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

[Objective] To establish a method for detecting the potency of recombinant human coagulation factor Ⅶa for injection. [Methods] By adding the sample and factor Ⅶ deficient plasma to the sample cup and activating the reaction with prothrombin time assay reagent (PT reagent), the coagulation time of the sample was determined by the change in magnetic bead swing amplitude in the sample cup. The logarithm of coagulation time was inversely proportional to the logarithm of human factor Ⅶa potency. [Results] Under the experimental conditions, the specificity of the methodology was evaluated through spiked recovery, and the recovery rates ranged from 90.0% to 110.0%. Within the range from 0.125 to 1.000 IU/mL, there was a good linear response between the potency and coagulation time of the standard and sample, with correlation coefficients r>0.99. As for the accuracy and repeatability, the recovery rates of various concentrations detected in the stock solution were 101.0%, 100.0% and 112.0%, respectively, with RSD values of 2.6%, 4.0% and 0.0%, respectively. The recovery rates of various concentrations in finished product testing were 104.0%, 94.7% and 112.0%, respectively, with RSD values of 1.9%, 2.4% and 0.0%, respectively. As for the intermediate precision, the RSD were 4.5% and 3.7%, respectively. After treated with sample diluent, the sample was tested at room temperature for 6 hours and still exhibited relatively stable biological activity. [Conclusion] This detection method is accurate, stable, easy to operate and highly automated, and is suitable for detecting the potency of recombinant human coagulation factor Ⅶa for Injection.

Biliary surgery has a long history,with biliary strictures being a common clinical issue in this field.These strictures primarily include benign strictures,malignant strictures,and biliary strictures of unknown etiology.The nature of the biliary stricture directly determines the treatment approach.For strictures that are difficult to characterize with CT and MRCP/MRI,endoscopic ultrasound,and related technologies are important tools for the diagnosis and treatment.The rise of technologies such as confocal laser endomicroscopy,optical coherence tomography,and next-generation sequencing has expanded the diagnostic and therapeutic options for biliary strictures.Furthermore,endoscopic surgeons or treatment teams who are proficient in both endoscopic techniques and surgical procedures have unique strengths when dealing with complex anatomical structures or resectable biliary tumors.Although significant advancements have been made in biliary surgery in recent years,particularly in endoscopic technology,surgical techniques,and diagnostic methods,several challenges still remain to be addressed.Here,the authors provide a review of the current status,advancements,and challenges in the endoscopic surgical treatment of biliary strictures,with the aim of offering insights for clinical practice.

Poly(lactic-co-glycolide)(PLGA)is a key excipient in long-acting sustained-release preparations,and its degradation properties directly affect the drug release behavior.In this study,PLGA microspheres were prepared by microfluidic techniques,and the morphology changes of the microspheres were observed by scanning electron microscopy(SEM).In alkaline environment,due to the accelerated hydrolysis of ester bonds,the surface of the microspheres was rapidly dissolved and eroded,and the degradation rate was significantly higher than that in acidic environment.High temperature accelerated the degradation of PLGA microspheres.Under neutral and alkaline conditions,the microspheres showed aggregation and adhesion.Under acidic conditions,the microspheres gradually decomposed into irregular fragments.The high ionic strength further promoted the surface corrosion of the microspheres,especially under extreme pH conditions.Simultaneously,PLGA microspheres encapsulating coumarin were prepared to simulate the microsphere formulation.The release rate of coumarin after degradation of the microspheres under different conditions was observed by measuring the absorbance with ultraviolet-visible spectrophotometry.The results were consistent with those of the blank microspheres.This study revealed that the degradation of PLGA microspheres was significantly pH-dependent,temperature sensitive and ion strength responsive.These findings not only helped to understand and optimize the long-term stability and controlled release performance of drug-carrying microspheres,but also provided a theoretical basis for further improvement of PLGA-based drug carrier design.

Objective To explore the targeted regulatory relationship of miR-330-5p on OY-TES-1 in glioblastoma and the effect of miR-330-5p/OY-TES-1 axis on the migration ability of glioblastoma.Methods Bioinformatics analysis was performed to analyze the expression level of miR-330-5p in patients with glioblastoma and its influence on prognosis and survival of patients.The glioblastoma cells U251 were divided into miR-330-5p minics group,minics-NC group,and miR-330-5p+OY-TES-1 overexpression group(miR-330-5p minics+pcDNA3.1-OY-TES-1).The effect of miR-330-5p on the activity of OY-TES-1 3'UTR region was detected by double luciferase reporter gene experiment.The expression of OY-TES-1 mRNA was detected by qRT-PCR.The effect of miR-330-5p/OY-TES-1 axis on the migration ability of glioblastoma cells was detected by Transwell migration assay.Results The expression of miR-330-5p in glioblastoma tissue was significantly lower than those in non-tumor brain tissue and low-grade glioma tissue(P<0.05).The survival time of glioblastoma patients with high expression of miR-330-5p was significantly longer than that of patients with low expression of miR-330-5p(P<0.05).After overexpression of miR-330-5p,the activity of OY-TES-1 3'UTR region was decreased(P<0.05).Compared with minics-NC group,the expression levels of OY-TES-1 mRNA of U251 and U87MG cells in miR-330-5p minics group were significantly decreased(P<0.01).Compared with minics-NC group,the numbers of migrating cells in miR-330-5p minics group and miR-330-5p+OY-TES-1 overexpression group were significantly decreased(P<0.05).Compared with miR-330-5p minics group,the number of migrating cells in miR-330-5p+OY-TES-1 overexpression group was significantly increased(P<0.01).Conclusion MiR-330-5p targets OY-TES-1 to inhibit the migration of glioblastoma.

Objective:To explore the diagnostic value of serum soluble semaphorin 4D (sSema4D) and soluble CD40 ligand (sCD40L) in left ventricular hypertrophy (LVH) in patients with primary hypertension (EH).Methods:Eighty-four patients with EH combined with LVH admitted to Qingdao Hospital of Shandong First Medical University from December 2022 to December 2023 were prospectively selected as the study group, and 84 patients with EH and without LVH admitted to Qingdao Hospital of Shandong First Medical University during the same period were regarded as the control group. Enzyme linked immunosorbent assay was applied to detect the levels of sSema4D and sCD40L. Employing Pearson correlation coefficient, the study assessed the association between concentrations of sSema4D and sCD40L in serum and various echocardiographic measurements. A multivariate Logistic regression model was engaged to probe into the contributing factors for the development of LVH. ROC curve was plotted to analyze the diagnostic value of serum sSema4D and sCD40L for EH combined with LVH.Results:Serum sSema4D and sCD40L levels were significantly higher in the study group than in the control group: (8.56 ± 2.19) μg/L vs. (5.12 ± 1.43) μg/L, (4.02 ± 1.03) μg/L vs. (3.22 ± 0.98) μg/L, and the differences were statistically significant ( P<0.05). The duration of hypertension, LVEDD, IVSTD, LVPWT, and LVMI were significantly higher in the study group than in the control group: (7.33 ± 1.53) years vs. (4.26 ± 1.35) years, (50.28 ± 3.33) mm vs. (44.45 ± 3.76) mm, (11.64 ± 3.21) mm vs. (9.53 ± 2.89) mm, (12.45 ± 1.52) mm vs. (9.13 ± 0.98) mm, (126.11 ± 15.28) g/m 2 vs. (81.15 ± 11.31) g/m 2, and the differences were statistically significant ( P<0.05). According to Pearson correlation analysis, it was known that both serum sSema4D and sCD40L were positively correlated with LVEDD, IVSTD, LVPWT and LVMI ( r = 0.425 and 0.533, 0.612 and 0.436, 0.513 and 0.628, 0.589 and 0.618; P<0.05). Multivariate Logistic regression analysis showed that hypertension duration, LVEDD, IVSTD, LVPWT, LVMI, sSema4D, sCD40L were risk factors for LVH in EH patients ( P<0.05). According to the ROC curve, the AUC for diagnosing EH combined with LVH with serum sSema4D was 0.848, the AUC for diagnosing EH combined with LVH with serum sCD40L was 0.725, and the AUC for diagnosing EH combined with LVH with serum sCD40L was 0.888, the combination of sCD40L and sCD40L was superior to their respective individual diagnoses ( Z = 2.651 and 2.526, P<0.05). Conclusions:The serum levels of sSema4D and sCD40L in patients with EH combined with LVH are obviously elevated, which are influencing factors for the occurrence of EH combined with LVH. Combined testing of the two has high diagnostic value for EH combined with LVH.

Biliary surgery has a long history,with biliary strictures being a common clinical issue in this field.These strictures primarily include benign strictures,malignant strictures,and biliary strictures of unknown etiology.The nature of the biliary stricture directly determines the treatment approach.For strictures that are difficult to characterize with CT and MRCP/MRI,endoscopic ultrasound,and related technologies are important tools for the diagnosis and treatment.The rise of technologies such as confocal laser endomicroscopy,optical coherence tomography,and next-generation sequencing has expanded the diagnostic and therapeutic options for biliary strictures.Furthermore,endoscopic surgeons or treatment teams who are proficient in both endoscopic techniques and surgical procedures have unique strengths when dealing with complex anatomical structures or resectable biliary tumors.Although significant advancements have been made in biliary surgery in recent years,particularly in endoscopic technology,surgical techniques,and diagnostic methods,several challenges still remain to be addressed.Here,the authors provide a review of the current status,advancements,and challenges in the endoscopic surgical treatment of biliary strictures,with the aim of offering insights for clinical practice.

Objective:To explore the diagnostic value of serum soluble semaphorin 4D (sSema4D) and soluble CD40 ligand (sCD40L) in left ventricular hypertrophy (LVH) in patients with primary hypertension (EH).Methods:Eighty-four patients with EH combined with LVH admitted to Qingdao Hospital of Shandong First Medical University from December 2022 to December 2023 were prospectively selected as the study group, and 84 patients with EH and without LVH admitted to Qingdao Hospital of Shandong First Medical University during the same period were regarded as the control group. Enzyme linked immunosorbent assay was applied to detect the levels of sSema4D and sCD40L. Employing Pearson correlation coefficient, the study assessed the association between concentrations of sSema4D and sCD40L in serum and various echocardiographic measurements. A multivariate Logistic regression model was engaged to probe into the contributing factors for the development of LVH. ROC curve was plotted to analyze the diagnostic value of serum sSema4D and sCD40L for EH combined with LVH.Results:Serum sSema4D and sCD40L levels were significantly higher in the study group than in the control group: (8.56 ± 2.19) μg/L vs. (5.12 ± 1.43) μg/L, (4.02 ± 1.03) μg/L vs. (3.22 ± 0.98) μg/L, and the differences were statistically significant ( P<0.05). The duration of hypertension, LVEDD, IVSTD, LVPWT, and LVMI were significantly higher in the study group than in the control group: (7.33 ± 1.53) years vs. (4.26 ± 1.35) years, (50.28 ± 3.33) mm vs. (44.45 ± 3.76) mm, (11.64 ± 3.21) mm vs. (9.53 ± 2.89) mm, (12.45 ± 1.52) mm vs. (9.13 ± 0.98) mm, (126.11 ± 15.28) g/m 2 vs. (81.15 ± 11.31) g/m 2, and the differences were statistically significant ( P<0.05). According to Pearson correlation analysis, it was known that both serum sSema4D and sCD40L were positively correlated with LVEDD, IVSTD, LVPWT and LVMI ( r = 0.425 and 0.533, 0.612 and 0.436, 0.513 and 0.628, 0.589 and 0.618; P<0.05). Multivariate Logistic regression analysis showed that hypertension duration, LVEDD, IVSTD, LVPWT, LVMI, sSema4D, sCD40L were risk factors for LVH in EH patients ( P<0.05). According to the ROC curve, the AUC for diagnosing EH combined with LVH with serum sSema4D was 0.848, the AUC for diagnosing EH combined with LVH with serum sCD40L was 0.725, and the AUC for diagnosing EH combined with LVH with serum sCD40L was 0.888, the combination of sCD40L and sCD40L was superior to their respective individual diagnoses ( Z = 2.651 and 2.526, P<0.05). Conclusions:The serum levels of sSema4D and sCD40L in patients with EH combined with LVH are obviously elevated, which are influencing factors for the occurrence of EH combined with LVH. Combined testing of the two has high diagnostic value for EH combined with LVH.

Objective To explore the targeted regulatory relationship of miR-330-5p on OY-TES-1 in glioblastoma and the effect of miR-330-5p/OY-TES-1 axis on the migration ability of glioblastoma.Methods Bioinformatics analysis was performed to analyze the expression level of miR-330-5p in patients with glioblastoma and its influence on prognosis and survival of patients.The glioblastoma cells U251 were divided into miR-330-5p minics group,minics-NC group,and miR-330-5p+OY-TES-1 overexpression group(miR-330-5p minics+pcDNA3.1-OY-TES-1).The effect of miR-330-5p on the activity of OY-TES-1 3'UTR region was detected by double luciferase reporter gene experiment.The expression of OY-TES-1 mRNA was detected by qRT-PCR.The effect of miR-330-5p/OY-TES-1 axis on the migration ability of glioblastoma cells was detected by Transwell migration assay.Results The expression of miR-330-5p in glioblastoma tissue was significantly lower than those in non-tumor brain tissue and low-grade glioma tissue(P<0.05).The survival time of glioblastoma patients with high expression of miR-330-5p was significantly longer than that of patients with low expression of miR-330-5p(P<0.05).After overexpression of miR-330-5p,the activity of OY-TES-1 3'UTR region was decreased(P<0.05).Compared with minics-NC group,the expression levels of OY-TES-1 mRNA of U251 and U87MG cells in miR-330-5p minics group were significantly decreased(P<0.01).Compared with minics-NC group,the numbers of migrating cells in miR-330-5p minics group and miR-330-5p+OY-TES-1 overexpression group were significantly decreased(P<0.05).Compared with miR-330-5p minics group,the number of migrating cells in miR-330-5p+OY-TES-1 overexpression group was significantly increased(P<0.01).Conclusion MiR-330-5p targets OY-TES-1 to inhibit the migration of glioblastoma.

Analyzing polysorbate 20(PS20)composition and the impact of each component on stability and safety is crucial due to formulation variations and individual tolerance.The similar structures and polarities of PS20 components make accurate separation,identification,and quantification challenging.In this work,a high-resolution quantitative method was developed using single-dimensional high-performance liquid chromatography(HPLC)with charged aerosol detection(CAD)to separate 18 key components with multiple esters.The separated components were characterized by ultra-high-performance liquid chro-matography-quadrupole time-of-flight mass spectrometry(UHPLC-Q-TOF-MS)with an identical gradient as the HPLC-CAD analysis.The polysorbate compound database and library were expanded over 7-time compared to the commercial database.The method investigated differences in PS20 samples from various origins and grades for different dosage forms to evaluate the composition-process relationship.UHPLC-Q-TOF-MS identified 1329 to 1511 compounds in 4 batches of PS20 from different sources.The method observed the impact of 4 degradation conditions on peak components,identifying stable components and their tendencies to change.HPLC-CAD and UHPLC-Q-TOF-MS results provided insights into fingerprint differences,distinguishing quasi products.