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: Glucocorticoid-induced osteoporosis (GIOP) is a common complication of prolonged glucocorticoid therapy. Chlorogenic acid (CGA), a polyphenol with antioxidant properties that is extracted from traditional Chinese medicines such as Eucommiae Cortex, has potential anti-osteoporotic activity. This study aimed to investigate the possible effects of CGA on GIOP in mice and murine long bone osteocyte Y4 (MLO-Y4) cells and explore the underlying molecular mechanisms. METHODS: The protective effects of CGA were initially evaluated in the GIOP mouse model induced by dexamethasone (Dex). The micro-computed tomography, hematoxylin-eosin staining, silver nitrate staining, and serum detection were used to assess the efficacy of CGA for improving bone formation in vivo. Then, network pharmacology analysis was used to predict the potential targets and molecular mechanisms underlying the therapeutic efficacy of CGA against GIOP. After that, 2',7'-dichlorofluorescein diacetate staining, flow cytometry, real-time quantitative reverse transcription polymerase chain reaction, and Western blotting were used to verify the mechanisms of CGA against GIOP in vitro. RESULTS: Animal experiments showed that CGA treatment effectively attenuated Dex-induced decreases in bone mass and strength and improved disrupted osteocyte morphology in mice. The protein-protein interaction analysis highlighted erb-b2 receptor tyrosine kinase (ERBB2), which is also known as human epidermal growth factor receptor 2 (HER2), caspase-3, kinase insert domain receptor, matrix metallopeptidase 9, matrix metallopeptidase 2, proto-oncogene tyrosine-protein kinase Src, and epidermal growth factor receptor as core targets. The Kyoto Encyclopedia of Genes and Genomes analysis revealed several significantly enriched pathways (P < 0.05), including the ERBB, phosphoinositide 3 kinase-AKT serine/threonine kinase 1 (AKT), and mechanistic target of rapamycin kinase (mTOR) pathways. Cellular experiments verified that CGA enhanced bone formation and promoted autophagy while inhibiting apoptosis in MLO-Y4 cells exposed to Dex, which was associated with the upregulated expression of HER2 and activation of the HER2/AKT/mTOR signaling pathway. CONCLUSION CGA exerted anti-osteoporotic effects against GIOP, partially through targeting osteocytes and modulating the HER2/AKT/mTOR signaling pathway. Please cite this article as: Xie AN, Zhang SZY, Zhang Y, Cao JL, Wang CL, Wang LB, Wu HJ, Zhang J, Dai WW. Chlorogenic acid mitigates glucocorticoid-induced osteoporosis via modulation of HER2/AKT/mTOR signaling pathway. J Integr Med. 2025; 23(6):670-682.
Animals ; Chlorogenic Acid/therapeutic use* ; Osteoporosis/metabolism* ; Signal Transduction/drug effects* ; Proto-Oncogene Proteins c-akt/metabolism* ; TOR Serine-Threonine Kinases/metabolism* ; Mice ; Glucocorticoids/adverse effects* ; Receptor, ErbB-2/metabolism* ; Proto-Oncogene Mas ; Dexamethasone/adverse effects* ; Osteocytes/drug effects* ; Osteogenesis/drug effects* ; Male ; Cell Line ; Mice, Inbred C57BL ; Humans

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*

Rheumatoid arthritis (RA) and myasthenia gravis (MG) are two distinct autoimmune diseases. Compared with the general population, the incidence of RA is notably higher among patients with MG. Similarly, the rate of MG in patients diagnosed with RA is also significantly increased. In this report, we presented an elderly female patient with a history usage of long-term glucocorticoid and conventional synthetic disease-modifying antirheumatic drugs (csDMARDs), whose RA symptoms remained inadequately controlled. She later exhibited drooping of the right eyelid and double vision, leading to a diagnosis of ocular myasthenia gravis (OMG). Then, we made a literature review and found that the RA patients with co-existing MG were relatively more common in middle-aged and elderly women, and most of them did not have thymoma. Thymoma wasn ' t found in our patient, which was consistent with the cli-nical characteristics of RA complicated with MG reported in previous reports. In addition, there was li-mited treatment experience in patients with both RA and MG. The treatment stratergies for RA or MG included glucocorticoids and immunosuppressants. Among the 18 patients we analyzed, 8 patients expe-rienced relief after csDMARDs, while other 8 patients received biologics or targeted DMARDs, including tumor necrosis factor inhibitors (TNFi) in 5 cases, JAK inhibitors in 2 cases, and B-cell depletion therapy (rituximab) in 2 cases. What called for special attention was that one RA patient was diagnosed with MG after using 23 months of methotrexate and 6 weeks of etanercept (TNFi), with rituximab 1 000 mg for the first time, followed by 500 mg every 6 months, and finally both RA and MG were well controlled. For the patient in this study, MG symptoms improved with increased dosage of prednisone. In order to tapper the dose of glucocorticoid, it was necessary for more potent immunosuppressant for both RA and MG. Given her history of cardiac conditions, JAK inhibitors were not considered, and due to the uncertain efficacy of TNFi, we chose to administer low-dose rituximab (100 mg). Subsequent follow-up revealed stable conditions for both RA and MG, allowing for discontinuance of glucocorticoid after 5 months. It reflected the potential efficacy and cost-effectiveness of low-dose, long-interval rituximab in treating RA patients combined with MG, while it also minimized infection risks. However, the duration for subsequent infusions remained uncertain and required further observation. In conclusion, RA combined with MG is rare. For patients exhibiting poor responses to csDMARDs, low-dose, long-interval rituximab might be a promising treatment option.
Humans ; Arthritis, Rheumatoid/drug therapy* ; Rituximab/administration & dosage* ; Myasthenia Gravis/drug therapy* ; Female ; Antirheumatic Agents/administration & dosage* ; Aged ; Glucocorticoids/therapeutic use*

OBJECTIVES: To investigate the change in the distribution of memory B cell subsets in children with frequently relapsing nephrotic syndrome (FRNS) during the course of the disease. METHODS: A total of 35 children with primary nephrotic syndrome (PNS) who attended the Department of Pediatrics of the Affiliated Hospital of Xuzhou Medical University from October 2020 to October 2021 were enrolled as subjects in this prospective study. According to the response to glucocorticoid (GC) therapy and frequency of recurrence, the children were divided into two groups: FRNS (n=20) and non-FRNS (NFRNS; n=15). Fifteen children who underwent physical examination were enrolled as the control group. The change in memory B cells after GC therapy was compared between groups, and its correlation with clinical indicators was analyzed. RESULTS: Before treatment, the FRNS and NFRNS groups had significantly increased percentages of total B cells, total memory B cells, IgD⁺ memory B cells, and IgE⁺ memory B cells compared with the control group, and the FRNS group had significantly greater increases than the NFRNS group (P<0.05); the FRNS group had a significantly lower percentage of class-switched memory B cells than the NFRNS and control groups (P<0.05). After treatment, the FRNS and NFRNS groups had significant reductions in the percentages of total B cells, total memory B cells, IgM⁺IgD⁺ memory B cells, IgM⁺ memory B cells, IgE⁺ memory B cells, IgD⁺ memory B cells, and IgG⁺ memory B cells (P<0.05) and a significant increase in the percentage of class-switched memory B cells (P<0.05). The FRNS group had a significantly higher urinary protein quantification than the NFRNS and control groups (P<0.05) and a significantly lower level of albumin than the control group (P<0.05). In the FRNS group, urinary protein quantification was negatively correlated with the percentage of class-switched memory B cells and was positively correlated with the percentage of IgE⁺ memory B cells (P<0.05). CONCLUSIONS Abnormal distribution of memory B cell subsets may be observed in children with FRNS, and the percentages of IgE⁺ memory B cells and class-switched memory B cells can be used as positive and negative correlation factors for predicting recurrence after GC therapy in these children.
Child ; Humans ; B-Lymphocyte Subsets/metabolism* ; Immunoglobulin E ; Immunoglobulin M ; Nephrotic Syndrome/immunology* ; Prospective Studies ; Glucocorticoids/therapeutic use*

Humans ; Glucocorticoids/therapeutic use* ; Cochlear Implantation

Dental erosion is characterized by progressively destroyed teeth, which has no relation to bacteria but to chemicals. Some internal factors, such as gastroesophageal reflux induced by bulimia, anorexia, gastrointestinal diseases, or drugs, and external factors, such as diet, drugs, and occupational acid exposure, are considered promotive factors for this disease. This article presents a patient suffering from severe dental erosion in the whole dentition, especially in the maxillary teeth, due to gastroesophageal reflux induced by glucocorticoid therapy for optic neuritis. This article discusses the mechanism between optic neuritis glucocorticoid therapy and dental erosion.
Humans ; Glucocorticoids/therapeutic use* ; Tooth Erosion/therapy* ; Gastroesophageal Reflux/complications*

INTRODUCTION: The study was performed to determine the psychological problems in children with idiopathic nephrotic syndrome (INS) while they were on steroid therapy, as compared to healthy children. METHODS: This prospective cohort study was conducted in a paediatric clinic of a tertiary hospital. Parents of the participants in the INS group and control group (comprising children without chronic illness) completed questionnaires using the Child Behavioural Checklist (CBCL). The CBCL measures a range of age-specific emotional and psychological problems, including internalising and externalising domains. Analyses of the CBCL scores between groups were done using Mann-Whitney U test. RESULTS: A total of 140 children were recruited with an equal number in the INS and control groups. There was a significant difference in the mean total CBCL scores between the INS group and the control group, specifically in the withdrawal, somatic, anxious and aggressiveness subdomains. Similar findings were demonstrated in correlation between total psychological problems and corticosteroid dosage. In the INS group, steroid dose and cushingoid features were found to have a significant positive association with internalising psychological problems. CONCLUSION Children with INS on corticosteroid treatment showed an increase in internalising and externalising scores, as compared to healthy children.
Child ; Humans ; Child Behavior Disorders/psychology* ; Nephrotic Syndrome/psychology* ; Problem Behavior/psychology* ; Prospective Studies ; Southeast Asian People ; Glucocorticoids/therapeutic use*

BACKGROUND: Lung cancer is the second most common cancer worldwide, with non-small-cell lung cancer (NSCLC) accounting for the majority of cases. Patients with NSCLC have achieved great survival benefits from immunotherapies targeting immune checkpoints. Glucocorticoids (GCs) are frequently used for palliation of cancer-associated symptoms, as supportive care for non-cancer-associated symptoms, and for management of immune-related adverse events (irAEs). The aim of this study was to clarify the safety and prognostic significance of glucocorticoid use in advanced patients with NSCLC treated with immune checkpoint inhibitors (ICIs). METHODS: The study searched publications from PubMed, Embase, Cochrane Library, Web of Science, China Biology Medicine disc, Chinese National Knowledge Infrastructure, Wanfang Data, and Chinese Science and Technology Journal Database up to March 1st, 2022, and conducted a meta-analysis to assess the effects of glucocorticoid use on overall survival (OS) and progression-free survival (PFS) in NSCLC patients treated with ICIs through the available data. The study calculated the pooled hazard ratios (HRs) and 95% confidence intervals (CIs). RESULTS: This study included data from 25 literatures that were mainly retrospective, with 8713 patients included. Patients taking GCs had a higher risk for tumor progression and death compared with those not taking GCs (PFS: HR = 1.57, 95% CI: 1.33-1.86, P <0.001; OS: HR = 1.63, 95% CI: 1.41-1.88, P <0.001). GCs used for cancer-associated symptoms caused an obviously negative effect on both PFS and OS (PFS: HR = 1.74, 95% CI: 1.32-2.29, P <0.001; OS: HR = 1.76, 95% CI: 1.52-2.04, P <0.001). However, GCs used for irAEs management did not negatively affect prognosis (PFS: HR = 0.68, 95% CI: 0.46-1.00, P = 0.050; OS: HR = 0.53, 95% CI: 0.34-0.83, P = 0.005), and GCs used for non-cancer-associated indications had no effect on prognosis (PFS: HR = 0.92, 95%CI: 0.63-1.32, P = 0.640; OS: HR = 0.91, 95% CI: 0.59-1.41, P = 0.680). CONCLUSIONS In advanced NSCLC patients treated with ICIs, the use of GCs for palliation of cancer-associated symptoms may result in a worse PFS and OS, indicating that they increase the risk of tumor progression and death. But, in NSCLC patients treated with ICIs, the use of GCs for the management of irAEs may be safe, and the use of GCs for the treatment of non-cancer-associated symptoms may not affect the ICIs' survival benefits. Therefore, it is necessary to be careful and evaluate indications rationally before administering GCs in individualized clinical management.
Humans ; Carcinoma, Non-Small-Cell Lung/drug therapy* ; Glucocorticoids/therapeutic use* ; Immune Checkpoint Inhibitors/therapeutic use* ; Lung Neoplasms/drug therapy* ; Retrospective Studies

Objective: To observe the efficacy and adverse reactions of a combination therapy regimen based on bortezomib and glucocorticoids in recurrent/refractory immune thrombocytopenic purpura (iTTP) . Methods: Six patients with recurrent/refractory TTP were included and treated with a glucocorticoid and two courses of bortezomib-based regimen. The clinical remission status of patients, changes in ADAMTS13 activity/ADAMTS13 inhibitor, and the occurrence of treatment-related adverse reactions were observed. Results: Of the 6 patients, 2 were males and 4 were females, with a median age of 21.5 (18-68) years. Refractory TTP was found in 1 case and recurrent TTP in 5 cases. Glucocorticoids were administered with reference to prednisone at 1 mg·kg(-1)·d(-1), and gradually reduced in dosage after achieving clinical remission. Bortezomib is subcutaneously administered at 1.3 mg/m(2) on days 1, 4, 8, and 11 with a 28-day treatment course consisting of 2 courses. Six patients achieved clinical remission after receiving bortezomib as the main treatment. ADMATS13 activity returned to normal in all patients with TTP after treatment, and the ADAMTS13 inhibitor turned negative. Thrombocytopenia is the most common adverse reaction after treatment, with other adverse reactions, including peripheral neuritis and abdominal pain, but ultimately all patients returned to normal. In a median follow-up of 26 (9-41) months, 5 patients maintained sustained remission, and 1 patient relapsed after 16 months of bortezomib treatment. Conclusion: Combination therapy of bortezomib and glucocorticoids has a satisfactory therapeutic effect and controllable adverse reactions for recurrent/refractory iTTP.
Male ; Female ; Humans ; Young Adult ; Adult ; Middle Aged ; Aged ; Bortezomib/therapeutic use* ; Glucocorticoids/therapeutic use* ; Rituximab/therapeutic use* ; Purpura, Thrombotic Thrombocytopenic/drug therapy* ; Purpura, Thrombocytopenic, Idiopathic/drug therapy* ; ADAMTS13 Protein/therapeutic use*