切换至 "中华医学电子期刊资源库"
高级检索
中华肥胖与代谢病电子杂志

中华肥胖与代谢病电子杂志 ›› 2022, Vol. 08 ›› Issue (03) : 181 -190. doi: 10.3877/cma.j.issn.2095-9605.2022.03.007

循证医学

腹腔镜袖状胃切除术治疗肥胖患者呼吸睡眠暂停综合征的Meta分析
张家鸣1, 孙晓芳2,†()   
  1. 1. 225001　扬州，扬州大学护理学院·公共卫生学院
    2. 225001　扬州，扬州大学护理学院·公共卫生学院；江苏省苏北人民医院内分泌科
  • 收稿日期:2022-07-22 出版日期:2022-08-30
  • 通信作者: 孙晓芳

The effect of laparoscopic sleeve gastrectomy on OSAHS in obesity patients: a Meta-Analysis

Jiaming Zhang1, Xiaofang Sun2,†()   

  1. 1. College of Nursing and Public Health, Yangzhou University, Yangzhou 225009, China
    2. College of Nursing and Public Health, Yangzhou University, Yangzhou 225009, China; Northern Jiangsu People’s Hospital, Yangzhou 225001, China
  • Received:2022-07-22 Published:2022-08-30
  • Corresponding author: Xiaofang Sun
全文 ( ) 下载PDF ( ) 导出引用
引用本文：

张家鸣, 孙晓芳. 腹腔镜袖状胃切除术治疗肥胖患者呼吸睡眠暂停综合征的Meta分析[J]. 中华肥胖与代谢病电子杂志, 2022, 08(03): 181-190.

Jiaming Zhang, Xiaofang Sun. The effect of laparoscopic sleeve gastrectomy on OSAHS in obesity patients: a Meta-Analysis[J]. Chinese Journal of Obesity and Metabolic Diseases(Electronic Edition), 2022, 08(03): 181-190.

目的

荟萃分析腹腔镜袖状胃切除术（LSG）对肥胖性阻塞性睡眠呼吸暂停低通气综合征（OSAHS）患者夜间低氧血症的影响。为肥胖患者OSAHS的治疗方案提供循证学依据。

方法

从1980年1月到2022年6月计算机检索数据库：PubMed，Embase，Cochrane Library，Web of Science，CNKI，万方数据库，维普数据库，CBM数据库。严格按照纳入与排除标准，检索以LSG手术为主要干预手段治疗肥胖患者OSAHS并以多导睡眠监测为结局指标的高质量临床研究。睡眠呼吸暂停低通气的严重程度以呼吸暂停和低通气指数（AHI）、睡眠期间最低血氧浓度、睡眠效率、爱泼沃斯嗜睡量表（ESS）评分作为评价标准，减重的效果以BMI、颈围为评价标准。提取筛选后文献的数据，并进行质量评估。

结果

纳入了7项合格研究，共316例患者，均为前后自我对照研究，纳入研究的异质性较高。LSG手术对以下指标都有明显改善且具有统计学意义，BMI（MD=13.36，95%CI：[11.55，15.18]，P<0.05），呼吸暂停低通气指数（AHI）（MD=24.54，95% CI：[15.44，33.73]，P<0.05)，Epworth嗜睡量表评分（ESS）（MD=5.17，95%CI：[1.99，8.35]，P<0.05），颈围（MD=5.65，95%CI：[4.52，6.78]，P<0.05），最低血氧饱和度（MinSaO2）（MD=–13.95，95%CI：[–22.61，–5.29]，P<0.05），快速眼动（REM）睡眠占总睡眠时间百分比（MD=–2.70，95% CI：[–4.37，–1.02]，P<0.05）。对睡眠效率（MD=–6.30，95% CI：[–12.88，0.28]，P=0.06）无明显影响。

结论

LSG在肥胖患者呼吸睡眠暂停综合征的治疗中具有良好的临床效果。然而，由于纳入文献的质量和数量有限，需要更多大样本和多中心的随机对照试验进一步验证。

关键词: 腹腔镜袖状胃切除术, 减重手术, 肥胖, 阻塞性睡眠呼吸暂停症, 腹腔镜检查, 荟萃分析
Objective

To evaluate the effectiveness of laparoscopic sleeve gastrectomy (LSG) in obese patients obstructive sleep apnea and hypopnea syndrome (OSAHS). To provide an evidence-based basis for LSG treatment of obesity OSAHS.

Methods

Computer search databases from January 1980 to June 2022: PubMed, Embase, Cochrane Library, Web of Science, CNKI, Wanfang Database, VIP Database, Chinese BioMedical Literature Database. We searched for high-quality clinical studies on obesity OSAHS patients, LSG as an intervention, and postoperative polysomnography monitoring as an outcome indicator, strictly according to the inclusion and exclusion criteria. Data extraction and assessment of publication bias were performed for the included literature. The postoperative apnea-hypopnea index (AHI), minimum SpO2 during sleep, sleep efficiency, and Epworth Sleepiness Scale (ESS) was used to objectively evaluate the severity of sleep apnea and hypoventilation. Body Mass Index (BMI) and neck circumference were used as indicators to objectively evaluate weight loss. They were compared with their preoperative baseline data. Forest plots showed a large heterogeneity among studies, which was mainly attributed to the small number of included literature and the fact that they were all owned before and after controlled studies.

Results

A total of 7 studies were included in 316 patients with obesity OSAHS and with a high risk of migration. The results of this meta-analysis showed that LSG has significant and statistically significant improvements in all of the following indicators, BMI (MD=13.36, 95%CI: [11.55, 15.18], P<0.05), apnea hypoventilation index (AHI)(MD=24.54, 95%CI: [15.44, 33.73], P<0.05) , minimum oxygen saturation (MinSaO2) (MD=–13.95, 95%CI: [–22.61, –5.29], P<0.05) , rapid eye movement (REM) sleep as a percentage of total sleep time (MD=–2.70, 95% CI: [–4.37, –1.02], P<0.05), Epworth Sleepiness Scale score (ESS) (MD=5.17, 95%CI: [1.99, 8.35], P<0.05) and neck circumference (MD=5.65, 95%CI: [4.52, 6.78], P<0.05).There was no significant effect on sleep efficiency (MD=–6.30, 95%CI:[–12.88, 0.28], P=0.06).

Conclusions

LSG has significant therapeutic effects on obesity and OSAHS in obese OSAHS patients, but further observation is needed for the long-term efficacy of this operation.

Key words: Laparoscopic sleeve gastrectomy, Bariatric surgery, Obesity, Obstructive sleep apnea-hypopnea syndrome, Meta-analysis
图1 通过搜索和选择过程检索的研究的PRISMA流程图
表1 纳入研究的特点
作者及发表年份 国家 研究类型 样本量 随访时间（月） BMI（kg/m2） AHI（events/h） REM/% NadirSaO2/% ESS SSE 颈围
术前 术后 术前 术后 术前 术后 术前 术后 术前 术后 术前 术后 术前 术后
艾克拜尔et al. 2020 中国 前瞻性 74 12 43±6 28±3 30±19 6±4 NS NS 64.9±11.3 88±3.1 19.4±2.6 9.2±1.5 NS NS 42.9±3 36.5±1.4
H.Shaarawy et al., 2015 埃及 回顾性 22 12 48.2±7.3 35.9±4.8 55.8±8.3 12.8±11.3 20.4±2.9 22.4±1.9 67.2±11.3 92.2±5.3 16.8±6.8 10.2±4.5 69.4±3.25 75.4±6.25 38.2±3.6 32.2±4.6
Suliman et al., 2015 埃及 回顾性 20 8.25±0.96 60.5±8.9 41.9±5.9 18（8.2-42） 10(3-22) NS NS 82.35±6.44 87.10±4.78 5.4±2.54 2.7±1.5 83.75±7.18 90.35±3.66 42.05±2.87 38.6±2.76
Salmanet al., 2019 埃及 前瞻性 79 12 46.23±3.8 34.2±2.7 27.3±12.2 14.0±9.8 NS NS NS NS 9.2±3.6 5.0±3.0 NS NS 45.1±2.6 38.24±2.7
Timmerman et al., 2019 法国 前瞻性 36 9.9±6.1 47.4±8.4 36.3±7.1 45.8±25.6 11.3±11.9 14.2±6.4 16.3±7.4 NS NS 7.2±5.0 3.3±3.4 NS NS 43.9±3.9 40.2±3.7
Kara et al., 2020 土耳其 前瞻性 31 12 49.8±8.5 33.2±8.2 36.1±27 10.3±11.8 14.0±6.3 18.9±5.8 74.3±12.1 79.2±14.7 5.1±3.7 1.6±1.6 NS NS 44.4±4.2 37.4±4.0
Yufei Chen et al., 2021 中国 回顾性 67 9.7±2.8 42.6±7.7 31.9 ± 5.9 31.9 ± 28.6 13.3 ± 15.8 NS NS 79.0 (63.0–83.0) 87.0 (82.0–90.0) NS NS NS NS NS NS
表2 每项纳入研究的偏倚风险
条目 研究
艾克拜尔et al., 2020 H.Shaarawy et al., 2015 Suliman et al., 2015 Salman et al., 2019 Timmerman et al., 2019 Kara et al., 2020 Yufei Chen et al., 2021
1.是否清晰地说明了研究的假设、目的和目标？ 1 1 1 1 1 1 1
2.是否描述了患者特点？ 1 1 1 1 1 1 1
3.是否在多中心收集病例？ 0 0 0 1 0 0 0
4.研究纳入标准和排除标准是否明确合理？ 1 1 1 1 1 1 1
5.患者的纳入是否连续？ 0 0 0 0 1 0 0
6.患者的病情是否一致？ 1 1 1 1 1 1 1
7.是否清楚地描述了主要的干预措施？ 1 1 0 0 0 0 1
8.是否明确描述了联合干预措施？ 1 0 0 0 0 0 1
9.是否事先确定研究要测量的结局？ 1 1 1 1 1 1 1
10.是否应用合理的客观和（或）主观方法测量了相关结局指标？ 1 1 1 1 1 1 1
11.干预前后是否均测量了结局指标？ 1 1 1 1 1 1 1
12.是否应用了合理的统计学检验来评价相关结局指标？ 1 1 1 1 1 1 1
13.是否报告了随访时间？ 1 1 1 1 1 1 1
14.是否报告了失访情况？ 1 1 1 1 1 1 1
15.是否在相关的结局指标的数据分析中提供了随机变量估计？ 1 1 1 1 1 1 1
16.是否报告了干预相关的不良事件？ 1 1 0 1 0 1 1
17.研究的结果是否支持其结论？ 1 1 1 1 1 1 1
18.是否说明了研究的利益冲突和支持来源？ 1 1 1 1 1 1 1
19.该研究是否为前瞻性研究？ 0 1 1 1 0 1 0
20.是否对结局评价人员施盲？ 0 0 0 0 0 0 0
总分 16 16 14 16 14 15 16
图2 肥胖型OSAHS患者LSG手术前后BMI水平比较的Meta分析
图3 肥胖型OSAHS患者LSG手术前后AHI水平比较的Meta分析
图4 肥胖型OSAHS患者LSG手术前后MinSaO2水平比较的Meta分析
图5 肥胖型OSAHS患者LSG手术前后快速眼动睡眠时间占总睡眠时间百分比比较的Meta分析
图6 肥胖型OSAHS患者LSG手术前后睡眠效率比较的Meta分析
图7 肥胖型OSAHS患者LSG手术前后ESS评分比较的Meta分析
图8 肥胖型OSAHS患者LSG手术前后颈围比较的Meta分析
图9 报道BMI文献的漏斗图
图10 报道AHI文献的漏斗图
图11 报道MinSaO2文献的漏斗图
图12 报道ESS评分文献的漏斗图
图13 报道颈围文献的漏斗图
[1]
Chi L, Comyn FL, Mitra N, et al. Identification of craniofacial risk factors for obstructive sleep apnoea using three-dimensional MRI [J]. The European respiratory journal, 2011, 38(2): 348-358.
[2]
Sung CM, Tan SN, Shin MH, et al. The Site of Airway Collapse in Sleep Apnea, Its Associations with Disease Severity and Obesity, and Implications for Mechanical Interventions [J]. Am J Respir Crit Care Med, 2021, 204(1): 103-106.
[3]
Dixon JB, Schachter LM, O'brien PE. Polysomnography before and after weight loss in obese patients with severe sleep apnea [J]. International journal of obesity (2005), 2005, 29(9): 1048-1054.
[4]
Beamish AJ. Comment on: is laparoscopic sleeve gastrectomy safer than laparoscopic gastric bypass? A comparison of 30-day complications using the MBSAQIP data registry [J]. Surgery for obesity and related diseases: official journal of the American Society for Bariatric Surgery, 2018, 14(3): 270.
[5]
Wu C, Wang FG, Yan WM, et al. Clinical Outcomes of Sleeve Gastrectomy Versus Roux-En-Y Gastric Bypass After Failed Adjustable Gastric Banding [J]. Obes Surg, 2019, 29(10): 3252-3263.
[6]
中华医学会外科学分会甲状腺及代谢外科学组，中国医师协会外科医师分会肥胖和糖尿病外科医师委员会. 中国肥胖及2型糖尿病外科治疗指南(2019版) [J]. 中国实用外科杂志, 2019, 39(4): 301-306.
[7]
Ashrafian Hutan, Toma Tania, Rowland Simon P, et al. Bariatric surgery or non-surgical weight loss for obstructive sleep apnoea? A systematic review and comparison of meta-analyses [J]. Obesity surgery, 2015, 25(7): 1239-1250.
[8]
Greenburg DL, Lettieri CJ, Eliasson AH. Effects of surgical weight loss on measures of obstructive sleep apnea: a meta-analysis [J]. Am J Med, 2009, 122(6): 535-542.
[9]
Wong Ai-Ming, Barnes Hayley N., Joosten Simon A., et al. The effect of surgical weight loss on obstructive sleep apnoea: A systematic review and meta-analysis [J]. Sleep Medicine Reviews, 2018, 42: 85-99.
[10]
Stewart LA, Clarke M, Rovers M, et al. Preferred Reporting Items for Systematic Review and Meta-Analyses of individual participant data: the PRISMA-IPD Statement [J]. Jama, 2015, 313(16): 1657-1665.
[11]
罗德惠，万翔，刘际明, 等. 如何实现从样本量、中位数、极值或四分位数到均数与标准差的转换 [J]. 中国循证医学杂志, 2017, 17(11): 1350-1356.
[12]
Moga Carmen, Guo Bing, Schopflocher Donald Peter, et al. Development of a quality appraisal tool for case series studies using a modified delphi technique: methodology paper [M]. Institute of Health Economics, 2012.
[13]
Chen Y, Chen L, Ye L, et al. Association of metabolic syndrome with prevalence of obstructive sleep apnea and remission after sleeve gastrectomy [J]. Front Physiol, 2021, 12: 650260.
[14]
Kara BY, Kalcan S, Ozyurt S, et al. Weight loss as the first-line therapy in patients with severe obesity and obstructive sleep apnea syndrome: the role of laparoscopic sleeve gastrectomy [J]. Obesity Surgery, 2021, 31(3): 1082-1091.
[15]
Salman Mohamed Abdalla, Othman Basem, Salman Ahmed Abdallah, et al. Improvement of obstructive sleep apnea–hypopnea syndrome in morbidly obese patients undergoing laparoscopic sleeve gastrectomy: prospective study [J]. Bariatric Surgical Practice and Patient Care, 2020, 15(3): 131-139.
[16]
Shaarawy H, Sarhan Abdelrahman, El Hawary A. Assessment of the effect of bariatric surgery on severe obstructive sleep apnea patients not tolerating CPAP therapy [J]. Egyptian Journal of Chest Diseases and Tuberculosis, 2016, 65(3): 661-666.
[17]
Suliman Lucy Abdel Mabood, Abdalla Dina Abouelkheir. Does sleeve gastrectomy improve obstructive sleep apnea? [J]. Egyptian Journal of Chest Diseases and Tuberculosis, 2016, 65(2): 505-510.
[18]
Timmerman M, Basille D, Basille-Fantinato A, et al. Short-term assessment of obstructive sleep apnea syndrome remission rate after sleeve gastrectomy: a cohort study [J]. Obes Surg, 2019, 29(11): 3690-3697.
[19]
艾克拜尔·艾力，阿巴伯克力·乌斯曼，皮尔地瓦斯·麦麦提玉素甫, 等. 腹腔镜袖状胃切除术治疗肥胖症合并阻塞性睡眠呼吸暂停综合征的临床疗效 [J]. 中华消化外科杂志, 2020, 19(11).
[20]
Muscogiuri G, Barrea L, Annunziata G, et al. Obesity and sleep disturbance: the chicken or the egg? [J]. Crit Rev Food Sci Nutr, 2019, 59(13): 2158-2165.
[21]
Lee Y, Doumouras AG, Yu J, et al. Laparoscopic sleeve gastrectomy versus laparoscopic roux-en-y gastric bypass: a systematic review and meta-analysis of weight loss, comorbidities, and biochemical outcomes from randomized controlled trials [J]. Annals of surgery, 2021, 273(1): 66-74.
[22]
Ahbab S, Ataoğlu HE, Tuna M, et al. Neck circumference, metabolic syndrome and obstructive sleep apnea syndrome; evaluation of possible linkage [J]. Med Sci Monit, 2013, 19: 111-117.
[23]
Cielo CM, Keenan BT, Wiemken A, et al. Neck fat and obstructive sleep apnea in obese adolescents [J]. Sleep, 2021, 44(11): 1-7.
[24]
Zhang X, Zhu C, Gao J, et al. Gender difference in the relationship between serum uric acid reduction and improvement in body fat distribution after laparoscopic sleeve gastrectomy in Chinese obese patients: a 6-month follow-up [J]. Lipids in health and disease, 2018, 17(1): 288.
[25]
Jordan AS, Mcsharry DG, Malhotra A. Adult obstructive sleep apnoea [J]. Lancet (London, England), 2014, 383(9918): 736-747.
[26]
Kuna ST, Reboussin DM, Strotmeyer ES, et al. Effects of weight loss on obstructive sleep apnea severity. ten-year results of the sleep AHEAD study [J]. American journal of respiratory and critical care medicine, 2021, 203(2): 221-229.
[27]
Veasey SC, Rosen IM. Obstructive sleep apnea in adults [J]. N Engl J Med, 2019, 380(15): 1442-1449.
[28]
Hultén LM, Levin M. The role of hypoxia in atherosclerosis [J]. Curr Opin Lipidol, 2009, 20(5): 409-414.
[29]
Murphy AM, Thomas A, Crinion SJ, et al. Intermittent hypoxia in obstructive sleep apnoea mediates insulin resistance through adipose tissue inflammation [J]. The European respiratory journal, 2017, 49(4).
[30]
Westerterp-Plantenga MS. Sleep, circadian rhythm and body weight: parallel developments [J]. The Proceedings of the Nutrition Society, 2016, 75(4): 431-439.
[31]
Yılmaz Kara B, Kalcan S, Özyurt S, et al. Weight loss as the first-line therapy in patients with severe obesity and obstructive sleep apnea syndrome: the role of laparoscopic sleeve gastrectomy [J]. Obesity surgery, 2021, 31(3): 1082-1091.
[32]
Naiman R. Dreamless: the silent epidemic of REM sleep loss [J]. Annals of the New York Academy of Sciences, 2017, 1406(1): 77-85.
[33]
Guo Q, Song WD, Li W, et al. Weighted Epworth sleepiness scale predicted the apnea-hypopnea index better [J]. Respiratory research, 2020, 21(1): 147.
[34]
Ghiasi F, Bagheri Ghaleh A, Salami, et al. Effects of laparoscopic sleeve gastrectomy and roux-en-y gastric bypass on the improvement of sleep quality, daytime sleepiness, and obstructive sleep apnea in a six-month follow-up [J]. Tanaffos, 2020, 19(1): 50-59.
[35]
Ramos AR, Weng J, Wallace DM, et al. Sleep patterns and hypertension using actigraphy in the hispanic community health study/study of latinos [J]. Chest, 2018, 153(1): 87-93.
[36]
Shan Z, Ma H, Xie M, et al. Sleep duration and risk of type 2 diabetes: a meta-analysis of prospective studies [J]. Diabetes care, 2015, 38(3): 529-537.
[37]
Liu Y, Wheaton AG, Chapman DP, et al. Prevalence of healthy sleep duration among Adults--United States, 2014 [J]. MMWR Morbidity and mortality weekly report, 2016, 65(6): 137-141.
[38]
Sperry SD, Scully ID, Gramzow RH, et al. Sleep duration and waist circumference in adults: a meta-analysis [J]. Sleep, 2015, 38(8): 1269-1276.
[39]
Meek CL, Lewis HB, Reimann F, et al. The effect of bariatric surgery on gastrointestinal and pancreatic peptide hormones [J]. Peptides, 2016, 77: 28-37.
[40]
Kirwan JP, Aminian A, Kashyap SR, et al. Bariatric surgery in obese patients with type 1 diabetes [J]. Diabetes care, 2016, 39(6): 941-948.
[1] 蒋敏, 刘馨竹, 李大伟, 冯柏塨, 申传安. 点阵CO2激光联合其他非手术方式治疗痤疮瘢痕有效性的网状荟萃分析[J]. 中华损伤与修复杂志(电子版), 2024, 19(05): 429-439.
[2] 陈嘉婷, 杜美君, 石冰, 黄汉尧. 母体系统性疾病对新生儿唇腭裂发生的影响[J]. 中华口腔医学研究杂志(电子版), 2024, 18(04): 262-268.
[3] 孟令凯, 李大勇, 王宁, 王桂明, 张炳南, 李若彤, 潘立峰. 袖状胃切除术对肥胖伴2型糖尿病大鼠的作用及机制研究[J]. 中华普外科手术学杂志(电子版), 2024, 18(06): 638-642.
[4] 李猛, 姜腊, 董磊, 吴情, 贾犇黎. 腹腔镜胃袖状切除术治疗肥胖合并2型糖尿病及脂肪胰的临床研究[J]. 中华普外科手术学杂志(电子版), 2024, 18(05): 554-557.
[5] 杨波, 胡旭, 何金艳, 谢铭. 腹腔镜袖状胃切除术管胃固定研究现状[J]. 中华普外科手术学杂志(电子版), 2024, 18(04): 452-455.
[6] 吉顺富, 汤晓燕, 徐进. 腹腔镜近端胃癌根治术中拓展胃后间隙在肥胖患者中的应用研究[J]. 中华普外科手术学杂志(电子版), 2024, 18(04): 393-396.
[7] 刘超凡, 王文越, 杨珵璨, 朱冬梓, 王兵. 胃袖状切除术上调循环Nrg4浓度抑制肝脏脂肪酸合成改善肥胖小鼠肝脏脂肪变性[J]. 中华普外科手术学杂志(电子版), 2024, 18(02): 133-136.
[8] 赵帅, 王伟, 李瑞奇, 周家杰, 王道荣. 3D腹腔镜下袖状胃切除术治疗肥胖合并2型糖尿病的临床疗效及影响因素分析[J]. 中华普外科手术学杂志(电子版), 2024, 18(02): 146-149.
[9] 李海亮, 俞云, 张星星, 陈管洁, 刘玲, 谢剑锋, 常炜. 经鼻高流量氧疗在危重症患者气管插管过程中效果的荟萃分析[J]. 中华重症医学电子杂志, 2024, 10(03): 227-235.
[10] 唐小久, 胡曼, 许必君, 肖亚. 肥胖合并胃食管反流病患者严重程度与其焦虑抑郁及营养状态的相关性研究[J]. 中华消化病与影像杂志(电子版), 2024, 14(04): 360-364.
[11] 王星, 陈园, 热孜万古丽·乌斯曼, 郭艳英. T2DM、Obesity、NASH、PCOS共同致病因素相关的分子机制[J]. 中华临床医师杂志(电子版), 2024, 18(05): 481-490.
[12] 崔磊, 徐东升. 减重手术治疗肥胖患者胰岛素抵抗的研究进展[J]. 中华肥胖与代谢病电子杂志, 2024, 10(02): 127-132.
[13] 邢颖, 闫文貌. 单孔腹腔镜袖状胃切除术发展现状[J]. 中华肥胖与代谢病电子杂志, 2024, 10(02): 133-137.
[14] 冯婷, 叶俊钊. 粪菌移植治疗肥胖及代谢相关脂肪性肝病的临床研究进展[J]. 中华肥胖与代谢病电子杂志, 2024, 10(02): 138-144.
[15] 中国医师协会外科医师分会肥胖和代谢病外科专家工作组, 中国医师协会外科医师分会肥胖代谢外科综合管理专家工作组, 中国肥胖代谢外科研究协作组. 中国肥胖代谢外科数据库：2023年度报告[J]. 中华肥胖与代谢病电子杂志, 2024, 10(02): 73-83.
阅读次数
全文


摘要

版权所有 中华医学会 中华医学电子音像出版社有限责任公司  京ICP备14006079号-1  网络出版服务许可证：(署)网出证(京)字第075号