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

The inclusion complex of taxifolin(TAX)with hydroxypropyl-β-cyclodextrin(HP-β-CD)was prepared by saturated aqueous solution method,and the preparation conditions such as molar ratio,volume ratio of solution,inclusion temperature and inclusion time were selected by single-factor experiment.The orthogonal design of three-level four-factor L9(34)was used to screen the preparation process of the inclusion complex,and the inclusion complex was prepared with optimal preparation process.The prepared inclusion complex was characterized by scanning electron microscopy(SEM),nuclear magnetic resonance(1H NMR,2D NMR),Fourier transform infrared spectroscopy(FT-IR),ultraviolet-visible(UV-Vis)absorption spectroscopy and X-ray powder diffraction(XRD).The inclusion ratio,biostability,solubility and in vitro release of the inclusion complex were investigated.The results of orthogonal experiments showed that the optimum conditions for preparation of the inclusion complex were as follows:the molar ratio of TAX to HP-β-CD was 1:1,the volume ratio of methanol to ultra-pure water was 1:8,the inclusion time was 8 h,and the inclusion temperature was 30℃.Under the optimal conditions,the inclusion ratio between TAX and HP-β-CD was calculated to be 1:1 by Job's curve method.According to the change of UV-vis absorption spectra,the host-guest complexation constant of 4.9488×104 L/mol was obtained by Benesi-Hildebrand curve method.The solubility of TAX increased from 1.2665 mg/mL to 19.3469 mg/mL after inclusion,demonstrating that HP-β-CD could serve as an effective host molecule for TAX,which could significantly enhance the bio-stability and solubility of the formed inclusion complex.

Objective:To explore the efficacy and safety of instantly generated inhaled nitric oxide (iNO) for treating neonatal pulmonary hypertension (PH) complicated with severe hypoxic respiratory failure.Methods:This single-center, single-arm, prospective study included 32 neonates with PH complicated with hypoxic respiratory failure who were hospitalized in the neonatal intensive care unit (NICU) of Beijing Children′s Hospital Affiliated to Capital Medical University from March 2023 to March 2025 and received immediate iNO generation therapy. The demographic data, maternal pregnancy, mechanical ventilation parameters, arterial blood gas indexes, other hospitalization data and safety indexes of iNO treatment were collected. The time point for starting iNO treatment was set as 0 h, and the observation time points were 1, 6, 12, 24, 48 h after treatment and when iNO treatment was stopped. The positive reaction of iNO treatment was defined as the decrease of oxygenation index (OI)>10% or the increase of arterial partial pressure of oxygen (PaO 2)>10% after treatment. The OI, mechanical ventilation parameters, arterial blood gas index changes and treatment positive reaction ratio were analyzed to evaluate the effectiveness of iNO treatment, and the nitrogen dioxide concentration, methemoglobin (MetHb) concentration and other indicators were analyzed to evaluate the safety of iNO treatment. Paired t test or Wilcoxon signed rank sum test was used to compare the observation indexes at different treatment times. Friedman test was used to compare the concentration of nitrogen dioxide and MetHb at multiple treatment times. Receiver operating characteristic (ROC) curve was used to analyze the best cut-off value of OI related indexes to distinguish the treatment outcome of iNO. Results:Among 32 neonates, 18 (56%) were males and 14 (44%) were females, the gestational age was 38 (35, 39) weeks, the birth weight was 3.1 (2.3, 3.4) kg, and the age of enrollment was 3 (2, 8) days. The OI and the mean airway pressure at 48 h after treatment were both lower than those at 0 h ((10.4±2.0 vs. 22.6±2.5, 13.0 (12.0, 14.0) vs. 14.0 (13.0, 16.0) cmH 2O, 1 cmH 2O=0.098 kPa, both P<0.05). The fraction of inspired oxygen at 24 and 48 h after treatment were both lower than those at 0 h (both P<0.05). The PaO 2 at 6, 12, 24 and 48 h after treatment were all higher than those at 0 h (all P<0.05). The proportion of positive reactions to iNO treatment was 20 neonates (63%), 22 neonates (69%), 23 neonates (72%), 23 neonates (72%) and 26 neonates (8%) at 1, 6, 12, 24, 48 h after treatment, respectively. No occurrence of methemoglobinemia, excessive nitrogen dioxide concentration, or device related adverse events were observed. Out of 32 neonates, a total of 24 neonates (75%) were cured or improved and discharged according to medical advice, while 8 neonates (25%) died in the hospital. The best cut-off value of OI at 0 h and the decline range of OI at 12 h to distinguish the outcome of hospitalization were 24.8 and 22.2%, respectively. Conclusion:It was effective and safe to use instantly generated iNO to treat neonatal PH with severe hypoxic respiratory failure.

Aim To explore the effect of hydroxysafflor yellow A(HSYA)on lipocalin 2(LCN2)-induced fer-roptosis in HT22 cells and the related mechanism.Methods Thirty male Sprague-Dawley(SD)rats were used to establish the middle cerebral artery occlu-sion/reperfusion(MCAO/R)model by the suture method.The rats were randomly divided into the Sham group,the MCAO/R group,and the MCAO/R+HSYA group.The infarct area was measured by TTC staining,and the degree of neurological deficit was evaluated by the Z-Longa scoring method.The expressions of LCN2 and 24P3R in brain tissues were detected by Western blot.LCN2 protein was added to HT-22 cells,and the cells were divided into the normal group,the LCN2 group,and the LCN2+HSYA group.The optimal con-centration of LCN2-induced neuronal ferroptosis was screened by LDH assay and Western blot,and the ex-pression levels of ferritin,FPN1,GPX4,SLC7A11,COX2,and 24P3R were detected.LCN2 was knocked down by siRNA transfection,and the expressions of GPX4 and ferritin were detected.The contents of glu-tathione(GSH),malondialdehyde(MDA),GPX4,and Fe2+were determined by colorimetry,and the expres-sion of GPX4 was detected by immunofluorescence.The binding force between HSYA and LCN2 was ana-lyzed by molecular docking technology.Results Ani-mal experiments showed that HSYA could reduce the cerebral infarction area and decrease the neurological function score of MCAO/R rats.Compared with the sham group,the levels of LCN2 and 24P3R increased in the MCAO/R group,while HSYA inhibited their ex-pressions.Cell experiments showed that the optimal concentration of LCN2 to induce ferroptosis in HT22 cells was 2 μmol·L-1.After knocking down LCN2 by siRNA transfection,compared with the LCN2 group,the expression levels of GPX4 and ferritin in the siLCN2 group increased significantly.Compared with the nor-mal group,the expressions of SLC7A11,GPX4,FPN1,ferritin,and GSH in the LCN2 group decreased signifi-cantly,while the concentration of Fe2+,and the expres-sions of MDA,COX2,and 24P3R increased.HSYA could increase the expressions of SLC7A11,GPX4,FPN1,ferritin,and GSH,reduce the contents of Fe2+and MDA,and inhibit the expressions of COX2 and 24P3R.Molecular docking showed that the binding en-ergy between HSYA and LCN2 was-8.0 kJ·mol-1.Conclusion HSYA can inhibit LCN2-induced ferrop-tosis in HT22 cells through the SLC7A11/GPX4 signa-ling pathway.

Aim To explore the effect of hydroxysafflor yellow A(HSYA)on lipocalin 2(LCN2)-induced fer-roptosis in HT22 cells and the related mechanism.Methods Thirty male Sprague-Dawley(SD)rats were used to establish the middle cerebral artery occlu-sion/reperfusion(MCAO/R)model by the suture method.The rats were randomly divided into the Sham group,the MCAO/R group,and the MCAO/R+HSYA group.The infarct area was measured by TTC staining,and the degree of neurological deficit was evaluated by the Z-Longa scoring method.The expressions of LCN2 and 24P3R in brain tissues were detected by Western blot.LCN2 protein was added to HT-22 cells,and the cells were divided into the normal group,the LCN2 group,and the LCN2+HSYA group.The optimal con-centration of LCN2-induced neuronal ferroptosis was screened by LDH assay and Western blot,and the ex-pression levels of ferritin,FPN1,GPX4,SLC7A11,COX2,and 24P3R were detected.LCN2 was knocked down by siRNA transfection,and the expressions of GPX4 and ferritin were detected.The contents of glu-tathione(GSH),malondialdehyde(MDA),GPX4,and Fe2+were determined by colorimetry,and the expres-sion of GPX4 was detected by immunofluorescence.The binding force between HSYA and LCN2 was ana-lyzed by molecular docking technology.Results Ani-mal experiments showed that HSYA could reduce the cerebral infarction area and decrease the neurological function score of MCAO/R rats.Compared with the sham group,the levels of LCN2 and 24P3R increased in the MCAO/R group,while HSYA inhibited their ex-pressions.Cell experiments showed that the optimal concentration of LCN2 to induce ferroptosis in HT22 cells was 2 μmol·L-1.After knocking down LCN2 by siRNA transfection,compared with the LCN2 group,the expression levels of GPX4 and ferritin in the siLCN2 group increased significantly.Compared with the nor-mal group,the expressions of SLC7A11,GPX4,FPN1,ferritin,and GSH in the LCN2 group decreased signifi-cantly,while the concentration of Fe2+,and the expres-sions of MDA,COX2,and 24P3R increased.HSYA could increase the expressions of SLC7A11,GPX4,FPN1,ferritin,and GSH,reduce the contents of Fe2+and MDA,and inhibit the expressions of COX2 and 24P3R.Molecular docking showed that the binding en-ergy between HSYA and LCN2 was-8.0 kJ·mol-1.Conclusion HSYA can inhibit LCN2-induced ferrop-tosis in HT22 cells through the SLC7A11/GPX4 signa-ling pathway.

Objective:To explore the efficacy and safety of instantly generated inhaled nitric oxide (iNO) for treating neonatal pulmonary hypertension (PH) complicated with severe hypoxic respiratory failure.Methods:This single-center, single-arm, prospective study included 32 neonates with PH complicated with hypoxic respiratory failure who were hospitalized in the neonatal intensive care unit (NICU) of Beijing Children′s Hospital Affiliated to Capital Medical University from March 2023 to March 2025 and received immediate iNO generation therapy. The demographic data, maternal pregnancy, mechanical ventilation parameters, arterial blood gas indexes, other hospitalization data and safety indexes of iNO treatment were collected. The time point for starting iNO treatment was set as 0 h, and the observation time points were 1, 6, 12, 24, 48 h after treatment and when iNO treatment was stopped. The positive reaction of iNO treatment was defined as the decrease of oxygenation index (OI)>10% or the increase of arterial partial pressure of oxygen (PaO 2)>10% after treatment. The OI, mechanical ventilation parameters, arterial blood gas index changes and treatment positive reaction ratio were analyzed to evaluate the effectiveness of iNO treatment, and the nitrogen dioxide concentration, methemoglobin (MetHb) concentration and other indicators were analyzed to evaluate the safety of iNO treatment. Paired t test or Wilcoxon signed rank sum test was used to compare the observation indexes at different treatment times. Friedman test was used to compare the concentration of nitrogen dioxide and MetHb at multiple treatment times. Receiver operating characteristic (ROC) curve was used to analyze the best cut-off value of OI related indexes to distinguish the treatment outcome of iNO. Results:Among 32 neonates, 18 (56%) were males and 14 (44%) were females, the gestational age was 38 (35, 39) weeks, the birth weight was 3.1 (2.3, 3.4) kg, and the age of enrollment was 3 (2, 8) days. The OI and the mean airway pressure at 48 h after treatment were both lower than those at 0 h ((10.4±2.0 vs. 22.6±2.5, 13.0 (12.0, 14.0) vs. 14.0 (13.0, 16.0) cmH 2O, 1 cmH 2O=0.098 kPa, both P<0.05). The fraction of inspired oxygen at 24 and 48 h after treatment were both lower than those at 0 h (both P<0.05). The PaO 2 at 6, 12, 24 and 48 h after treatment were all higher than those at 0 h (all P<0.05). The proportion of positive reactions to iNO treatment was 20 neonates (63%), 22 neonates (69%), 23 neonates (72%), 23 neonates (72%) and 26 neonates (8%) at 1, 6, 12, 24, 48 h after treatment, respectively. No occurrence of methemoglobinemia, excessive nitrogen dioxide concentration, or device related adverse events were observed. Out of 32 neonates, a total of 24 neonates (75%) were cured or improved and discharged according to medical advice, while 8 neonates (25%) died in the hospital. The best cut-off value of OI at 0 h and the decline range of OI at 12 h to distinguish the outcome of hospitalization were 24.8 and 22.2%, respectively. Conclusion:It was effective and safe to use instantly generated iNO to treat neonatal PH with severe hypoxic respiratory failure.

This study was aimed at exploring the epidemiological characteristics of Salmonella typhimurium(S.typhi-murium)and Salmonella typhimurium monophasic variants(S.1,4,[5],12:i:-)at the genome-wide level in Ningxia.Estab-lishment of a whole genome genotyping database would provide a theoretical basis for source and prevention and control of fu-ture outbreaks.We conducted serotyping,MLST,cgMLST typing,and virulence gene and drug resistance phenotype prediction of 92 strains of S.typhimurium and its monophasic variants through whole genome sequencing.Among all strains,21 were S.typhomurium,accounting for 22.83％,71 strains were S.1,4,[5],12:i:-,accounting for 77.17％.MLST and cgMLST typing results indicated that all S.typhimurium strains were ST19-type,and were divided into five evolutionary bran-ches.Five clusters were found,and S.1,4,[5],12:i:-were all ST34-type;on the same evolutionary branch,17 clusters were found.VFDB predicted 155 virulence genes in eight classes,of which 33.33％were S.typhimurium carried nine virulence genes on plasmids,and both serotypes carried virulence genes related to SPI virulence island on chromosomes,12:I:-resistant to 4-14 antibiotics,resulting in 22 multi-drug resistance spectrum.S.typhimurium was resistant to 2-13 antibiotics and produced eight multi-drug resistance profiles.S.1,4,[5],12:i:-was the predominant serotype of S.enteritidis in Ningxia.Typhimurium carried fewer virulence genes than S.typhimurium,and showed a high risk of local outbreaks.

This study was aimed at exploring the epidemiological characteristics of Salmonella typhimurium(S.typhi-murium)and Salmonella typhimurium monophasic variants(S.1,4,[5],12:i:-)at the genome-wide level in Ningxia.Estab-lishment of a whole genome genotyping database would provide a theoretical basis for source and prevention and control of fu-ture outbreaks.We conducted serotyping,MLST,cgMLST typing,and virulence gene and drug resistance phenotype prediction of 92 strains of S.typhimurium and its monophasic variants through whole genome sequencing.Among all strains,21 were S.typhomurium,accounting for 22.83％,71 strains were S.1,4,[5],12:i:-,accounting for 77.17％.MLST and cgMLST typing results indicated that all S.typhimurium strains were ST19-type,and were divided into five evolutionary bran-ches.Five clusters were found,and S.1,4,[5],12:i:-were all ST34-type;on the same evolutionary branch,17 clusters were found.VFDB predicted 155 virulence genes in eight classes,of which 33.33％were S.typhimurium carried nine virulence genes on plasmids,and both serotypes carried virulence genes related to SPI virulence island on chromosomes,12:I:-resistant to 4-14 antibiotics,resulting in 22 multi-drug resistance spectrum.S.typhimurium was resistant to 2-13 antibiotics and produced eight multi-drug resistance profiles.S.1,4,[5],12:i:-was the predominant serotype of S.enteritidis in Ningxia.Typhimurium carried fewer virulence genes than S.typhimurium,and showed a high risk of local outbreaks.

Objective To investigate the differences in the influencing factors for acute necrotizing pancreatitis (ANP) and infectious pancreatic necrosis (IPN) between Eastern and Western countries, and to provide a theoretical basis for the prediction and prevention of ANP. Methods Databases including PubMed, Embase, the Cochrane Library, and Web of Science were searched for articles on the influencing factors for ANP and IPN published up to January 21, 2021, and a Meta-analysis was performed. Results A total of 59 studies were included, with 22 studies from Eastern countries and 37 studies from Western countries.The Meta-analysis showed that in Eastern countries, male sex (odds ratio[ OR ]=1.51, 95% confidence interval[ CI ]: 1.18-1.91, P < 0.01), C-reactive protein (CRP)(standardized mean difference[ SMD ]=1.39, 95% CI : 1.06-1.71, P < 0.01), D-dimer ( SMD =0.44, 95% CI : 0.07-0.81, P =0.02), Acute Physiology and Chronic Health Evaluation Ⅱ (APACHE-Ⅱ) score (mean difference[ MD ]=3.51, 95% CI : 1.38-5.64, P < 0.01), alcoholic etiology ( OR =3.57, 95% CI : 2.68-4.75, P < 0.01), and biliary etiology ( OR =0.60, 95% CI : 0.46-0.77, P < 0.01) were the influencing factors for ANP, and in Western countries, male sex ( OR =1.63, 95% CI : 1.30-2.05, P < 0.01), CRP ( SMD =2.09, 95% CI : 1.12-3.05, P < 0.01), APACHE-Ⅱ score ( MD =4.28, 95% CI : 2.73-5.83, P < 0.01), Ranson score ( MD =2.99, 95% CI : 2.50-3.47, P < 0.01), and organ failure ( OR =10.87, 95% CI : 2.62-45.04, P < 0.01) were the influencing factors for ANP.In Eastern countries, age ( MD =2.16, 95% CI : 0.43-3.89, P =0.01), body mass index (BMI)( MD =1.74, 95% CI : 1.23-2.25, P < 0.01), albumin level ( SMD =-0.43, 95% CI : -0.75 to-0.12, P < 0.01), CRP ( SMD =0.58, 95% CI : 0.04-1.11, P =0.03), procalcitonin ( SMD =0.80, 95% CI : 0.56-1.04, P < 0.01), D-dimer ( MD =0.23, 95% CI : 0.15-0.31, P < 0.01), APACHE-Ⅱ score ( MD =2.47, 95% CI : 0.73-4.22, P < 0.01), Ranson score ( MD =1.60, 95% CI : 1.46-1.73, P < 0.01), and extent of necrosis ≥30%( OR =2.52, 95% CI : 1.26-5.06, P < 0.01) were the influencing factors for IPN, while in Western countries, age ( MD =4.07, 95% CI : 1.82-6.31, P < 0.01), APACHE-Ⅱ score ( MD =3.28, 95% CI : 1.39-5.17, P < 0.01), Ranson score ( MD =2.18, 95% CI : 1.75-2.62, P < 0.01), SIRS score ( OR =3.88, 95% CI : 1.58-9.51, P < 0.01), alcoholic etiology ( OR =0.61, 95% CI : 0.42-0.87, P < 0.01), and organ failure ( OR =3.63, 95% CI : 1.11-11.92, P =0.03) were the influencing factors for IPN. Conclusion Current evidence shows that biliary etiology and alcoholic etiology are unique influencing factors for ANP in the Eastern population, while Ranson score is a unique influencing factor in the Western population.BMI and extent of necrosis ≥30% are unique influencing factors for IPN in the Eastern population, while alcoholic etiology is a unique influencing factor in the Western population.

Humans ; Mpox (monkeypox) ; China