Zhijun Li

Objectives: This phase II trial aimed to evaluate the efficacy and safety of SSGJ‐613, a fully human anti‐interleukin 1β monoclonal antibody, compared with compound betamethasone (CB) in Chinese patients with acute gouty arthritis. Methods: In this multicenter, double‐blind, double‐dummy, active‐controlled study, 90 adults with gout according to the 2015 American College of Rheumatology (ACR) criteria and who had experienced an acute gouty arthritis flare within 7 days were randomized (1:1:1) to receive a single subcutaneous injection of SSGJ‐613 (200 mg or 300 mg) or intramuscular CB. The primary endpoint was the change from baseline in visual analog scale (VAS) pain scores at 72 h post‐dosing. Safety was evaluated through monitoring of adverse events and laboratory parameters. Results: The mean changes from baseline in VAS scores at 72 h were comparable between SSGJ‐613200 mg (−45.8 mm), 300 mg (−40.4 mm), and CB (−48.2 mm) groups. However, SSGJ‐613 significantly reduced the risk of new flares: 16.7% (200 mg) and 14.3% (300 mg) of patients experienced new flares versus 54.8% with CB ( p = 0.0037 and p = 0.0019, respectively). The safety profile of SSGJ‐613 was similar to CB, with no drug‐related serious adverse events reported. Conclusion: A single injection of SSGJ‐613 demonstrated rapid pain relief comparable to corticosteroid therapy at 72 h and provided superior protection against gout flare recurrence over 12 weeks in Chinese patients, supporting its potential as an effective treatment option for acute gouty arthritis with prolonged therapeutic benefits. Clinical Trials: NCT06169891.

Background: The labial salivary glands (LSGs) are important for the diagnosis, evaluation of therapeutic efficacy, and genetic analyses of primary Sjögren’s syndrome (pSS). In autoimmune diseases, the recognition of self nucleic acids and viral RNA and DNA through endogenous Toll-like receptor(TLR) triggers the production of type I IFN and pro-inflammatory cytokines, leading to the occurrence and progression of the disease. Here, we detected the expression of TLR7 in LSGs and analyse its correlation with clinical features and serum cytokines in pSS patients. Methods: LSGs and serum samples were obtained from 56 pSS patients and 19 non-SS patients (non-pSS patients). The expression of TLR7 in the LSGs was evaluated with immunohistochemistry. The serum levels of interferon-α (IFN-α) and interleukin-6 (IL-6) were quantified by ELISA. Laboratory parameters were measured by clinical standard laboratory techniques. Results: TLR7-positive cells in pSS were localized in the ductal epithelial cells and lymphocytes of LSGs. The expression of TLR7 was upregulated in pSS patients compared with controls. Patients with anti-Ro52 antibody positivity showed higher TLR7 levels than those who were negative but not those with anti-Ro60 and anti-SSB. TLR7 levels were positively associated with the levels of IgG, IgA, ANA, IL-6, IFN-α and serum globulin but were not associated with IgM, C3, C4, or rheumatoid factor (RF) in serum. Conclusion: TLR7 may be involved in the inflammatory response and the production of antibodies in pSS and plays an important role in local and systemic pSS manifestations. This research showed that TLR7 is involved in pSS pathogenesis.

Primary Sjogren's syndrome (pSS) is a common autoimmune disorder that affects up to 0.3-3% of the global population. Ferroptosis has recently been identified to play a significant role in autoimmune diseases. However, the molecular mechanisms of ferroptosis in the initiation and progression of pSS remains unclear. To investigate the molecular mechanisms underlying the occurrence and progression of pSS, we utilized a comprehensive approach by integrating data obtained from the Gene Expression Omnibus (GEO) database with data from the FerrDb database to identify the ferroptosis-related differentially expressed genes (DEGs). Furthermore, we implemented an innovative transcriptomic analysis method utilizing a computer-aided algorithm to establish a network between hub genes associated with ferroptosis and the immune microenvironment in pSS patients. Our results revealed significant differences in the gene expression profiles of pSS samples compared to normal tissues, with 1,830 significantly up-regulated genes and 1,310 significantly down-regulated genes. In addition, our results showed a significant increase in the proportions of B cells and CD4+ T cells in pSS samples compared to normal tissues. AND then, our analysis revealed that a combination of six ferroptosis-related genes, including TBK1, SLC1A4, PIK3CA, ENO3, EGR1, and ATG5, could serve as optimal markers for the diagnosis of pSS. The combined analysis of these six genes accurately diagnosed the occurrence of pSS. This study offers valuable insights into the pathogenesis of pSS and highlights the importance of targeting ferroptosis-related DEGs, which suggests a novel treatment strategy for pSS.

Background The labial salivary glands (LSGs) are important for the diagnosis, evaluation of therapeutic efficacy, and genetic analyses of primary Sjogren's syndrome (pSS). In autoimmune diseases, the recognition of self nucleic acids and viral RNA and DNA through endogenous Toll-like receptor(TLR) triggers the production of type I IFN and pro-inflammatory cytokines, leading to the occurrence and progression of the disease. Here, we detected the expression of TLR7 in LSGs and analyse its correlation with clinical features and serum cytokines in pSS patients. Methods LSGs and serum samples were obtained from 56 pSS patients and 19 non-SS patients (non-pSS patients). The expression of TLR7 in the LSGs was evaluated with immunohistochemistry. The serum levels of interferon-α (IFN-α) and interleukin-6 (IL-6) were quantified by ELISA. Laboratory parameters were measured by clinical standard laboratory techniques. Results TLR7-positive cells in pSS were localized in the ductal epithelial cells and lymphocytes of LSGs. The expression of TLR7 was upregulated in pSS patients compared with controls. Patients with anti-Ro52 antibody positivity showed higher TLR7 levels than those who were negative but not those with anti-Ro60 and anti-SSB. TLR7 levels were positively associated with the levels of IgG, IgA, ANA, IL-6, IFN-α and serum globulin but were not associated with IgM, C3, C4, or rheumatoid factor (RF) in serum. Conclusion TLR7 may be involved in the inflammatory response and the production of antibodies in pSS and plays an important role in local and systemic pSS manifestations. This research showed that TLR7 is involved in pSS pathogenesis.

Telitacicept, an injectable recombinant human B‐lymphocyte stimulating factor receptor‐antibody fusion protein, is a new dual B lymphocyte stimulator (BLyS)/APRIL (a proliferation‐inducing ligand) inhibitor that effectively blocks proliferation of B lymphocytes. This study evaluates the pharmacokinetic characteristics, tolerability, and safety of a single subcutaneous injection of various doses (80, 160, and 240 mg) of telitacicept in healthy Chinese subjects. This trial is a single‐center, randomized, open‐label phase I clinical study that includes three dose groups (80, 160, and 240 mg) with 12 subjects in each dose group. The subjects were randomly assigned to different dose groups in a 1:1:1 ratio for a single subcutaneous administration trial. After a single dose, the maximum serum concentration (C_max) of total and free telitacicept was reached within 0.5‐1 days. The elimination half‐lives of total and free telitacicept at doses of 80–240 mg were 10.9–11.9 days and 11–12.5 days, respectively. The formation and elimination of the BLyS‐telitacicept complex were much slower; the median time to C_max was 15–57 days and was significantly prolonged with increasing dose. Only two of the 36 healthy subjects had positive antidrug antibodies with antibody titers of 1:15. The severity of adverse events was mild or moderate, and no higher treatment‐emergent adverse events were reported. In conclusion, total telitacicept within a dose range of 80–240 mg and free telitacicept within a dose range of 160–240 mg had linear pharmacokinetic characteristics.

Systemic lupus erythematosus (SLE) is a chronic, systemic, autoimmune inflammatory disease characterized by the production of numerous autoantibodies and cytokines, as well as multiple organ damage. Specific B cell subsets negatively regulate immune responses and have been termed regulatory B cells (Bregs). Bregs are characterized by the production of the immunoregulatory cytokines interleukin (IL)-10, IL-35, and transforming growth factor (TGF)-β. Bregs suppress other immune cells through the secretion of these immunosuppressive cytokines and have thus been studied extensively for their potential role in the treatment of various autoimmune diseases. The progress of the research on Bregs and SLE in recent years is reviewed in this paper.

The objectives of this study were to assess the maintenance of effect of duloxetine 60 mg once-daily (QD) in Chinese patients with chronic pain due to osteoarthritis (OA) of the knee or hip and to provide additional long-term safety data. This was an open-label, extension phase of a randomized, double-blind, placebo-controlled clinical trial. Eligible patients were outpatients who met the American College of Rheumatology clinical and radiographic criteria for OA with a rating ≥4 on Brief Pain Inventory (BPI) 24-h average pain. After completing the 13-week placebo-controlled phase, patients originally assigned to placebo were titrated to duloxetine 60 mg QD (PLA_DLX), whereas patients originally assigned to duloxetine 60 mg QD remained on the same dose of duloxetine (DLX_DLX) for another 13 weeks. The maintenance effect of duloxetine 60 mg QD during the extension phase was evaluated by a 1-sided 97.5% confidence interval (CI) of the baseline-to-endpoint change in the extension phase for patients who took duloxetine and reported ≥30% reduction in BPI average pain at the end of placebo-controlled phase (placebo-controlled phase duloxetine responders). Other BPI severity and interference items, as well as safety and tolerability, were assessed. Of 342 patients entering the extension phase, 162 (97.6%) DLX_DLX-treated patients and 157 (89.2%) PLA_DLX-treated patients completed this phase. Most patients (76.0%) were female. Mean age was 60.6 years. Mean BPI average pain was 5.5 at baseline of the placebo-controlled phase. Among 113 placebo-controlled phase duloxetine responders, mean change in BPI average pain during the extension phase was − 0.59 (from 2.47 to 1.88); the upper bound of the 1-sided 97.5% CI was − 0.31 and less than the pre-specified non-inferiority margin of a 1.5-point increase (p < 0.001). Significant within-group improvements in all BPI items were observed for both PLA_DLX and DLX_DLX groups during the extension phase (all p < 0.01). No deaths or suicide-related events occurred. Seven (4.0%) PLA_DLX-treated patients and no DLX_DLX-treated patients discontinued due to an adverse event. The analgesic effect of duloxetine 60 mg QD among treatment responders was maintained for the entire duration of the extension phase. Duloxetine 60 mg QD was well tolerated during the extension phase. ClinicalTrials.gov identification number NCT01931475 . Registered 29 August 2013.

The authors regret that the Fig. 1 in the original version of this article contained an error. In the left column, 211 cases in the TGP group should be followed up for 8 weeks before 12 weeks. The...

Objective To detect serum levels of interleukin-10 (IL-10) and transforming growth factor-β1 (TGF-β1) in patients with systemic lupus erythematosus (SLE) with bone damage, and analyze their clinical significance. Methods The study included 56 patients with SLE. Serum IL-10 and TGF-β1 levels were detected by ELISA. The clinical data of 56 patients were retrospectively analyzed, mainly recording the cases of osteoporosis and osteonecrosis. According to different bone mass, they were divided into normal bone mass group (14 cases), reduced bone mass group (26 cases) and osteoporosis group (16 cases). According to whether or not there was osteonecrosis, the patients were divided into: no osteonecrosis group (49 cases) and osteonecrosis group (7 cases). SPSS18.0 software was used for statistical analysis. Kolmogorov-smirnov t test whether the data is normally distributed. The measurement data of normal distribution are analyzed by the two-tailed t test. For the measurement data of non-normal distribution, mann-whitney U test was used to analyze. Results Compared to the SLE patients with normal bone mass, SLE patients complicated with osteoporosis lowly expressed TGF-β1 and highly expressed IL-10. The serum level of IL-10 was higher in SLE patients with osteonecrosis than that in SLE patients without osteonecrosis. No difference was found in the TGF-β1 between two groups. Conclusion TGF-β1 level is reduced but IL-10 level is elevated in SLE patients with osteoporosis. Serum IL-10 levels in SLE patients with osteonecrosis are higher than that in those without osteonecrosis.