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

ObjectiveTo establish a UHPLC-MS/MS quantitative method for the determination of glucuronic acid， tartaric acid， glycolic acid， malic acid， lactic acid， citric acid， DL-2-hydroxybutyric acid sodium， mandelic acid， benzilic acid， hydroxycaprylic acid， lactobionic acid， gluconic acid and N-acetylneuraminic acid in cosmetics. MethodsSamples were prepared by ultrasonic extraction， cleansed by precipitating reagent and followed by high-speed centrifugation of the extraction solution. The supernatant was filtered by 0.22 μm Millipore filter. The continued filtrate was taken for analysis. A reversed phase column， Poroshell 120 EC-C₁₈ （2.7 μm， 4.6 mm×1 000 mm） was used with 0.1% formic acid buffer and acetonitrile as the mobile phase under the condition of gradient elution. The analytes were detected with electrospray ionization source in negative ion mode （ESI^-） and multiple reactions monitoring （MRM）， and quantified by external standard curve. ResultsThe method showed a good linearity of glucuronic acid， tartaric acid， malic acid， DL-2-hydroxybutyric acid sodium， benzilic acid， hydroxycaprylic acid and N-acetylneuraminic acid within the concentration range of 50.0‒2 000.0 μg·L^-1 （r>0.995）. The method showed a good linearity of glycolic acid， lactic acid， citric acid and mandelic acid within the concentration range of 100.0‒5 000.0 μg·L^-1 （r>0.995）. The method showed a good linearity of lactobionic acid and gluconic acid within the concentration range of 50.0‒5 000.0 μg·L^-1 （r>0.995）. The recoveries were in the range of 92.3%‒114.1%； the relative standard deviations （RSD） were in the range of 0.9%‒6.0% （n=3）. The detection limits of glucuronic acid， tartaric acid， malic acid， citric acid， DL-2-hydroxybutyric acid sodium， mandelic acid， benzilic acid， hydroxycaprylic acid， lactobionic acid， gluconic acid and N-acetylneuraminic acid were 0.003% while the detection limits of glycolic acid， lactic acid and mandelic acid were 0.006%. In 10 batches of commercially available cosmetics， eight batches showed positive result. ConclusionThe UHPLC-MS/MS method is efficient， sensitive and accurate and is applicable to the determination of 13 α-hydroxy acidic components in cosmetics.

Corticosteroid switching can reverse abiraterone resistance in some patients with metastatic castration-resistant prostate cancer (mCRPC). Here, we investigated the potential biomarkers for predicting the efficacy of corticosteroid switching during treatment with abiraterone acetate (AA). We retrospectively analyzed 101 mCRPC patients receiving corticosteroid switching from West China Hospital and Sun Yat-Sen University Cancer Center between January 2016 and December 2018. All cases received AA plus prednisone as first-line therapy during mCRPC. Primary end points were biochemical progression-free survival (bPFS) and overall survival (OS). The risk groups were defined based on multivariate analysis. A total of 42 (41.6%) and 25 (24.8%) patients achieved 30% and 50% decline in prostate-specific antigen (PSA), respectively, after corticosteroid switching. The median bPFS and median OS on AA plus dexamethasone were 4.9 (95% confidence interval [CI]: 3.7-6.0) months and 18.8 (95% CI: 16.2-30.2) months, respectively. Aldo-keto reductase family 1 member C3 (AKR1C3) expression (hazard ratio [HR]: 2.15, 95% Cl: 1.22-3.80, P = 0.008) and baseline serum alkaline phosphatase (ALP; HR: 4.95, 95% Cl: 2.40-10.19, P < 0.001) were independent predictors of efficacy before corticosteroid switching in the multivariate analysis of bPFS. Only baseline serum ALP >160 IU l^-1 (HR: 3.41, 95% Cl: 1.57-7.38, P = 0.002) together with PSA level at switch ≥50 ng ml^-1 (HR: 2.59, 95% Cl: 1.22-5.47, P = 0.013) independently predicted poorer OS. Based on the predictive factors in multivariate analysis, we developed two risk stratification tools to select candidates for corticosteroid switching. Detection of serum ALP level, PSA level, and tissue AKR1C3 expression in mCRPC patients could help make clinical decisions for corticosteroid switching.
Abiraterone Acetate/therapeutic use* ; Adrenal Cortex Hormones/therapeutic use* ; Androstenes ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Dexamethasone/therapeutic use* ; Disease-Free Survival ; Humans ; Male ; Prednisone/therapeutic use* ; Prostate-Specific Antigen ; Prostatic Neoplasms, Castration-Resistant/pathology* ; Retrospective Studies ; Treatment Outcome

SARS-CoV-2 infection causes complicated clinical manifestations with variable multi-organ injuries, however, the underlying mechanism, in particular immune responses in different organs, remains elusive. In this study, comprehensive transcriptomic alterations of 14 tissues from rhesus macaque infected with SARS-CoV-2 were analyzed. Compared to normal controls, SARS-CoV-2 infection resulted in dysregulation of genes involving diverse functions in various examined tissues/organs, with drastic transcriptomic changes in cerebral cortex and right ventricle. Intriguingly, cerebral cortex exhibited a hyperinflammatory state evidenced by significant upregulation of inflammation response-related genes. Meanwhile, expressions of coagulation, angiogenesis and fibrosis factors were also up-regulated in cerebral cortex. Based on our findings, neuropilin 1 (NRP1), a receptor of SARS-CoV-2, was significantly elevated in cerebral cortex post infection, accompanied by active immune response releasing inflammatory factors and signal transmission among tissues, which enhanced infection of the central nervous system (CNS) in a positive feedback way, leading to viral encephalitis. Overall, our study depicts a multi-tissue/organ transcriptomic landscapes of rhesus macaque with early infection of SARS-CoV-2, and provides important insights into the mechanistic basis for COVID-19-associated clinical complications.
Animals ; COVID-19/genetics* ; Macaca mulatta ; SARS-CoV-2/genetics* ; Transcriptome

Acute Disease ; Aneurysm, Dissecting/surgery* ; Aortic Aneurysm/surgery* ; Hospitals ; Humans ; Retrospective Studies ; Treatment Outcome

OBJECTIVE: This study tests whether long-term intake of Allium tuberosum (AT) can alleviate pulmonary inflammation in ovalbumin (OVA)-induced asthmatic mice and evaluates its effect on the intestinal microbiota and innate lymphoid cells (ILCs). METHODS: BALB/c mice were divided into three groups: phosphate buffer saline, OVA and OVA + AT. The asthmatic murine model was established by sensitization and challenge of OVA in the OVA and OVA + AT groups. AT was given to the OVA + AT group by oral gavage from day 0 to day 27. On day 28, mice were sacrificed. Histopathological evaluation of lung tissue was performed using hematoxylin and eosin, and periodic acid-Schiff staining. The levels of IgE in serum, interleukin-5 (IL-5) and IL-13 from bronchoalveolar lavage fluid (BALF) were measured by enzyme-linked immunosorbent assay. The ILCs from the lung and gut were detected by flow cytometry. 16S ribosomal DNA sequencing was used to analyze the differences in colon microbiota among treatment groups. RESULTS: We found that long-term intake of AT decreased the number of inflammatory cells from BALF, reduced the levels of IL-5 and IL-13 in BALF, and IgE level in serum, and rescued pulmonary histopathology with less mucus secretion in asthmatic mice. 16S ribosomal DNA sequencing results showed that AT strongly affected the colonic bacteria community structure in asthmatic mice, although it had no significant effect on the abundance and diversity of the microbiota. Ruminococcaceae and Desulfovibrionaceae were identified as two biomarkers of the treatment effect of AT. Moreover, AT decreased the numbers of ILCs in both the lung and gut of asthmatic mice. CONCLUSION The results indicate that AT inhibits pulmonary inflammation, possibly by impeding the activation of ILCs and adjusting the homeostasis of gut microbiota in asthmatic mice.

OBJECTIVE: To investigate the value of serum and bronchoalveolar lavage fluid (BALF) chitinase-3-like-1 protein (YKL-40) in the diagnosis of anti-melanoma differentiation-associated gene 5 (MDA5)-positive dermatomyositis (DM) patients complicated with serious pulmonary injury, including rapidly progressive interstitial lung disease (RP-ILD) and pulmonary infection. METHODS: Anti-MDA5 antibodies positive patients with DM who were hospitalized in the Department of Rheumatology of China-Japan Friendship Hospital from 2013 to 2018 were involved in this study. Demographic information, clinical, laboratory and imaging data were retrospectively collected. ELISA was used to detect the serum and BALF levels of YKL-40. The receiver operating characteristic (ROC) curve was drawn, and the area under ROC curve (AUC) was used to evaluate the diagnostic value of serum YKL-40 for pulmonary injury.Interstitial lung disease (ILD) was confirmed by chest high-resolution CT (HRCT). RP-ILD was defined as progressive respiratory symptoms such as dyspnea and hypoxemia within 3 months, and/or deterioration of interstitial changes or appearace of new pulmonary interstitial lesions on chest HRCT. Pulmonary infection was considered as positive pathogens detected in qualified sputum, blood, bronchoalveolar lavage fluid or lung biopsy specimens. RESULTS: A total of 168 anti-MDA5-positive DM patients including 108 females and 60 males were enrolled in the study. Of these patients, 154 had ILD, and 66(39.3%) of them presented RP-ILD. Seventy patients with pulmonary infection were confirmed by etiology. In the patients with RP-ILD, 39 (59.1%) of them were complicated with pulmonary infection. While only 31 cases(30.4%) had pulmonary infection in the non-RP-ILD patients. The incidence of pulmonary infection in the patients with RP-ILD was significantly higher than that of those with non-RP-ILD (P < 0.001). The serum YKL-40 levels in the RP-ILD patients with pulmonary infection were the highest compared with RP-ILD without pulmonary infection, non-RP-ILD with pulmonary infection and non-RP-ILD without pulmonary infection groups among all the patients [83 (42-142) vs. 42 (21-91) vs. 43 (24-79) vs. 38 (22-69), P < 0.01].The sensitivity, specificity and AUC of serum YKL-40 in the diagnosis of RP-ILD complicated with pulmonary infection were 75%, 67%, and 0.72, respectively. The AUC of diagnosed of anti-MDA5 positive DM patients complicated with RP-ILD and pulmonary infection was higher than that of patients complicated with only RP-ILD and only pulmonary infection (0.72 vs. 0.54 and 0.55, Z=2.10 and 2.11, P < 0.05). CONCLUSION The prognosis of anti-MDA5-positive DM patients with RP-ILD and pulmonary infection were poor. Serum YKL-40 level can be used as a helpful tool for the diagnosis of coexistence of these conditions in the patients.
Chitinase-3-Like Protein 1 ; Dermatomyositis/complications* ; Female ; Humans ; Lung Diseases, Interstitial/diagnosis* ; Lung Injury ; Male ; Retrospective Studies

Objective:This study was designed to compare inflammatory response, water carriage and gut brain axis in rats with ulcerative colitis (UC) after treatment of three regiments, Huangqintang (HQT), Sishenwan (SSW), and Tongxie Yaofang(TXYF). Method:After approved by Institute of Chinese Materia Medica Ethics Committees in China Academy of Chinese Medical Sciences, UC in rats was induced by using a compound method (trinitrobenzenesulfonic acid plus ethanol). Rats were randomly divided into control, disease, positive control salazosulfapyridine (SASP, 0.5 g·kg^-1), HQT (20 g·kg^-1), SSW(26 g·kg^-1), and TXYF group(22 g·kg^-1). After 5 days of treatment, colonic tissues and the blood were taken for various assays. Damage of colonic tissues was detected by hematoxylin-eosin staining (HE). The distribution of Vasoactine intrestinal (VIP), 5-hydroxytrytamine (5-HT), P-substance (SP) in the blood and serum were detected by enzymelinked immunosorbent assay (ELISA) and immunohistochemistry (IHC), the levels of aquaporin3 (AQP3) and Aquaporin4 (AQP4) in the serum were detected by Western blot, the mRNA expression of Extracellular regulated protein kinases 1 (Erk1) and p38 mitogen-activated protein kinase (p38 MAPK) in the serum were detected by Real-time fluorescence quantitative polymerase chain reaction (Real-time PCR). Result:The brain-gut peptide results showed that compared with the normal group, the content of 5-HT and VIP in model group were significantly decreased (P<0.01), the content of SP were decreased, but there was no significant statistical difference, compared with the disease group, the content of 5-HT in SASP and TXYF group were clearly increased (P<0.05), the increment of VIP and SP in SASP, HQT, TXYF group were significant (P<0.05). Compared with the normal group, the content of AQP3 in model group were significantly increased(P<0.01), the content of AQP4 were clearly decreased(P<0.01), compared with the disease group, the content of AQP4 in SASP and HQT group were clearly increased (P<0.05), whereas the levels of AQP3 in HQT group were most significant reduced (P<0.01). Compared with the disease group, the expression of Erk1 and p38 were clearly reduced (P<0.01), with the most significant reduce being the expression in HQT group. Conclusion:Three regiments all have therapeutic effects on UC, manifested by improvements of the signs and mental status of UC rats. However, in terms of gut-brain axis disturbance improvement, the therapeutic effect of TXYF was superior than HQT and SSW, whereas in terms of inflammatory response suppression and water carriage accomodation, the therapeutic effect of HQT was superior than SSW and TXYF.