,0.821～0.936),respectively.The combined AUC of the two was significantly higher than those of SII and CysC alone(Z=-2.234,-3.500,P＜0.05 or＜0.01).Based on the above independent risk factors,the AUC values of the 1-year and 3-year unfavorable outcome nomogram models were 92.9 and 88.2,respectively.The calibration prediction curve and the ideal curve fitted well.The decision curve showed that the model had a good net benefit.Conclusion:SII and CysC are significant positively correlated with the severity of APE and they are independent risk factors for unfavor-able outcome of APE,and the combination of the two indicators has a good predictive value for the prognosis of APE.The nomogram constructed has good accuracy and practicability.

Objective To investigate the influence of different disinfectants on the ultrasound-guided internal jugular vein puncture and adhesive application.Methods A total of 102 emergency patients with traumatic hemorrhage who underwent ultrasound-guided internal jugular vein puncture and catheterization were selected as the study subjects and randomly divided into the iodine group(51 cases)and the chlorhexidine-alcohol group(51 cases).Iodophor(0.5%effective iodine)and 2.0%chlorhexidine gluconate+70.0%ethanol were used for disinfection before puncture,respectively.The disinfection effect of the puncture site,puncture condition,ultrasound imaging,and adhesive force of the application of patients were statistically compared between the two groups.Results There was no significant difference in the bacterial count before disinfection,the bacterial count after disinfection or the qualified rate of disinfection at the puncture site of patients between the two groups(P>0.05).There were significant differences in the success rate of one-time puncture,the number of puncture and the time of puncture and catheterization between the two groups(P<0.05).There were significant differences in the rate of clear ultrasound images,adhesive force and rate of warping or shedding of the application between the two groups(P<0.05).Conclusion For emergency patients with traumatic hemorrhage,using iodophor(0.5%effective iodine)and 2.0%chlorhexidine gluconate+70.0%ethanol disinfection before ultrasound-guided internal jugular vein puncture can achieve good disinfection effects.Iodine disinfection can obtain clearer ultrasound images and a higher success rate of one-time puncture,but the adhesive force of the application is poor,making it prone to warping or shedding.

Objective:To investigate the predictive value of pre-infarction angina(PIA)combined with serum lipo-protein-associated phospholipase A2(Lp-PLA2)for no-reflow during primary percutaneous coronary interven-tion(PCI)in elderly patients with new-onset acute ST-segment elevation myocardial infarction(STEMI).Meth-ods:A total of 189 patients who hospitalized because of acute STEMI and underwent primary PCI within 12h in De-partment of Cardiology,Cangzhou People's Hospital between January 2018 and December 2022 were enrolled.Ac-cording to their TIMI blood flow during PCI,the patients were divided into no reflow group(n=42)and normal re-flow group(n=147).The baseline data were compared between two groups.Multivariate Logistic regression analy-sis was used to analyze the risk factors of no-reflow during PCI.The receiver operating characteristic(ROC)curve was plotted to evaluate the predictive value of PIA and Lp-PLA2 for no-reflow.Results:PI A occurred in 73 cases(38.6％),and no reflow occurred in 42 cases(22.2％)during primary PCI.Compared with patients in normal re-flow group,those in no reflow group had significant higher Lp-PLA2[(341.33±98.32)ng/ml vs.(261.95±75.21)ng/ml]and onset to reperfusion time[(7.02±1.28)h vs.(5.14±1.48)h],and significant lower incidence of PIA(23.8％ vs.42.9％)(P＜0.05 or＜0.01).Multivariate Logistic regression analysis showed that Lp-PLA2(OR=1.528,95％CI 1.028～2.030,P＜0.001),onset to reperfusion time(OR=2.602,95％CI 1.848～3.665,P＜0.001)were independent risk factors for no reflow during PCI in elderly STEMI patients,while PIA was an inde-pendent protective factor(OR=0.261,95％CI 0.101～0.671,P=0.005).The area under ROC curve of Lp-PLA2 combined PIA was 0.863(95％CI 0.806～0.909),which was significantly higher than those of Lp-PLA2[0.733(95％CI 0.664～0.794),Z=2.690,P=0.007]and PIA alone[0.609(95％CI 0.535～0.679),Z=5.657,P＜0.001].Conclusion:Pre-infarction angina has an important protective effect on no-reflow in STEMI patients.High Lp-PLA2 and absence of pre-infarction angina at admission may be good predictors of no-reflow during primary PCI in elderly patients with newly-onset acute STEMI,and it contributes to risk stratification of high risk patients.

Objective:To investigate the association of systemic immune-inflammation index(SII)and serum cysta-tin C(CysC)with the severity of acute pulmonary embolism(APE),and their predictive value for prognosis.Meth-ods:A total of 181 patients who were first diagnosed with APE in Cangzhou People's Hospital between January 2018 and January 2023 were retrospectively selected.The severity of APE was determined according to risk stratification criteria for pulmonary embolism,and the patients were divided into low-risk group(n=67),middle-risk group(n=81)and high-risk group(n=33).General clinical data and venous blood neutrophils,platelet and lymphocyte counts,CysC and other indicators were collected,and SII was calculated according to the formula.The relevant in-dicators were compared among three groups,and their correlation with the severity of APE was analyzed by Spearman correlation analysis.According to the prognosis,all APE patients were divided into favorable outcome group(n=129)and unfavorable outcome group(n=52).The general clinical data were compared and multivariate Cox regression analysis was used to study the influencing factors of unfavorable outcome in APE patients.The re-ceiver operating characteristic curve(ROC)was drawn to evaluate the predictive value of SII,CysC and their com-bination for the prognosis of APE patients.Nomogram model for prognosis was constructed.Results:Compared with patients in low-risk group,those in the middle-risk group and the high-risk group had significantly higher levels of serum creatinine,CysC and uric acid(P＜0.05 or＜0.01).The SII in the high-risk group was significant-ly higher than those of middle-risk group and low-risk group(P＜0.001 all).Spearman correlation analysis showed that serum creatinine,CysC,uric acid and SII were significant positively correlated with the severity of APE(r=0.356,0.358,0.233,0.353,P＜0.01 all).Compared with patients in the favorable outcome group,those in the unfavorable outcome group had significantly higher levels of D-dimer,serum creatinine,CysC,uric acid and SII(P＜0.01 all).There was a statistically significant difference in the severity of APE between the two groups(P=0.001).Multivariate Cox regression analysis showed that CysC,SII,and middle or high risk of disease severity were independent risk factors for unfavorable outcome in APE patients(HR=1.001～14.453,P＜0.05 or＜0.01).ROC curve indicated that the AUC of SII,CysC and their combination in predicting unfavorable outcome of APE patients were 0.815(95％CI 0.749～0.881),0.747(95％CI 0.661～0.832)and 0.878(95％CI,0.821～0.936),respectively.The combined AUC of the two was significantly higher than those of SII and CysC alone(Z=-2.234,-3.500,P＜0.05 or＜0.01).Based on the above independent risk factors,the AUC values of the 1-year and 3-year unfavorable outcome nomogram models were 92.9 and 88.2,respectively.The calibration prediction curve and the ideal curve fitted well.The decision curve showed that the model had a good net benefit.Conclusion:SII and CysC are significant positively correlated with the severity of APE and they are independent risk factors for unfavor-able outcome of APE,and the combination of the two indicators has a good predictive value for the prognosis of APE.The nomogram constructed has good accuracy and practicability.

Objective To investigate the influence of different disinfectants on the ultrasound-guided internal jugular vein puncture and adhesive application.Methods A total of 102 emergency patients with traumatic hemorrhage who underwent ultrasound-guided internal jugular vein puncture and catheterization were selected as the study subjects and randomly divided into the iodine group(51 cases)and the chlorhexidine-alcohol group(51 cases).Iodophor(0.5%effective iodine)and 2.0%chlorhexidine gluconate+70.0%ethanol were used for disinfection before puncture,respectively.The disinfection effect of the puncture site,puncture condition,ultrasound imaging,and adhesive force of the application of patients were statistically compared between the two groups.Results There was no significant difference in the bacterial count before disinfection,the bacterial count after disinfection or the qualified rate of disinfection at the puncture site of patients between the two groups(P>0.05).There were significant differences in the success rate of one-time puncture,the number of puncture and the time of puncture and catheterization between the two groups(P<0.05).There were significant differences in the rate of clear ultrasound images,adhesive force and rate of warping or shedding of the application between the two groups(P<0.05).Conclusion For emergency patients with traumatic hemorrhage,using iodophor(0.5%effective iodine)and 2.0%chlorhexidine gluconate+70.0%ethanol disinfection before ultrasound-guided internal jugular vein puncture can achieve good disinfection effects.Iodine disinfection can obtain clearer ultrasound images and a higher success rate of one-time puncture,but the adhesive force of the application is poor,making it prone to warping or shedding.

OBJECTIVES: To investigate the clinical characteristics of cytokine release syndrome (CRS) in children with thalassemia major (TM) after haploidentical hematopoietic stem cell transplantation (haplo-HSCT) and their prognosis. METHODS: A retrospective analysis was performed for the clinical data of 280 children with TM who underwent haplo-HSCT in the Department of Hematology and Oncology, Shenzhen Children's Hospital, from January 2019 to December 2021. According to the CRS criteria, they were divided into two groups: CRS grade <3 (260 children) and CRS grade ≥3 (20 children). The children with TM were analyzed in terms of clinical characteristics of CRS after haplo-HSCT and their prognosis. RESULTS: There were significant differences between the two groups in neutrophil engraftment time, clinical manifestations of CRS, and the rate of use of glucocorticoids within 4 days after haplo-HSCT (P=0.012, 0.040, and <0.001 respectively). For the CRS grade <3 group, the incidence rate of acute graft-versus-host disease (aGVHD) was 9.6% within 3 months after transplantation, while no aGVHD was observed in the CRS grade ≥3 group within 3 months after transplantation, but there was no significant difference in the incidence of aGVHD between the two groups within 3 months after transplantation (P=0.146). No transplantation-related death was observed in either group within 3 months after haplo-HSCT. CONCLUSIONS The children with CRS grade≥3 have an early neutrophil engraftment time, severe and diverse clinical manifestations of CRS, and a high rate of use of glucocorticoids within 4 days after haplo-HSCT. For these children, early use of low-dose glucocorticoids after transplantation may alleviate CRS response and reduce the incidence of aGVHD, thereby bringing more benefits to the children. CRS after haplo-HSCT has no significant impact on the prognosis of the children.
Humans ; Hematopoietic Stem Cell Transplantation/adverse effects* ; Male ; Female ; Child ; Retrospective Studies ; Child, Preschool ; Graft vs Host Disease/prevention & control* ; beta-Thalassemia/therapy* ; Adolescent ; Cytokine Release Syndrome/etiology* ; Transplantation, Haploidentical/adverse effects* ; Infant ; Prognosis ; Glucocorticoids/therapeutic use*

Objective To evaluate the bioequivalence and safety of ezetimibe tablets in healthy Chinese subjects.Methods The study was designed as a single-center,randomized,open-label,two-period,two-way crossover,single-dose trail.Subjects who met the enrollment criteria were randomized into fasting administration group and postprandial administration group and received a single oral dose of 10 mg of the subject presparation of ezetimibe tablets or the reference presparation per cycle.The blood concentrations of ezetimibe and ezetimibe-glucuronide conjugate were measured by high-performance liquid chromatography-tandem mass spectrometry(HPLC-MS/MS),and the bioequivalence of the 2 preparations was evaluated using the WinNonlin 7.0 software.Pharmacokinetic parameters were calculated to evaluate the bioequivalence of the 2 preparations.The occurrence of all adverse events was also recorded to evaluate the safety.Results The main pharmacokinetic parameters of total ezetimibe in the plasma of the test and the reference after a single fasted administration:Cmax were(118.79±35.30)and(180.79±51.78)nmol·mL-1;tmax were 1.40 and 1.04 h;t1/2 were(15.33±5.57)and(17.38±7.24)h;AUC0-t were(1 523.90±371.21)and(1 690.99±553.40)nmol·mL-1·h;AUC0-∞ were(1 608.70±441.28),(1 807.15±630.00)nmol·mL-1·h.The main pharmacokinetic parameters of total ezetimibe in plasma of test and reference after a single meal:Cmax were(269.18±82.94)and(273.93±87.78)nmol·mL-1;Tmax were 1.15 and 1.08 h;t1/2 were(22.53±16.33)and(16.02±5.84)h;AUC0_twere(1 463.37±366.03),(1 263.96±271.01)nmol·mL-1·h;AUC0-∞ were(1 639.01±466.53),(1 349.97±281.39)nmol·mL-1·h.The main pharmacokinetic parameters Cmax,AUC0-tand AUC0-∞ of the two preparations were analyzed by variance analysis after logarithmic transformation.In the fasting administration group,the 90％CI of the log-transformed geometric mean ratios were within the bioequivalent range for the remaining parameters in the fasting dosing group,except for the Cmax of ezetimibe and total ezetimibe,which were below the lower bioequivalent range.The Cmax of ezetimibe,ezetimibe-glucuronide,and total ezetimibe in the postprandial dosing group was within the equivalence range,and the 90％CI of the remaining parameters were not within the equivalence range for bioequivalence.Conclusion This test can not determine whether the test preparation and the reference preparation of ezetimibe tablets have bioequivalence,and further clinical trials are needed to verify it.