Efficacy and safety of once weekly semaglutide 2·4 mg for weight management in a predominantly east Asian population with overweight or obesity (STEP 7): a double-blind, multicentre, randomised controlled trial.

BACKGROUND: Data on the benefits of the once weekly GLP-1 receptor agonist semaglutide 2·4 mg for weight management in people from east Asia are insufficient. The objective of this study was to determine the efficacy and safety of once weekly semaglutide 2·4 mg versus placebo for weight management in a predominantly east Asian adult population. METHODS: This randomised phase 3a, double-blind multicentre controlled trial (STEP 7) recruited participants from 23 hospitals and trial centres in China, Hong Kong, Brazil, and South Korea. Adults with overweight or obesity, with or without type 2 diabetes, were randomly assigned (2:1) to receive a subcutaneous injection of either semaglutide 2·4 mg or placebo once a week for 44 weeks, plus a diet and physical activity intervention. Randomisation was done in blocks of six with an interactive web response system and was stratified by diagnosis of type 2 diabetes. Participants, investigators, and the trial sponsor were masked to treatment allocation until after database lock. Primary endpoints were percentage change in mean bodyweight and proportion of participants having reached a weight reduction of at least 5% of bodyweight from baseline to week 44. Safety was assessed in all participants who received at least one dose of study drug. This study is registered with ClinicalTrials.gov, NCT04251156, and is now complete. FINDINGS: From Dec 8, 2020, to Aug 23, 2022, 448 participants were screened, of whom 375 were randomly assigned to either the semaglutide 2·4 mg group (n=249) or the placebo group (n=126). Estimated mean percentage change in bodyweight from baseline to week 44 was -12·1% (SE 0·5) with semaglutide 2·4 mg versus -3·6% (0·7) with placebo (estimated treatment difference -8·5 percentage points [95% CI -10·2 to -6·8]; p<0·0001). At week 44, the proportion of participants who lost 5% or more of their bodyweight was higher in the semaglutide 2·4 mg group than in the placebo group (203/238 [85%] vs 36/116 [31%]); odds ratio 13·1 (95% CI 7·4-23·1; p<0·0001). Adverse events were reported by 231 (93%) of 249 participants in the semaglutide 2·4 mg group and 108 (86%) of 126 participants in the placebo group, the most common of which were gastrointestinal disorders (168/249, 67% vs 45/126, 36%). INTERPRETATION: The results of this study support the use of semaglutide 2·4 mg for weight management in people of east Asian ethnicity with overweight or obesity and with or without type 2 diabetes. FUNDING: Novo Nordisk. TRANSLATIONS: For the Mandarin, Portuguese and South Korean translations of the abstract see Supplementary Materials section.

[Preliminary Study of Lonicera hypoglauca on Germination Conditions of Sand Culture Seeds and Sterilization Method of Sand Culture Seedling Sterilization].

OBJECTIVE: To explore the germination conditions of Lonicera hypoglauca sand culture seeds and the effects of sand culture seedlings sterilization. METHODS: 0.1% HgCl2 with different sterilization time, different illumination time and temperature culture condition were adopted to study the germination conditions of sand culture seeds. Different sterilization treatments and different hardening-seedling days were used to test the sterilization effect of sand culture seedlings. RESULTS: The sterilization effect of the combination of 75% ethanol 30 s + 0.1% HgCl2 5 min on Lonicera hypoglauca seeds was the optimum,with the average pollution rate of 15.56%, and the average germination rate reached 51.11%. The combination of varied temperature-room temperature under light for 12 h/d was the best, with the average germination rate peaked at 75.49%, and the average germination potential reached 68.36%. The treatment of detergent liquor scrub-tap water wash on the part above the hypocotyl, which was sand cultured under the opening condition and had no root, showed the best sterilization effect, with the average pollution rate was zero, and the average survival rate peaked at 100.00%. The sterilization effect of sand culture seedlings, which was disinfected after cleaning by detergent liquor scrub-tap water wash after hardening-seeding for 30 days, was the best, with the average pollution rate of 50.00%, and the average survival rate of 100.00%. CONCLUSION: The best sterilization effect is the combination of 75% ethanol 30 s + 0.1% HgCl2 5 min; Lighting for 12 h/d of varied temperature-room temperature is regarded as the optimum culture condition. The treatment of detergent liquor scrub-tap water wash treatment on the part above the hypocotyl,which is sand cultured under the opening condition and had no root, shows the best sterilization effect. For the sand culture seedlings, before inoculated in subculture medium, should be hardening-seedling for some days and sterilized after detergent liquor scrub-tap water wash.

Chylothorax and chylopericardium in Behçet's diseases: case report and literature review.

Behçet's disease (BD) with chylothorax and/or chylopericardium is uncommon. Here, we report a case of a 32-year-old man suffering BD with chylothorax and chylopericardium complications. We also review the literature and discuss clinical characteristics, possible pathogenesis, and treatment strategy of patients suffering BD with chylothorax and/or chylopericardium complications.

Clinical significance of peripheral blood lymphocyte subsets in patients with polymyositis and dermatomyositis.

Peripheral blood lymphocyte subsets were determined by flow cytometry in 89 Chinese patients with polymyositis (PM) and dermatomyositis (DM). We aimed to investigate the clinical significance of peripheral blood lymphocyte subsets in PM/DM. Patients with active DM showed significant decreases in numbers of CD3(+) cells, CD3(+)CD4(+) cells, and CD3(+)CD8(+) cells, as compared to patients with inactive DM and healthy controls (P < 0.05). CD3(+) and CD3(+)CD4(+) cell counts were significantly lower in DM before treatment, compared with after treatment (t = -5.714 and -3.665, P < 0.05). Counts of CD3(+) cells, CD3(+)CD4(+) cells, CD3(+)CD8(+) cells, and CD19(+)CD5(-) cells were all correlated with the total disease activity score as determined by the Myositis Disease Activity Assessment Visual Analogue Scale (P < 0.05). The decreased number of CD3(+) cells and the decreased percentage of CD3(+)CD4(+) cells were additionally correlated with the presence of interstitial lung disease in PM/DM (P < 0.05). The presence of levels of CD3(+)CD8(+) cells was risk factor for death (b = -0.011, OR = 0.989, P < 0.05). The identification of peripheral blood T lymphocyte subsets in PM/DM appears to be useful as a reference marker in the evaluation of clinical disease activity, and be useful in the comprehensive assessment of clinical lung involvement. A decrease in CD8(+) T cells may predict a poor outcome in patients with PM/DM.

Cardiac involvement in adult polymyositis or dermatomyositis: a systematic review.

BACKGROUND: To investigate the clinical features of cardiac involvement in polymyositis (PM) or dermatomyositis (DM). HYPOTHESIS: More attention will be focused on the heart in PM/DM as we would have wished, which contribute to improve the prognosis. METHODS: All articles published in English were retrieved by searching MEDLINE via PubMed (1975-2011). After selecting eligible articles according to the predefined inclusion and exclusion criteria, a systemic review was carried out. RESULTS: A total of 26 articles were included in this study, which included 1530 patients. The incidence of cardiac involvement was 9% to 72%. Heart failure was the most frequent (32% to 77%) clinical symptom. Among the abnormal electrocardiogram and ultrasonic cardiogram, the incidence of conduction abnormalities, left ventricular diastolic dysfunction, and hyperkinetic left ventricular contraction were 25% to 38.5%, 42%, and 6% to 12%, respectively. The pathologic findings revealed myocardial inflammation, degenerative changes and necrosis similar to that in skeletal muscles. Cardiac manifestations of some patients improved after glucocorticoid and immunosuppressant treatment. Thirty-seven patients (46.3%) died as a direct result of heart disease. CONCLUSIONS: Heart abnormalities are frequent in patients with PM/DM, most of which were subclinical. The efficacy of glucocorticoids and immunosuppressants is uncertain. Cardiac involvement is a common cause of death.

Intravenous immunoglobulin therapy in adult patients with polymyositis/dermatomyositis: a systematic literature review.

The objectives of this study are to review and summarize published information on the use, effectiveness, and adverse effects of intravenous immunoglobulin (IVIG) in patients with polymyositis (PM) or dermatomyositis (DM) and to search MEDLINE and CNKI (Chinese) databases from 1985 to 2011 to retrieve clinical research articles concerning IVIG in adult patients with PM/DM. Of the 14 articles selected, two were randomized controlled trials, nine prospective open studies, and three retrospective studies with a total of 308 adult patients. IVIG has been used successfully in the treatment of PM/DM. The standard dose is 2 g/kg, given in two to five individual daily doses. The course of IVIG treatment is usually 3~6 months. IVIG therapy seemed rarely employed as first-line therapy in PM/DM. In a double-blind study conducted in patients with refractory DM, IVIG combined with corticosteroid significantly improved muscle strength and decreased serum creatine kinase level, compared with placebo. The beneficial effect of IVIG in refractory, flare-up, rapidly progressive, or severe PM/DM has been documented in many open-label trials. IVIG was shown to be effective in most of PM/DM patients with lung involvement and esophageal involvement. In some patients, IVIG can lower the corticosteroid dose required for maintenance, demonstrating the most effective steroid-sparing effect. Adverse effects were generally tolerable. IVIG is effective in the treatment of adult patients with PM/DM and appears to be relatively well tolerated and safe. IVIG may be a good choice especially in patients with refractory, flare-up, rapidly progressive, or severe PM/DM, and can be tried in patients with a contraindication for corticosteroid.

[Expression of interferon and its correlation with clinical features in idiopathic inflammatory myopathies].

OBJECTIVE: To detect the expression levels of interferons IFNα, IFNß and IFNγ in the peripheral blood and muscle of patients with idiopathic inflammatory myopathies (IIM) so as to analyze their relationships with organ manifestations. METHODS: The serum levels of IFNα, IFNß, IFNγ and anti-Jo-1antibody were measured with ELISA (enzyme-linked immunosorbent assay). And the method of SYBR green dye based real-time quantitative PCR (polymerase chain reaction) was used to compare the expression levels of IFNα, IFNß, interferon α receptor 1 (IFNαR1), signal transducer and activator of transcription 1 (STAT1) in the IIM patients and normal controls. RESULTS: The serum levels of IFNα (50.2 ± 21.0) ng/L and IFNß (10.7 ± 5.4) ng/L in IIM patients were significantly higher than those in normal controls (18.6 ± 3.6) ng/L, (3.9 ± 0.8) ng/L (P < 0.01). And the serum levels of IFNα (55.7 ± 21.9) ng/L and IFNß (11.3 ± 2.3) ng/L in DM patients were significantly higher than those in PM patients (26.1 ± 8.2) ng/L, (6.2 ± 3.5) ng/L (P < 0.05). The serum levels of IFNα and IFNß correlated with the presence of skin rash (P < 0.05). And their serum concentrations correlated positively with erythrocyte sedimentation rate (r = 0.442, P = 0.000; r = 0.562, P = 0.000) and C-reactive protein (r = 0.348, P = 0.004; r = 0.432, P = 0.005)respectively. The serum levels of IFNα and IFNß decreased significantly after treatment in 12 PM/DM (polymyositis/dermatomyositis) patients (P < 0.01). The mRNA expression levels of IFNα, IFNß, IFNαR1 and STAT1 in PM/DM patients were higher than those in normal controls (P < 0.05). CONCLUSION: The expression levels of IFNα and IFNß in PM/DM patients are significantly higher than those in normal controls. And the increments had correlations with disease activity and severity. STAT1 has been implicated in signal transduction of IFNα and IFNß in the muscles of PM/DM patients.

[The expression of the type I interferon system in muscle and lung of autoimmune myositis rat model].

OBJECTIVE: To investigate the expression levels of the type I IFN system in muscle and lung of experimental autoimmune myositis (EAM) model and to evaluate whether the type I IFN system associates with the pathogenesis of the EAM model in rats. METHODS: The EAM model was established to determine creatine kinase (CK) in blood serum. The pathology of muscle and lung tissue was examined by hematoxylin-eosin staining. The concentration of type I IFN system mRNA in muscle and lung tissue was detected by real-time PCR. RESULTS: The concentration of CK in model group [(209.17 ± 91.95) IU/L] was significantly higher than that of two control groups (P < 0.05). The scores of muscle and lung in EAM model were significantly higher than that of control groups (all P < 0.05). The expression levels of the type I IFN system in muscle of EAM model were significantly higher than that of control groups (all P < 0.05). The expression levels of the type I IFN system in muscle with EAM model were positively correlated with CK and the scores of muscle (all P < 0.05). The expression levels of IFNα, IFNß, IFNαR1, signal transducer and activator of transcription 1 (STAT1), myxovirus resistance protein 1 (MX1) in lung of EAM model were significantly higher than those of control groups (P < 0.05), but not seen in INF-induced protein with tetratricopeptide repeats 1 (IFIT1) and IFN-stimulated gene 15 (ISG15). The expression levels of IFNα, IFNß, IFNαR1, STAT1 and MX1 in lung with EAM model were positively correlated with the scores of lung pathology (all P < 0.05). CONCLUSION: The type I IFN system probably played a crucial role in the pathogenesis and the pathology of muscle and lung of EAM model.

Mechanism of saikosaponin-d in the regulation of rat mesangial cell proliferation and synthesis of extracellular matrix proteins.

Glomerulosclerosis is a common disorder in many types of chronic kidney diseases. Previous studies have shown that glomerular mesangial cells (MCs) play an important role in the pathogenesis of glomerulosclerosis. The ability of saikosaponin-d (SSd) to reduce the damage of kidney in progressive glomerulosclerosis has been demonstrated. In this study, the effects of saikosaponin-d on MC proliferation and synthesis of extracellular matrix proteins were investigated. Rat MCs were isolated from Wistar rats and cultured in Dulbecco's modified Eagle's medium. MCs were challenged with lipopolysacchorides and incubated with different concentrations of SSd. Cell proliferation and cytotoxicity were determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), flow cytometry, and lactate dehydrogenase assays. Type IV collagen, fibronectin, and TGF-beta1 in the conditioned medium were measured. The expression of cyclin-dependent kinase 4, c-Jun, and c-Fos was determined by immunohistochemistry. At a concentration of 4 microg/mL or lower, SSd inhibited MC proliferation but did not cause cell death. SSd also inhibited lipopolysaccharide-induced secretion of type IV collagen, fibronectin, and TGF-beta1 in MCs. Additionally, SSd reduced the expression of CDK4, c-Jun, and c-Fos in MCs. We conclude that SSd inhibited MC proliferation and synthesis of extracullular matrix proteins through the downregulation of the CDK4, c-Jun, and c-Fos genes.

[Effect of saikosaponin-d on rat's glomerular mesangial cell proliferation and extracellular matrix hyperplasia in vitro].

OBJECTIVE: To investigate the effects of saikosaponin-d (SSd) on glomerular mesangial cells (MCs) proliferation and hyperplastic extracellular matrix (ECM) induced by lipopolysaccharide (LPS) to provide experimental proof for its use in prevention and treatment of glomerulosclerosis. METHODS: Rat's MCs were cultivated and identified. The cultured MCs were stimulated by LPS and incubated with different concentrations of SSd. Cell proliferation was determined by MTT assay, LDH assay and flow cytometry, respectively. Type IV collagen (Col IV), fibronectin (FN) and transforming growth factor beta1 (TGF-beta1) in the conditioned medium were measured by ELISA. The expressions of cyclin-dependent kinase 4 (CDK4), c-Jun and c-Fos were detected by immunohistochemistry. RESULTS: After treated by SSd, MC proliferation was inhibited, cells in G0/G1 phase increased, and apoptosis induced. Moreover, secretion of Col IV, FN and TGF-beta1 and the expressions of CDK4, c-Jun and c-Fos in MC were inhibited. CONCLUSION: The inhibitory action of SSd on glomerulosclerosis was realized through inhibiting the expressions of CDK4, c-J un and c-Fos.

Therapeutic mechanism of Saikosaponin-d in anti-Thy1 mAb 1-22-3-induced rat model of glomerulonephritis.

AIMS: Mesangioproliferative glomerulonephritis is a common kidney disease and at present, there is no effective treatment. Our previous studies have demonstrated that Sairei-to can significantly prevent progression of experimental glomerulonephritis in rats. Although we have reported that the active component of Sairei-to in treatment of glomerulonephritis was Saikosaponin-d (Ssd), mechanism of Ssd in prevention of mesangioproliferative glomerulonephritis progression is still unknown. Therefore, current study examines the effects of Ssd on progression of mesangioproliferative glomerulonephritis induced by anti-Thy1 monoclonal antibody 1-22-3 (mAb 1-22-3) in uninephrectomized rats. METHODS: Eighteen female Wistar rats first received uninephrectomy and mAb 1-22-3 injection and were then divided into 3 groups: treated daily with phosphate-buffered saline (PBS), 0.6 or 1.8 mg/kg of Ssd. Urinary protein concentration and systolic blood pressure were evaluated and the kidneys were collected and subjected to histological and immunohistological evaluation. The mRNA and protein of the kidneys were extracted and subjected to reverse transcriptase polymerase chain reaction and Western blot analysis, respectively. RESULTS: Ssd reduced the amount of urinary protein and systolic blood pressure. Ssd administration also decreased extracellular matrix expansion, crescentic formation as well as infiltration of macrophages and CD8+ T lymphocytes. Moreover, Ssd significantly reduced expression of transforming growth factor beta 1 (TGF-beta1) and type I collagen in the kidneys. CONCLUSION: Ssd inhibits the progression of mesangioproliferative glomerulonephritis through reduction of the expression of TGF-beta1 and the infiltration of macrophages and CD8+ T lymphocytes.