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Real-World Efficacy and Safety of Setmelanotide in Adults With Monogenic or Syndromic Obesity: A Prospective Cohort Study 赛特美拉肽治疗成人单基因或综合征性肥胖的实际疗效和安全性:一项前瞻性队列研究。
IF 4.7 2区 医学 Q1 ENDOCRINOLOGY & METABOLISM Pub Date : 2025-09-02 DOI: 10.1002/oby.70002
Francois Mifsud, Sarah Chalopin, Emilie Guillon, Pauline Faucher, Jean Muller, Johanne Le Bihan, Karine Clément, Christine Poitou

Objective

The melanocortin-4 receptor agonist setmelanotide has demonstrated effectiveness in phase 3 clinical trials for patients with monogenic obesity caused by biallelic variants in the leptin receptor (LEPR) and pro-opiomelanocortin (POMC), as well as for individuals with Bardet–Biedl syndrome (BBS). However, real-world evidence remains limited. This study evaluates the long-term effectiveness and safety of setmelanotide in patients who received treatment under a pre-marketing early-access authorization.

Methods

This ongoing prospective monocentric cohort includes 17 patients with obesity due to BBS (n = 11) or biallelic variants in LEPR (n = 4) or POMC (n = 2) who either started setmelanotide in routine care between 2022 and 2024 or continued therapy after participating in the RM-493-022 clinical trial. The average follow-up time was 14.4 months.

Results

Patients experienced a clinically significant weight reduction of 20% from their highest pre-treatment weight within the first year. Those previously treated in a clinical trial maintained their weight loss over time. Additionally, eating behavior improved, with significant reductions in hunger (−62%), food craving (−41%), and external eating evaluated by DEBQ. The overall safety profile was consistent with phase 3 trials data, without any new safety signals.

Conclusions

These findings confirm the drug's long-term clinical benefit and safety profile in a routine-care setting.

目的:黑素皮素-4受体激动剂setmelanotide在3期临床试验中证明了对由瘦素受体(LEPR)和前opiomelanocortin (POMC)双等位基因变异引起的单基因肥胖患者以及baret - biedl综合征(BBS)患者的有效性。然而,真实世界的证据仍然有限。本研究评估了setmelanotide在上市前早期获得许可接受治疗的患者中的长期有效性和安全性。方法:这项正在进行的前瞻性单中心队列研究包括17例因BBS (n = 11)或LEPR (n = 4)或POMC (n = 2)双等位基因变异而肥胖的患者,这些患者要么在2022年至2024年期间在常规护理中开始setmelanotide,要么在参加RM-493-022临床试验后继续治疗。平均随访时间14.4个月。结果:患者在第一年内经历了临床显著的体重减轻,比治疗前的最高体重减少了20%。那些先前在临床试验中接受治疗的人随着时间的推移保持了体重下降。此外,饮食行为得到改善,饥饿感(-62%)、食物渴望(-41%)和外部进食(DEBQ评估)显著减少。总体安全性与3期试验数据一致,没有任何新的安全信号。结论:这些发现证实了该药在常规护理环境中的长期临床获益和安全性。
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引用次数: 0
CRISPLD2: A Weight Loss-Induced Adipokine With Antifibrotic Capabilities in Adipose Tissue CRISPLD2:一种在脂肪组织中具有抗纤维化能力的减肥诱导脂肪因子。
IF 4.7 2区 医学 Q1 ENDOCRINOLOGY & METABOLISM Pub Date : 2025-08-28 DOI: 10.1002/oby.70034
David Mendoza, Jacqueline M. Stephens
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引用次数: 0
Using Time-Weighted Averages of Total Daily Energy Expenditure to Estimate Energy Intake During a Weight Loss Intervention 使用每日总能量消耗的时间加权平均值来估计减肥干预期间的能量摄入。
IF 4.7 2区 医学 Q1 ENDOCRINOLOGY & METABOLISM Pub Date : 2025-08-28 DOI: 10.1002/oby.70008
Matthew J. Breit, Zhaoxing Pan, Danielle M. Ostendorf, Jared H. Dahle, Victoria A. Catenacci, Seth A. Creasy, Edward L. Melanson

Objective

The doubly labeled water (DLW) intake-balance method estimates energy intake (EI) during weight loss using the time-weighted average of total daily energy expenditure (TDEE) and changes in body energy stores. Because TDEE declines rapidly during the early phase of weight loss, an early additional measurement is recommended. This study aimed to develop regression models that estimate time-weighted TDEE using fewer interim measurements and determine if EI accuracy is maintained during a 12-month weight loss intervention.

Methods

Data from a behavioral weight loss intervention (Dietary Caloric Restriction versus intermittent Fasting Trial, “DRIFT”) were used. TDEE, body weight, and body composition were measured at months 0, 1, 6, and 12. Regression models using only two or three time points were used to estimate time-weighted TDEE at months 6 and 12, respectively. Models were validated using bootstrap sampling, and time-weighted TDEE and percent caloric restriction (% CR) were compared to a reference approach.

Results

Models demonstrated strong predictive performance (R 2 = 0.911–0.982). Limits of agreement with the reference model were 121.1–274.5 kcal/day for TDEE and 4.5%–10.3% for % CR, without significant bias.

Conclusions

Using a regression modeling approach, we demonstrate the DLW intake-balance method maintains accuracy during weight loss without early-phase TDEE measurements.

Trial Registration

ClinicalTrials.gov identifier: NCT03411356

目的:双标签水(DLW)摄入平衡法使用每日总能量消耗(TDEE)的时间加权平均值和身体能量储存的变化来估计减肥期间的能量摄入(EI)。由于TDEE在减肥初期迅速下降,建议尽早进行额外测量。本研究旨在建立回归模型,使用较少的中期测量来估计时间加权TDEE,并确定EI在12个月的减肥干预期间是否保持准确性。方法:使用行为减肥干预(饮食热量限制与间歇性禁食试验,“DRIFT”)的数据。在第0、1、6和12个月测量TDEE、体重和体成分。仅使用两个或三个时间点的回归模型分别用于估计第6个月和第12个月的时间加权TDEE。采用自举抽样验证模型,并将时间加权TDEE和卡路里限制百分比(% CR)与参考方法进行比较。结果:模型具有较强的预测能力(R2 = 0.911-0.982)。TDEE与参考模型的一致性限为121.1-274.5千卡/天,% CR为4.5%-10.3%,无显著偏差。结论:使用回归建模方法,我们证明DLW摄入平衡法在没有早期TDEE测量的情况下保持减肥的准确性。试验注册:ClinicalTrials.gov标识符:NCT03411356。
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引用次数: 0
Associations of Metal Mixtures During Early Pregnancy With Midlife Obesity and Body Composition: A Prospective Study 妊娠早期金属混合物与中年肥胖和身体组成的关系:一项前瞻性研究。
IF 4.7 2区 医学 Q1 ENDOCRINOLOGY & METABOLISM Pub Date : 2025-08-26 DOI: 10.1002/oby.24368
Mingyu Zhang, Izzuddin M. Aris, Andres Cardenas, Sheryl L. Rifas-Shiman, Pi-I Debby Lin, Long H. Ngo, Emily Oken, Stephen P. Juraschek, Marie-France Hivert

Objective

To examine the prospective associations of metal mixtures during pregnancy with midlife adiposity and explore metal-folate interactions.

Methods

In 500 participants from Project Viva, we measured six non-essential metals (arsenic, barium, cadmium, cesium, mercury, and lead) and five essential metals (copper, magnesium, manganese, selenium, and zinc) in red blood cells and folate in plasma collected during early pregnancy (mean gestational age: 10.0 weeks; mean age: 32.9 years). We assessed midlife (mean age: 51.2 years) adiposity using BMI and dual-energy X-ray absorptiometry (DXA) measures. We used multivariable-adjusted linear and multinomial logistic regression models to analyze individual exposures and Bayesian kernel machine regression to examine exposure mixtures.

Results

Higher arsenic, cesium, and mercury levels were associated with lower midlife DXA percentage fat, total fat mass index, and/or trunk fat mass index, even after adjustments for diet in pregnancy. We observed an antagonistic interaction between folate and arsenic: arsenic was associated with higher obesity risk at lower folate levels but lower obesity risk at higher folate levels. The essential metal mixture tended to be associated with lower midlife BMI and obesity risk.

Conclusions

Higher pregnancy levels of arsenic, cesium, mercury, and the mixture of essential metals were associated with lower midlife adiposity.

目的:探讨孕期金属混合物与中年肥胖的潜在关联,并探讨金属-叶酸的相互作用。方法:在500名来自Viva项目的参与者中,我们测量了红细胞中的六种非必需金属(砷、钡、镉、铯、汞和铅)和五种必需金属(铜、镁、锰、硒和锌),以及在妊娠早期(平均胎龄:10.0周;平均年龄:32.9岁)收集的血浆中的叶酸。我们使用BMI和双能x线吸收仪(DXA)测量来评估中年(平均年龄:51.2岁)的肥胖。我们使用多变量调整线性和多项逻辑回归模型来分析个体暴露,并使用贝叶斯核机回归来检查暴露混合物。结果:较高的砷、铯和汞水平与较低的中年DXA百分比脂肪、总脂肪质量指数和/或躯干脂肪质量指数相关,即使在孕期调整饮食后也是如此。我们观察到叶酸和砷之间的拮抗相互作用:叶酸水平较低时,砷与较高的肥胖风险相关,而叶酸水平较高时,肥胖风险较低。这种必需的金属混合物往往与较低的中年体重指数和肥胖风险有关。结论:较高的孕期砷、铯、汞和必需金属混合物水平与较低的中年肥胖有关。
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引用次数: 0
CRISPLD2, a novel insulin-sensitizing adipokine that alters adipocyte size CRISPLD2,一种改变脂肪细胞大小的新型胰岛素致敏脂肪因子。
IF 4.7 2区 医学 Q1 ENDOCRINOLOGY & METABOLISM Pub Date : 2025-08-26 DOI: 10.1002/oby.24342
Beth A. Griesel, Kylie Williams, Nagib Ahsan, Philipp E. Scherer, Ann Louise Olson, David P. Sparling

Objective

Both obesity and adipose tissue fibrosis are associated with insulin resistance, which can improve with weight loss. We previously found increased adipocyte-specific secretion of the novel adipokine CRISPLD2 during weight loss. In this study, we further explore the function of adipose CRISPLD2, which others suggest may regulate inflammation and fibrosis in a variety of tissues.

Methods

We designed mice with adipose-specific doxycycline-inducible overexpression of CRISPLD2 (CLD2AD) to assess adipose-specific effects on tissue structure and function on chow or high-fat diets. The effects of prolonged excess CRISPLD2 were determined after 7 months, including stromal vascular fraction analysis by single-cell RNA-seq. CRISPLD2 cell surface signaling was explored in 3T3-L1 adipocytes via transwell assays, and adipocyte binding partners were determined in unbiased binding screening by mass spectrometry.

Results

CLD2AD mice had decreased adipocyte size but unchanged fat mass. Long-term CRISPLD2 overexpression led to downregulation of collagen transcription and decreased fibrosis. CRISPLD2 induced Ifng transcription in adipocytes in vitro and bound multiple adipocyte cell surface proteins, including nucleolin. Finally, obese CLD2AD mice had decreased adipocyte size and improved glucose tolerance, with no change in fat mass.

Conclusions

These data suggest a model wherein CRISPLD2 can both regulate adipose tissue fibrosis and improve insulin sensitivity.

目的:肥胖和脂肪组织纤维化均与胰岛素抵抗有关,胰岛素抵抗可随着体重减轻而改善。我们之前发现,在体重减轻期间,新型脂肪因子CRISPLD2的脂肪细胞特异性分泌增加。在这项研究中,我们进一步探索了脂肪CRISPLD2的功能,其他人认为它可能调节多种组织的炎症和纤维化。方法:我们设计了脂肪特异性多西环素诱导的CRISPLD2 (CLD2AD)过表达小鼠,以评估脂肪特异性对鼠粮或高脂肪饮食组织结构和功能的影响。延长过量CRISPLD2的影响在7个月后被确定,包括通过单细胞RNA-seq分析基质血管分数。通过transwell实验探索3T3-L1脂肪细胞中的CRISPLD2细胞表面信号传导,并通过质谱法无偏结合筛选确定脂肪细胞结合伙伴。结果:CLD2AD小鼠脂肪细胞大小减小,脂肪质量不变。长期过表达CRISPLD2导致胶原转录下调,纤维化减少。CRISPLD2在体外诱导脂肪细胞中Ifng转录,并结合多种脂肪细胞表面蛋白,包括核蛋白。最后,肥胖的CLD2AD小鼠脂肪细胞大小减少,葡萄糖耐量提高,脂肪量没有变化。结论:这些数据表明CRISPLD2既可以调节脂肪组织纤维化,又可以改善胰岛素敏感性。
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引用次数: 0
Alcoholic Use Disorder Outcomes After Roux-en-Y Gastric Bypass in Patients Taking GLP-1 RAs: A Multicenter Analysis 多中心分析:服用GLP-1 RAs患者Roux-en-Y胃旁路术后酒精使用障碍的结局
IF 4.7 2区 医学 Q1 ENDOCRINOLOGY & METABOLISM Pub Date : 2025-08-26 DOI: 10.1002/oby.70001
Olanrewaju Adeniran, Luis M. Nieto, Chima Amadi, Katherine Shepherd, Joshua Kirkpatrick, Kanith Farah, Farirai Marwizi, Budoor Alqinai, Sharon I. Narvaez, Samuel Mensah, Ayowumi Adekolu, Ethan M. Cohen, Raja S. Khan, Swapna Gayam, Lawrence E. Tabone, Laura Davisson

Objective

Roux-en-Y gastric bypass (RYGB) has been linked with increased alcohol-related outcomes, whereas glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have been associated with reduced risks. We performed the first multicenter retrospective cohort study to identify alcohol use outcomes of GLP-1 RAs post RYGB.

Methods

Using TriNetX, adults (≥ 18 years old) with obesity (BMI ≥ 30 kg/m2) who underwent RYGB between January 1, 2019, and May 31, 2023, were identified. Two cohorts were analyzed: patients initiated on GLP-1 RA versus non-GLP-1 RA users. Patients with other liver diseases and other bariatric surgeries were excluded. Covariates were balanced via propensity score matching (PSM). Participants were followed for at least 1 year post RYGB and GLP-1 RA initiation. Outcomes include the risk of alcohol use disorders (AUD), alcohol liver diseases (ALD), and all-cause mortality. Hazard ratio (HR) was calculated through Cox regression analysis.

Results

After PSM, 3438 were matched in each cohort. GLP-1 RA initiation was associated with a reduced incidence rate of AUD versus control (1.1% vs. 1.8%) (HR 0.77, [95% CI: 0.549–0.840, p = 0.041]) and all-cause mortality (1.2% versus 3.9%) (HR 0.497, [95% CI: 0.346–0.715, p = 0.039]).

Conclusions

Post RYGB, GLP-1 RAs provide the potential to reduce AUD and all-cause mortality.

目的:Roux-en-Y胃旁路术(RYGB)与酒精相关的预后增加有关,而胰高血糖素样肽-1受体激动剂(GLP-1 RAs)与风险降低有关。我们进行了首个多中心回顾性队列研究,以确定RYGB后GLP-1 RAs的酒精使用结果。方法:使用TriNetX对2019年1月1日至2023年5月31日期间接受RYGB治疗的肥胖成人(≥18岁)(BMI≥30 kg/m2)进行识别。分析了两个队列:开始使用GLP-1 RA的患者与非GLP-1 RA使用者。其他肝脏疾病和其他减肥手术的患者被排除在外。通过倾向得分匹配(PSM)平衡协变量。参与者在RYGB和GLP-1 RA开始后随访至少1年。结果包括酒精使用障碍(AUD)、酒精性肝病(ALD)和全因死亡率的风险。通过Cox回归分析计算风险比(HR)。结果:PSM后,每个队列匹配3438例。与对照组相比,GLP-1 RA起始与AUD发生率降低(1.1%对1.8%)(HR 0.77, [95% CI: 0.549-0.840, p = 0.041])和全因死亡率(1.2%对3.9%)(HR 0.497, [95% CI: 0.346-0.715, p = 0.039])相关。结论:RYGB后,GLP-1 RAs具有降低AUD和全因死亡率的潜力。
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引用次数: 0
Multimodal Neuroimaging of Brain Structure, Metabolism, and Function in Obesity: Current Landscape and Future Perspectives 肥胖症中脑结构、代谢和功能的多模态神经成像:现状和未来展望。
IF 4.7 2区 医学 Q1 ENDOCRINOLOGY & METABOLISM Pub Date : 2025-08-21 DOI: 10.1002/oby.24353
Tao Ju, Zhen Li, Xiaozu Zhang, Yang Liu, Xiaotian Gao, Haimo Zhang, Xizhen Wang, Xiaodong Sun, Xiaoli Wang

Obesity is a systemic disease that not only increases the incidence of diabetes and cardiovascular disease but also contributes to central nervous system disorders such as cognitive impairment, depression, and anxiety. Neuroimaging studies have confirmed that obesity leads to various forms of brain damage, as well as abnormalities in the function and metabolism of different brain regions. Multimodal neuroimaging, a collection of detection tools capable of visualizing neural diseases, has shown potential in diagnosing various brain disorders, and it provides insights from multiple perspectives to explore the pathological mechanisms of brain damage associated with obesity. Structural imaging techniques within multimodal imaging have identified changes in the volume and microstructure of the brain's gray and white matter. Functional imaging has detected abnormal activation and disrupted circuits in specific brain regions, while metabolic imaging has revealed neurochemical changes in the brain. In this review, we provide an overview of multimodal neuroimaging in obesity-related brain diseases, systematically analyzing these diseases from three aspects: structure, metabolism, and function. Additionally, we introduce novel multimodal imaging techniques that hold potential but have not yet been applied to obesity-related studies, aiming to provide a theoretical foundation for future clinical diagnosis and treatment.

肥胖是一种全身性疾病,不仅会增加糖尿病和心血管疾病的发病率,还会导致认知障碍、抑郁、焦虑等中枢神经系统疾病。神经影像学研究已经证实,肥胖会导致各种形式的脑损伤,以及大脑不同区域的功能和代谢异常。多模态神经成像是一种能够可视化神经疾病的检测工具集合,它在诊断各种脑部疾病方面显示出潜力,并从多个角度探索与肥胖相关的脑损伤病理机制。多模态成像中的结构成像技术已经确定了大脑灰质和白质的体积和微观结构的变化。功能成像检测到大脑特定区域的异常激活和中断电路,而代谢成像显示了大脑中的神经化学变化。本文就肥胖相关脑部疾病的多模态神经影像学研究进展进行综述,从结构、代谢和功能三个方面对肥胖相关脑部疾病进行系统分析。此外,我们还介绍了具有潜力但尚未应用于肥胖相关研究的新型多模态成像技术,旨在为未来的临床诊断和治疗提供理论基础。
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引用次数: 0
Evolution of multidisciplinary obesity treatments: past, present, and future role of nutrition 多学科肥胖症治疗的发展:营养在过去、现在和未来的作用。
IF 4.7 2区 医学 Q1 ENDOCRINOLOGY & METABOLISM Pub Date : 2025-08-20 DOI: 10.1002/oby.24340
Steven B. Heymsfield, Philip J. Atherton, Sandra Christensen, Colleen Tewksbury, Amanda Velazquez, Jens Walter, Ellen E. Blaak

Obesity is a complex chronic disease requiring lifelong comprehensive treatment. In addition to lifestyle counseling that improves nutrition and physical activity, a promising new generation of obesity medications has been added to bariatric procedures as therapeutic options to achieve weight reduction and improve health outcomes. With the promise of effective and safe treatments comes the need to emphasize maximal reduction of body fat and minimal loss of vital body components, including skeletal muscle and bone. Nutrition is a critical aspect of obesity care and is leveraged to support preservation of lean tissues, such as skeletal muscle, through adequate, daily, high-quality protein intake and intake of key micronutrients. More targeted nutrition approaches that promote muscle protein synthesis include amino acid supplementation with leucine and its metabolite β-hydroxy β-methylbutyrate. Another potential target for support is the gut microbiome, as its adequate function is increasingly seen as playing a role in human health and metabolism. Obesity is a heterogenous disease, and there is considerable interest in specific metabolic phenotypes that might be used to tailor nutrition strategies. As research advances on these and other fronts, there is the potential to identify precision nutrition strategies for individualized, more effective approaches to lifelong obesity management.

肥胖是一种复杂的慢性疾病,需要终生综合治疗。除了改善营养和身体活动的生活方式咨询之外,新一代的肥胖药物已经被添加到减肥程序中,作为实现减肥和改善健康结果的治疗选择。随着有效和安全的治疗方法的出现,需要强调最大限度地减少身体脂肪和最小限度地减少重要身体成分,包括骨骼肌和骨骼。营养是肥胖治疗的一个关键方面,通过每日摄入充足的高质量蛋白质和摄入关键微量营养素,可以支持骨骼肌等精瘦组织的保存。促进肌肉蛋白质合成的更有针对性的营养方法包括氨基酸补充亮氨酸及其代谢产物β-羟基β-甲基丁酸盐。另一个潜在的支持目标是肠道微生物群,因为它的适当功能越来越被视为在人类健康和新陈代谢中发挥作用。肥胖是一种异质性疾病,人们对可能用于定制营养策略的特定代谢表型非常感兴趣。随着这些和其他方面的研究进展,有可能确定个性化的精确营养策略,更有效的终身肥胖管理方法。
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引用次数: 0
Correction to “MicroRNA Profiling in Adipose Before and After Weight Loss Highlights the Role of miR-223-3p and the NLRP3 Inflammasome” 对“减肥前后脂肪中的MicroRNA谱分析强调了miR-223-3p和NLRP3炎症小体的作用”进行了更正。
IF 4.7 2区 医学 Q1 ENDOCRINOLOGY & METABOLISM Pub Date : 2025-08-19 DOI: 10.1002/oby.70007

Macartney-Coxson, D., Danielson, K., Clapham, J., et al., “ MicroRNA Profiling in Adipose Before and After Weight Loss Highlights the Role of miR-223-3p and the NLRP3 Inflammasome,” Obesity 28 (2020): 570580, https://doi.org/10.1002/oby.22722.

In Table 2 of this article, the headings for columns 3 and 6 and footnote “a” are incorrect.

Below is the correct Table 2.

In addition, in the Methods section, under the heading "Differential expression analysis of miRNA arrays," the text should read: “Fold change was calculated using 2absolute log2FC. Decreased fold change (i.e. less expression after vs. before gastric bypass) is represented as −2absolute log2FC.”

Under the "RT-qPCR" heading, in two instances, the text should read: “Fold change in expression between time points was calculated for each paired sample using 2−ΔΔCt. For values < 1 (indicating a decrease in gene expression after vs. before gastric bypass and weight loss) the negative reciprocal of 1/2−ΔΔCt was calculated. Mean relative fold change for a given tissue and gene was calculated using each of these individual fold change values from the paired samples.”

We apologize for these errors.

Macartney-Coxson, D, Danielson, K., Clapham, J.,等,“体重减轻前后脂肪中miR-223-3p和NLRP3炎症体的MicroRNA分析”,肥胖28 (2020):570-580,https://doi.org/10.1002/oby.22722。在本文的表2中,第3列和第6列的标题以及脚注“a”不正确。下面是正确的表2。此外,在方法部分,标题为“miRNA阵列的差异表达分析”的文字应该是:“Fold change was calculate using 2absolute log2FC。减少的折叠变化(即胃旁路后与胃旁路前的表达减少)表示为- 2绝对log2FC。”在“RT-qPCR”标题下,在两种情况下,文本应该是:“使用2−ΔΔCt计算每个配对样本在时间点之间的表达变化。对于值<; 1(表示胃旁路和体重减轻后基因表达减少),计算1/2−ΔΔCt的负倒数。给定组织和基因的平均相对折叠变化是使用来自成对样本的每个单个折叠变化值来计算的。”我们为这些错误道歉。
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引用次数: 0
Cancer Risk—Comparing Metabolic Bariatric Surgery and the General Population 比较代谢减肥手术和普通人群的癌症风险。
IF 4.7 2区 医学 Q1 ENDOCRINOLOGY & METABOLISM Pub Date : 2025-08-18 DOI: 10.1002/oby.70018
Lance E. Davidson, Ted D. Adams
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引用次数: 0
期刊
Obesity
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