GZR18 is a long-acting glucagon-like peptide-1 receptor agonist that is under development for the treatment of type 2 diabetes mellitus (T2DM). In this randomized, double-blind, placebo-controlled phase 1b/2a trial in Chinese adults with T2DM, the safety and efficacy of once-weekly GZR18 are evaluated using different dose-titration regimens in two separate parts: Part A (0.5-4 mg over 26 weeks) and Part B (1.5-13 mg over 23 weeks). Overall, 72 participants are enrolled, of whom 62 complete the trial. GZR18 significantly reduces glycated hemoglobin (HbA1c) in both parts (Part A: -1.32% for GZR18 versus 0.86% for placebo; Part B: -1.81% for GZR18 versus 0.12% for placebo). Improvements in body weight and other metabolic parameters are also observed. GZR18 is safe and well tolerated, with mostly mild-to-moderate gastrointestinal adverse events; no severe hypoglycemia or treatment-related serious adverse events occurred. These findings support further development of GZR18 in larger, longer-term trials. The trial is registered at ClinicalTrials.gov (NCT06256523).

Objective:Recaticimab (SHR-1209) significantly reduces low-density lipoprotein cholesterol levels. However, its effect on glucose metabolism remains unclear. This study aimed to evaluate its effect on glycemic parameters in a Chinese population. Methods:Recaticimab versus placebo was administered in a 5:1 ratio to 110 hyperlipidemia patients who were followed up for 24 weeks. Glycated hemoglobin (HbA1c) levels were measured at baseline every 12 weeks. Fasting plasma glucose (FPG) levels were measured at baseline at week 1, 3, 5, 8, 12, 16, 20, and 24. Repeated-measures mixed-effects models were used to determine the longitudinal association between reacticimab and FPG and HbA1c levels. Results:Among the 81 participants with normal glucose metabolism, HbA1c levels significantly decreased ( F = 4.568, P = 0.036). In the 29 participants with abnormal glucose metabolism, a significant time effect was observed for FPG levels ( F = 2.492, P = 0.016). For participants with normal and abnormal glucose metabolism, no significant group × time interaction effects on FPG or HbA1c levels were identified. Conclusion:Recaticimab showed no adverse glycemic effects in participants with normal or abnormal glucose metabolism, indicating its safety in patients with or without diabetes.

This study assessed the pharmacokinetics, bioequivalence, and food effect of two enteric-coated aspirin tablets (100 mg) in healthy Chinese subjects. Ninety subjects were enrolled and divided into fasted (n = 42) and fed cohorts (n = 48) in a single-center, randomized, open-label, single-dose, four-period, two-sequence and crossover study. The pharmacokinetic characteristics of acetylsalicylic acid (aspirin) and its metabolite salicylic acid, including Cmax and AUC, were compared after subjects received single oral doses of enteric-coated aspirin tablet using a validated LC–MS/MS method. Bioequivalence was evaluated using the reference-scaled average bioequivalence (RSABE) approach when the within-subject standard deviation of the reference product (SWR) exceeded 0.29, while the average bioequivalence (ABE) method was applied for SWR values below 0.29. Pharmacokinetic profiles of two enteric-coated aspirin tablets were comparable after single-dose administration. The mean Tmax, Cmax, and AUC0-t were 5.5 h, 603.97 ng/mL and 786.47 h·ng/mL for acetylsalicylic acid, and 6.50 h, 4033.66 ng/mL, and 20,115.18 h·ng/mL for salicylic acid, respectively. Food delayed the Tmax and increased the Cmax but had no effect on the aspirin’s overall exposure. 90

AIMS:To investigate the safety, tolerability, pharmacokinetics, and pharmacodynamics of multiple ascending doses of GZR4 in patients with type 2 diabetes mellitus (T2DM). METHODS:This randomized, active-controlled, phase 1b trial was conducted in adults with T2DM on stable daily basal insulin therapy. Eligible participants were randomized in 3:1 ratio within three cohorts to receive either a fixed once-weekly dose of GZR4 or once-daily insulin degludec (IDeg) subcutaneously for six weeks. Primary endpoints were incidence of adverse events (AEs), serious adverse events (SAEs), and hypoglycemia. RESULTS:The most commonly reported treatment-emergent AE across all treatment groups was hypoglycemia. No SAEs or severe hypoglycemia was observed. At steady state, the mean Cmax of GZR4 was 289.0 ± 17.1 to 1,016.0 ± 262.4 ng/mL; mean AUCGZR4, 0-168h ranged from 34,449.6 ± 2,055.7 to 137,064.2 ± 41,496.5 h.ng/mL. Mean change in FPG from baseline to week 6 was -1.77 ± 0.20 to -2.75 ± 0.71 mmol/L for GZR4 groups and -1.12 ± 0.36 mmol/L for IDeg group; corresponding change in HbA1c was -0.38 ± 0.64 % to -0.76 ± 0.14 % versus -0.13 ± 0.21 %. CONCLUSIONS:GZR4 was safe and well tolerated in patients with diabetes in present trial with pharmacokinetic and pharmacodynamic profiles enabling once-weekly dosing.

ABSTRACT This study assessed the bioequivalence and food effect of two fixed‐dose combination (FDC) formulations of telmisartan‐hydrochlorothiazide tablets (telmisartan 40 mg, hydrochlorothiazide 12.5 mg) in healthy Chinese subjects. Seventy‐two subjects were enrolled and divided into fasted and fed cohorts in a single‐center, randomized, open‐label, single‐dose, three‐period, three‐sequence, and crossover study. The pharmacokinetic characteristics of telmisartan and hydrochlorothiazide, including Cmax and AUC, were compared after subjects received single oral doses of telmisartan‐hydrochlorothiazide tablets using a validated LC–MS/MS method. Safety and tolerability of treatments were monitored. Pharmacokinetic profiles of two FDC telmisartan‐hydrochlorothiazide tablets were comparable after single‐dose administration. 90% CI of geometric mean ratios (GMRs) of AUC0‐t, AUC0‐∞, and Cmax of telmisartan and hydrochlorothiazide of two FDC formulations fell within the predefined bioequivalence range of 80.0%–125.0% under both fasted and fed conditions. Administration with food had significant effects on telmisartan pharmacokinetic parameters but a slight impact on hydrochlorothiazide. Notably, Cmax and AUC of telmisartan were significantly decreased by 39.6%–43.7% in the fed versus fasted conditions. Safety assessments revealed all treatments were safe and well tolerated. Two telmisartan‐hydrochlorothiazide FDC formulations were bioequivalent in healthy Chinese subjects in both fasted and fed states. All treatments were well tolerated.

ObjectiveThe aim of this study was to establish a pharmacodynamic model of tapentadol analgesia under dose titration conditions, to quantitatively analyze the time-effect relationship of the drug, and to identify relevant influencing factors. This model is intended to provide a pharmacodynamic reference for designing rational tapentadol dose titration schemes in clinical research.MethodsRandomized controlled trials assessing the efficacy of tapentadol in the management of chronic pain were retrieved from public databases (PubMed and EMBASE). A time-effect relationship model of the percent change in Numerical Rating Scale (NRS) scores post-tapentadol intervention from baseline was constructed, along with a covariate model to identify factors significantly impacting the analgesic effects of tapentadol. Potential influencing factors that were clinically significant but not included in the final covariate model were examined for their impact trends on tapentadol analgesia through subgroup analysis.ResultsA total of 16 studies involving 4,508 participants were included in the analysis. Covariate analysis indicated that age significantly affected the maximum reduction in NRS scores following tapentadol treatment, with the reduction rate being 40.9% for patients aged 45 and 60.7% for those aged 65, suggesting that older patients have a higher demand for pain relief. Furthermore, studies published after 2014 and placebo-controlled trials showed a slower rate of NRS reduction, indicating a more cautious approach to tapentadol dosing titration post the U.S. opioid crisis and in placebo-controlled contexts. Additionally, subgroup analysis suggested that higher titration doses, higher baseline NRS levels, the use of extended-release tapentadol, and a smaller proportion of male participants were trends associated with better analgesic effects, although the differences were not statistically significant. Moreover, the study found that tapentadol was significantly more effective in treating lower back pain compared to non-lower back pain.ConclusionThis research successfully developed a pharmacodynamic model for dose-titrated tapentadol administration, which can simulate the temporal changes in analgesic effects of tapentadol across different clinical scenarios. This model can guide the formulation of dosing titration protocols for tapentadol in clinical research.Systematic Review Registrationhttps://inplasy.com/inplasy-2024-5-0014/

Background and ObjectivePerfluoropropane (PFP), a lipidbased microbubble preparation, is a novel ultrasound contrast agent. This study aims to evaluate the pharmacokinetics, pharmacodynamics, and liver ultrasound enhancement characteristics of PFP microbubble, a novel ultrasound contrast agent, in healthy Chinese subjects.MethodsThis study is a multicenter, open-label, three-doses, single-dose Phase I clinical trial of the PFP ultrasound contrast agent conducted in healthy male and female volunteers. Screening healthy subjects for inclusion in the trial, with a pre-trial and three dose groups of low (6 μL/kg), medium (12 μL/kg), and high (18 μL/kg), were conducted sequentially from the low-dose group to the high-dose group.ResultsIn this study, a total of 146 volunteers were screened, and 39 subjects were enrolled, including 3 participants in the pilot study and 12 participants in each of the low, medium, and high dose groups. No subjects withdrew early from the trial, and all 39 individuals completed the entire trial. After injection, PFP is primarily distributed in the blood and rapidly peaks and disappears in both blood and exhaled gas. Pulmonary excretion is the primary excretion pathway for PFP. The cumulative excretion rates of peak concentration (Cmax), area under the curve (AUC0-t and AUC 0−∞), and exhaled gas in blood and exhaled gas do not follow a dose linear relationship due to individual differences; however, the observed average values demonstrate an increasing trend. Significant contrast enhancement was observed after injection of various doses of PFP. With low doses (6 μL/kg), the agent meets the requirements for liver ultrasound diagnosis in this study. Overall, PFP has good safety among healthy Chinese subjects.ConclusionThis study systematically evaluated the pharmacokinetics and pharmacodynamics of PFP in blood and exhaled breath, as well as the ultrasound characteristics of the liver. We observed for the first time the dynamic changes in blood and exhaled breath between different doses of PFP, and also determined for the first time the appropriate ultrasound diagnostic dose for the experimental formulation. This study presents a valuable methodological framework and reference point for future research in this field.Clinical Trial RegistrationThis study was registered on 24 November 2020 at the Chinese Clinical Trial Registry (CTR20202343).

Diabetes mellitus represents a significant global health threat characterized by hyperglycemia caused by inadequate insulin secretion and/or insulin resistance. Exogenous insulin supplements had been recognized as a crucial treatment for achieving successful glycemic control in patients with Type 1 and most patients with Type 2 diabetes. Over the past century, substantial progress has been made in the development of novel insulin formulations, including the super-fast-acting and long-acting basal insulin analogs, of which the latter is indispensable for the management of nocturnal fasting and intraprandial blood glucose within the normal physiological range. Recently, combining chemical and genetic engineering with drug optimization have resulted in a formidable evolution in ultra-long-acting weekly insulin. Here, the current state of once-weekly insulin analogs and the euglycemic clamp technique used in the early clinical development to elucidate the pharmacokinetics and pharmacodynamics of this type of novel weekly insulin analogs were systematically overviewed.

目的:探讨首都医科大学附属北京潞河医院Ⅰ期临床试验药房试验用药品管理模式,总结经验和分析不足,为其他临床试验机构中心药房管理模式提供参考.方法:本文分析总结了 Ⅰ期临床试验药房基本情况、试验用药品管理流程、智能冷链监控系统的使用、药物信息化管理等.结果与结论:首都医科大学附属北京潞河医院Ⅰ期临床试验药房不同存储区域可满足试验用药品不同温度存储要求.采用智能冷链温度监控系统监测24 h环境及仪器设备温度,可及时发现超温情况,能尽早采取措施,将试验风险降到最低.试验用药品的电子化管理可在线动态管理与实时记录,提高数据管理的安全性和可靠性,方便数据溯源,提高数据质量.

FCN-159 is a novel, oral, potent, selective MEK1/2 inhibitor in clinical development for the treatment of NRAS-mutant advanced melanoma and neurofibromatosis type 1. We investigated the effect of food on the pharmacokinetics (PK), safety, and tolerability of FCN-159. In this single-center, open-label, phase 1 study with a three-period, three-sequence, crossover design, healthy Chinese male subjects (n = 24) were randomized (1:1:1) to receive a single, oral 8 mg dose of FCN-159 in the fasted state (overnight, > 10 h), and with a low-fat and a high-fat meal, separated by a 10-day washout. PK parameters including time to maximum plasma concentration (Cmax) and area under the concentration–time curve (AUC) were compared using geometric least-squares mean ratios (GLSMR), with the fasted state as the reference. A 90

Background: In recent years, the prevalence of thyroid nodules (TNs) has been increasing, but the relationship between metabolic abnormalities and the incidence of TNs is not well defined, and there is scant data evaluating this relationship stratified by gender. This study aims to analyze the prevalence of TNs and possible risk factors for TNs across gender lines and various metabolic states in Beijing, China. Patients and Methods: A total of 6001 subjects who underwent thyroid ultrasounds as part of a routine medical checkup at Luhe Hospital between 2017 and 2018 were enrolled in this study. Multivariate adjustment logic was used to analyze possible demographic and clinical risk factors of TN stratified by gender. Results: The prevalence of TNs was 44.1%, of which 45.9% were female and 40% were male. In general, the prevalence of TNs increased in parallel with advancing age. These findings were even starker among females, with TN prevalences of 37.5%, 46.5%, 52.9%, and 54.1%, among participants in <55-, 55–65-, 65–75-, and >75-year-old age groups, respectively. The prevalence of TNs was significantly higher among patients with obesity (46.8% vs. 43%, P = 0.008), central obesity (45% vs. 40.4%, P = 0.005), hypertension (47.1% vs. 42.4%, P < 0.001), metabolic syndrome (MetS) (46.1% vs. 41%, P < 0.001), and low TSH levels (46.5% vs. 37.1%, P < 0.001). MetS and obesity were independent risk factors for the prevalence of TNs (odds ratio [OR] = 1.167, [1.002–1.277] and (OR = 0.038, [1.01–1.396]), respectively). TSH had a protective effect on the prevalence of TNs (OR = 0.664, [0.585–0.75]). Conclusions: The present study supports the existing research that contends a strong correlation between older age, MetS, and other clinical risk factors and the prevalence of TNs. This relationship only persisted among women when stratified by gender. These results set the precedent for further research on how gender influences the incidence of TNs, particularly in the setting of other clinical and demographic risk factors.

Abstract Background Recaticimab (SHR-1209, a humanized monoclonal antibody against PCSK9) showed robust LDL-C reduction in healthy volunteers. This study aimed to further assess the efficacy and safety of recaticimab in patients with hypercholesterolemia. Methods In this randomized, double-blind, placebo-controlled phase 1b/2 trial, patients receiving stable dose of atorvastatin with an LDL-C level of 2.6 mmol/L or higher were randomized in a ratio of 5:1 to subcutaneous injections of recaticimab or placebo at different doses and schedules. Patients were recruited in the order of 75 mg every 4 weeks (75Q4W), 150Q8W, 300Q12W, 150Q4W, 300Q8W, and 450Q12W. The primary endpoint was percentage change in LDL-C from the baseline to end of treatment (i.e., at week 16 for Q4W and Q8W schedule and at week 24 for Q12W schedule). Results A total of 91 patients were enrolled and received recaticimab and 19 received placebo. The dose of background atorvastatin in all 110 patients was 10 or 20 mg/day. The main baseline LDL-C ranged from 3.360 to 3.759 mmol/L. The least-squares mean percentage reductions in LDL-C from baseline to end of treatment relative to placebo for recaticimab groups at different doses and schedules ranged from −48.37 to −59.51%. No serious treatment-emergent adverse events (TEAEs) occurred. The most common TEAEs included upper respiratory tract infection, increased alanine aminotransferase, increased blood glucose, and increased gamma-glutamyltransferase. Conclusion Recaticimab as add-on to moderate-intensity statin therapy significantly and substantially reduced the LDL-C level with an infrequent administration schedule (even given once every 12 weeks), compared with placebo. Trial registration ClinicalTrials.gov , number NCT03944109

Thyroid hormone resistance syndrome (THRS) is a rare disease characterized by reduced sensitivity to thyroid hormones. Mutations in the thyroid hormone receptor beta (THRB) gene are considered as contributing to the pathogenesis. This report describes a Chinese pedigree with THRS and Hashimoto's thyroiditis (HT) due to novel point mutation in the 11th exon of the THRB gene (c. 1378 G > A). The proband complained of goitre with increased thyroid hormone and normal thyroid stimulating hormone levels. Gene sequencing was performed to confirm the diagnosis. HT was also diagnosed based on positive thyroid autoantibodies and diffuse, grid-like changes in the thyroid on ultrasound examination. Additionally, a comprehensive examination of the proband's pedigree was conducted. The patient's father exhibited the same gene mutation site and was diagnosed with THRS and HT. No mutation site was detected in three patients with HT only and three healthy volunteers. Thus, gene sequencing should be considered the gold standard for diagnosing THRS. Furthermore, treatment should be individualized to control the patient's symptoms rather than normalizing thyroid hormone levels. Further studies that determine the relationship between THRS and TH are warranted.

Background Papillary renal cell carcinoma (pRCC) is the largest histologic subtype of non-clear-cell RCC. To date, there is no reliable nomogram to predict the prognosis of patients with pRCC after nephrectomy. We aimed to first establish an effective nomogram to predict the overall survival (OS) of patients with pRCC after nephrectomy. Methods A total of 3,528 eligible patients with pRCC after nephrectomy were identified from the Surveillance, Epidemiology, and End Results (SEER) database between 2010 and 2015. The patients were randomized into the training cohort (n = 2,472) and the validation cohort (n = 1,056) at a 7:3 ratio. In total, 122 real-world samples from our institute (titled the AHMU-pRCC cohort) were used as the external validation cohort. Univariate and subsequent multivariate Cox regression analyses were conducted to identify OS-related prognostic factors, which were further used to establish a prognostic nomogram for predicting 1-, 3-, and 5-year OS probabilities. The performance of the nomogram was evaluated by using the concordance index (C-index), receiver operating characteristic curve (ROC), calibration plot, and decision curve analysis (DCA). Results Multivariate Cox analysis showed that age, race, marital status, TNM stage, tumor size, and surgery were significant OS-related prognostic factors. A prognostic model consisting of these clinical parameters was developed and virtualized by a nomogram. High C-index and area under the ROC curve (AUC) values of the nomogram at 1, 3, and 5 years were found in the training, validation, and AHMU-pRCC cohorts. The calibration plot and DCA also showed that the nomogram had a satisfactory clinical application value. A risk classification system was established to risk-stratify patients with pRCC. Conclusion Based on a large cohort from the public SEER database, a reliable nomogram predicting the OS of patients with pRCC after nephrectomy was constructed, which could optimize the survival assessment and clinical treatment.

目的 通过美国食品药品监督管理局公共数据项目(the US Food and Drug Administration Public Data Open Project,OpenFDA)数据库中对前蛋白转化酶枯草溶菌素/溶菌素9(PCSK9)抑制剂依洛尤单抗和阿利西尤单抗的药品不良反应(adverse drug reaction,ADR)进行检索,对其ADR的具体隋况进行对比分析,为临床合理使用提供借鉴.方法 依据OpenFDA数据库中ADR端点交互式图表板块中的应用程序接口(API)功能,对依洛尤单抗和阿利西尤单抗在2004年1月1日至2021年1月18日的ADR报告数据进行详细检索.结果 依洛尤单抗和阿利西尤单抗的ADR报告数分别为76412和8004份;ADR上报职业中依洛尤单抗主要为医师和消费者或非卫生专业人员,阿利西尤单抗主要为消费者或非卫生专业人员和其他卫生专业人员;ADR多数发生于美国;用药患者女性多于男性且年龄主要在成年人和老年人;用药的适应证主要为心血管疾病;ADR常见的类型:依洛尤单抗是注射部位疼痛,阿利西尤单抗是肌肉疼痛;转归情况多数未知.结论 临床使用过程中应关注依洛尤单抗和阿利西尤单抗的ADR,促进药物的合理使用.

目的:挖掘分析我国上市的四种钠-葡萄糖共转运蛋白2抑制剂(SGLT2i)达格列净、恩格列净、卡格列净和艾托格列净在真实世界临床应用中药品不良事件(ADE)发生情况,为临床合理用药提供参考.方法:采用回顾性研究方法,收集美国食品药品监督管理局不良事件报告系统、世界卫生组织个例安全性病例报告数据库及欧盟药品不良反应数据库接收的4种药品ADE进行信号挖掘,检测药品安全信号.结果:SGLT2i的ADE主要集中在18～64岁人群.发生感染、代谢营养类疾病比例最高.4种药品中达格列净相关内分泌系统疾病及药品问题ADE较多;恩格列净高危安全信号主要集中在先天性、家族性、遗传性疾病,生殖系统及乳腺疾病;卡格列净应注意在内外科操作治疗、妊娠期、产褥期、围产期的应用;艾托格列净报告数量少且较分散.结论:临床应用SGLT2i需结合患者年龄及合并疾病进行个体化治疗,警惕并及时处理ADE.

Introduction: The objective of this study was to evaluate the effect of selenium supplementation on autoantibody titres, thyroid ultrasonography, and thyroid function in patients with Hashimoto's thyroiditis (autoimmune thyroiditis) and normal thyroid reference range. Material and methods: A total of 100 patients were given 200 ug/d selenium yeast orally, their thyroid function, levels of serum selenium, thyroid peroxidase antibodies (TPOAb), thyroglobulin antibodies (TGAb), and urine iodine were measured, and thyroid ultrasonography was performed before administration and three and six months afterwards, and the data were statistically analysed. Results: The subjects exhibited a selenium deficiency before the administration of selenium, and the serum levels increased to moderate levels three and six months after the selenium supplementation (p < 0.05). The titres of TGAb decreased significantly in patients after six months of selenium supplementation (p < 0.05). In the high antibody group, TgAb decreased after 6 months compared with baseline (p = p < 0.05), and TPOAb decreased after 3 and 6 months of selenium supplementation compared with baseline (p < 0.05). Conclusion: In patients with autoimmune thyroiditis and normal thyroid reference range, there was a general selenium deficiency, but after six months of treatment it was shown that selenium supplementation may be effective in reducing the titres of TGAb and TPOAb.

Background Prostate cancer (PC) is one of the most common malignancies in males. Extensive and complex connections between circadian rhythm and cancer were found. Nonetheless, in PC, the potential role of the core components of the mammalian circadian clock (CCMCCs) in prognosis prediction has not been fully clarified. Methods We firstly collected 605 patients with PC from The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) databases. Survival analysis was carried out for each CCMCC. Then, we investigated the prognostic ability of CCMCCs by Cox regression analysis. Independent prognostic signatures were extracted for the establishment of the circadian clock-based risk score model. We explored the predictive performance of the risk score model in the TCGA training cohort and the independent GEO dataset. Finally, the relationships between risk score and clinicopathological parameters, biological processes, and signaling pathways were evaluated. Results The expression levels of CCMCCs were widely correlated with age, tumor status, lymph node status, disease-free survival (DFS), progression-free survival (PFS), and overall survival (OS). Nine circadian clock genes, including CSNK1D, BTRC, CLOCK, CSNK1E, FBXL3, PRKAA2, DBP, NR1D2, and RORB, were identified as vital prognostic factors in PC and were used to construct the circadian clock-based risk score model. For DFS, the area under the 3-year or 5-year receiver operating characteristic curves ranged from 0.728 to 0.821, suggesting better predictive performance. When compared with T3-4N1 stage, PC patients at T2N0 stage might be benefited more from the circadian clock-based risk score model. Furthermore, a high circadian clock-based risk score indicated shorter DFS (p < 0.0001), early progression (p < 0.0001), and higher 5-year death rate (p = 0.007) in PC. The risk score was related to tumor status (p < 0.001), lymph node status (p < 0.001), and ribosome-related biogenesis and pathways. Conclusions The vital roles of circadian clock genes in clinical outcomes were fully depicted. The circadian clock-based risk score model could reflect and predict the prognosis of patients with PC.

Mesenchymal stem cells (MSCs) can be obtained from almost all tissues and present promising therapeutic effects for metabolic diseases. Human adipose-derived MSCs (hASCs) have recently been widely studied due to their easy access and low immunity. Thus, we intended to figure out the effects and potential mechanism of hASCs on obesity in high-fat-diet (HFD)-induced obese mice. Following 16 weeks of being fed HFD, hASCs were intravenously injected. Two weeks later, body weight, body composition, and energy expenditure were evaluated. Additionally, the phenotypes of macrophages infiltrating adipose tissue were analyzed. The results revealed that hASCs administration significantly reduced adipose tissue weight, adipocyte size, and fat mass and exerted beneficial effects in serum lipid profile. This anti-obesity effect was mediated by the increased O2 consumption, CO2 production, and energy expenditure, which was further evidenced by the upregulation of uncoupling protein-1 (UCP-1) and metabolism-associated genes. Furthermore, hASCs infusion increased the amount of alternatively activated (M2) macrophages in adipose tissue, and the expression of pro-inflammatory cytokines-related genes was reduced. Taken together, these results indicated that hASCs suppressed obesity by increasing UCP-1 expression and enhancing energy expenditure, and this effect might be due to the increased M2 macrophages.

Objective:To investigate the prevalence and its related factors of thyroid nodules in elderly residents in Tongzhou District of Beijing.Methods:This is a cross-sectional study with cluster sampling.A total of 3 639 elderly volunteers aged 60 years and over receiving annual multiphasic health checkups were enrolled in Yongshun, Tongzhou District of Beijing from June to December 2017.A uniformly designed questionnaire was used to investigate the subject's basic information and previous medical history.All volunteers received a B-ultrasound examination of the thyroid gland, and were divided into the nodular group and non-nodular group based on the results of the B-ultrasound.The differences between the two groups in blood pressure, body mass index, triglycerides, total cholesterol, fasting blood glucose, thyroid peroxidase antibodies, urine iodine and other indicators were compared so as to analyze the risk factors for thyroid nodules.Results:A total of 3 639 elderly residents were included.The prevalence of thyroid nodules was 49.68%(1 808/3 639). Univariate analysis showed that there were significant differences between nodule group and non-nodule group in the age, gender, systolic blood pressure, body mass index, urea nitrogen, uric acid, aspartate aminotransferase, triglycerides, thyroid stimulating hormone and carcinoembryonic antigen( P<0.05). Multivariate Logistic regression analysis showed that women( OR=1.577, 95% CI: 1.358-1.832), age( OR=1.025, 95% CI: 1.012-1.038), body mass index( OR=1.032, 95% CI: 1.013-1.052)were risk factors for thyroid nodules.Increasing levels of urea nitrogen( OR=0.945, 95% CI: 0.902-0.990), thyroid stimulating hormone( OR=0.925, 95% CI: 0.882-0.970)and carcinoembryonic antigen( OR=0.967, 95% CI: 0.941-0.994)were protective factors for thyroid nodules. Conclusions:Women and obesity are risk factors for thyroid nodules and increasing levels of thyroid stimulating hormone, urea nitrogen and carcinoembryonic antigen may be unique protective factors for thyroid nodules in the elderly.