肥胖对肠屏障和炎症的影响及干预研究
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摘要
第一部分肥胖对大鼠肠屏障的影响及n-3多不饱和脂肪酸的干预研究研究背景：肥胖是一种低度的炎症反应状态,肠屏障的改变是诱发肥胖及相关炎症的重要原因,主要表现为肠道菌群的紊乱和肠道通透性增加,导致内毒素入血,从而引发机体炎症反应。n-3多不饱和脂肪酸(n-3Polyunsaturated fatty acids, n-3PUFAs)用于心血管疾病的治疗及预防,可以减轻肥胖患者的体重,改善代谢综合征,研究显示肥胖患者体内n-3PUFAs含量少于非肥胖患者。补充-3PUFAs可以改善炎性肠病、部分肝切除动物的肠道通透性,而对高脂饮食导致的肠屏障损害的作用报道较少。
目的：观察高脂饮食诱发肥胖模型,是否引起肠屏障(肠道菌群及肠通透性)的改变,补充n-3多不饱和脂肪酸对高脂饮食导致的肥胖大鼠肠道屏障的影响及减重作用,为将来临床应用提供理论依据。
方法：36只雄性Sprague-Dawley (SD)大鼠随机分为普通饮食组(Control diet, CD,n=10)、高脂饮食组(High-fat diet, HFD, n=10)、CD+n-3PUFAs组(n=7)、HFD+n-3PUFAs组(n=9)。饲养10周后,取大鼠新鲜粪便提取DNA,通过实时定量PCR检测肠道菌群组成。应用ELISA检测血浆中炎症因子水平。应用改良偶氮基质显色鲎试剂法检测门静脉血清内毒素水平。通过乳果糖／甘露醇方法检测肠通透性,Western blot检测小肠粘膜紧密连接蛋白的表达。
结果：HFD组大鼠体重明显高于CD组、CD+n-3PUFAs组和HFD+n-3PUFAs组。HFD组大鼠粪便中厚壁菌门(Firmicutes)和肠杆菌科(Enterobacteriales)含量高于CD组和HFD+n-3PUFAs组大鼠,而拟杆菌门(Bacteroidetes)、双歧杆菌属(Bifidobacterium spp.)及Bacteroidetes与Firmicutes比值低于CD组和HFD+n-3PUFAs组大鼠。CD+n-3PUFAs组大鼠粪便中Bacteroidetes含量高于CD组大鼠。Peaeson相关性分析结果显示Bacteroidetes与Firmicutes比值与体重具有负相关性。HFD组大鼠尿中乳果糖／甘露醇比值高于CD组和HFD+n-3PUFAs组大鼠。CD组和CD+n-3PUFAs组大鼠尿中乳果糖／甘露醇比值无明显差异。HFD组门静脉血浆中内毒素和炎症因子水平高于CD组大鼠和HFD+n-3PUFAs组大鼠。HFD组大鼠大鼠肠粘膜紧密连接蛋白(claudin和occludin)的表达低于CD组大鼠和HFD+n-3PUFAs组大鼠。
结论：高脂饮食导致的肥胖引起肠道菌群改变、肠通透性增加,而补充n-3PUFAs可以部分修复肥胖导致肠道菌群紊乱,降低肠道通透性,减轻炎症因子和内毒素水平,减少体重。
第二部分肥胖症患者血清、皮下及内脏脂肪组织脂肪酸谱测定及与炎症因子、胰岛素抵抗的相关研究
背景：肥胖是体内的异常的脂肪蓄积,脂肪组织分泌多种炎症因子,参与胰岛素抵抗等代谢综合征的形成。然而导致肥胖症患者炎症因子升高的原因未知。研究显示无论是血中还是脂肪组织中脂肪酸谱,均反映了饮食中脂肪酸的摄入及体内的代谢,尤其是脂肪组织中的脂肪酸谱更是反映了长期的脂肪酸摄入情况,而且与代谢综合征、肥胖及炎症因子相关,但有关中国重度肥胖症患者脂肪酸谱的研究较少,特别是肥胖症脂肪组织脂肪酸谱的检测在国外研究较少,国内尚无研究。
目的：检测中国重度肥胖症患者及非肥胖患者血清及脂肪组织中脂肪酸谱、炎症因子水平并分析差异,分析脂肪酸谱与炎症因子及胰岛素抵抗的相关性。材料与方法：选取在北京协和医院接受手术的27例肥胖患者和24例非肥胖患者作为研究对象。通过气相色谱技术检测患者血清、脂肪组织脂肪酸构成,通过产物与底物计算脱氢酶活性：SCD (C16:1n-7/C16:0,C18:1n-9/C18:0)、D6D (C20:3n-6/C18:2n-6)、D5D(C20:4n-6/C20:3n-6),应用ELISA方法检测血清及脂肪组织中炎症因子(hsCRP, TNF-α, IL-6)水平,比较肥胖组与非肥胖组患者脂肪酸谱、脱氢酶活性及炎症因子水平的差异,分析脂肪酸谱与炎症因子及胰岛素抵抗指数(HOMA-IR)的相关性。
结果：肥胖症患者血清中含有更高比例的棕榈酸(C16：0)、油酸(C18：ln-9)、二十碳三烯酸(C20：3n-3),更低比例的亚油酸(C18：2n-6)、γ亚麻酸(C18：3n-6)。肥胖症患者脂肪组织中含有更高比例的C16：0、油酸(C18：1n-9)、丫亚麻酸(C18：3n-6),更低比例的硬脂酸(C18：0)、亚油酸(C18：2n-6)、α-亚麻酸(C18：3n-3)和二十二碳六烯酸(DHA, C22:6n-3)。饱和脂肪酸(Saturated fatty acids, SFAs)和单不饱和脂肪酸(Monounsaturated fatty acids, MUFAs)的含量在肥胖组患者内脏脂肪组织中含量更高,而n-3多不饱和脂肪酸(n-3polyunsaturated fatty acids, n-3PUFAs)和多不饱和脂肪酸(Polyunsaturated fatty acids, PUFAs)的含量更低。肥胖症患者皮下脂肪组织中含有更高比例的C16：0、棕榈油酸(C16:ln-7). C18:1n-9、C18:3n-6,更低比例的C18:0、C18:2n-6、DHA、MUFAs和SFAs。SCD18和D6D的活性在肥胖组脂肪组织中高于非肥胖组。肥胖组患者内脏脂肪组织比皮下脂肪组织含有更多的SFAs及MUFAs。肥胖组患者内脏及皮下脂肪组织中炎症因子水平较高(hsCRP、TNF-α、IL-6)。肥胖组患者内脏脂肪组织中SFAs、MUFAs、SCD18、D6D活性与hsCRP. TNF-α、IL-6水平具有正相关。与hsCRP、TNF-α的含量具有负相关性的是肥胖组患者内脏脂肪中的n-3PUFAs。与胰岛素抵抗(HOMA-IR)呈正相关的是内脏脂肪组织中的SFAs、MUFAs、SCD18、D6D和皮下脂肪组织中的D6D,与胰岛素抵抗(HOMA-IR)呈负相关的是内脏脂肪组织中的PUFAs、n-3PUFAs和皮下脂肪组织中的PUFAs。
结论：肥胖组患者与非肥胖组患者血浆及脂肪组织中脂肪酸谱存在明显的差异。不同部位脂肪组织脂肪酸谱及炎症因子水平的差异显示其不同的代谢活性,脂肪组织内饱和脂肪酸、单不饱和脂肪酸含量、脱氢酶(SCD18、D6D)活性与炎症因子、胰岛素抵抗呈正相关,而多不饱和脂肪酸与炎症因子、胰岛素抵抗呈负相关,这种相关性在肥胖患者特别显著。脂肪酸摄入与体内代谢可能参与肥胖相关炎症及代谢综合征发生。
第三部分术前口服葡萄糖溶液减轻术后胰岛素抵抗及炎症反应研究背景：手术应激导致术后炎症反应及高血糖,增加了术后并发症的风险。传统观念认为延长禁食时间有助于减少术中误吸等并发症。1999年美国麻醉医师协会提出：针对术前需要禁食的病人,在术前2小时仍可进食温和液体,如水或者葡萄糖溶液,并且术前口服葡萄糖溶液已经被欧洲肠外肠内营养与快速康复协会推荐。尽管术前口服葡萄糖溶液可以改善病人术后糖代谢,但对于是否增加胃液量和麻醉手术风险尚存争议。虽然国内大多数医师已意识到减少禁食时间的重要性,但传统常规及考虑到手术安全并未推广实施。由此,需要术前口服葡萄糖溶液的临床研究。目的：1.观察术前胃液量及pH值及麻醉手术并发症评估术前口服葡萄糖溶液的安全性及可行性；2.观察术前口服葡萄糖溶液对胃肠手术后炎症反应、血糖及胰岛素抵抗(Insulin resistance, IR)的影响。
方法：胃肠手术48例患者术前签署知情同意书,随机分研究组23例,对照组25例。研究组术前3h一次性口服25%葡萄糖溶液300ml(75g),比较两组术前胃内容物量、pH值及术后第1天的血清高敏C反应蛋白(high sensitivity C-reactive protein, hsCRP)、空腹血糖、胰岛素水平、胰岛素抵抗指数稳态模型(Homeostasis model assessment-Insulin resistance, HOMA-IR)。
结果：所有病人按计划口服葡萄糖溶液后均无不适主诉,两组均无麻醉及手术并发症。麻醉前两组胃内容物量(30.88±25.93vs27.94±24.04ml)、pH值(1.99±0.34vs2.13±0.43)无明显差异；术前两组hsCRP、血糖、胰岛素水平、HOMA-IR无明显差异。术后第1天研究组空腹血糖、HOMA-IR及hsCRP均明显低于对照组(6.51±1.15vs7.49±0.57mmol/L, P=0.038),(4.34±1.60vs6.09±2.81, P=0.043),(40.45±27.02vs80.02±38.98mg/L, P=0.03),术后第2天研究组hsCRP均明显低于对照组(70.33±32.19vs101.12±42.73,P=0.041)。
结论：术前口服葡萄糖溶液安全可行,可明显改善患者术后应激所致的高血糖及IR、炎症反应。
第四部分腹腔镜减重手术治疗重度肥胖症患者的临床研究研究背景：肥胖症已经严重影响健康及生活质量,是导致代谢综合征和诸多合并症的主要原因。近10年来国内外的研究实践证实减重手术是病态性肥胖症患者获得稳定减重效果的方法,国内减重外科处于起步发展阶段,存在诸多问题和困难,但由于手术适应症及方式选择,手术效果不理想,术后复胖及术后并发症的问题,需要针对中国肥胖症患者大样本、多中心的临床研究证实减重手术的效果。肥胖症患者就诊时合并多系统的问题,需要在术前多学科评估及术后专业团队的随诊才能保证手术安全与效果。为了规范我国肥胖症外科治疗流程,北京协和医院在国内率先开展多学科模式下手术治疗病态性肥胖症患者。
目的：肥胖症综合治疗的多科协作模式腹腔镜可调节胃束带术(Laparoscopic adjustable gastric banding, LAGB)及腹腔镜袖状胃切除术(Laparoscopic sleeve gastrectomy, LSG)的临床减重效果、安全性及对合并症的治疗效果,比较两种手术方式对肥胖症相关炎症及减重效果,为中国肥胖症患者手术方式的选择上提供依据。方法：分析2009年10月至2014年3月多学科模式下北京协和医院基本外科施行LAGB31例及LSG14例病态性肥胖患者临床资料和术后的随访数据。总结在多科协作模式下肥胖症患者的围手术期和术后随访管理流程,观察手术安全性和术后长期减重效果及合并症的改善情况。
结果：全部患者均顺利施行手术,未出现围手术期死亡病例。LAGB组患者术前平均体重121.7±22.5kg,平均体重指数(BMI)42.86±6.95kg/m2。术后48个月平均体重和BMI分别为82.7±12.43kg和32.5±4.64kg/m2,LSG组患者术前平均体重126.3±38.9kg,平均BMI43.57±10.21kg/m2。术后12月平均体重和BMI分别为91.67±51.63kg和30.59±14.98kg/m2。术后LAGB组早期并发症1例全身炎症反应综合征及肺呼吸功能衰竭,远期并发症2例注水泵处皮肤感染、注水泵突出皮肤。LSG组患者有1例因上消化道不全梗阻。术后体重和体质指数逐渐下降,LAGB组患者术后48个月平均额外体重减轻48.0%。规律随诊、依从性良好组额外体重减轻百分比显著高于不规律随诊、依从性差组。LSG组患者术后12个月平均额外体重减轻89.5%。术后12月LSG减重效果优于LAGB。两组患者术后肥胖症相关代谢性疾病均有不同程度改善。
结论：LAGB与LSG安全可靠,有效减轻病态性肥胖症患者体重,减轻炎症、改善合并症,多科协作模式可优化疾病诊治流程,保障围手术期安全及疗效更优。术后规律随诊对获得长期减重效果有重要影响。LSG的减重效果优于LAGB
Part.1Effect of obesity and intervention of n-3polyunsaturatedfatty acids on intestinal barrier
Background:Growing evidences showed that an important characteristic of obesity is low-grade inflammation. Changes in intestinal barrier, which included the gut microbiota dysbiosis, increased intestinal permeability and elevated endotoxin in blood, thereby triggering the inflammatory response. N-3polyunsaturated fatty acids were used for the treatment and prevention of cardiovascular disease, could reduce the body weight of obese patients, improve the metabolic syndrome. Our previous study showed that there were less contents of n-3PUFAs in the obese patients than non-obese patients. Supplementation of n-3PUFAs can improve the intestinal permeability in the models of inflammatory bowel disease and partial hepatectomy animal, but the effect of n-3PUFAs on the intestinal barrier impaered by high fat died is less reported.
Objective:The aim of the present study is to investigate the effect of high fat diet incduced obeisty on the the intestinal barrier and protection effects of supplementation with n-3polyunsaturated fatty acids, which provides theoretical basis for clinical application in the future.
Methods:Thirty-six Sprague-Dawley rats were divided into four groups randomly, fed control diet(CD), high-fat diet(HFD), control diet supplemented with n-3polyunsaturated fatty acids and high-fat diet supplemented with n-3polyunsaturated fatty acids respectively. Fresh fecal samples were collected to analyze the gut microbiota after10weeks feeding. DNA was exacted from the fresh fecal samples. Real-time PCR was used to detect the composition of the gut microbiota. The levels of hsCRP, TNF-α and IL-6in plasma were measured through ELISA, respectively. The endotoxin levels were detected though modified azo chromogenic substrate limulus amebocyte lysate assay. Intestinal permeability(lactose/mannitol ratio in the urine, L/M)was determined on the end of this study. Western blotting method was used to detect tight junction protein of intestinal mucosa.
Results:The HFD induced a more increase in the body weight than the CD, CD+n-3PUFAs, HFD+n-3PUFAs groups. There were more contents of the Firmicutes, Enterobacteriales, and less contents of Bacteroidetes, Bifidobacterium spp. and ratios of Bacteroidetes to Firmicutes in the fecal of the rats from HFD group compared to the CD and HFD+n-3PUFAs groups. There were more contents of the Bacteroidetes in the fecal of the rats from CD+n-3PUFAs group compared to the CD group. The Pearson's correlation coefficient shows that there is a negative correlation between the body weight and the ratios of Bacteroidetes-to-Firmicutes. Intestinal permeability(L/M) was increased significantly in HFD group compared to CD and HFD+n-3PUFAs groups, but there is no significant difference in the L/M ratio between the CD and CD+n-3PUFAs groups. The endotoxin and inflammatory factors in plasma in portal vein from rats of HFD group were higher than CD and HFD+n-3PUFAs groups, but expression of claudin and occludin in intestinal mucosa of HFD group were lower than CD and HFD+n-3PUFAs groups.
Conclusion:HFD-induced obesity changed the gut microbiota and increased intestinal permeability. Supplement with n-3PUFAs could counteract these gut dysbiosis and reduce the intestinal permeability as well as improve inflammatory factors and the body weight.
Part.2Fatty acid composition and estimated desaturase activities in visceral and subcutaneous adipose tissues of morbidly obese patients, and are associated with inflammatory factors and insulin resistance
Background:Obesity is characterized by abnormal fat storage and low-grade inflammation in adipose tissue and serum. Adipose tissue from obese patients abnormally secretes abundant inflammatory factors that promote the insulin resistance and metabolic syndrome. However, the cause of elevated infalmmatory factors is still unknown. Previous studies showed that fatty acid composition in both blood and adipose tissue reflected the diet intake of fatty acid, and was associated with metabolic syndrome, obesity and inflammatory factors. But the studies on the fatty acid composition in serum and adipose tissue from Chinese morbidly obese patiens are limited.
Objective:The objective of this study was to investigate the differences in fatty acid composition and estimates desaturase activities in visceral and subcutaneous adipose tissue between morbidity obese and non-obese subjects, and to investigate the correlation between fatty acid composition and desaturase activities with obesity-associated inflammatory factors, such as high sensitivity C-reactive protein (hsCRP), tumour necrosis factor alpha (TNF-a) and interleukin-6(IL-6) in adipose tissue, and insulin resistance.
Methods:Visceral and subcutaneous adipose tissues were obtained from27obese subjects with metabolic syndrome or type2diabetes and24non-obese subjects. Analysis of fatty acid composition in adipose tissue was performed using gas chromatography. The desaturase activities were estimated from the ratio of product to precursor:SCD (C16:ln-7/C16:0and C18:ln-9/C18:0), D6D (C20:3n-6/C18:2n-6) and D5D (C20:4n-6/C20:3n-6). The levels of hsCRP, TNF-a and IL-6in adipose tissue and serum were measured through ELISA, respectively. The differences in fatty acid composition, estimated desaturase activities and inflammatory factors levels between both groups were compared, and the correlations between fatty acid composition and inflammatory factors levels, HOMA-IR were analyzed.
ResultscObese subjects had higher levels of oleic (C18:ln-9), palmitic (C16:0), palmitoleic (C16:ln-7) and dihomo--y-linolenic (C18:3n6) acids in both visceral and subcutaneous adipose tissue, and lower levels of stearic acid (C18:0), linoleic acid (C18:2n6) and C18:3n3than the non-obese controls. There were more oleic acid, saturated fatty acids and monounsaturated fatty acids in visceral adipose tissue of obese group, more saturated fatty acids in visceral adipose tissue of non-obese group,compared to subcutaneous adipose tissue. The levels of hsCRP,TNF-a, IL-6and the estimated activities of SCD18and D6D were significantly higher in visceral and subcutaneous adipose tissue of the obese subjects. Also, we found that there were more hsCRP and IL-6in the visceral adipose tissue than in the subcutaneous adipose tissue. hsCRP, TNF-a and IL-6in adipose tissue were positively associated with the cotents of SFAs, MUFAs and estimated activities of SCD18and D6D. hsCRP in adipose tissue was negatively associated with the cotents of n-3PUFAs. HOMA-IR was positively associated with the cotents of SFAs, MUFAs, estimated activities of SCD18and D6D in visceral adipose tissue and estimated activities of D6D in subcutaneous adipose tissue, while it was negatively associated with the cotents of PUFAs and n-3PUFAs in visceral adipose tissue and n-3PUFAs in subcutaneous adipose tissue.
Conclusion:There were differences in fatty acid composition and estimated desaturase activities of adipose tissue between obese and non-obese subjects. These difference reflected the a long period of fatty acid intake and metabolism in both groups. Differsence fatty acid composition and inflammtory facors levels between the visceral and subcutaneous adipose tissue showed the discrepant metabolic activities of different fat depots. The high correlations of contents of some fatty aicd and desaturases activities with hsCRP, TNF-a, IL-6in adipose tissue and HOMA-IR suggest that fatty acid intake and metabolsim may play a role in the development of chronic inflammation commonly found in morbid obesity and metabolic syndrome.
Part.3Preoperative oral carbohydrate alleviates postoperative insulin resistance and inflammatory reaction
Background:Stress of operation induces postoperative hyperglycemia and inflammatory response that increases the risk of postoperative complications. Long preoperative fasting has been a standard practice for patients undergoing elective surgery to avoid vomiting and pulmonary aspiration during anesthesia induction.In1999, the American Society of Anesthesiologists (ASA) issued a practice guideline for preoperative fasting in which patients (except those with delayed gastric emptying) are allowed to have clear fluids such as water, carbonated beverages until2h before surgery. Preoperative oral carbohydrate administration for adult patients has been recommended by European Society for Parenteral and Enteral Nutrition and Enhanced Recovery After Surgery. Although preoperative oral carbohydrate may improve patient perioperative glucose metabolism, its effects on the gastric contents and anesthesia operation risk remain controversial. Although most domesticphysicians aware of the importance of reduced fasting time and preoperative oral carbohydrate, but management is not implemented considering the operation safety. Therefore, the similar research will contribute to clinical application.
Objective:The purpose of the present study is to assess the safety of effect of preoperative oral glucose solution through observe the gastric contents and pH as well as anesthesia and operation complicationson. The effects of preoperative oral blood glucose solution on the perioperative glucose, insulin resistance and inflammatory reaction of ptients after gastrointestinal operation were observed.
Methods:48patients received gastrointestinal operation signed informed consent and were randomly divided into the study group (n=23) and the control group (n=25). Patients in study group were given300ml oral administration of25%glucose solution in3hours before operation. Before anesthesia induction, gastric contents were aspirated through nasogastric tube to examine its volume and pH. Serum hsCRP, fasting blood glucose, insulin level and HOMA-IR were detected before operation and in the first morning after operation between both groups.
Results:There were no anesthesia and operation complications in both groups. Patients had similar gastric contents volume(30.88±25.93vs27.94±24.04ml) and the pH value of gastric contents(1.99±0.34vs2.13±0.43). There were no significant differences in serum hsCRP, fasting blood glucose and HOMA-IR of patients in the two groups preoperatively. But on the first postoperative day, fasting blood glucose and HOMA-IR of the patients in the study group were significantly lower than those in the control group (6.51±1.15vs7.49±0.57mmol/L, P=0.038;4.34±1.60vs6.09±2.81, P=0.043), and hsCRP level of the patients in the study group was significantly lower than the control group (40.45±27.02vs80.02±38.98mg/L, P=0.03). On the second postoperative day, hsCRP level of the patients in the study group was significantly lower than the control group(70.33±32.19vs101.12±42.73, P=0.041)
Conclusion:Preoperative oral glucose solution(25%) is safe and feasible, obviously improved blood glucose and insulin resistance after operation, at the same time, alleviated postoperative inflammatory reaction.
Part.4A clinical study of Laparoscopic bariatric surgery in treating modality for
Background:Obesity has seriously affected the health and quality of life, become a important reason that induce the metabolic syndrome and complication of obesity. The recent10years studies show that the effect of conservative treatment on patients with severe obesity is limitied and bariatric surgery is the most effective method in weight control of morbid obesity patients. However, bariatric surgery is at the initial stage in China. There are many problems, such as the operation indication, unsatisfactory operation effect, the problem of postoperative complications and regain obesity, so there are still more research whcih need large sample, multi-center to confirm its effect. Obese patients accompany with multi-system problems, that need to multidisciplinary professional team to follow up and ensure the operation safety and effect. In order to standardize the process of treating obesity surgery in China, the Peking Union Medical College Hospital launched a model of multidisciplinary in treating morbid obese patients.
Objective:To investigate the multidisciplinary modality for obesity treatment and evaluate the safety and long-term efficacy of laparoscopic adjustable gastric banding(LAGB) and laparoscopic sleeve gastrectomy(LSG) on weight loss, inflammation and obesity related metabolic diseases in obesity patients. Comparison effects of two kinds of bariatric surgeries provides the basis in the choice of mode of operation for the Chinese obese patients.
Methods:The clinical and follow-up data of31and14morbidly obese patients, receiving LAGB and LSG respectively in Dept. General Surgery of PUMC hospitM in a multidisciplinary modality from Oct2009to March2014were retrospectively analyzed. The strategy of perioperative and follow-up management was summarized and the safety and long-term efficacy of LAGB and LSG on weight loss and comorbidity were evaluated.
Results:All patients were successfully performed operation, without death case. Mean body weight of the subjects was121.7±22.5kg and mean BMI42.86±6.95kg/m2in LAGB group preoperatively, while mean body weight of the subjects was126.3±38.9kg and mean BMI43.57±10.21kg/m2in LSG group. All patients underwent LAGB and LSG successfully without perioperative mortality. Early postoperative complications included1case(3.2%) in LAGB of systemic inflammatory response syndrome and1case(7.1%) in LSG of incomplete obstruction. Long-term complications included2cases(6.5%) in LAGB of port infection and elevation. Mean body weight and BMI decreased gradually after LAGB and LSG. The mean percentage of excess weight loss(%EWL) at postoperative48months in LAGB group and12months in LSG group were48.0%and89.5%respectively. LSG was more effective in controling weight than LAGB at postoperative12months.%EWL of the group with regular follow-up and good compliance after LAGB was significantly higher than the other group. Complete or partial remission was observed in obesity related metabolic diseases at the last follow-up after LAGB and LSG.
Conclusion:LAGB and LSG are safe and have good long-term efficacy on weight loss, reduce obesity-associated inflammation and improve comorbidity of morbidly obese patients. Better services can be provided for obesity patients in a muhidiseiplinaly modabty. It is important for the patients to follow up regularly after surgery in order to maintain long-term weight loss. LSG has a better effect on weight loss than LAGB
目的：观察高脂饮食诱发肥胖模型,是否引起肠屏障(肠道菌群及肠通透性)的改变,补充n-3多不饱和脂肪酸对高脂饮食导致的肥胖大鼠肠道屏障的影响及减重作用,为将来临床应用提供理论依据。
方法：36只雄性Sprague-Dawley (SD)大鼠随机分为普通饮食组(Control diet, CD,n=10)、高脂饮食组(High-fat diet, HFD, n=10)、CD+n-3PUFAs组(n=7)、HFD+n-3PUFAs组(n=9)。饲养10周后,取大鼠新鲜粪便提取DNA,通过实时定量PCR检测肠道菌群组成。应用ELISA检测血浆中炎症因子水平。应用改良偶氮基质显色鲎试剂法检测门静脉血清内毒素水平。通过乳果糖／甘露醇方法检测肠通透性,Western blot检测小肠粘膜紧密连接蛋白的表达。
结果：HFD组大鼠体重明显高于CD组、CD+n-3PUFAs组和HFD+n-3PUFAs组。HFD组大鼠粪便中厚壁菌门(Firmicutes)和肠杆菌科(Enterobacteriales)含量高于CD组和HFD+n-3PUFAs组大鼠,而拟杆菌门(Bacteroidetes)、双歧杆菌属(Bifidobacterium spp.)及Bacteroidetes与Firmicutes比值低于CD组和HFD+n-3PUFAs组大鼠。CD+n-3PUFAs组大鼠粪便中Bacteroidetes含量高于CD组大鼠。Peaeson相关性分析结果显示Bacteroidetes与Firmicutes比值与体重具有负相关性。HFD组大鼠尿中乳果糖／甘露醇比值高于CD组和HFD+n-3PUFAs组大鼠。CD组和CD+n-3PUFAs组大鼠尿中乳果糖／甘露醇比值无明显差异。HFD组门静脉血浆中内毒素和炎症因子水平高于CD组大鼠和HFD+n-3PUFAs组大鼠。HFD组大鼠大鼠肠粘膜紧密连接蛋白(claudin和occludin)的表达低于CD组大鼠和HFD+n-3PUFAs组大鼠。
结论：高脂饮食导致的肥胖引起肠道菌群改变、肠通透性增加,而补充n-3PUFAs可以部分修复肥胖导致肠道菌群紊乱,降低肠道通透性,减轻炎症因子和内毒素水平,减少体重。
第二部分肥胖症患者血清、皮下及内脏脂肪组织脂肪酸谱测定及与炎症因子、胰岛素抵抗的相关研究
背景：肥胖是体内的异常的脂肪蓄积,脂肪组织分泌多种炎症因子,参与胰岛素抵抗等代谢综合征的形成。然而导致肥胖症患者炎症因子升高的原因未知。研究显示无论是血中还是脂肪组织中脂肪酸谱,均反映了饮食中脂肪酸的摄入及体内的代谢,尤其是脂肪组织中的脂肪酸谱更是反映了长期的脂肪酸摄入情况,而且与代谢综合征、肥胖及炎症因子相关,但有关中国重度肥胖症患者脂肪酸谱的研究较少,特别是肥胖症脂肪组织脂肪酸谱的检测在国外研究较少,国内尚无研究。
目的：检测中国重度肥胖症患者及非肥胖患者血清及脂肪组织中脂肪酸谱、炎症因子水平并分析差异,分析脂肪酸谱与炎症因子及胰岛素抵抗的相关性。材料与方法：选取在北京协和医院接受手术的27例肥胖患者和24例非肥胖患者作为研究对象。通过气相色谱技术检测患者血清、脂肪组织脂肪酸构成,通过产物与底物计算脱氢酶活性：SCD (C16:1n-7/C16:0,C18:1n-9/C18:0)、D6D (C20:3n-6/C18:2n-6)、D5D(C20:4n-6/C20:3n-6),应用ELISA方法检测血清及脂肪组织中炎症因子(hsCRP, TNF-α, IL-6)水平,比较肥胖组与非肥胖组患者脂肪酸谱、脱氢酶活性及炎症因子水平的差异,分析脂肪酸谱与炎症因子及胰岛素抵抗指数(HOMA-IR)的相关性。
结果：肥胖症患者血清中含有更高比例的棕榈酸(C16：0)、油酸(C18：ln-9)、二十碳三烯酸(C20：3n-3),更低比例的亚油酸(C18：2n-6)、γ亚麻酸(C18：3n-6)。肥胖症患者脂肪组织中含有更高比例的C16：0、油酸(C18：1n-9)、丫亚麻酸(C18：3n-6),更低比例的硬脂酸(C18：0)、亚油酸(C18：2n-6)、α-亚麻酸(C18：3n-3)和二十二碳六烯酸(DHA, C22:6n-3)。饱和脂肪酸(Saturated fatty acids, SFAs)和单不饱和脂肪酸(Monounsaturated fatty acids, MUFAs)的含量在肥胖组患者内脏脂肪组织中含量更高,而n-3多不饱和脂肪酸(n-3polyunsaturated fatty acids, n-3PUFAs)和多不饱和脂肪酸(Polyunsaturated fatty acids, PUFAs)的含量更低。肥胖症患者皮下脂肪组织中含有更高比例的C16：0、棕榈油酸(C16:ln-7). C18:1n-9、C18:3n-6,更低比例的C18:0、C18:2n-6、DHA、MUFAs和SFAs。SCD18和D6D的活性在肥胖组脂肪组织中高于非肥胖组。肥胖组患者内脏脂肪组织比皮下脂肪组织含有更多的SFAs及MUFAs。肥胖组患者内脏及皮下脂肪组织中炎症因子水平较高(hsCRP、TNF-α、IL-6)。肥胖组患者内脏脂肪组织中SFAs、MUFAs、SCD18、D6D活性与hsCRP. TNF-α、IL-6水平具有正相关。与hsCRP、TNF-α的含量具有负相关性的是肥胖组患者内脏脂肪中的n-3PUFAs。与胰岛素抵抗(HOMA-IR)呈正相关的是内脏脂肪组织中的SFAs、MUFAs、SCD18、D6D和皮下脂肪组织中的D6D,与胰岛素抵抗(HOMA-IR)呈负相关的是内脏脂肪组织中的PUFAs、n-3PUFAs和皮下脂肪组织中的PUFAs。
结论：肥胖组患者与非肥胖组患者血浆及脂肪组织中脂肪酸谱存在明显的差异。不同部位脂肪组织脂肪酸谱及炎症因子水平的差异显示其不同的代谢活性,脂肪组织内饱和脂肪酸、单不饱和脂肪酸含量、脱氢酶(SCD18、D6D)活性与炎症因子、胰岛素抵抗呈正相关,而多不饱和脂肪酸与炎症因子、胰岛素抵抗呈负相关,这种相关性在肥胖患者特别显著。脂肪酸摄入与体内代谢可能参与肥胖相关炎症及代谢综合征发生。
第三部分术前口服葡萄糖溶液减轻术后胰岛素抵抗及炎症反应研究背景：手术应激导致术后炎症反应及高血糖,增加了术后并发症的风险。传统观念认为延长禁食时间有助于减少术中误吸等并发症。1999年美国麻醉医师协会提出：针对术前需要禁食的病人,在术前2小时仍可进食温和液体,如水或者葡萄糖溶液,并且术前口服葡萄糖溶液已经被欧洲肠外肠内营养与快速康复协会推荐。尽管术前口服葡萄糖溶液可以改善病人术后糖代谢,但对于是否增加胃液量和麻醉手术风险尚存争议。虽然国内大多数医师已意识到减少禁食时间的重要性,但传统常规及考虑到手术安全并未推广实施。由此,需要术前口服葡萄糖溶液的临床研究。目的：1.观察术前胃液量及pH值及麻醉手术并发症评估术前口服葡萄糖溶液的安全性及可行性；2.观察术前口服葡萄糖溶液对胃肠手术后炎症反应、血糖及胰岛素抵抗(Insulin resistance, IR)的影响。
方法：胃肠手术48例患者术前签署知情同意书,随机分研究组23例,对照组25例。研究组术前3h一次性口服25%葡萄糖溶液300ml(75g),比较两组术前胃内容物量、pH值及术后第1天的血清高敏C反应蛋白(high sensitivity C-reactive protein, hsCRP)、空腹血糖、胰岛素水平、胰岛素抵抗指数稳态模型(Homeostasis model assessment-Insulin resistance, HOMA-IR)。
结果：所有病人按计划口服葡萄糖溶液后均无不适主诉,两组均无麻醉及手术并发症。麻醉前两组胃内容物量(30.88±25.93vs27.94±24.04ml)、pH值(1.99±0.34vs2.13±0.43)无明显差异；术前两组hsCRP、血糖、胰岛素水平、HOMA-IR无明显差异。术后第1天研究组空腹血糖、HOMA-IR及hsCRP均明显低于对照组(6.51±1.15vs7.49±0.57mmol/L, P=0.038),(4.34±1.60vs6.09±2.81, P=0.043),(40.45±27.02vs80.02±38.98mg/L, P=0.03),术后第2天研究组hsCRP均明显低于对照组(70.33±32.19vs101.12±42.73,P=0.041)。
结论：术前口服葡萄糖溶液安全可行,可明显改善患者术后应激所致的高血糖及IR、炎症反应。
第四部分腹腔镜减重手术治疗重度肥胖症患者的临床研究研究背景：肥胖症已经严重影响健康及生活质量,是导致代谢综合征和诸多合并症的主要原因。近10年来国内外的研究实践证实减重手术是病态性肥胖症患者获得稳定减重效果的方法,国内减重外科处于起步发展阶段,存在诸多问题和困难,但由于手术适应症及方式选择,手术效果不理想,术后复胖及术后并发症的问题,需要针对中国肥胖症患者大样本、多中心的临床研究证实减重手术的效果。肥胖症患者就诊时合并多系统的问题,需要在术前多学科评估及术后专业团队的随诊才能保证手术安全与效果。为了规范我国肥胖症外科治疗流程,北京协和医院在国内率先开展多学科模式下手术治疗病态性肥胖症患者。
目的：肥胖症综合治疗的多科协作模式腹腔镜可调节胃束带术(Laparoscopic adjustable gastric banding, LAGB)及腹腔镜袖状胃切除术(Laparoscopic sleeve gastrectomy, LSG)的临床减重效果、安全性及对合并症的治疗效果,比较两种手术方式对肥胖症相关炎症及减重效果,为中国肥胖症患者手术方式的选择上提供依据。方法：分析2009年10月至2014年3月多学科模式下北京协和医院基本外科施行LAGB31例及LSG14例病态性肥胖患者临床资料和术后的随访数据。总结在多科协作模式下肥胖症患者的围手术期和术后随访管理流程,观察手术安全性和术后长期减重效果及合并症的改善情况。
结果：全部患者均顺利施行手术,未出现围手术期死亡病例。LAGB组患者术前平均体重121.7±22.5kg,平均体重指数(BMI)42.86±6.95kg/m2。术后48个月平均体重和BMI分别为82.7±12.43kg和32.5±4.64kg/m2,LSG组患者术前平均体重126.3±38.9kg,平均BMI43.57±10.21kg/m2。术后12月平均体重和BMI分别为91.67±51.63kg和30.59±14.98kg/m2。术后LAGB组早期并发症1例全身炎症反应综合征及肺呼吸功能衰竭,远期并发症2例注水泵处皮肤感染、注水泵突出皮肤。LSG组患者有1例因上消化道不全梗阻。术后体重和体质指数逐渐下降,LAGB组患者术后48个月平均额外体重减轻48.0%。规律随诊、依从性良好组额外体重减轻百分比显著高于不规律随诊、依从性差组。LSG组患者术后12个月平均额外体重减轻89.5%。术后12月LSG减重效果优于LAGB。两组患者术后肥胖症相关代谢性疾病均有不同程度改善。
结论：LAGB与LSG安全可靠,有效减轻病态性肥胖症患者体重,减轻炎症、改善合并症,多科协作模式可优化疾病诊治流程,保障围手术期安全及疗效更优。术后规律随诊对获得长期减重效果有重要影响。LSG的减重效果优于LAGB
Part.1Effect of obesity and intervention of n-3polyunsaturatedfatty acids on intestinal barrier
Background:Growing evidences showed that an important characteristic of obesity is low-grade inflammation. Changes in intestinal barrier, which included the gut microbiota dysbiosis, increased intestinal permeability and elevated endotoxin in blood, thereby triggering the inflammatory response. N-3polyunsaturated fatty acids were used for the treatment and prevention of cardiovascular disease, could reduce the body weight of obese patients, improve the metabolic syndrome. Our previous study showed that there were less contents of n-3PUFAs in the obese patients than non-obese patients. Supplementation of n-3PUFAs can improve the intestinal permeability in the models of inflammatory bowel disease and partial hepatectomy animal, but the effect of n-3PUFAs on the intestinal barrier impaered by high fat died is less reported.
Objective:The aim of the present study is to investigate the effect of high fat diet incduced obeisty on the the intestinal barrier and protection effects of supplementation with n-3polyunsaturated fatty acids, which provides theoretical basis for clinical application in the future.
Methods:Thirty-six Sprague-Dawley rats were divided into four groups randomly, fed control diet(CD), high-fat diet(HFD), control diet supplemented with n-3polyunsaturated fatty acids and high-fat diet supplemented with n-3polyunsaturated fatty acids respectively. Fresh fecal samples were collected to analyze the gut microbiota after10weeks feeding. DNA was exacted from the fresh fecal samples. Real-time PCR was used to detect the composition of the gut microbiota. The levels of hsCRP, TNF-α and IL-6in plasma were measured through ELISA, respectively. The endotoxin levels were detected though modified azo chromogenic substrate limulus amebocyte lysate assay. Intestinal permeability(lactose/mannitol ratio in the urine, L/M)was determined on the end of this study. Western blotting method was used to detect tight junction protein of intestinal mucosa.
Results:The HFD induced a more increase in the body weight than the CD, CD+n-3PUFAs, HFD+n-3PUFAs groups. There were more contents of the Firmicutes, Enterobacteriales, and less contents of Bacteroidetes, Bifidobacterium spp. and ratios of Bacteroidetes to Firmicutes in the fecal of the rats from HFD group compared to the CD and HFD+n-3PUFAs groups. There were more contents of the Bacteroidetes in the fecal of the rats from CD+n-3PUFAs group compared to the CD group. The Pearson's correlation coefficient shows that there is a negative correlation between the body weight and the ratios of Bacteroidetes-to-Firmicutes. Intestinal permeability(L/M) was increased significantly in HFD group compared to CD and HFD+n-3PUFAs groups, but there is no significant difference in the L/M ratio between the CD and CD+n-3PUFAs groups. The endotoxin and inflammatory factors in plasma in portal vein from rats of HFD group were higher than CD and HFD+n-3PUFAs groups, but expression of claudin and occludin in intestinal mucosa of HFD group were lower than CD and HFD+n-3PUFAs groups.
Conclusion:HFD-induced obesity changed the gut microbiota and increased intestinal permeability. Supplement with n-3PUFAs could counteract these gut dysbiosis and reduce the intestinal permeability as well as improve inflammatory factors and the body weight.
Part.2Fatty acid composition and estimated desaturase activities in visceral and subcutaneous adipose tissues of morbidly obese patients, and are associated with inflammatory factors and insulin resistance
Background:Obesity is characterized by abnormal fat storage and low-grade inflammation in adipose tissue and serum. Adipose tissue from obese patients abnormally secretes abundant inflammatory factors that promote the insulin resistance and metabolic syndrome. However, the cause of elevated infalmmatory factors is still unknown. Previous studies showed that fatty acid composition in both blood and adipose tissue reflected the diet intake of fatty acid, and was associated with metabolic syndrome, obesity and inflammatory factors. But the studies on the fatty acid composition in serum and adipose tissue from Chinese morbidly obese patiens are limited.
Objective:The objective of this study was to investigate the differences in fatty acid composition and estimates desaturase activities in visceral and subcutaneous adipose tissue between morbidity obese and non-obese subjects, and to investigate the correlation between fatty acid composition and desaturase activities with obesity-associated inflammatory factors, such as high sensitivity C-reactive protein (hsCRP), tumour necrosis factor alpha (TNF-a) and interleukin-6(IL-6) in adipose tissue, and insulin resistance.
Methods:Visceral and subcutaneous adipose tissues were obtained from27obese subjects with metabolic syndrome or type2diabetes and24non-obese subjects. Analysis of fatty acid composition in adipose tissue was performed using gas chromatography. The desaturase activities were estimated from the ratio of product to precursor:SCD (C16:ln-7/C16:0and C18:ln-9/C18:0), D6D (C20:3n-6/C18:2n-6) and D5D (C20:4n-6/C20:3n-6). The levels of hsCRP, TNF-a and IL-6in adipose tissue and serum were measured through ELISA, respectively. The differences in fatty acid composition, estimated desaturase activities and inflammatory factors levels between both groups were compared, and the correlations between fatty acid composition and inflammatory factors levels, HOMA-IR were analyzed.
ResultscObese subjects had higher levels of oleic (C18:ln-9), palmitic (C16:0), palmitoleic (C16:ln-7) and dihomo--y-linolenic (C18:3n6) acids in both visceral and subcutaneous adipose tissue, and lower levels of stearic acid (C18:0), linoleic acid (C18:2n6) and C18:3n3than the non-obese controls. There were more oleic acid, saturated fatty acids and monounsaturated fatty acids in visceral adipose tissue of obese group, more saturated fatty acids in visceral adipose tissue of non-obese group,compared to subcutaneous adipose tissue. The levels of hsCRP,TNF-a, IL-6and the estimated activities of SCD18and D6D were significantly higher in visceral and subcutaneous adipose tissue of the obese subjects. Also, we found that there were more hsCRP and IL-6in the visceral adipose tissue than in the subcutaneous adipose tissue. hsCRP, TNF-a and IL-6in adipose tissue were positively associated with the cotents of SFAs, MUFAs and estimated activities of SCD18and D6D. hsCRP in adipose tissue was negatively associated with the cotents of n-3PUFAs. HOMA-IR was positively associated with the cotents of SFAs, MUFAs, estimated activities of SCD18and D6D in visceral adipose tissue and estimated activities of D6D in subcutaneous adipose tissue, while it was negatively associated with the cotents of PUFAs and n-3PUFAs in visceral adipose tissue and n-3PUFAs in subcutaneous adipose tissue.
Conclusion:There were differences in fatty acid composition and estimated desaturase activities of adipose tissue between obese and non-obese subjects. These difference reflected the a long period of fatty acid intake and metabolism in both groups. Differsence fatty acid composition and inflammtory facors levels between the visceral and subcutaneous adipose tissue showed the discrepant metabolic activities of different fat depots. The high correlations of contents of some fatty aicd and desaturases activities with hsCRP, TNF-a, IL-6in adipose tissue and HOMA-IR suggest that fatty acid intake and metabolsim may play a role in the development of chronic inflammation commonly found in morbid obesity and metabolic syndrome.
Part.3Preoperative oral carbohydrate alleviates postoperative insulin resistance and inflammatory reaction
Background:Stress of operation induces postoperative hyperglycemia and inflammatory response that increases the risk of postoperative complications. Long preoperative fasting has been a standard practice for patients undergoing elective surgery to avoid vomiting and pulmonary aspiration during anesthesia induction.In1999, the American Society of Anesthesiologists (ASA) issued a practice guideline for preoperative fasting in which patients (except those with delayed gastric emptying) are allowed to have clear fluids such as water, carbonated beverages until2h before surgery. Preoperative oral carbohydrate administration for adult patients has been recommended by European Society for Parenteral and Enteral Nutrition and Enhanced Recovery After Surgery. Although preoperative oral carbohydrate may improve patient perioperative glucose metabolism, its effects on the gastric contents and anesthesia operation risk remain controversial. Although most domesticphysicians aware of the importance of reduced fasting time and preoperative oral carbohydrate, but management is not implemented considering the operation safety. Therefore, the similar research will contribute to clinical application.
Objective:The purpose of the present study is to assess the safety of effect of preoperative oral glucose solution through observe the gastric contents and pH as well as anesthesia and operation complicationson. The effects of preoperative oral blood glucose solution on the perioperative glucose, insulin resistance and inflammatory reaction of ptients after gastrointestinal operation were observed.
Methods:48patients received gastrointestinal operation signed informed consent and were randomly divided into the study group (n=23) and the control group (n=25). Patients in study group were given300ml oral administration of25%glucose solution in3hours before operation. Before anesthesia induction, gastric contents were aspirated through nasogastric tube to examine its volume and pH. Serum hsCRP, fasting blood glucose, insulin level and HOMA-IR were detected before operation and in the first morning after operation between both groups.
Results:There were no anesthesia and operation complications in both groups. Patients had similar gastric contents volume(30.88±25.93vs27.94±24.04ml) and the pH value of gastric contents(1.99±0.34vs2.13±0.43). There were no significant differences in serum hsCRP, fasting blood glucose and HOMA-IR of patients in the two groups preoperatively. But on the first postoperative day, fasting blood glucose and HOMA-IR of the patients in the study group were significantly lower than those in the control group (6.51±1.15vs7.49±0.57mmol/L, P=0.038;4.34±1.60vs6.09±2.81, P=0.043), and hsCRP level of the patients in the study group was significantly lower than the control group (40.45±27.02vs80.02±38.98mg/L, P=0.03). On the second postoperative day, hsCRP level of the patients in the study group was significantly lower than the control group(70.33±32.19vs101.12±42.73, P=0.041)
Conclusion:Preoperative oral glucose solution(25%) is safe and feasible, obviously improved blood glucose and insulin resistance after operation, at the same time, alleviated postoperative inflammatory reaction.
Part.4A clinical study of Laparoscopic bariatric surgery in treating modality for
Background:Obesity has seriously affected the health and quality of life, become a important reason that induce the metabolic syndrome and complication of obesity. The recent10years studies show that the effect of conservative treatment on patients with severe obesity is limitied and bariatric surgery is the most effective method in weight control of morbid obesity patients. However, bariatric surgery is at the initial stage in China. There are many problems, such as the operation indication, unsatisfactory operation effect, the problem of postoperative complications and regain obesity, so there are still more research whcih need large sample, multi-center to confirm its effect. Obese patients accompany with multi-system problems, that need to multidisciplinary professional team to follow up and ensure the operation safety and effect. In order to standardize the process of treating obesity surgery in China, the Peking Union Medical College Hospital launched a model of multidisciplinary in treating morbid obese patients.
Objective:To investigate the multidisciplinary modality for obesity treatment and evaluate the safety and long-term efficacy of laparoscopic adjustable gastric banding(LAGB) and laparoscopic sleeve gastrectomy(LSG) on weight loss, inflammation and obesity related metabolic diseases in obesity patients. Comparison effects of two kinds of bariatric surgeries provides the basis in the choice of mode of operation for the Chinese obese patients.
Methods:The clinical and follow-up data of31and14morbidly obese patients, receiving LAGB and LSG respectively in Dept. General Surgery of PUMC hospitM in a multidisciplinary modality from Oct2009to March2014were retrospectively analyzed. The strategy of perioperative and follow-up management was summarized and the safety and long-term efficacy of LAGB and LSG on weight loss and comorbidity were evaluated.
Results:All patients were successfully performed operation, without death case. Mean body weight of the subjects was121.7±22.5kg and mean BMI42.86±6.95kg/m2in LAGB group preoperatively, while mean body weight of the subjects was126.3±38.9kg and mean BMI43.57±10.21kg/m2in LSG group. All patients underwent LAGB and LSG successfully without perioperative mortality. Early postoperative complications included1case(3.2%) in LAGB of systemic inflammatory response syndrome and1case(7.1%) in LSG of incomplete obstruction. Long-term complications included2cases(6.5%) in LAGB of port infection and elevation. Mean body weight and BMI decreased gradually after LAGB and LSG. The mean percentage of excess weight loss(%EWL) at postoperative48months in LAGB group and12months in LSG group were48.0%and89.5%respectively. LSG was more effective in controling weight than LAGB at postoperative12months.%EWL of the group with regular follow-up and good compliance after LAGB was significantly higher than the other group. Complete or partial remission was observed in obesity related metabolic diseases at the last follow-up after LAGB and LSG.
Conclusion:LAGB and LSG are safe and have good long-term efficacy on weight loss, reduce obesity-associated inflammation and improve comorbidity of morbidly obese patients. Better services can be provided for obesity patients in a muhidiseiplinaly modabty. It is important for the patients to follow up regularly after surgery in order to maintain long-term weight loss. LSG has a better effect on weight loss than LAGB
引文
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