A Quantitative Tissue-Specific Landscape of Protein Redox Regulation during Aging.

Mammalian tissues engage in specialized physiology that is regulated through reversible modification of protein cysteine residues by reactive oxygen species (ROS). ROS regulate a myriad of biological processes, but the protein targets of ROS modification that drive tissue-specific physiology in vivo are largely unknown. Here, we develop Oximouse, a comprehensive and quantitative mapping of the mouse cysteine redox proteome in vivo. We use Oximouse to establish several paradigms of physiological redox signaling. We define and validate cysteine redox networks within each tissue that are tissue selective and underlie tissue-specific biology. We describe a common mechanism for encoding cysteine redox sensitivity by electrostatic gating. Moreover, we comprehensively identify redox-modified disease networks that remodel in aged mice, establishing a systemic molecular basis for the long-standing proposed links between redox dysregulation and tissue aging. We provide the Oximouse compendium as a framework for understanding mechanisms of redox regulation in physiology and aging.

Aberrant phenotypes of circulating γδ-T cells may be involved in the onset of systemic lupus erythematosus.

OBJECTIVE: Human gamma-delta T cells (γδ-T cells) play crucial roles in both innate and adaptive immune responses. However, much less is known about the immune status of γδT cells in systemic lupus erythematosus (SLE) patients. The objective of this study was to explore potential relationships between the frequency of γδ-T-cell subpopulations and disease activity, autoantibody titres and renal involvement in patients with SLE. METHODS: Circulating γδ-T cells and their subsets (Vδ1+ T cells, Vδ2+ T cells and γδ-T-cell subpopulations defined by expression of surface receptors, including NKG2D, NKp30, NKp46 and PD-1), were identified via flow cytometry. Sixty active SLE patients were selected, including 41 new-onset and 19 relapsing cases. One hundred healthy controls (HCs) were enrolled as the control group. Percentages of these cell subsets in SLE patients and HCs and their relationships with disease activity were analysed. Twenty-two of the 41 new-onset SLE patients were assessed before and after treatment. Changes in the frequencies of these cell subsets and their relationships with renal involvement were also analysed. RESULTS: Compared with that in HCs, the percentage of total γδ-T cells among CD3+ T cells in SLE patients was significantly lower. An imbalance in the proportions of Vδ1+ and Vδ2+ T cells among γδ-T cells was observed. The proportion of Vδ1+ T cells among γδ-T cells was significantly greater in SLE patients than in HCs, while the proportion of Vδ2+ T cells was significantly lower. Expression levels of PD-1, NKG2D, NKp30 and NKp46 in Vδ1+ T cells and Vδ2+ T cells from SLE patients were generally significantly increased, except for expression of NKG2D in Vδ2+ T cells. Moreover, Vδ2+ T cells, Vδ1+ T cells and Vδ1+PD-1+ T cells were associated with disease activity, and an increase in Vδ2+ T-cell frequency and a decrease in PD-1 expression by γδ-T cells might be associated with effective treatment. Interestingly, our results indicated that Vδ2+ T cells and their Vδ2+NKp30+ T-cell subpopulation might be associated with renal involvement in SLE. CONCLUSION: A broad range of anomalies in the proportions of γδ-T-cell subsets and γδ-T cells in SLE patients may be involved in the pathogenesis of SLE. There is a strong association between Vδ2+ T cells and their Vδ2+NKp30+ T-cell subpopulation and LN occurrence. Our results indicate that γδ-T cells and their subpopulations might be key players in disease immunopathology and renal involvement in SLE.

Plasticity in binding confers selectivity in ligand-induced protein degradation.

Heterobifunctional small-molecule degraders that induce protein degradation through ligase-mediated ubiquitination have shown considerable promise as a new pharmacological modality. However, we currently lack a detailed understanding of the molecular basis for target recruitment and selectivity, which is critically required to enable rational design of degraders. Here we utilize a comprehensive characterization of the ligand-dependent CRBN-BRD4 interaction to demonstrate that binding between proteins that have not evolved to interact is plastic. Multiple X-ray crystal structures show that plasticity results in several distinct low-energy binding conformations that are selectively bound by ligands. We demonstrate that computational protein-protein docking can reveal the underlying interprotein contacts and inform the design of a BRD4 selective degrader that can discriminate between highly homologous BET bromodomains. Our findings that plastic interprotein contacts confer selectivity for ligand-induced protein dimerization provide a conceptual framework for the development of heterobifunctional ligands.

Development of CDK2 and CDK5 Dual Degrader TMX-2172.

Cyclin-dependent kinase 2 (CDK2) is a potential therapeutic target for the treatment of cancer. Development of CDK2 inhibitors has been extremely challenging as its ATP-binding site shares high similarity with CDK1, a related kinase whose inhibition causes toxic effects. Here, we report the development of TMX-2172, a heterobifunctional CDK2 degrader with degradation selectivity for CDK2 and CDK5 over not only CDK1, but transcriptional CDKs (CDK7 and CDK9) and cell cycle CDKs (CDK4 and CDK6) as well. In addition, we demonstrate that antiproliferative activity in ovarian cancer cells (OVCAR8) depends on CDK2 degradation and correlates with high expression of cyclin E1 (CCNE1), which functions as a regulatory subunit of CDK2. Collectively, our work provides evidence that TMX-2172 represents a lead for further development and that CDK2 degradation is a potentially valuable therapeutic strategy in ovarian and other cancers that overexpress CCNE1.

A Melting Curve-Based Multiplex RT-qPCR Assay for Simultaneous Detection of Four Human Coronaviruses.

Human coronaviruses HCoV-OC43, HCoV-229E, HCoV-NL63 and HCoV-HKU1 are common respiratory viruses associated with acute respiratory infection. They have a global distribution. Rapid and accurate diagnosis of HCoV infection is important for the management and treatment of hospitalized patients with HCoV infection. Here, we developed a melting curve-based multiplex RT-qPCR assay for simultaneous detection of the four HCoVs. In the assay, SYTO 9 was used to replace SYBR Green I as the fluorescent dye, and GC-modified primers were designed to improve the melting temperature (Tm) of the specific amplicon. The four HCoVs were clearly distinguished by characteristic melting peaks in melting curve analysis. The detection sensitivity of the assay was 3 × 10² copies for HCoV-OC43, and 3 × 10¹ copies for HCoV-NL63, HCoV-229E and HCoV-HKU1 per 30 µL reaction. Clinical evaluation and sequencing confirmation demonstrated that the assay was specific and reliable. The assay represents a sensitive and reliable method for diagnosis of HCoV infection in clinical samples.

[Expression of regulatory B cells in peripheral blood of patients with systemic lupus erythematosus].

OBJECTIVE: To explore the expression of regulatory B cells (Bregs) in peripheral blood of patients with systemic lupus erythematosus (SLE) and elucidate the function of Bregs in the pathogenesis of SLE. METHODS: A total of 38 active SLE patients, 22 inactive SLE subjects and 20 healthy controls were enrolled. The expressions of IL-10+ CD19+ Breg and CD19+ CD24hi CD38hi Breg in peripheral blood mononuclear cells (PBMC) were evaluated by flow cytometry. And IL-10 was measured in the culture supermatants by enzyme-linked immunosorbent assay (ELISA). RESULTS: The expression of IL-10+ CD19+ Breg in PBMCs of active SLE patients was (1.54±0.64)%. And it was lower than those in inactive SLE patients (2.42±0.75)% (P<0.01) and healthy controls (4.35±1.00)% (P<0.01). And the expression of CD19+ CD24hi CD38hi Breg was (1.26±0.45)%. Also it was lower than those in inactive SLE subjects (2.01±0.61)% (P<0.01) and healthy controls (3.14±0.87)% (P<0.01).The level of IL-10 significantly decreased in culture supermatants of active SLE patients. And it was lower than those in inactive SLE subjects (P<0.05) and healthy controls (P<0.01). The percentage of IL-10+ CD19+ Breg and CD19+ CD24hi CD38hi Breg in PBMCs of SLE patients was positively correlated with the level of IL-10 in culture supernatants (r=0.652, P<0.01 and r=0.574, P<0.01). CONCLUSION: The expression of IL-10-related Bregs significantly decreases in PBMCs of active SLE patients. And Bregs may play some role in the pathogenesis of SLE.

Prolactin increases tumor necrosis factor alpha expression in peripheral CD14 monocytes of patients with rheumatoid arthritis.

Tumor necrosis factor (TNF)-α is one of the major proinflammatory mediators of rheumatic arthritis (RA); the regulatory factors for TNF-α release is not fully understood. This study aims to investigate the role of prolactin receptor (PRLR) activation in regulating the expression and release of TNF-α from CD14(+) monocytes. The results showed that the expression of PRLR was detectable in CD14(+) monocytes of healthy subjects, which was markedly increased in RA patients. Exposure to PRL in the culture increased the expression and release of TNF-α from CD14(+) monocytes, which was abolished by the PRLR gene silencing or blocking the mitogen activated protein (MAPK) pathway. We conclude that exposure to PRL increases TNF-α release from CD14(+) monocytes of RA patients, which can be abolished by PRLR gene silencing or treating with MAPK inhibitor.

Hypomethylation of interleukin 6 correlates with renal involvement in systemic lupus erythematosus.

OBJECTIVE: To analyze peripheral blood interleukin 6 (IL-6) methylation status and its clinical significance in patients with systemic lupus erythematosus (SLE). MATERIAL AND METHODS: Blood samples from 41 adult patients with SLE, and 20 healthy controls were collected. The methylation status of IL-6 was determined by methylation specific polymerase chain reaction (MSP). The IL-6 expression was detected by real-time PCR. Correlations between IL-6 methylation status and clinical features or laboratory findings in patients with SLE were investigated. RESULTS: The methylation status and expression of IL-6 in peripheral blood could reflect the level in peripheral blood mononucleated cells (PBMCs) of SLE. Significantly positive correlation was found between IL-6 hypomethylation and renal disorder. Interleukin 6 hypomethylation was found negatively correlated with serum C3. CONCLUSIONS: The detection of IL-6 methylation status in peripheral blood could reflect the status in PBMC with SLE. Interleukin 6 may play a role in renal disorder with SLE patients. Interleukin 6 could be considered as a new biomarker for predicting SLE flare.

Study on the anti-retrogradation of wheat amylopectin by addition of alkali-soluble glutenin.

The retrogradation of wheat amylopectin during cold storage is the main reason for the increasing hardness of flour products such as steamed bread, bread and pastries, etc. Addition of gluten protein components is a green, safe, cheap and efficient method to inhibit the retrogradation of wheat amylopectin. In this paper, as being stored at 4 °C for 7 d, retrogradation rate of wheat amylopectin decreased from 55.02 % to 14.37 % after it was mixed with 20 % alkali-soluble glutenin (ASG) at 30 °C for 90 min, a 73.8 % reduction. The infrared results showed that the intensity of bending vibration of water molecules and intra-molecular ß-sheet content of ASG decreased during the interaction between amylopectin and ASG. Meanwhile, intermolecular ß-sheet and random coil contents of ASG increased. The results of 13C Solid-state NMR indicated that Qß, Pγ and Lγ of ASG involved in interaction of wheat amylopectin, ASG and molecule of water. Under the optimal conditions, the interaction of wheat amylopectin and ASG began to form spheres containing disulfide bonds, resulting in the attenuation or disappearance of the diffraction peak at 2θ 19.7°, which may be marked as the criterion for the best mixing time of wheat amylopectin and ASG. The retrogradation kinetic index (n) of wheat amylopectin decreased significantly with the addition of ASG and formation of disulfide bond was the key factor. ASG could be potentially used as an anti-retrogradation agent for amylopectin.

Discovery of bivalent small molecule degraders of cyclin-dependent kinase 7 (CDK7).

Cyclin-dependent kinase 7, along with cyclin H and MAT1, forms the CDK-activating complex (CAK), which directs cell cycle progression via T-loop phosphorylation of cell cycle CDKs. Pharmacological inhibition of CDK7 leads to selective anti-cancer effects in cellular and in vivo models, motivating several ongoing clinical investigations of this target. Current CDK7 inhibitors are either reversible or covalent inhibitors of its catalytic activity. We hypothesized that small molecule targeted protein degradation (TPD) might result in differentiated pharmacology due to the loss of scaffolding functions. Here, we report the design and characterization of a potent CDK7 degrader that is comprised of an ATP-competitive CDK7 binder linked to a CRL2VHL recruiter. JWZ-5-13 effectively degrades CDK7 in multiple cancer cells and leads to a potent inhibition of cell proliferation. Additionally, compound JWZ-5-13 displayed bioavailability in a pharmacokinetic study conducted in mice. Therefore, JWZ-5-13 is a useful chemical probe to investigate the pharmacological consequences of CDK7 degradation.

Broad-spectrum activity against mosquito-borne flaviviruses achieved by a targeted protein degradation mechanism.

Viral genetic diversity presents significant challenges in developing antivirals with broad-spectrum activity and high barriers to resistance. Here we report development of proteolysis targeting chimeras (PROTACs) targeting the dengue virus envelope (E) protein through coupling of known E fusion inhibitors to ligands of the CRL4CRBN E3 ubiquitin ligase. The resulting small molecules block viral entry through inhibition of E-mediated membrane fusion and interfere with viral particle production by depleting intracellular E in infected Huh 7.5 cells. This activity is retained in the presence of point mutations previously shown to confer partial resistance to the parental inhibitors due to decreased inhibitor-binding. The E PROTACs also exhibit broadened spectrum of activity compared to the parental E inhibitors against a panel of mosquito-borne flaviviruses. These findings encourage further exploration of targeted protein degradation as a differentiated and potentially advantageous modality for development of broad-spectrum direct-acting antivirals.

Discovery of Potent Degraders of the Dengue Virus Envelope Protein.

Targeted protein degradation has been widely adopted as a new approach to eliminate both established and previously recalcitrant therapeutic targets. Here we report the development of small molecule degraders of the envelope (E) protein of dengue virus. We developed two classes of bivalent E-degraders, linking two previously reported E-binding small molecules, GNF-2 and CVM-2-12-2, to a glutarimide-based recruiter of the CRL4CRBN ligase to effect proteosome-mediated degradation of the E protein. ZXH-2-107 (based on GNF-2) is an E degrader with ABL inhibition while ZXH-8-004 (based on CVM-2-12-2) is a selective and potent E-degrader. These two compounds provide proof-of-concept that difficult-to-drug targets such as a viral envelope protein can be effectively eliminated using a bivalent degrader and provide starting points for the future development of a new class antiviral drugs.

[Detection significance of Th17 cells in peripheral blood of patients with rheumatoid arthritis in clinical remission].

OBJECTIVE: To explore the significance and evaluate the early structural erosion through the expressions of Th17 cells in peripheral blood of patients with rheumatoid arthritis (RA) in clinical remission. METHODS: A total of 41 active RA patients without structural erosion were selected. Intracelluar flow cytometric detection of Th17 cells in peripheral blood was performed. And the supernatant level of interleukin (IL)-17A was determined simultaneously in RA patients and control groups at baseline and endpoint of 24-month therapy. The correlations were analyzed between Th17 cells and RA disease activity index DAS28. They were classified into radiographic progression (P, n = 10) and radiographic non-progression groups (NP, n = 26) by the Sharp/van der Heijde score (SHS) at the endpoint. The differences of Th17 cells and IL-17A levels were analyzed between P (SHS > 0.5) and NP groups (SHS ≤ 0.5). RESULTS: The expression of Th17 cells in active RA patients was significantly higher than that of controls [(1.63 ± 0.45)% vs (0.91 ± 0.26)%, P < 0.01]. And the results of IL-17A level were similar [1510 ± 280) vs (320 ± 31) ng/L, P < 0.05]. The expression of Th17 cells was positively correlated with DAS28 score (r = 0.87, P < 0.01). Thirty-six RA patients were followed up at the endpoint and all of them stayed in clinical remission (DAS28 < 2.6). The peripheral blood expressions of Th17 cells of P group were significantly higher than those of NP group . At the same time, no differences of IL-17A levels existed between two groups. CONCLUSION: Structural erosion still progresses in some RA patients despite an apparent clinic remission. And a high-level peripheral expression of Th17 hints at structural erosion.

Threshold effects and inflection points of flavonoid intake in dietary anti-inflammatory effects: Evidence from the NHANES.

Flavonoids have been shown to be beneficial in a variety of inflammatory and metabolic diseases because of their anti-inflammatory and antioxidant properties. However, previous epidemiological studies have only demonstrated a negative correlation between flavonoid intake on inflammatory markers, and the optimal intake of dietary flavonoids and subclasses in terms of dietary anti-inflammatory efficacy remains undetermined. This study was based on 3 cycles (2007-2010, 2017-2018) of the National Health and Nutrition Examination Survey and the corresponding expanded flavonoid database. Weighted multiple linear regression was used to assess linear relationships between flavonoid intake and Dietary inflammation index (DII). Smoothed curve fit and a generalized additive model were used to investigate the nonlinear relationships and threshold effects, the 2-tailed linear regression model was used to find potential inflection points. A total of 12,724 adults were included in the study. After adjusting for potential confounders, flavonoid intake was significantly associated with DII, with the strongest negative association effect for flavonols (-0.40 [-0.45, -0.35]). In subgroup analyses stratified by sex, race, age, body mass index, education levels, and diabetes, flavonol intake maintained a significant negative linear correlation with DII. In addition, we found significant nonlinear relationships (L-shaped relationships) and threshold effects between total flavonoids, flavan-3-ols, and flavanols and DII, with inflection points of 437.65 mg/days, 157.79 mg/days, and 46.36 mg/days, respectively. Our results suggest a threshold for the dietary anti-inflammatory capacity of flavonoid intake in U.S. adults.

The relationship between demographic factors and syncopal symptom in pediatric vasovagal syncope.

This research proposed to retrospectively analyze 20 years of clinical data and investigate the relationship between demographic factors and syncopal symptom in pediatric vasovagal syncope. A total of 2513 children, 1124 males and 1389 females, age range 3-18 years, who presented to Department of Pediatric Cardiovasology, Children's Medical Center, The Second Xiangya Hospital, Central South University with unexplained syncope or pre-syncope and were diagnosed with vasovagal syncope were retrospectively collected and divided into syncope group (n = 1262) and pre-syncope group (n = 1251). (1) Females had a 36% increased risk of syncope compared to males, a 27% increased risk of syncope for every 1-year increase in age, and a 2% decreased risk of syncope for every 1 cm increase in height. (2) A non-linear relationship between age, height, weight and syncope was observed. When age > 10.67 years, the risk of syncope increases by 45% for each 1-year increase in age; when height < 146 cm, the risk of syncope decreases by 4% for each 1 cm increase in height; when weight < 28.5 kg, the risk of syncope decreases by 10% for each 1 kg increase in weight. Demographic factors are strongly associated with syncopal symptom in pediatric vasovagal syncope and can help to predict the risk.

Development of a Covalent Inhibitor of c-Jun N-Terminal Protein Kinase (JNK) 2/3 with Selectivity over JNK1.

The c-Jun N-terminal kinases (JNKs) are members of the mitogen-activated protein kinase (MAPK) family, which includes JNK1-JNK3. Interestingly, JNK1 and JNK2 show opposing functions, with JNK2 activity favoring cell survival and JNK1 stimulating apoptosis. Isoform-selective small molecule inhibitors of JNK1 or JNK2 would be useful as pharmacological probes but have been difficult to develop due to the similarity of their ATP binding pockets. Here, we describe the discovery of a covalent inhibitor YL5084, the first such inhibitor that displays selectivity for JNK2 over JNK1. We demonstrated that YL5084 forms a covalent bond with Cys116 of JNK2, exhibits a 20-fold higher Kinact/KI compared to that of JNK1, and engages JNK2 in cells. However, YL5084 exhibited JNK2-independent antiproliferative effects in multiple myeloma cells, suggesting the existence of additional targets relevant in this context. Thus, although not fully optimized, YL5084 represents a useful chemical starting point for the future development of JNK2-selective chemical probes.

New scaffolds for type II JAK2 inhibitors overcome the acquired G993A resistance mutation.

Recurrent JAK2 alterations are observed in myeloproliferative neoplasms, B-cell acute lymphoblastic leukemia, and other hematologic malignancies. Currently available type I JAK2 inhibitors have limited activity in these diseases. Preclinical data support the improved efficacy of type II JAK2 inhibitors, which lock the kinase in the inactive conformation. By screening small molecule libraries, we identified a lead compound with JAK2 selectivity. We highlight analogs with on-target biochemical and cellular activity and demonstrate in vivo activity using a mouse model of polycythemia vera. We present a co-crystal structure that confirms the type II binding mode of our compounds with the "DFG-out" conformation of the JAK2 activation loop. Finally, we identify a JAK2 G993A mutation that confers resistance to the type II JAK2 inhibitor CHZ868 but not to our analogs. These data provide a template for identifying novel type II kinase inhibitors and inform further development of agents targeting JAK2 that overcome resistance.

[Expression and significance of Th17 and Treg cells in peripheral blood of patients with systemic lupus erythematosus].

OBJECTIVE: To explore the expression and significance of Th17 and Treg cells in peripheral blood of patients with systemic lupus erythematosus (SLE). METHODS: Thirty active SLE patients (including 17 SLE patients with lupus nephritis), 20 inactive SLE patients and 20 healthy controls were enrolled. The expressions of Th17 cells and CD4+CD25+Foxp3+Treg cells in peripheral blood mononuclear cells (PBMC) were evaluated by flow cytometry. The correlations between the expression of Th17 cells, CD4+CD25+Foxp3+Treg cells and disease activity (SLEDAI), as well as the ratios of Th17 cells and Treg cells (Th17/Treg) in SLE patients and healthy controls were analyzed respectively. RESULTS: The expression of Th17 cells in PBMC of SLE patients was higher than that in healthy controls [(1.39 ± 0.60)% vs (0.80 ± 0.33)%, P < 0.01] while the expression of CD4+CD25+Foxp3+Treg cells decreased in SLE patients [(3.09 ± 1.54)% vs (6.04 ± 1.49)%, P < 0.01]. The increased expression of Th17 cells and reduced CD4+CD25+Foxp3+Treg cells in PBMC were positively correlated with SLEDAI and negatively correlated with complements C3 and C4. There were increased expression of Th17 cells and reduced CD4+CD25+Foxp3+Treg cells in PBMC of lupus nephritis versus SLE patients without nephritis. CONCLUSION: There is an abnormal elevation of Th17 cells and decrease of CD4+CD25+Foxp3+Treg cells in PBMC of SLE patients. The imbalance between Th17 and Treg cells may play a critical role in the pathogenesis of SLE.

The anti-retrogradation properties of maize amylopectin treated by being co-crystallized with NaCl.

Long-term retrogradation of amylopectin always leads to the quality deterioration of starch-based food. In this paper, the purified maize amylopectin was co-crystallized with NaCl to obtain anti-retrograded amylopectin. The results showed that the retrogradation rate of maize amylopectin dropped directly from 27.92 % to 19.05 % at the conditions of amylopectin: 5 % NaCl (m/v) = 1.7:10, eutectic times 24 h at 4 °C. The co-crystals with a dendritic shape consisted of a center and several large branches and the length of the largest branch reached up to 10,000 µm. The results of the maximum absorbance of iodine-attached amylopectin, molecular weight and chain length distributions showed that hydrolysis and graft of amylopectin happened in the eutectic process. Residues produced by acid hydrolysis linked to the main chains via α-1,6 glycosidic linkage at the late stage of eutectic reaction. The marked signs for single helix of maize amylopectin with Mw >20 × 105 g/mol were the enhancement of weak resonance at 100.0 ppm (104.1, 100.0, 94.6, 82.9 ppm). Single-helix maize amylopectin was more likely to form sharp X-ray diffraction during being dried without gelatinization. The possible mechanism for anti-retrogradation of maize amylopectin by co-crystal treatment was deduced. Co-crystallization with NaCl to produce single-helix amylopectin was a promising strategy to prepare anti-retrogradation amylopectin.

Inflammatory markers and risk factors of RA patients with depression and application of different scales in judging depression.

To evaluate the association of inflammatory markers and depression in RA patients and the risk factors in RA with depression, a cross-sectional study was conducted in a cohort of RA patients from southern China.Two hundred-fifteen RA patients were enrolled. The demographic and disease-related characteristics were recorded and inflammatory markers in sera were measured. RA patients were guided to fill out PHQ-9 scale by themselves, the psychological state was evaluated by psychiatry experts and graded according to the HAMD-17 scale. The consistency of the two scales in judging depression was evaluated. RA with depression group had HAMD-17 scores greater than 7. The levels of CRP, ESR, fibrinogen, SAA, IL-2, IL-6, TNF-α, IFN-γ, IL-4, and IL-10 were measured and compared. Logistic regression analysis was performed to find the risk factors of RA with different depression levels. One hundred-five (48.84%) RA patients had HAMD-17 scores greater than 7. High consistency was found between HAMD-17 and PHQ-9 in predicting depression. RA patients with depression were more likely to have tender joints, lower income, no employment, higher disease activity, joint deformities and glucocorticoid treatment. The depressed RA patients had higher serum levels of IL-6, CRP, fibrinogen, and SAA. IL-6, CRP, fibrinogen, and SAA were positive correlated with depression in RA patients. PHQ-9 can replace HAMD-17 in clinical application to judge depression.