Divergent Copper-salt-controlled Reactions of Donor-Acceptor Cyclopropanes and N-Fluorobenzene Sulfonimide: Access to the 1,3-Haloamines and Aminoindanes.

We herein report a method for divergent copper salt controlled reactions of donor-acceptor cyclopropanes and N-fluorobenzene sulfonimide (NFSI). Specifically, in the presence of CuX2 (X=Cl, Br), the cyclopropanes underwent formal umpolung 1,3-aminohalogenation bifunctionalization via a free radical mediated ring-opening process to afford 1,3-aminochlorination and 1,3-aminobromination products in moderate to good yields. In addition, by using CuI as a catalyst, we synthesized various aminoindane derivatives via 1,3-aminoarylation cyclization of D-A cyclopropanes, the reactions involved a free radical mediated ring-opening and subsequent ring expansion via C-H bond activation.

Automatic Time Picking for Weak Seismic Phase in the Strong Noise and Interference Environment: An Hybrid Method Based on Array Similarity.

The extraction of travel-time curve of seismic phase is very important for the subsequent inference of the structural properties of underground media in seismology. In recent years, with the increase in the amount of data, manual processing is facing significant challenges, and automatic signal processing has gradually become the mainstream. According to the similarity of array signals and considering the elimination of outliers, we propose an improved multi-channel cross-correlation method using the L1 norm measure to obtain preliminary results, which builds on a new controllable measurement mode. Then, the post-correction step is carried out in combination with the signal gain property of beamforming technique. Based on these two methods, this paper proposes a new scheme of automatic arrival time picking. We apply the scheme to actual data to verify the effects of the two methods step by step. The entire scheme achieves fine results: direct water waves, seismic waves refracted by the crust and seismic waves reflected by the upper mantle are automatically detected. In addition, compared with the two traditional methods, the scheme proposed in this paper has a better overall effect and a reasonable computation cost.

Acute effects of air pollution on lupus nephritis in patients with systemic lupus erythematosus: A multicenter panel study in China.

Air pollution may trigger systemic lupus erythematosus (SLE). However, few studies have investigated the associations between air pollution and complications of SLE, such as lupus nephritis (LN). In this study, multicenter longitudinal data from 13 hospitals in China, including 8552 SLE patients with 24,762 visits, were used. Based on the generalized estimating equation (GEE) model, we assessed the associations of LN occurrence with short-term exposures to different air pollutants including particulate matter with an aerodynamic diameter < 2.5 µm (PM2.5), sulfur dioxide (SO2), nitrogen dioxide (NO2), carbon monoxide (CO), and ozone (O3). We identified 2672 LN patients, and about half of them were from east China. Our results based on the entire data set showed that PM2.5 and NO2 were risk factors for LN within one month after exposure, with odds ratio of 1.16 (95% confidence interval (CI), 1.08-1.19) at lag 18 day and 1.19 (95% CI, 1.12-1.26) at lag 16 day relative to an interquartile range (IQR) increase in PM2.5 and NO2, respectively. This positive association between LN and NO2 was also observed for south, west, and east China. In addition, we found that the short term exposure to CO and O3 was not generally associated with LN. Finally, the negative associations of LN with SO2 were found for the entire region and east China. Our results implied that SLE patients may gain the health benefits of air quality improvement in China. Our work also provided evidence that short-term variations in air pollution may trigger LN, and further studies are needed to confirm these findings and the potential pathogenic mechanisms should be explored.

Stereospecific Synthesis of cis-2,5-Disubstituted Pyrrolidines via N,O-Acetals Formed by Hydroamination Cyclization-Hydroalkoxylation of Homopropargylic Sulfonamides in HFIP.

We reported a novel two-step stereoselective synthesis of functionalized pyrrolidines from homopropargylic sulfonamides and nucleophiles via an isolable N,O-acetal intermediates. This reaction features mild conditions and good scope of substrates. In addition, the use of hexafluoroisopropanol, acting as a solvent, an additive, a weak nucleophile, and a good leaving group, is pivotal to the success of the method. Moreover, reactions of chiral homopropargylic sulfonamides afford only 2,5-cis-disubstituted pyrrolidines with high diastereoselectivity (up to >99:1 dr) and enantioselectivity (up to >99% ee). The overall reaction constitutes a formal 1,1-bifunctionalization of terminal alkynes, which has hitherto been reported only rarely. Additionally, this method provides efficient access to pharmaceutical intermediate and to carry out postmodification of natural products.

Increased frequency of CCR7+CD4+ T cells from patients with primary Sjögren's syndrome: An indicator of disease activity rather than of damage severity.

Expression of CCR7 on T cells has been reported to be associated with the lymphocytic migration and infiltration, which is recognized as a vital part of the pathogenesis of Primary Sjögren's syndrome (pSS). Here, we compared the expression of CCR7 on CD4+T cells between pSS patients and control groups, including healthy donors (HD) and patients with systemic lupus erythematosus (SLE) and examined correlations with disease activity and damage severity, which were evaluated by EULAR Sjögren's Syndrome Disease Activity Index (ESSDAI) and Sjogren's Syndrome Disease Damage Index (SSDDI), respectively. Peripheral blood mononuclear Cells (PBMC) were obtained from patients and controls and expressions of CCR7 were evaluated by flow cytometry. CCR7 was selectively and frequently expressed on CD4+T cells, but less on CD8+ T cells of patients with pSS. In contrast, this phenomenon was neither seen in normal subjects nor in patients with SLE. The expression level of CCR7 in the peripheral blood CD4+ T cells is closely correlated with ESSDAI, but not SSDDI. Correspondently, the chemotactic index (CI) of CD4+T cells was higher than CD8+T cells in patients with pSS. Furthermore, the CI of CD4+T cells is also higher than that of other controls, which is correlated with ESSDAI. All the findings suggested that CCR7 might play an important role in the development of pSS by mediating the migration of CD4+cells. Thus, the expression of CCR7 in CD4+ T cells is probably a useful biomarker to evaluate and monitor disease activity. CCR7 can also potentially be a novel target for the therapy of pSS.

TNFR1 and TNFR2 differentially mediate TNF-α-induced inflammatory responses in rheumatoid arthritis fibroblast-like synoviocytes.

TNF-α has long been implicated in the progression of rheumatoid arthritis (RA). However, how the receptors of TNF-α, namely TNFR1 and TNFR2, mediate TNF-α-induced inflammatory responses in fibroblast-like synoviocytes (FLS) in RA has not been elucidated. In the present study, primary FLS cells were isolated from RA patients and treated with TNF-α in vitro. The exogenous TNF-α induced the expression and release of endogenous TNF-α in FLS. In addition, TNF-α led to gradual downregulation of TNFR1 following 1 h treatment. By contrast, the expression of TNFR2 was markedly upregulated after 12 h treatment with TNF-α. Moreover, following TNF-α treatment, the expression of interleukin (IL)-2, IL-6, and IL-8 was gradually increased with time, but their mRNA levels dropped significantly at 48 h. We further investigated the differential functions of TNFR1 and TNFR2 in FLS by conducting siRNA-mediated knockdown. The TNF-α autocrine was inhibited to a greater extent in TNFR1-silenced FLS compared with TNFR2-silenced FLS. Silencing of TNFR1, not TNFR2, activated intrinsic apoptosis and inhibited TNF-α-induced cytokine production in FLS. These results suggest that TNFR1 is the major pro-inflammatory mediator of TNF-α in FLS, whereas TNFR2, which is upregulated in response to prolonged TNF-α stimulation, may act as an immunosuppressor in FLS for the prevention of overwhelming inflammatory reactions.

Increased levels of serum galectin-3 in patients with primary Sjögren's syndrome: associated with interstitial lung disease.

OBJECTIVES: To explore the potential values of serum galectin-3 (Gal-3) levels in diagnosis of interstitial lung disease (ILD) for patients with primary Sjögren's syndrome (pSS). METHODS: The concentrations of serum Gal-3 and interleukin (IL)-17 were measured by enzymelinked immunosorbent assay (ELISA) in 87 patients with pSS and 30 healthy controls (HC). The levels of plasma C-reactive protein (CRP), rheumatoid factor (RF), immunoglobulin (Ig)G, complement (C3), albumin (ALB) and Fibrinogen (FIB) and erythrocyte sedimentation rate (ESR) were measured. ILD was identified on high-resolution computed tomography. RESULTS: The levels of serum Gal-3 and IL-17 were significantly higher in pSS patients than in HC. Stratification analyses indicated significantly higher levels of Gal-3 in pSS patients with ILD and in those with positive ANCA. In comparison with that of pSS patients without ILD, significantly higher levels of ESR, CRP, FIB, IgG, C3 and lower ALB were detected in pSS patients with ILD. The levels of galectin-3 were correlated positively with the values of CRP, FIB, IgG or IL-17 in patients with pSS. CONCLUSIONS: These findings suggest that higher levels of serum galectin-3 may be associated with the development of pSS, particularly with ILD.

Knockdown of sphingosine kinase 1 inhibits the migration and invasion of human rheumatoid arthritis fibroblast-like synoviocytes by down-regulating the PI3K/AKT activation and MMP-2/9 production in vitro.

To investigate the potential regulation of sphingosine kinase 1 (SPHK1) on the migration, invasion, and matrix metalloproteinase (MMP) expression in human rheumatoid arthritis fibroblast-like synoviocytes (RA-FLS). RA-FLS were transfected control siRNA or SPHK1 siRNA. The migration and invasion of unmanipulated control, control siRNA or SPHK1 siRNA- transfected RA-FLS in vitro were measured by the transwell system. The relative levels of SPHK1, PI3K, and AKT as well as AKT phosphorylation in RA-FLS were determined by Western blot. The levels of MMP-2/9 secreted by RA-FLS were detected by ELISA. Knockdown of SPHK1 significantly inhibited the spontaneous migration and invasion of RA-FLS, accompanied by significantly reduced levels of PI3K expression and AKT phosphorylation. Similarly, treatment with LY294002, an inhibitor of the PI3K/AKT pathway, inhibited the migration and invasion of RA-FLS. Knockdown of SPHK1 and treatment with the inhibitor synergistically inhibited the migration and invasion of RA-FLS, by further reducing the levels of PI3K expression and AKT phosphorylation. In addition, knockdown of SPHK1 or treatment with LY294002 inhibited the secretion of MMP-2 and MMP-9, and both synergistically reduced the production of MMP-2 and MMP-9 in RA-FLS in vitro. Knockdown of SPHK1 expression inhibits the PI3K/AKT activation, MMP-2 and MMP-9 expression, and human RA-FLS migration and invasion in vitro. Potentially, SPHK1 may be a novel therapeutic target for RA.

Retroperitoneal fibrosis: a clinical and outcome analysis of 58 cases and review of literature.

The purpose of the study was to investigate the clinical features and outcomes of retroperitoneal fibrosis (RPF). Fifty-eight RPF treatment cases in the First Affiliated Hospital of China Medical University were retrospectively analyzed, including clinical characteristics and laboratory data. RPF was found predominantly in elderly men with atypical clinical manifestations of back pain, abdominal pain, and lower limb edemas. In laboratory examinations, the acute-phase reactants such as erythrocyte sedimentation rate and C-reactive protein levels increased significantly. Renal function failure was frequently found in patients with urethral obstruction. All patients had retroperitoneal soft tissue shadows or urethral obstructions on computed tomography (CT) or magnetic resonance imaging (MRI), seven of which had histological diagnosis of idiopathic RPF. Forty-two patients received surgical interventions; 29 patients received medication treatment alone including corticosteroids, immunosuppressants, and tamoxifen; 17 patients received corticosteroids after surgical intervention. Surgery followed by medication was most effective for RPF. CT and MRI help to exclude secondary causes, but biopsy remains the gold standard for diagnosis. Long-term low-dose corticosteroids and immunosuppressants may prevent relapse of RPF.

Practical synthesis of allylic amines via nickel-catalysed multicomponent coupling of alkenes, aldehydes, and amides.

Molecules with an allylic amine motif provide access to important building blocks and versatile applications of biologically relevant chemical space. The need for diverse allylic amines requires the development of increasingly general and modular multicomponent reactions for allylic amine synthesis. Herein, we report an efficient catalytic multicomponent coupling reaction of simple alkenes, aldehydes, and amides by combining nickel catalysis and Lewis acid catalysis, thus providing a practical, environmentally friendly, and modular protocol to build architecturally complex and functionally diverse allylic amines in a single step. The method is remarkably simple, shows broad functional-group tolerance, and facilitates the synthesis of drug-like allylic amines that are not readily accessible by other methods. The utilization of accessible starting materials and inexpensive Ni(ii) salt as the alternative precatalyst offers a significant practical advantage. In addition, the practicality of the process was also demonstrated in an efficient, gram-scale preparation of the prostaglandin agonist.

Ketone α-alkylation at the more-hindered site.

Control of the regioselectivity of α-alkylation of carbonyl compounds is a longstanding topic of research in organic chemistry. By using stoichiometric bulky strong bases and carefully adjusting the reaction conditions, selective alkylation of unsymmetrical ketones at less-hindered α-sites has been achieved. In contrast, selective alkylation of such ketones at more-hindered α-sites remains a persistent challenge. Here we report a nickel-catalysed alkylation of unsymmetrical ketones at the more-hindered α-sites with allylic alcohols. Our results indicate that the space-constrained nickel catalyst bearing a bulky biphenyl diphosphine ligand enables the preferential alkylation of the more-substituted enolate over the less-substituted enolate and reverses the conventional regioselectivity of ketone α-alkylation. The reactions proceed under neutral conditions in the absence of additives, and water is the only byproduct. The method has a broad substrate scope and permits late-stage modification of ketone-containing natural products and bioactive compounds.

CpG-ODN 2006 and human parvovirus B19 genome consensus sequences selectively inhibit growth and development of erythroid progenitor cells.

Recent studies have shown that anemia is commonly observed after exposure to pathogens or pathogen-derived products, which are recognized via Toll-like receptor 9 (TLR9). In the current study, we demonstrate that CpG oligodeoxynucleotide-2006, a TLR9 ligand with phosphodiester (PO; 2006-PO) but not with the phosphorothioate backbone, selectively inhibits the erythroid growth derived from human CD34(+) cells. The 2006-PO was internalized by the erythroid progenitors within 30 minutes; however, expression of TLR9 mRNA was not detected in these cells. The 2006-PO directly inhibited burst-forming unit-erythroid growth, resulted in the accumulation of cells in S and G(2)/M phases, and increased cell size and frequency of apoptotic cells. These features were similar to those observed in erythroid progenitors infected with human parvovirus B19 that causes pure red cell aplasia. The consensus sequence of 2006-PO was defined as 5'-GTTTTGT-3', which was located in the P6-promoter region of B19 and inhibited erythroid growth in a sequence-specific manner and down-regulated expression of erythropoietin receptor (EPOR) mRNA and EPOR. B19 genome extracted from serum also inhibited erythroid growth and down-regulated expression of EPOR on glycophorin A(+) cells. These results provide a possible insight into our understanding of the mechanisms of human parvovirus B19-mediated inhibition of erythropoiesis.

Corporate climate risk and stock market reaction to performance briefings in China.

This study aims to enrich our understanding of the valuation consequence of climate risk in financial markets. The primary focus of our study is on the stock price reaction to firms' climate-risk-related information. We employ transcripts of Chinese listed firms' performance briefings to capture the climate risk at the firm level. Using a sample of Chinese listed firms between 2009 and 2021, we find that greater corporate climate risks lead to negative market reactions over a short time window, consistent with the market quickly comprehending corporate climate risks. This result holds for a series of robustness checks. We further find that the negative impact of corporate climate risk on the stock price reaction operates through the increased market trading activities, greater investor attention, and reduced positive media coverage. Finally, we demonstrate that industry carbon emission, local abnormal temperature, state ownership, institutional shareholding, and dividend payout are important moderators that shape the association of the corporate climate risk and the adverse market reaction. Our evidence suggests that disclosures of climate-related information can help the stock market to price climate risk more efficiently.

A clinical practice guideline for the screening and assessment of enthesitis in patients with spondyloarthritis.

Objective: The aim of this review is to provide guidance on the selection of approaches to the screening and assessment of enthesitis in patients with spondyloarthritis (SpA). Methods: Twenty-four questions regarding the approaches to the screening and assessment of enthesitis and the implementation details were devised, followed by a systemic literature review. The Grading of Recommendations Assessment, Development, and Evaluation methodology was employed in the development of this guideline, with modifications to evaluate non-interventional approaches under comprehensive consideration of costs, accessibility, and evidence strength. A consensus from the voting panel was required for the inclusion of the final recommendations and the strength of each recommendation. Results: Seventeen recommendations (including five strong recommendations) were included in this guideline. The voting panel expressed unequivocal support for the necessity of screening and assessment of enthesitis in patients with SpA. It was agreed unanimously that symptom evaluation and physical examination should serve as the initial steps to the recognition of enthesitis, whereas Maastricht Ankylosing Spondylitis Enthesitis Score is a reliable tool in both clinical trials and daily medical practice. Ultrasound examination is another reliable tool, with power Doppler ultrasound as an informative addition. Notwithstanding its high resolution, MRI is limited by the costs and relatively low accessibility, whereas radiographs had low sensitivity and therefore should be rendered obsolete in the assessment of enthesitis. PET/CT was strongly opposed in the detection of enthesitis. Conclusion: This guideline provides clinicians with information regarding the screening and assessment of enthesitis in patients with SpA. However, this guideline does not intend on dictating choices, and the ultimate decisions should be made in light of the actual circumstances of the facilities.

Increased serum TWEAK levels in Psoriatic arthritis: relationship with disease activity and matrix metalloproteinase-3 serum levels.

OBJECTIVES: We measured serum levels of Tumor necrosis factor (TNF)-like weak inducer of apoptosis (TWEAK), interleukin 15 (IL-15), monocyte chemoattractant protein 1 (MCP-1), and matrix metalloproteinase (MMP)-3 for patients with Psoriatic arthritis (PsA), and investigated whether TWEAK levels are associated with clinical disease activity and expression of proinflammatory cytokines. METHODS: Forty five patients with PsA and forty five patients with osteoarthritis (OA) were involved in this study between January 2008 and December 2009. At the time of blood sample collection, the disease activity of patients with PsA was assessed according to the 28-joint count Disease Activity Score (DAS28). Serum levels of TWEAK, IL-15, MCP-1, and MMP-3 were measured using commercial enzyme-linked immunosorbent assay (ELISA) kits according to the manufacturers' protocol. RESULTS: In patients with PsA, serum TWEAK, IL-15, MCP-1 and MMP-3 levels were significantly elevated, and serum TWEAK levels showed a significant correlation with DAS28 (r=0.405, p=0.006) and serum MMP-3 levels (r=0.375, p=0.011). CONCLUSIONS: Serum TWEAK levels positively correlate with disease activity of PsA and confirm that TWEAK plays a crucial role in the pathogenesis of PsA. TWEAK may be a new important target for therapy in PsA.

Anti-macrophage-derived chemokine antibody relieves murine lupus nephritis.

We observed the distribution of monocyte's changes in damage to renal tissue and the expression of macrophage-derived chemokine (MDC) in MRL/lpr mice. The 8-week-old MRL/lpr mice were randomly assigned to receive either MDC antibodies (n = 6) or placebo (n = 6) at a once-every-other-day dose of 300 µl from week 4. We then quantified the differences in 24-h urine protein and serum creatinine concentrations, performed a histological evaluation of renal tissue and assessed the expression of MDC protein and mRNA between the two groups 4 weeks after treatment was initiated. Antibody-treated mice demonstrated significantly lower urine protein and serum creatinine concentrations and had fewer renal lesions compared with control mice. The expression of MDC protein and mRNA in renal tissues was significantly lower in the antibody-treated mice than in control mice, suggesting that the elevated expression of MDC, which led to monocyte infiltration in the kidney, may play an important role in the development of lupus nephritis. Furthermore, the anti-MDC antibodies may act to alleviate the renal lesions of murine lupus nephritis by inhibiting the infiltration of monocytes in the renal tissue of the lupus mice.

[Clinical study of total glucosides of paeony in patients with systemic lupus erythematosus].

OBJECTIVE: To study the therapeutic efficacy and adverse reaction of total glucosides of paeony (TGP, extracted from Paeonia lactiflora Pall.) in patients with systemic lupus erythematosus (SLE). METHODS: Clinical data of patients with SLE were analyzed. Those who orally took TGP continuously for five years or more were taken as TGP1 group (29 cases). Those who orally took TGP continuously or intermittently for more than one year but less than five years were taken as TGP2 group (47 cases). Twenty patients matched with the TGP1 group and the TGP2 group in age, affected duration, urine protein, and SLE disease activity index (SLEDAI) were selected as the control group. The average daily dose of prednisone, total cyclophosphamide (CTX) dose, urine protein, SLEDAI score, recurrent case, and episodes of infection were compared among the three groups after five-year treatment. RESULTS: The average daily dose of prednisone, total CTX dose, and SLEDAI score were obviously lower in the TGP1 group than in the control group (P<0.01). The average daily dose of prednisone, total CTX dose, and SLEDAI score were obviously lower in the TGP1 group than in the TGP2 group, Significant difference was shown (P <0. 05). The average daily dose of prednisone and total CTX dose were lower in the TGP2 group than in the control group (P<0.05, P<0.01). There was no statistical difference in the urine protein among the three groups. As for the recurrence, one case occurred in the TGP1 group, nine in the TGP2 group, and seven in the control group. As for episodes of infection, there were three cases in the TGP1 group, seventeen in the TGP2 group, and eighteen in the control group during the five years. No adverse reaction correlated to TGP was found in the three groups. CONCLUSIONS: TGP had definite therapeutic efficacy in treatment of patients with SLE. It could reduce the average daily dose of prednisone and the total CTX dose, lower the recurrent cases and episodes of infection, especially for the medication of more than five years.

Acid Sphingomyelinase and Acid ß-Glucosidase 1 Exert Opposite Effects on Interleukin-1ß-Induced Interleukin 6 Production in Rheumatoid Arthritis Fibroblast-Like Synoviocytes.

Acid sphingomyelinase (ASM) and acid ß-glucosidase 1 (GBA1) catalyze ceramide formation through different routes, and both are involved in rheumatoid arthritis (RA) pathogenesis as well as IL-6 production. However, whether ASM and GBA1 regulate IL-6 production in RA remains unknown. Serum ASM, GBA1, and ceramide levels were measured in RA patients and healthy controls by enzyme-linked immunosorbent assay, and their correlations with clinical indicators of patients were evaluated. Pharmacologic inhibitors or small hairpin RNAs of ASM and GBA1 were employed to explore the roles of ASM and GBA1 in IL-6 production, cell behavior, and MAPK signaling in fibroblast-like synoviocytes from RA patients (RAFLS). ASM, GBA1, and ceramide serum levels were significantly elevated in patients with RA. GBA1 and ceramide serum levels were negatively and positively correlated with IL-6 serum level in RA patients, respectively. ASM inhibitor or knockdown of ASM abolished IL-1ß-induced IL-6 expression and secretion. Functionally, ASM inhibitor suppressed IL-1ß-induced cell proliferation, migration, and invasion in RAFLS. Mechanistically, ASM inhibitor or knockdown of ASM effectively countered IL-1ß-induced activation of p38 MAPK signaling. The pharmacologic inhibitor or knockdown of GBA1 exhibited the opposite effects. Importantly, p38 inhibitor blocked IL-1ß-induced IL-6 production in RAFLS. ASM plays a pathogenic role in RA, whereas GBA1 plays a protective role in RA possibly by regulating IL-6 production in RAFLS at least partially via p38 signaling, serving as potential therapeutic targets in RA treatment.

Safety and Efficacy of Prefilled Liquid Etanercept-Biosimilar Yisaipu for Active Ankylosing Spondylitis: A Multi-Center Phase III Trial.

INTRODUCTION: The aim of this work is to examine the efficacy and safety of prefilled liquid etanercept-biosimilar Yisaipu versus lyophilized Yisaipu in active ankylosing spondylitis (AS) patients. METHODS: This double-blind, phase III trial with non-inferiority design randomized adult patients with active AS in a 3:1:1 ratio to receive twice-weekly 25-mg prefilled liquid Yisaipu for a total of 48 injections (group I, n = 330), once-weekly 50-mg prefilled liquid Yisaipu for 24 injections (group II, n = 110), or twice-weekly 25-mg lyophilized Yisaipu for 48 injections (group III, n = 110). Both physicians and patients who received 25-mg twice-weekly lyophilized or liquid Yisaipu were blinded to treatment assignment while patients who received 50-mg once-weekly liquid Yisaipu received treatment in an open-label design. In addition, 90 patients in the PK/PD study were randomized in a 1:1:1 ratio to each group. The primary outcome was the proportion of patients who achieved ASAS20 at week 24. RESULTS: A total of 640 subjects were enrolled. The proportion of patients who attained ASAS20 at week 24 was 85.56% in group I, 85.71% in group II, and 83.45% in group III (group I vs. III, P = 0.545; group II vs. III, P = 0.605). The difference between group I and III was 2.10% (95% CI - 5.06%, 9.27%) and 2.26% (95% CI - 6.21%, 10.73%) between group II and III, meeting the non-inferiority threshold (Δ = - 15%) (P < 0.001). Except for a statistical difference between group I (75.83%) and group III at week 8 (64.75%, P = 0.011), there was no statistical difference in the ASAS20 attainment rate among the three groups at other time points. The incidence of serious adverse events was comparable among the three groups (group I, 2.50%, II, 2.86% and III, 1.43%; P > 0.05). No deaths were reported. CONCLUSIONS: Once-weekly 50-mg or twice-weekly 25-mg prefilled liquid Yisaipu is safe and non-inferior to twice-weekly 25-mg lyophilized Yisaipu. TRIAL REGISTRATION: CTR20130124 and NCT04345458.

2018 Chinese Guidelines for the Diagnosis and Treatment of Rheumatoid Arthritis.

A multidisciplinary guideline development group was established to formulate this evidence-based diagnosis and treatment guidelines for rheumatoid arthritis (RA) in China. The grading of recommendations, assessment, development, and evaluation (GRADE) system was used to rate the quality of the evidence and the strength of recommendations, which were derived from research articles and guided by the analysis of the benefits and harms as well as patients' values and preferences. A total of 10 recommendations for the diagnosis and treatment of RA were developed. This new guideline covered the classification criteria, disease activity assessment and monitoring, and the role of disease modifying antirheumatic drugs (DMARDs), biologics, small molecule synthetic targeting drugs, and glucocorticoids in the treat-to-target approach of RA. This guideline is intended to serve as a tool for clinicians and patients to implement decision-making strategies and improve the practices of RA management in China.