IF 6.9 2区医学 Q1 Nursing

Obesity

Pub Date : 2024-04-21 DOI: 10.1002/oby.24017

Nana Merabova, Lierni Ugartemendia, Andrea G. Edlow, Claudia Ibarra, Nune Darbinian, Gabriel Tatevosian, Laura Goetzl

Objective

Maternal obesity affects 39.7% of reproductive-age women in the United States. Emerging research has suggested that in utero exposure to maternal obesity is associated with adverse neurodevelopmental outcomes, but knowledge of underlying mechanisms in human samples is lacking.

Methods

A matched case–control study was performed in women with singleton fetuses who were undergoing elective pregnancy termination at gestational ages 15 to 21 weeks. Maternal adiponectin levels from plasma were measured using ELISA kits. RNA was extracted from fetal brain tissue using RNeasy Mini Kit (QIAGEN). mRNA expression from ADIPOR1, ADIPOR2, MTOR, ATG5, ATG7, BECN1, and MAP1LC3B was quantified through the ΔΔCt method and using GAPDH as a housekeeping gene.

Results

We have identified transcription patterns associated with inhibition of autophagy in male fetal brain tissue exposed to maternal obesity (↑MTOR, ↓ATG5, ↓ATG7, and ↓MAP1LC3B), with female fetuses demonstrating either no change in transcription or nonsignificant changes associated with increased autophagy. There was significant downregulation of the autophagy-associated gene BECN1 in both male and female individuals who were exposed to obesity in utero.

Conclusions

We present novel evidence suggesting that in utero exposure to maternal obesity in humans may significantly affect neurodevelopment, especially in male fetuses, through alterations in normal autophagy molecular mechanisms and with adiponectin as a potential mediator.

目的在美国，39.7% 的育龄妇女患有肥胖症。新近的研究表明，在子宫内暴露于母体肥胖与不良的神经发育结果有关，但缺乏对人类样本潜在机制的了解。使用酶联免疫吸附试剂盒测定了母体血浆中的脂肪连素水平。采用ΔΔCt法，以GAPDH为对照基因，对ADIPOR1、ADIPOR2、MTOR、ATG5、ATG7、BECN1和MAP1LC3B的mRNA表达进行量化。结果我们在暴露于母体肥胖的雄性胎儿脑组织中发现了与抑制自噬相关的转录模式（↑MTOR、↓ATG5、↓ATG7和↓MAP1LC3B），而雌性胎儿的转录要么没有变化，要么与自噬增加相关的变化不显著。结论我们提出了新的证据，表明人类在子宫内暴露于母体肥胖可能会通过改变正常的自噬分子机制而严重影响神经发育，尤其是男性胎儿的神经发育，而脂肪连素是潜在的介导因素。

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引用次数: 0

Effect of a low-carbohydrate diet on pain and quality of life in female patients with lipedema: a randomized controlled trial 低碳水化合物饮食对女性脂肪性水肿患者疼痛和生活质量的影响：随机对照试验

IF 6.9 2区医学 Q1 Nursing

Obesity

Pub Date : 2024-04-16 DOI: 10.1002/oby.24026

Julianne Lundanes, Frida Sandnes, Kari Hanne Gjeilo, Patrik Hansson, Sissel Salater, Catia Martins, Siren Nymo

Objective

The primary objective of this study was to evaluate the effect of a low-carbohydrate diet (LCD) compared with a control diet on pain in female patients with lipedema. The secondary objectives were to compare the impact of the two diets on quality of life (QoL) and investigate potential associations of changes in pain with changes in body weight, body composition, and ketosis.

Methods

Adult female patients with lipedema and obesity were randomized to either the LCD or control diet (energy prescription: 1200 kcal/day) for 8 weeks. Body weight and body composition, pain (Brief Pain Inventory measured pain), and QoL (RAND 36-Item Health Survey [RAND-36], Impact of Weight on Quality of Life [IWQOL]-Lite, and Lymphoedema Quality of Life [LYMQOL]) were measured at baseline and at postintervention.

Results

A total of 70 female patients (age, mean [SD], 47 [11] years; BMI 37 [5] kg/m²) were included. The LCD group had greater weight loss (−2.8 kg; 95% CI: −4.1 to −1.0; p < 0.001) and larger reduction in pain now (−1.1; 95% CI: −1.9 to −0.3; p = 0.009) compared with the control group. No association was found between changes in pain now and weight loss. Both groups experienced improvements in several QoL dimensions.

Conclusions

Diet-induced weight loss in women with lipedema can improve QoL. An energy-restricted LCD seems to be superior to a standard control diet in reducing pain.

目的本研究的主要目的是评估低碳水化合物饮食（LCD）与对照饮食相比对女性脂肪性水肿患者疼痛的影响。次要目标是比较两种饮食对生活质量（QoL）的影响，并研究疼痛变化与体重、身体成分和酮病变化之间的潜在关联。方法将患有脂肪性水肿和肥胖症的成年女性患者随机分配到 LCD 或对照饮食（能量处方：1200 千卡/天）中，为期 8 周。结果共纳入了 70 名女性患者（平均年龄 [SD] 47 [11] 岁；体重指数 37 [5] kg/m2）。与对照组相比，LCD 组体重减轻幅度更大（-2.8 千克；95% CI：-4.1 至-1.0；p < 0.001），疼痛减轻幅度更大（-1.1；95% CI：-1.9 至-0.3；p = 0.009）。目前疼痛的变化与体重减轻之间没有关联。结论患有脂肪性水肿的女性通过饮食减肥可以改善 QoL。在减轻疼痛方面，限制能量的 LCD 似乎优于标准控制饮食。

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引用次数: 0

Interindividual differences of dietary fat-inducible Mest in white adipose tissue of C57BL/6J mice are not heritable C57BL/6J 小鼠白色脂肪组织中膳食脂肪诱导的 Mest 的个体间差异不是遗传性的

IF 6.9 2区医学 Q1 Nursing

Obesity

Pub Date : 2024-04-14 DOI: 10.1002/oby.24020

Rea Victoria P. Anunciado-Koza, Haifeng Yin, Crystal L. Bilodeau, Diana Cooke, Gene P. Ables, Sergey Ryzhov, Robert A. Koza

Objective

Differences in white adipose tissue (WAT) expression of mesoderm-specific transcript (Mest) in C57BL6/J mice fed a high-fat diet (HFD) are concomitant with and predictive for the development of obesity. However, the basis for differences in WAT Mest among mice is unknown. This study investigated whether HFD-inducible WAT Mest, as well as susceptibility to obesity, is transmissible from parents to offspring.

Methods

WAT biopsies of mice fed an HFD for 2 weeks identified parents with low and high WAT Mest for breeding. Obesity phenotypes, WAT Mest, hepatic gene expression, and serum metabolites were determined in offspring fed an HFD for 2 weeks.

Results

Offspring showed no heritability of obesity or WAT Mest phenotypes from parents but did show hepatic and serum metabolite changes consistent with their WAT Mest. Importantly, retired male breeders showed WAT Mest expression congruent with initial WAT biopsies even though HFD exposure occurred early in life.

Conclusions

Disparity of HFD-induced Mest in mice is not heritable but, rather, is reestablished during each generation and remains fixed from an early age to adulthood. Short-term HFD feeding reveals variation of WAT Mest expression within isogenic mice that is positively associated with the development of obesity.

目的在以高脂饮食（HFD）喂养的 C57BL6/J 小鼠中，白色脂肪组织（WAT）中胚层特异性转录本（Mest）的表达差异与肥胖同时存在，并可预测肥胖的发生。然而，不同小鼠WAT Mest差异的基础尚不清楚。本研究调查了 HFD 诱导的 WAT Mest 以及肥胖易感性是否会从亲代传给子代。方法对喂食 HFD 2 周的小鼠进行 WAT 活检，找出 WAT Mest 低和 WAT Mest 高的亲代进行繁殖。结果子代的肥胖或WAT Mest表型与亲代无遗传性，但肝脏和血清代谢物的变化与其WAT Mest一致。重要的是，退役的雄性种鼠表现出的 WAT Mest 表达与最初的 WAT 活检结果一致，即使 HFD 暴露发生在生命早期。短期饲喂高氟酸脱氢饲料揭示了同源小鼠体内WAT Mest表达的差异，这种差异与肥胖的发生呈正相关。

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引用次数: 0

Pre-pregnancy maternal obesity and infant neurodevelopmental outcomes in Latino infants 拉美裔婴儿孕前母亲肥胖与婴儿神经发育结果

IF 6.9 2区医学 Q1 Nursing

Obesity

Pub Date : 2024-04-10 DOI: 10.1002/oby.24010

Mahsa Babaei, Christopher J. Machle, Pari Mokhtari, Jonatan Ottino González, Kelsey A. Schmidt, Tanya L. Alderete, Shana Adise, Bradley S. Peterson, Michael I. Goran

Objective

This study explores the impact of maternal pre-pregnancy BMI on infant neurodevelopment at 24 months in low-income Latino families. It also investigates whether infant diet mediates this relationship.

Methods

Latino mother-infant pairs (n = 163) were enrolled at 1 month post partum and were followed for 2 years, with assessments at 6-month intervals. Maternal pre-pregnancy anthropometrics were self-reported at baseline, and child neurodevelopment was assessed at 24 months using the Bayley Scales of Infant Development. Diet quality of infants was measured using the Healthy Eating Index (HEI)-2015 and HEI-Toddlers-2020 scores at multiple time points. Mediation and regression models that adjust for maternal factors were used to examine the associations.

Results

Pre-pregnancy BMI showed significant negative associations with child cognitive scores (β = −0.1, 95% CI: −0.2 to −0.06, p < 0.001) and language scores (β = −0.1, 95% CI: −0.2 to −0.03, p = 0.01) at 24 months. Infant HEI-2015 scores at 24 months partly mediated these associations, explaining 23% and 30% of the total effect on cognitive and language subscales, respectively. No specific dietary components in infants mediated the relationship, except for the total HEI-2015 score.

Conclusions

Managing maternal obesity pre-pregnancy is crucial for improving infant neurodevelopmental outcomes, especially in low-income Latino families. Promoting healthy weight and enhancing infant diet quality can enhance neurodevelopment in these populations.

本研究探讨了在低收入拉丁裔家庭中，母亲孕前体重指数对婴儿 24 个月时神经发育的影响。方法拉美裔母婴（163 人）在产后 1 个月入组，随访 2 年，每隔 6 个月进行一次评估。母亲怀孕前的人体测量数据是在基线时自我报告的，儿童神经发育情况是在 24 个月时使用贝利婴儿发育量表进行评估的。婴儿的饮食质量是通过多个时间点的健康饮食指数（HEI）-2015 和 HEI-Toddlers-2020 分数来衡量的。结果怀孕前 BMI 与 24 个月时儿童认知得分（β = -0.1，95% CI：-0.2 至 -0.06，p < 0.001）和语言得分（β = -0.1，95% CI：-0.2 至 -0.03，p = 0.01）呈显著负相关。婴儿在 24 个月时的 HEI-2015 分数部分介导了这些关联，分别解释了对认知和语言分量表的总影响的 23% 和 30%。除了 HEI-2015 总分外，婴儿的特定饮食成分都不能调节这种关系。促进健康体重和提高婴儿饮食质量可以促进这些人群的神经发育。

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引用次数: 0

Impact of sustained calorie restriction and weight cycling on body composition in high-fat diet-fed male and female C57BL/6J mice 持续热量限制和体重循环对高脂饮食喂养的雌雄 C57BL/6J 小鼠身体成分的影响

IF 6.9 2区医学 Q1 Nursing

Obesity

Pub Date : 2024-04-10 DOI: 10.1002/oby.24015

Daniel L. Smith Jr, Yongbin Yang, Luis M. Mestre, Beate Henschel, Erik Parker, Stephanie Dickinson, Amit Patki, David B. Allison, Tim R. Nagy

Objective

The objective of this study was to investigate body composition changes with weight cycling (WC) among adult C57BL/6J mice with diet-induced obesity.

Methods

A total of 555 single-housed mice were fed a high-fat diet ad libitum (AL) from 8 to 43 weeks of age. The 200 heaviest mice of each sex were randomized to the following four groups: ever obese (EO, continued AL feeding); obese weight loser (OWL, calorie-restricted); obese weight loser moderate (OWLM, body weight halfway between EO and OWL); and WC (diet restricted to OWL followed by AL refeeding cycles). Body weight and composition data were collected. Linear regression was used to calculate residuals between predicted and observed fat mass. Linear mixed models were used to compare diet groups.

Results

Although weight loss and regain resulted in changes in body weight and composition, fat mass, body weight, and relative body fat were not significantly greater for the WC group compared with the EO group. During long-term calorie restriction, males (but not females) in the OWLM group remained relatively fatter than the EO group.

Conclusions

WC did not increase body weight or relative fat mass for middle-aged, high-fat diet-fed adult mice. However, long-term moderate calorie restriction resulted in lower body weight but greater “relative” fat in male mice.

本研究的目的是调查饮食诱导肥胖的成年 C57BL/6J 小鼠的身体成分随体重循环（WC）而发生的变化。方法从 8 周龄到 43 周龄，共饲养了 555 只高脂饮食（AL）小鼠。将雌雄各200只体重最重的小鼠随机分为以下四组：曾经肥胖组（EO，继续喂食AL）；肥胖体重失败者组（OWL，卡路里限制）；肥胖体重中等失败者组（OWLM，体重介于EO和OWL之间）；以及WC组（饮食限制为OWL，然后进行AL再喂食循环）。收集了体重和成分数据。线性回归用于计算预测脂肪量和观察脂肪量之间的残差。结果虽然体重减轻和恢复导致体重和成分发生变化，但与 EO 组相比，WC 组的脂肪量、体重和相对体脂并没有显著增加。在长期卡路里限制期间，OWLM 组的雄性（而非雌性）仍然比 EO 组相对较胖。然而，长期适度限制热量会导致雄性小鼠体重降低，但 "相对 "脂肪量增加。

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引用次数: 0

Mutations in the leptin-melanocortin pathway and weight loss after bariatric surgery: a systematic review and meta-analysis 瘦素-黑色素皮质素通路中的突变与减肥手术后的体重减轻：系统回顾和荟萃分析

IF 6.9 2区医学 Q1 Nursing

Obesity

Pub Date : 2024-04-05 DOI: 10.1002/oby.24007

Nianrong Zhang, Hao Wang, Shuman Ran, Zhe Wang, Biao Zhou, Siqi Wang, Zhengqi Li, Baoyin Liu, Yuntao Nie, Yishan Huang, Hua Meng

Objective

The objective of this meta-analysis was to quantify the overall effects of gene mutations in the leptin-melanocortin pathway on short- and long-term weight loss after bariatric surgery.

Methods

MEDLINE, PubMed, and Embase were searched, and data were analyzed using ReviewManager (RevMan) version 5.4. The datasets were divided into two subgroups based on postoperative time, and the outcome measure was the percentage of total weight loss. Meta-regression analysis was performed, and the outcome was presented as the weighed mean difference of percentage of total weight loss.

Results

The results showed that patients with mutations in the leptin-melanocortin pathway experienced 3.03% lower total weight loss after bariatric surgery (mean difference, −3.03; 95% CI: −3.63 to −2.44), mainly reflected in lower long-term postoperative weight loss (mean difference, −3.43; 95% CI: −4.09 to −2.77), whereas mutation carriers exhibited a magnitude of short-term postoperative weight loss that was similar to patients without such mutations (total difference value, −1.13; 95% CI: −2.57 to 0.31).

Conclusions

Mutations in leptin-melanocortin pathway genes reduce long-term weight loss after bariatric surgery, whereas this effect may not be reflected during the period of rapid weight loss within 12 months. These genetic variants increase the difficulties in maintaining patients' long-term weight loss.

方法检索MEDLINE、PubMed和Embase，并使用ReviewManager（RevMan）5.4版分析数据。根据术后时间将数据集分为两个亚组，结果指标为总重量减少的百分比。结果显示，瘦素-黑皮素通路突变的患者在减肥手术后的总体重减轻率降低了3.03%（平均差异为-3.03；95% CI：-3.63至-2.44），主要体现在术后长期体重减轻率较低（平均差异为-3.结论瘦素-黑色素皮质素通路基因的变异会减少减肥手术后的长期体重减轻，而这种影响在 12 个月内体重快速下降期间可能无法体现。这些基因变异增加了患者维持长期体重减轻的难度。

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引用次数: 0

Correction to “Predictors of racial differences in weight loss: The PROPEL trial” 更正 "减肥中种族差异的预测因素：PROPEL 试验"

IF 6.9 2区医学 Q1 Nursing

Obesity

Pub Date : 2024-04-04 DOI: 10.1002/oby.24029

Newton, RL, Zhang, D, Johnson, WD, et al. Predictors of racial differences in weight loss: the PROPEL trial. Obesity (Silver Spring). 2024; 32(3): 476–485. doi: 10.1002/oby.23936.

In this published article, the spelling of Dachuan Zhang's name was incorrect, and it has now been corrected.

We apologize for this error.

Newton, RL, Zhang, D, Johnson, WD, et al. 减肥种族差异的预测因素：PROPEL 试验。肥胖症（银泉）。2024; 32(3):476-485.doi：10.1002/by.23936.在这篇发表的文章中，Dachuan Zhang 的名字拼写有误，现已更正，我们对此表示歉意。

引用次数: 0

Maternal folic acid supplementation during pregnancy in association with childhood overweight or obesity 母亲孕期补充叶酸与儿童超重或肥胖的关系

IF 6.9 2区医学 Q1 Nursing

Obesity

Pub Date : 2024-04-04 DOI: 10.1002/oby.24012

Chi-Yen Hung, Hsin-Ju Lee, Zhao-Ting Tsai, Shu-Jung Huang, Hsin-Yi Huang, Hui-Ju Tsai, Tsung-Chieh Yao

Objective

This study aimed to examine associations of maternal folic acid supplementation (FAS) during pregnancy with childhood overweight or obesity (OWO) or adiposity.

Methods

In a population-based cohort of 1479 children, maternal FAS during pregnancy was assessed retrospectively by questionnaires. BMI and body fat percentages were measured at a mean age of 6.4 years. Pertinent factors were accounted for in data analyses.

Results

Maternal FAS during pregnancy was negatively associated with OWO (adjusted odds ratio: 0.70; 95% CI: 0.50 to 0.99). There were inverse associations of maternal FAS during pregnancy with BMI z score (β: −0.22; 95% CI: −0.39 to −0.05), whole body fat percentage (β: −1.28; 95% CI: −2.27 to −0.30), trunk fat percentage (β: −1.41; 95% CI: −2.78 to −0.04), and limb fat percentage (β: −1.31; 95% CI: −2.32 to −0.30). Stratified analyses found inverse associations of FAS during pregnancy with OWO, BMI z score, and body fat percentages predominantly among children without breastfeeding and whose parents had a below-tertiary educational level.

Conclusions

This study provides novel evidence that maternal FAS during pregnancy was significantly associated with a decreased risk of childhood OWO and adiposity, particularly among children with no breastfeeding and lower parental educational level.

本研究旨在探讨孕期补充叶酸（FAS）与儿童超重或肥胖（OWO）或脂肪过多之间的关系。方法在一个包含 1479 名儿童的人群队列中，通过问卷对孕期补充叶酸的情况进行了回顾性评估。对平均年龄为 6.4 岁的儿童的体重指数和体脂百分比进行了测量。在数据分析中考虑了相关因素。结果孕妇在怀孕期间出现的 FAS 与 OWO 呈负相关（调整后的几率比：0.70；95% CI：0.50 至 0.99）。孕产妇孕期 FAS 与体重指数 z 值（β：-0.22；95% CI：-0.39 至 -0.05）、全身脂肪百分比（β：-1.28；95% CI：-2.27 至 -0.30）、躯干脂肪百分比（β：-1.41；95% CI：-2.78 至 -0.04）和四肢脂肪百分比（β：-1.31；95% CI：-2.32 至 -0.30）呈负相关。分层分析发现，妊娠期母体脂肪过多症与OWO、BMI z评分和体脂肪百分比呈反向关系，这主要发生在未进行母乳喂养且父母受教育程度低于高等教育的儿童中。结论这项研究提供了新的证据，表明妊娠期母体脂肪过多症与儿童OWO和脂肪过多的风险降低有显著关系，尤其是在未进行母乳喂养且父母受教育程度较低的儿童中。

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引用次数: 0

Adipocyte-derived inflammatory molecules induce senescent B cells through metabolic pathways 源自脂肪细胞的炎症分子通过代谢途径诱导衰老的 B 细胞

IF 4.2 2区医学 Q1 ENDOCRINOLOGY & METABOLISM

Obesity

Pub Date : 2024-04-04 DOI: 10.1002/oby.24013

Daniela Frasca, Maria Romero, Denisse Garcia, Seth Thaller, Valquiria Bueno

Objective

The aim of this study was to demonstrate that an adipocyte tissue-derived conditioned medium (ACM) contains inflammatory molecules that induce senescence in B cells.

Methods

We incubated blood-derived B cells from lean donors with ACM obtained from the adipose tissue of adult female donors with obesity undergoing weight reduction surgery or with medium as control. After 24 h, cells were harvested, and the expression of transcripts for proinflammatory cytokines (TNF/IL-6), chemokines (IL-8), and for markers of the senescence-associated secretory phenotype (SASP) was measured by quantitative polymerase chain reaction. B cells were also stained with the marker of immunosenescence β-galactosidase, and their metabolic status was evaluated in Seahorse using a Mito Stress Test.

Results

We show that the incubation of B cells from lean donors with ACM induces the expression of transcripts for inflammatory and SASP transcripts, increases the amount of β-galactosidase staining, and induces a metabolic phenotype characterized by higher basal and maximal oxygen consumption, spare respiratory capacity (difference between maximal and basal respiration), nonmitochondrial oxygen consumption, ATP production, and proton leak.

Conclusions

These results demonstrate that B cells from lean individuals, after incubation with ACM, become inflammatory and senescent, and this occurs through metabolic pathways needed to support their secretory phenotype.

本研究旨在证明脂肪细胞组织衍生的条件培养基（ACM）含有诱导 B 细胞衰老的炎症分子。

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引用次数: 0

Repeated photodynamic therapy using a chlorin e6-embedded device to prolong the therapeutic effects on obesity 使用嵌入氯素 e6 的装置进行重复光动力疗法，以延长对肥胖症的治疗效果。

IF 6.9 2区医学 Q1 Nursing

Obesity

Pub Date : 2024-04-01 DOI: 10.1002/oby.23958

Jung-Hoon Park, Ji Won Kim, Dae Sung Ryu, Hyeonseung Lee, Hee Kyong Na, Jin Hee Noh, Do Hoon Kim, Sanghee Lee, Kun Na, Hwoon-Yong Jung

Objective

This study aimed to investigate the efficacy and safety of repeated photodynamic therapy (PDT) with a chlorin e6 (Ce6)-embedded intragastric satiety-inducing device (ISD) to maintain therapeutic effects of obesity in a juvenile pig.

Methods

The Ce6-embedded ISD was fabricated with a dipping method. Twelve pigs were divided into four groups of three and were administered control, single, biweekly, or weekly PDT, respectively. The therapeutic effects were assessed by comparing the results of phototoxicity, endoscopy, fluoroscopy, hormone and weight changes, and histological examination.

Results

The percentage of total body weight gain was significantly suppressed in PDT-treated pigs compared with control pigs (all p < 0.001). This suppression persisted in the repeated PDT groups, but percentage of total body weight gain gradually increased when PDT was stopped. Ghrelin levels in the PDT-treated groups were significantly lower and leptin levels were significantly higher than those in the control group (all p < 0.05). Inflammatory cell infiltration, collagen, TUNEL, and anti-ghrelin-positive deposition in the weekly group were significantly higher than those in the control, single, and biweekly groups (all p < 0.01).

Conclusions

Repeated and periodic PDT was technically feasible and safe and successfully maintained the therapeutic effects against obesity while eliminating the indwelling time and reducing ISD-related complications in pigs.

研究目的本研究旨在探讨使用氯素 e6（Ce6）嵌入式胃内饱腹感诱导装置（ISD）反复进行光动力疗法（PDT）以保持对幼年猪肥胖症治疗效果的有效性和安全性：方法：用浸渍法制作了嵌入 Ce6 的 ISD。将 12 头猪分为四组，每组 3 头，分别给予对照组、单次组、双周组或每周组 PDT。通过比较光毒性、内窥镜检查、透视检查、激素和体重变化以及组织学检查的结果来评估治疗效果：结果：与对照组相比，PDT 治疗猪的总增重百分比显著下降（均为 p 结论：PDT 治疗猪的总增重百分比显著低于对照组（均为 p 结论：PDT 治疗猪的总增重百分比显著低于对照组（均为 p）：重复和定期的光动力疗法在技术上是可行和安全的，并成功地保持了对肥胖症的治疗效果，同时消除了猪的留置时间并减少了与 ISD 相关的并发症。

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引用次数: 0

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