We assessed the efficacy and safety of duloxetine (60 mg, once daily), compared with placebo, during a 13-week treatment period in Chinese patients with chronic pain due to osteoarthritis (OA). Patients were at least 40 years old (male or female) who met American College of Rheumatology clinical and radiographic criteria for the diagnosis of OA of the knee or hip. The primary efficacy measure in this phase 3, randomized, double-blind, placebo-controlled clinical trial was assessment of pain severity by the Brief Pain Inventory (BPI) 24-h Average Pain rating. The clinical trial was conducted at 17 study centers. Statistical approaches included mixed-effects model repeated measures and analysis of covariance. A Fisher exact test was applied to categorical variables. Of 407 patients randomized (duloxetine: N = 205; placebo: N = 202), 166 (81.0%) patients from the duloxetine group and 176 (87.1%) patients from the placebo group completed the 13-week treatment phase. The majority (76.4%) of patients was female; mean age was 60.5 years. Duloxetine-treated patients reported significant pain reduction, compared with placebo treatment, on the BPI 24-h Average Pain rating (least-squares mean (LS Mean) change from baseline to endpoint [95% confidence interval (CI)], duloxetine: -2.23; placebo: -1.73; difference = -0.50 [-0.80, -0.20]; P = 0.001). The incidence of discontinuations due to adverse events was 9.0% in duloxetine-treated patients and 4.5% in placebo-treated patients (P = 0.109). This study demonstrated the efficacy of duloxetine in Chinese patients with chronic pain due to OA. The safety profile of duloxetine observed in this study was consistent with that in previous duloxetine trials. This trial is registered with ClinicalTrials.gov (NCT01931475).

We investigated the characteristics of Chinese SLE patients by analyzing the association between specific autoantibodies and clinical manifestations of 2104 SLE patients from registry data of CSTAR cohort. Significant (P<0.05) associations were found between anti-Sm antibody, anti-rRNP antibody, and malar rash; between anti-RNP antibody, anti-SSA antibody, and pulmonary arterial hypertension (PAH); between anti-SSB antibody and hematologic involvement; and between anti-dsDNA antibody and nephropathy. APL antibody was associated with hematologic involvement, interstitial lung disease, and a lower prevalence of oral ulcerations (P<0.05). Associations were also found between anti-dsDNA antibody and a lower prevalence of photosensitivity, and between anti-SSA antibody and a lower prevalence of nephropathy (P<0.05). Most of these findings were consistent with other studies in the literature but this study is the first report on the association between anti-SSA and a lower prevalence of nephropathy. The correlations of specific autoantibodies and clinical manifestations could provide clues for physicians to predict organ damages in SLE patients. We suggest that a thorough screening of autoantibodies should be carried out when the diagnosis of SLE is established, and repeated echocardiography annually in SLE patients with anti-RNP or anti-SSA antibody should be performed.

The present study aimed to examine the status and clinical significance of cluster of differentiation (CD) 19+CD24highCD38high regulatory B cells (Bregs), serum interleukin (IL)‑10, serum transforming growth factor (TGF)‑β and IL‑10 receptor (IL‑10R) expression in peripheral blood from patients with systemic lupus erythematosus (SLE). A total of 56 patients with SLE and 35 healthy individuals were recruited to the present study. The SLE disease activity index (SLEDAI) was calculated, and other laboratory parameters were measured. Peripheral blood was collected from all participants. The frequency of CD19+CD24highCD38high Bregs and IL‑10R+ expression on circulating lymphocytes was examined by flow cytometry. The serum levels of IL‑10 and TGF‑β were measured using enzyme‑linked immunosorbent assay. The associations between these measurements and SLEDAI or other laboratory parameters were analyzed by correlation analysis. The percentage of CD19+CD24highCD38high Bregs and the serum levels of IL‑10 were significantly increased, whereas the expression of IL‑10R on circulating lymphocytes was markedly reduced in patients with SLE compared with in healthy controls. The serum levels of TGF‑β1 were not markedly different between the groups. In addition, these factors were correlated with other SLE laboratory parameters, and inter‑correlations were presented with different degrees of significance. The percentage of CD19+CD24highCD38high Bregs was positively correlated with the percentage of IL‑10R+ lymphocytes, mean fluorescence intensity (MFI) of IL‑10R+ lymphocytes and serum IL‑10 levels. In addition, the percentage of IL‑10R+ lymphocytes was positively correlated with its expression level (MFI), whereas serum TGF‑β1 levels were negatively correlated with serum IL‑10 levels. The present results indicated that expansion of CD19+CD24highCD38high Bregs, upregulation of IL‑10 and deficient lymphocyte‑associated IL‑10R may serve as novel SLE biomarkers. It may be hypothesized that deficient IL‑10R expression results in compensatory enhanced IL‑10 expression, expansion of Bregs, and/or compromised Breg and IL‑10 functions, thus contributing to SLE development. Therefore, targeting the 'Bregs/IL‑10/IL‑10R' system may provide a novel therapeutic approach for the treatment of SLE.

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.

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.