Patients with inflammatory bowel disease (IBD) require long-term pharmacotherapy. Due to the wide variety of clinically available drugs, medication safety has become increasingly concerning. As an indispensable component of pharmaceutical formulations, drug excipients may induce various adverse reactions, including rash, allergic responses, and gastrointestinal discomfort, and may even lead to severe organic injury. However, they are often overlooked in clinical practice. Therefore, identifying and managing excipient-related adverse reactions is crucial for ensuring medication safety. To address this issue, this article systematically reviews common excipients in IBD therapeutics, the underlying mechanisms of excipient-induced adverse reactions, and corresponding management strategies, aiming to enhance clinicians' awareness of excipient-related issues, improve their ability to recognize and manage such reactions, and ultimately ensure patient safety.

OBJECTIVE: To evaluate the efficacy and safety of Shexiang Tongxin Dropping Pill (STDP) in treating stable angina patients with phlegm-heat and blood-stasis syndrome by exercise duration and metabolic equivalents. METHODS: This multicenter, randomized, double-blind, placebo-controlled clinical trial enrolled stable angina patients with phlegm-heat and blood-stasis syndrome from 22 hospitals. They were randomized 1:1 to STDP (35 mg/pill, 6 pills per day) or placebo for 56 days. The primary outcome was the exercise duration and metabolic equivalents (METs) assessed by the standard Bruce exercise treadmill test after 56 days of treatment. The secondary outcomes included the total angina symptom score, Chinese medicine (CM) symptom scores, Seattle Angina Questionnaire (SAQ) scores, changes in ST-T on electrocardiogram and adverse events (AEs). RESULTS: This trial enrolled 309 patients, including 155 and 154 in the STDP and placebo groups, respectively. STDP significantly prolonged exercise duration with an increase of 51.0 s, compared to a decrease of 12.0 s with placebo (change rate: -11.1% vs. 3.2%, P<0.01). The increase in METs was significantly greater in the STDP group than in the placebo group (change: -0.4 vs. 0.0, change rate: -5.0% vs. 0.0%, P<0.01). The improvement of total angina symptom scores (25.0% vs. 0.0%), CM symptom scores (38.7% vs. 11.8%), reduction of nitroglycerin consumption (100.0% vs. 11.3%), and all domains of SAQ, were significantly greater with STDP than placebo (all P<0.01). The changes in Q-T intervals at 28 and 56 days from baseline were similar between the two groups (both P>0.05). Twenty-five participants (16.3%) with STDP and 16 (10.5%) with placebo experienced AEs (P=0.131), with no serious AEs observed. CONCLUSION STDP could improve exercise tolerance in patients with stable angina and phlegm-heat and blood stasis syndrome, with a favorable safety profile. (Registration No. ChiCTR-IPR-15006020).
Humans ; Double-Blind Method ; Drugs, Chinese Herbal/adverse effects* ; Male ; Female ; Middle Aged ; Angina, Stable/physiopathology* ; Aged ; Syndrome ; Treatment Outcome ; Placebos ; Tablets

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

Abstract In recent years, the prevalence of overweight and obesity among children and adolescents has risen rapidly, posing a serious threat to their physical and mental health. To provide scientific, systematic, and standardized weight management guidance for overweight and obese children and adolescents, the study focuses on the core concept of healthy lifestyle intervention, integrates multidisciplinary expert opinions and research findings,and proposes a comprehensive multidisciplinary intervention framework covering scientific exercise intervention, precise nutrition and diet, optimized sleep management, and standardized psychological support. It calls for the establishment of a multi agent collaborative management mechanism led by the government, implemented by families, fostered by schools, initiated by individuals, optimized by communities, reinforced by healthcare, and coordinated by multiple stakeholders. Emphasizing a child and adolescent centered approach, the consensus advocates for comprehensive, multi level, and personalized guidance strategies to promote the internalization and maintenance of a healthy lifestyle. It serves as a reference and provides recommendations for the effective prevention and control of overweight and obesity, and enhancing the health level of children and adolescents.

Objective To explore the influencing factors of different types of small intestinal bacterial overgrowth(SIBO).Methods A total of 539 patients who were hospitalized in the Department of Gastroenterology,the Sixth Medical Center of PLA General Hospital from June 2021 to December 2021 and who underwent methane-hydrogen breath test were retrospectively selected.Based on breath test results,patients were divided into SIBO-negative group(n=300)and SIBO-positive group(n=239).The clinical data were compared between two groups.According to the specific values of breath test results,SIBO-positive patients were further divided into hydrogen-producing bacterial overgrowth(hydrogen-positive,n=103),intestinal methanogen overgrowth(methanogen-positive,n=80),and simultaneous methanogen and hydrogen-producing bacterial overgrowth(double positive,n=56)groups.Multivariate logistic regression analysis was employed to identify influencing factors of different SIBO types.Additionally,SIBO-positive patients were categorized by age into<45 years(n=23),45-60 years(n=82),60-75 years(n=124),and≥75 years(n=10)to compare SIBO positivity rates across age groups.Results The patients in SIBO-positive and double positive groups were older and had a lower body mass index(BMI)than those in SIBO-negative group,with statistically significant differences(P<0.05).Compared with the patients in SIBO-negative group,those in hydrogen-positive group showed a higher proportion of history of coronary heart disease,those in methanogen-positive group were older,and higher proportion of statin use,with statistically significant differences(P<0.05).Multivariate logistic regression analysis revealed that,among different SIBO types,a history of coronary heart disease served as an independent risk factor for hydrogen-producing bacterial overgrowth(OR=2.728,95%CI 1.271-5.857,P=0.010).For methanogen overgrowth,increasing age was identified as an independent risk factor(OR=1.040,95%CI 1.009-1.063,P=0.010),while the application of statin played the role of an independent protective factor(OR=0.420,95%CI 0.236-0.754,P=0.003).As for the simultaneous overgrowth of methane-producing and hydrogen-producing bacteria,increased BMI was found to be an independent protective factor(OR=0.870,95%CI 0.786-0.964,P=0.008).In SIBO-positive group,it was found that for patients aged<45 years,both the methane-positive rate and the double-positive rate were significantly lower than the hydrogen positivity rate(P<0.05).Moreover,among patients aged 45-60 years,the double-positive rate was significantly lower than the hydrogen positivity rate(P<0.01).When it comes to the hydrogen-positive rate,it was significantly lower for patients aged 45-60 and 60-75 years compared with that of patients aged<45 years(P<0.05).In contrast,the methane-positive rate and the double-positive rate were significantly higher for patients aged 45-60 and 60-75 years than those of patients aged<45 years(P<0.01).Conclusion A history of coronary heart disease and increasing age are independent risk factors for intestinal hydrogen-producing bacterial overgrowth and methanogen overgrowth,respectively.The application of statins and increased BMI are independent protective factors for intestinal methanogen simultaneous overgrowth of methanogen and hydrogen-producing bacteria,respectively.

Objective To investigate the regulatory effect and molecular mechanism of circ_0044556 on the malignant biological behavior of triple negative breast cancer(TNBC)cells by targeting the miR-338-3p/bromodomain-containing protein 4(BRD4)axis.Methods The TargetScan online website was used to predict the binding sites of circ_0044556 with miR-338-3p and miR-338-3p with BRD4.Dual-luciferase reporter gene assays were performed to determine the relationship among circ_0044556,miR-338-3p,and BRD4 in MDA-MB-231 cells.Quantitative real-time PCR(qRT-PCR)and Western blotting were employed to detect the expression of circ_0044556,miR-338-3p,and BRD4 protein in human TNBC cell line MDA-MB-231 and human normal breast epithelial cells MCF-10A.MDA-MB-231 cells were divided into NC group,si-NC group(transfected with si-NC),si-circ_0044556 group(transfected with si-circ_0044556),si-circ_0044556+inhibitor NC group(transfected with si-circ_0044556 and inhibitor NC),and si-circ_0044556+miR-338-3p inhibitor group(transfected with si-circ_0044556 andmiR-338-3p inhibitor).qRT-PCR was applied to detect the expression of circ_0044556 and miR-338-3p;Western blotting was used to detect the expression of BRD4,E-cadherin,N-cadherin and Vimentin;the CCK-8 assay was applied to detect cell proliferation;flow cytometry was applied to detect cell apoptosis;and Transwell assays were used to detect cell invasion and migration.Thirty nude mice were randomly divided into NC group(tail vein injection of normal saline),si-NC group(tail vein injection of LV-NC),si-circ_0044556 group(tail vein injection of LV-circ_0044556),si-circ_0044556+inhibitor NC group(tail vein injection of LV-circ_0044556 and antiagomir NC),and si-circ_0044556+miR-338-3p inhibitor group(tail vein injection of LV-circ_0044556 and antiagomir miR-338-3p),with 6 mice per group.A xenograft tumor model was constructed by subcutaneous injection of MDA-MB-231 cells into nude mice,and tumor volume and weight were measured.Results TargetScan prediction results showed that the downstream miRNA of circ_0044556 was miR-338-3p,and the downstream target gene of miR-338-3p might be BRD4.Compared with transfecting mimic NC,transfection with miR-338-3p mimic significantly reduced the luciferase activities of WT-circ_0044556(0.34±0.03 vs.1.00±0.15,P<0.05)and WT-BRD4(0.41±0.05 vs.1.05±0.13,P<0.05)in MDA-MB-231 cells.Compared with MCF-10A cells,the expression levels of circ_0044556 and BRD4 protein in MDA-MB-231 cells were significantly increased,while the expression level of miR-338-3p was significantly decreased(P<0.05).Compared with NC group and si-NC group,the expression levels of circ_0044556,the protein expression levels of BRD4,N-cadherin,and Vimentin,and the OD450 value in MDA-MB-231 cells of si-circ_0044556 group and si-circ_0044556+inhibitor NC group were significantly decreased(P<0.05),the number of migrated and invaded cells was significantly reduced(P<0.05),and the expression level of miR-338-3p,the protein expression level of E-cadherin,and the cell apoptosis rate in MDA-MB-231 cells were significantly increased(P<0.05);downregulation of miR-338-3p rescued the inhibitory effect of circ_0044556 knockdown on invasion,migration,and proliferation of MDA-MB-231 cells.Compared with NC group and si-NC group,the tumor volume and weight in si-circ_0044556 group and si-circ_0044556+inhibitor NC group were significantly decreased(P<0.05);compared with si-circ_0044556 group and si-circ_0044556+inhibitor NC group,the tumor volume and weight in si-circ_0044556+miR-338-3p inhibitor group were significantly increased(P<0.05).Conclusion circ_0044556 may promote the malignant biological behaviors of TNBC cells through the miR-338-3p/BRD4 axis.

AIM To study the chemical constituents from Citri reticulatae Pericarpium Viride and their anti-triple negative breast cancer activities in vitro.METHODS The ethanolic extract of Citri reticulatae Pericarpium Viride was isolated and purified by silica gel,polyamide,MCI,Sephadex LH-20 and semi-preparative HPLC,then the structures of obtained compounds were identified by physicochemical properties and spectral data.The anti-triple negative breast cancer activities were screened by SRB assay,and their effects on the proliferation of triple negative breast cancer cell lines HCC1806,HCC1937 and MDA-MB-231 in vitro were evaluated.RESULTS Twenty compounds were isolated and identified as nobiletin(1),tangeritin(2),5,4'-dihydroxy-7,8-dimethoxy flavonoid(3),naringenin(4),artemetin(5),5-demethynobiletin(6),3,5,6,7,8,3',4'-pentamethoxy flavonoid(7),5,4'-dihydroxy-3,6,7,8,3'-pentamethoxyflavone(8),xanthomicrol(9),p-hydroxycinnamic acid(10),5,4'-dihydroxy-6,7,8,3'-tetramethoxyflavone(11),pectolinarigenin(12),4'-dihydroxy-5,6,7-tetramethoxyflavone(13),hispidulin(14),4',5,6,7-tetramethoxy-flavone(15),1-methyl-4-(prop-1-en-2-yl)cyclohexane-1,2-diol(16),umbelliferone(17),5-hydroxymethyl furfural(18),hydroquinone(19),1H-indole-3-carbaldehyde(20).Compound 8 showed a significant inhibitory effect with the IC50 value of(5.36±0.24)μmol/L on HCC1806 cells.CONCLUSION Compound 20 is isolated from genus Citrus for the first time,8,12-13,16-17 are isolated from this plant for the first time.Compound 8 show inhibitory effects on the proliferation of HCC1806,HCC1937 and MDA-MB-231 cells in vitro and have the strongest activities.Compounds 3-4,11-12,15,17 and 19 show strong inhibitory effect on HCC1806 cells.Compounds 15,19 also inhibit the proliferation of HCC1937 cells in vitro.

Paraplegia caused by spinal cord injury is a serious neurological complication, for which surgery is currently the main treatment method. Due to different surgical approaches, patients are usually expected to maintain a passive prone position for a long time or switch between the supine and prone positions. Affected by multiple factors such as neurogenic sensory disorders, pathological changes in muscle tone and operative duration, the risk of intraoperative acquired pressure injury (IAPI) is significantly increased. Current clinical prevention strategies for IAPI in these patients predominantly focus on localized pressure relief during positioning, lacking systematic, standardized comprehensive prevention protocols or evidence-based guidelines. To address it, Department of Nursing, Orthopedics Branch, China International Exchange and Promotive Association for Medical and Health Care, Spinal Trauma Professional Committee, Orthopedics Branch, Chinese Medical Doctor Association, Nursing Group of Spine and Spinal Cord Professional Committee of Chinese Association of Rehabilitation Medicine organized experts in relevant fields to formulate Guideline for the prevention of intraoperative acquired pressure injury in paraplegic patients with spinal cord injury ( version 2025), based on evidence-based medical evidence and latest research results and clinical practice at home and abroad. Eleven recommendations were put forward from the aspects of preoperative risk assessment, intraoperative prevention strategies, postoperative handover and monitoring, and supportive mechanisms for IAPI prevention, aiming to standardize the prevention measures and management strategies of IAPI in paraplegic patients with spinal cord injury and accelerate the recovery of patients and improve the therapeutic effect.

Objective:To evaluate the efficacy and safety of the CLAE (cladribine + cytarabine + etoposide) regimen in refractory/relapsed T cell acute lymphoblastic leukemia/lymphoma (R/R T-ALL/LBL) .Methods:Patients with R/R T-ALL/LBL received the CLAE regimen in a prospective, multicenter, single-arm clinical study or compassionate use. From March 2019 to August 2024, data from 25 patients (18 in the study across five centers and 7 receiving compassionate treatment in Peking University Third Hospital) were collected. Outcomes included objective response rate, complete response (CR) rate, partial response (PR) rate after 1–2 cycles, bridging to allo-HSCT, progression-free survival (PFS), overall survival (OS), and treatment-related adverse effects.Results:Median age was 29 years (range, 13–63) ; 17 were male. Among the 24 evaluable patients, CR rate was 33.3% overall and 41.2% among enrolled patients. Median OS and PFS time were 199 (46–1 310) and 49 (28–1 310) days, respectively. Cumulative OS rate at 6 months, 1 year, and 2 years was (52.1±10.2) %, (29.7±9.3) %, and (27.1±9.1) %, respectively; cumulative PFS rate was (32.6±9.6) %, (24.9±8.9) %, and (23.8±8.7) %, respectively. Among patients achieving CR or PR (8 cases), median OS and PFS were not reached. Cumulative OS rate at 6 months, 1 year, and 2 years was (86.8±12.0) %, (78.3±14.6) %, and (72.9±15.7) %, respectively, and the cumulative PFS rate was (86.4±12.1) %, (74.8±15.3) %, and (72.9±15.7) %, respectively. Adverse events were mainly hematologic; no treatment-related mortality occurred. Seven patients achieving CR were bridged to allo-HSCT, with 5 remaining in continuous remission.Conclusion:The CLAE regimen is safe and effective for R/R T-ALL/LBL, facilitating CR as a bridge to allo-HSCT and potentially improving patient prognosis.