1.Glucocorticoid Discontinuation in Patients with Rheumatoid Arthritis under Background of Chinese Medicine: Challenges and Potentials Coexist.
Chuan-Hui YAO ; Chi ZHANG ; Meng-Ge SONG ; Cong-Min XIA ; Tian CHANG ; Xie-Li MA ; Wei-Xiang LIU ; Zi-Xia LIU ; Jia-Meng LIU ; Xiao-Po TANG ; Ying LIU ; Jian LIU ; Jiang-Yun PENG ; Dong-Yi HE ; Qing-Chun HUANG ; Ming-Li GAO ; Jian-Ping YU ; Wei LIU ; Jian-Yong ZHANG ; Yue-Lan ZHU ; Xiu-Juan HOU ; Hai-Dong WANG ; Yong-Fei FANG ; Yue WANG ; Yin SU ; Xin-Ping TIAN ; Ai-Ping LYU ; Xun GONG ; Quan JIANG
Chinese journal of integrative medicine 2025;31(7):581-589
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
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Aged
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Female
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Humans
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Male
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Middle Aged
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Arthritis, Rheumatoid/drug therapy*
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Glucocorticoids/therapeutic use*
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Medicine, Chinese Traditional
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Retrospective Studies
2.Correlation analysis between eNOS gene single nucleotide polymorphism and systemic lupus erythematosus in Hainan
Xuan ZHANG ; Hui-Tao WU ; Qi ZHANG ; Gui-Ling LIN ; Xi-Yu YIN ; Wen-Lu XU ; Zhe WANG ; Zi-Man HE ; Ying LIU ; Long MI ; Yan-Ping ZHUANG ; Ai-Min GONG
Medical Journal of Chinese People's Liberation Army 2024;49(9):986-991
Objective To investigate the relationship between single nucleotide polymorphisms(SNPs)in the eNOS gene and genetic susceptibility to systemic lupus erythematosus(SLE)in Hainan.Methods Blood samples were collected from SLE patients(SLE group,n=214)and healthy controls(control group,n=214)from January 2020 to December 2022 at the First Affiliated Hospital of Hainan Medical College and Hainan Provincial People's Hospital.The bases of eNOS gene rs3918188,rs1799983 and rs1007311 loci in each group were detected by SNaPshot sequencing technology.Logistic regression was used to analyze the correlation between genotypes,alleles and gene models(dominant model,recessive model,and overdominant model)of the above 3 target loci of the eNOS gene and genetic susceptibility to SLE.Haplotype analysis was conducted using HaploView 4.2 software to investigate the relationship between haploid and genetic susceptibility to SLE at each site.Results The results of logistic regression analysis revealed that the CC genotype and the C allele at rs3918188 locus were risk factors for genetic susceptibility to SLE(CC vs.AA:OR=2.449,P<0.05;C vs.A:OR=2.133,P<0.001).In recessive model at rs3918188 locus,CC genotype carriers had an increased risk of SLE development compared with AA+AC genotype carriers(OR=2.774,P<0.001).In contrast,in overdominant model at this locus,AC genotype carriers had a decreased risk of SLE occurrence compared with AA+CC genotype carriers(OR=0.385,P<0.001).In addition,polymorphisms of rs1799983 and rs1007311 were not associated with susceptibility to SLE in genotype,allele type and the 3 genetic models(P>0.05).Haplotype analysis revealed a strong linkage disequilibrium between the rs1007311 and rs1799983 loci of the eNOS gene,but no significant correlation was found between haplotype and genetic susceptibility to SLE(P>0.05).Conclusion The CC genotype and C allele at rs3918188 locus of eNOS gene may be risk factors for SLE in Hainan,while the risk of SLE occurrence is reduced in carriers of AC genotype under the overdominant model.
3.Phagocytosis of microglia in neurodegenerative diseases.
Yue-Ying LIU ; Tian-Shu DU ; Yang LIU ; Zhen ZHANG ; Ai-Niwaer AIZIER ; Xiao-Li GONG ; Xiao-Min WANG ; Ting ZHANG
Acta Physiologica Sinica 2022;74(2):283-293
With the acceleration of the aging society, neurodegenerative diseases, such as Alzheimer's disease (AD) and Parkinson's disease (PD), have become a rapidly growing global health crisis. Recent studies have indicated that microglia-neuron interactions are critical for maintaining homeostasis of the central nervous system. Genome-Wide Association Studies and brain imaging studies have suggested that microglia are activated in early stage of neurodegenerative diseases. Microglia are specialized phagocytes in the brain. The discovery of a new phagocytic pathway, trogocytosis, suggests that there is a close interaction between microglia and surviving neurons. In this review, we summarize the important roles of microglia in neurodegenerative diseases, and further analyze the functions and molecular mechanisms of microglia phagocytosis and trogocytosis.
Alzheimer Disease
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Genome-Wide Association Study
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Humans
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Microglia/metabolism*
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Neurodegenerative Diseases
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Phagocytosis/physiology*
4.Virulence-associated gene detection and analysis of Staphylococcus aureus isolates from pediatric patients′ feces
Xiaolan AI ; Yan LONG ; Bingshao LIANG ; Shuwen YAO ; Yunfeng LIU ; Fei GAO ; Jialiang MAI ; Zhile XIONG ; Zhuwei LIANG ; Jielin WANG ; Xiantang CHEN ; Min YANG ; Sitang GONG ; Zhenwen ZHOU
Chinese Journal of Laboratory Medicine 2021;44(4):291-297
Objective:To investigate the multilocus sequence typing feature of the virulence-associated genes of Staphylococcus aureus(S. aureus) separated from the clinical specimens of a multi-center cohort children in Guangzhou area. Methods:A total number of 412 Staphylococcus aureus strains isolated from 2 059 non-repeated fecal specimens of children by three groups′ researchers in Guangzhou Women and Children′s Medical Center from August 2018 to November 2018. While collecting specimens, patient clinical information is also properly collected and preserved. After extracting the DNA of the strain, the virulence-associated genes were detected by polymerase chain reaction (PCR), including the staphylococcal enterotoxin (SE) genes ( sea, seb, sec, sed, see) and the Panton-Valentine leucocidin-encoding gene ( pvl).The multi-locus sequence typing (MLST) method was performed to reveal the MLST feature of these genes and the statistical difference were examined by the the χ 2 test. Results:Among the 412 isolates of S. aureus, 256 strains (256/412, 62.1%) contains at least one SE gene. Among the enterotoxin gens, the sec (125/412, 30.3%), seb(98/412, 23.8%)and sea (66/412, 16.0%)genes were the three most prevalent members of SEs. The frequency of pvl gene in Staphylococcus aureus was 18.7%(77/412).Among them, the frequency of Staphylococcus aureus sea gene isolated from patients with gastroenteritis (58/319, 18.2%) was significantly higher than that from the non-gastroenteritis group (8/93, 8.6%)(χ2=4.912, P=0.027). The frequency of Staphylococcus aureus pvl gene isolated from the patients with pneumonia (8/21, 38.1%) was greater than that from the non-pneumonia group (6/47, 12.8%)(χ2=4.252, P=0.039). In addition, the virulence-associated gene of S. aureus was closely related to the specific ST type, 82.4% (28/34) of ST6 carried sea gene, all ST338 and ST59 carried seb gene, 96% (48/50) ST45 carried sec gene, and the pvl gene carrying rate of ST338 was 5/5. Conclusions:The SEA toxin produced by ST6 Staphylococcus aureus may be closely related to the diagnosis of gastroenteritis in children. The frequency of pvl virulence gene in Staphylococcus aureus in children with community-acquired pneumonia was higher than that in the non-pneumonia group, and closely related to the CC59.
5.Investigation and analysis of an outbreak of brucellosis in Guangdong rural areas in 2015
Jun WANG ; Zhi-yong GONG ; Meng ZHANG ; Yong-qing YE ; Hua-mei FENG ; Ai-ping DENG ; Min KANG
Shanghai Journal of Preventive Medicine 2021;33(8):692-696
Objective:To investigate a foodborne brucellosis outbreak in a county in Guangdong Province in 2015, which may provide suggestions for the prevention and control of similar incidents. Methods:Case search was carried out by visiting cases, accessing the hospital medical record system, and collecting the registration information of rural health stations, and the results were described and analyzed. Results:A total of 169 cases were found, with an attack rate of 2.0‰ (169/85 000). The onset time of the cases was from January 19 to June 2, 2015, showing a continuous and homogenous outbreak pattern. The clinical manifestations of the cases were fever (72%), fatigue (40%), hyperhidrosis (26%), testicular enlargement (5.3%), headache (2.4%), and hepatomegaly (1.2%). In addition, 54 cases of latent infection were found. A total of 13 strains of brucella ovis type 3 were cultured from the patients’ serum samples. After all sheep in the farm were sampled, 16 samples of serum test tube agglutination test were positive, with a positive rate of 37% (16/44); after analysis, drinking fresh goat milk was a risk factor for brucellosis (
7.Study on metabolites of Laportea bulbifera extract in rat feces based on UHPLC-Q-TOF-MS~E technique.
Dan WU ; Ying LI ; Si-Ying CHEN ; Juan TANG ; Yue-Ting LI ; Jie PAN ; Yong HUANG ; Lin ZHENG ; Ai-Min WANG ; Yong-Jun LI ; Yan-Yu LAN ; Zi-Peng GONG
China Journal of Chinese Materia Medica 2020;45(13):3220-3227
This project is to study the metabolites of Laportea bulbifera extract in rat feces. After the SD rats were gavaged with the extract(136 g·kg~(-1), according to the crude drug dose), the metabolites in their feces were detected by UHPLC-Q-TOF-MS~E technique, and the obtained mass spectrometry data was combined with UNIFI software for prediction. The prototype components and metabolites in rat feces were identified with reference materials and related literature. A total of 43 metabolites were identified(including 8 prototype components and 35 metabolites). The metabolic pathways mainly include monocaffeoylquinic acid(hydrogenation reduction, ring-opening cracking, sulfation, hydroxylation, glucuronidation), quercetin(O-C2 bond ring-opening cleavage, C2-C3 double bond reduction, rutin carbonylation) and so on. The metabolites and metabolic process of L. bulbifera extract in rat feces were clarified, which provided a basis for the study of the active substances and its mechanism of action.
Administration, Oral
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Animals
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Chromatography, High Pressure Liquid
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Feces
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Plant Extracts
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Rats
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Rats, Sprague-Dawley
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Urticaceae
8.Simultaneous determination of four components of Shuganning Injection in rat plasma by UPLC-MS/MS and its application to a pharmacokinetic study.
Ning-Fang KANG ; Mei LI ; He-Jia HU ; Hong-Qin XIAO ; Li-Qin LIU ; Yin LI ; Yue-Ting LI ; Ai-Min WANG ; Yong-Lin WANG ; Yun ZHANG ; Feng HE ; Zi-Peng GONG
China Journal of Chinese Materia Medica 2020;45(11):2626-2633
This study aims to reveal the pharmacokinetics of Shuganning Injection in normal rats. In this experiment,ultra-high performance liquid chromatography-electrospray-tandem mass spectrometry( UPLC-ESI-MS/MS) was used to establish an analytical method for simultaneous determination of chlorogenic acid,gardenioside,oroxylin A and baicalin in rat plasma. Then,the non-compartmental model( NCA) in Phoenix WinN onL in 6. 4 software was used to fit pharmacokinetic parameters. The methodological validation showed that the linear relationship of the components in rat plasma samples were good( r>0. 995). The recovery rate and matrix effect of plasma samples with low,middle and high concentration were 79. 14%-101. 4%. The intra-day and inter-day precision,accuracy and stability meet the requirements of biological sample analysis. The half-life( t1/2) of chlorogenic acid,gardenioside,oroxylin A did not change significantly and the area under blood concentration-time curve( AUC0-t) is proportional to the dose,which suggested that three components showed a linear kinetic characteristics,but baicalin showed nonlinear kinetic characteristics. Moreover,the retention time of each component in rats was short. The established UPLC-MS/MS quantitative analysis method is rapid,sensitive and accurate,which can be used for the determination of chlorogenic acid,gardenioside,oroxylin A and baicalin in rat plasma and pharmacokinetic study of Shuganning Injection.
Animals
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Chlorogenic Acid
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Chromatography, High Pressure Liquid
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Chromatography, Liquid
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Plasma
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Rats
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Rats, Sprague-Dawley
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Reproducibility of Results
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Tandem Mass Spectrometry
9.Intestinal absorption properties of Gastrodiae Rhizoma powder with different particle size by circulation pass perfusion model in rats.
Mei LI ; Fan LIU ; Yan CHEN ; Ting-Ting CHEN ; Yue-Ting LI ; Si-Ying CHEN ; Yong HUANG ; Lin ZHENG ; Yong-Jun LI ; Ai-Min WANG ; Zi-Peng GONG
China Journal of Chinese Materia Medica 2020;45(1):179-187
This study is to study the absorption properties of different particle size of Gastrodiae Rhizoma powder in rats. In vivo circulation pass perfusion model combined with ultra high performance liquid chromatography-mass spectrometry(UPLC-MS/MS) method was used to determine the cumulative absorption of each component in different particle size of Gastrodiae Rhizoma powder, and the effect of different particle size, different concentrations, different intestine segments and bile on the intestine absorption of gastrodin and other compositions in Gastrodiae Rhizoma powder was investigated to illuminate the absorption properties and compare the absorption difference of gastrodin and other compositions in Gastrodiae Rhizoma powder in different particle size. The results showed that the absorption of gastrodin in each intestinal segment has no significant difference, pointing out that gastrodin may be passive absorption and the absorption of barrison glycosides may be active absorption; the absorption of gastrodin in ultrafine powder was better than that of common powder and superfine powder of Gastrodiae Rhizoma; the absorption of these barrison glycosides was good in ultrafine powder of Gastrodiae Rhizoma under the high concentration. However, an appropriate degree of superfine grinding can promote the absorption of active ingredients of Gastrodiae Rhizoma. This test can provide information for the deep development of Gastrodiae Rhizoma.
Animals
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Chromatography, High Pressure Liquid
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Drugs, Chinese Herbal/pharmacokinetics*
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Gastrodia
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Intestinal Absorption
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Particle Size
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Powders
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Rats
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Tandem Mass Spectrometry
10. Protective Effect of Gastrodiae Rhizoma Powder with Different Particle Sizes on Cerebral Ischemia Reperfusion Injury in Rats
Ting-ting CHEN ; Fan LIU ; Yan CHEN ; Zi-peng GONG ; Tao TAO ; Ai-min WANG
Chinese Journal of Experimental Traditional Medical Formulae 2019;25(8):71-76
Objective: To study the protective effect of Gastrodiae Rhizoma ultrafine powder with different particle sizes on focal cerebral ischemia-reperfusion injury in rats, in order to provide theoretical basis for the application of ultrafine powder technology in related products. Method: The SD rats were randomly divided into six groups, namely sham-operated group, ischemia-reperfusion group, Gastrodiae Rhizoma ultramicro-powder Ⅰ group(1.2 g·kg-1), Gastrodiae Rhizoma ultramicro-powder Ⅱ group(1.2 g·kg-1), Gastrodiae Rhizoma ultramicro-powder Ⅲ group(1.2 g·kg-1), and nimodipine positive drug group(12.6 g·kg-1). The cerebral ischemia-reperfusion model was established after 7 days of drug administration. The focal ischemia reperfusion injury model was prepared by middle cerebral artery occlusion (MCAO) for 1 h followed by reperfusion for 24 h. The infarct size of brain tissue was measured by triphenyltetrazolium Chloride(TTC) staining. The activities of superoxide dismutase (SOD), malondialdehyde (MDA) and nitricoxide synthase (NOS) in brain homogenate and serum were measured by colorimetry. The contents of glutamate(Glu), aspartic acid(Asp) and glycine(Gly) in hippocampus were determined by liquid chromatography-tandem mass spectrometry (LC/MSMS). Result:The model group showed obvious signs of neurobehavioral deficit (P<0.01) compared with the sham operation group. The area ratio of cerebral infarction was decreased significantly, the contents of Glu, Asp, MDA and the activity of NOS were significantly decreased, while the activity of SOD and content of Gly were significantly increased (P<0.05,P<0.01) in Gastrodiae Rhizoma ultramicro-powder Ⅰ, Ⅱ, Ⅲ groups compared with the model group. SOD activity and Gly content in the Gastrodiae Rhizoma ultramicro-powder Ⅲ group were significantly higher than those in the Gastrodiae Rhizoma ultramicro-powder Ⅰ group and the Gastrodiae Rhizoma ultramicro-powder Ⅱ group (P<0.05), and Glu, Asp, MDA content and NOS activity in the Gastrodiae Rhizoma ultramicro-powder Ⅰ group were significantly lower than those in the Gastrodiae Rhizoma ultramicro-powder Ⅱ group (P<0.05). Conclusion:Gastrodiae Rhizoma ultramicro-powder with different particle sizes has a protective effect on cerebral ischemia-reperfusion injury, and the Gastrodiae Rhizoma ultramicro-powder Ⅲ group has a more obvious protective effect than the the Gastrodiae Rhizoma ultramicro-powder Ⅰ group. The results showed that the protective effect of Gastrodiae Rhizoma ultramicro-powder on middle cerebral artery ischemia-reperfusion in rats was related to its particle size.

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